• Audrey Tanguy Melac, Caterina Mariotti, Antoine Filipovic Pierucci, Paola Giunti, Javier Arpa, Sylvia Boesch, Thomas Klopstock, Jennifer Müller Vom Hagen, Thomas Klockgether, Katrin Bürk, Jörg B Schulz, Kathrin Reetz, Massimo Pandolfo, Alexandra Durr, Tezenas du MontcelSophieS0000-0002-2866-4330Department of Biostatistics and Medical Informatics, AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France.Sorbonne Universités, UPMC Univ Paris 06 UMR_S1136, Paris, France.INSERM UMR_S 1136, I, and EFACTS group.
• Department of Biostatistics and Medical Informatics, AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France.
• J. Neurol. Neurosurg. Psychiatr. 2018 Jun 1; 89 (6): 559-565.

BackgroundSensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction.MethodsWe evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively.ResultsThere were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores.ConclusionsCerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated.Trial Registration NumberClinicalTrials.gov: NCT02069509.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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