To report a case of fulminant aquaporin-4 (AQP4)–IgG positive neuromyelitis optica spectrum disorder (NMOSD) precipitated by immune checkpoint inhibitor (ICI) therapy.

Neurological immune-related adverse events (irAEs) occur in 1–5% of ICI-treated patients, but AQP4-positive NMOSD remains exceptionally rare. Checkpoint blockade can unmask latent humoral autoimmunity, and the optimal management of fulminant ICI-related NMOSD refractory to first-line immunotherapy is undefined.

Case report.

A 53-year-old woman with a 30-year history of type 1 diabetes mellitus received first-cycle carboplatin, paclitaxel and dostarlimab (anti–PD-1) for a high-grade endometrial carcinoma. Sixteen days later she developed right thigh burning paraesthesia, progressing over 5 days to bilateral lower-limb numbness with a T6 sensory level, sequential lower-limb weakness, and persistent hiccups. 

MRI spine demonstrated diffuse longitudinally extensive enhancement from the craniocervical junction to the conus. CSF showed lymphocytic pleocytosis (WBC 181/µL, protein 1.39 g/L); cytology was negative. She received methylprednisolone 1 g/day and IVIg 2 g/kg. Despite this, weakness progressed and left optic neuritis developed, with MRI showing T2/FLAIR hyperintensity along the left optic nerve to the chiasm. After 6 cycles of plasma exchange, she remained paraplegic with evolving upper-limb involvement. AQP4-IgG returned positive at 1:1000.

Intravenous ravulizumab was commenced, after which neurological deterioration halted. Follow-up MRI showed evolution of cord oedema without new lesions, and CSF pleocytosis improved (181 to 28/µL). The endometrial carcinoma progressed without further ICI; salvage chemotherapy (gemcitabine, doxorubicin) failed. The clinical course was complicated by septicaemia, and she died 4 months after neurological onset.

ICI-triggered AQP4-positive NMOSD can present as fulminant longitudinally extensive myelitis with sequential optic neuritis and area postrema involvement, refractory to steroids, IVIg and plasma exchange. Complement inhibition with ravulizumab achieved disease stabilisation and warrants early consideration when first-line immunotherapy fails, although permanent ICI discontinuation may compromise tumour control.