How is a cerebrospinal fluid (CSF) study interpreted in diagnosing and treating meningitis?

CSF Study Interpretation in Meningitis

Cerebrospinal fluid (CSF) analysis is the single most important diagnostic tool for meningitis, with specific patterns of findings helping to distinguish between bacterial, viral, and other causes of meningitis to guide appropriate treatment.

Key CSF Parameters to Analyze

• Cell Count and Differential:

  • Bacterial meningitis typically shows pleocytosis with predominance of polymorphonuclear neutrophils (PMNs) 1
  • Viral meningitis/encephalitis typically shows pleocytosis with predominance of lymphocytes 1
  • However, PMN predominance can occur in both bacterial (90%) and aseptic meningitis (57%), making this parameter alone insufficient for differentiation 2

• Glucose Levels:

  • Low glucose level in CSF with low CSF-to-blood glucose ratio is characteristic of bacterial meningitis 1
  • Normal or slightly decreased glucose levels are typical in viral encephalitis 1
  • Decreased CSF glucose ratio is one of the most reliable independent predictors of bacterial infection (AUROC 0.870) 3

• Protein Levels:

  • Elevated protein levels are typical in bacterial meningitis (usually markedly elevated) 1
  • Moderately elevated protein levels are seen in viral encephalitis 1

• CSF Lactate:

  • Increased CSF lactate is an independent predictor of bacterial infection (AUROC 0.780) 3

Microbiological Testing

• Gram Stain:

  • Should be performed in all suspected cases of meningitis 4
  • Up to 75% of cases of meningococcal meningitis have positive Gram stain results, while 25% may be negative 5

• Culture:

  • Gold standard for bacterial identification 4
  • Blood cultures should be obtained before antimicrobial therapy 6

• PCR Testing:

  • Positive PCR for HSV or other neurotropic viruses is diagnostic of viral encephalitis 1

Timing Considerations

• PMN Predominance in Viral Meningitis:
  • Contrary to traditional teaching, PMN predominance is not limited to the first 24 hours of illness in viral meningitis 2
  • 51% of patients with aseptic meningitis and duration of illness >24 hours still had a PMN predominance 2

Diagnostic Algorithm

1. Initial CSF Analysis:

   • Measure opening pressure
   • Cell count with differential
   • Glucose and protein levels
   • Gram stain and culture 4

2. Bacterial Meningitis Pattern:

   • PMN predominance
   • Low glucose (especially CSF-to-blood glucose ratio <0.4)
   • Elevated protein (usually >100 mg/dL)
   • Elevated lactate (>4 mmol/L) 1, 3

3. Viral Meningitis/Encephalitis Pattern:

   • Lymphocyte predominance (though PMNs may predominate early)
   • Normal or slightly decreased glucose
   • Moderately elevated protein 1
   • Presence of red blood cells may be seen in HSV encephalitis 1

Important Caveats

• Contraindications to Lumbar Puncture:

  • Presence of focal neurological findings suggesting mass lesion
  • Evidence of significant intracranial hypertension
  • Decerebrate posturing 6, 4
  • In these cases, blood cultures should be obtained and empiric antimicrobial therapy started immediately before any diagnostic procedures 6

• Partially Treated Meningitis:

  • Prior antibiotic administration may reduce the yield of CSF cultures and Gram stain
  • However, CSF findings (elevated WBC count, decreased glucose, elevated protein) will likely still provide evidence for or against bacterial meningitis 7

• Normal CSF Does Not Rule Out Meningitis:

  • A normal CSF analysis does not completely rule out meningitis, especially in patients with high clinical suspicion 5
  • Consider repeat lumbar puncture if clinical suspicion remains high 5

• Novel Biomarkers:

  • Phosphatidylcholine PC ae C44:6 shows promise as a sensitive biomarker for bacterial meningitis
  • It has higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%) compared to CSF cell count 8
  • A diagnostic algorithm combining cell count, lactate, and PC ae C44:6 had 97% sensitivity and 99% negative predictive value 8

Treatment Implications

• Empiric Antimicrobial Therapy:

  • Should be started immediately after obtaining blood cultures if lumbar puncture is delayed 5
  • Delay in antimicrobial therapy increases mortality 6

• Adjunctive Dexamethasone:

  • Should only be used in confirmed bacterial meningitis
  • Use in clinically suspected but unproven cases has been associated with increased mortality and poor outcomes 9