What is the diagnostic algorithm for Myelin Oligodendrocyte Glycoprotein (MOG) encephalitis?

Diagnostic Algorithm for MOG Encephalitis

Cell-based assays using full-length human MOG as target antigen are the gold standard for diagnosing MOG antibody-associated encephalitis. 1

Clinical Presentations Warranting MOG Antibody Testing

Neurological Manifestations

• Acute encephalitis with seizures
• ADEM or ADEM-like presentations with:
  • Large white matter lesions
  • Disturbance of consciousness
  • Brainstem lesions
• Psychotic features or movement disorders
• Prominent limbic symptoms
• Acute respiratory insufficiency with radiological signs of demyelination
• Behavioral changes with demyelination
• Brainstem encephalitis
• Area postrema syndrome 1, 2

MRI Findings

• Large cortical/subcortical white matter lesions (not involving inferior temporal lobe)
• Brain MRI abnormal but without MS-typical lesions
• Large, confluent T2 brain lesions suggestive of ADEM
• Bilateral thalamic lesions (particularly in ADEM)
• Normal supratentorial MRI in patients with brainstem encephalitis 1, 2

Laboratory Features

• CSF pleocytosis (>5 WBC/μl)
• Neutrophilic CSF pleocytosis or CSF white cell count >50/μl
• Absence of CSF-restricted oligoclonal bands (OCB-negative)
• Good response to steroids or plasma exchange 1, 2

Diagnostic Testing Algorithm

Step 1: Initial Evaluation

• Collect comprehensive CSF sample (at least 20cc if possible)
  • Opening pressure, WBC count with differential, RBC count, protein, glucose
  • Oligoclonal bands and IgG index
  • Rule out infectious causes (HSV, VZV, enterovirus PCR, etc.) 1

Step 2: Neuroimaging

• Brain MRI (preferred over CT)
• Look for characteristic patterns:
  • Cortical encephalitis with leptomeningeal enhancement
  • Leukodystrophy-like pattern
  • Multifocal hazy lesions
  • Large cortical/subcortical white matter lesions 1, 3

Step 3: MOG Antibody Testing

• Specimen collection:

  • Serum (specimen of choice)
  • Ship at 4°C or on dry ice if samples won't arrive within 1-2 days 1

• Testing methodology:

  • Cell-based assays (IFT/FACS) using full-length human MOG as target antigen
  • Use Fc-specific or IgG1-specific secondary antibodies
  • Avoid peptide-based ELISA and Western blot (insufficiently specific) 1

• Immunoglobulin class:

  • Test for MOG-IgG (recommended)
  • Testing for MOG-IgM and/or MOG-IgA not currently recommended 1

Step 4: Rule Out Differential Diagnoses

• Test for AQP4-IgG to rule out NMOSD
• Consider other autoimmune encephalitis (anti-NMDAR)
• Rule out infectious causes
• Consider MS (though MOG encephalitis patients often lack OCBs) 1, 2

Step 5: Interpret Results

• Document immunoglobulin class detected, assay type, antigenic substrate, biomaterial used, titer/concentration/units
• Interpret positive results in clinical context
• Consider re-testing if "red flags" are present 1

Special Considerations

Timing Issues

• MOG-IgG serum concentrations depend on:

  • Disease activity (higher during acute attacks)
  • Treatment status (lower while on immunosuppression)
  • May transiently vanish after plasma exchange 1

• If MOG-IgG is negative but MOG encephalitis still suspected:

  • Re-test during acute attacks
  • Re-test during treatment-free intervals
  • Re-test 1-3 months after plasma exchange or IVIG 1

Pediatric Considerations

• Testing criteria should be less stringent in children
• MOG antibody-associated disease is significantly more frequent in young children with acquired demyelinating disease (up to 70%) compared to adults (≤1% in Western countries, ≤5% in Asian countries) 2

Red Flags for False Positive Results

• Clinical presentation atypical for MOG antibody disease
• Presence of OCBs (though not exclusionary)
• Dawson's finger-type lesions on MRI
• Juxtacortical U fiber lesions
• Lesions adjacent to lateral ventricles that are ovoid 1

Clinical Pearls

• MOG encephalitis can present with extensive brainstem involvement, which may be confused with infectious encephalitis 4
• Chronically progressive encephalitis may be a phenotype of MOG antibody disease, presenting with leukodystrophy-like MRI patterns 3
• MOG antibody testing should be considered in patients with subacute and chronic progressive dementia with leukodystrophy-like MRI lesions 3
• MOG encephalitis can be distinguished from MS by the absence of silent lesions that progressively increase lesion volume 5

By following this diagnostic algorithm, clinicians can appropriately identify and manage patients with MOG antibody-associated encephalitis, leading to earlier treatment and potentially better outcomes.