The pathophysiology of chorea/ballism and Parkinsonism

Recent neurobiological investigations indicate the presence of three principles of basal ganglia organization-the existence of segregated striatal output pathways, the differential regulation of these segregated outputs by dopamine, and the importance of the subthalamic nucleus-that provide insight into the pathophysiology of parkinsonism and chorea/ ballism. Choreic movement disorders result probably from diminished output from the basal ganglia, either from lesions of the subthalamic nucleus or from disordered regulation of subthalamic afferents. Parkinsonism results probably from excessive output of the basal ganglia to the thalamus. Recent data from animal experiments and human surgical studies are consistent with predictions of this model. Further articulation of this model suggests a hypothesis for the mechanism of peak dose dyskinesias. Some deficiencies of the model include its neglect of some potentially important connections within the basal ganglia, its failure to provide an adequate hypothesis for the mechanism of dystonias or tardive disorders, and an oversimplified conception of thalamic function. The model does provide a framework for future laboratory and clinical studies.