We present a case of MOG-antibody disease (MOGAD) and NMDA receptor (NMDAr) overlap syndrome in which the patient exhibited cortical FLAIR hyperintense lesions on brain MRI, a MOGAD phenotype known as “FLAIR hyperintense cortical lesions in MOG associated encephalitis with seizures” or “FLAMES”. It is important to recognize this clinical entity to differentiate it from its infectious mimickers.

Patient is a 42-year-old female with hyperlipidemia and pre-diabetes who presented with acute onset altered mental status associated with headache. She began speaking nonsensically and having staring spells which prompted her presentation. She was afebrile with mild leukocytosis, but otherwise unrevealing toxic, metabolic, and initial infectious workup. Lumbar puncture notable for elevated opening pressure >50cm H2O, moderate lymphocytic pleocytosis with 240 cells/µL, and protein elevation to 111 mg/dL. MRI revealed diffuse leptomeningeal post-contrast FLAIR hyperintensity. Despite completing an empiric course of antimicrobial meningitis coverage, she clinically declined and progressed to a completely nonverbal state with dystonic and choreiform facial movements as well as catatonic features.  Further testing revealed CSF NMDA antibody positivity (1:128) and serum MOG antibody positivity (1:100). She was treated with immunosuppression with steroids, intravenous immunoglobulin, and plasmapheresis, after which she exhibited significant clinical improvement and was discharged to acute inpatient rehabilitation. She was unfortunately lost to follow up.

This patient had MOGAD-NMDAr overlap syndrome with FLAMES phenotype, which may present clinically with cognitive and psychiatric symptoms, seizures, movement disorders, and fluctuations of consciousness. Diagnosis of this syndrome relies on clinical recognition, ruling out mimickers, and evaluation of antibody status. Treatment is the same for single antibody and dual antibody disease—immunosuppression. Recurrence rate of this overlap syndrome is higher than single-antibody disease alone, and it is generally accepted that maintenance immunotherapy is necessary though exact course of treatment remains uncertain.