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Journal Articles Neurology Year : 2017

Clinical and Genetic Characteristics of Sporadic Adult-Onset Degenerative Ataxia

Ilaria Giordano
  • Function : Author
Florian Harmuth
  • Function : Author
Heike Jacobi
  • Function : Author
Brigitte Paap
  • Function : Author
Stefan Vielhaber
  • Function : Author
Judith Machts
  • Function : Author
Ludger Schöls
  • Function : Author
Matthis Synofzik
  • Function : Author
Marc Sturm
  • Function : Author
Chantal Tallaksen
  • Function : Author
Iselin M. Wedding
  • Function : Author
Sylvia Boesch
  • Function : Author
Andreas Eigentler
  • Function : Author
Bart van De Warrenburg
  • Function : Author
Judith Van Gaalen
  • Function : Author
Christoph Kamm
  • Function : Author
Ales Dudesek
  • Function : Author
Jun-Suk Kang
  • Function : Author
Dagmar Timmann
  • Function : Author
Gabriella Silvestri
  • Function : Author
Marcella Masciullo
  • Function : Author
Thomas Klopstock
  • Function : Author
Christiane Neuhofer
  • Function : Author
Christos Ganos
  • Function : Author
Alessandro Filla
  • Function : Author
Peter Bauer
  • Function : Author
Thomas Klockgether
  • Function : Author

Abstract

Objective: To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations. Methods: The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing. Results: The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94 ± 0.74, p < 0.0001) and disease duration (0.22 ± 0.06 per additional year, p = 0.0007) were associated with a higher SARA score. Forty-eight participants who did not fulfill MSA-C criteria and had a disease duration of >10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6 ± 6.0 vs 16.0 ± 5.8, p = 0.0200) and a slower annual SARA increase (1.1 ± 2.3 vs 3.3 ± 3.2, p = 0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made. Conclusions: Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort. ClinicalTrials.gov registration: NCT02701036.

Dates and versions

hal-03888710 , version 1 (07-12-2022)

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Ilaria Giordano, Florian Harmuth, Heike Jacobi, Brigitte Paap, Stefan Vielhaber, et al.. Clinical and Genetic Characteristics of Sporadic Adult-Onset Degenerative Ataxia. Neurology, 2017, 89 (10), pp.1043--1049. ⟨10.1212/WNL.0000000000004311⟩. ⟨hal-03888710⟩
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