Inter-attack serum GFAP and NfL remain stable over 9 years in AQP4 IgG NMOSD

BACKGROUND AND OBJECTIVES: Disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum disease (AQP4-IgG NMOSD) is considered relapse-driven although subclinical injury has been suggested by neuroimaging and visual pathway assessments. We investigated longitudinal changes in serum glial fibrillar acidic protein (sGFAP) and neurofilament light chain (sNfL) during relapse-free periods. METHODS: We conducted a retrospective longitudinal study (2008-2025) at a UK national referral centre for NMOSD. Patients with ≥3 serum samples collected over ≥3 years were included; samples within 3 months of relapses were excluded. Longitudinal changes in sGFAP and sNfL were assessed using linear mixed-effects models with random intercepts and generalised estimating equations, adjusting for age, sex and time. RESULTS: 40 patients (87.5% females; 162 samples; median onset age 40.1 years) and 28 matched controls were included. Over the course of four measurements and a median sampling over 9 years, stability was observed in sGFAP levels (99.2 pg/mL at 0-2.5 years (95% CI 84.2 to 117.0) to 90.3 pg/mL at 7.5-10 years (95% CI 74.7 to 109.0), p=0.65) and sNfL levels (12.0 pg/mL at 0-2.5 years (95% CI 10.8 to 13.3) to 10.4 pg/mL (9.1 to 11.8) at 7.5-10 years, p=0.12) after adjustment for covariates. DISCUSSION: In this longitudinal study, mean sGFAP and sNfL levels remained stable over 9 years of sequential measurements during relapse-free periods, supporting the relapse-driven nature of NMOSD pathology.