Adjunctive strategies in multiple sclerosis treatment: non-pharmacological approaches and their potential clinical implications.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS), and represents the most common non-traumatic cause of disability among young adults. Although current immunomodulatory therapies have demonstrated beneficial effects in mitigating disease progression, their associated side effects and limitations render MS a condition without a definitive cure. A major obstacle in achieving effective treatment and recovery is the pathological microenvironment within the MS-affected CNS, which severely impairs endogenous tissue repair and diminishes the efficacy of existing interventions. MAIN BODY: Recently, non-pharmacological approaches have gained increasing attention for their potential to treat MS-related pathology. In this review, we summarize how non-pharmacotherapeutic interventions, including physical exercise, dietary adjustments, cognitive training, social participation, and mixed rehabilitation programs, can affect key pathological elements of neuroinflammation in MS by elucidating the molecular mechanisms, such as modulation of neuroinflammation, suppression of glial cell activation, promotion of remyelination, and enhancement of neuroprotective processes. By integrating preclinical experimental data from animals with clinical evidence from MS patients, we also illustrate how various non-pharmacological strategies can dynamically modulate the disease microenvironment. CONCLUSIONS: We emphasize the capacity of non-pharmacological approaches to enhance endogenous repair by fostering a more supportive CNS microenvironment, highlighting their potential to transform disease management.