What additional labs or imaging can help differentiate meningitis from an aseptic process?

Differentiating Meningitis from Aseptic Process: Laboratory and Imaging Approaches

CSF analysis is the most critical diagnostic tool for differentiating bacterial meningitis from aseptic processes, with CSF lactate having the highest sensitivity (93%) and specificity (96%) when obtained before antibiotic administration. 1

CSF Parameters for Differentiation

Cell Count and Differential

• Bacterial meningitis typically shows:
  • Higher white cell counts (average 2,000 cells/mm³)
  • Polymorphonuclear (PMN) predominance 1
• Important exceptions:
  • 10% of bacterial meningitis cases have <100 cells/mm³ 1
  • 57% of aseptic meningitis cases also show PMN predominance, even beyond 24 hours of illness 2
  • PMN predominance alone cannot reliably differentiate between bacterial and aseptic meningitis 2

CSF Biochemistry

• Glucose measurements:

  • CSF:plasma glucose ratio <0.36 has 93% sensitivity for bacterial meningitis 1
  • CSF glucose >2.6 mmol/L makes bacterial meningitis unlikely 1
  • Always measure plasma glucose simultaneously for accurate interpretation 1

• Protein levels:

  • Bacterial meningitis: typically higher protein levels
  • CSF protein <0.6 g/L makes bacterial meningitis unlikely 1

• CSF lactate:

  • Most discriminatory single test: 93% sensitivity, 96% specificity 1
  • Cut-off of 35 mg/dL for distinguishing bacterial from viral meningitis
  • Note: sensitivity drops to <50% if antibiotics were given before testing 1

Microbiological Testing

• Essential tests:

  • Gram stain (sensitivity 50-99%, depending on prior antibiotic use)
  • CSF culture 1
  • PCR for viral pathogens (HSV, enterovirus) 1

• Additional tests based on clinical suspicion:

  • Cryptococcal antigen
  • Fungal stains/cultures
  • Acid-fast bacillus smears/cultures
  • PCR for other viruses (CMV, JC virus, West Nile virus, adenovirus) 1

Imaging Considerations

• Neuroimaging (CT/MRI) should be performed before LP if:

  • Focal neurological signs present
  • Papilledema present
  • Continuous/uncontrolled seizures
  • GCS ≤12 1

• Value of imaging:

  • Helps exclude mass lesions or abscesses that would contraindicate LP
  • Can identify complications of meningitis (hydrocephalus, infarction)
  • Should not delay antibiotic administration if bacterial meningitis is suspected 3

Special Considerations

Repeat Lumbar Puncture

• Performed in approximately 8% of bacterial meningitis cases 4
• Most valuable when:
  • Clinical deterioration occurs (42% of repeat LPs) 4
  • Initial CSF examination was normal but clinical suspicion remains high 5
  • Confirming clearance of infection in complicated cases 4

Timing Considerations

• CSF cell counts typically decrease by:
  • 19% when repeated within 2 days
  • 84% within 3-7 days
  • 93% within 8-14 days 4

Common Pitfalls

1. Relying solely on PMN predominance to differentiate bacterial from aseptic meningitis (both can show PMN predominance) 2
2. Not measuring plasma glucose simultaneously with CSF glucose 1
3. Collecting inadequate CSF volume (at least 22 mL should be collected in adults) 1
4. Delaying LP too long after antibiotic administration (reduces sensitivity of culture and lactate testing) 1
5. Not considering repeat LP when clinical suspicion remains high despite initial normal results 5

Algorithm for Differentiation

1. Obtain CSF via LP (unless contraindicated)
2. Order comprehensive CSF analysis:
   • Opening pressure
   • Cell count with differential
   • Glucose (with simultaneous plasma glucose)
   • Protein
   • Lactate (most discriminatory if pre-antibiotics)
   • Gram stain and culture
   • PCR for viral pathogens
3. Consider bacterial meningitis likely if:
   • CSF:plasma glucose ratio <0.36
   • CSF protein >0.6 g/L
   • CSF lactate >35 mg/dL
   • WBC >2000 cells/mm³
4. Consider repeat LP if:
   • Clinical deterioration occurs
   • Initial CSF was normal but suspicion remains high
   • Need to confirm clearance of infection

Remember that no single parameter is absolutely diagnostic, and results must be interpreted in the clinical context 1.