Hypothalamic Atrophy and Textural Changes in Polyglutamine Ataxias

Background. Spinocerebellar ataxia (SCA) presents a complex genetic landscape, with over 40 subtypes. These autosomal dominant disorders manifest late onset and severe disability, primarily impacting the cerebellum but also involving other nervous system structures. While a single study has linked hypothalamic atrophy to SCA3, further research is needed to confirm and/or expand this association. This study aimed to investigate hypothalamic involvement in PolyQ SCAs, focusing on SCA 1, 2, 3, and 6. Methods. We studied 135 adult patients with genetically confirmed SCA (SCA1, SCA2, SCA3, and SCA6) and 117 healthy controls. Hypothalamic subregions were segmented using H-SynEx, and both volumetric and texture features were extracted from MR images. Group differences were assessed with the Mann–Whitney U test, and associations with disease duration and severity (measured by SARA) were examined using Spearman’s rank correlation. Results. Significant atrophy of hypothalamic subregions was observed in SCA1, SCA3, and SCA6 when compared with controls, with the anterior subregion being affected in all cases. Texture analysis revealed widespread alterations in SCA1, SCA3, and SCA6 across all subregions. In SCA1 and SCA3, both volumetric and texture measures correlated with disease duration and SARA scores. These findings suggest that hypothalamic involvement in SCAs is complex and may occur before overt clinical manifestations. Key words: Ataxia, Polyglutamine disease, Hypothalamus, MRI, Volumetry