Tract-specific spinal damage in SCA2, SCA3 and SCA6

J Neurol. 2024 Dec 12;272(1):6. doi: 10.1007/s00415-024-12791-6.

Abstract

Background: Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders characterized by progressive ataxia. Although previous studies have focused on cerebral and cerebellar damage, spinal cord involvement in SCAs remains underexplored.

Objectives: This study aims to characterize spinal cord abnormalities in SCA2, SCA3, and SCA6 and to identify its phenotypic correlates.

Methods: We conducted a multimodal spinal neuroimaging study on 26 SCA3, 16 SCA2, and 14 SCA6 patients, along with matched healthy controls. MRI scanning was performed using a 3 Tesla device, and the Spinal Cord Toolbox (SCT) was employed for morphometric and diffusivity analyses of the cervical spinal cord.

Results: Our findings revealed significant spinal cord atrophy and altered white matter microstructural metrics in SCA3 and SCA2 patients compared to controls, with no abnormalities in SCA6. A strong negative correlation was observed between cross-sectional cord area and disease duration in SCA2, suggesting its potential as a biomarker for disease progression.

Conclusions: This study highlights the importance of spinal cord imaging in understanding the pathophysiology of SCAs and demonstrates the utility of MRI-based metrics in identifying structural deviations and their clinical correlates. Further longitudinal studies are needed to validate these findings and explore their implications for clinical trials and therapeutic interventions.

Keywords: MRI; SCA2; SCA3; SCA6; Spinal cord toolbox; Spinocerebellar ataxia.

MeSH terms

  • Adult
  • Aged
  • Ataxin-2
  • Atrophy / pathology
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Machado-Joseph Disease / diagnostic imaging
  • Machado-Joseph Disease / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / pathology
  • Spinocerebellar Ataxias* / diagnostic imaging
  • Spinocerebellar Ataxias* / pathology
  • White Matter / diagnostic imaging
  • White Matter / pathology

Substances

  • ATXN2 protein, human
  • Ataxin-2

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