MOG Antibody Testing Indications
MOG antibody testing is recommended for patients with monophasic or relapsing acute optic neuritis, myelitis, brainstem encephalitis, encephalitis, or any combination thereof, who have radiological or electrophysiological findings compatible with CNS demyelination, along with specific clinical and paraclinical features atypical for multiple sclerosis. 1
Clinical Presentations That Warrant MOG-IgG Testing
Optic Neuritis Presentations
- Simultaneous bilateral acute optic neuritis
- Unusually high frequency of optic neuritis episodes
- Particularly severe visual deficit or blindness in one or both eyes
- Longitudinally extensive optic nerve lesions (>1/2 of pre-chiasmal optic nerve)
- Perioptic gadolinium enhancement during acute optic neuritis
- Prominent papilledema/papillitis/optic disc swelling during acute episodes 1
Myelitis Presentations
- Longitudinally extensive transverse myelitis (≥3 vertebral segments)
- Longitudinally extensive spinal cord atrophy in patients with history of acute myelitis
- Conus medullaris lesions, especially at disease onset
- Particularly severe or frequent episodes of myelitis
- Permanent sphincter and/or erectile disorders after myelitis 1
Brain/Brainstem Presentations
- Acute disseminated encephalomyelitis (ADEM) or ADEM-like presentations
- Recurrent or multiphasic ADEM
- ADEM with recurrent optic neuritis (ADEM-ON)
- Acute respiratory insufficiency, disturbance of consciousness, behavioral changes
- Epileptic seizures with radiological signs of demyelination
- Area postrema syndrome (unexplained intractable nausea, vomiting, hiccups) 1, 2
MRI Findings
- 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
- Middle cerebellar peduncle fluffy infiltrates
- Thalamic and pontine lesions 1, 3
CSF Findings
- Neutrophilic CSF pleocytosis or CSF white cell count >50/μl
- Absence of CSF-restricted oligoclonal bands (particularly in European patients) 1
Special Considerations
Pediatric Patients
- Testing criteria should be less stringent in children, as MOG-EM is significantly more frequent in young children with acquired demyelinating disease (up to 70%, declining with age) compared to adults (≤1% in Western countries) 1
Timing of Disease Onset
- Disease onset within 4 days to ~4 weeks after vaccination 1
Treatment Response Patterns
- 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 1
Testing Approach
When to test for both MOG-IgG and AQP4-IgG:
- If costs are not a concern, test both antibodies in parallel
- If disease is active and requires fast decision-making, test both simultaneously
When to test AQP4-IgG first:
- If costs are a concern and disease is stable (AQP4-IgG is more frequent in NMOSD) 1
Important Caveats
- MOG-IgG testing should be performed using cell-based assays with native MOG as the substrate, as older assay methods (immunoblot, ELISA) lack specificity 4
- 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-EM 1
- MOG antibody-associated disease (MOGAD) is distinct from both multiple sclerosis and AQP4-positive NMOSD, with different treatment responses and prognosis 4, 2
- MOG-IgG can be associated with seizures, particularly during steroid taper or during ADEM episodes 5
Early identification of MOGAD is crucial for appropriate treatment selection, as some MS therapies may be ineffective or potentially harmful in these patients. The diagnosis impacts long-term management decisions and helps predict disease course.