Impact of Exercise Training on Serum Neurofilament Light Chain (NfL), Brain Volumetry, and Functional Outcomes in Multiple Sclerosis

The Effect of an Exercise Intervention on Serum Neurofilament Light Chain and Brain Volumetry in Patients With Multiple Sclerosis: A Randomized Controlled Trial

This single-blind, randomized controlled trial will employ a two-arm parallel design (exercise group vs. control group) with a 12-week intervention period. Randomization will be implemented using SPSS 25.0 (IBM Corporation, Armonk, NY, USA) to ensure balanced group allocation. All outcome measures will be assessed at baseline and post-intervention.

The exercise intervention will consist of supervised progressive resistance training sessions conducted three times weekly (with a minimum 48-hour rest period between sessions) at Firat University Hospital. Control participants will maintain their usual daily activities without participating in any structured exercise programs.A blinded neurologist will perform all clinical assessments to eliminate measurement bias. To control for circadian variations, all evaluations will be scheduled at consistent times of day for each participant. Environmental conditions will be strictly maintained during testing sessions (ambient temperature: 21-22°C; humidity: 55-60%). This study will be designed and reported in accordance with CONSORT guidelines for randomized trials, incorporating all essential elements for transparent randomized controlled reporting, including allocation concealment, blinding procedures, and intention-to-treat principles.

Inclusion Criteria:

• Clinically confirmed relapsing-remitting multiple sclerosis (RRMS) diagnosis according to revised McDonald criteria (2017)
• Mild-to-moderate disability (EDSS score 1.0-5.5)
• No corticosteroid treatment within the previous 3 months

Exclusion Criteria:

• Acute MS relapse within 90 days prior to enrollment
• Regular participation in structured exercise programs (>3 hours/week)
• Comorbid conditions that may limit exercise participation, including; significant orthopedic impairments, unstable cardiopulmonary conditions and other systemic disorders affecting physical activity
• Standard MRI contraindications (metallic implants, claustrophobia, etc.)
• Concurrent neurological disorders (other than MS)
• Initiation or modification of disease-modifying therapy within 6 months
• Severe spasticity (Modified Ashworth Scale ≥3 in any major muscle group)