Acute Disseminated Encephalomyelitis (ADEM): Current View into Etiopathogenesis and Clinical Features

Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system (CNS) that predominantly affects children and young adults. ADEM typically follows an infectious or, less commonly, immunization-related trigger, and despite decades of clinical observation, its etiopathogenesis remains only partially understood. Clinically, the diagnosis of ADEM continues to pose significant challenges due to the absence of disease-specific biomarkers and its clinical and radiological overlap with other acquired demyelinating syndromes. This narrative review aims to summarize and critically discuss current knowledge on ADEM, with particular emphasis on its etiopathogenesis and clinical characteristics, highlighting the potential implications of recent research for clinical practice and management of this disease. Particular emphasis is placed on post-infectious immune mechanisms, including molecular mimicry, blood–brain barrier (BBB) disruption, loss of immune tolerance, and neuroinflammatory cascades. A wide spectrum of infectious triggers—viral, bacterial, parasitic—as well as post-vaccination, post-transplantation, paraneoplastic, metabolic, and host-related genetic factors are discussed in the context of immune dysregulation leading to CNS demyelination. We also highlight characteristic clinical and neuroimaging features that may aid in differentiating ADEM from other demyelinating syndromes, while acknowledging current diagnostic limitations. The integration of recent advances in ADEM immunopathogenesis with established clinical and radiological insights underscores the complexity of this disorder and highlights the evolving nature of current concepts regarding its diagnosis and clinical heterogeneity.