Abstract
This study examines the association of myelin oligodendrocyte glycoprotein immunoglobulin G–associated disorder with pediatric optic neuritis to guide prognosis and treatment.
Myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG)–associated disorder (MOGAD) is a recently described entity that is distinct from multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG–positive neuromyelitis optica spectrum disorder.1,2,3 A small cohort from the Pediatric Optic Neuritis Prospective Outcomes Study4 underwent MOG-IgG testing and we compared those whose results were MOG-IgG positive with those whose results were negative.
Methods
The study, protocol, and Health Insurance Portability and Accountability Act–compliant informed consent forms were approved by each site’s institutional review board. Each patient’s parent or guardian provided written informed consent. Children also provided written consent when applicable as determined by the local institutional review board. Parents of 13 of 44 study participants who underwent MOG-IgG testing also provided written consent to provide their child’s serum to the Neuroimmunology Research Laboratory at the Mayo Clinic, Rochester, Minnesota, to measure AQP4-IgG and MOG-IgG with Clinical Laboratory Improvement Amendments–certified fluorescence-activated cell sorting cell-based assays. We compared demographic and clinical characteristics at enrollment and visual outcomes after 6 months for MOG-IgG–positive participants and MOG-IgG–negative participants. Analyses were conducted using SAS version 9.4 (SAS Institute).
Results
Among 13 participants with MOG-IgG testing and 31 without MOG-IgG testing, the mean (SD) age was 10.9 (3.1) and 10.0 (3.6) years, respectively. Bilateral disease was found in 7 patients (54%) with MOG-IgG testing vs 9 patients (29%) without. Mean (SD) visual acuity (VA) from all eyes at enrollment was 0.83 (0.72) logMAR (Snellen equivalent of 20/140) for patients with testing vs 1.02 (0.69) logMAR (Snellen equivalent of 20/200) for those without.
MOG-IgG was positive in 7 of 13 children (54%; 95% CI, 25-81) (Table). Six of 7 MOG-IgG–positive participants and 3 of 6 MOG-IgG–negative participants were male (Table). Mean (SD) age was 10.3 (3.7) years for participants who were MOG-IgG positive and 11.5 (2.3) years for those who were MOG-IgG negative. Both eyes were affected in 4 of 7 MOG-IgG–positive participants and in 2 of 6 MOG-IgG–negative participants.
Table. Patient Data.
| Patient No. | MOGa | Eye(s) | Onset | Symptoms | Optic disc edema | White matter lesions on masked MRI review | Lesions | Enhancement | logMAR (Snellen equivalent) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subcortical white matter | Cortical | Deep gray hyper | Optic nerve | Perineural | Sheath | Baseline | 6 mo | |||||||
| 1 | Positive | Both | Bilateral simultaneous | Headache | Both | Yes | Absent | 1 or 2 | Absent | Both | NA | Both | OS: 1.70 (<20/800); OD: 0.16 (20/30) | NA |
| 2 | Positive | Right | Bilateral simultaneous | Difficulty with coordination, headache | Right | No | Absent | None | Absent | Left | NA | Left | OD: 1.70 (<20/800) | OD: 0.04 (20/20) |
| 3 | Positive | Left | Unilateral | Headache | Left | Yes | Absent | None | Absent | Left | Left | Left | OS: 0 (20/20) | OS: −0.10 (20/15) |
| 4 | Positive | Both | Bilateral simultaneous | NA | NA | Yes | Absent | None | Absent | Both | NA | Both | OS: 1.70 (<20/800); OD: 1.70 (<20/800) | OS: 0.60 (20/80; OD: 0.60 (20/80) |
| 5 | Positive | Right | Unilateral | Headache | NA | Yes | Absent | None | Present | Right | NA | NA | OD: 0.70 (20/100) | OD: 0 (20/20) |
| 6 | Positive | Left | Unilateral | NA | Left | Yes | Absent | ≥3 | Absent | Left | Left | Left | OS: 1.70 (<20/800) | OS: 0.30 (20/40) |
| 7 | Positive | Both | Bilateral simultaneous | NA | Both | No | Absent | None | Absent | Both | NA | Both | OS: 1.70 (<20/800); OD: 0.20 (20/30) | OS: 0.10 (20/25); OD: −0.10 (20/15) |
| 8 | Negative | Right | Unilateral | Focal weakness, headache | NA | Yes | Absent | ≥3 | NA | NA | NA | NA | OD: 0.10 (20/25) | OD: −0.16 (20/15) |
| 9 | Negative | Right, then left | Bilateral sequential | NA | Right | No | Absent | None | Absent | Both | NA | NA | OD: 0.70 (20/100) | OD: 1.40 (20/500) |
| 10 | Negative | Left | Unilateral | NA | NA | No | Absent | None | Absent | NA | NA | NA | OS: −0.06 (20/20) | OS: 0 (20/20) |
| 11 | Negative | Right | Unilateral | Headache | Right | No | Absent | None | Absent | Right | NA | Both | OD: 0.20 (20/30) | OD: 0 (20/20) |
| 12 | Negative | Both | Bilateral simultaneous | NA | Both | Yes | Present | None | Absent | Both | NA | Both | OS: 0.10 (20/25); OD: 0.50 (20/60) | OS: 0 (20/20); OD: 0 (20/20) |
| 13 | Negative | Both | Bilateral simultaneous | NA | Both | No | Absent | None | Absent | Both | Both | Left | OS: 1.30 (20/400); OD: 0.80 (20/125) | NA |
Abbreviations: Deep gray hyper, deep gray matter hyperintense lesions; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance imaging; NA, not applicable.
MOG was determined by the Mayo Clinic.
At presentation, the 10 MOG-IgG–positive eyes with optic neuritis (ON) had a median (range) VA of 1.7 (0-1.7) logMAR (Snellen equivalent of worse than 20/800), with 6 MOG-IgG–positive eyes worse than 20/800, for which a logMAR of 1.7 was assigned (Table). The 8 MOG-IgG–negative eyes with ON had a median (range) VA of 0.4 (−0.1 to 0.8) logMAR (Snellen equivalent of 20/50), with none having VA worse than 20/800. After 6 months, the median (range) VA for MOG-IgG–positive eyes with ON was 0.1 (−0.1 to 0.6) logMAR (Snellen equivalent of 20/25), while the median (range) VA for MOG-IgG–negative eyes with ON was 0 (−0.2 to 1.4) logMAR (Snellen equivalent of 20/20).
None of the participants who were MOG-IgG positive had periventricular white matter lesions or met the 2017 McDonald diagnostic criteria for MS. None were positive for AQP4-IgG.
Discussion
Of the 13 participants tested in this prospective observational study on pediatric ON,4 7 (54%) tested positive for MOG-IgG. Our results are consistent with prior studies that suggest that more than 30% of children with demyelinating disease will be positive for MOG-IgG, with higher rates in association with pediatric ON and acute disseminated encephalomyelitis because of MOG-IgG predilection for these types of attacks.3,5 This varies from adults where MOG-IgG is positive in approximately 5% of individuals with demyelinating disease.3
In this small cohort, MOG-IgG–positive individuals with ON tended to have bilateral disease at presentation and present with severe VA loss. Despite the severity of VA loss at presentation, individuals who were MOG-IgG positive generally had substantial recovery, similar to previous reports.1,3,5,6 The present study also supports the lack of predominance of MOGAD among female individuals that has been demonstrated in previous studies.1,2,3,5
One limitation in this study was that not all participants underwent MOG-IgG testing. While demographic characteristics and severity of VA loss were similar between the 2 groups, individuals with bilateral disease were more often tested for MOG-IgG, which may have produced some bias in the analyzed subgroup.
In summary, the Pediatric Optic Neuritis Prospective Outcomes Study found MOGAD to be commonly associated with pediatric ON. Therefore, MOG-IgG testing may be considered for pediatric patients with new-onset ON to help guide prognosis and treatment.3 Diagnosing MOGAD in these individuals is important, because patients with MOGAD do not typically develop MS and because treatments differ between MOGAD and MS.
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