How does headache present in cryptococcal meningitis?

Headache Presentation in Cryptococcal Meningitis

Headache in cryptococcal meningitis typically presents as severe, persistent, and progressively debilitating, often accompanied by fever, but classic meningeal signs like neck stiffness and photophobia are present in only 25-33% of patients. 1

Clinical Presentation

Cardinal Symptoms

• Headache characteristics:
  • Gradual onset, becoming progressively more debilitating
  • Severe intensity
  • Persistent and consistent
  • Often the predominant symptom
  • May be immediately relieved after CSF drainage 1

Associated Symptoms and Signs

• Fever (common but not universal)
• Altered mental status (confusion, lethargy)
• Nausea and vomiting (unexplained)
• Bizarre behavior
• Progressive dementia
• Seizures (in some cases)
• Papilledema (29% of patients with elevated ICP >35 cm H₂O) 1
• Cranial nerve abnormalities
• Impaired mentation (18% of patients with elevated ICP >35 cm H₂O) 1

Important Clinical Observation

• Classic meningeal signs (neck stiffness, photophobia) are notably absent in 67-75% of patients 1
• Symptoms may mimic other conditions (e.g., one case report described symptoms mimicking subarachnoid hemorrhage) 2

Pathophysiology and Pressure Findings

Intracranial Pressure

• Approximately 50% of patients have CSF pressure >25 cm H₂O 1, 3
• 25% have pressures >35 cm H₂O 1
• Elevated pressure is associated with:
  • Higher mortality (patients who died in first 2 weeks of therapy had baseline pressures ≥25 cm H₂O) 1
  • Higher CSF cryptococcal antigen titers 4
  • More frequent positive India ink smears 4
  • More severe clinical manifestations 4

CSF Findings

• Mildly elevated serum protein
• Glucose ranging from low to normal
• Pleocytosis (mostly lymphocytes), though some patients have no cells
• Positive Gram or India ink stain for numerous yeasts 1
• Cryptococcal antigen almost invariably detected at high titer 1

Diagnostic Considerations

Imaging Findings

• MRI is more effective than CT in identifying CNS cryptococcal lesions 1
• In HIV patients, radiographic images commonly show:
  • No abnormality (common)
  • Cerebral atrophy without obstruction
  • Rarely, classic hydrocephalus or mass lesions 1
• In non-HIV patients:
  • Higher risk of cryptococcal cerebral mass lesions
  • More robust inflammatory responses in meninges
  • Potential cerebral vasculitis 1

High-Risk Presentations

• Patients with altered mental status have up to 25% mortality 5
• Patients with CD4+ counts <50 cells/μL are at highest risk 1
• Impaired consciousness state correlates with higher mortality 6

Clinical Pitfalls and Caveats

1. Diagnostic delay: Headache is common (21%) in uncomplicated primary coccidioidal pneumonia, creating diagnostic confusion 1

   • If headache is modest and dissipates in approximately a week, lumbar puncture may not be required
   • If headache is predominant, consistent, persistent, and progressive, lumbar puncture is required 1

2. Missing elevated ICP: Failure to measure CSF opening pressure can lead to poor outcomes despite appropriate antifungal therapy 3

3. Atypical presentation: Particularly in immunosuppressed patients, presentation may be subtle or atypical 2

4. Neurological deterioration: New or worsening headache after initial improvement may indicate recurrence of elevated ICP requiring repeat intervention 1

5. Imaging limitations: Normal neuroimaging does not exclude cryptococcal meningitis 1

By recognizing this characteristic presentation pattern of headache in cryptococcal meningitis and measuring CSF pressure, clinicians can initiate appropriate management promptly, which is critical for reducing morbidity and mortality in this serious infection.