What are the subtypes of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)?

Subtypes of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)

MOGAD presents with distinct clinical phenotypes that are considered subtypes of the disease, primarily characterized by the anatomical location of CNS demyelination.

Major Clinical Phenotypes of MOGAD

Optic Neuritis (ON)

• Most frequent presenting phenotype in adults 1
• Can present as:
  • Isolated bilateral acute optic neuritis (43% of cases) 2
  • Isolated unilateral optic neuritis (19% of cases) 2
  • Often characterized by severe visual deficit or blindness during or after acute episodes 3
  • Frequently shows perioptic gadolinium enhancement and longitudinally extensive optic nerve lesions on MRI 3
  • May present as chronic relapsing inflammatory optic neuropathy (CRION) 3

Transverse Myelitis

• Presents as:
  • Isolated myelitis (5% of cases) 2
  • Longitudinally extensive transverse myelitis (LETM) affecting ≥3 vertebral segments 3
  • Short segment myelitis can also occur 3
  • Often involves the thoracic cord 2
  • May cause permanent sphincter and/or erectile disorders 3
  • Conus medullaris lesions are particularly characteristic 3

Acute Disseminated Encephalomyelitis (ADEM)

• Most common presentation in children 4
• Characterized by:
  • Large, confluent T2 brain lesions 3
  • Disturbance of consciousness, behavioral changes, or epileptic seizures 3
  • In children, typically presents as a one-time incident 4
  • Can occur as "recurrent ADEM," "multiphasic ADEM" or "ADEM-ON" (ADEM with recurrent optic neuritis) 3

Brainstem Encephalitis

• Presents as acute brainstem syndrome (19% of cases) 2
• Can involve:
  • Upper brainstem lesions 2
  • Area postrema syndrome with intractable nausea, vomiting, or hiccups 3
  • Acute respiratory insufficiency in severe cases 3
  • Can be extensive, affecting cerebellar peduncles and pons 5

Cortical Encephalitis

• Characterized by:
  • Cortical/subcortical white matter lesions 3
  • Can present with seizures 3
  • Less common than other phenotypes 6

Combined Presentations

• Simultaneous optic neuritis with myelitis (9% of cases) 2
• ADEM with optic neuritis (ADEM-ON) (5% of cases) 2

Special Clinical Scenarios

Post-Vaccination MOGAD

• Disease onset within 4 days to approximately 4 weeks after vaccination 3
• Can present with any of the above phenotypes 3

MOGAD with Associated Conditions

• Can co-exist with teratoma or NMDAR encephalitis (though evidence is limited) 3

Disease Course Patterns

• Monophasic course: Single episode with no recurrence, more common in children with ADEM 4
• Relapsing course: Observed in approximately 50% of patients, more common in adults 6
• Steroid-dependent course: Frequent flare-ups after intravenous methylprednisolone withdrawal 3

Important Distinguishing Features

• MOGAD is distinct from multiple sclerosis (MS) and aquaporin-4 (AQP4)-positive neuromyelitis optica spectrum disorder 1
• Characteristic MRI features help differentiate MOGAD:
  • Perineural optic nerve enhancement
  • Spinal cord H-sign
  • T2-lesion resolution over time 6
• CSF typically shows neutrophilic pleocytosis or white cell count >50/μl 3
• Usually lacks CSF-restricted oligoclonal bands (particularly in continental European patients) 3

Clinical Pitfalls and Caveats

• Indiscriminate testing for MOG-IgG in unselected populations can lead to false positive results 6
• Progressive disease course is very atypical for MOGAD and should prompt consideration of alternative diagnoses 3
• The type of cell-based assay used (fixed vs. live) and antibody end-titer (low vs. high) can influence diagnostic accuracy 6
• MOGAD is significantly more frequent among young children with acquired demyelinating disease (up to 70%) than adults (≤1% in Western countries, ≤5% in Asian countries) 3