Treatment Approaches for MOG-Ab-Associated Demyelination in Children

Abstract

Purpose of review: The purpose of this review is to summarize current understanding regarding the treatment of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelination in children. Emphasis is placed on the unique obstacles we face when predicting the risk of relapse and the important implications of such challenges when planning treatment protocols.

Recent findings: MOG-Abs are consistently identified in a range of acquired demyelinating syndromes (ADS) in adults and children with a clinical phenotype distinct of MS and AQP4-Ab neuromyelitis optica spectrum disorder. Although initially thought to be associated with a benign disease, recent reports of children who are treatment-resistant and developed progressive disability over time raise important questions about how children with relapsing MOG-Ab disease should be managed. MOG-Abs are common in children with ADS with both monophasic and relapsing disease courses. Treatment of patients with MOG-Ab-associated demyelination includes management of acute relapses and chronic immunotherapy for those with relapsing disease. Emerging consensus supports distinction of treatment strategies from those typically used for relapsing remitting MS, and several groups debate whether to follow treatment protocols akin to those for AQP4-Ab NMOSD. A key challenge remains predicting the severity of the disease at onset. Collaborative international consensus to derive shared clinical evaluative platforms standardized biological and neuroimaging protocols which can be used clinically, and partnered research programs are required to advance personalized treatment for children with MOG-Ab-associated demyelination.

Keywords: Acquired demyelination syndromes (ADS); Acute disseminating encephalomyelitis (ADEM); Autoantibodies; Myelin oligodendrocyte glycoprotein (MOG); Neuromyelitis optica spectrum disorder (NMOSD).

Fig. 1

MRI findings in children with MOG-Ab-associated disease. A 10-year-old boy presented with encephalopathy, limb weakness (but able to walk), bilateral optic neuritis with only light perception, and urinary incontinence. MRI revealed longitudinally extensive transverse myelitis (a) and bilateral optic neuritis with enhancement (b). He relapsed 4 months later with headaches, fever, and encephalopathy. MRI revealed confluent lesions involving the pons, midbrain, and the superior cerebellar peduncles (c) as well as the left frontal opercular cortex. The previous spinal lesion has significantly improved (d). A 4-year-old girl presented with encephalopathy, seizures, and lethargy progressed to weakness of her right arm and bilateral 6th nerve palsies. MRI demonstrated a focus of signal change in the right thalamus (e). She relapsed 4 months later with brainstem cerebellar syndrome and lesions in both middle cerebellar peduncles (f) as well as a new lesion in the left side of the midbrain (not shown). At 4 years of age, she presented with bilateral optic neuritis. MRI showed diffuse bilateral white matter signal abnormality involving the cortical and subcortical regions extending inferiorly along the cerebral peduncles, pons, and right middle cerebellar peduncle, as well as swelling and signal abnormality of the corpus callosum (g). She had a further episode of bilateral optic neuritis 1 year later. A 4-year-old girl presented with encephalopathy, headache, and lethargy and MRI findings revealed diffuse bilateral and asymmetric signal abnormalities of the basal ganglia and thalamus with similar non-enhancing disease of the cortex, subcortical and deep white matter of both hemispheres (h). Repeat imaging 3 months later demonstrated near complete resolution of all lesions, concurrent with clinical recovery. She relapsed 15 months later with new onset headaches, encephalopathy characterized by behavioral change with hallucinations and confusion, and MRI evidence of new cortical and juxtacortical T2 lesions (j).

Fig. 2

Treatment algorithm for children with MOG-Ab-associated disease. IVMP intravenous methylprednisolone, PLEX plasma exchange, IVIG intravenous immunoglobulin, AZA azathioprine, MMF mycophenalate mofetil.