Background

Efficacy of nusinersen in adult 5q-spinal muscular atrophy (SMA) patients regarding motor function has recently been demonstrated. However, additional outcome measures are needed to capture non-motor improvements. Fatigue is a common and disabling symptom in neurologic diseases, but little is known about its frequency, characteristics and associated factors in SMA.

Objective

To characterize fatigue in SMA patients receiving nusinersen, identify associated factors and evaluate fatigue as potential patient-reported outcome measure (PRO).

Methods

We assessed fatigue in adults with genetically confirmed 5q-SMA in a prospective longitudinal monocentric study using the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Factors associated with fatigue including health-related quality of life (HRQOL) were evaluated.

Results

75% of participants were abnormally fatigued with highest scores in the dimensions physical, followed by general fatigue and reduced activity. 53% agreed that fatigue was among their three most disabling symptoms. Reduced activity was reported more extensively by participants with ≥ 4 copies of the survival of motor neuron 2 gene and better motor function. General and mental fatigue correlated positively with age and disease duration. HRQOL was inversely correlated with physical fatigue, which was not associated with disease or participant characteristics. During 14 months of nusinersen treatment, fatigue measures remained mostly stable with a trend towards improvement in reduced activity, general and physical fatigue.

Conclusion

Fatigue is a frequent and relevant complaint in adult SMA patients. Fatigue should be taken into consideration as additional outcome measure, but needs further evaluation in a larger patient cohort over a longer observation period.

中文翻译：

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一项观察队列研究，对接受nusinersen治疗的成年5q型脊柱肌肉萎缩患者的感觉疲劳的影响，大小和结果

背景

最近已经证实了努西尔森在成人5q型脊柱肌萎缩症（SMA）患者中关于运动功能的功效。但是，还需要采取其他措施来捕获非运动性改善。疲劳是神经系统疾病的常见和致残症状，但对于SMA的频率，特征和相关因素知之甚少。

目的

为了表征接受Nusinersen的SMA患者的疲劳，确定相关因素并评估疲劳，作为潜在的患者报告的结局指标（PRO）。

方法

在一项前瞻性纵向单中心研究中，我们使用疲劳严重程度量表（FSS）和多维疲劳量表（MFI）对成年人进行了遗传学证实的5q-SMA评估。评估与疲劳相关的因素，包括健康相关的生活质量（HRQOL）。

结果

75％的参与者异常疲倦，在身体维度上得分最高，其次是整体疲劳和活动减少。53％的人认为疲劳是他们三个最致残的症状之一。具有≥4个运动神经元2基因存活率和更好的运动功能的参与者报告了活动减少。通用和心理疲劳与年龄和病程呈正相关。HRQOL与身体疲劳程度呈负相关，与疾病或参与者特征无关。在Nusinersen治疗的14个月中，疲劳措施基本保持稳定，并有减少活动，全身和身体疲劳的趋势。

结论

在成年SMA患者中，疲劳是常见且相关的主诉。疲劳应作为额外的结局指标加以考虑，但需要在更长的观察期内对更大的患者队列进行进一步评估。