What is MOG (myelin oligodendrocyte glycoprotein) positive?

MOG-Positive (MOGAD): A Distinct Autoimmune CNS Demyelinating Disease

MOG-positive refers to the presence of IgG antibodies against myelin oligodendrocyte glycoprotein (MOG), defining a distinct inflammatory demyelinating disease of the central nervous system called MOG-IgG-associated encephalomyelitis (MOG-EM) or MOGAD, which is immunopathogenetically separate from both multiple sclerosis and aquaporin-4-positive neuromyelitis optica spectrum disorders. 1

What MOG Antibodies Target

• MOG is a glycoprotein located on the outermost surface of myelin sheaths in the brain, spinal cord, and optic nerves, making it uniquely vulnerable to autoimmune attack 2, 3
• The antibodies demonstrate direct pathogenic impact through humoral immune mechanisms, causing primary demyelination with intralesional complement and IgG deposits 2
• MOG-IgG antibodies are nearly always absent in patients with aquaporin-4 antibodies, establishing these as distinct disease entities 1, 2

Clinical Presentations of MOGAD

The disease manifests through several characteristic syndromes:

Optic Neuritis (Most Common in Adults)

• Occurs in approximately 55% of patients at onset, frequently bilateral (35% of optic neuritis cases) 4
• Presents with severe visual deficit or blindness, prominent papilledema, papillitis, or optic disc swelling 2
• Optic nerve lesions are characteristically long (>50% of nerve length), predominantly anterior, but can extend to the chiasm 2, 4

Transverse Myelitis

• Longitudinally extensive transverse myelitis (LETM) affecting ≥3 vertebral segments is characteristic 2
• Conus medullaris involvement is particularly typical of MOGAD 2, 4
• Can result in permanent sphincter and erectile dysfunction 2

Acute Disseminated Encephalomyelitis (ADEM)

• Most frequent presentation in children, often monophasic in pediatric cases 2, 3
• Presents with large, confluent T2 brain lesions, altered consciousness, behavioral changes, or seizures 2
• Can manifest as "recurrent ADEM," "multiphasic ADEM," or "ADEM-ON" (ADEM with recurrent optic neuritis) 2

Brainstem and Cortical Encephalitis

• Brainstem encephalitis with area postrema syndrome (intractable nausea, vomiting, hiccups) 5
• Cortical encephalitis with seizures has been reported, representing an important phenotype 2, 4

Disease Course Patterns

• Adults experience relapsing disease in at least 80% of cases, while children more commonly have monophasic disease 2
• Cumulative relapse probability at 1 year is 42.8% and at 4 years is 62.8% 4
• High risk of flare-ups after steroid cessation, requiring slow tapering 2, 6
• Relapses often occur in different CNS locations from the initial attack 4

Diagnostic Testing Requirements

Antibody Detection

• Testing requires cell-based assays (CBA) using full-length, conformationally intact human MOG protein 1, 2
• Serum is the specimen of choice over CSF 1, 2
• MOG-IgG titers are disease-activity dependent (higher during acute attacks, lower during remission and on immunosuppression) 1, 2
• If initially negative but clinical suspicion remains high, retest during acute attacks, treatment-free intervals, or 1-3 months after plasma exchange/IVIG 1, 6

Distinguishing Laboratory Features

• Cerebrospinal fluid often shows neutrophilic pleocytosis or white cell count >50/μl 2
• Absence of CSF-restricted oligoclonal bands (unlike MS) 2
• Testing for MOG-IgM or MOG-IgA is currently not recommended 1

When to Test for MOG-IgG

Based on international consensus, test in patients presenting with: 1

• Longitudinally extensive transverse myelitis (≥3 segments)
• Severe or bilateral optic neuritis
• ADEM-like presentations
• Recurrent optic neuritis or myelitis
• AQP4-antibody negative NMOSD phenotypes

Critical Diagnostic Pitfalls

• Progressive disease course is very atypical for MOGAD and should prompt reconsideration of the diagnosis 2
• 33% of MOGAD patients meet McDonald's criteria for MS at some point, leading to frequent historical misdiagnosis 2
• Up to 70% have brain MRI lesions at onset, which can be confused with MS 5
• "Double-positive" AQP4-IgG/MOG-IgG results are extremely rare and should prompt retesting with alternative methodologies 5
• When cost is a factor and disease is stable, test AQP4-IgG first since it is more frequent in NMOSD; if disease is active or costs are not a concern, test both antibodies in parallel 5

Treatment Implications

Acute Attack Management

• High-dose intravenous methylprednisolone is first-line therapy 2, 6
• Plasma exchange or immunoadsorption should be initiated early if steroids fail 2, 6
• Mandatory slow steroid taper due to high flare-up risk after rapid cessation 2, 6

Long-Term Preventive Therapy

• Reserved for relapsing disease only (not indicated after monophasic presentations) 2, 6
• Observational benefit reported from rituximab, IVIG, and oral immunosuppressants 2, 6
• Beta-interferons, natalizumab, and fingolimod are contraindicated and can exacerbate disease due to different immunopathogenesis from MS 2, 6

Prognosis

• MOGAD has a more favorable prognosis than AQP4-positive NMOSD, with lower disability scores at follow-up 2, 6
• Brainstem involvement in the first event does not indicate worse prognosis in MOGAD (unlike MS) 2, 6
• Good response to initial steroid therapy occurs in 74% of patients 4
• Some monophasic adult cases show permanent disappearance of MOG-IgG following clinical recovery 1

Epidemiology

• Prevalence is approximately 1.3-2.5 per 100,000 population 7
• Annual incidence is approximately 3.4-4.8 per million 7
• Significantly more frequent in young children, with frequency declining with age 2
• Median disease onset age is 29 years (range 3-62 years), with approximately 30% of cases in the pediatric age group 4, 7
• No apparent female preponderance (unlike AQP4-positive NMOSD) 7
• Precedent infection reported in approximately 20-40% of cases 7