Levodopa-induced dyskinesias and their management

This paper reviews the epidemiology, pathophysiology, clinical features and rationale for managing dyskinesias associated with Parkinson's disease. These are a common clinical problem occurring in up to 90% of patients and more frequently affect those with early-onset. Dyskinesias have a negative impact on quality of life and are an important cause of disability. Their precise etiology is still poorly understood, although it is recognized that dopaminergic pre-synaptic and post-synaptic mechanisms are involved together with extra-dopaminergic factors. The phenomenology of dyskinesias encompasses a variable mixture of two prevalent features: dystonia and chorea. We have studied their time course following a single acute levodopa challenge and have found that dystonia occurs throughout the duration of the on period, whereas choreiform movements occur only at the peak of therapeutic dopaminergic motor responses. This allows a schematic relationship to be drawn between a short duration motor response and the occurrence of dystonia and chorea. There is currently no satisfactory treatment for dyskinesias. Managing the therapeutic window does not provide an adequate solution due to the appearance of a dyskinesia threshold dose that narrows the therapeutic margin. High frequency stimulation of the subthalamic nucleus probably has some specific anti-dyskinetic action, but is limited by the small number of patients who are candidates for this treatment. Research efforts are currently focused on the development of specific anti-dyskinetic medications. Their availability will certainly change the current clinical practice and will widen again the therapeutic window of dopaminergic medications that has now become too narrow.