A rare but distinct and unique phenotype of MOGAD.

Abstract

Myelin oligodendrocyte-immunoglobulin G–associated disorders (MOGADs) are a newly defined entity of acquired demyelinating syndromes (ADSs). The three main clinical phenotypes consist of acute disseminated encephalitis (ADEM), optic neuritis (ON) and transverse myelitis (TM)/longitudinally extensive transverse myelitis (LETM). The clinical presentation is very much influenced by the age of the patient with ADEM occurring more often in children and ON in adults. Depending on the study, a relapsing disease course can occur in up to 40% of patients. In addition to the main phenotypes, other manifestations include myelin oligodendrocyte (MOG)-encephalitis with a unique clinical presentation, typical magnetic resonance imaging (MRI) features and good response to steroid treatment.1 Another unique and even rarer phenotype is described in the teaching case of this month issue of MSJ.2 The authors report a 4-year-old child who initially presented with all the hallmarks of ADEM, remained well until the age of 17 years and then developed progressive neurological decline over several years. MRI of the brain showed changes reminiscent of a progressive leukodystrophy. Despite treatment, the patient’s condition further deteriorated. Several aspects are remarkable. First, the child presented with ADEM. At the time, serum myelin oligodendrocyte-antibodies (MOG-abs) were not measured. One hypothesis is that the child already harboured MOG-abs with a presumed monophasic disease course but then developed another episode 13 years later (!). Second, the further course is reminiscent of a primary-progressive disease course with elements of neuroinflammation and neurodegeneration. The clinical course accompanied by MRI changes with confluent white matter changes and contrast medium enhancement is in stark contrast to the usually observed variants with good response to immunotherapy. The role of MOG-IgG antibodies in this subtype of MOGAD remains unclear. Serum MOG-IgG antibodies are mainly of the IgG1 subtype, induce complement-mediated cytotoxicity and transiently disrupt microtubule organization of oligodendrocyte.3,4 In this subtype of MOGAD, additional host and environmental factors are most likely instrumental in the disease process. As the authors conclude MOG-IgG antibodies should be tested in cases with leukodystrophy of unclear origin in the future.