Effects of exercise training among adults with multiple sclerosis Protocol for a systematic review that informs an updated prescriptive guideline

Background: Research demonstrates that exercise training is both safe and beneficial for individuals with multiple sclerosis (MS). There is a timely opportunity for updating the guidelines for exercise training in MS, as the number of RCTs examining the effects of exercise training on a range of functional and biomedical outcomes among adults with MS has increased substantially in the past decade. The evidence for updating the guidelines should be gathered through rigorous methodology, thereby ensuring a comprehensive analysis. This systematic review of the literature will evaluate the type and dose of exercise training necessary to improve fitness, biomarkers of health and disease, physical and cognitive functions, symptoms of MS, quality of life, and/or participation in activities of daily life among adults with MS presenting with mild, moderate, or severe disability. Methods: This protocol for a systematic review follows the PRISMA-P guidelines and was registered on Prospero. We will undertake a systematic and comprehensive search will be conducted across 8 electronic bibliographic databases. Retrieved references will be screened by two authors based on pre-established inclusion and exclusion criteria. Relevant data will be extracted into piloted tables and synthesized qualitatively. Methodological quality of the included studies will be determined using the Tool for the Assessment of Study quality and Reporting in Exercise (TESTEX). Risk of bias will be assessed through the revised Cochrane risk-of-bias tool for RCTs (RoB 2). Finally, the certainty of evidence provided for the outcomes of interest will be evaluated through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Discussion: The evidence gathered and analyzed through this review will be crucial for our next step of updating the exercise guidelines for MS. These updated guidelines will provide people with MS, their families and/or their caregivers, as well as health care professionals and MS services organization or advocates, with clear information to promote exercise training among patients with MS. This will subsequently facilitate implementation of exercise training programs into MS-care. Registration details: PROSPERO registration number CRD42025628825