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Motor fluctuations and dyskinesia in Parkinson disease

Author
Daniel Tarsy, MD
Section Editor
Howard I Hurtig, MD
Deputy Editor
John F Dashe, MD, PhD

INTRODUCTION

Motor fluctuations and dyskinesia are important complications of levodopa therapy that affect many patients with advancing Parkinson disease (PD). This topic review will discuss the medical management of patients with PD who are experiencing motor fluctuations. The general approach to therapy of PD is discussed separately. (See "Pharmacologic treatment of Parkinson disease".)

Deep brain stimulation of the subthalamic nucleus or globus pallidus is another therapeutic option that improves motor function in selected patients with advanced typical PD and motor fluctuations, whose condition cannot be further improved by medical therapy. The surgical management of advanced PD is discussed elsewhere. (See "Surgical treatment of Parkinson disease".)

NATURE OF THE PROBLEM

As many as 50 percent of patients on levodopa for several years will experience motor fluctuations and dyskinesia [1]. Motor fluctuations are alterations between periods of being "on," during which the patient experiences a positive response to medication, and being "off," during which the patient experiences a reemergence of the Parkinson symptoms suppressed during the "on" state. Dyskinesia consists of levodopa-related abnormal, involuntary movements. While caused by a relative excess amount of levodopa, dyskinesia can occur at a dose that is otherwise therapeutic and does not necessarily represent an overdose. Dyskinesia are especially common in patients with young-onset (eg, before age of 50 years) PD; they are mostly associated with the use of levodopa but can occur with dopamine agonists, especially when added to enhance the effect of levodopa. (See "Pharmacologic treatment of Parkinson disease".)

Patients with PD typically experience a smooth and even response to the early stages of levodopa treatment. As the disease advances, however, the effect of levodopa begins to wear off several hours after some or even all doses, leaving patients aware that the duration of action of a dose of levodopa is not being sustained. The reason motor fluctuations occur is not entirely clear, but current thinking holds that motor fluctuations evolve as PD progresses because progressive degeneration of the nigro-striatal dopaminergic pathway reduces the ability of nerve terminals to store and release dopamine physiologically. As a result of this loss of storage capacity, the response to exogenous levodopa defaults to a more pulsatile or bolus impact on postsynaptic dopamine receptors (the short duration response) in keeping with levodopa's short (90 minute) half-life and its rapid cycling pharmacokinetics. Plasma levels of levodopa may fluctuate because of the additional problem of erratic intestinal absorption related to slowed intestinal motility and other factors.

There are several types of motor fluctuations, including the following:

                       

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Literature review current through: Nov 2016. | This topic last updated: Mon May 02 00:00:00 GMT+00:00 2016.
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