Perivenous demyelination: Association with anti‐myelin oligodendrocyte glycoprotein antibody

Abstract

By the discovery of an antibody to aquaporin 4 (AQP4), the clinical and radiological findings of neuromyelitis optica (NMO) such as diffuse cerebral or longitudinally extended spinal cord lesions had been clarified as distinct features from multiple sclerosis (MS). Pathological studies in NMO demonstrated loss of immunoreactivity to AQP4 and glial fibrillary acidic protein but a relative preservation of myelin basic protein, especially at the lesions with perivascular deposition of immunoglobulins and complements, suggesting autoimmune disease against astrocytes. In recent years, the antibody against myelin oligodendrocyte glycoprotein (MOG) has been studied for its association with acute demyelinating diseases such as acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM), optic neuritis, AQP4 antibody–negative NMOSD, and brainstem or cerebral cortical encephalomyelitis. We could identify the dominance of perivenous inflammatory demyelination like ADEM in our biopsied case series with MOG antibody. In recent brain‐biopsied cases with MOG antibody, the deposition of humoral immunity, perivascular inflammation, and perivenous demyelination were observed especially in atypical cases including cortical encephalitis or disseminated encephalitis. In this review, we focus on MOG antibody–related diseases, which we considered it as a differentiated disease from MS by means of the disease‐specific autoantibody and the distinct pathophysiology.

Myelin oligodendrocyte glycoprotein antibody‐associated disorders: An overview

“…In contrast, it has long been controversial whether MOG antibodies could have a pathogenic role in multiple sclerosis (MS) because of possible epiphenomena in CNS diseases. 5,6 In recent studies with human MOG-transfected cell-based assays, conformation-sensitive MOG antibodies were detected in a fraction of patients with CNS inflammatory demyelinating diseases such as ADEM, bilateral ON, transverse myelitis, NMOSD without AQP4 antibody and brainstem/cortical encephalitis but were rarely detected in classic MS. [7][8][9] Several recent pathological reports have suggested the dominance of humoral immunity and demyelination in MOGAD patients, and we suggested the development of perivenous inflammatory demyelination, such as ADEM pathology, in our studies, 10,11 which is also confirmed by other groups. 12 Similar to NMOSD, MOG antibodies are produced mainly by plasmablasts and/or plasma cells in peripheral tissues, 13 and demyelination is probably caused by MOG antibodies mainly coming from crossing the blood-brain barrier.…”

“…They microinjected human MOG‐IgG into mouse brains and compared the histopathological changes with those induced by AQP4‐antibody, 52 and they showed that human MOG‐antibody produced reversible myelin changes and altered the expression of axonal proteins in the injected site of CNS without astrocyte or neuron loss. Histopathological studies in MOG antibody‐positive cases are rare, but it is not yet completely resolved whether these cases should truly be classified as MS or MOGAD 11 …”

Neurologic disorders caused by autoantibodies

“…Misu et al reviewed MOG antibody-associated disease (MOGAD). 1 MOGAD is a newly proposed disease concept, while the pathogenicity of anti-MOG antibodies has been debated for many years. The diagnostic criteria for MOGAD were published in 2023 2 ; however, qualified diagnosis is often confounded because the clinical features of MOGAD share similarities with NMOSD or multiple sclerosis (MS).…”

“…Misu et al reviewed MOG antibody‐associated disease (MOGAD) 1 . MOGAD is a newly proposed disease concept, while the pathogenicity of anti‐MOG antibodies has been debated for many years.…”