MOGAD-related epilepsy: a systematic characterization of age-dependent clinical, fluid, imaging and neurophysiological features

Abstract

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare central nervous system (CNS) demyelinating disease presenting heterogeneously across lifespan. Although frequent, epilepsy remains a poorly characterized MOGAD-associated manifestation.

Methods: To describe age-related clinical, fluid, imaging, and neurophysiological features in MOGAD patients with epilepsy, we systematically reviewed online repositories up to April 2025, identifying 178 eligible studies.

Results: A total of 2487 MOGAD patients were included from clinical studies, and of 337 from case reports/series, 140 with adult-onset and 197 with pediatric-onset disease. Seizures prevalence was 30.6% (95% confidence interval [95%CI] = 28%; 33.3%) in pediatric-onset and 7% (95%CI = 4.1%; 11.2%) in adult-onset cohorts. Pediatric-onset patients were significantly more likely to be female (p = 0.003). Cortical encephalitis was the most common presentation in both age groups, followed by acute demyelinating encephalomyelitis in pediatric-onset and acute demyelinating syndrome in adult-onset patients. In both groups, epileptic manifestations predominantly occurred at disease onset. Pediatric-onset patients were more likely to experience status epilepticus (p = 0.005) and encephalopathy (p = 0.002), whereas adult-onset exhibited higher frequency of cerebrospinal fluid pleocytosis (p < 0.001). Co-positivity with antibodies related to other encephalitides was present in 37.3% of patients, most commonly with anti-N-methyl-D-aspartate receptor (anti-NMDAR) IgG (88.3%), showing no age-dependent differences. No significant age-related differences were observed in leptomeningeal enhancement. Adult-onset patients more frequently showed parietal lobe involvement (p = 0.018) and fewer temporal lobe lesions (p = 0.004) compared to pediatric-onset. Despite comparable use of immunotherapy and anti-seizure medications across groups, chronic epilepsy was more prevalent among pediatric-onset patients (p < 0.001).

Conclusions: Epilepsy is a relevant MOGAD-associated condition with a risk of chronic persistence. Prospective studies are warranted to establish an age-specific therapeutic approach.

Keywords: ADEM; Anti-seizure medication; Cortical encephalitis; Epilepsy; Immunosuppressive treatment; MOGAD; Pediatric; Seizures.