Myelin oligodendrocyte glycoprotein (MOG) is a minor component of the myelin sheath membrane in the central nervous system (CNS), located at its outermost surface. Its function remains elusive, even though it may play a role as an adhesion molecule or regulator of microtubule stability and is considered as a marker of oligodendrocyte maturity [1]. Its location and molecular structure with an extracellular immunoglobulin domain are thought to explain its encephalitogenic properties, which have extensively been studied in animal models of experimental autoimmune encephalomyelitis (EAE) [2]. As MOG is highly conserved between species, previous studies have attempted to demonstrate a humoral immune response directed against MOG in patients with inflammatory demyelinating diseases, especially multiple sclerosis (MS) [3]. Using cell-transfected-based antibody assays (CBA), MOG-IgG directed against conformational epitopes were finally considered in patients with non-MS demyelinating events, including acute disseminated encephalomyelitis (ADEM) and anti-AQP4 seronegative neuromyelitis optica spectrum disorder (NMOSD) [4], [5].

Both pediatric and adult patients are affected by MOGAD (MOG antibody associated disease), with a balanced sex ratio [6]. MOGAD can manifest with various clinical phenotypes including unilateral or bilateral optic neuritis (ON), transverse myelitis (TM), acute disseminated encephalomyelitis (ADEM), brainstem and cerebellar encephalitis, or less commonly cortical encephalitis (CE) [7].

Available pathology data come from biopsies of MOGAD patients presenting with ADEM, a multifocal lesion without encephalitis, cortical encephalitis or leukoencephalopathy. They reveal an ADEM-like perivenous and disseminated demyelination, coexisting with confluent demyelination [8], [9]. Intra-cortical demyelination is also observed, associated with subpial demyelination [9]. The inflammatory infiltrates in MOGAD are composed with a majority of CD4+ T-cells within the lesions along with granulocytes, and there is no sign of chronic expanding demyelinating lesions. B cells can be found in a small proportion, however some of the reported biopsies and autopsies were performed in patients receiving anti-CD20 therapies [9]. AQP4 is conserved in MOGAD. There is no direct astrocytic damage, necrosis nor cavitation. Complement deposition is not consistently observed in MOGAD [8], [9], and oligodendrocyte progenitor cells remain preserved [10].

MOG-IgG are mostly IgG1, favoring immune enhancement [11]. Also, MOG-IgG induce antibody-dependent cellular cytotoxicity (ADCC) in vitro [4], and antigen presentation through opsonization in animal model [12]. MOG-specific T-cells are essential in MOG-EAE models to induce the disease [13], and human MOG-IgG is not pathogenic by itself, in vivo [14].

These pathophysiological elements suggest different mechanisms and, consequently, varying degrees of severity compared to other pathologies. Recent findings on MOGAD have highlighted its significant heterogeneity, and the prognosis of MOGAD patients remains challenging to measure.

In this review, we aim to establish what clinical, biological and imaging data are available to answer the questions concerning better attack management and better long-term monitoring.