What is the treatment approach for patients testing positive for Myelin Oligodendrocyte Glycoprotein (MOG) Immunoglobulin G (IgG) antibodies?

Treatment Approach for MOG-IgG Positive Patients

Patients testing positive for MOG-IgG antibodies require immediate high-dose intravenous methylprednisolone (1000 mg daily for 3-5 days) for acute attacks, followed by a prolonged oral steroid taper over 2-3 months, and should never receive MS disease-modifying therapies like interferon-beta or natalizumab as these can worsen disease. 1, 2

Acute Attack Management

First-Line Treatment

• Initiate high-dose IV methylprednisolone at 1000 mg/day for 3-5 days immediately upon diagnosis of an acute MOG-associated demyelinating attack 2, 3, 4
• This applies to all presentations including optic neuritis, transverse myelitis, brainstem encephalitis, and cortical encephalitis 1, 5

Second-Line Treatment for Steroid-Refractory Cases

• Proceed to plasma exchange (5-7 exchanges) or immunoadsorption if no improvement occurs after 3-5 days of IV steroids, as MOG-IgG positive patients show particular responsiveness to antibody-depleting treatments 1, 2, 4
• Intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days is an alternative for patients who cannot undergo plasma exchange 3

Critical Steroid Tapering Strategy

• Begin oral prednisone at 1 mg/kg/day after IV steroids and taper slowly over 2-3 months, as MOG-EM carries a high risk of flare-ups with rapid steroid cessation 1, 2, 3, 4
• Close monitoring during the taper is mandatory to detect early relapse 1, 4

Long-Term Maintenance Therapy

Indications for Preventive Treatment

• Reserve maintenance immunotherapy for patients with relapsing disease only (≥2 attacks), not for monophasic presentations 4, 6
• The median annualized relapse rate before treatment is typically 1.6, which decreases substantially with appropriate immunotherapy 6

Treatment Options by Efficacy

Most Effective:

• IVIG emerges as the most effective maintenance therapy, with only 20% of patients experiencing breakthrough relapses (ARR 0) in the largest retrospective study 6, 7
• Dosing typically follows standard protocols for autoimmune neurological conditions 3

Moderately Effective:

• Rituximab shows 61% breakthrough relapse rate (ARR 0.59) but remains a commonly used B cell-targeted therapy 1, 6
• Relapses occur immediately after B cell reconstitution, requiring monitoring of CD19+ counts 2
• Azathioprine demonstrates 59% breakthrough relapse rate (ARR 0.2) 6
• Mycophenolate mofetil shows 74% breakthrough relapse rate (ARR 0.67) 6

Treatments to Absolutely Avoid

• Never use interferon-beta, natalizumab, or fingolimod - these MS disease-modifying therapies are ineffective or harmful in MOG-EM due to differences in immunopathogenesis 1, 2, 4, 6
• All 9 patients treated with MS agents in one study had breakthrough relapses with ARR 1.5 6

Diagnostic Confirmation Requirements

Antibody Testing Standards

• Ensure MOG-IgG was detected by cell-based assay using full-length human MOG as the target antigen - this is the gold standard methodology 2, 4
• Serum is the preferred specimen, not CSF, as MOG-IgG is produced extrathecally 2, 4

Timing Considerations for Testing

• MOG-IgG concentrations fluctuate with disease activity (higher during attacks) and treatment status (lower during immunosuppression) 2, 3, 4
• If initial testing is negative but clinical suspicion remains high, retest during acute attacks, treatment-free intervals, or 1-3 months after plasma exchange/IVIG 2, 4

Prognostic Retesting

• Retest MOG-IgG antibodies 6-12 months after the initial attack to assess prognosis, as antibody disappearance may indicate monophasic disease 2

Common Clinical Pitfalls

Misdiagnosis as Multiple Sclerosis

• 33% of adult MOG-EM patients meet McDonald criteria for MS at some point, and 15% meet Barkhof criteria, leading to frequent misclassification 1
• This misdiagnosis has serious therapeutic implications as MS treatments can worsen MOG-EM 1

CSF Interpretation Errors

• CSF may show neutrophilic pleocytosis or white cell count >50/μl, which can mimic CNS infection rather than demyelinating disease 2, 3
• Oligoclonal bands are typically absent in MOG-EM, unlike MS 2

Rapid Steroid Tapering

• The most common treatment error is tapering steroids too quickly, resulting in early relapses that could have been prevented 1, 3
• This requires close monitoring and consideration of steroid-sparing agents early in the disease course 2

Monitoring Strategy

Regular Assessment Schedule

• Conduct clinical assessments every 3-6 months to evaluate treatment response and detect early signs of relapse 3
• Monitor for breakthrough relapses during any immunosuppression adjustments 4

MRI Documentation

• Obtain MRI of brain and spine to document demyelinating lesions compatible with the clinical presentation 2
• Brain lesions typically show vague, focal appearances with irregular margins in subcortical or brainstem regions 5