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, with serum being the preferred specimen for testing. 1

Clinical Presentations Warranting MOG Antibody Testing

MOG antibody-associated encephalitis presents with diverse clinical manifestations that should prompt testing:

• Acute encephalitis with:

  • Seizures
  • ADEM or ADEM-like presentations
  • Psychotic features
  • Movement disorders
  • Prominent limbic symptoms
  • Acute respiratory insufficiency
  • Behavioral changes
  • Brainstem encephalitis
  • Area postrema syndrome 1

• Additional clinical scenarios requiring MOG antibody testing:

  • Acute CNS demyelinating disorders
  • Longitudinally extensive transverse myelitis
  • Normal supratentorial MRI with brainstem symptoms
  • Neutrophilic CSF pleocytosis or CSF white cell count >50/μl
  • Frequent flare-ups after IV methylprednisolone
  • Steroid-dependent symptoms 1
  • Cortical encephalitis with leptomeningeal enhancement 2

Diagnostic Workup

Step 1: Neuroimaging

Brain MRI should be performed to identify characteristic patterns:

• Large cortical/subcortical white matter lesions
• Brain MRI abnormal but without MS-typical lesions
• Large, confluent T2 brain lesions suggestive of ADEM
• Bilateral thalamic lesions
• Normal supratentorial MRI in patients with brainstem encephalitis 1
• Cortical encephalitis with leptomeningeal enhancement/brain atrophy (present in 76.9% of cases) 2
• Perineural optic nerve enhancement
• Spinal cord H-sign 3

Step 2: CSF Analysis

• Look for:
  • CSF pleocytosis (especially neutrophilic)
  • CSF white cell count >50/μl
  • Absence of CSF-restricted oligoclonal bands (OCB-negative) 1

Step 3: Antibody Testing

• Serum MOG-IgG testing using cell-based assays (IFT/FACS)

  • Ship specimens at 4°C or on dry ice if samples won't arrive within 1-2 days 1
  • Test for MOG-IgG specifically (not MOG-IgM or MOG-IgA) 1
  • If negative but clinical suspicion remains high, consider re-testing:
    • During acute attacks
    • During treatment-free intervals
    • 1-3 months after plasma exchange or IVIG 1

• AQP4 antibody testing

  • Important for differential diagnosis with NMOSD 1

Interpretation of Results

• MOG-IgG serum concentrations depend on:

  • Disease activity
  • Treatment status
  • May transiently disappear after plasma exchange 1

• Consider less stringent testing criteria in children, as MOG antibody-associated disease is significantly more frequent in young children with acquired demyelinating disease 1

Differential Diagnosis

• Aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (NMOSD)
• Anti-NMDAR encephalitis
• Multiple sclerosis (MS)
• Infectious encephalitis 1
• Chronically progressive encephalitis (an atypical presentation of MOGAD) 2

Special Considerations

• Atypical Presentations: Be aware of chronically progressive encephalitis as a potential phenotype of MOGAD, which may present with:

  • Leukodystrophy-like pattern on MRI
  • Multifocal hazy lesions
  • Cortical encephalitis 2

• Treatment Response: Good response to steroids or plasma exchange is characteristic of MOG antibody-associated encephalitis and can help confirm diagnosis 1

• Pitfalls to Avoid:

  • False positive results can occur with indiscriminate testing of unselected populations 3
  • The type of cell-based assay used (fixed vs. live) and antibody end-titer (low vs. high) can influence diagnostic accuracy 3
  • MOG-IgG may transiently disappear after treatment, leading to false negatives 1

• Early identification of MOGAD is crucial as some MS therapies may be ineffective or potentially harmful in these patients 1