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Cerebellar degeneration in adult spinal muscular atrophy patients

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Abstract

Background

Spinal muscular atrophy (SMA) is a genetic motor neuron disease related to deletions in the SMN1 gene. There is mounting evidence that the disease is not restricted to motor neurons. In this neuroimaging study, we aimed to investigate the presence of in-vivo cerebellar damage in adult SMA patients not treated with disease-modifying treatment.

Methods

Twenty-five molecularly confirmed patients with SMA type III or IV and 25 healthy controls underwent MRI with cerebellar focused structural analysis by the CERES automated pipeline. Volumetry (total and gray matter—GM) as well as cortical thickness of the cerebellar lobules were compared in both groups. Full clinical and demographic data were then assessed for correlations with cerebellar imaging findings.

Results

Volumes of cerebellar lobules VIIIB (right), IX and X were significantly smaller in patients with SMA. Lobule IX also had GM atrophy in comparison to controls. We found no significant correlation between clinical findings and cerebellar damage.

Conclusions

Neuroimaging detects cerebellar structural changes in adult SMA patients, suggesting that neurodegeneration is not confined to the lower motor neurons in the disease.

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Acknowledgements

We would like to thank Ms. Rosa Marcuso and Dr. Carlos Roberto Martins Jr. for the invaluable advice on statistical analysis and study design. We thank Mm. Sophie Blancho (IRME) for the management of the project. We thank the clinicians who recruited patients (Drs Pascal Laforet, Tanya Stojkovic, Anthony Behin, François Salachas, Nadine le Forestiers). We also acknowledge the kindness and willingness of our patients and volunteer healthy controls for contributing to science and a greater good.

Funding

This study was supported by the Association Française contre les Myopathies (AFM) and the Institut pour la Recherche sur la Moelle épinière et l’Encéphale (IRME). The research leading to these results has also received funding from the program “Investissements d’avenir” ANR 10-IAIHU-06.

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Authors and Affiliations

  1. Department of Neurology, University of Campinas, Campinas, Brazil

    Fabrício Castro de Borba & Marcondes Cavalcante França Jr

  2. Laboratoire d’Imagerie Biomédicale, Sorbonne Université, CNRS, INSERM, Paris, France

    Giorgia Querin & Pierre-François Pradat

  3. Département de Neurologie, APHP, Hôpital Pitié-Salpêtrière, Centre référent SLA, 47 Boulevard de l’Hôpital, 75634, Paris, Cedex 13, France

    Pierre-François Pradat

  4. Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute Ulster University, C-TRIC, Altnagelvin Hospital, Derry/Londonderry, UK

    Pierre-François Pradat

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  1. Fabrício Castro de Borba
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Corresponding author

Correspondence to Pierre-François Pradat.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures of this study followed the institution’s ethic committee standards and the Declaration of Helsinki.

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de Borba, F.C., Querin, G., França, M.C. et al. Cerebellar degeneration in adult spinal muscular atrophy patients. J Neurol 267, 2625–2631 (2020). https://doi.org/10.1007/s00415-020-09875-4

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  • DOI: https://doi.org/10.1007/s00415-020-09875-4

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