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Turning movements in real life capture subtle longitudinal and preataxic changes in cerebellar ataxia

Annika Thierfelder, Jens Seemann, Natalie John, Martin Giese, Ludger Schöls, Dagmar Tinmann, Matthis Synofzik, Winfried Ilg

biorXiv:2021.03.22.436330, 2021.


OBJECTIVES Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints which capture change in ataxia severity in patients’ real life. This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real life turning movements which are sensitive for changes both longitudinally and at the preataxic stage.METHODS Combined cross-sectional (n=30) and longitudinal (n=14, 1-year interval) observational study in degenerative cerebellar disease (including 8 pre-ataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body-worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real-life movements.RESULTS Measures which quantified dynamic balance during turning – lateral velocity change (LVC) and outward acceleration –, but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life with high effect size (δ=0.68), with LVC also differentiating preataxic against healthy subjects (δ=0.53). LVC was highly correlated with clinical ataxia severity (SARA score, effect size ρ=0.79) and subjective balance confidence (ABC score, ρ=0.66). Moreover, LVC in real life – but not general turning measures, gait measures, or the SARA score – allowed detecting significant longitudinal change in one-year follow-up with high effect size (rprb=0.66).CONCLUSIONS Measures of turning allow to capture specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers for capturing change in real life, even in the highly treatment-relevant early stages of degenerative cerebellar disease.



@techreport{thierfelder21_biorxiv, author = {Thierfelder, Annika and Seemann, Jens and John, Natalie and Giese, Martin and Schöls, Ludger and Tinmann, Dagmar and Synofzik, Matthis and Ilg, Winfried}, title = {Turning movements in real life capture subtle longitudinal and preataxic changes in cerebellar ataxia}, year = {2021}, doi = {10.1101/2021.03.22.436330} }