The evolution and origin of motor complications in Parkinson's disease

Levodopa is the major symptomatic therapy for Parkinson's disease (PD), having revolutionized the treatment of PD and provided benefit to virtually all patients. However, after 5-10 years of treatment, levodopa therapy is complicated by the development of motor complications, which include dyskinesia and motor fluctuations. The initial long duration response to a dose of levodopa becomes progressively shorter, and periods in which the patient responds to the drug become complicated by involuntary dyskinetic movements. Thus, patients may cycle between "on" periods that are complicated by dyskinesia and "off" periods in which they are severely parkinsonian. As a consequence they may experience profound disability despite the fact that levodopa remains an effective anti-parkinson agent throughout the course of the disease. In this article we review the various motor complications associated with the treatment of PD and present current concepts on the origin of these problems.