MOGAD-Like Encephalitic Syndromes Without MOG Antibodies in Children

BACKGROUND AND OBJECTIVES: Although acute disseminated encephalomyelity (ADEM) can be myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) positive or negative, it is unclear whether other MOG-antibody-associated disease (MOGAD)-like encephalitis syndromes occur without MOG-IgG. We aimed to define the frequency, clinico-radiologic features, outcomes, and antibody associations of such cases in children. METHODS: Prospective cohort study of children (<18 years) with encephalitis meeting clinico-radiologic MOGAD criteria, regardless of MOG-IgG status. Serum from all patients and CSF when available were tested by live cell-based assays (CBA-IIF, CBA-FACS) at 2 laboratories. Brain MRIs were centrally reviewed for MOGAD-like patterns (ADEM, cortical encephalitis, isolated/predominant central gray matter). Additional testing included CBAs for MOG-IgA, MOG-IgM, PLP1-IgG, glial fibrillary acidic protein-IgG, and AQP4-IgG, along with rat brain immunohistochemistry. RESULTS: = 0.017). Immunohistochemistry revealed myelin immunostaining in 14 (12%) MOG-IgG-positive cases (CBA confirmed cross-reactivity with rodent MOG-epitopes) and 10 (25%) MOG-IgG-negative patients (no cross-reactivity with rodent MOG-epitopes); this included a fulminant case with autopsy showing perivenous demyelination and C4d complement deposition, suggesting autoantibodies against an unknown myelin antigen. MOG-IgA, MOG-IgM, or PLP1-IgG occurred in 36/111 (32%) MOG-IgG-positive and 7/37 (19%) MOG-IgG-negative cases, without clinical differences between groups. DISCUSSION: Children can develop the full spectrum of MOGAD-like encephalitis without MOG-IgG. Clinical features and immunotherapy response are similar to MOGAD, but relapses are uncommon.