Serum brain injury biomarkers in patients with NMOSD: dynamic changes and clinical significance

To investigate the dynamic changes of serum brain injury biomarkers [neurofilament light chain (NfL), neurofilament heavy chain (NfH), monocyte chemoattractant protein 1 (MCP-1), and matrix metalloproteinase 9 (MMP-9)] between the acute and remission phases of neuromyelitis optica spectrum disorder (NMOSD) in this cross-sectional study, and their associations with clinical parameters, thereby exploring their potential clinical utility in NMOSD management.

A total of 69 aquaporin-4 (AQP4) antibody-positive NMOSD patients were enrolled, including 32 in the acute phase (onset ≤ 60 days) and 37 in the remission phase (onset > 60 days with stable/improved symptoms). Serum NfL, NfH, MCP-1, and MMP-9 levels were measured using enzyme-linked immunosorbent assay (ELISA) with commercially available kits. Clinical data were collected. Mann–Whitney U test was used for between-group comparisons. Spearman correlation analysis was performed to explore associations.

Serum NfL [31.95 (26.20, 58.40) pg/mL vs. 18.70 (13.60, 26.00) pg/mL, U = 925.0, P < 0.001, Cohen’s r = 0.482] and MMP-9 [679202 (395189, 991328) pg/mL vs. 519329 (118174, 776604) pg/mL, U = 762.5, P = 0.041, Cohen’s r = 0.247] were significantly higher in the acute phase than in the remission phase. In contrast, serum MCP-1 was significantly elevated in the remission phase [368.00 (258.00, 401.00) pg/mL vs. 200.50 (126.80, 252.80) pg/mL, U = 260.5, P < 0.001, Cohen’s r = 0.480]. No significant difference in NfH was observed between phases (P = 0.180). NfL was strongly positively correlated with EDSS score (r = 0.467, 95% CI 0.259–0.634, P < 0.001) and AQP4 antibody titer (r = 0.540, 95% CI 0.312–0.716, P < 0.001), while strongly negatively correlated with time from last attack to sampling (r = −0.499, 95% CI −0.660 to −0.294, P < 0.001). MCP-1 was moderately positively correlated with time from last attack to sampling (r = 0.408, 95% CI 0.190–0.588, P < 0.001). NfL showed a strong positive correlation with NfH (r = 0.504, 95% CI 0.293–0.669, P < 0.001), and MCP-1 showed a moderate negative correlation with MMP-9 (r = −0.367, 95% CI −0.577–-0.125, P < 0.001).

Serum NfL, MCP-1, and MMP-9 exhibit phase-specific changes in AQP4 antibody-positive NMOSD patients in this cross-sectional study. NfL shows promise as a potential biomarker for indicating disease activity and axonal damage. MCP-1 may be valuable for evaluating chronic inflammation in the remission phase. Combined detection of these biomarkers provides a potential non-invasive approach for personalized NMOSD management, though prospective validation is required.