Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 58-year-old woman is seen for a follow-up evaluation of Parkinson disease, which she has had for 12 years. She was initially treated with ropinirole to which levodopa-carbidopa was added as the disease progressed. After 5 years of good control on medication, she began to experience involuntary generalized twisting and writhing movements after taking each dose of levodopa-carbidopa and noticed that the medication’s effect waned after several hours.

Over the past 2 years, she has tried to manage her disease by taking higher and more frequent doses of levodopa-carbidopa, a long-acting preparation of levodopa-carbidopa, entacapone to prolong the levodopa effect, and amantadine for choreic movements. She now requires medication treatment every 2 hours and has twisting and writhing with each dose. Her symptoms vary between good mobility, accompanied by generalized and at times ballistic movements, and wearing-off motor fluctuations, with generalized tremors, slowness, and gait impairment.

Which of the following is the best treatment for this patient?

A: Deep brain stimulation
B: Gene therapy
C: Physical therapy and use of a walker or wheelchair
D: Supervised discontinuation of all medications followed by gradual reintroduction

MKSAP Answer and Critique

The correct answer is A: Deep brain stimulation.

The best management option for this patient is deep brain stimulation surgery. She developed Parkinson disease at age 46 years and, after many years of treatment, has now developed wearing-off motor fluctuations and drug-induced dyskinesia, two of the most serious complications of chronic treatment of Parkinson disease. Her condition is difficult to correct because efforts to reduce the dyskinesia by lowering the medication dosage lead to more pronounced wearing-off episodes, and attempts to improve the wearing-off motor fluctuations by increasing the medication exacerbate the dyskinesia. It is unlikely that further medical treatment or medication adjustments will substantially improve her quality of life.

Deep brain stimulation of the subthalamic nucleus or globus pallidus bilaterally can dramatically improve dyskinesia and wearing-off motor fluctuations and should be considered for this patient. She is an ideal candidate for this surgery because her idiopathic Parkinson disease is still responsive to individual doses of levodopa and she has no contraindications to surgery, including severe medical illness, dementia, or depression. Deep brain stimulation, although effective for wearing-off fluctuations and dyskinesia, has limitations in that it does not slow or reverse disease progression and is an elective procedure that carries operative risks.

Although under investigation, gene therapy currently is not a standard treatment option for treating Parkinson disease.

Physical therapy and the use of devices to increase mobility and prevent falls can be helpful adjuncts in the treatment of advanced Parkinson disease but do not specifically address the pharmacologic issues of wearing-off motor fluctuations and dyskinesia and thus are not the best treatment option.

A drug holiday (discontinuation and then reintroduction of her medications) is most likely to trigger acute parkinsonian symptoms in this patient and thus is inappropriate treatment.

Key Point

• Incapacitating wearing-off motor fluctuations and dyskinesia are primary indications for deep brain stimulation in patients with Parkinson disease.

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