Early and Progressive Spinal Cord Atrophy in Spinocerebellar Ataxia Type 1

Area of Science:

• Neurodegenerative disorders
• Neuroimaging biomarkers
• Spinal cord imaging

Background:

• Spinocerebellar Ataxia type 1 (SCA1) is a rare, autosomal dominant neurodegenerative disorder.
• SCA1 involves progressive cerebellar and brainstem degeneration, with spinal cord atrophy also being a key neuropathological feature.
• Previous research on spinal cord atrophy in SCA1 was limited to cross-sectional studies, leaving longitudinal changes unexplored.

Purpose of the Study:

• To investigate cross-sectional and longitudinal cervical spinal cord alterations in SCA1 mutation carriers versus healthy controls.
• To evaluate the utility of spinal cord measurements as a biomarker for SCA1 staging and monitoring.

Main Methods:

• Assessed baseline and 1-year MRI changes in 40 controls, 16 preataxic, and 58 symptomatic SCA1 mutation carriers.
• Utilized FreeSurfer and Spinal Cord Toolbox for T1-weighted image processing.
• Analyzed clinico-genetic associations using linear mixed models and calculated standardized response means.

Main Results:

• Significant differences in cross-sectional area (CSA) at all spinal cord levels were observed at baseline across the three groups.
• CSA at C1 and C2 levels decreased longitudinally in preataxic and symptomatic SCA1 carriers compared to controls.
• Preataxic SCA1 carriers exhibited pronounced spinal cord atrophy, while pontine changes appeared later in the disease course.

Conclusions:

• Cervical spinal cord atrophy is an early and progressive feature of SCA1, detectable even before clinical onset.
• Spinal cord measurements serve as a promising imaging biomarker for identifying early disease stages in SCA1.
• Findings suggest a caudal-to-rostral progression of atrophy in SCA1, with region-specific biomarkers varying by disease stage.