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 disease 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 fluctuations 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. Patients who developed fluctuations had a significantly better response to L-dopa than nonfluctuators. Nonfluctuators also had significantly greater "midline" motor disability affecting cranial and truncal muscles and gait. The development of motor fluctuations may simply reflect a retained capacity to respond to L-dopa as endogenous dopaminergic neurotransmission declines with progressive nigral cell loss. Many patients who show no sign of motor fluctuation 5 or 6 years into the disease course have a relatively blunted response to L-dopa. The proportion of such cases seems to correspond to the percentage that have coexisting striatal pathologic changes in postmortem studies.