Gait Variability in Spinocerebellar Ataxia Assessed Using Wearable Inertial Sensors

Abstract

A BS TRACT: Background: Quantitative assessment of severity of ataxia-specific gait impairments from wearable technology could provide sensitive performance outcome measures with high face validity to power clinical trials. Objectives: The aim of this study was to identify a set of gait measures from body-worn inertial sensors that best discriminate between people with prodromal or manifest spinocerebellar ataxia (SCA) and age-matched, healthy control subjects (HC) and determine how these measures relate to disease severity. Methods: One hundred and sixty-three people with SCA (subtypes 1, 2, 3, and 6), 42 people with prodromal SCA, and 96 HC wore 6 inertial sensors while performing a natural pace, 2-minute walk. Areas under the receiver operating characteristic curves (AUC) were compared for 25 gait measures, including standard deviations as variability, to discriminate between ataxic and normal gait. Pearson's correlation coefficient assessed the relationships between the gait measures and severity of ataxia.Results: Increased gait variability was the most discriminative gait feature of SCA; toe-out angle variability (AUC = 0.936; sensitivity = 0.871; specificity = 0.896) and double-support time variability (AUC = 0.932; sensitivity = 0.834; specificity = 0.865) were the most sensitive and specific measures. These variability measures were also significantly correlated with the scale for the assessment and rating of ataxia (SARA) and disease duration. The same gait measures discriminated gait of people with prodromal SCA from the gait of HC (AUC = 0.610, and 0.670, respectively). Conclusions: Wearable inertial sensors provide sensitive and specific measures of excessive gait variability in both manifest and prodromal SCAs that are reliable and related to the severity of the disease, suggesting they may be useful as clinical trial performance outcome measures.

Digital gait biomarkers, but not clinical ataxia scores, allow to capture 1-year longitudinal change in Spinocerebellar ataxia type 3 (SCA3)

“…Measures describing the variability of gait pattern have proven cross-sectional sensitivity to ataxia severity in a wide range of recording methods 30, 31 including marker-based capturing systems as gold standard 9, 10, 21 , gait mattresses 13, 20 , wearable inertial sensors 4, 5, 7, 8 , and camera-based systems 6 like the multi-kinect system 19 .…”

“…Thus, larger future studies are needed, including in particular a higher number of pre-ataxic subjects, to further validate the promises of gait measures. In future multi-center studies, the gait measures identified here might also be assessed not by a stationary analysis set-up, but rather by wearable inertial sensors 4, 5, 8 , which would -as important for ecological relevance-also allow assessments of these measures in patients’ real life 4, 34 .…”

“…With disease-modifying drugs on the horizon for degenerative ataxias 1,2 , sensitive motor biomarkers are highly warranted. Gait variability measures including step variability and body sway have shown their sensitivity to ataxia severity in multiple cross-sectional studies, correlating with clinical ataxia scores [3][4][5][6][7][8][9][10][11][12][13][14][15] . However, correlations with ataxia scores in cross-sectional studies are strongly influenced by the range of disease severity (range of observations 16 ): For cohorts that encompass a wide range of disease stages, many gait measures -including unspecific ones like gait speed-show significant correlation to disease severity, often predominantly driven by subjects at the ends of the spectrum of disease severity 16 .…”

Real-life Wrist Movement Patterns Capture Motor Impairment in Individuals with Ataxia-Telangiectasia

“…Wearable sensors with inertial measurement units (IMU) that contain triaxial accelerometers have been used in A-T and other pediatric ataxias to measure aspects of limb motor impairment during in-clinic administered tasks [ 12 – 15 ]. Multi-sensor IMU systems have been successfully used both inside [ 16 – 19 ] and outside [ 20 ] the clinic to quantify gait impairments in different ataxias. These are promising technologies for objective quantification of motor impairment but have limitations in that they are not applicable across all ages and are not designed to accommodate frequent, at-home use in children.…”

System Comparison for Gait and Balance Monitoring Used for the Evaluation of a Home-Based Training

“…Due to their broad availability and the convenient option to implement applications, they may provide an attractive hands-on tool for measuring gait and balance in home-based settings. However, this set-up has been applied only recently in the field of motion analyses [10,11] and is not yet part of the standard clinical tools of measuring gait and balance.…”