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Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6

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Abstract

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

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Acknowledgments

The study was supported by a grant from the European Union (LSHM-CT-2004-503304) to EUROSCA.

Conflict of Interest

Dr. Linnemann reports no disclosures. Dr. Tezenas du Montcel received research support from the European Union (EU) EUROSCA. Dr. Rakowicz received research support from the EU EUROSCA and from the Polish Ministry of Science. Dr. Schmitz-Hübsch received research support from the EU EUROSCA. Dr. Szymanski received research support from the EU EUROSCA. Dr. Berciano received research support from the EU EUROSCA. Dr. van de Warrenburg received research support from the EU EUROSCA, from the Gossweiler Foundation, from the Radboud University Medical Center, and from BBMRI-NL. Dr. Depondt served on a scientific advisory board for UCB; has received funding for travel from Pfizer Inc; and received research support from the EU EUROSCA and from the Fonds National de la Recherche Scientifique (FNRS, Belgium). Dr. Rola received research support from the EU EUROSCA and from the Polish Ministry of Science. Dr. Klockgether received/receives research support from the EU EUROSCA, the German Research Foundation (DFG), and the German Federal Ministry of Education and Research (BMBF). Dr. Garcia received research support from the EU EUROSCA. Dr. Mutlu reports no disclosures. Dr. Schöls received research grants of the DFG, BMBF, EU to EUROSCA, and HSP-Selbsthilfegruppe Deutschland e.V.

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Authors and Affiliations

  1. Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany

    Christoph Linnemann & Ludger Schöls

  2. Center of Old Age Psychiatry, Psychiatric University Hospital, Basel, Switzerland

    Christoph Linnemann

  3. AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Biostatistics Unit, Paris, France

    Sophie Tezenas du Montcel & Gurkan Mutlu

  4. Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, UMR_S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France

    Sophie Tezenas du Montcel

  5. INSERM, UMR_S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France

    Sophie Tezenas du Montcel

  6. Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland

    Maryla Rakowicz & Rafal Rola

  7. Department of Neurology, University of Bonn, Bonn, Germany

    Tanja Schmitz-Hübsch & Thomas Klockgether

  8. Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany

    Sandra Szymanski

  9. Department of Neurology, University Hospital Marqués de Valldecilla, IDIVAL, CIBERNED and UC, Santander, Spain

    Jose Berciano & Antonio García

  10. Department of Clinical Neurophysiology, University Hospital Marqués de Valldecilla, IDIVAL, CIBERNED and UC, Santander, Spain

    Jose Berciano & Antonio García

  11. Department of Neurology, Radboud University Medical Center, Nijmegen, Netherlands

    Bart P. van de Warrenburg

  12. Department of Neurology, University of Brussels, Brussels, Belgium

    Karine Pedersen & Chantal Depondt

  13. German Research Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Thomas Klockgether

  14. German Research Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany

    Ludger Schöls

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  1. Christoph Linnemann
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  2. Sophie Tezenas du Montcel
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  3. Maryla Rakowicz
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  4. Tanja Schmitz-Hübsch
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  9. Chantal Depondt
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  10. Rafal Rola
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  11. Thomas Klockgether
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  12. Antonio García
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  13. Gurkan Mutlu
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  14. Ludger Schöls
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Correspondence to Ludger Schöls.

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Linnemann, C., Tezenas du Montcel, S., Rakowicz, M. et al. Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6. Cerebellum 15, 165–173 (2016). https://doi.org/10.1007/s12311-015-0684-6

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  • DOI: https://doi.org/10.1007/s12311-015-0684-6

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