Frequency and Phenotype of Coexisting Aquaporin‐4 and Autoimmune Encephalitis Autoantibodies

Among 9457 aquaporin-4 (AQP4) immunoglobulin G-positive patients, 2071 underwent autoimmune encephalitis antibody testing and 85 (4%) had coexisting antibodies, most commonly cerebrospinal fluid glial fibrillary acidic protein-IgG and N-methyl-D-aspartate receptor-IgG, or serum high-titer GAD65-IgG. Compared with AQP4-IgG positive neuromyelitis optica spectrum disorder controls, dual-positive patients were younger and more frequently exhibited encephalopathy, psychiatric symptoms, seizures, ovarian teratomas, and deep gray matter, temporal lobe, or diencephalic MRI abnormalities. GAD65-IgG-positive patients developed stiff-person syndrome. These findings define a distinct mixed glial-neuronal autoimmune phenotype and support additional neural antibody testing in atypical AQP4-IgG-positive presentations.