Metabolic and cognitive changes in hereditary ataxia.

Fourteen subjects (affected, n = 7; at risk, n = 7) from one well-known kindred with adult onset autosomal dominant olivopontocerebellar atrophy (OPCA), were studied with [18F]-2-deoxy-D-glucose (FDG) positron emission tomography (PET), magnetic resonance imaging (MRI), cognitive testing and scored neurological examination, and compared with normal controls. The neurological examination, MRI and cognitive tests showed no significant differences between at risk and normal control subjects. Mild cognitive deficits were seen in affected subjects; the degree of cognitive change appeared to relate to the severity of the illness. MRI demonstrated cerebellar and brainstem atrophy in all affected subjects. PET studies showed higher global metabolic rates (mean [SD]) in at risk subjects (10.5 [1.5] mg per min per 100 g) as compared to affected (9.0 [0.8] mg per min per 100 g) and normal control subjects (9.1 [1.5] mg per min per 100 g). Normalized (region/global average) regional metabolic rates were reduced in cerebellar hemispheres and vermis, and in frontal and prefrontal areas of affected subjects in comparison to at risk and normal control subjects. These findings indicate that functional changes in some forms of autosomal dominant hereditary cerebellar ataxia may extend beyond the cerebellum and brainstem to involve other parts of the neuraxis.