Investigation of the association of serum GFAP and NfL with brain and upper cervical MRI volumes in AQP4-IgG-positive NMOSD and MOGAD.

Background: Serum glial fibrillary acidic protein (sGFAP) is associated with disease activity in aquaporin-4-immunoglobulin G-seropositive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSD). Serum neurofilament light chain (sNfL) is a biomarker for neuroaxonal damage. However, the association of sGFAP and sNfL with magnetic resonance imaging (MRI) volumes in AQP4-IgG+NMOSD is unclear.

Objectives: To investigate the associations of sGFAP and sNfL with brain MRI volumes in AQP4-IgG+NMOSD.

Design: Monocentric, retrospective, observational study.

Methods: In 33 clinically stable patients with AQP4-IgG+NMOSD, 17 patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and 15 healthy controls (HC), sGFAP and sNfL were measured at 2 (HC = 1) and 3-Tesla MRIs were obtained at 4 (HC = 1) yearly visits. Associations between biomarkers and MRI metrics were evaluated using linear models.

Results: In AQP4-IgG+NMOSD, but not in MOGAD and HC, higher sGFAP was associated with lower hippocampus (β = -2.0 (95% confidence interval: -3.4, -0.7),  = 0.004) and thalamus volumes (β = -2.5 (-4.3, -0.7),  = 0.006) and higher MRI cerebrospinal fluid volume (β = 1.8 (0.7, 3.2),  = 0.01), and, statistically less robust, with lower whole brain (β = -2.3 (-5.3, 0.8),  = 0.15) and gray matter volumes (β = -1.8 (-4.0, 0.4),  = 0.10). Furthermore, higher sGFAP (β = -0.06 (-0.11, -0.002),  = 0.04), but not sNfL (β = -0.02 (-0.08, 0.03),  = 0.38), was associated with percent brain volume change in AQP4-IgG+NMOSD.

Conclusion: The specific associations of sGFAP with brain MRI volumes corroborate sGFAP as a biomarker for disease activity in AQP4-IgG+NMOSD.