Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): Pathophysiology, Clinical Patterns, and Therapeutic Challenges of Intractable and Severe Forms

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Abstract
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is characterized by the predominance of optic neuritis, myelitis, acute disseminated encephalomyelitis, and cortical encephalitis, which can be diagnosed by the presence of pathogenic immunoglobulin G (IgG) antibodies targeting the extracellular domain of MOG in the serum and cerebrospinal fluid (CSF). Initially considered a variant of multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), it is now widely recognized as a separate entity, supported by converging evidence from serological, pathological, and clinical studies. Pa-tients with MOGAD often exhibit better recovery from acute attacks, but their clinical and pathological features vary based on the immunological role of MOG-IgG via antibody-mediated or complement-mediated perivenous demyelinating pathology in addition to MOG-specific cellular immunity, resulting in heterogeneous demyelinated lesions from vanishing benign form to tissue necrosis. The key is the immunological mechanism of devastating lesion coalescence and long-term degenerating mechanisms, which may still accrue, particularly in the relapsing, progressing, and aggressive clinical course of encephalomyelitis. The warning features of the severe forms are: 1. fulminant acute multifocal lesions transitioning to diffuse or tumefactive lesions; 2. cortical lesions related to status epilepsy; 3. Longitudinally extended spinal cord lesions not well subsided. Persistent MOG-IgG high-titration, intrathecal production of MOG-IgG, and suggestive markers of higher disease activity like cerebrospinal fluid inter-leukin-6 and complement C5b-9 could be identified as promising markers of higher disease activity, disability worsening, and poor prognosis, for identifying sign of escalating treatment strategies.

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