Factors associated with the development of motor fluctuations and dyskinesias in parkinson disease

Background Motor fluctuations and dyskinesias can cause disability and reduce quality of life for patients with Parkinson disease (PD). Objectives To evaluate factors associated with the development of motor fluctuations and dyskinesias and to assess the sequence in which they occur in individual patients. Design We performed a retrospective analysis of data from a randomized clinical trial comparing pramipexole dihydrochloride and levodopa as initial treatment for PD. Subjects were followed up for 48 to 58 months and evaluated at 3-month intervals for the presence of motor fluctuations and dyskinesias. Setting Academic and private practices. Patients Three hundred one patients with early Parkinson disease were enrolled in this study between October 2, 1996, and August 21, 1997, and were observed through August 24, 2001, when the last patient enrolled completed 4 years of follow-up. Main Outcome Measures Order of appearance of motor fluctuations and dyskinesias, time to the first occurrence of motor fluctuations, and time to the first occurrence of dyskinesias. Results One hundred eighty-nine subjects (62.8%) developed motor complications. Of these, 71 (37.6%) developed fluctuations but not dyskinesias, 23 (12.2%) developed dyskinesias but not fluctuations, 48 (25.4%) developed fluctuations before dyskinesias, 33 (17.5%) developed dyskinesias before fluctuations, and 14 (7.4%) developed both at the same time. Factors significantly associated with earlier occurrence of dyskinesia were Hoehn and Yahr stage of 2 or higher, cumulative levodopa dose, cumulative levodopa equivalent dose (levodopa plus pramipexole), and occurrence of motor fluctuations. Pramipexole treatment was associated with later occurrence of dyskinesias. Factors associated with earlier occurrence of motor fluctuations were cumulative levodopa dose, cumulative levodopa equivalent dose, and occurrence of dyskinesias. Factors associated with later occurrence of motor fluctuations were age at onset of 65 years or older and pramipexole treatment. Conclusions Higher cumulative levodopa doses and higher cumulative levodopa equivalent doses (levodopa plus pramipexole) were associated with the earlier occurrence of motor complications. Motor fluctuations and dyskinesias appear to be interrelated because the presence of one is associated with the earlier development of the other