Huntington’s Disease

Huntington’s disease (HD) is inherited in an autosomal dominant manner, with complete penetrance. The responsible gene has been localized to the short arm of chromosome 4. The patients often become symptomatic by the age 50 and usually present with affect and personality problems. As the disease progresses dementia becomes evident and motor abnormalities emerge. Choreoathetoid movements are typically described in these patients. A group of patients may have rigidity as the dominant motor abnormality, the Westphal variant. The classic pathological finding in HD patients is atrophy of the basal ganglia, particularly the caudate nuclei (Fig. 3.6.12). Interestingly, the atrophy progresses from medial-to-lateral and dorsal-to-ventral direction. The earliest atrophic changes can be detected in the head of the caudate. The frontal and temporal cortices may also be affected. On the molecular level, diminished neurotransmitter concentrations of acetylcholine and γ-aminobutyric acid occur in the affected regions. A number of investigators have reported that areas of abnormal T2 prolongation in the basal ganglia occur in HD patients. There are reports that all patients with the rigid form of HD have these changes, but they only seldom present in patients with the classic hyperkinetic form of the disease (Oliva 1993; Savoiardo et al. 1991). In severe cases the patients may have atrophy of other parts including the olives, pons, cerebellum, thalamus, white matter tracts, mesial temporal lobe, and the cortex.