Double positivity for anti-N-methyl-d-aspartate receptor and anti-aquaporin-4 antibodies in a patient presenting with hypersomnolence, personality change, and reduced spontaneity

Background: Recently, the coexistence of anti-aquaporin-4 antibody (AQP4-ab) and anti-N-methyl-d-aspartate receptor antibody (NMDAR-ab) were reported in a single case. However, its clinical significance is not well defined. Case presentation: A 42-year-old woman developed hypersomnolence, personality change, and childish or bizarre behavior. Four months later, she exhibited marked reduction of verbal and motor spontaneity. Serum AQP4-ab was positive. Cerebrospinal fluid (CSF) was positive for oligoclonal bands. Brain magnetic resonance imaging (MRI) detected multiple T2-hyperintense lesions without gadolinium enhancement in the pons, midbrain, bilateral internal capsule, basal ganglia, corpus callosum, and deep cerebral white matter. Spinal MRI was negative. Because clinical symptoms and clinical course were atypical for neuromyelitis optica spectrum disorders (NMOSD), CSF NMDAR-ab was tested and found to be positive. Whole-body examination revealed cystic lesions in the right ovary, which were later found not to be malignant tumors. In accordance with the proposed algorithm for the treatment of NMDAR encephalitis (NMDARE), she was treated with three courses of intravenous methylprednisolone pulse therapy, followed by oral prednisolone, intravenous immunoglobulin therapy, and five courses of bimonthly intravenous cyclophosphamide pulse therapy. Her symptoms gradually improved, and she returned to her daily life without major sequelae. Conclusions: Although her main symptoms were compatible with NMDARE, MRI findings were more compatible with NMOSD. Therefore, we interpreted her clinical and imaging features as a mixed phenotype of NMOSD and NMDARE. This case report provides additional evidence that double positivity for AQP4-ab and NMDAR-ab is associated with a mixed phenotype of NMOSD and NMDARE.