Pediatric MOGAD: Phenotype-Driven Presentation, Steroid Responsiveness, and Relapse-Guided Management

What is MOGAD and Phenotypic Presentations

Myelin oligodendrocyte glycoprotein associated disease (MOGAD) is an immune-mediated demyelinating disorder that can be monophasic or relapsing.¹ There is a growing spectrum of clinico-radiologic phenotypes. The most common manifestations in the pediatric population include acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM), and cerebral cortical encephalitis (CCE), a subset of which can be classified asFLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES).^1–3 These phenotypes can occur in isolation or together in an overlapping fashion. MOG+ADEM presents with encephalopathy and focal neurologic deficits, with or without seizures; MRI classically reveals large ill-defined T2 hyperintense supratentorial white matter lesions along with frequent involvement of the deep grey nuclei, pons, and/or middle cerebellar peduncles.^1,4,5 MOG+ON is typically anterior and long segment, and can be bilateral in approximately fifty percent of pediatric cases; despite excellent visual recovery, nadir visual acuity is often very poor, worse than 20/200 in about half of all cases.^1,4,6,7 MOG+TM is most commonly longitudinally extensive and has a predilection for the central grey and the conus.^1,4,8 MOG+CCE and FLAMES are meningocortical syndromes that often present with headache, seizures, and cortical lesions with overlying leptomeningeal enhancement on MRI.^2,3 ADEM is the most common phenotype among young children, whereas ON is the predominant phenotype among adolescents and teens.^9–11

Fortunately, most children recover well from MOGAD attacks. In prospective studies, the long-term median expanded disability severity score (EDSS) was 0 (IQR 0-1), with 67% of patients achieving complete neurological recovery and 85% having minimal to no residual deficits.^4,11 Residual symptoms and disability depend on phenotype of the initial presentation. In particular, bladder and/or bowel dysfunction can persist after MOGAD-associated TM, and CCE can result in encephalomalacia with risk of post-encephalitis epilepsy and residual cortical deficits.^2,3,11,12 In addition, a very rare leukodystrophy-like phenotype can arise following recurrent ADEM or multiphasic disseminated encephalomyelitis (MDEM) in young children; these cases portend poor neurocognitive recovery and a less favorable prognosis.^4,11

Relapses

Approximately 17-29% of incident pediatric MOGAD cases will relapse at least once.^4,11,13,14 One can find significantly higher relapse rates in non-incident cohorts, which are often enriched for relapsing cases due to study design. Relapse is notoriously difficult to predict. However, an onset attack of isolated optic neuritis and adolescent age at diagnosis have emerged as 2 risk factors for relapse in the pediatric population.¹⁵ Young children with ADEM have the lowest relapse risk,¹⁵ with 1 study reporting a relapse rate of only 9% among pediatric MOG+ ADEM.¹³

Acute Immunotherapy Considerations

Acute treatment response appears generally favorable across phenotypes. In a large Spanish cohort of 116 children with MOGAD, 85% achieved complete or near-complete recovery.¹¹ As MOGAD can be highly steroid responsive, first line treatment is a high dose corticosteroid pulse, regardless of onset phenotype. The most common dosing regimen is intravenous methylprednisolone 30mg/kg/day (max 1g/day) x 3-5 days.⁴ Approximately 97% of pediatric MOGAD cases demonstrate clinical improvement in 1 week of glucocorticoid initiation, with 61.8% achieving complete clinical recovery in 1 month.¹⁶ Following the high dose steroid pulse, most neuroimmunologists recommend an oral steroid taper, though there is considerable practice variation surrounding the duration of the taper. Adult onset MOGAD is often treated with prolonged oral steroid courses of three months or longer, whereas pediatric MOGAD tapers are generally shorter to avoid the metabolic consequences and other side effects associated with chronic steroids in children.¹⁷ These authors typically favor 4-6 week tapers, though there is a current trend in the field to consider even shorter tapers.

For patients with poor or incomplete response to corticosteroids, IVIg (2 g/kg divided over two to five days) or 5-7 sessions of plasma exchange (PLEX) are effective second-line options.⁴ Given the more rapid and, in our experience, dramatic improvement with plasma exchange, PLEX is preferred in cases of severe residual deficits and for patients requiring intensive care. In some cases, such as those with refractory seizures, cerebral edema, bilateral optic neuritis with near complete vision loss, and/or severe myelitis, these authors consider concurrent high dose steroids and PLEX. In a multicenter study of MOG+ON, escalation to PLEX was associated with improved visual acuity from median 20/400 to 20/20 and with decrease in EDSS from 4.0 to 1.0; 93% of patients achieved clinically significant improvement and 44% achieved complete remission following PLEX, with better recovery among younger patients and those with earlier initiation of PLEX.¹⁸ Lastly, the IL-6 inhibitor, tocilizumab, is emerging as an acute treatment option for severe pediatric MOGAD. Case reports document remarkable responses in life-threatening MOGAD presentations associated with malignant cerebral edema, and a pediatric case series demonstrated a 73% rate of significant clinical improvement in 72 hours of IV tocilizumab administration.^19,20

Refractory Cases and Maintenance Therapy Needs

Given the generally good recovery and relatively high probability of a monophasic course, most pediatric neuroimmunologists treat incident cases of pediatric MOGAD acutely but do not recommend maintenance immunotherapy after onset attack. However, most do recommend maintenance immunotherapy after relapse.¹⁷ In addition, these authors find it reasonable to consider immunotherapy in cases with incomplete recovery, although this decision should be made on a case-by-case basis.

Available evidence supports IVIg as the most effective established maintenance therapy. In a landmark European pediatric MOGAD study, IVIg reduced annualized relapse rate from 2.16 to 0.51 and improved EDSS scores, rendering IVIg the only maintenance therapy associated with both relapse risk reduction and improved disability⁹. Data from 7 large retrospective studies showed 70% of pediatric patients remained relapse-free on monthly IVIg, 52% relapse-free on mycophenolate, 44% relapse-free on azathioprine, and 47% relapse-free on rituximab.⁴ Though IL-6 inhibition is not yet widely used as a maintenance therapy given the efficacy and favorable adverse effect profile of IVIg, it is emerging as a potentially highly effective treatment that may warrant consideration, particularly in rare cases refractory to IVIg. In another study, tocilizumab reduced the annualized relapse rate from 1.75 to 0, with 79% of patients remaining relapse-free during a median two years of treatment.²¹

Summary

Pediatric MOGAD encompasses a heterogeneous, age-dependent spectrum of clinical phenotypes with overall favorable outcomes, though residual deficits remain phenotype-specific. The disease is often highly corticosteroid-responsive, with timely escalation to second-line therapies improving outcomes in severe presentations. Although most cases are monophasic, a clinically meaningful subset relapse, necessitating maintenance therapy. In this context, IVIg emerges as the most consistently effective long-term treatment, supporting a relapse-driven, stepwise management strategy.

Editor’s Note: Dr. Santoro disclosed that he serves as a consultant for UCB, TG therapeutics, and Dianthus. He has received research funding from the National Institutes of Health, Thrasher Research Foundation, and the Race to Erase MS Society.

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