When fever and headache hide NMOSD: A 29‑year‑old woman with an atypical cerebral presentation: A case report

Cerebral involvement in neuromyelitis optica spectrum disorder (NMOSD) is rare. An initial presentation with an isolated severe headache and high fever is exceptionally uncommon, posing significant diagnostic challenges. Misdiagnosis is frequent even after cerebrospinal fluid (CSF) analysis and any delay in recognition or inappropriate treatment carries risks of clinical deterioration and mortality. A 29‑year‑old woman presented with recurrent fever (lasting >1 month) and severe headache (lasting >2 weeks) as the sole initial symptoms and was eventually diagnosed with NMOSD with cerebral syndrome. Initial empiric antimicrobial and antiviral therapy (ceftriaxone, acyclovir), along with symptomatic management, were unsuccessful. Meropenem was also ineffective. A pivotal shift occurred with intravenous dexamethasone administration (5 mg), which rapidly reduced fever and inflammation. Treatment was subsequently escalated to high‑dose intravenous methylprednisolone (0.5 g/day for 3 days), followed by a carefully tapered oral prednisone regimen. Acyclovir was gradually discontinued. Mannitol was administered concurrently to manage intracranial pressure. At the one‑month follow‑up, CSF analysis showed only mild pleocytosis and brain MRI revealed minimal residual punctate lesions. The patient achieved complete symptomatic resolution without neurological deficits. No recurrence occurred during the documented follow‑up period. This case highlights a rare NMOSD cerebral presentation masked by intractable headache and fever. NMOSD should be considered in the differential diagnosis for unexplained fever and severe headache, even when initial CSF findings are inconclusive. In the present case, clinical improvement followed multiple therapeutic interventions. However, the marked response observed after glucocorticoid administration suggests it was a critical turning point in management, leading to rapid symptom control and excellent recovery. Timely initiation of glucocorticoid can result in full neurological recovery and prevent progression. This emphasizes the need for heightened awareness and timely steroid use in suspected cases.