Can Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) present with headache and fever for 3 months?

MOGAD Typically Does Not Present with Prolonged Headache and Fever for 3 Months

While MOGAD can present with headache and fever, a 3-month duration of these symptoms is atypical and should prompt consideration of alternative diagnoses. 1, 2

Clinical Presentation of MOGAD

MOGAD typically presents with:

• Acute or subacute onset of neurological symptoms
• Common presentations include:
  • Optic neuritis (often bilateral)
  • Transverse myelitis
  • Acute disseminated encephalomyelitis (ADEM)-like syndrome
  • Brainstem encephalitis
  • Cerebral cortical encephalitis 1, 2, 3

When MOGAD does present with headache and fever:

• These symptoms are typically acute or subacute, not chronic
• Often associated with other neurological manifestations
• Cerebral cortical encephalitis variant may present with headache, fever, and seizures 4
• Brain stem encephalitis variant may present with fever and impaired consciousness 5

Diagnostic Red Flags for MOGAD

The following features make MOGAD less likely:

• Chronic progressive disease course (very rare in MOG-IgG-positive patients) 1
• Continuous worsening of symptoms over weeks (suggests tumor, sarcoidosis, etc.) 1
• Prolonged symptoms without other characteristic neurological findings 1, 2

Differential Diagnosis for Prolonged Headache and Fever

For a 3-month history of headache and fever, consider:

1. Infectious causes:

   • Viral encephalitis (may present with headache and fever but typically not for 3 months) 1
   • Chronic meningitis (tuberculosis, fungal, etc.)
   • Parameningeal infections 1

2. Autoimmune encephalitis:

   • NMDA receptor antibody encephalitis (can present with headache and fever in early phase) 1
   • VGKC complex antibody encephalitis (though fever is uncommon) 1

3. Neoplastic conditions:

   • CNS lymphoma
   • Gliomatosis cerebri 1

4. Other inflammatory conditions:

   • Neurosarcoidosis
   • Vasculitis 1

Diagnostic Approach

For a patient with 3-month history of headache and fever:

1. Neuroimaging:

   • MRI brain with and without contrast (looking for demyelinating lesions, leptomeningeal enhancement) 1, 6
   • FLAIR and SWI/GRE sequences are most sensitive 1

2. CSF analysis:

   • Cell count (MOGAD may show pleocytosis, sometimes with neutrophils) 1, 2
   • Protein and glucose
   • Oligoclonal bands (typically absent in MOGAD, present in 84-98% of MS) 2
   • MOG-IgG antibodies in CSF (though serum testing is preferred) 1
   • Infectious studies (bacterial culture, viral PCR, etc.)

3. Serum studies:

   • MOG-IgG antibodies using cell-based assay 1, 2, 3
   • AQP4-IgG antibodies to rule out NMOSD 2
   • Other autoimmune antibody panels (NMDA, VGKC complex) 1
   • Inflammatory markers (ESR, CRP)

Clinical Pearls and Pitfalls

• MOGAD can mimic CNS infection with neutrophilic pleocytosis and impaired blood-CSF barrier function 1
• Leptomeningeal enhancement on MRI favors MOGAD over AQP4+ NMOSD and MS 6
• MOG-IgG serum concentrations depend on disease activity (higher during acute attacks) and treatment status 1
• Cerebral cortical encephalitis due to MOGAD may be misdiagnosed as viral encephalitis in early stages 4
• Prolonged symptoms without characteristic MRI findings should prompt consideration of alternative diagnoses 1, 2

In conclusion, while MOGAD can initially present with headache and fever, a 3-month duration of these symptoms without other characteristic neurological findings is atypical and should prompt thorough investigation for alternative diagnoses.