Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: A longitudinal cohort study

Heike Jacobi, Sophie Tezenas du Montcel, Peter Bauer, Paola Giunti, Arron Cook, Robyn Labrum, Michael H. Parkinson, Alexandra Durr, Alexis Brice, Perrine Charles, Cecilia Marelli, Caterina Mariotti, Lorenzo Nanetti, Marta Panzeri, Maria Rakowicz, Anna Sulek, Anna Sobanska, Tanja Schmitz-Hübsch, Ludger Schöls, Holger HengelLaszlo Baliko, Bela Melegh, Alessandro Filla, Antonella Antenora, Jon Infante, José Berciano, Bart P. van de Warrenburg, Dagmar Timmann, Sandra Szymanski, Sylvia Boesch, Jun Suk Kang, Massimo Pandolfo, Jörg B. Schulz, Sonia Molho, Alhassane Diallo, Thomas Klockgether

Research output: Contribution to journalArticlepeer-review


Background: Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6. Furthermore, we aimed to establish the order and occurrence of non-ataxia symptoms, and identify predictors of disease progression. Methods: In this longitudinal cohort study (EUROSCA), we enrolled men and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplained ataxia who were aged 18 years or older from 17 ataxia referral centres in ten European countries. Patients were seen every year for 3 years, and at irregular intervals thereafter. The primary outcome was the scale for the assessment and rating of ataxia (SARA), and the inventory of non-ataxia signs (INAS). We used linear mixed models to analyse progression. To account for dropouts, we applied a pattern-mixture model. This study is registered with ClinicalTrials.gov, number NCT02440763. Findings: Between July 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled. We analysed data for 462 patients with at least one follow-up visit. Median observation time was 49 months (IQR 35-72). SARA progression data were best fitted with a linear model in all genotypes. Annual SARA score increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6. The increase of the number of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3. In patients with SCA6, the number of non-ataxia symptoms increased linearly, but more slowly than in patients with SCA1, SCA2, and SCA3 (p

Original languageEnglish
Article number147
Pages (from-to)1101-1108
Number of pages8
JournalThe Lancet Neurology
Issue number11
Publication statusPublished - Nov 1 2015

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)


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