Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers

Abstract

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.

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

“…In particular, our study cohort was not sufficiently powered for detecting longitudinal change within the pre-ataxic group only. Therefore, larger future studies, including a larger number of pre-ataxic subjects, are needed to further validate the promises of gait measures and relate longitudinal changes in gait to patientcentered outcomes and patient-meaningful aspects of health 53,57,58 as well as to corresponding changes in molecular (such as blood neurofilament light chain) 59,60 and imaging biomarkers. 61 G A I T…”

At-home Wearable-based Monitoring and Machine Learning Predicts Clinical Measures and Biological Biomarkers of Disease Severity in Friedreich's Ataxia

“…Recent studies have yielded encouraging outcomes by using wearable sensors to quantify clinical evaluations such as SARA and mFARS, aiming to mitigate the inaccuracies associated with subjective clinical assessments [23][24][25][26][27][28]. However, these approaches still require supervised assessments, which is only feasible within clinical settings.…”

“…This is of paramount importance due to the potential discrepancy between a brief examination in an outpatient clinic, where an individual with ataxia may appear to walk and maintain balance better than what caregivers report witnessing in their daily lives. Furthermore, relying on a single, or infrequently administered, mobility assessment cannot adequately capture day-to-day variations or other clinically pertinent periods of change, such as daily uctuations in motor function or the in uence of fatigue [23].…”

Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation

“…The ST, feet apart conditions were based on the Modified Clinical Test of Sensory Integration in Balance (mCTSIB), which is used to detect abnormal sensory–motor integration for postural control [ 38 ]. Other groups, including ours, have used similar protocols to analyze postural control under conditions of altered sensory input and narrowing the base of support while measuring postural sway with wearable inertial sensors in patients with movement disorders [ 34 , 39 , 40 ]. Participants also performed four trials in firm stance conditions under a DT condition.…”