MID-STAGE PARKINSONISM WITH MILD MOTOR FLUCTUATIONS

Most patients with Parkinson's disease who undergo levodopa therapy ev entually develop fluctuations in the diurnal control of their symptoms . These fluctuations, when mild, consist mostly of the ''wearing-off'' effect-the re-emergence of symptoms several hours after the ingestion of each dose of levodopa. In some patients, ''wearing-off'' in the da ytime is preceded by, or associated with, the development of nocturnal and early morning akinesia. Some patients at this stage also have mil d (mostly peak dose or square-wave) choreoathetoid dyskinesias. In pat ients with ''wearing-off,'' ''on'' periods tend to occur when plasma l evels of levodopa are high; nocturnal and early morning akinesia and d iurnal ''of'' periods tend to occur at times when plasma levodopa leve ls are low, reflecting insufficient concentrations of dopamine in the striatum. Treatment strategies in patients with mid-stage parkinsonism and mild fluctuations are primarily directed toward enhancing dopamin ergic transmission in the striatum. This is achieved by increasing the supply of levodopa to the brain or by administering drugs that either prolong the effect of synaptic dopamine from levodopa, or activate po stsynaptic dopamine receptors. This presentation will discuss the adva ntages and possible drawbacks of these different strategies, which inc lude the use of controlled-release levodopa preparations, deprenyl, an d the new monoamine oxidase (MAO)-B inhibitors, catechol-O-methyl tran sferase (COMT) inhibitors, acid the various ''direct'' dopamine agonis ts.