What is the treatment for MOGAD (Myelin Oligodendrocyte Glycoprotein Antibody Disease)?

Treatment of MOGAD (Myelin Oligodendrocyte Glycoprotein Antibody Disease)

High-dose intravenous methylprednisolone (1000 mg daily for 3-5 days) should be initiated immediately for acute MOGAD attacks, followed by a slow oral prednisone taper (starting at 1 mg/kg/day) over 2-3 months to prevent early relapses. 1, 2

Acute Attack Management

First-Line Treatment

• Administer IV methylprednisolone 1000 mg/day for 3-5 days as the immediate first-line therapy for all acute MOGAD presentations including optic neuritis, transverse myelitis, brainstem encephalitis, or ADEM-like presentations 1, 3
• The slow corticosteroid taper is critical because 50-60% of patients experience relapses during steroid dose reduction 1
• Start oral prednisone at 1 mg/kg/day after completing IV steroids, then taper gradually over 2-3 months rather than rapidly 1, 2

Second-Line Treatment for Severe or Refractory Cases

• Proceed to plasma exchange (5-7 exchanges) or immunoadsorption if no improvement occurs after 3-5 days of IV steroids 1, 2, 3
• Plasma exchange should be implemented early for severe attacks (such as bilateral blindness, complete myelitis, or brainstem involvement with respiratory compromise) rather than waiting for steroid failure 1, 2
• Intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days is an alternative for patients who cannot undergo plasma exchange due to hemodynamic instability or vascular access issues 2

Long-Term Preventative Therapy

Indications for Maintenance Immunosuppression

• Initiate long-term immunosuppression after the acute phase in patients with relapsing disease or those at high risk for relapse 1
• The decision for maintenance therapy should be made after the first attack in patients with severe disability, incomplete recovery, or high-titer MOG-IgG antibodies 1

Treatment Options

• B cell-depleting therapies (rituximab, ocrelizumab, ofatumumab) show particularly good responses, though relapses occur immediately after B cell reconstitution 1, 4
• Rituximab is commonly used as first-line maintenance therapy based on retrospective evidence, though prospective trials are ongoing 3
• Other immunosuppressants including azathioprine, mycophenolate mofetil, and oral corticosteroids have been used, though evidence is limited to retrospective studies 3

Monitoring Strategy

• Retest MOG-IgG antibodies 6-12 months after the initial attack to assess prognosis, as antibody disappearance may indicate monophasic disease 4, 1
• However, transient seronegativity can occur during immunosuppression or after treatment, so a single negative test should not solely guide discontinuation of therapy 4
• Conduct regular clinical assessments every 3-6 months to evaluate treatment response and detect early relapse signs 2

Critical Diagnostic Verification

Confirm Proper Testing

• Ensure MOG-IgG was detected by cell-based assay using full-length human MOG as the target antigen with Fc-specific secondary antibodies, as this is the gold standard 1, 4
• Serum is the specimen of choice for MOG-IgG testing, not CSF, since MOG-IgG is produced extrathecally 1
• 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 when antibody levels are higher 2

Imaging Confirmation

• Obtain MRI of brain and spine to document demyelinating lesions compatible with the clinical presentation 1
• MOGAD lesions typically lack Dawson's finger-type lesions (absent in 95-98% of cases) and U-fiber lesions (absent in 94% of cases), which helps distinguish from MS 4

Critical Pitfalls to Avoid

Medications That Worsen MOGAD

• Do not use interferon-beta or natalizumab, as these MS disease-modifying therapies can worsen MOG-positive disease and increase relapse rates 1, 2
• Avoid treating MOGAD as MS, as the pathophysiology and optimal treatments differ fundamentally 2

Steroid Tapering Errors

• Do not taper steroids too rapidly, as symptom flare-ups frequently occur with rapid steroid reduction 1, 2
• Consider initiating steroid-sparing agents early rather than prolonging high-dose corticosteroids 1

Diagnostic Confusion

• Recognize that CSF may show neutrophilic pleocytosis (present in 64% of cases with pleocytosis) and lack oligoclonal bands (absent in 87-88% of cases), which can mimic CNS infection 4, 1, 2
• CSF white cell counts can range from 6-306 cells/μl (median 33), with counts ≥100 cells/μl in 28% of patients 4
• The absence of oligoclonal bands does NOT exclude MOGAD, unlike MS where OCBs are present in 98% of Central/Northern European patients 4

Red Flags Suggesting Alternative Diagnosis

• Challenge the MOG-IgG result if the patient has chronic progressive disease (SPMS or PPMS), Dawson's finger lesions, or bi/trispecific MRZ reaction in CSF 4
• MOG-IgG levels at or just barely above the assay cut-off should prompt retesting, especially if the clinical picture is atypical 4