Evolution of motor fluctuations in Parkinson's disease: A longitudinal study over 6 years

A prospective longitudinal 6-year study of 34 patients with Parkinson's dis ease from the time of initiation of drug treatment explored changes in the motor response to L-dopa over the early to mid disease course. Motor fluctu ations developed in 41% after a mean L-dopa treatment interval of 25 months and dyskinesia developed in 53% after a mean of 15 months' treatment. Pati ents who developed fluctuations had a significantly better response to L-do pa than nonfluctuators. Nonfluctuators also had significantly greater "midl ine" motor disability affecting cranial and truncal muscles and gait. The d evelopment of motor fluctuations may simply reflect a retained capacity to respond to L-dopa as endogenous dopaminergic neurotransmission declines wit h progressive nigral cell loss. Many patients who show no sign of motor flu ctuation 5 or 6 years into the disease course have a relatively blunted res ponse to L-dopa. The proportion of such cases seems to correspond to the pe rcentage that have coexisting striatal pathologic changes in postmortem stu dies.