To report a case of paraneoplastic aquaporin-4 (AQP4)-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD) associated with a pathology-confirmed AQP4-positive ovarian teratoma.

NMOSD is a relapsing autoimmune CNS disease characterized by optic neuritis, transverse myelitis, and brainstem syndromes, driven by AQP4-IgG targeting astrocytic water channels. Approximately 3–5% of AQP4-IgG-seropositive cases may have a paraneoplastic etiology, with tumors ectopically expressing AQP4 hypothesized to break immune tolerance. Ovarian teratoma-associated NMOSD is exceedingly rare, with approximately nine prior reported cases.

This case is notable for isolated bilateral optic neuritis without the brainstem involvement typical of teratoma-associated NMOSD (83% in prior series), AQP4 expression in epithelial rather than neural tissue, and concurrent ovarian torsion. A systematic review of 72 paraneoplastic NMOSD cases demonstrated heterogeneous phenotypes, supporting cancer screening in all newly diagnosed AQP4-IgG NMOSD regardless of age.

This case reinforces the importance of considering paraneoplastic etiology in young women with NMOSD and supports pelvic imaging in newly diagnosed AQP4-IgG-seropositive patients.