Early anti-C5 therapy in NMOSD: rationale and clinical evidence

Complement-mediated astrocyte injury is central to aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). Although C5 inhibitors are approved for relapse prevention, their role as rescue therapy during severe acute attacks remains unclear.We describe a 39-year-old woman with AQP4-IgG+ NMOSD presenting with longitudinally extensive myelitis, optic neuropathy, and a basal ganglia lesion. Despite two courses of intravenous methylprednisolone, five plasma exchanges, and intravenous immunoglobulin, disability progressed to an Expanded Disability Status Scale (EDSS) score of 9.0. Ravulizumab was initiated on day 34 after meningococcal vaccination and prophylactic antibiotics. Clinical course, cerebrospinal fluid (CSF) parameters, and total hemolytic complement activity (CH50) were followed for 1 year. After a 2400-mg loading dose of ravulizumab, CH50 became undetectable, indicating effective terminal complement inhibition, whereas C3/C4 remained within reference ranges. Neurological deterioration stopped promptly, followed by marked recovery in motor and visual function. EDSS improved from 9.0 to 6.0 at transfer and to approximately 1.5-2.0 at 1 year. CSF pleocytosis and protein levels normalized in parallel with CH50 suppression. The patient regained ambulation with an orthosis, returned to work on day 220, and remained relapse-free without treatment-related adverse events during 8-weekly maintenance therapy. This case supports the biological plausibility and practical feasibility of early ravulizumab rescue therapy in severe refractory AQP4-IgG+ NMOSD. Prospective studies are needed to define optimal timing, patient selection, and the incremental benefit beyond prior acute immunotherapies.