Seizures and epilepsy in MOG antibody-associated disease: from cortical neuroimmunology to clinical practice

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder distinct from multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD). Seizures are an important but incompletely characterized manifestation. Their reported prevalence is strongly age-dependent—approximately 30% in pediatric-onset versus 7% in adult-onset cohorts, although these estimates are influenced by referral and publication bias—and clusters around cerebral cortical encephalitis (CCE) and FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES). This raises a mechanistic question: why is cortical MOGAD particularly ictogenic, and how does demyelination interact with lesion anatomy and inflammatory composition to promote cortical hyperexcitability? This review places the neuroimmunology of MOGAD-related seizures at its center. We summarize the epidemiology, age gradient and clinical spectrum—CCE/FLAMES, acute disseminated encephalomyelitis (ADEM)-associated seizures, isolated sentinel seizures, status epilepticus, new-onset refractory status epilepticus (NORSE), and MOG–N-methyl-D-aspartate receptor (NMDAR) overlap—together with the distinction between acute symptomatic seizures and autoimmune-associated epilepsy. We then examine MOG-IgG effector biology, the CD4+ T-cell- and macrophage-predominant pathology, B-cell compartmentalization, the meningo-cortical axis, and the Th17/interleukin-6-weighted cerebrospinal fluid (CSF) milieu. Candidate downstream pathways of inflammatory ictogenesis are presented with an explicit separation between MOGAD-specific associations and mechanisms extrapolated from epilepsy. Finally, we translate this framework into differential diagnosis, assay interpretation, electroencephalographic evaluation, immunotherapy-first management, antiseizure medication (ASM) review, neuropsychological follow-up and testable research priorities.