What is MOG-EM (myelin oligodendrocyte glycoprotein-associated encephalomyelitis)?

MOG-EM (Myelin Oligodendrocyte Glycoprotein-Associated Encephalomyelitis)

MOG-EM is a distinct autoimmune inflammatory demyelinating disease of the central nervous system, characterized by the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), and is now recognized as a separate entity from both multiple sclerosis and aquaporin-4-positive neuromyelitis optica spectrum disorders. 1

Disease Definition and Pathophysiology

MOG-EM represents an antibody-mediated inflammatory condition where autoantibodies target MOG, a protein located on the outer surface of myelin sheaths in the brain, spinal cord, and optic nerves. 1 The disease is driven by both humoral and cellular immune responses that lead to perivenous inflammatory demyelination. 2

The key distinguishing feature is that MOG-EM is immunopathogenetically distinct from classic MS and AQP4-IgG-positive NMOSD, based on:

• Direct pathogenic impact of MOG-IgG demonstrated in immunological studies
• Discrete histopathological features showing primary demyelination with intralesional complement and IgG deposits
• Lack of AQP4-IgG in almost all MOG-IgG-positive patients
• Different clinical presentation, treatment response, and prognosis compared to MS 1

Clinical Presentations

The disease manifests with heterogeneous clinical phenotypes that vary by age:

In Adults:

• Recurrent optic neuritis (most frequent)
• Myelitis
• Brainstem encephalitis
• Disease typically follows a relapsing course 1, 3

In Children:

• Acute disseminated encephalomyelitis (ADEM) is most common
• ADEM-like presentations often occur as a single episode
• Up to 70% of young children with acquired demyelinating disease may have MOG-EM (frequency declines with age) 1, 4

Other phenotypes include:

• Longitudinally extensive transverse myelitis (LETM)
• Cerebral cortical encephalitis
• Brainstem/cerebellar syndromes
• Simultaneous bilateral optic neuritis 1, 3

Critical Diagnostic Pitfall

A major clinical challenge is that MOG-EM shows substantial phenotypic overlap with MS - approximately 33% of adult MOG-EM patients meet McDonald's criteria for MS at some point during their disease course, and 15% meet Barkhof's criteria. 1 This has led to widespread historical misdiagnosis, which carries serious therapeutic implications since some MS-approved drugs may be ineffective or even harmful in MOG-EM. 1

Diagnostic Approach

Diagnosis requires:

1. Detection of MOG-IgG antibodies using cell-based assays (not older ELISA methods with denatured peptides) in serum or CSF 1, 3
2. Compatible clinical-MRI phenotypes 3

Testing should NOT be performed indiscriminately. Screening large unselected populations for this rare biomarker dramatically reduces positive predictive value - even with 99% specific assays, false positives can outnumber true positives when prevalence is low. 1

Selective indications for MOG-IgG testing include:

• Longitudinally extensive transverse myelitis (≥3 vertebral segments)
• Bilateral or recurrent optic neuritis with severe visual deficit
• ADEM or ADEM-like presentations
• Normal supratentorial MRI in patients with acute optic neuritis, myelitis, or brainstem encephalitis
• Neutrophilic CSF pleocytosis or CSF white cell count >50/μL
• Absence of CSF-restricted oligoclonal bands (particularly in continental European patients)
• Frequent flare-ups after IV methylprednisolone or steroid-dependent symptoms
• Increased relapse rate following interferon-beta or natalizumab treatment in patients diagnosed with MS 1

Red flags that should prompt challenging a positive MOG-IgG result:

• MOG-IgG at assay cutoff (borderline positive)
• MRI lesions highly suggestive of MS (periventricular ovoid lesions, Dawson's fingers, juxtacortical U-fiber lesions)
• Presence of CSF-specific oligoclonal bands 5

Key Distinguishing Features from MS

CSF-specific oligoclonal bands are significantly less frequent in definite MOG-EM compared to MS 5, making their presence a useful differentiating factor.

In patients with LETM as first presentation of MOG-EM:

• Lack of gadolinium enhancement in spinal cord MRI
• Marked pleocytosis
• Negative oligoclonal bands
• History of preceding infections or vaccinations
• Good response to antibody-depleting treatments 6

Treatment Implications

The distinction from MS is therapeutically critical because:

1. Acute treatment: MOG-EM patients may be particularly responsive to:

   • High-dose intravenous methylprednisolone with careful tapering
   • Plasma exchange or immunoadsorption for incomplete recovery
   • Intravenous immunoglobulins (especially in children) 1, 3

2. Relapse prevention: MOG-EM requires close monitoring after steroid cessation due to high flare-up risk, and may benefit from:

   • B cell-targeted therapies (rituximab)
   • Immunosuppressive treatments
   • Chronic treatment in relapsing patients 1, 3

3. MS therapies may be harmful: Some MS-approved drugs might be ineffective or worsen MOG-EM due to different immunopathogenesis 1

Disease Course and Prognosis

Relapses occur in 40-80% of cases, with adults more likely to have a multiphasic course than children. 3, 4 Monitoring antibody titers may offer guidance on relapse risk, though no single factor reliably predicts disease course after onset. 3 Severe disability is less frequent than in NMOSD when treated appropriately. 7