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.
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