CSF Analysis Procedure and Meningitis Management
Recommended CSF Collection Volume
Collect at least 22 mL of CSF from adults for comprehensive diagnostic testing, as CSF is produced at approximately 15 mL/hour and this volume can be safely removed. 1, 2 The first 2-2.5 mL should be allocated for cell count with differential, microscopy, culture, and sensitivities, with a minimum of 5 mL optimal for standard diagnostic procedures. 2
Additional Volume Requirements by Suspected Pathogen
- Viral studies: Additional 2 mL 2
- Tuberculous meningitis: Additional 6 mL 2
- Standard testing: 1-2 mL for protein and glucose measurements 2
Essential CSF Tests to Perform
Core Diagnostic Panel (All Patients)
- Cell count with differential 1
- Glucose concentration with concurrent plasma glucose 1
- Protein concentration 1
- Opening pressure (unless performed in sitting position) 1
- Gram stain (sensitivity 50-99%, specificity 97-100%) 1
- Bacterial culture (diagnostic in 70-85% of untreated cases) 1
Advanced Molecular Testing
CSF PCR should be performed, especially if antibiotics were given prior to lumbar puncture, as it has sensitivity of 87-100% and specificity of 98-100%. 1 PCR remains positive even after CSF sterilization occurs within 2 hours for meningococci and 4 hours for pneumococci following antibiotic administration. 1
Additional Tests Based on Clinical Context
- Immunocompromised patients: PCR for HSV, CMV, JC virus, West Nile virus, adenovirus, enterovirus 1
- Cryptococcal antigen testing: Based on immune status 1
- Fungal stains and cultures: If fungal infection suspected 1
- Acid-fast bacillus smears and cultures: If tuberculous meningitis suspected 1
- CSF lactate: Particularly useful in neurosurgical patients to distinguish infection from postoperative aseptic meningitis 1
Critical CSF Findings by Meningitis Type
Bacterial Meningitis (Classical Pattern)
- Opening pressure: Elevated (>20 cm CSF) 1
- Appearance: Turbid, cloudy, or purulent 1
- WBC count: Typically >100 cells/μL (often >2,000/μL) 1
- Predominant cell type: Neutrophils 1
- Glucose: Very low (typically <35 mg/dL) 1
- CSF/plasma glucose ratio: Very low (<0.23, typically <0.4) 1, 3
- Protein: Markedly elevated (typically >220 mg/dL) 1
Viral Meningitis
- Opening pressure: Normal or mildly raised 1
- Appearance: Clear 1
- WBC count: Typically 5-1,000 cells/μL 1
- Predominant cell type: Lymphocytes (may be neutrophils early in enteroviral disease) 1
- Glucose: Normal or slightly low 1
- Protein: Mildly raised 1
Critical Pitfalls and Exceptions
When CSF May Appear Normal Despite Meningitis
Meningitis can occur without pleocytosis in the CSF, particularly early in disease course or in immunocompromised patients—maintain high suspicion and administer empiric antibiotics regardless of initial WBC count. 1, 4 In one systematic review, 124 cases of culture-confirmed meningitis lacked pleocytosis, with 31% mortality in bacterial cases. 4
- 10% of bacterial meningitis patients have <100 cells/mm³ 1
- Immunocompromised patients: Normal CSF parameters do not exclude meningitis 1, 5
- Early disease: Minimal or no white cells may be present 1
Atypical Presentations
- Listeria monocytogenes: May show lymphocytic predominance rather than neutrophils 1
- Partially treated bacterial meningitis: May show lymphocytic predominance 1
- Early enteroviral meningitis: May show neutrophil predominance 1
Timing and Processing Requirements
Process CSF within 30-60 minutes of collection to avoid cellular degradation and false-negative results. 2 Delay beyond 30 minutes significantly affects test accuracy. 2
CSF analysis remains helpful up to 48 hours after commencing parenteral antibiotics, though culture yield decreases. 1
When Imaging is Required Before Lumbar Puncture
Delay lumbar puncture and obtain neuroimaging first if any of the following are present: 1
- Signs of severe sepsis or rapidly evolving rash 1
- Respiratory or cardiac compromise 1
- Focal neurologic findings suggesting disease above foramen magnum 1
- Signs suggesting mass lesion 1
- Anticoagulant therapy or known thrombocytopenia 1
- Infection at LP site 1
Special Populations
Patients with Intracranial Devices
In febrile patients with ventriculostomy or VP shunt, obtain CSF from the reservoir; if CSF flow is obstructed, also obtain lumbar CSF as one space may be infected while the other is sterile. 1 Remove ventriculostomy catheters in patients who develop stupor or meningitis signs and culture the tip. 1
Adjunctive Diagnostic Measures
Obtain blood cultures in all suspected meningitis cases, as they are positive in 71% of cases with meningitis lacking CSF pleocytosis. 4 Blood cultures may be the only positive diagnostic test in some cases. 4
Consider nasopharyngeal swabs for meningococcal disease when antibiotics were given before LP, as nasal swabs may remain positive when blood and CSF cultures are negative. 1
Diagnostic Accuracy Thresholds
The following CSF parameters have the highest diagnostic accuracy for bacterial meningitis: 3
- CSF/blood glucose ratio ≤0.4: Likelihood ratio 18 (95% CI 12-27)
- CSF WBC ≥500/μL: Likelihood ratio 15 (95% CI 10-22)
- CSF lactate ≥31.53 mg/dL (≥3.5 mmol/L): Likelihood ratio 21 (95% CI 14-32)
In immunologically normal hosts, normal opening pressure, <5 WBC/μL, and normal CSF protein essentially exclude meningitis. 1, 5
Treatment Implications
If bacterial meningitis is suspected and lumbar puncture is delayed for any reason, start empirical antibiotic therapy immediately after obtaining blood cultures—do not wait for CSF results. 1, 5
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