What is the appropriate management for Mog disease?

Management of MOG Antibody-Associated Disease (MOGAD)

Acute Attack Management

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

First-Line Acute Treatment

• Intravenous methylprednisolone is the cornerstone of acute management for all MOGAD presentations including optic neuritis, transverse myelitis, brainstem encephalitis, and ADEM 1, 2, 3
• The prolonged oral steroid taper (2-3 months) is critical because relapses occur in 50-60% of patients during corticosteroid dose reduction 2, 3
• Stopping steroids too quickly represents a major treatment pitfall, as MOGAD has a particularly high risk of flare-ups after premature steroid cessation 1, 2

Second-Line Acute Treatment for Refractory Cases

• Plasma exchange (5-7 exchanges) or immunoadsorption should be implemented early if there is inadequate response to steroids after 3-5 days 4, 1, 2
• Intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days is an alternative for patients who cannot undergo plasma exchange 1, 3
• MOGAD demonstrates particularly good response to plasma exchange and immunoadsorption compared to conventional MS 4

Long-Term Maintenance Therapy

For relapsing cases (approximately 50% of patients), initiate long-term immunosuppression with rituximab or other steroid-sparing agents after the acute phase. 2, 3

Indications for Maintenance Therapy

• Relapsing disease course (occurs in approximately 50% of patients) 3, 5
• Severe residual disability after the presenting attack 3
• Steroid-dependent symptoms or frequent flare-ups after intravenous methylprednisolone 4, 6

Treatment Options

• B cell-depleting therapies (rituximab, ocrelizumab, ofatumumab) show particularly good responses, with relapses occurring immediately after re-occurrence of B cells 4
• Various steroid-sparing immunosuppressants can be considered based on observational data, though randomized controlled trials are lacking 3

Diagnostic Confirmation Requirements

MOG-IgG must be detected by cell-based assay using full-length human MOG as the target antigen with Fc-specific secondary antibodies—this is the current gold standard. 4, 2

Critical Testing Parameters

• Serum is the specimen of choice for MOG-IgG testing, not CSF, since MOG-IgG is produced mostly extrathecally 4
• Test for MOG-IgG only; testing for MOG-IgM or MOG-IgA is currently not recommended due to unknown clinical relevance 4
• Peptide-based ELISA and Western blot are insufficiently specific and obsolete 4

Timing of Testing

• MOG-IgG serum concentrations are higher during acute attacks than during remission and lower while on immunosuppression 4, 1
• If MOG-IgG is negative but MOGAD is still suspected, re-test during acute attacks, treatment-free intervals, or 1-3 months after plasma exchange or IVIG 4, 1
• Some cases of monophasic MOG-positive disease show permanent antibody disappearance following clinical recovery 4
• Retest MOG-IgG antibodies 6-12 months after the initial attack to assess prognosis, as antibody disappearance may indicate monophasic disease 2

Monitoring and Follow-Up

• Regular clinical assessments every 3-6 months to evaluate treatment response and detect early signs of relapse 1
• Obtain MRI of brain and spine to document demyelinating lesions and monitor for T2 lesion normalization, which is characteristic of MOGAD 2, 7
• Serial imaging is important because T2 lesion resolution over time is a distinguishing feature of MOGAD versus MS 7, 3

Critical Treatment Pitfalls to Avoid

Do not use interferon-beta or natalizumab, as these MS disease-modifying therapies can worsen MOG-positive disease and increase relapse rates. 4, 2

Medications to Avoid

• Interferon-beta causes clear increase in relapse rate in MOGAD patients previously misdiagnosed with MS 4, 2
• Natalizumab similarly worsens disease activity in MOGAD 4, 2
• This represents a critical distinction from MS management and underscores the importance of accurate diagnosis 2, 3

Diagnostic Pitfalls

• Low MOG-IgG titers at or just barely above the assay-specific cut-off should prompt re-testing, especially if the clinical picture is atypical 4
• Chronic progressive disease course (SPMS or PPMS) is very rare in MOG-IgG-positive patients and should prompt challenging of a positive test result 4, 6
• CSF typically shows neutrophilic pleocytosis or white cell count >50/μl, which can mimic CNS infection and lead to misdiagnosis 1, 2, 6
• Absence of CSF-restricted oligoclonal bands is typical in MOGAD (particularly in continental European patients), unlike MS 4, 6

Special Clinical Considerations

Disease Presentations Warranting MOG-IgG Testing

• Bilateral optic neuritis or unusually severe visual deficit/blindness during acute ON 4, 6
• Longitudinally extensive transverse myelitis (LETM) affecting ≥3 vertebral segments 4, 6
• Permanent sphincter and/or erectile disorder after myelitis, particularly with conus lesions 4, 6
• ADEM, recurrent ADEM, multiphasic ADEM, or ADEM-ON presentations 4, 6
• Brainstem encephalitis with area postrema syndrome (intractable nausea, vomiting, hiccups) or acute respiratory insufficiency 4, 6, 8
• Disease onset within 4 days to ~4 weeks after vaccination 4, 6
• Prominent papilledema/optic disc swelling during acute optic neuritis 4

Age-Related Considerations

• 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) 4, 6
• Indications for MOG-IgG testing in young children need not be as rigorous as in adults due to higher disease prevalence 4