What is mogad?

What is MOGAD?

MOGAD (Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease) is a distinct autoimmune inflammatory demyelinating disease of the central nervous system, separate from multiple sclerosis and neuromyelitis optica spectrum disorder, characterized by antibodies against MOG protein that cause recurrent or monophasic attacks of optic neuritis, myelitis, brainstem encephalitis, or ADEM-like presentations. 1

Disease Definition and Pathophysiology

MOGAD is now recognized as its own disease entity based on:

• Immunological evidence showing direct pathogenic impact of MOG-IgG antibodies 1
• Neuropathological studies demonstrating discrete histopathological features distinct from MS 1
• Serological studies showing almost complete absence of aquaporin-4 (AQP4)-IgG in MOG-IgG-positive patients 1
• Clinical differences in presentation, treatment response, and prognosis compared to MS and AQP4-positive NMOSD 1

The disease is diagnosed using cell-based assays that detect antibodies to full-length, conformationally intact human MOG protein, not the older denatured peptide assays that were incorrectly associated with MS 1

Clinical Presentations

Primary Phenotypes

Optic Neuritis (Most Common)

• Presents with severe visual deficit or blindness, often bilateral and simultaneous 2
• Shows perioptic gadolinium enhancement and longitudinally extensive optic nerve lesions on MRI 2
• May manifest as chronic relapsing inflammatory optic neuropathy (CRION) 1, 2
• Prominent papilledema/papillitis/optic disc swelling during acute attacks 1

Transverse Myelitis

• Frequently presents as longitudinally extensive transverse myelitis (LETM) affecting ≥3 vertebral segments 1, 2
• Conus medullaris lesions are particularly characteristic 2
• Can cause permanent sphincter and/or erectile dysfunction 1, 2
• May show H-sign on spinal cord imaging 3

Acute Disseminated Encephalomyelitis (ADEM)

• Large, confluent T2 brain lesions 1, 2
• Disturbance of consciousness, behavioral changes, or epileptic seizures 2
• Can present as "recurrent ADEM," "multiphasic ADEM," or "ADEM-ON" (ADEM with recurrent optic neuritis) 1, 2

Brainstem Encephalitis

• Area postrema syndrome with intractable nausea, vomiting, or hiccups 1, 2
• Acute respiratory insufficiency in severe cases 2

Cortical Encephalitis

• Cortical/subcortical white matter lesions with seizures 2

Epidemiology and Demographics

• Age distribution: Occurs approximately in the fourth decade of life in adults 4
• Pediatric prevalence: Up to 70% of young children with acquired demyelinating disease, declining with age 1, 2
• Adult prevalence: ≤1% in Western countries, ≤5% in Asian countries 2
• Gender: No marked female predominance, unlike MS 4

Disease Course

Relapsing Pattern (Most Common in Adults)

• Approximately 50% of patients experience relapses 3
• 44-83% undergo relapsing episodes within 8 months, mostly involving the optic nerve 4
• Follows a relapsing course in most adult cases 1
• High risk of flare-ups after steroid cessation, requiring careful tapering 1, 5

Monophasic Pattern

• More common in children, especially with ADEM presentation 1
• MOG-IgG may disappear over time in monophasic cases 1

Diagnostic Features

Laboratory Findings

CSF Analysis

• Neutrophilic pleocytosis or white cell count >50/μl (can mimic CNS infection) 1, 5, 2
• White cell counts range 6-306 cells/μl (median 33) 1
• Neutrophils present in 64.3% of patients with pleocytosis 1
• Absence of CSF-restricted oligoclonal bands (particularly in continental European patients) 1, 2
• No bi- or trispecific MRZ reaction (unlike MS) 1

Serology

• MOG-IgG detected in serum using cell-based assays 3
• MOG-IgG is typically produced extrathecally (serum positive, not CSF-only) 1
• Antibody levels vary with disease activity (higher during attacks, lower during immunosuppression) 5
• AQP4-IgG/MOG-IgG "double-positive" results are extremely rare and should prompt retesting 1

MRI Characteristics

Brain Imaging

• Normal supratentorial MRI in patients with acute ON, myelitis, or brainstem encephalitis 1
• Large, confluent T2 lesions in ADEM presentations 1
• Absence of MS-typical features: No lesions adjacent to lateral ventricles that are ovoid/round, no Dawson's finger-type lesions, no juxtacortical U fiber lesions 1
• T2-lesion resolution over time (characteristic feature) 3

Spinal Cord Imaging

• Longitudinally extensive lesions common but not universal 1
• Short lesions present in 44-52% of cases at some point 1
• H-sign may be present 3

Optic Nerve Imaging

• Perineural/perioptic enhancement 2, 3
• Longitudinally extensive optic nerve lesions 2

Key Distinguishing Features from MS and NMOSD

Differences from MS

• No chronic progressive course (very rare in MOGAD; should prompt reconsideration of diagnosis) 1, 2
• Absence of typical MS MRI features (periventricular ovoid lesions, Dawson's fingers) 1
• No MRZ reaction in CSF 1
• Some MS disease-modifying therapies may be ineffective or harmful in MOGAD (IFN-beta, natalizumab) 1, 5

Differences from AQP4-NMOSD

• Mutually exclusive antibody profiles (almost never both positive) 1
• Generally better functional prognosis than NMOSD 4
• Different treatment responses 1

Treatment Principles

Acute Attack Management

First-Line Therapy

• High-dose intravenous methylprednisolone (1000 mg daily for 3-5 days) 5, 6
• Followed by slow oral prednisone taper (starting at 1 mg/kg/day) over 2-3 months 5, 6
• Prolonged steroid taper critical to prevent early relapses 5, 6

Second-Line/Adjunctive Therapies

• Plasma exchange (5-7 exchanges) for severe attacks or inadequate steroid response 5, 6
• Immunoadsorption as alternative to plasma exchange 1, 5
• Intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days, especially in children 1, 5, 6

Maintenance Therapy (for Relapsing Cases)

Emerging Evidence

• IVIG emerging as probably the most effective therapy for relapsing MOGAD 7
• B cell-targeted therapies such as rituximab 1
• Various immunosuppressants (retrospective evidence only) 1, 6
• Chronic low-dose corticosteroids 7

Critical Pitfalls to Avoid

Diagnostic Pitfalls

• Do not screen unselected MS populations for MOG-IgG (high false-positive rate due to low prevalence) 1
• Borderline MOG-IgG results at or just above cut-off should prompt retesting, especially with atypical clinical picture 1
• Progressive disease course should trigger reconsideration of diagnosis 1, 2
• Combined central and peripheral demyelination excludes MOGAD (MOG not expressed peripherally) 1

Treatment Pitfalls

• Never stop steroids abruptly - high risk of flare-ups requires slow taper over 2-3 months 1, 5
• Do not treat as MS - some MS therapies (IFN-beta, natalizumab) may worsen MOGAD 1, 5
• Clear increase in relapse rate following IFN-beta or natalizumab should prompt MOG-IgG testing 1

When to Test for MOG-IgG

High-Yield Testing Scenarios 1

• Longitudinally extensive transverse myelitis (≥3 vertebral segments)
• Bilateral simultaneous acute optic neuritis
• Recurrent optic neuritis or disease mainly characterized by ON
• ADEM, recurrent ADEM, multiphasic ADEM, or ADEM-ON presentations
• Area postrema syndrome (intractable nausea/vomiting/hiccups)
• Steroid-dependent symptoms or frequent flare-ups after IV methylprednisolone
• Disease onset within 4 days to 4 weeks after vaccination
• AQP4-IgG negative NMOSD-like presentations

Timing of Testing

• Test during acute attacks for highest sensitivity 5
• If initially negative but suspicion remains, retest during treatment-free intervals or 1-3 months after plasma exchange/IVIG 5
• Consider retesting 6-12 months after first attack (disappearance may indicate monophasic course) 1