What is mogad?

What is MOGAD?

MOGAD (Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease) is a distinct autoimmune demyelinating disease of the central nervous system, separate from both multiple sclerosis and aquaporin-4-positive neuromyelitis optica spectrum disorders, characterized by antibodies against MOG protein that typically presents with optic neuritis, myelitis, brainstem encephalitis, or ADEM-like presentations. 1

Disease Definition and Pathophysiology

MOG-IgG-associated encephalomyelitis (MOG-EM) is now recognized as a disease entity in its own right, distinct from classic MS and AQP4-IgG-positive NMOSD, based on:

• Immunological evidence suggesting direct pathogenic impact of MOG-IgG 1
• Discrete histopathological features with primary demyelination showing intralesional complement and IgG deposits 1
• Serological studies showing lack of AQP4-IgG in almost all MOG-IgG-positive patients 1
• Differences in clinical presentation, treatment response, and prognosis compared to MS 1

Clinical Presentations

The disease manifests through several characteristic phenotypes 2, 3:

Primary manifestations include:

• Optic neuritis (ON) - often bilateral, severe, with prominent papilledema/papillitis and longitudinally extensive optic nerve lesions (median 23.1 mm) 1
• Transverse myelitis - frequently longitudinally extensive (≥3 vertebral segments), may show H-sign on MRI 1
• Brainstem encephalitis - including area postrema syndrome with intractable nausea/vomiting or hiccups 1
• ADEM-like presentations - large, confluent T2 brain lesions, particularly common in children 1, 4
• Cortical encephalitis - with seizures, behavioral changes, or altered consciousness 1, 2

Epidemiology and Demographics

• Disease onset typically occurs around the fourth decade of life in adults 2
• No marked female predominance, unlike MS and AQP4-NMOSD 2
• Much more common in children - up to 70% of young children with acquired demyelinating disease may have MOGAD, with frequency declining with age 1
• Prevalence ≤1% in Western countries among adults with demyelinating disease, possibly ≤5% in Asian countries 1

Disease Course

Approximately 44-83% of patients experience relapsing episodes, typically within 8 months, most commonly involving the optic nerve 2. In adults, MOG-EM follows a relapsing course in most cases, though children more frequently have monophasic disease 1. Notably, 33% of adult patients meet McDonald's criteria for MS at some point during disease course, leading to frequent historical misdiagnosis 1.

Diagnostic Features

Key diagnostic indicators that distinguish MOGAD from MS include 1:

MRI findings:

• Longitudinally extensive transverse myelitis (LETM) ≥3 vertebral segments
• Longitudinally extensive optic nerve lesions (>50% distance from nerve head to chiasm)
• Perineural optic nerve enhancement with prominent optic disc swelling 3
• Spinal cord H-sign 3
• Large, confluent T2 brain lesions suggestive of ADEM 1
• Absence of MS-typical features: no lesions adjacent to lateral ventricles that are ovoid/round, no Dawson's fingers, no juxtacortical U-fiber lesions 1

CSF findings:

• Neutrophilic pleocytosis or white cell count >50/μl (can mimic CNS infection) 1, 5
• Absence of CSF-restricted oligoclonal bands (applies particularly to continental European patients) 1

Clinical red flags for MOGAD:

• Simultaneous bilateral acute optic neuritis 1
• Particularly severe visual deficit/blindness during or after acute ON 1
• Frequent flare-ups after intravenous methylprednisolone or steroid-dependent symptoms 1
• Clear increase in relapse rate following IFN-beta or natalizumab treatment in patients diagnosed with MS 1

Diagnostic Testing

MOG-IgG antibody testing should use cell-based assays with full-length, conformationally intact human MOG protein, as older ELISA methods using denatured peptides produced false associations with MS 1. Testing should be performed on serum (MOG-IgG is typically produced extrathecally) 1.

Critical caveat: Indiscriminate screening of large unselected populations significantly reduces positive predictive value, even with highly specific assays (≥99%), because false-positive results can outnumber true-positive results when disease prevalence is low 1. Therefore, testing should be reserved for patients with compatible clinical-radiological phenotypes 1.

Treatment Implications

MOGAD requires different treatment approaches than MS 1:

Acute treatment:

• High-dose intravenous methylprednisolone (1000 mg daily for 3-5 days) followed by slow oral prednisone taper (starting 1 mg/kg/day) over 2-3 months 5
• Plasma exchange (5-7 exchanges) or immunoadsorption for severe attacks or inadequate steroid response 1, 5
• IVIG (2 g/kg divided over 2-5 days) as alternative 1, 5

Critical treatment pitfalls:

• Some MS disease-modifying therapies may be ineffective or harmful in MOGAD (similar to AQP4-NMOSD), including IFN-beta and natalizumab 1, 5
• High risk of flare-ups after rapid steroid cessation requires close monitoring and careful tapering 1, 5

Maintenance therapy for relapsing cases:

• B cell-targeted therapies such as rituximab show efficacy, with 55% of patients remaining relapse-free and significant reduction in annualized relapse rate (ARR decreased by 1.36) and EDSS scores (improved by 0.52) 1, 6
• IVIG particularly effective in children 1
• Various immunosuppressive treatments 1

Prognosis

MOGAD generally responds well to immunotherapy and has better functional prognosis compared to NMOSD 2. However, persistently observed MOG-IgG and severe clinical presentation may indicate a polyphasic course 2. Some patients, particularly children with monophasic disease, may lose MOG-IgG over time, suggesting potential prognostic value of re-testing 6-12 months after initial attack 1.