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Multicenter Study
. 2024 May;39(5):788-797.
doi: 10.1002/mds.29757. Epub 2024 Feb 28.

Digital Gait Measures Capture 1-Year Progression in Early-Stage Spinocerebellar Ataxia Type 2

Jens Seemann  1   2 , Lina Daghsen  3 , Matthieu Cazier  3 , Jean-Charles Lamy  3 , Marie-Laure Welter  3 , Martin A Giese  1   2 , Matthis Synofzik  4   5 , Alexandra Durr  3 , Winfried Ilg  1   2 , Giulia Coarelli  3
Affiliations
Multicenter Study

Digital Gait Measures Capture 1-Year Progression in Early-Stage Spinocerebellar Ataxia Type 2

Jens Seemann et al. Mov Disord. 2024 May.

Abstract

Background: With disease-modifying drugs in reach for cerebellar ataxias, fine-grained digital health measures are highly warranted to complement clinical and patient-reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease.

Objective: Our aim is to unravel gait measures sensitive to longitudinal change in the-particularly trial-relevant-early stage of spinocerebellar ataxia type 2 (SCA2).

Methods: We performed a multicenter longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n = 23, including nine pre-ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focused on gait measures of spatio-temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation).

Results: We found significant changes for gait measures between baseline and 1-year follow-up with large effect sizes (lateral step deviation P = 0.0001, effect size rprb = 0.78), whereas the SARA score showed no change (P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test-retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1-year change.

Conclusions: Gait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just 1 year-in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: SCA2; gait; longitudinal analysis; motor performance measure; spinocerebellar ataxia.

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References

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