Gray and white matter alterations in spinocerebellar ataxia type 7: an in vivo DTI and VBM study

Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder characterized by cerebellar ataxia and visual loss. It is caused by a CAG repeat expansion in the gene encoding the ataxin 7 protein. Visual loss is due to a progressive atrophy of photoreceptor cells that results in macular degeneration in more advanced stages. Initial semiautomatic measures in magnetic resonance imaging (MRI) studies on the brain stem have shown a diminished volume mainly in the cerebellum and pons, while T2 images have shown hyperintensities in transverse fibers at the pons. Neuropathological research, however, has shown more widespread brain damage including loss of myelinated fibers. In this study we decided to take advantage of recent MRI methodological advances to further explore the gray and white matter changes that occur in SCA7 patients. We studied nine genetically confirmed SCA7 patients and their matched controls using voxel based morphometry and tract-based spatial statistics. As expected, we found significant bilateral gray matter volume reductions (p<0.05, corrected for multiple comparisons) in patients' cerebellar cortex. However, we also found significant bilateral gray matter reductions in pre and postcentral gyrus, inferior and medial frontal, parietal inferior, parahippocampal and occipital cortices. The analysis also showed a decrement in fractional anisotropy (p<0.05, corrected) of SCA7 patients in the cerebellum's white matter, brainstem, cerebellar and cerebral peduncles, midbrain, anterior and posterior internal capsule, external/extreme capsule, corpus callosum, corona radiata, optical radiations, and the occipital, temporal and frontal lobe's white matter. These results confirm previous evidence of widespread damage beyond the cerebellum and the pons in SCA7 patients. They also confirmed previous results that had been only detectable through neuropathological analyses and, more importantly, identified new regions affected by the disease that previous methods could not detect. These new results could help explain the symptom's spectrum that affects these patients.