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Topics in Primary Care Medicine Parkinson's Disease Diagnosis and Treatment DON C. NG, MD, San Francisco, California
Although Parkinson's disease is primarily a neurologic disorder, primary care physicians should be knowledgeable about the disease and its treatment because most patients will see their primary care physician first for their symptoms. Furthermore, in today's setting of managed care, primary care physicians will likely be called on even more to assume primary responsibility for the treatment of patients afflicted with Parkinson's disease; neurologists will likely play the role of consultants who see a patient only periodically and offer recommendations and advice for the primary care physicians to implement. (Ng DC: Parkinson's disease-Diagnosis and treatment. West J Med 1996; 165:234-240)
The prevalence of Parkinson's disease in communitybased studies is 128 to 187 per 100,000, with an annual incidence of 20 per 100,000 in the United States.' As many as 1.5 million Americans are affected, and 1% of the population older than 60 years may be affected.2 Men may be more frequently affected than women, but most community-based studies from other countries worldwide do not show a gender preference.' The mean age of onset is in the mid-SOs, with increasing incidence and prevalence thereafter; of note, 10% of all patients have recognizable symptoms before the age of 40 and 30% before age 50.3 The cause is unknown; many causes have been proposed but not borne out by subsequent studies. A leading theory is that oxidative stress may be a contributing factor to the loss of melanized cells of the substantia nigra. The clinical importance of these oxidative mechanisms has yet to be proved.
Natural History Parkinson's disease is usually slowly progressive decades in both treated and untreated patients, but the rate of progression varies widely among individual patients, ranging from 2 to 30 years until severe disability or death. The tremor-dominant type of Parkinson's disease and an older age of onset may be associated with a faster rate of progression and a higher risk of cognitive failure developing.* Treatment with levodopa does seem to decrease the severity and to delay the onset of severe disability and related death, hence improving the quality of life. The use of levodopa has increased the mean duration of disease from about 10 to 14 years and reduced the mortality rate among Parkinson's patients. over
*See also the editorial by Michael J. Aminoff, MD, FRCP, "Parkinson's Disease-A Progress Report," on pages 248-249 of this issue.
Before the development of levodopa therapy, mortality was three times higher for patients with Parkinson's disease than for the general population for the same age, sex, and race; for patients treated with levodopa, this ratio has been reduced to 1.2 to 1.3'4
Diagnosis The diagnosis of Parkinson's disease is entirely clinical and mostly one of exclusion because there are no diagnostic tests or studies for the disease. It is defined histologically as a loss of pigmented neurons mostly in the substantia nigra, along with characteristic eosinophilic cytoplasmic inclusions known as Lewy bodies. The pathologic neurochemical process is an insufficiency of striatal neurotransmitters, predominantly dopamine, which has to be reduced to 20% to 30% of normal before clinical manifestations occur. Early Parkinson's disease can be difficult for primary care physicians to diagnose because the early symptoms, sometimes referred to as the preclinical or subclinical phase, may precede the "clinical" onset-when clinical criteria are met-by a decade or two.4 Early symptoms such as slowness, weakness, fatigue, loss of appetite, and sleep disturbances are nonspecific and can lead to a misdiagnosis of hypothyroidism or depression. Another common misdiagnosis is stroke because early symptoms are often unilateral.5 The cardinal symptoms of Parkinson's disease are resting tremor (classic pill-rolling type); muscular rigidity with "cogwheeling" resistance to passive movement; bradykinesia manifesting as decreased blinking, masklike facies, and slowness of movement; postural instability manifesting as retropulsion; gait disturbance with a wide-based, shuffling gait and flexed posture; and a unilateral onset of symptoms with an asymmetric development of disease.'6 The diagnostic accuracy using
From the Division of General Internal Medicine, University of Califomia, San Francisco (UCSF), School of Medicine. Reprint requests to Don C. Ng, MD, Division of General Internal Medicine, UCSF, 400 Pamassus Ave, A-405, San Francisco, CA 94143-0320; E-mail:
[email protected].
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ABBREVIATIONS USED IN TEXT DATATOP = Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism MAO = monoamine oxidase MPTP = methylphenyltetrahydropyridine MRI = magnetic resonance imaging
these criteria is poor in clinical practice; 20% to 30% of patients with clinical parkinsonism other than histologically verified Parkinson's disease are erroneously diagnosed during life.' Another criterion used is a good to excellent response to levodopa or a dopamine agonist. Exclusionary criteria include the absence of substantial changes on brain imaging other than mild diffuse cortical atrophy on computed tomography or magnetic resonance imaging (MRI) or mild periventricular disease on MRI; the absence of pyramidal and cerebellar signs; the absence of a history of drugs, toxic substances, or encephalitis that may cause parkinsonism; and the absence of features atypical for Parkinson's disease. The presence of substantial dementia or autonomic failure out of proportion to the degree of parkinsonism points to other neurodegenerative disorders, although the presence of either in a mild to moderate degree may still be consistent with Parkinson's disease.' One study assessed the accuracy of nine clinical features of patients diagnosed with Parkinson's disease by the postmortem histologic examination of brain tissue.' The results showed that the clinical criteria for Parkinson's disease had varying degrees of sensitivity and specificity. This may explain why there is no universally accepted set of clinical criteria for the diagnosis. Attempting to learn and apply the differing sets of criteria proposed by various research groups for the diagnosis of Parkinson's disease would prove to be a daunting task and an unwieldy tool for primary care physicians. Many of the proposed criteria were put forth in an attempt to improve the accuracy of the diagnosis for research purposes. Thus, although more specific, the proposed criteria are less sensitive and exclude many patients with the disease. In a clinical setting, it may be better to be more sensitive and less specific so that more patients with true Parkinson's disease will have a better chance of being treated. A simple approach for primary care physicians is to remember the cardinal features of tremor, rigidity, bradykinesia, postural instability, and gait disturbances and think of the other features mentioned earlier as "supporting evidence," namely, asymmetry, a good response to an adequate dose (as much as 1,500 mg per day) of levodopa in a formulation that includes carbidopa, the absence of atypical features, and no evidence for other parkinsonian disorders or causes of secondary parkinsonism (discussed later). Even with this in mind, the diagnosis can still be difficult in elderly patients-those 65 years of age and older-because there are many causes of tremor, postural instability, and gait disturbances in the elderly. Tremor in an older patient may be due to medica-
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tion, metabolic disturbances such as hyperthyroidism, Parkinson's disease, or essential. Characteristics such as asymmetry, tremor occurring at rest and decreasing with use of the affected limb, and especially a pill-rolling type of tremor when the fingers are involved point to Parkinson's disease. Sometimes this last characteristic can be elicited by asking the patient to walk or distracting the patient by requesting he or she do simple calculations. Parkinsonian tremor may involve the head, the lips, the tongue, and the jaw. Some patients with Parkinson's disease have a notable action component to their tremor. Because tremors are additive, differentiating Parkinson's disease from essential tremor can be a challenge, particularly early in the course of the disease. Features of essential tremor include absence at rest, an increase with stress or excitement, head or voice involvement, onset at an early age, and a family history. Of note, 15% of patients with Parkinson's disease also have an increase in their tremor with excitement, a tremor that involves the head or voice, an early age at onset, and a family history. Careful attention to details in the history and physical examination will help to distinguish these two disorders. Gait disturbances are common in elderly persons, affecting as many as 15% of people older than 60; in fact, 25% of persons older than 80 use ambulatory assistive devices. There are many causes of gait disorders and postural disturbances, and thus physicians need to observe a patient's gait carefully and note the abnormal and normal features. A parkinsonian gait is characterized by a flexed posture, diminished or absent arm swings, small steps, en bloc turning (turning with little or no rotation of the axial skeleton), difficulty initiating gait and turning, and festination. Gait abnormalities accompany many diseases and may be mistaken for Parkinson's disease. An apraxic gait is characterized by shuffling, hesitation in starting (the feet may appear glued to the floor), poor standing balance, and improvement after the first few steps. Gait apraxia is usually caused by bilateral frontal lobe lesions due to multiple infarcts, degenerative processes such as Alzheimer's disease, or hydrocephalus. A spastic gait is a stiff-legged gait with reduced toe clearance (there is some plantar flexion in the feet that may superficially appear like footdrop) and circumduction associated with bilateral spastic weakness of the legs. It can be caused by spinal cord compression, subacute spinal cord degeneration in vitamin B12 deficiency, or brain tumors involving bilateral parasagittal areas. A steppage gait, where a patient lifts the feet higher than normal and then strikes the ground heavily with each step, is the result of diseases causing an impairment of the position and joint sense in the legs and feet (usually a peripheral neuropathy involving large sensory fibers) such as vitamin B12 deficiency, tabes dorsalis of neurosyphilis, and other disorders that cause dysfunction of the posterior columns of the spinal cord.8 Other Parkinsonian Disorders Although most patients with clinical features of parkinsonism have Parkinson's disease, a few have other
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neurodegenerative disorders that have parkinsonian features. Differentiating these disorders from Parkinson's disease can be difficult and depends on the presence of other additional characteristic clinical findings. Hence, these diseases are often referred to as "parkinsonism plus" syndromes. Four fairly well characterized syndromes are progressive supranuclear palsy, the ShyDrager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy. These are sometimes referred to as multiple system atrophy because they involve various nervous systems and patients may present with any combination of extrapyramidal, pyramidal, cerebellar, and autonomic symptoms.6 Progressive Supranuclear Palsy Progressive supranuclear palsy occurs more often in men and about ten years later than Parkinson's disease does on average. The earliest symptoms are gait and balance impairment: in contrast to patients with Parkinson's disease, the gait is stiff and broad-based, with the knees and trunk extended rather than flexed. Instead of turning en bloc, patients tend to pivot. The most distinguishing feature is paralysis of the downward gaze, resulting in difficulty reading and feeding (patients are often described by others as "sloppy eaters"). Patients are unable to converge their eyes, and loss of upward and lateral eye movement later develops as well. Other features include palilalia (repetition of syllables), stuttering, and pseudobulbar symptoms such as dysarthria, dysphagia, and emotional lability. Mild dementia may be present in the early stages of disease. Computed tomography and MRI typically show generalized and brain stem atrophy. Treatment success with antiparkinsonian drugs is poor, and treatment is best left to a neurologist.
Shy-Drager Syndrome The Shy-Drager syndrome, also known as multiple system atrophy, is characterized chiefly by a loss of autonomic function out of proportion to parkinsonian features. Two subtypes of multiple system atrophy can be distinguished: predominant striatonigral degeneration with bradykinesia and rigidity out of proportion to resting tremor, and an olivopontocerebellar atrophy with prominent truncal ataxia, intention tremor, and slurred speech. Most patients show an overlap of the two symptom constellations. Orthostatic hypotension, bladder incontinence, and impotence are often presenting features. Bowel incontinence, emotional lability, severe obstructive sleep apnea, and vocal cord paralysis with stridor are often seen in more advanced stages. An MRI often shows areas of decreased signal bilaterally in the posterolateral putamen. Treatment is mostly symptomatic. Striatonigral Degeneration Striatonigral degeneration can be similar to Parkinson's disease. Differentiating features include an absence of tremor (an important distinguishing feature), an early onset of falling, severe dysarthria and dysphonia, excessive snoring and sleep apnea, hyperreflexia,
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and extensor plantar responses. Patients typically show a poor response to levodopa. Olivopontocerebellar Atrophy Olivopontocerebellar atrophy has cerebellar ataxia as its distinguishing feature and progressive parkinsonism as a less dominant feature./Gaze impairment, dysarthria and dysphagia, incontinende, dementia, and both upper and lower motor neuron signs occur as the disease progresses. Computed tomographic and MRI scans typically show pancerebellar and brain stem atrophy and demyelination of transverse pontine fibers. The response to levodopa treatment is poor.9 Secondary Parkinsonism Secondary parkinsonism is caused by drugs, for instance, antiemetics (metoclopramide and prochlorperazine), antipsychotics (haloperidol and chlorpromazine), reserpine, methyldopa, and lithium; encephalitis; vascular disease (multiple infarcts); trauma; normal-pressure hydrocephalus; and toxins, such as carbon monoxide poisoning, mercury, manganese, methanol, ethanol, and notably methylphenyltetrahydropyridine (MPTP). This last-named compound is a meperidine-like "designer drug" that causes clinical and pathophysiologic disease similar to Parkinson's disease.9 Whereas the diagnosis of Parkinson's disease can be straightforward, it can also be difficult. Careful attention to the clinical abnormalities during the physical examination, with particular attention to any atypical features, and a thorough medical, occupational, and medication history, both past and present, will help differentiate Parkinson's disease from "Parkinson's plus" syndromes or secondary parkinsonism. Any doubts about the diagnosis should be allayed by consultation with an experienced neurologist.
Treatment of Parkinson's Disease If the symptoms are mild and do not cause any substantial impairment in a patient's activities of daily living and work, then medical treatment may be withheld until the symptoms progress further. An alternative approach is to start treatment with the monoamine oxidase (MAO) type B inhibitor selegiline hydrochloride once the diagnosis is made. Selegiline may exert a neuroprotective effect by reducing the amount of hydrogen peroxide and free radicals generated by the breakdown of levodopa by striatal MAO type B. This hypothesis was proposed after studies of animals showed that selegiline blocked the metabolism of MPTP and prevented the development of parkinsonism. The use of selegiline as a neuroprotective agent began when the preliminary results of a large multicenter study, the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, showed that patients treated with selegiline progressed substantially less than did those given placebo. (The DATATOP study also showed that vitamin E had no neuroprotective effects.) When the final results of the DATATOP study were pub-
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lished in 1993,10 however, whether selegiline was actually neuroprotective was less clear because it exerted a mild symptomatic effect that may have been interpreted as less progression. Recently published results of extended treatment of DATATOP sLijects converted to treatment with open-label deprenyl failed to show any notable neuroprotective effect."',2 Yet, another separate study did show a benefit of the use of deprenyl on the progression of Parkinson's disease.'3 Thus, this issue remains controversial. Many neurologists advocate offering selegiline as monotherapy in the early stage of the disease or at least to use concomitantly with levodopa in patients being started on levodopa therapy9-after discussing with the patient its possible benefit, the current lack of more definitive proof, and its substantial cost.'4"5 The common side effects of selegiline use are insomnia (its metabolites are L-amphetamine and L-methamphetamine) and dysphoria; psychotic episodes can occur in elderly patients. The usual dose is 5 mg at breakfast and lunch; no dietary tyramine restriction is necessary because at this low dose, selegiline inhibits only MAO type B. The use of meperidine should be avoided in patients taking selegiline, however, because of possible fatal interactions with MAO inhibitors.'6 Symptomatic treatment should be started once the disease progresses to the point where a patient's ability to work or perform activities of daily living is impaired. Levodopa has proved to be the most effective drug for treating patients with Parkinson's disease. Initially, there was some theoretical concern that its administration might lead to increased free radical production and hence increase the rate of disease progression. This consideration led to the withholding of levodopa therapy for as long as possible. As more long-term experience accumulated with patients taking levodopa, it became evident that this theoretical concern was not seen clinically. The current recommendation is that levodopa treatment should be started as soon as necessary.2"4"5 In North America, levodopa is combined with the peripherally acting dopa decarboxylase inhibitor carbidopa as Sinemet (DuPont Pharmaceuticals). Carbidopa blocks the peripheral conversion of levodopa to dopamine, which allows the delivery of more levodopa to the brain and also reduces the incidence of nausea, the major side effect of peripheral dopamine. At least 75 to 100 mg of carbidopa daily is necessary to counteract levodopa-induced nausea. Hence, it is preferable to start treatment with 25-100 tablets (25 mg of carbidopa per 100 mg of levodopa) rather than the 10-100 formulation. Therapy should begin with half a tablet of 25-100 Sinemet taken three times a day 30 to 60 minutes before meals. If the patient experiences intolerable nausea, then it can be taken with or after meals. Although the efficacy of levodopa will be substantially reduced by decreased absorption through interference from dietary protein, this may result in less frequent nausea. Once a patient adapts to the drug, it should then be taken before meals again to maximize absorption and hence ensure the chance of an adequate response. The onset of action usually takes
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place within an hour, and most patients know within three days whether a new dosage regimen is working (it may take as long as 7 days in elderly patients). Dosages can be increased every three to five days (weekly in an elderly patient) until sufficient improvement is achieved. Because carbidopa is a noncompetitive inhibitor of dopa decarboxylase, no benefit is attained with doses of carbidopa greater than 200 to 300 mg, and thus patients requiring high doses of levodopa should be switched to the 25-250 formulation. Once a levodopa dose of 600 to 800 mg per day is reached, adjunctive medications are preferable to further increases of levodopa.'6"7 Sinemet CR, a controlled-release formulation, can also be used as initial therapy, starting with half a tablet of the 25-100 formulation twice a day. Note that the bioavailability of the controlled-release formulation is about 30% less than the standard formulation, so a patient being switched to a controlled-release formulation may require a 30% increase in dosage to achieve the same clinical effect. In patients who achieve good clinical response at low dosages of levodopa-doses insufficient to provide at least 100 mg per day of carbidopa-and who have considerable nausea, taking supplemental carbidopa three to four times a day may prove helpful. For others having nausea at reasonable carbidopa doses, controlled-release formulations may be better tolerated owing to the slower rise and lower peak concentrations achieved. Domperidone has been effective in ameliorating nausea in this setting, but the drug is not yet approved for use in the United States. Drugs such as metoclopramide and prochlorperazine should be avoided because they can counteract the central effects of levodopa. Other side effects of levodopa include postural hypotension (in as many as 20% of patients), confusion, vivid dreams and nightmares, paranoia, and outright psychosis (especially in the elderly). Adverse psychiatric effects usually begin nocturnally, so reducing, stopping, or giving the last evening dose earlier may help; in general, the use of neuroleptic drugs is contraindicated because they may induce a protracted worsening of parkinsonism.17 Amantadine hydrochloride has been used in the past to treat Parkinson's disease; its precise mode of action is unknown. The efficacy is modest compared with that of levodopa, but it may be effective in patients with mild disease. Amantadine may begin to lose its effectiveness in 6 to 12 months, however. The usual dose is 100 to 200 mg a day. Side effects include dry mouth, constipation, insomnia, and other effects similar to those of anticholinergics. Particular to amantadine are pedal edema and livedo reticularis. 4'17 Anticholinergic drugs, such as trihexyphenidyl hydrochloride, 6 to 15 mg per day; benztropine mesylate (Cogentin), 1 to 6 mg per day; biperiden hydrochloride (Akineton), 2 to 10 mg per day; and procyclidine hydrochloride (Kemadrin), 7.5 to 20 mg per day, are useful for treating the tremor of Parkinson's disease. They may be useful as monotherapy in early disease when tremor is the predominant symptom, or as adjunctive
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therapy in more advanced disease in patients whose tremor is poorly controlled by levodopa. Side effects are dose-related and tend to be greater than those of levodopa. The anticholinergic side effects include constipation, urinary retention, blurred vision, impaired memory, hallucinations, and acute confusion; these problems are especially more common in elderly patients, and thus great care must be exercised when administering these drugs. Trihexyphenidyl and benztropine are the more potent anticholinergics, but some patients failing to improve with these may respond to the use of others.5"8
Adjunctive Therapy Dopamine Agonists
Dopamine agonists directly stimulate the postsynaptic dopamine receptors and have proved to be useful adjuncts in patients taking levodopa. Their use can allow clinical effectiveness to be achieved with lower doses of levodopa, and motor fluctuations in patients on long-term levodopa therapy can be smoothed over. Many neurologists advocate starting adjunctive dopamine agonist medication when the daily dose of levodopa reaches 600 mg because early use can lead to sustained benefit and a reduced incidence of later motor fluctuations and dyskinesias.15'17 The side effects of dopamine agonists are more common and more severe than those of levodopa. They include nausea, orthostatic hypotension, and psychiatric disturbances (especially in the elderly and patients with cognitive dysfunction) such as hallucinations, nightmares, agitation, paranoia, and psychotic episodes. Other less common side effects include erythromelalgia and pleuropulmonary and retroperitoneal fibrosis.'8 Monotherapy with dopamine agonists has been investigated and found to be less effective than levodopa, but some neurologists advocate their use as initial therapy in younger patients who are better able to tolerate the side effects. The hope is to delay initiating levodopa treatment due to the later development of management problems in patients on long-term levodopa therapy. The two dopamine agonists currently available in the United States are bromocriptine mesylate (Parlodel) and pergolide mesylate (Permax). Bromocriptine therapy is started at half a 2.5-mg tablet once a day, titrated upward every three to five days to a dose of 5 to 7.5 mg three times a day, with a maximum of 60 mg a day. Effective response is usually attained at 15 to 30 mg a day. Higher doses usually result in more pronounced side effects. Similarly, pergolide therapy is started at 0.05 mg once a day and titrated upward every three to five days to a threetimes-a-day dosing regimen until the usual therapeutic dose range of 1 to 6 mg a day. More side effects occur when daily doses exceed 4 mg a day. Studies comparing bromocriptine use with that of pergolide seem to show that pergolide retains effectiveness for a longer time.'9 Monoamine Oxidase Type B Inhibitors As mentioned before, the MAO type B inhibitor selegiline may provide a neuroprotective effect when
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used alone or in conjunction with levodopa. It can also be used as an adjunct to achieve a response with a lower dose of levodopa and to smooth over the "wearing-off' and on-off motor response fluctuations in more advanced disease. The benefits are modest, however.'8'10 Physical and Occupational Therapy Physical therapy is an important adjunct in the treatment of Parkinson's disease. Although few studies have rigorously assessed the clinical benefit of physical therapy, many neurologists think that it does improve patients' quality of life and mobility. Specific exercises tailored to each patient's disabilities and needs help mitigate stiffness and slowness and prevent disuse atrophy, weakness, and the deterioration of fine motor control. Appropriate regimens can be designed to maintain mobility, flexibility, stamina, and strength; gait training helps with postural instability and decreases the likelihood of falls.5 Patients need to be seen by physical therapists routinely to encourage them to maintain their exercises because, if left on their own, they gradually resume a more sedentary lifestyle and stop doing the exercises. The benefits gained from physical therapy are thus lost within six months.2' Occupational therapy helps patients maintain more independence by helping them continue their activities of daily living. Patients' homes should be assessed by physical and occupational therapists for the installation of aids such as strategically placed railings, special toilet seats, safety equipment for the bathroom, and specially designed eating utensils and kitchenware. A patient's ability to self-dress can be improved with clothing that has zippers or Velcro closures, and shoes should be the slip-on type with soles that do not grip the floor too tenaciously (causing the patient to fall forward).5
Progression of Disease After several years (typically about 5) of levodopa treatment, the disease progresses to the point where patients begin to have shortened responses to levodopa, often manifesting as a wearing-off phenomenon wherein their symptoms worsen before the next dose of levodopa is due. They may also respond less predictably to each dose and may become extremely sensitive to dietary protein, giving a history of becoming immobilized after eating a high-protein meal. Gastric emptying, which is erratic in patients with Parkinson's disease, can also account for response fluctuations. The wearing-off phenomenon may be lessened by more frequent dosing and taking the medication on an empty stomach; a diet in which the amount of protein eaten is reduced and is saved until the last meal of the day may allow the patient to maintain mobility during the day and be less bothered by increased rigidity and bradykinesia in the evenings when patients are more sedentary. As the disease progresses further, patients may begin to have unpredictable periods of suddenly becoming immobilized, even in the midst of a good medication effect-an on-off phenomenon. This problem may not
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respond as well to dietary measures, so selegiline may be tried instead (if the patient is not already taking it). Dopamine agonists are more effective and can be added if the motor fluctuations are more severe. Controlledrelease Sinemet may also be effective in smoothing over response fluctuations and can be used with judiciously timed standard Sinemet to counter the wearing-off and on-off phenomena.'5""6,22 As the disease progresses and increasingly higher doses of levodopa are used, dyskinesias may develop in the form of athetosis, chorea, and choreoathetosis, which when severe, can resemble ballismus. Lowering the doses of levodopa to reduce peak concentrations and increasing the dosing frequency or adding controlledrelease Sinemet may lessen these dyskinesias, but note that drug-induced dyskinesias may result from either too much or too little levodopa. Patients may also have painful dystonias that usually involve the feet and lower legs when levodopa levels ebb before the next dose. Dystonias are common early in the morning and can awaken a patient; taking a controlled-release Sinemet at bedtime may help. Adding a dopamine agonist or increasing its dose may help lessen dyskinesias and dystonias; switching from bromocriptine to pergolide or vice versa may also help. Patients experiencing pain from the dystonias may have some relief with the use of baclofen, lithium, or muscle relaxants. Patients with advanced Parkinson's disease who are having substantial levodopa-induced dyskinesias and disabling akinetic-rigid states may be candidates for stereotactic pallidotomy, whereby a small area of the internal segment of the globus pallidus is ablated through a stereotactically guided microelectrode introduced through a small burr hole. Recent studies have shown a considerable reduction in levodopa-induced dyskinesias and a lessening in rigidity, bradykinesia, imbalance, and tremor lasting at least a year postoperatively and with relatively low complication rates.2>2' As the disease progresses from the early mild stages, other problems become more prominent. Depression, which may be endogenous or reactive, can be present in more than 50% of patients. Many are depressed over the loss of their independence and function, increasing dependence on family and others, and the progressive nature of their disease. They can lose their drive, initiative, and motivation and become passive, withdrawn, and anhedonic. For those who complain of a lack of energy, serotonin reuptake inhibitors such as fluoxetine, paroxetine, or sertraline can be effective. For patients with difficulties sleeping, taking tricyclic antidepressants can be beneficial, especially because their anticholinergic properties may further reduce tremor.'626 Dementia occurs in 15% to 20% of patients with Parkinson's disease and usually develops late in the course. Of note, however, is that as many as a third of patients with Alzheimer's disease can have extrapyramidal signs and symptoms. The presence of dementia early in the course of a patient with parkinsonism should lead to a consideration of Alzheimer's disease (sometimes
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referred to as Alzheimer's disease with parkinsonism), diffuse Lewy body disease (which some consider to be a variant of Alzheimer's disease), or progressive supranuclear palsy."9 Drooling may become a problem as the disease advances because of decreased automatic swallowing. Patients often lose weight due to a variety of factors, and constipation can become a serious problem for many, causing a preoccupation with bowel function. Adequate dietary fiber and liquids are important, and promotility agents such as cisapride may be helpful for more severe cases. Bladder hyperspasticity may develop as well as bladder outlet obstruction. Autonomic dysfunction in advanced stages can manifest as sweating, orthostatic hypotension, impotence, constipation, and urinary bladder dysfunction." Sorting out these problems can be challenging because many of the medications-especially those with anticholinergic properties-can cause hallucinations, confusion, impaired memory, constipation, and urinary retention as well, especially in elderly patients and in those with existing cognitive dysfunction.
Primary Care Primary care physicians play a central role in the overall care of patients with Parkinson's disease. At the time of the initial diagnosis, patients and family need help in learning about and understanding the disease and its progressive course. They also need reassurance that severe disability usually occurs many years later and that a reasonable quality of life can be maintained with medication, exercise, and continued social activities. Physicians can help to counter the tendency toward immobilization and apathy by encouraging patients to contact national Parkinson's disease organizations, such as American Parkinson's Disease Foundation, 1250 Hyland Boulevard, Staten Island, NY 10305 ([800] 2232732); National Parkinson's Disease Foundation, 1501 Northwest Ninth Avenue, Miami, FL 33136 ([800] 4337022); and Parkinson's Disease Foundation, 710 West 168th Street, New York City, NY 10032-9982 ([800] 457-6676), for information about local support groups and newsletters. Referrals for physical and occupational therapy should be made periodically as the disease advances. Speech therapy is beneficial for those with difficulty swallowing and speech problems. In more advanced stages, attendance at a senior day care center is recommended because many centers provide social activities, physical and occupational therapy, and meals for patients. Visiting home nurses and physical and occupational therapists can help improve a patient's activities of daily living, and these professionals can also evaluate the home for safety and make appropriate adaptations of household furnishings. Because caring for patients with more advanced disease can be extremely taxing for spouses and families, respite care should be offered periodically. In addition to managing other health problems-cardiac disease, diabetes mellitus, hypertension, and the
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like-primary care physicians should not overlook routine immunizations and screening because many patients with Parkinson's disease will live for decades after the disease occurs. In summary, primary care physicians should be knowledgeable about the cardinal features of Parkinson's disease. Treatment can be started in those who meet many of the criteria; failure to respond to adequate doses of levodopa, the presence of any atypical features, or any doubt about the diagnosis should lead to a consultation with an experienced neurologist. In more advanced disease and in patients taking many antiparkinsonian medications, they will benefit from the experience of a neurologist in the management of the disease and from a primary care physician's overall management of their health problems, both related and unrelated to the disease. REFERENCES 1. Tanner CM: Epidemiology of Parkinson's disease. Neurol Clin 1992; 10:317-329 2. Paulson GW: Management of the patient with newly-diagnosed Parkinson's disease. Geriatrics 1993; 48:30-40 3. Hoehn MM: The natural history of Parkinson's disease in the pre-levodopa and post-levodopa eras. Neurol Clin 1992; 10:331-339 4. Marttila RJ, Rinne UK: Progression and survival in Parkinson's disease. Acta Neurol Scand Suppl 1991; 136:24-28 5. Goetz CG, Jankovic J, Paulson GW: Update on Parkinson's disease. Patient Care 1992; 26:172-208 6. Larsen JP, Dupont E, Tandberg E: Clinical diagnosis of Parkinson's disease-Proposal of diagnostic subgroups classified at different levels of confidence. Acta Neurol Scand 1994; 89:242-251 7. Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ: What features improve the accuracy of clinical diagnosis in Parkinson's disease: A clinicopathologic study. Neurology 1992; 42:1142-1145 [erratum published in Neurology 1992; 42:1436] 8. Rubino FA: Gait disorders in the elderly. Postgrad Med 1993; 93:185-190 9. Stacy M, Jankovic J: Differential diagnosis of Parkinson's disease and parkinsonism plus syndromes. Neurol Clin 1992; 10:341-359 10. Parkinson Study Group: Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1993; 328:176-183
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This article is one of a series on topics in primary care in which common diagnostic or therapeutic problems encountered in primary care practice are presented. Physicians interested in contributing to the series are encouraged to contact the series' editors. STEPHEN J. McPHEE, MD TERRIE MENDELSON, MD Assistant Editors
