Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a general term for central nervous system (CNS) demyelinating diseases characterized by MOG-IgG antibodies. MOG is a glycoprotein expressed on the outermost layer of myelin and the surface of oligodendrocytes, widely distributed throughout the CNS.
MOGAD is classified as an oligodendrogliopathy. This contrasts with aquaporin-4 (AQP4) antibody-positive NMOSD, which targets astrocytes. The annual incidence is estimated at 1.6–4.8 per million, and the prevalence at 1.3–2.5 per 100,000. Dutch data show that the prevalence in children (0.31 per 100,000) exceeds that in adults (0.13 per 100,000).
The age of onset shows a bimodal distribution, with peaks at 5–10 years and 20–45 years. Approximately 50% of all cases are children, and about 50% of acute demyelinating syndromes in children under 11 years old correspond to MOGAD. The male-to-female ratio is 1:1.
In children, ADEM (acute disseminated encephalomyelitis) is the most common phenotype (40–50%), while optic neuritis (ON) and myelitis, which are more common in adults, increase with age. Children tend to have a higher rate of complete recovery (75–96%) and a lower relapse rate than adults. For details, see “Main Symptoms and Clinical Findings” and “Prognosis”.
The subjective symptoms of MOGAD vary depending on the phenotype.
The phenotype of MOGAD changes depending on age.
Under 11 years old
ADEM (acute disseminated encephalomyelitis): Most common phenotype (40–50%). Presents with multifocal demyelination and encephalopathy.
Cortical encephalitis (CCE/FLAMES): Seen in 13.5% of children with MOGAD. Characterized by unilateral cortical T2-FLAIR hyperintensity and meningeal enhancement. Beware of misdiagnosis as viral encephalitis.
Optic neuritis (ON): Less common in younger children, increasing with age.
Age 11 and older
Optic neuritis (ON): Frequency increases after age 11, transitioning to a pattern similar to adults. Some patients with initial ADEM may later relapse as ON as they grow older.
ADEM-ON: Accounts for up to 40% of relapsing MOGAD. 94% of relapses take the form of ON.
NMO (neuromyelitis optica): Approximately 4% of pediatric MOGAD. 58% of pediatric NMOSD are MOG-positive.
Characteristic findings of MOGAD-ON are shown below.
Regarding cortical encephalitis, a case series of 5 children reported seizures in all cases, prodromal fever in 4/5 cases, and frontal lobe lesions in all cases, with a median treatment delay of 12 days 1). Four of the 5 cases (80%) progressed to chronic epilepsy and were maintained on levetiracetam monotherapy 1).
Other phenotypes include limbic encephalitis (cognitive impairment tends to persist as a sequela) 1), leukodystrophy-like pattern (more common in children under 7 years) 2), and MOGAD-NMOS spectrum (MNOS) 2).
Differential diagnoses include multiple sclerosis (MS), AQP4-positive NMOSD, viral encephalitis, CNS vasculitis, malignancy, and hemophagocytic lymphohistiocytosis (HLH).
Typical presentation includes fever and headache followed by seizures. Suspicion should arise when MRI shows unilateral cortical T2-FLAIR hyperintensity and meningeal enhancement. Since misdiagnosis as viral meningoencephalitis is a concern, MOG-IgG testing should be actively considered in treatment-resistant encephalitis 1).
The etiology of MOGAD is not fully understood, but post-infectious and post-vaccination onset accounts for approximately 20% of cases.
For detection of MOG-IgG, live cell-based assay (CBA) is the gold standard. Fixed CBA is also widely used but does not provide titer information and requires combination with supportive features.
MOG-IgG is mainly of the IgG1 subclass, but cases with only IgG3 positivity also exist 2). Since the detection sensitivity for IgG3 varies depending on the type of secondary antibody used, subclass-specific analysis is important 2).
The performance of the MOGAD diagnostic criteria established in 2023 is shown below.
| Indicator | Children | Adults |
|---|---|---|
| Sensitivity | 100% | 91.9% |
| Specificity | 98.9% | 98.9% |
| Vitrectomy (positive predictive value) | 98.0% | 89.4% |
| NPV (negative predictive value) | 100% | — |
| Accuracy | 99.2% | — |
Children tend to fulfill more supportive features than adults (p=0.0011).
The IPMSSG ADEM diagnostic criteria are used for diagnosing ADEM. Initial multifocal CNS symptoms and encephalopathy are essential requirements, and a comprehensive assessment is made by combining MRI findings and MOG-IgG testing.
The first-line treatment for the acute phase is intravenous methylprednisolone therapy (IVMP). In Japan, steroid pulse therapy is the standard treatment for pediatric optic neuritis.
In MOGAD-associated optic neuritis, starting steroids/IVMP within 7 days of onset has been associated with good final visual outcome (for example BCVA 20/25 or better), with an odds ratio of 6.7. This is not a relapse-risk reduction statistic5).
IVMP
Dose: 20–30 mg/kg/day (max 1 g/day)
Duration: 3–5 days
Tapering: Within 3 months total. Tapering over 5 weeks or more reduces relapse risk.
IVIG
Dose: 1–2 g/kg (not exceeding 1 g/kg per day)
Duration: 1–5 days
Indication: Early transition if no rapid response to IVMP.
PLEX (Plasma Exchange)
Position: Escalation therapy after IVMP
Key point: Shorter time to PLEX is the strongest predictor of complete recovery
Indications: Severe cases unresponsive to IVMP and IVIG
Long-term immunosuppressive therapy is administered for recurrent or multiphasic cases.
Multidisciplinary team management involving pediatric neurology, ophthalmology, rehabilitation medicine, and psychology is recommended.
In the acute phase, treatment centers on IVMP; initiation within 7 days is associated with better final visual outcome. A sufficient tapering period (5 weeks or more) is important for reducing relapse risk. Relapses are more likely within 3 to 6 months after starting immunosuppressants, so concomitant use of oral steroids is recommended. In children, attention must also be paid to the impact of long-term immunosuppression on growth.
MOG is a glycoprotein expressed on oligodendrocytes and the outermost layer of myelin sheaths, widely distributed on myelinated nerve fibers in the CNS 2). MOGAD is an oligodendrogliopathy, distinct from the astrocytopathy of AQP4-positive NMOSD.
Pathological findings include activation of macrophages and microglia, appearance of MOG-containing macrophages, and deposition of complement and immunoglobulins. The persistence of premyelinating oligodendrocytes is considered one of the reasons why remyelination and good recovery are more likely in MOGAD.
It has been hypothesized that both NMDA receptors and MOG antigens are expressed on the surface of oligodendrocytes, and that viral infection-induced disruption of the blood-brain barrier (BBB) leads to exposure to both antigens, resulting in dual antibody production 2). During immunosuppression tapering, autoreactive immune cells are reactivated, leading to relapse. Good responsiveness to steroids has been reported 2).
Cases of MOG-IgG positive only for IgG3 have been reported 2). The clinical significance of IgG3 remains unclear, but the choice of secondary antibody used affects the detection of IgG3, so caution is needed when interpreting negative results 2).
Tocilizumab has been considered as a maintenance therapy candidate for relapsing or refractory MOGAD in case reports and reviews, but it is not established as a standard treatment in children2).
Telitacicept is a TACI-Fc fusion protein that suppresses B cells and plasma cells by simultaneously blocking BLyS and APRIL.
Treatments targeting B cells and plasma cells, such as telitacicept, are being investigated as research-stage options for refractory cases, including those resistant to RTX4).
Differences in MOG-IgG subclasses and measurement methods can affect diagnostic sensitivity and clinical interpretation, so standardization of testing methods and elucidation of clinical significance remain future challenges2).
In pediatric MOGAD, various central nervous system phenotypes such as cortical encephalitis and meningocortical symptoms have been reported, and evaluation of long-term outcomes including cognitive function is important 1).
Reports of MOGAD following COVID-19 vaccination are accumulating 3). Research is ongoing to elucidate the pathogenesis, optimal treatment, and long-term outcomes. No randomized controlled trials (RCTs) in children exist yet, and improving the quality of evidence remains a challenge.
The prognosis for pediatric MOGAD is generally better than for adults.
