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Giordano, Ilaria; Harmuth, Florian; Jacobi, Heike; Paap, Brigitte; Vielhaber, Stefan; Machts, Judith; Schöls, Ludger; Synofzik, Matthis; Sturm, Marc; Tallaksen, Chantal; Wedding, Iselin M.; Bösch, Sylvia; Eigentler, Andreas; Warrenburg, Bart van de; Gaalen, Judith van; Kamm, Christoph; Dudesek, Ales; Kang, Jun-Suk; Timmann, Dagmar; Silvestri, Gabriella; Masciullo, Marcella; Klopstock, Thomas; Neuhofer, Christiane; Ganos, Christos; Filla, Alessandro; Bauer, Peter; Montcel, Sophie Tezenas du; Klockgether, Thomas (2017): Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia. In: Neurology, Vol. 89, No. 10: pp. 1043-1049


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.