A Systematic Review of Management of Cramping Pain in Patients with Amyotrophic Lateral Sclerosis.

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.