Journal of Neurology

, Volume 261, Issue 2, pp 291–299 | Cite as

White matter damage is related to ataxia severity in SCA3

  • J.-S. Kang
  • J. C. Klein
  • S. Baudrexel
  • R. Deichmann
  • D. Nolte
  • R. Hilker
Original Communication


Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.


Spinocerebellar ataxia 3 Machado-Joseph disease DTI Diffusion Ataxia 



This study was funded by Goethe-University of Frankfurt.

Conflicts of interest

Jun-Suk Kang received honoraria and travel funding from GlaxoSmithKline, Ipsen Pharma, Merz Pharma, Teva Pharma, and Medtronic. Johannes C Klein reports no financial disclosures. Simon Baudrexel reports no financial disclosures. Dagmar Nolte reports no financial disclosures. Ruediger Hilker has received speaker honoraria from Medtronic, Orion, GlaxoSmithKline, TEVA, Cephalon, Solvay, Desitin, and Boehringer Ingelheim as well as travel funding from Medtronic and Cephalon; serves or has served on a scientific advisory board for Cephalon; and has received research funding from the Deutsche Parkinson Vereinigung (dPV), Bundesministerium für Bildung und Forschung and the Goethe-University of Frankfurt.

Supplementary material

415_2013_7186_MOESM1_ESM.pdf (23 kb)
Supplementary Table 1: Clusters of grey and white matter loss, together with the MNI-space coordinate and p-value of the cluster peak. (PDF 22 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • J.-S. Kang
    • 1
    • 2
  • J. C. Klein
    • 1
    • 2
  • S. Baudrexel
    • 1
    • 2
  • R. Deichmann
    • 2
  • D. Nolte
    • 3
  • R. Hilker
    • 1
  1. 1.Department of NeurologyGoethe-University of FrankfurtFrankfurt am MainGermany
  2. 2.Brain Imaging Center (BIC)Goethe-University of FrankfurtFrankfurt am MainGermany
  3. 3.Institute of Human GeneticsUniversity of GiessenGiessenGermany

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