title: Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.
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.
authors.affiliation: Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.|Center of Old Age Psychiatry, Psychiatric University Hospital, Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Linnemann
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Biostatistics Unit, Paris, France.|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.|INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tezenas du Montcel
authors.affiliation: Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Maryla
authors.initials: M
authors.lastname: Rakowicz
authors.affiliation: Department of Neurology, University of Bonn, Bonn, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schmitz-Hübsch
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Szymanski
authors.affiliation: Department of Neurology, University Hospital Marqués de Valldecilla, IDIVAL, CIBERNED and UC, Santander, Spain.|Department of Clinical Neurophysiology, University Hospital Marqués de Valldecilla, IDIVAL, CIBERNED and UC, Santander, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Berciano
authors.affiliation: Department of Neurology, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Bart P
authors.initials: BP
authors.lastname: van de Warrenburg
authors.affiliation: Department of Neurology, University of Brussels, Brussels, Belgium.
authors.forename: Karine
authors.initials: K
authors.lastname: Pedersen
authors.affiliation: Department of Neurology, University of Brussels, Brussels, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Depondt
authors.affiliation: Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Rola
authors.affiliation: Department of Neurology, University of Bonn, Bonn, Germany.|German Research Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klockgether
authors.affiliation: Department of Neurology, University Hospital Marqués de Valldecilla, IDIVAL, CIBERNED and UC, Santander, Spain.|Department of Clinical Neurophysiology, University Hospital Marqués de Valldecilla, IDIVAL, CIBERNED and UC, Santander, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Biostatistics Unit, Paris, France.
authors.forename: Gurkan
authors.initials: G
authors.lastname: Mutlu
authors.affiliation: Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. Ludger.Schoels@uni-tuebingen.de.|German Research Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Ludger.Schoels@uni-tuebingen.de.
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015220:Calcium Channels / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009431:Neural Conduction / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000235:genetics*; D055815:Young Adult
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins
keywords: Electrophysiology; Nerve conduction; Peripheral neuropathy; Progression marker; Spinocerebellar ataxia