The Expanding Clinical Spectrum of Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Associated Disease in Children and Adults

In this review, we organize the clinical presentations of MOGAD by neuroanatomic compartments. This organization is useful for didactic purposes but should not be taken to imply that MOGAD affects one CNS compartment to the exclusion of others. Quite the contrary: Another interesting feature of MOGAD is that it manifests differently in children and adults.MOGADChildren under the age of 11, usually present with ADEM (encephalopathy, multifocal neurologic deficits and 'fluffy' cerebral lesions in a bilateral distribution). In adolescents and adults, focal syndrome -optic neuritis, longitudinally extensive myelitis, and focal encephalitis predominate . Unlike MS, where relapse rates are higher in children and decline with age, in MOGAD, 80% of pediatric patients had monophasic course ).However, the rate of monophasic disease may be an overestimate due short follow up (right censoring): recent case reports documented disease reemergence years and even decades after the initial episode in childhood Numa et al., 2015). Given the important differences in pediatric and adult MOGAD, we will qualify discussion of specific syndromes with reference to the respective age group. Optic neuritis (ON) is the most common presentation of MOGAD in adolescence and adulthood.ON is associated with a higher risk of subsequent relapse compared to the other presentations (Chen & Bhatti, 2019;Jurynczyk et al., 2017). At the onset, vision loss is often severe and up to 80% of patients have bilateral optic nerve involvement, which is highly unusual in MS (Ramanathan et al., 2015;Lock et al., 2019). Despite the severity of vision loss in the acute phase, recovery is usually good, especially in children: 89-98% of children had visual acuity to 20/25 or better at 6 months (Lock et al., 2019). In adults, only 6-14% of patients had ³20/200 in the affected eye in the long term (Chen & Bhatti, 2019).Optic disc edema is rare in MS or NMOSD but was present in 86% of patients with MOGAD-ON (Chen & Bhatti, 2019). Bilateral ON with disk edema may be mistaken for idiopathic intracranial In young children, MOGAD typically presents as ADEM (Reindl & Waters, 2019). MRI of the brain shows, ill-defined bilateral lesions (Fig. 1E)Brainstem involvement can be seen in 30% of MOGAD patients, and is a risk factor for a higher EDSS at long-term follow-up and more active disease . Brainstem inflammation can occur concomitantly with inflammation in optic nerves (40%), spinal cord (89%) and cerebrum (66%) . However, there are reports of isolated brainstem inflammation as well (Fig H) . Any part of the brainstem can be affected, medulla being the most common, followed by the pons and midbrain; cerebellum and cerebellar peduncles can also be affected (Jarius et al., 2017;Juryncyzk et al., 2017b). Since the first cases of MOG Ab associated neurologic diseases appeared just a few years ago (Rostasy et al., 2012), the floodgates of case reporting have been opened and our understanding of MOGAD has grown exponentially. We now recognize that there are certain clinical radiologic features that help to differentiate MOG-ON and MOG-TM from NMOSD syndromes; that pediatric ADEM is frequently associated with MOG Ab, especially if recurrent or followed by episodes of ADEM or ON; that in adults, MOG can be associated with seizures and focal cerebral edema ('FLAMES syndrome'); that brainstem inflammation is seen in a significant minority of MOGAD patients and may even be an isolated finding; that MOG antibody is almost never found in MS or AQ4 Ab positive NMOSD, but may co-exist with NMDA and other autoimmune encephalidites (Kunchok et al., 2019). Yet much remains to be learned. We need to determine sensitivity, specificity, positive and negative predictive value of MOG Ab in the various neurologic syndromes; whether MOG Ab be tested in CSF if it is negative in serum (Marrioto et al., 2019); whether isolated seizures without brain lesions, CLIPPERS, and CNS vasculitis should be subsumed under MOGAD rubric. Most importantly, we need to better stratify risk of disease recurrence after first or second episode and determine best treatments to prevent recurrence. With the rapid pace of progress, we can expect to answer these and other questions, and, no doubt, find new surprises along the way.