MOG-IgG-Associated Optic Neuritis, Encephalitis, and Myelitis: Lessons Learned From Neuromyelitis Optica Spectrum Disorder

Abstract

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been found in some cases diagnosed as seronegative neuromyelitis optica spectrum disorder (NMOSD). MOG-IgG allowed the identification of a subgroup with a clinical course distinct from that of NMOSD patients who are seropositive for aquaporin-4-IgG antibodies. MOG-IgG is associated with a wider clinical phenotype, not limited to NMOSD, with the majority of cases presenting with optic neuritis (ON), encephalitis with brain demyelinating lesions, and/or myelitis. Therefore, we propose the term MOG-IgG-associated Optic Neuritis, Encephalitis, and Myelitis (MONEM). Depending on the clinical characteristics, these patients may currently be diagnosed with NMOSD, acute disseminated encephalomyelitis, pediatric multiple sclerosis, transverse myelitis, or ON. With specific cell-based assays, MOG-IgG is emerging as a potential biomarker of inflammatory disorders of the central nervous system. We review the growing body of evidence on MONEM, focusing on its clinical aspects.

Keywords: encephalitis; myelin oligodendrocyte glycoprotein antibody; myelitis; neuromyelitis optica spectrum disorder; optic neuritis.

Figure 1

MOG-IgG-associated optic neuritis, encephalitis, and myelitis (MONEM). The clinical phenotypes associated with MOG-IgG are encompassed under the term MONEM. MONEM is not limited to aquaporin-4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD).

Figure 2

Magnetic resonance imaging (MRI) findings and evolution in a MOG-IgG-positive case fulfilling the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). A young adult presented with recurrent optic neuritis followed by transverse myelitis. Spinal MRI showed a T2-hyperintense, centrally located longitudinally extensive transverse myelitis extending from C4 to C7, with mild cord swelling (A,B). Brain MRI showed a T2/FLAIR-hyperintense lesion on the left superior frontal gyrus (C), with gadolinium enhancement (D). In cell-based assays, aquaporin-4 immunoglobulin G (AQP4-IgG) was negative, and MOG-IgG was positive. Response to immunotherapy was excellent. Follow-up MRI showed complete resolution of the brain and spinal lesions (E,F). This case illustrates that the imaging patterns of MOG-IgG-associated ON, encephalitis, and myelitis (MONEM) often overlap with those of NMOSD, and some cases may even fulfill the 2015 criteria for the diagnosis of NMOSD without AQP4-IgG.