How is cerebrospinal fluid (CSF) interpreted?

How to Interpret Cerebrospinal Fluid (CSF)

CSF interpretation requires systematic evaluation of opening pressure, cell count with differential, protein, glucose (with simultaneous plasma glucose for ratio calculation), and appearance, with patterns varying distinctly by etiology—bacterial meningitis shows neutrophilic pleocytosis (>100 cells/μL), elevated protein, very low glucose (<2.6 mmol/L), and CSF:plasma glucose ratio <0.36, while viral meningitis demonstrates lymphocytic pleocytosis (5-1000 cells/μL), mildly elevated protein, and normal/slightly low glucose. 1

Essential Parameters to Measure

Opening Pressure

• Normal range: 12-20 cm CSF (or 6-25 cmH₂O with mean ~18 cmH₂O) 1, 2
• Raised in bacterial, tuberculous, and fungal meningitis 1
• Normal or mildly raised in viral meningitis 1, 3

Cell Count and Differential

• Normal: <5 cells/μL 1
• Bacterial meningitis: Typically >100 cells/μL with neutrophil predominance 1
  • May be lymphocytic if antibiotics given before LP (partially treated) or with Listeria monocytogenes 1
• Viral meningitis: 5-1000 cells/μL with lymphocyte predominance 1, 3
  • Neutrophils may predominate early, especially in enteroviral disease, but total WCC unlikely to exceed 2000 cells/μL 1, 3
• Tuberculous/Fungal: 5-500 cells/μL with lymphocyte predominance 1

Critical pitfall: Traumatic LP falsely elevates white cells—correct by subtracting 1 white cell per 7000 red cells 1

Protein

• Normal: <0.4 g/L 1
• Bacterial: Raised; CSF protein <0.6 g/L makes bacterial meningitis unlikely 1
• Viral: Mildly raised 1, 3
• Tuberculous: Markedly raised 1
• Correct for bloody tap by subtracting 0.1 g/dL protein per 100 red cells 1

Glucose and CSF:Plasma Glucose Ratio

• Normal CSF glucose: 2.6-4.5 mmol/L (approximately 2/3 of plasma glucose) 1, 2
• Normal CSF:plasma ratio: >0.66 1
• Bacterial meningitis: Very low glucose; CSF:plasma ratio <0.36 has 93% sensitivity and specificity 1
• Isolated CSF glucose >2.6 mmol/L makes bacterial meningitis unlikely 1
• Viral meningitis: Normal or slightly low glucose 1, 3
• Tuberculous/Fungal: Very low glucose 1

Critical requirement: Always obtain plasma glucose simultaneously with LP for accurate ratio calculation 1

Appearance

• Normal/Viral: Clear 1, 3
• Bacterial: Turbid, cloudy, or purulent 1
• Tuberculous/Fungal: Clear or cloudy 1

Adjunctive Tests for Bacterial vs. Viral Differentiation

CSF Lactate

• Cut-off 35 mg/dL (or <2 mmol/L): 93% sensitivity and 96% specificity for distinguishing bacterial from viral meningitis if measured before antibiotics 1
• High negative predictive value—useful to rule out bacterial meningitis and support withholding/stopping antibiotics 1
• Sensitivity drops to <50% after antibiotic administration 1

Microbiological Studies

• Gram stain: 50-99% sensitivity (organism and antibiotic-dependent), 97-100% specificity 1
• Culture: Gold standard for bacterial meningitis 1
• PCR: Should be performed for HSV (1 and 2), VZV, and enteroviruses—identifies 90% of viral cases 3

Special Considerations

Viral Encephalitis (HSV)

• Opening pressure moderately elevated 1
• Moderate pleocytosis (tens to hundreds of cells) with possible neutrophil predominance 1
• 5-10% may have normal initial CSF with negative HSV PCR 1, 3
• If first CSF normal, repeat in 24-48 hours likely to be abnormal 1, 3
• Red cell count elevated in ~50% due to hemorrhagic nature 1, 3

Alzheimer's Disease Biomarkers

• AD pattern: Decreased Aβ1-42 with increased tau and phospho-tau 1
• Conflicting results (low Aβ1-42 but normal tau/p-tau) make AD less likely but still possible 1
• Normal Aβ1-42, tau, and p-tau make AD unlikely as dementia cause 1
• Results near cut-offs require careful interpretation due to 10% analytical variability 1

Inflammatory Markers

• Single inflammatory markers insufficient—interpret as part of network-based approach 1, 4
• Consider context-dependent functions, co-pathologies, and disease stage 1, 4
• CSF inflammatory markers may show nonlinear trajectories in aging/disease progression 4

Algorithmic Approach to Interpretation

1. Assess opening pressure for raised vs. normal 1
2. Examine appearance for turbidity suggesting bacterial etiology 1
3. Evaluate WCC and differential:
   • Neutrophilic pleocytosis >100 cells/μL → suspect bacterial 1
   • Lymphocytic 5-1000 cells/μL → suspect viral 1, 3
4. Calculate CSF:plasma glucose ratio:
   • <0.36 → strongly suggests bacterial 1
   • Normal/slightly low → supports viral 1, 3
5. Check protein level:
   • <0.6 g/L makes bacterial unlikely 1
   • Markedly raised → consider tuberculous 1
6. If available, measure CSF lactate before antibiotics:
   • ≥35 mg/dL → bacterial 1
   • <2 mmol/L → rules out bacterial 1, 3
7. Send appropriate microbiological studies based on suspected etiology 1, 3

No CSF parameter gives absolute indication of cause—always interpret in clinical context 1