The interaction between exercise and neurofilament light chain in multiple sclerosis: a systematic review and meta-analysis.

Background: Exercise in patients with multiple sclerosis (pwMS) found to improve symptom management and regain function. Whether exercise lowers neurofilament light chain (NfL), neuroaxonal injury biomarker, in MS remains unknown with conflicting findings. In this study, we aimed to assess the interaction between exercise and NfL levels in pwMS.

Methods: Systematic search of Medline, CENTRAL, Embase, and Web of Science was conducted until March 2024 to identify relevant reports. We included studies that investigated the mean change in NfL levels pre- and post-training programs and compared them to different exercise programs or no exercise activity control groups. A standardized mean difference (SMD) with a 95 % confidence interval were applied using a random-effects model.

Results: Of 222 articles, 7 studies met the inclusion criteria. Patients who underwent structured exercise programs had a significant decrease in blood NfL levels post-training (SMD -0.55; 95 % CI -1.00, -0.09). Specifically, outdoor Pilates and home-based trainings were significantly associated with blood NfL reduction (SMD -2.08; 95 % CI -2.99, -1.17) and (SMD -1.46; 95 % CI -2.28, -0.64), respectively. Patients in the control group did not show significant differences in blood NfL levels between the baseline and at the end of the study (SMD 0.04; 95 % CI -0.17, 0.24). Subgroup analysis based on duration revealed that 8 weeks of exercise significantly reduced blood NfL levels (SMD -0.73; 95 % CI -1.35, -0.11).

Conclusion: Our study provides preliminary evidence for the potential role of training in reducing blood NfL levels in pwMS. However, more rigorous, and well-designed studies are warranted to confirm these findings.