Sequential MOG antibody–associated disease and anti-NMDAR encephalitis in a patient with an MEFV E148Q variant

Overlap between myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) and anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis has increasingly been recognized, suggesting shared mechanisms of central nervous system autoimmunity. However, the contribution of innate immune dysregulation to this overlap spectrum remains largely unexplored. Variants in the MEFV gene, which encodes the pyrin inflammasome component, have been associated with autoinflammatory syndromes and recurrent aseptic meningitis. We report a 36-year-old woman with sequential neuroimmunological manifestations associated with an MEFV gene variant. The patient had a history of optic neuritis at age 9 that improved after steroid therapy. At age 36, several months after childbirth, she developed seizures and neuropsychiatric symptoms accompanied by cerebrospinal fluid pleocytosis. Brain magnetic resonance imaging showed no definite encephalitic lesions, whereas N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography demonstrated focal hyperperfusion in the right parietal cortex. Subsequent testing revealed anti-NMDAR antibodies in the cerebrospinal fluid and serum anti-MOG antibodies detected using a live cell-based assay. Genetic analysis identified a heterozygous E148Q variant in MEFV . During follow-up, the patient experienced recurrent headaches and steroid-responsive inflammatory episodes suggestive of recurrent aseptic meningitis. This case highlights a rare overlap of MOGAD, anti-NMDAR encephalitis, and an MEFV variant, suggesting potential interaction between adaptive autoimmunity and innate immune dysregulation in the central nervous system. MEFV variants may represent background susceptibility factors that could modify the clinical phenotype of antibody-mediated neuroinflammation. Recognition of autoinflammatory mechanisms may be important in patients with atypical relapses or complex neuroimmunological overlap syndromes.