Blood Glial Fibrillary Acidic Protein in MRI ‐Negative Attack‐Like Episodes of Neuromyelitis Optica Spectrum Disorder

ABSTRACT Objectives Magnetic resonance imaging (MRI) is widely used to support relapse diagnosis in neuromyelitis optica spectrum disorder (NMOSD), yet some patients present with attack‐like symptoms without corresponding lesions. We assessed serum glial fibrillary acidic protein (sGFAP) levels in MRI‐negative attack‐like episodes. Methods We retrospectively analyzed aquaporin‐4‐IgG–positive NMOSD patients presenting with relapse‐like symptoms but without corresponding new MRI lesions. sGFAP was measured from stored serum collected at presentation and converted to demographic‐adjusted z ‐scores. A predefined attack‐associated threshold ( z ‐score ≥ 3.0) was based on prior work. Results We identified 39 MRI‐negative attack‐like episodes from 34 patients. Most episodes were clinically mild or subjective, with objective worsening observed in 23%. Eight episodes (21%) showed elevated sGFAP levels (median z ‐score 4.56 [1748 pg/mL]). Compared with episodes without elevated sGFAP, these episodes occurred closer to prior attacks (8 vs. 33 months) and more frequently met objective worsening criteria (50% vs. 16%). In all episodes with elevated sGFAP, remission samples showed normalization below the threshold. Discussion Marked sGFAP elevation in a subset of MRI‐negative episodes suggests that some events may represent relapse not captured by conventional imaging. sGFAP may serve as a complementary biomarker to support attack identification when clinical and MRI findings are inconclusive.