Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)
MOGAD is a distinct autoimmune demyelinating disorder of the central nervous system characterized by the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG), typically presenting with optic neuritis, myelitis, brainstem encephalitis, or acute disseminated encephalomyelitis-like presentations. 1
Definition and Pathophysiology
MOGAD is now recognized as a disease entity in its own right, immunopathogenetically distinct from both multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). 1, 2
The pathophysiology involves:
- Antibodies targeting MOG, a glycoprotein expressed on the outer membrane of myelin in the central nervous system
- T-cell mediated inflammation with CD4+ T cells as the dominant T cell type in lesions 3
- Potential mechanisms of tissue damage include:
- Opsonization of MOG
- Complement activation
- Antibody-dependent cellular cytotoxicity 3
- Infectious prodromes are commonly reported (37-70% of cases), suggesting potential immune trigger mechanisms 3
Clinical Presentations
MOGAD manifests with various clinical phenotypes:
- Optic neuritis (MOG-ON): Often bilateral with optic disc swelling 4
- Transverse myelitis: Frequently longitudinally extensive
- Acute disseminated encephalomyelitis (ADEM): More common in children
- Brainstem encephalitis
- Cortical encephalitis 2
Approximately 50% of patients follow a relapsing course, while others may have monophasic disease. 2
Diagnostic Features
MRI Characteristics
- Optic nerve: Longitudinally extensive lesions, perineural enhancement, optic perineuritis 4
- Spinal cord: Longitudinally extensive transverse myelitis (LETM), H-sign on axial images 2
- Brain: Multifocal T2 hyperintensities, often with better resolution over time compared to MS 2
- Absence of MS-typical features: Lacks the central vein sign typical of MS lesions 3
Laboratory Findings
- Serum MOG-IgG: Detection using cell-based assays (live cell-based assays preferred for specificity) 2
- CSF: May show pleocytosis; MOG antibodies sometimes detectable in CSF 2, 5
- Biomarkers: Elevated neurofilament light chain (NFL), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) during acute attacks 3
Differential Diagnosis
MOGAD must be distinguished from:
- Multiple sclerosis (MS)
- AQP4-IgG-positive NMOSD
- Acute disseminated encephalomyelitis (ADEM)
- Other inflammatory or infectious CNS disorders 1
Treatment Approach
Acute Attack Management
- First-line: High-dose intravenous methylprednisolone (IVMP) 2, 5
- For refractory cases: Plasma exchange or intravenous immunoglobulin (IVIG) 1, 2
Relapse Prevention
For patients with relapsing disease or severe residual disability:
- Immunosuppressive options:
Prognosis and Monitoring
- Disease course: Variable, with approximately 50% developing relapsing disease 2
- Treatment response: Generally good response to steroids in acute attacks, but relapses are common, especially with rapid steroid tapering 4
- Monitoring: Optical coherence tomography (OCT) may be useful for monitoring disease activity and predicting outcomes 4
Clinical Pitfalls and Caveats
- Misdiagnosis risk: MOGAD can be misdiagnosed as MS due to clinical and radiological overlap, potentially leading to inappropriate treatment 1, 6
- Testing considerations: Indiscriminate MOG-IgG testing in unselected populations increases false-positive results; testing should be guided by appropriate clinical and radiological features 1, 2
- Variable disease severity: While many patients respond well to treatment, some cases can follow an aggressive course with significant morbidity and mortality despite intensive immunotherapy 5
- Relapse risk: Relapses often occur during or after rapid corticosteroid tapering, suggesting the need for gradual steroid reduction 4