Beyond the cerebellum: perivascular space burden in spinocerebellar ataxia type 3 extends to multiple brain regions.

Abstract

Spinocerebellar ataxia type 3 (SCA3) is an uncommon inherited (autosomal dominant) neurodegenerative disorder caused by abnormal accumulation of ataxin-3 protein. The perivascular space (PVS) burden reflects protein clearance and may worsen in SCA3 disease. This study aimed to quantify the PVS burden and investigate the relationship between the PVS burden and clinical characteristics in individuals with SCA3. This study enrolled 43 SCA3 patients and 43 age- and sex-matched healthy controls (HCs). The cross-sectional study assessed the severity of ataxia in SCA3 patients using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Various cognitive functions were evaluated in all subjects using the Montreal Cognitive Assessment (MoCA), Rapid Verbal Retrieval (RAR) and Digital Span Test (DST) scales. MRI was used to automatically segment the PVS in all subjects and quantify the PVS burden in 15 brain regions. Compared with the HCs, the SCA3 patients showed a significantly higher PVS burden in the basal ganglia, temporal lobe, right parietal lobe and right cerebellum. There was a positive correlation in motor dysfunction between the PVS volume in the left parietal lobe, right cerebellum and PVS number in the right cerebellum with the SARA and ICARS scores. This study showed that SCA3 patients have an increased PVS burden in many brain regions, leading to motor impairment. The PVS burden could be a new imaging biomarker for disease monitoring and a therapeutic target for SCA3.