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.

FIGURE 8–1

Laboratory techniques for identifying MOG autoantibodies. A, In enzyme-linked immunosorbent assays (ELISA), plates are coated with myelin oligodendrocyte glycoprotein (MOG) peptide. Patient serum is applied, followed by a horseradish peroxidase (HRP)-conjugated secondary antibody. Application of 3,3′,5,5′- tetramethylbenzidine (TMB) substrate causes a colorimetric reaction when bound antibody is present, which is measured on a plate reader. B, For cell-based assays, full-length MOG is transfected into a living human cell line, translated and expressed on the cell surface. Patient serum is applied, and any anti-MOG antibodies present can bind the protein in its native conformation. Fluorescently tagged secondary antibodies are applied (these may be isotype-specific) and quantified using flow cytometry. HEK = human embryonic kidney cells. Figure created with BioRender.

FIGURE 8–2

MRI findings associated with myelin oligodendrocyte glycoprotein (MOG) phenotypes. A, Coronal (left) T2-weighted image and axial (right) postgadolinium T1-weighted image demonstrate bilateral optic neuritis with T2 hyperintensity and mild diffuse enhancement of the bilateral optic nerves. B, Sagittal short tau inversion recovery (STIR) (left) and postgadolinium T1-weighted (right) images demonstrate longitudinally extensive cervical spine lesions with minimal associated enhancement. C, Axial fluid-attenuated inversion recovery (FLAIR) images demonstrate bilateral hemispheric white matter lesions with involvement of bilateral basal ganglia and thalami in a child with acute disseminated encephalomyelitis (ADEM). D, Axial FLAIR (left) and postgadolinium T1-weighted (right) images demonstrate diffuse left hemispheric cortical FLAIR signal changes with associated diffuse leptomeningeal enhancement in a patient with encephalopathy.