Temporal Dynamics of the Scale for the Assessment and Rating of Ataxia in Spinocerebellar Ataxias

Paul Moulaire (1, 2, 3, 4) , Pierre Emmanuel Poulet , Emilien Petit (1, 2, 5, 6, 4) , Thomas Klockgether (7) , Alexandra Durr (1, 2, 5, 6, 4) , Tetsuo Ashisawa (8) , Sophie Tezenas Du Montcel (2, 5, 6, 4, 9)

1 SU - Sorbonne Université
2 ICM - Institut du Cerveau = Paris Brain Institute
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
5 INSERM - Institut National de la Santé et de la Recherche Médicale
6 CNRS - Centre National de la Recherche Scientifique
7 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
8 Houston Methodist Hospital [Houston, TX, USA]
9 ARAMIS - Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris]

Background The Scale for the Assessment and Rating of Ataxia (SARA) is the reference clinical scale to assess the severity of cerebellar ataxia. In the context of upcoming therapeutic trials, a reliable clinical outcome is needed to assess the efficiency of treatments. Objective The aim is to precisely assess and compare temporal dynamics of SARA and a new f-SARA. Methods We analyzed data from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) comprising 1210 participants and 4092 visits. The linearity of the progression and the variability were assessed using an ordinal Bayesian mixed-effect model (Leaspy). We performed sample size calculations for therapeutic trials with different scenarios to improve the responsiveness of the scale. Results Seven of the eight different items had a nonlinear progression. The speed of progression was different between most of the items, with an average time for a one-point increase from 3.5 years [3.4; 3.6] (median, 95% credible interval) for the fastest item to 11.4 [10.9; 12.0] years. The total SARA score had a linear progression with an average time for a one-point increase of 0.95 [0.92; 0.98] years. After removing the four last items and rescaling all items from 0 to 4, variability increased and progression was slower and thus would require a larger sample size in a future therapeutic trial. Conclusion Despite a heterogeneous temporal dynamics at the item level, the global progression of SARA was linear. Changing the initial scale deteriorates the responsiveness. This new information about the temporal dynamics of the scale should help design the outcome of future clinical trials.

Mots clés: disease course mapping; spinocerebellar ataxia; Scale for the Assessment and Rating of Ataxia

Domaines: Méthodologie [stat.ME]; Neurobiologie

Paul Moulaire, Pierre Emmanuel Poulet, Emilien Petit, Thomas Klockgether, Alexandra Durr, et al.. Temporal Dynamics of the Scale for the Assessment and Rating of Ataxia in Spinocerebellar Ataxias. Movement Disorders, 2023, 38 (1), pp.35-44. ⟨10.1002/mds.29255⟩. ⟨hal-03831598v2⟩