Case Report: AQP4-IgG-positive neuromyelitis optica spectrum disorder with CSF anti- NMDAR1 IgG positivity and...

Overlap between aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is uncommon and may be difficult to recognize, especially when NMOSD initially presents with brain-predominant lesions and nonspecific symptoms.

A 47-year-old woman initially presented with anorexia, dizziness, nausea, and intractable vomiting. Brain MRI showed a non-enhancing lesion along the anterior wall of the third ventricle involving the hypothalamic region and adjacent periependymal diencephalon, and she was initially treated for possible Wernicke encephalopathy with only partial transient improvement. Seven months later, she developed bilateral blurred vision, and repeat MRI showed persistent diencephalic involvement together with a new lesion in the left cerebellar hemisphere. Over the following three months, she developed progressive cognitive decline and neuropsychiatric symptoms. Neuro-ophthalmologic assessment supported bilateral optic neuritis. Brain MRI later revealed bilateral thalamic and mesial temporal abnormalities, while cervical MRI disclosed a subtle dorsal medullary lesion corresponding to the area postrema. Cerebrospinal fluid (CSF) showed no pleocytosis or protein elevation, but serum and CSF were positive for AQP4-IgG, and CSF anti-NMDAR1 IgG was positive at a low titer (1:10). The patient was treated with high-dose intravenous methylprednisolone followed by oral prednisone taper and maintenance inebilizumab. During follow-up, cognition, mood, and visual acuity improved substantially, and serial MRI showed no new lesions.

This case highlights that persistent vomiting with a periependymal diencephalic or area postrema-region lesion may indicate brain-predominant AQP4-IgG-positive NMOSD rather than nutritional encephalopathy alone. In patients with AQP4-IgG-positive NMOSD who later develop prominent psychiatric or cognitive deterioration with mesial temporal-thalamic abnormalities, CSF anti-NMDAR1 IgG positivity with encephalitic features should be interpreted carefully as a possible overlap rather than definite anti-NMDAR encephalitis. Correlation of the clinical course, serial MRI findings, and CSF and serum antibody results may help support earlier diagnosis and treatment in autoimmune overlap syndromes.