Functional neuropathology in Parkinson's disease.
The pathophysiology of akinesia and chorea involve disruption of the motor basal ganglia circuit. This circuit begins with cortical output to the striatum, followed by projections from striatum to pallidum, pallidum to thalamus, and finally thalamus to cortex. Abnormal thalamic output to the frontal cortex, particularly the supplementary motor cortex, is responsible for chorea and akinesia. The substantia nigra and subthalamic nucleus are also important parts of this circuit. Chemical or pathological changes in these nuclei that lead to reduced thalamic outflow to the cortex are associated with parkinsonism. Most disorders affect the nigrostriatal dopaminergic projection. The overall consequence of loss of nigrostriatal dopamine is a loss of inhibitory input to the striatum. This feeds through the circuit resulting in reduced thalamic outflow. Local factors that may affect symptoms are the degree of dopamine loss, the involvement of ventral or dorsal parts of substantia nigra, effect on direct and indirect pallidal pathways, topographical representation of the body in the striatum, and the presence of parallel basal ganglia circuits serving cognition and mood. Ageing, dopa-responsive dystonia, juvenile dystonia-Parkinson syndrome and Parkinson's disease have different effects on the nigrostriatal tract. In Parkinson's disease the speed and regional variation in nigrostriatal dopamine loss are associated with a significant pre-symptomatic period, steady rate of progression and a particular topography of L-dopa dyskinesias.
Gibb
W R
WR
Wessex Neurological Centre, Southampton General Hospital, UK.
D001479:Basal Ganglia / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D013787:Thalamic Nuclei / Q000473:pathology / Q000503:physiopathology
D004298:Dopamine