Brain Structural Impairment in Spinocerebellar Ataxia Type 6: Not Restricted to the Cerebellum

Spinocerebellar ataxias (SCA) refer to a group of autosomal dominant ataxic disorders that result from the degeneration of the cerebellum and its connections. SCA6 is described as the prototype of pure cerebellar ataxia, with preservation of other brain regions. However, the calcium receptor subunit affected in SCA6 appears to be ubiquitous in neurons throughout the brain. Additionally, there are observations of clinical involvement of non-cerebellar systems, structural cerebral damage and hypometabolism in various brain areas. To characterize the structural brain signature in SCA6 patients. Eighteen SCA6 patients underwent cross-sectional analyses using multimodal MRI-based techniques, which combined cerebral and cerebellar volumetric analyses with diffusion tensor imaging (DTI). Furthermore, we investigated whether structural abnormalities correlated with clinical findings. Individuals with SCA6, compared to non-ataxic controls, exhibited significant volumetric reduction in cerebellar white matter, cortex, and several lobules. There was increased axial diffusivity (AD) in the left inferior cerebellar peduncle, bilateral middle cerebellar peduncle, left superior cerebellar peduncle, bilateral midbrain, right cerebral peduncle, left superior corona radiata, bilateral fornix-stria terminalis, left sagittal stratum, left genu of the corpus callosum, right body of the corpus callosum, and left optic tract. Significant correlations were found between AD and the Inventory of Non-ataxia Symptoms Count, and between cerebellar volumetry and both the International Cooperative Ataxia Rating Scale and the Epworth Sleepiness Scale. We provided valuable insights into the possible extracerebellar structural abnormalities associated with SCA6. However, further studies, ideally including longitudinal follow-up, are needed before DTI-based analyses of cerebellar connections and supratentorial structures can be considered potential sources of biomarkers.