Ronald N. Rubin, MD

A 71-year-old man presents with stiffness, clumsiness, and a sense of weakness in his left arm that began about 4 months earlier. He is concerned that he has had a stroke. Although he is right-handed, the weakness in his left arm interferes with his ability to play golf. Repetitive movement that involves his left hand and arm (eg, using tools) also causes difficulty. He notes no gait disturbance, urinary symptoms, or cognitive difficulties. However, friends and family have told him that his left hand and fingers sometimes shake while he watches television. He is unaware of this, and as soon as he begins to use his left hand, the movements cease.

The patient has hypertension that is well controlled with an angiotensin-converting enzyme (ACE) inhibitor. He also takes a statin to lower his cholesterol level. He is retired and lives at home with his wife.

This well-appearing man has normal vital signs. Extraocular movements are normal. There are no carotid bruits. Chest is clear, and heartbeat is regular without gallops or significant murmurs. There are no rashes or edema.

Neurologic examination reveals a relatively normal, narrow-based gait, although arm swing on the left is diminished. Strength in both upper extremities is normal; however, reflexes in the left arm are diminished compared with the right, as is dexterity in the left hand (tested by finger tapping). The ring finger and little finger of the left hand tremble intermittently at rest or while walking. The tremor immediately resolves with voluntary use of the hand.

Hemogram is normal, as are results of a chemistry panel (including cholesterol levels that are normal for a man of his age).

Which of the following is the most appropriate management strategy?
  

 Initiate aspirin and clopidogrel therapy.

 Initiate therapy with a non-ergot dopamine agonist.

 Discontinue the ACE inhibitor and substitute another antihypertensive.

The findings here are consistent with parkinsonism--and most likely, Parkinson disease (PD). PD is the second most prevalent neurologic syndrome in elderly persons (after Alzheimer disease). It is most common in persons older than 60 years and more common in men than in women. The disease is found in all racial and ethnic groups and has a clearly deleterious effect on quality of life and mortality in affected persons.

The diagnosis remains a clinical one; there is no laboratory or imaging finding specific to PD. The disease has 4 classic presentations:

Unlike essential tremor, which is symmetric and is not reversible with voluntary movement, this is typically a resting tremor that abates with movement of the affected part and is almost always asymmetric at the time of presentation.

 Asymmetric in most patients, the clumsy or “weak” limb reflects the bradykinesia (slowness and clumsiness but no true strength deficits) associated with PD.  

 This is also asymmetric in most patients and reflects the muscular rigidity associated with PD. 

 This is a well-known sign of PD. Arm swing is diminished, and in late cases, the classic shuffling, small-step gait is evident.

This patient has a variety of typical signs and symptoms and is in the appropriate age group. He exhibits slowness and clumsiness but no true paresis. Repetitive acts are difficult. He thus manifests the rigidity and bradykinesia associated with PD rather than the deficits of a stroke. He has an asymmetric resting tremor that disappears with voluntary movement--perhaps the most specific sign of PD. These abnormal findings are confirmed and amplified on neurologic examination. In a patient such as this, a clinical diagnosis of PD can be made.

Most authorities would order an MRI scan, not because this study can confirm PD but to exclude the unlikely presence of structural disease mimicking PD or parkinsonism associated with another disease. Nonetheless, the clinical findings are strong enough here to start treatment.

 Although this patient apparently has early and mild PD, his symptoms bother him and affect his quality of life sufficiently that therapy should be initiated. A variety of agents are available, including levodopa, dopamine agonists, and anticholinergic agents.

Levodopa is the most effective PD therapy, and this agent will be prescribed for almost all patients with PD at some point in the course of their disease. This would not be an incorrect choice here, had it been offered. However, levodopa has more side effects than do dopamine agonists (eg, greater risk of dyskinesia); thus, many authorities would use a non-ergot dopamine agonist (choice 

) initially in a patient such as this man.

 Because of adverse effects, anticholinergics are rarely used as single agents early in the disease or in patients older than 70 years. Of the answers offered here, a non-ergot dopamine agonist is clearly the best choice.

Aspirin and clopidogrel (choice A) and β-blocker therapy (choice B) represent treatments for other neurologic disorders that can resemble PD. Aspirin and clopidogrel are effective platelet-inhibiting therapy for stroke and cerebrovascular disease. Unless an MRI scan in this patient reveals striking evidence of concomitant cerebrovascular disease, in which antiplatelet agents are indicated for prophylaxis, neither aspirin nor clopidogrel will have any effect. 

β-Blockers have been used successfully to treat essential tremor, one of the main entities in the differential diagnosis here. However, this patient's tremor is a resting tremor, is asymmetric, and resolves with voluntary movement. Thus, essential tremor is not the correct diagnosis, and a β-blocker will not be effective.

Discontinuing the ACE inhibitor (choice D) reflects the possibility that the parkinsonism is drug-induced, which is reported to account for up to 20% of parkinsonism.

 However, the drugs typically implicated are neuroleptics, dopamine antagonists, antiemetics, and some calcium channel blockers. ACE inhibitors are not usually associated with parkinsonism, and stopping them is very unlikely to have any effect here.

An MRI scan did not reveal significant pathology, supporting the diagnosis of PD. Therapy with pramipexole was started. Three months later, the patient had significantly less clumsiness of the left arm and more fluid movements, and he was able to play golf again. The tremor also diminished. He has not reported any adverse effects from his medication.

Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990. 

Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y. Ten-year follow-up of three different initial treatments of de-novo PD: a randomized trial. 

 Nutt JG, Wooten GF. Diagnosis and initial management of Parkinson's disease. 

Miyasaki JM, Martin W, Suchowersky O, et al. Practice parameter: initiation of treatment for Parkinson's disease: an evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. 

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A 71-year-old man presents with stiffness, clumsiness, and a sense of weakness in his left arm. He is concerned that he has had a stroke. What is the most appropriate management strategy?

Ronald N. Rubin, MD

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