Blood neurofilament light chain in patients with multiple sclerosis: A systematic review and updated meta-analysis.

BACKGROUND: This study aims to thoroughly evaluate blood neurofilament light chain (NfL) levels in multiple sclerosis (MS) patients compared to controls and across various MS subtypes. METHODS: We conducted a systematic search of PubMed and Web of Science up to February 20, 2025, focusing on studies that reported blood NfL levels in individuals with MS and in control groups. Effect sizes were determined using Hedges' g, applying a random effects model for significant heterogeneity (I2 > 50 %), and a fixed effects model otherwise. RESULTS: From 1380 records, 68 studies with a total of 19,159 participants were included. Blood NfL levels were significantly higher in MS patients compared to controls (SMD = 0.78; 95 % CI [0.67, 0.89], p < 0.001; I2 = 87.29 %). We also found elevated NfL levels in all major MS subtypes: RRMS (SMD = 0.71; 95 % CI [0.52, 0.91], p < 0.001; I2 = 90.26 %), SPMS (SMD = 0.94; 95 % CI [0.60, 1.28], p < 0.001; I2 = 88.43 %), PPMS (SMD = 0.79; 95 % CI [0.16, 1.42], p = 0.01; I2 = 95.75 %), and combined PMS (SMD = 0.96; 95 % CI [0.79, 1.12], p < 0.001; I2 = 80.28 %) compared to controls. Also, GFAP levels were significantly higher in PMS than in RRMS. CONCLUSIONS: Our findings highlight the potential of blood NfL as a useful biomarker for tracking disease progression and distinguishing MS subtypes. However, additional studies are essential to confirm its effectiveness in clinical settings (Graphical abstract).