Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Essen, Germany.
Institute for Medical Informatics, Biometrics and Epidemiology, University Hospital Essen, Essen, Germany.
Muscle Nerve. 2024 Dec;70(6):1223-1229. doi: 10.1002/mus.28269. Epub 2024 Oct 3.
INTRODUCTION/AIMS: Persons with spinal muscular atrophy (pwSMA) report progressive muscle weakness but also reduced endurance when performing repetitive tasks in daily life, referred to as "performance fatigability" (PF). Data regarding the effects of the new disease-modifying drugs on PF are scarce. Thus, our main objective was to examine PF in adult ambulatory pwSMA treated long-term with nusinersen.
Six-minute walk test (6MWT) data from 14 adult pwSMA treated with nusinersen for up to 70 months were retrospectively analyzed to determine PF. Performance fatigability was defined as the percentage change in the distance covered between the last and first minute of the 6MWT. In addition, relationships between PF and other clinical features were assessed.
Performance fatigability was found in 12/14 pwSMA (85.7%) prior to treatment. The mean distance walked in the sixth minute (71.1 m) was shorter than the distance covered in the first minute (81.8 m), corresponding to a mean PF of 13.1% (95% confidence interval (CI): 6.5-19.6, p = .0007). During treatment with nusinersen, there was a mean reduction in PF of 5.6% (95% CI: -10.0 to -1.3, p = .0148). We found no relationship between PF and fatigue as measured by the Fatigue Severity Scale.
This study demonstrates the presence of PF as an independent component of motor impairment and as a potential therapeutic target in our cohort of adult ambulatory pwSMA. Furthermore, the observations in our cohort suggest that nusinersen may have a beneficial effect on PF.
介绍/目的：患有脊髓性肌萎缩症（SMA）的患者报告肌肉力量逐渐减弱，但在日常生活中进行重复任务时也会出现耐力降低，称为“表现性疲劳”（PF）。关于新型疾病修饰药物对 PF 的影响的数据很少。因此，我们的主要目的是研究长期接受 nusinersen 治疗的成年活动性 SMA 患者的 PF。
回顾性分析了 14 名接受 nusinersen 治疗长达 70 个月的成年 SMA 患者的 6 分钟步行测试（6MWT）数据，以确定 PF。PF 定义为 6MWT 最后 1 分钟与第 1 分钟之间覆盖距离的百分比变化。此外，还评估了 PF 与其他临床特征之间的关系。
在治疗前，14 名 SMA 患者中有 12 名（85.7%）存在 PF。第 6 分钟行走的平均距离（71.1m）短于第 1 分钟的距离（81.8m），平均 PF 为 13.1%（95%置信区间（CI）：6.5-19.6，p=0.0007）。在接受 nusinersen 治疗期间，PF 平均降低了 5.6%（95%CI：-10.0 至-1.3，p=0.0148）。我们没有发现 PF 与疲劳严重程度量表测量的疲劳之间存在关系。
本研究证明了 PF 是运动障碍的一个独立组成部分，也是我们成年活动性 SMA 患者队列中的一个潜在治疗靶点。此外，我们队列中的观察结果表明，nusinersen 可能对 PF 有有益的影响。
