Differential progression of motor impairment in levodopa-treated Parkinson's disease

OBJECTIVE: To monitor comparative progression of clinical impairment over 4 years in patients with Parkinson's disease (PD) who present on levodopa at two different levels of Hoehn and Yahr (HY) stages, II and III. BACKGROUND: The rate of clinical impairment progression in patients with PD being treated with levodopa has not been studied in detail using current, standardized assessment tools. Sample size estimates for all levodopa adjun ctive treatment studies and proper definition of study groups require a sol id estimate of longitudinal motor impairment progression. DESIGN/METHODS: From our computer database, we identified two groups of pat ients with PD being treated with levodopa based on their initial HY stage a t presentation to our center (II or III). Fifty randomly selected subjects in each stage were monitored in the ON state with annual Unified Parkinson' s Disease Rating Scale (UPDRS) motor scores, dyskinesia ratings, and antipa rkinsonian medication doses using a repeated measures analysis of variance. RESULTS: The stage II and stage III subjects had similar disease duration. In stage II subjects, parkinsonian impairment was maintained without progre ssion over 4 years, but in association with significantly higher dyskinesia scores and dopaminergic medication doses. In stage III subjects, UPDRS mot or scores deteriorated despite more medication and increased dyskinesias. O f the established six factors comprising the UPDRS motor scale, bradykinesi a accounted for the increased impair ment. Initial UPDRS motor score and di sease duration did not influence progression of motor impairment. CONCLUSION: In subjects with similar disease duration, progression of PD mo tor impairment differs significantly between stage II and stage III subject s over 4 years. Whereas in stage II subjects, parkinsonian impairment can b e stabilized at the expense of increased dyskinesia and dopaminergic drugs, once subjects reach stage III, motor impairment progresses. Power estimate s and sample size calculations for these groups of patients should be calcu lated separately.