@incollection{beichert2024longitudinal,
author = "Lukas Beichert and Jens Seemann and Christoph Kessler and Andreas Trasch{\"u}tz and Ivana Ricca and Sara Satolli and Ayşe Nazli Başak and Giulia Coarelli and Dagmar Timmann and Cynthia Gagnon and van de Warrenburg, Bart P. and PROSPAX consortium and Winfried Ilg and Matthis Synofzik and Rebecca Sch{\"u}le",
abstract = "Background and Objective: With treatment trials on the horizon, sensitive outcome measures are highly needed for the >100 spastic ataxias. Digital-motor gait measures, assessed by wearable sensors, are considered prime outcome candidates for spastic ataxias and have shown favourable cross-sectional properties in spastic paraplegia type 7 (SPG7). However, their longitudinal sensitivity to change is yet unknown. This study aimed to assess 1-year progression of digital gait measures in patients with SPG7.
Methods: Longitudinal multi-center study (7 centers, 6 countries), assessments at baseline and after 1 year. Gait was analysed in 49 SPG7 patients (baseline, median [min-max]: age=52 [22-69], SARA=9.0 [3.5-17.0], SPRS=14 [3-28]) using 3 wearable motion sensors (Opal APDM) during laboratory-based walking and ‘supervised free walking’, resembling real-life walking. Assessments included rating of the Scale for the assessment and rating of ataxia (SARA) and the Spastic paraplegia rating scale (SPRS). Effect size and significance of 1-year changes were assessed using non-parametric matched-pairs rank biserial correlation (rprb) and Wilcoxon signed-rank test, respectively.
Results: In laboratory-based walking, 1-year progression was observed for measures of trunk range of motion variability (CoronalRoM_CV: rprb=0.46, p=0.0051), of gait smoothness (harmonicRatioML: rprb=-0.40, p=0.015) and of spatiotemporal stride variability (e.g. DoubleSupport_MADN: rprb=0.31-0.37). In the trial-relevant subcohort of mildly affected patients (SPRS items 1-6≤9; n=34), CoronalRoM_CV (rprb=0.59, p=0.0027) exhibited larger effect size than clinician-reported outcomes like SARA (rprb=0.53, p=0.0055) or SPRS (rprb=0.30, p=0.087). In supervised free walking, progression was observed for measures of gait smoothness and temporal variability (e.g. harmonicRatioML, DoubleSupport_MADN: |rprb|=0.28-0.44).
Discussion and Conclusion: In this first longitudinal multi-center study of digital gait measures in SPG7, 1-year progression was captured for several gait measures, with effect sizes partly exceeding those of key clinician-reported outcomes (SARA, SPRS). These gait measures could thus improve sensitivity to treatment effects in future clinical trials in SPG7 and possibly also other spastic ataxias.",
booktitle = "2024 International Congress for Ataxia Research (ICAR) London",
title = "{L}ongitudinal progression of digital gait measures in patients with spastic paraplegia type 7 ({SPG}7): an international multi-center study ({PROSPAX})",
year = "2024",
}