Subcortical shape alterations in spinocerebellar ataxia type 2: a longitudinal MRI-based analysis

Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominant neurodegenerative disorder characterized by cerebellar and extracerebellar involvement. Although volumetric MRI studies have demonstrated cerebellar and supratentorial gray matter changes, region-specific shape alterations of subcortical structures remain insufficiently characterized. This study aimed to investigate cross-sectional and longitudinal subcortical gray matter shape changes in genetically confirmed SCA2 using a vertex-based morphometric approach.

Structural T1-weighted MRI data from nine patients with genetically confirmed SCA2 and sixteen age- and sex-matched healthy controls were obtained from the publicly available OpenNeuro repository. All participants underwent baseline imaging and follow-up scans after a mean interval of approximately 3.5 years. Subcortical structures were segmented using the FSL-FIRST framework. Vertex-wise shape analyses were performed using permutation-based statistics adjusted for age, sex, and total brain volume. eTIV-normalized subcortical volumetric analyses were also performed to assess cross-sectional and longitudinal volume differences between groups.

Compared with healthy controls, patients with SCA2 demonstrated localized outward shape deformations in the right hippocampus, left caudate nucleus, and left putamen (p < 0.05, FWE-corrected). Longitudinal analyses revealed more pronounced deformation patterns involving the left caudate nucleus, left pallidum, and left putamen in the SCA2 group compared with temporal changes observed in controls (p < 0.05, FWE-corrected). eTIV-normalized volumetric analyses demonstrated significantly reduced brainstem and bilateral thalamic volumes in patients with SCA2 at both baseline and follow-up assessments. In longitudinal analyses, significantly greater volume loss was observed in the left pallidum and bilateral hippocampi in the SCA2 group.

Vertex-based shape analysis demonstrated progressive and region-specific subcortical abnormalities in SCA2 and revealed morphological alterations that were only partially captured by conventional volumetric measurements. The partial concordance between shape-based and volumetric findings, particularly in the left pallidum, supports the biological relevance of the observed structural changes. Together, shape and volumetric analyses provide complementary information and may improve the characterization of subcortical involvement and longitudinal disease-related changes in SCA2.