In this study, we investigated the effects of changes at the maternal–fetal interface during pregnancy on the pathogenesis and recurrence of ADEM, as well as the possible role of the HMGB1/TLR4/Nf-κB/IL-6 pathway in the pathogenesis of pregnancy-related ADEM. The gene discussed is HMGB1; the disease is acute disseminated encephalomyelitis.