Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct acquired central nervous system (CNS) demyelinating disorder, separate from multiple sclerosis (MS) and aquaporin-4 (AQP4)-seropositive neuromyelitis optica spectrum disorder (NMOSD). The presence of MOG-IgG, detected by cell-based assays, is central to diagnosis. MOGAD can present as monophasic or relapsing, with variable clinical features and outcomes.
Definition and Epidemiology
- Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an immune-mediated demyelinating disorder of the CNS characterized by IgG autoantibodies against MOG.
- MOGAD is now classified as a distinct clinical entity, separate from MS and AQP4-positive NMOSD.
- The incidence of MOGAD is rare: estimated at 1–3 per 1,000,000 person-years; prevalence is around 2 per 100,000.
- This incidence is similar to AQP4-NMOSD but far lower than MS.
- Unlike MS and AQP4-NMOSD, MOGAD shows no strong gender bias (male:female ratio ~1:1).
- No clear ethnic predisposition has been identified.
- MOGAD can affect all ages but is more common in children and young adults.
- Mean age of onset in adults is early 30s; in children, it's more frequently diagnosed than MS or AQP4-NMOSD.
- In children with ADEM or other first demyelinating episodes, ~40–50% are MOG-IgG positive.
Pathophysiology and Immunological Basis
- MOG is a glycoprotein expressed on the outer surface of CNS myelin and oligodendrocytes.
- Its role may include maintaining myelin integrity and mediating immune signaling.
- MOG-IgG (mostly IgG1 subclass) induces inflammatory demyelination through complement activation and ADCC.
- Complement-mediated injury is less severe in MOGAD than in AQP4-NMOSD.
- MOGAD is an oligodendrocytopathy, unlike AQP4-NMOSD (astrocytopathy) and MS (primarily T-cell driven).
- MOGAD features a Th17-dominated cytokine profile (e.g., IL-6, IL-17), shared with AQP4-NMOSD but distinct from MS (Th1).
- Commonly follows a viral illness, especially in pediatric ADEM cases.
- Serum MOG-IgG can wane or disappear after the acute phase, especially in monophasic disease.
Clinical Features
- Optic Neuritis: The most common presentation, especially in adults. Bilateral optic neuritis is more frequent in MOGAD (31–58%) than in MS or AQP4-IgG NMOSD. Optic disc swelling is common (45–95%), and visual acuity loss can be severe but often recovers well after corticosteroid treatment. Relapses are frequent, especially during or after corticosteroid tapering.
- Acute Disseminated Encephalomyelitis (ADEM): Typical first manifestation in children, particularly under 11 years. MOG-IgG is found in about 50% of pediatric ADEM cases, but less often in adults. Children with MOG-IgG-positive ADEM are younger on average than seronegative cases. ADEM is often preceded by infection and fever.
- Transverse Myelitis: Another common presentation, which can occur alone, with ADEM, or with optic neuritis. Lesions are often longitudinally extensive (≥3 vertebral segments), centrally located, and may show the H-sign (grey matter involvement). Most patients recover well motorically, though residual sphincter or sexual dysfunction can occur.
- Brainstem/cerebellar syndromes: ~30% of cases. Symptoms: dysphagia, dysarthria, vertigo, ataxia; less frequent area postrema syndrome vs AQP4-NMOSD.
- Cortical encephalitis (FLAMES): Characterized by seizures, fever, focal deficits; shows FLAIR hyperintensities in cortex.
- Recurrent aseptic meningitis: CSF pleocytosis, leptomeningeal enhancement; responds to steroids.
- Seizures: Seen in 10–15% of pediatric MOGAD cases, usually with ADEM or encephalitis.
- Peripheral nervous system involvement: Rare; features myeloradiculitis or overlapping central + peripheral demyelination.
Login to Read More
