Severe progression of bilateral optic neuritis associated with extensive neuroaxis involvement in an AQP4-seronegative patient: a case report

Abstract

Case Presentation: A previously healthy 45-year-old female presented in March 2025 with left optic neuritis, partially responsive to methylprednisolone pulse therapy. In August 2025, she developed severe, painless bilateral visual loss (counting fingers) and multifocal neurological signs, including nystagmus, left hemiparesis, hemihypesthesia, and cerebellar ataxia, at which time she was referred to a tertiary healthcare service. MRI revealed multiple T2/FLAIR hyperintense lesions in periventricular regions, brainstem, and cerebellum. Optic nerves showed thickening and hypersignal. Spinal MRI demonstrated LETM extending from from the bulb to the C3 level. CSF showed mild hyperproteinorrhachia without pleocytosis or oligoclonal bands; AQP4-IgG was non-reactive. The patient was refractory to high-dose corticosteroids and deteriorated to tetraparesis. Six sessions of plasmapheresis were performed without improvement. Immunosuppression with rituximab was initiated. Despite interventions, she progressed to respiratory failure requiring intubation and tracheostomy. After a second rituximab dose and further plasmapheresis, she stabilized. She was discharged in December 2025 with severe sequelae: spastic tetraparesis, tracheostomy dependence, 20/200 visual acuity, and a score greater than nine on the Expanded Disability Status Scale (EDSS). Discussion: This case illustrates a fulminant phenotype of seronegative NMOSD. Diagnosis was established based on current international criteria, combining core clinical characteristics (optic neuritis, LETM, brainstem syndrome) with typical neuroimaging, after excluding mimics. The refractoriness to corticosteroids and limited response to plasmapheresis highlight the severity of the inflammatory attack. While plasmapheresis is the standard rescue therapy for steroid-refractory relapses, delayed response or failure can occur in fulminant cases. Rituximab is established for relapse prevention, but its efficacy in reversing established massive neuronal damage is limited. Factors associated with poor prognosis—bilateral optic neuritis, LETM, and brainstem involvement—were present. This report emphasizes that seronegativity does not imply a benign course. Early recognition of high-risk patterns is crucial, although aggressive escalation of therapy may not always prevent permanent disability in patients with extensive neuroaxis injury. Final Comments: Seronegative NMOSD can manifest with a fulminant course and high morbidity. This case emphasizes that serological negativity does not exclude severity. Refractoriness to standard therapies reinforces the need for early recognition of poor prognostic factors and rapid therapeutic escalation. Treatment decisions must rely on clinical and radiological phenotypes to limit disease progression, even if permanent sequelae cannot always be avoided.