Indications for Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Testing
MOG antibody testing is indicated for patients presenting with acute CNS demyelinating disorders including optic neuritis (particularly if bilateral or severe), longitudinally extensive transverse myelitis, acute disseminated encephalomyelitis (ADEM), or brainstem encephalitis that are atypical for multiple sclerosis. 1
Primary Clinical Presentations Warranting MOG Antibody Testing
Optic Neuritis Presentations
- Simultaneous bilateral acute optic neuritis
- Unusually high frequency of optic neuritis episodes
- Particularly severe visual deficit or blindness during/after acute optic neuritis
- Prominent papilledema/papillitis/optic disc swelling
- Longitudinally extensive optic nerve lesions
- Perioptic gadolinium enhancement during acute optic neuritis 2, 1
Myelitis Presentations
- Longitudinally extensive transverse myelitis (LETM) spanning ≥3 vertebral segments
- Conus medullaris lesions, especially if present at onset
- Particularly severe or frequent episodes of myelitis
- Permanent sphincter and/or erectile disorders after myelitis 2, 1
Brain/Brainstem Presentations
- ADEM or ADEM-like presentations
- Recurrent or multiphasic ADEM
- ADEM with recurrent optic neuritis (ADEM-ON)
- Acute respiratory insufficiency, disturbance of consciousness, behavioral changes, or epileptic seizures with radiological signs of demyelination
- Brainstem encephalitis
- Area postrema syndrome with intractable nausea, vomiting, or hiccups 2, 1
Radiological Findings Prompting Testing
- Normal supratentorial MRI in patients with acute ON, myelitis, or brainstem encephalitis
- Brain MRI abnormal but without MS-typical lesions (no periventricular ovoid lesions, Dawson's fingers, or juxtacortical U-fiber lesions)
- Large, confluent T2 brain lesions suggestive of ADEM
- Bilateral thalamic lesions (particularly in ADEM) 2, 3
Laboratory Findings Supporting Testing
- Neutrophilic CSF pleocytosis or CSF white cell count >50/μl
- Absence of CSF-restricted oligoclonal bands
- Elevated IgG synthesis rate is rare in MOG antibody disease 2, 4
Treatment Response Patterns Suggesting Testing
- Frequent flare-ups after intravenous methylprednisolone
- Steroid-dependent symptoms (including chronic relapsing inflammatory optic neuropathy)
- Clear increase in relapse rate following treatment with interferon-beta or natalizumab in patients diagnosed with MS 2, 1
Special Considerations
Pediatric Population
- Testing criteria should be less stringent in children
- MOG antibody-associated disease is significantly more frequent in young children with acquired demyelinating disease (up to 70%) compared to adults (≤1% in Western countries, ≤5% in Asian countries) 2
- Encephalopathy is a more common presentation in pediatric patients 3
Testing Strategy
- Cell-based assays with native MOG as the substrate are strongly recommended for MOG-IgG testing, as older assay methods lack specificity 1
- If costs are a concern, consider testing AQP4-IgG first in stable patients, since it's more frequent in NMOSD 1
- "Double positive" results for both AQP4 and MOG antibodies are extremely rare and should prompt retesting 1
Important Pitfalls to Avoid
- MOG antibody testing is generally not recommended in patients with a progressive disease course due to very low pre-test probability 1
- A positive MOG-IgG result should be challenged if the clinical presentation includes "red flags" atypical for MOG antibody disease 2
- Relying on older, less sensitive assay methods can lead to false results 1
- Testing all patients with typical MS is not recommended and may lead to overdiagnosis 5
Clinical Impact of Diagnosis
Early identification of MOG antibody-associated disease is crucial for appropriate treatment selection, as some MS therapies may be ineffective or potentially harmful in these patients 1. MOG antibody disease is distinct from both multiple sclerosis and AQP4-positive neuromyelitis optica spectrum disorder, with different treatment approaches and prognosis 5, 6.