Abstract：
BACKGROUND: With treatment trials on the horizon, this study aimed to identify candidate digital-motor gait outcomes for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), capturable by wearable sensors with multicenter validity, and ideally also ecological validity during free walking outside laboratory settings.
METHODS: Cross-sectional multicenter study (four centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body-worn sensors (Opal, APDM) in laboratory settings and free walking in public spaces. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (ie, clinical and patient relevance) validity by correlations with SPRSmobility (primary outcome) and Scale for the Assessment and Rating of Ataxia (SARA), Spastic Paraplegia Rating Scale (SPRS), and activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS-ADL) (exploratory outcomes).
RESULTS: Of 30 hypothesis-based digital gait measures, 14 measures discriminated ARSACS patients from controls with large effect sizes (|Cliff\'s δ| > 0.8) in laboratory settings, with strongest discrimination by measures of spatiotemporal variability Lateral Step Deviation (δ = 0.98), SPcmp (δ = 0.94), and Swing CV (δ = 0.93). Large correlations with the SPRSmobility were observed for Swing CV (Spearman\'s ρ = 0.84), Speed (ρ = -0.63), and Harmonic Ratio V (ρ = -0.62). During supervised free walking in a public space, 11/30 gait measures discriminated ARSACS from controls with large effect sizes. Large correlations with SPRSmobility were here observed for Swing CV (ρ = 0.78) and Speed (ρ = -0.69), without reductions in effect sizes compared with laboratory settings.
CONCLUSIONS: We identified a promising set of digital-motor candidate gait outcomes for ARSACS, applicable in multicenter settings, correlating with patient-relevant health aspects, and with high validity also outside laboratory settings, thus simulating real-life walking with higher ecological validity. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
METHODS: Cross-sectional multicenter study (four centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body-worn sensors (Opal, APDM) in laboratory settings and free walking in public spaces. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (ie, clinical and patient relevance) validity by correlations with SPRSmobility (primary outcome) and Scale for the Assessment and Rating of Ataxia (SARA), Spastic Paraplegia Rating Scale (SPRS), and activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS-ADL) (exploratory outcomes).
RESULTS: Of 30 hypothesis-based digital gait measures, 14 measures discriminated ARSACS patients from controls with large effect sizes (|Cliff\'s δ| > 0.8) in laboratory settings, with strongest discrimination by measures of spatiotemporal variability Lateral Step Deviation (δ = 0.98), SPcmp (δ = 0.94), and Swing CV (δ = 0.93). Large correlations with the SPRSmobility were observed for Swing CV (Spearman\'s ρ = 0.84), Speed (ρ = -0.63), and Harmonic Ratio V (ρ = -0.62). During supervised free walking in a public space, 11/30 gait measures discriminated ARSACS from controls with large effect sizes. Large correlations with SPRSmobility were here observed for Swing CV (ρ = 0.78) and Speed (ρ = -0.69), without reductions in effect sizes compared with laboratory settings.
CONCLUSIONS: We identified a promising set of digital-motor candidate gait outcomes for ARSACS, applicable in multicenter settings, correlating with patient-relevant health aspects, and with high validity also outside laboratory settings, thus simulating real-life walking with higher ecological validity. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
摘要：
背景：随着治疗试验的临近，这项研究旨在确定Charlevoix-Saguenay常染色体隐性遗传性痉挛性共济失调（ARSACS）的候选数字运动步态结果，可由具有多中心有效性的可穿戴传感器捕获，理想情况下，在实验室外自由行走期间也具有生态有效性。
方法：横断面多中心研究（四个中心），使用三个身体穿戴传感器（Opal，APDM）在实验室环境中，在公共场所自由行走。分析了传感器步态测量与对照的区分有效性，和收敛(即，临床和患者相关性）与SPRSmobility（主要结果）和共济失调评估和评级量表（SARA）的相关性的有效性，痉挛性截瘫评定量表（SPRS），和Friedreich共济失调评定量表（FARS-ADL）的日常生活活动评分（探索性结果）。
结果：在30种基于假设的数字步态测量中，在实验室设置中，14项措施将ARSACS患者与具有大效应大小（|Cliffδ|>0.8）的对照区分开来，通过时空变异性测量具有最强的辨别横向阶跃偏差(δ=0.98)，SPcmp(δ=0.94)，和摆动CV(δ=0.93)。对于SwingCV(Spearman'sρ=0.84)，观察到与SPRS流动性的相关性很大，速度（ρ=-0.63），和谐波比V(ρ=-0.62)。在公共场所有监督的自由行走期间，11/30步态测量将ARSACS与具有较大效应大小的对照区分开。在这里观察到SwingCV（ρ=0.78）和速度（ρ=-0.69）与SPRS迁移率的大相关性，与实验室设置相比，效果大小没有减少。
结论：我们确定了ARSACS的一组有希望的数字运动候选步态结果，适用于多中心设置，与患者相关的健康方面，在实验室环境之外也具有很高的有效性，从而以更高的生态有效性模拟现实生活中的步行。©2024作者（S）。由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
方法：横断面多中心研究（四个中心），使用三个身体穿戴传感器（Opal，APDM）在实验室环境中，在公共场所自由行走。分析了传感器步态测量与对照的区分有效性，和收敛(即，临床和患者相关性）与SPRSmobility（主要结果）和共济失调评估和评级量表（SARA）的相关性的有效性，痉挛性截瘫评定量表（SPRS），和Friedreich共济失调评定量表（FARS-ADL）的日常生活活动评分（探索性结果）。
结果：在30种基于假设的数字步态测量中，在实验室设置中，14项措施将ARSACS患者与具有大效应大小（|Cliffδ|>0.8）的对照区分开来，通过时空变异性测量具有最强的辨别横向阶跃偏差(δ=0.98)，SPcmp(δ=0.94)，和摆动CV(δ=0.93)。对于SwingCV(Spearman'sρ=0.84)，观察到与SPRS流动性的相关性很大，速度（ρ=-0.63），和谐波比V(ρ=-0.62)。在公共场所有监督的自由行走期间，11/30步态测量将ARSACS与具有较大效应大小的对照区分开。在这里观察到SwingCV（ρ=0.78）和速度（ρ=-0.69）与SPRS迁移率的大相关性，与实验室设置相比，效果大小没有减少。
结论：我们确定了ARSACS的一组有希望的数字运动候选步态结果，适用于多中心设置，与患者相关的健康方面，在实验室环境之外也具有很高的有效性，从而以更高的生态有效性模拟现实生活中的步行。©2024作者（S）。由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
