Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease typically presenting with bulbar or limb weakness. There is increasing evidence that amyotrophic lateral sclerosis is a multisystem disease with early and frequent impacts on cognition, behaviour, sleep, pain and fatigue. Dysfunction of normal physiological and metabolic processes also appears common. Evidence from pre-symptomatic studies and large epidemiological cohorts examining risk factors for the future development of amyotrophic lateral sclerosis have reported a high prevalence of changes in behaviour and mental health before the emergence of motor weakness. This suggests that changes beyond the motor system are underway at an early stage with dysfunction across brain networks regulating a variety of cognitive, behavioural and other homeostatic processes. The full impact of non-motor dysfunction continues to be established but there is now sufficient evidence that the presence of non-motor symptoms impacts overall survival in amyotrophic lateral sclerosis, and with up to 80% reporting non-motor symptoms, there is an urgent need to develop more robust therapeutic approaches. This review provides a contemporary overview of the pathobiology of non-motor dysfunction, offering readers a practical approach with regard to assessment and management. We review the current evidence for pharmacological and non-pharmacological treatment of non-motor dysfunction in amyotrophic lateral sclerosis and highlight the need to further integrate non-motor dysfunction as an important outcome measure for future clinical trial design.

肌萎缩侧索硬化症是一种进行性和致命的神经退行性疾病，通常表现为延髓或肢体无力。越来越多的证据表明，肌萎缩侧索硬化症是一种多系统疾病，对认知、行为、睡眠、疼痛和疲劳具有早期和频繁的影响。正常生理和代谢过程的功能障碍也很常见。来自症状前研究和检查肌萎缩侧索硬化症未来发展风险因素的大型流行病学队列的证据表明，在运动无力出现之前，行为和心理健康的变化发生率很高。这表明运动系统以外的变化正在早期阶段进行，大脑网络的功能障碍调节各种认知、行为和其他稳态过程。非运动功能障碍的全部影响仍在继续确定，但现在有足够的证据表明，非运动症状的存在会影响肌萎缩侧索硬化症的总体生存率，并且高达 80% 的人报告了非运动症状，因此迫切需要需要开发更强大的治疗方法。这篇综述提供了当代非运动功能障碍病理学的概述，为读者提供了一种关于评估和管理的实用方法。我们回顾了肌萎缩侧索硬化症中非运动功能障碍的药物和非药物治疗的现有证据，并强调需要进一步整合非运动功能障碍作为未来临床试验设计的重要结果指标。