Clinical and MRI phenotype of children with MOG antibodies

Abstract

Objective: To investigate the clinical and magnetic resonance imaging (MRI) features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-seropositive pediatric demyelinating syndromes.

Methods: Serum samples collected from 74 children with suspected demyelinating disorders whom were being followed at Massachusetts General Hospital were incubated with control green fluorescent protein (GFP)- and MOG-GFP-transfected Jurkat cell clones. The binding ratios were calculated using flow cytometry. Using statistical analyses, we compared the demographic, clinical and radiological features in our seropositive and seronegative patients.

Results: We found that 13 out of 74 (17.5%) patients were seropositive for MOG. The MOG-seropositive patients were younger than the seronegative patients (p = 0.049). No single disease category predominated among the seropositive patients, nor was one group more likely to have a polyphasic course. There were two out of four neuromyelitis optica (NMO) patients who had MOG antibodies; both were seronegative for aquaporin -4 (AQP4) antibodies. One had monophasic disease and the other had frequent relapses. There was a bimodal distribution of the MOG-seropositive patients by age at onset, with a distinct younger group (4-8 years) having a high prevalence of encephalopathy and an older group (13-18 years), whom presented almost exclusively with optic neuritis. MRI analysis demonstrated the absence of corpus callosum lesions in the seropositive patients (p = 0.012). The annualized relapse rate (ARR) and the Expanded Disability Status Scale (EDSS) results at 2 years did not differ between the seropositive and seronegative patients.

Conclusion: MOG antibodies are found across a variety of pediatric demyelinating syndromes having some distinct clinical and MRI features.

Keywords: Acute disseminated encephalomyelitis; demyelinating syndromes; encephalopathy; glycoprotein; magnetic resonance imaging; multiple sclerosis; myelin; myelin oligodendrocyte glycoprotein; neuromyelitis optica; optic neuritis; pediatric multiple sclerosis; serology.

Figure 1

MOG antibody binding ratios by disease category: 74 children with demyelinating diseases were tested for MOG antibody status., and compared to 23 pediatric healthy controls. Binding ratio>5 was consider positive. Some children within different categories of demyelinating disease including ADEM, CIS, MS and NMO were seropositive for MOG.

Figure 2

Age at first symptom for MOG seropositive and seronegative patients: Shows two distinct age groups amongst MOG seropositive patients of children a younger group between the ages of 4–8; and an older group between the ages of 10–13. The distribution of age at onset in the seropositive group was distinctly bimodal (Silverman’s test for one mode: p=0.03), with a subset of seven young patients having onset between ages 3.3–7.7, while six older patients had an onset between 13.8–17.9. None of the older seropositive patients presented with encephalopathy as the first symptom, while 5/7 (71.4%) of the younger seropositive patients had encephalopathy as the first symptom was (p=0.02). In contrast 5/6 of the older seropositive children presented with optic neuritis, compared to 3/7 of the younger seropositive children.