From the Departments of Cognitive Neurology (W.I., J.S., M.G.) and Neurodegeneration (A.T., L.S.), Hertie Institute for Clinical Brain Research; Centre for Integrative Neuroscience (CIN) (W.I., J.S., M.G.); German Research Center for Neurodegenerative Diseases (DZNE) (A.T., L.S., M.S.), Tübingen; and Department of Neurology (D.T.), University of Duisburg-Essen, Germany.
Neurology. 2020 Sep 1;95(9):e1199-e1210. doi: 10.1212/WNL.0000000000010176. Epub 2020 Jul 1.
With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid motor biomarkers are highly warranted. In this observational study, we aimed to unravel and validate markers of ataxic gait in real life by using wearable sensors.
We assessed gait characteristics of 43 patients with degenerative cerebellar disease (Scale for the Assessment and Rating of Ataxia [SARA] 9.4 ± 3.9) compared with 35 controls by 3 body-worn inertial sensors in 3 conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n = 21). Movement analysis focused on measures of spatiotemporal step variability and movement smoothness.
A set of gait variability measures was identified that allowed us to consistently identify ataxic gait changes in all 3 conditions. Lateral step deviation and a compound measure of spatial step variability categorized patients vs controls with a discrimination accuracy of 0.86 in real life. Both were highly correlated with clinical ataxia severity (effect size ρ = 0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the clinical SARA subscore, with highest effect sizes for real-life walking ( = 0.67).
We identified measures of ataxic gait that allowed us not only to capture the gait variability inherent in ataxic gait in real life, but also to demonstrate high sensitivity to small differences in disease severity, with the highest effect sizes in real-life walking. They thus represent promising candidates for motor markers for natural history and treatment trials in ecologically valid contexts.
This study provides Class I evidence that a set of gait variability measures, even if accessed in real life, correlated with the clinical severity of ataxia in patients with degenerative cerebellar disease.
随着针对退行性共济失调的疾病修正药物的出现，非常需要具有生态效度的运动生物标志物。在这项观察性研究中，我们旨在通过使用可穿戴传感器揭示和验证现实生活中共济失调步态的标志物。
我们评估了 43 名退行性小脑疾病患者（共济失调严重程度评定量表[SARA]为 9.4 ± 3.9）与 35 名对照者的步态特征，使用 3 个身体佩戴式惯性传感器在 3 种情况下进行：（1）实验室基础行走；（2）监督下的自由行走；（3）日常生活中的现实生活行走（亚组 n = 21）。运动分析侧重于时空步幅变异性和运动平滑度的测量。
确定了一组步态变异性测量值，这些测量值使我们能够在所有 3 种情况下一致地识别出共济失调步态的变化。横向步幅偏差和空间步幅变异性的综合测量值将患者与对照组区分开来，在现实生活中的分类准确率为 0.86。两者与临床共济失调严重程度高度相关（效应大小 ρ = 0.76）。这些措施甚至可以检测到临床 SARA 亚评分仅相差 1 分的患者之间的组间差异，在现实生活行走中具有最高的效应大小（ = 0.67）。
我们确定了一些共济失调步态的测量值，这些测量值不仅使我们能够捕捉现实生活中共济失调步态固有的步态变异性，而且还能够证明对疾病严重程度的微小差异具有高度敏感性，在现实生活行走中具有最高的效应大小。因此，它们是具有生态效度的自然史和治疗试验中运动标志物的有希望的候选者。
本研究提供了 I 级证据，表明即使在现实生活中获得，一组步态变异性测量值也与退行性小脑疾病患者的临床共济失调严重程度相关。
