Exercise in Multiple Sclerosis: Mechanisms, Clinical Benefits, Potential Disease-Modifying Effects, and Practical Recommendations

The role of exercise in the management of multiple sclerosis (MS) has undergone a remarkable shift. Exercise was once discouraged due to concerns over symptom worsening; this view has since been overturned, and exercise is now recognized as an important component of contemporary MS care. It is increasingly recognized as a safe and effective non-pharmacological, symptomatic intervention improving quality of life, and several disabling symptoms including fatigue, pain, muscle weakness, spasticity, poor balance and cognitive complaints. Beyond its established role in symptomatic management, this review examines the potential role of exercise as a disease-modifying intervention in MS. Mechanistic evidence regarding peripheral immunomodulation, blood–brain barrier integrity, microglial activation, neurotrophic signaling and neuroplasticity is examined, alongside data from clinical trials and meta-analyses on clinical, imaging and biochemical outcomes, suggesting potential effects on disease biology and progression. Finally, based on the available literature and existing published frameworks we provide updated practical recommendations for individualized exercise prescription according to disability level, baseline fitness, individual preferences, and available resources. Together, these recommendations aim to contribute to the integration of exercise into routine MS care, while emerging evidence for its disease-modifying potential provides an important direction for future research.