Myelin Oligodendrocyte Glycoprotein–Associated Disorders

Abstract

PURPOSE OF REVIEW: Anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies have become a recognized cause of a pathophysiologically distinct group of central nervous system (CNS) autoimmune diseases. MOG-associated disorders can easily be confused with other CNS diseases such as multiple sclerosis or neuromyelitis optica, but they have a distinct clinical phenotype and prognosis.RECENT FINDINGS: Most patients with MOG-associated disorders exhibit optic neuritis, myelitis, or acute disseminated encephalomyelitis (ADEM) alone, sequentially, or in combination; the disease may be either monophasic or relapsing. Recent case reports have continued to expand the clinical spectrum of disease, and increasingly larger cohort studies have helped clarify its pathophysiology and natural history. SUMMARY: Anti-MOG-associated disorders comprise a substantial subset of patients previously thought to have other seronegative CNS diseases. Accurate diagnosis is important because the relapse patterns and prognosis for MOG-associated disorders are unique. Immunotherapy appears to successfully mitigate the disease, although not all agents are equally effective. The emerging large-scale data describing the clinical spectrum and natural history of MOG-associated disorders will be foundational for future therapeutic trials. UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE:Dr Longbrake discusses the unlabeled/investigational use of immunomodulators, none of which is approved for the treatment of myelin oligodendrocyte glycoprotein-associated disorders.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): current understanding and challenges

“…Importantly, the phenotypic expression of MOGAD may vary with age, such that ADEM-like lesions are more likely to affect children, whereas optic neuritis and isolated myelitis tend to be more common among adults [ 5 ]. In addition, relapse risk in MOGAD patients is often higher in adults than children [ 3 ].…”

“…The pathogenicity of MOG autoantibodies is the subject of ongoing debate. In vivo and in vitro studies suggest that MOG autoantibodies may cause primary demyelination in the CNS with loss of microtubule cytoskeleton in oligodendrocytes and altered expression of proteins [ 3 , 4 ]. Evidence of the pathogenicity of MOG autoantibodies has also been inferred from models of experimental autoimmune encephalitis (EAE) [ 3 , 4 ].…”

“…MOGAD also has the greatest predilection in children, representing 20–30% of inflammatory CNS syndromes in this population as compared to approximately 5% in adults. The current estimated range of incidence in the pediatric population is 3.1 per 1 million, as compared to 1.6 and 2.39 per 1 million among adults [ 3 ]. Notably, these numbers, along with the estimated worldwide prevalence of 20 million [ 5 ], are likely to increase with growing recognition of the disease and improved availability of serological testing.…”

“…Notably, these numbers, along with the estimated worldwide prevalence of 20 million [ 5 ], are likely to increase with growing recognition of the disease and improved availability of serological testing. Unlike NMOSD, cases of MOGAD are not strongly associated with other systemic autoimmune disorders or circulating autoantibodies [ 3 ]. Yet, disease manifestations may occur after prodromal infections, particularly those caused by viral pathogens, such as influenza, Epstein–Barr virus, herpes simplex virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to name a few [ 3 ].…”

“…Unlike NMOSD, cases of MOGAD are not strongly associated with other systemic autoimmune disorders or circulating autoantibodies [ 3 ]. Yet, disease manifestations may occur after prodromal infections, particularly those caused by viral pathogens, such as influenza, Epstein–Barr virus, herpes simplex virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to name a few [ 3 ]. Occasionally, patients with MOGAD have an overlap syndrome with anti-NMDA receptor encephalitis, characterized by clinical features of demyelination associated with encephalopathy, seizures, dyskinesias, or psychosis [ 5 ].…”