Supplementary Material for: A Systematic Review of Management of Cramping Pain in Patients with Amyotrophic Lateral Sclerosis

Background/Introduction: Pain, particularly cramping, in people living with Amyotrophic Lateral Sclerosis (ALS) is often underrecognized and under-treated. Despite affecting over 70% of people living with ALS (plwALS), cramping pain remains inadequately managed due to its complex nature and the difficulties plwALS face in communicating their symptoms as the disease progresses. This systematic review explores both pharmacological and non-pharmacological treatments for cramping pain in ALS, aiming to assess and compare their efficacy. Methods: The systematic review was conducted following PRISMA guidelines and the protocol was registered with PROSPERO (ID CRD42024521649). A comprehensive search was performed across MEDLINE, Embase, Scopus, and Cochrane databases from inception until February 1, 2024, using specific search terms related to ALS and cramping. Results: The search resulted in the identification of 368 studies. After duplicates were removed, abstracts screened, and full texts reviewed, nine studies were included. Pharmacological interventions such as Mexiletine demonstrated significant reductions in cramp frequency and intensity in several trials, with varying doses showing distinct levels of effectiveness. Other medications like Dronabinol and Levetiracetam were also tested but showed limited efficacy in reducing cramp severity. Among non-pharmacological options, supervised exercise programs, particularly those incorporating stretching and functional mobility, were effective in reducing cramping pain intensity, while unsupervised home exercise programs did not show significant improvements. Conclusion: The review demonstrates the scarcity of high-quality research on cramping pain management in ALS. Mexiletine emerged as the most promising pharmacological intervention, providing notable relief, while supervised exercise therapy demonstrated beneficial effects.

背景/引言：肌萎缩侧索硬化症（Amyotrophic Lateral Sclerosis, ALS）患者所经历的疼痛，尤其是痉挛痛，常未被充分识别与治疗。尽管超过70%的ALS患者会出现痉挛痛，但由于其病理机制复杂，且随着疾病进展，患者难以清晰表述自身症状，此类疼痛始终未能得到妥善管理。本系统综述旨在探讨ALS患者痉挛痛的药物与非药物治疗方案，对其疗效进行评估与对比。
方法：本系统综述严格遵循PRISMA指南开展，研究方案已在PROSPERO国际系统综述注册平台注册（注册号：CRD42024521649）。本研究于2024年2月1日前，针对MEDLINE、Embase、Scopus及Cochrane数据库进行了全面检索，检索词涵盖ALS与痉挛痛相关的特异性术语。
结果：本次检索共识别出368项研究，经去重、摘要筛选及全文审阅后，最终纳入9项研究。多项试验显示，美西律（Mexiletine）等药物干预手段可显著降低痉挛发作频率与强度，且不同给药剂量的疗效存在差异。其余受试药物如屈大麻酚（Dronabinol）与左乙拉西坦（Levetiracetam）在减轻痉挛严重程度方面疗效有限。在非药物干预手段中，带监督的运动方案（尤其是包含拉伸与功能活动训练的方案）可有效减轻痉挛痛强度，而无监督的居家运动方案则未展现出显著改善效果。
结论：本综述显示，针对ALS患者痉挛痛管理的高质量研究仍较为匮乏。美西律是目前最具前景的药物干预手段，可显著缓解痉挛痛，而带监督的运动疗法也展现出积极疗效。