Clinical and Genetic Characteristics of Sporadic Adult-Onset Degenerative Ataxia

Neurology. 2017 Sep 5;89(10):1043-1049. doi: 10.1212/WNL.0000000000004311. Epub 2017 Aug 9.

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.

Conclusion

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.

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Authors

  • Ilaria Giordano , MD
  • Florian Harmuth
  • Heike Jacobi , MD
  • Brigitte Paap , PhD
  • Stefan Vielhaber , MD
  • Judith Machts
  • Ludger Schöls , MD
  • Matthis Synofzik , MD
  • Marc Sturm , PhD
  • Chantal Tallaksen , MD
  • Iselin Wedding , MD
  • Sylvia Boesch , MD
  • Andreas Eigentler , MD
  • Bart van de Warrenburg , MD
  • Judith van Gaalen , MD
  • Christoph Kamm , MD
  • Ales Dudesek , MD
  • Jun-Suk Kang , MD
  • Dagmar Timmann , MD
  • Gabriella Silvestri , MD
  • Marcella Masciullo , MD
  • Prof. Thomas Klopstock , MD
  • Christiane Neuhofer , MD
  • Christos Ganos , MD
  • Alessandro Filla , MD
  • Dr. Peter Bauer , MD
  • Sophie Tezenas du Montcel , MD, PhD
  • Thomas Klockgether , MD

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