Early and Progressive Spinal Cord Atrophy in Spinocerebellar Ataxia Type 1

Spinocerebellar ataxia type 1 (SCA1) is a rare, autosomal dominant neurodegenerative disorder characterized by progressive cerebellar and brainstem degeneration. Previous studies have shown that spinal cord atrophy is also a key aspect of SCA1 neuropathology. Magnetic resonance imaging (MRI)-based spinal cord measurements could, therefore, serve as staging or monitoring biomarkers. However, previous findings were limited to cross-sectional analyses, and longitudinal changes remain unexplored.

This study investigates both cross-sectional and longitudinal cervical spinal cord alterations in SCA1 mutation carriers compared to healthy controls, evaluating the utility of this biomarker.

Baseline and 1-year MRI changes were assessed in 40 controls, 16 preataxic and 58 symptomatic SCA1 mutation carriers. T1-weighed images were processed with FreeSurfer and the Spinal Cord Toolbox. We related Z-scores to disease duration, calculated standardized response means, and analyzed clinico-genetic associations using a linear mixed model.

The three groups differed significantly in cross-sectional area (CSA) at all levels at baseline. Over time, CSA at levels C1 and C2 decreased in the preataxic and symptomatic groups compared to controls. Preataxic carriers already showed pronounced spinal cord atrophy, whereas pontine changes emerged later in the disease course. Standardized response means were highest for CSA at C2 in preataxic stage, whereas this was pontine volume at symptomatic stage, indicating region-specific biomarkers across disease stages.

Cervical spinal cord atrophy is an early and progressive feature of SCA1, detectable before clinical onset, providing a promising imaging biomarker for early disease stages. Our findings suggest a caudal to rostral progression of atrophy in SCA1. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.