III. Diseases primarily affecting the basal ganglia
A. Huntington Disease - expanded polyglutamine repeat
1. Age of Onset: usually occurs between the ages of 30 and 50; death in 5‑25 years.
2. Location of Lesions: caudate, putamen, globus pallidus and cerebral cortex.
3. Clinical Presentation: may begin with some combination of mood and personality changes, cognitive decline, clumsiness, extrapyramidal motor abnormalities, especially chorea (bursts of movement). Thus two types of symptoms occur:
a. Behavioral and cognitive changes, leading to dementia
b. Increasingly severe movement disorder
4. Pathogenesis: loss of projection neurons in basal ganglia with resulting deficiency of GABA, enkephalin, and substance P. One theory proposes that an excitotoxic mechanism may be involved in the pathogenesis of cell death.