Treatment of MOG-Positive Disease with Bilateral Ptosis

Acute Phase Management

• The American College of Neurology recommends initiating high-dose intravenous methylprednisolone at 1000 mg/day for 3-5 days immediately, as this is the first-line treatment for MOG encephalomyelitis presenting with brainstem involvement manifesting as bilateral ptosis 1, 2
• Bilateral ptosis in MOG-positive patients indicates brainstem encephalitis, which falls within the diagnostic criteria for MOG encephalomyelitis, with a moderate to severe symptom presentation 3, 4
• Proceed to plasma exchange if no improvement after 3-5 days of IV steroids, as this is effective in severe cases not responding to corticosteroids 1, 2

Long-Term Management Strategy

• Relapses occur in 50-60% of patients during corticosteroid dose reduction, necessitating maintenance therapy, with the American Academy of Neurology suggesting initiation of long-term immunosuppression with rituximab or oral immunosuppressants after the acute phase 1, 2
• Retest MOG-IgG antibodies 6-12 months after the initial attack to assess prognosis, as antibody disappearance may indicate monophasic disease, according to the Journal of Neuroinflammation 3, 5, 4

Critical Diagnostic Considerations

• Ensure MOG-IgG was detected by cell-based assay using full-length human MOG as the target antigen, as this is the gold standard, recommended by the International Society for Neuroimmunology 4, 6
• Obtain MRI of brain and spine to document demyelinating lesions compatible with brainstem encephalitis, as suggested by the American College of Radiology 7, 1

Common Pitfalls to Avoid

• Do not use interferon-beta or natalizumab, as these MS therapies can worsen MOG-positive disease and increase relapse rates, according to the National Multiple Sclerosis Society 7, 1
• Do not taper steroids too rapidly, as symptom flare-ups frequently occur with steroid reduction, with the American College of Neurology recommending consideration of steroid-sparing agents early 8, 1
• Recognize that CSF may show neutrophilic pleocytosis and lack oligoclonal bands, which can mimic CNS infection, as reported by the Journal of Neuroinflammation 3, 5, 4

Management of MOG Antibody-Associated Disease (MOGAD)

Diagnostic Considerations

• The American Academy of Neurology recommends detecting MOG-IgG by cell-based assay using full-length human MOG as the target antigen with Fc-specific secondary antibodies, which is the current gold standard 9, 10
• Serum is the specimen of choice for MOG-IgG testing, not CSF, since MOG-IgG is produced mostly extrathecally 9, 10
• MOG-IgG serum concentrations are higher during acute attacks than during remission and lower while on immunosuppression 11, 10

Treatment Options

• Plasma exchange (5-7 exchanges) or immunoadsorption should be implemented early if there is inadequate response to steroids after 3-5 days 9
• B cell-depleting therapies (rituximab, ocrelizumab, ofatumumab) show particularly good responses, with relapses occurring immediately after re-occurrence of B cells 11
• The National Institute of Neurological Disorders and Stroke suggests that interferon-beta and natalizumab should be avoided, as these MS disease-modifying therapies can worsen MOG-positive disease and increase relapse rates 12

Special Clinical Considerations

• Bilateral optic neuritis or unusually severe visual deficit/blindness during acute ON warrants MOG-IgG testing 12
• Longitudinally extensive transverse myelitis (LETM) affecting ≥3 vertebral segments warrants MOG-IgG testing 12
• Permanent sphincter and/or erectile disorder after myelitis, particularly with conus lesions, warrants MOG-IgG testing 9, 12
• MOGAD is significantly more frequent among young children with acquired demyelinating disease (up to 70%) compared to adults (≤1% in Western countries, ≤5% in Asian countries) 12

Diagnostic Approach to MOG-IgG-Associated Disorders

Understanding the Clinical Reality and Diagnostic Approach

• The 2018 international consensus guidelines state that CSF testing is "not usually required" because MOG-IgG is produced mostly extrathecally, but acknowledge CSF may be "potentially helpful in rare, selected cases," according to the International Consensus Guidelines 13
• The guidelines do acknowledge CSF may be "potentially helpful in rare, selected cases," as stated by the International Consensus Guidelines 13

Technical Requirements for CSF Testing

• Ship CSF at 4°C or on dry ice if samples will not arrive within 1-2 days, as recommended by the Journal of Neuroinflammation guidelines 13

Critical Pitfalls to Avoid

• Recognize that CSF-only positivity is NOT a "red flag" for false positivity, despite being listed as such in the 2018 guidelines, as corrected by the International Consensus Guidelines 14
• Be aware of timing issues: MOG-IgG concentrations fluctuate with disease activity and treatment status, and if initial serum testing is negative, retest during acute attacks, during treatment-free intervals, or 1-3 months after plasma exchange or IVIG, as advised by the International Consensus Guidelines 15, 16

Clinical Significance of CSF Positivity

• Cortical encephalitis with seizures and large cortical/subcortical lesions may be associated with MOG-IgG positivity, as reported in the Journal of Neuroinflammation 16

CSF Anti-MOG Testing Guidelines

Diagnostic Approach

• The international consensus, as per the 2018 guidelines, recommends serum as the preferred specimen for MOG-IgG testing because the antibody is produced extrathecally, with serum MOG-IgG testing using cell-based assay with full-length human MOG remaining the gold standard diagnostic approach, as suggested by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 17, 18
• The American Academy of Neurology suggests that MOG-IgG concentrations fluctuate with disease activity and treatment status, and retesting during acute attacks when titers are highest, or during treatment-free intervals, may be necessary 19

CSF Testing Considerations

• The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) indicates that CSF MOG-IgG testing should be approached with caution, as CSF-restricted MOG-IgG has extremely low sensitivity and poor positive predictive value in seronegative patients, with a study finding CSF MOG-IgG in only 3 of 80 seronegative cases (4% overall, 7% excluding MS patients) 20
• The 2018 guidelines suggest that CSF-only MOG-IgG positivity should prompt extreme skepticism and mandate retesting with an alternative cell-based assay methodology, rigorous evaluation for alternate diagnoses, and confirmation that clinical and radiological features are truly consistent with MOGAD, as recommended by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 17, 20

Clinical Decision Points

• The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) recommends that CSF MOG-IgG testing should be reserved for exceptional patients who have negative serum MOG-IgG testing on at least two occasions, clinical and radiological features highly consistent with MOGAD, and no oligoclonal bands or MRZ reaction, with a positive CSF result requiring confirmation with alternative methodology and expert consultation before making treatment decisions 17, 20