White matter functional and structural alterations of spinocerebellar ataxia type 3: A longitudinal MRI study

Widespread white matter (WM) microstructural abnormalities have been reported in patients with spinocerebellar ataxia type 3 (SCA3) using diffusion tensor imaging (DTI), whereas the ability of DTI to detect WM degeneration over short-term period remains insufficiently explored. Additionally, WM dysfunction remains entirely unknown in this disease. This study aims to investigate WM structural and functional alterations in SCA3, and provide promising progression biomarkers for short-term clinical trials. DTI and resting-state functional magnetic resonance imaging data of 52 SCA3 patients and 56 healthy controls (HCs) were collected at baseline. After a mean follow-up of 1 year, MRI scans were performed on a subset of 28 SCA3 patients. Compared with HCs, widespread WM structural and functional abnormalities were observed in patients with SCA3. Between-group differences of both structural and functional MR metrics showed remarkable similarities, with large differences located in pons and corticospinal tracts, involving cerebellar WM, cerebellar and cerebral peduncles, medial lemniscus and bilateral posterior limb of internal capsule (PLIC). The longitudinal analysis further showed decreased ALFF in the right PLIC and increased mean diffusivity in the left inferior cerebellar peduncle and right medial lemniscus over time in SCA3 patients. These findings emphasized that pons and the CST were the most vulnerable WM areas in SCA3, and have the potential to become therapeutic targets of SCA3 for upcoming interventional trials. In addition, both DT metrics and WM ALFF were efficient progression biomarkers for SCA3 even in short-term period.