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Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study

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Abstract

Background

Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations.

Methods

We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations.

Results

We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt–Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich’s ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01).

Conclusion

Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

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Funding

The authors received a grant from the association “Connaître les syndromes cérébelleux” (CSC).

Author information

Author notes

  1. T. Bogdan, T. Wirth have contributed equally to this work.

Authors and Affiliations

  1. Neurology Department, Strasbourg University Hospital, Strasbourg, France

    T. Bogdan, T. Wirth, A. Iosif, S. Montaut, C. Bonnard, G. Carre, O. Lagha-Boukbiza, C. Reschwein, E. Albugues, S. Demuth, H. Landsberger, M. Einsiedler, T. Parratte, A. Nguyen, F. Lamy, H. Durand, P. Fahrer, P. Voulleminot, K. Bigaut, J. B. Chanson, C. Tranchant & M. Anheim

  2. Strasbourg Federation of Translational Medicine (FMTS), Strasbourg University, Strasbourg, France

    T. Wirth, A. Schalk, C. Tranchant & M. Anheim

  3. INSERM-U964; CNRS-UMR7104, University of Strasbourg, Illkirch-Graffenstaden, France

    T. Wirth, C. Tranchant & M. Anheim

  4. Laboratory of Genetic Diagnosis, IGMA, Strasbourg University Hospital, Strasbourg, France

    A. Schalk, J. Chelly & N. Calmels

  5. Department of Genetics and CNRMAJ, FHU G4 Génomique, Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, 76000, Rouen, France

    G. Nicolas

  6. Neurogenetics Laboratory, Department of Genetics, APHP, University Hospital Pitié-Salpêtrière, Paris, France

    C. Cazeneuve

  7. Laboratory of Molecular Genetics, Montpellier University Hospital, Montpellier, France

    M. Koenig

  8. Department of Nuclear Medicine, Strasbourg University Hospital, Strasbourg, France

    C. Bund & I. J. Namer

  9. Department of Nuclear Medicine and Molecular Imaging, ICANS, Strasbourg, France

    C. Bund & I. J. Namer

  10. Department of Radiology, Strasbourg University Hospital, Strasbourg, France

    S. Kremer

Authors
  1. T. Bogdan
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  2. T. Wirth
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  3. A. Iosif
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  4. A. Schalk
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  5. S. Montaut
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  8. O. Lagha-Boukbiza
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  9. C. Reschwein
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  15. A. Nguyen
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  16. F. Lamy
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  20. K. Bigaut
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  22. G. Nicolas
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  30. C. Tranchant
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  31. M. Anheim
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Contributions

All authors contributed to the investigation and writing—review and editing of the study. Project administration and supervision were performed by Christine Tranchant and Mathieu Anheim. Visualization and writing–original draft preparation were performed by Thomas Bogdan, Thomas Wirth, and Mathieu Anheim. Conceptualization and methodology were performed by Thomas Bogdan, Thomas Wirth, Andra Iosif, Christine Tranchant, and Mathieu Anheim. Formal analysis was performed by Thomas Bogdan and Thomas Wirth. Data curation was performed by Thomas Bogdan, Thomas Wirth, and Andra Iosif. Resources were obtained from Audrey Schalk, Jean-Baptiste Chanson, Gaël Nicolas, Jamel Chelly, Michel Koenig, Cécile Cazeneuve, Caroline Bund, Izzie-Jacques Namer, Stéphane Kremer, and Nadège Calmels. Funding acquisition was performed by Mathieu Anheim.

Corresponding author

Correspondence to T. Bogdan.

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The authors declare that they have no conflict of interest.

Ethical approval

Approval was obtained from the local ethics committee of Strasbourg University Hospital.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

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Bogdan, T., Wirth, T., Iosif, A. et al. Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study. J Neurol 269, 6354–6365 (2022). https://doi.org/10.1007/s00415-022-11253-1

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  • DOI: https://doi.org/10.1007/s00415-022-11253-1

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