How do you interpret CSF results for CNS infection?

Interpreting CSF Results for CNS Infection

The interpretation of cerebrospinal fluid (CSF) analysis for CNS infection should focus on five key parameters: opening pressure, cell count with differential, protein level, glucose level, and specific microbiological studies, with results interpreted in the context of the patient's clinical presentation.

Normal CSF Values and Pathological Changes

• Normal CSF values:

  • Opening pressure: 10-20 cmH₂O
  • Appearance: Clear and colorless
  • WBC count: 0-5 cells/μL (predominantly lymphocytes)
  • Protein: 15-45 mg/dL
  • Glucose: >60% of serum glucose 1

• Bacterial meningitis typically shows:

  • Elevated opening pressure
  • CSF glucose <35 mg/dL
  • CSF:blood glucose ratio <0.23
  • CSF protein >220 mg/dL

  • 2,000 WBCs/μL or >1,180 neutrophils/μL 2

  • Predominance of polymorphonuclear cells (neutrophils)

• Viral encephalitis/meningitis typically shows:

  • Mild to moderate lymphocytic pleocytosis (though polymorphonuclear cells may predominate early)
  • Mildly or moderately elevated protein
  • Normal glucose ratio
  • Possible RBCs in hemorrhagic encephalitis 2

Essential Diagnostic Algorithm

Step 1: Determine Need for Neuroimaging Before LP

Perform CT scan before LP if any of these are present:

• Immunocompromised state (HIV/AIDS, immunosuppressive therapy, transplant)
• History of CNS disease (mass lesion, stroke, focal infection)
• New-onset seizure within 1 week of presentation
• Papilledema
• Abnormal level of consciousness
• Focal neurologic deficit 2

Step 2: Collect and Process CSF Properly

• Collect 8-15 mL total CSF in 3-4 sequential tubes
• Process within 30-60 minutes of collection
• Use a 22G atraumatic needle to reduce post-LP headache risk 1

Step 3: Order Appropriate CSF Tests

For all suspected CNS infections:

• Opening pressure measurement
• Cell count with differential
• Protein and glucose (with simultaneous blood glucose)
• Gram stain and bacterial culture 2

Additional tests based on clinical suspicion:

• For suspected viral encephalitis:

  • PCR for HSV 1 & 2, VZV, enteroviruses
  • In immunocompromised patients: add EBV, CMV, HHV-6/7, JC virus 2

• For suspected bacterial meningitis:

  • Bacterial antigen testing (though routine use not recommended)
  • Consider PCR multiplex testing, particularly valuable in patients already on antibiotics 3

• For suspected fungal infection:

  • India ink staining and/or cryptococcal antigen testing
  • Fungal culture 2

• For suspected autoimmune encephalitis:

  • Neural autoantibody panel in both CSF and serum 1

Step 4: Interpret Results

Cell Count and Differential

• >2000 WBCs/μL with neutrophil predominance: Strongly suggests bacterial meningitis
• 10-1000 WBCs/μL with lymphocyte predominance: Suggests viral, fungal, or tuberculous infection
• Eosinophils in CSF: Consider parasitic infections, fungal infections, or certain bacterial infections (T. pallidum, M. pneumoniae) 2
• Normal cell count: Does not exclude infection, especially in immunocompromised patients 2

Glucose and Protein

• Low glucose ratio (<0.6) with high protein: Suggests bacterial, fungal, or tuberculous infection
• Normal glucose with mildly elevated protein: Suggests viral infection
• CSF lactate >2 mmol/L: Suggests bacterial rather than viral infection 2

Microbiological Studies

• Gram stain: Positive in 60-90% of untreated bacterial meningitis
• PCR: High sensitivity for viral pathogens (HSV PCR sensitivity 96-98%, specificity 95-99%) 2
• Consider repeat HSV PCR if initially negative but high clinical suspicion (3-7 days later) 2

Special Considerations

Immunocompromised Patients

• May present with subtle, subacute symptoms
• CSF may be acellular despite infection
• Broader range of potential pathogens
• Perform CSF microbial investigations regardless of cell count 2

Partially Treated Bacterial Meningitis

• Prior antibiotics may reduce yield of CSF cultures and Gram stain
• PCR multiplex testing may be particularly valuable in these cases 3
• CSF findings (elevated WBC, low glucose, high protein) still provide evidence for diagnosis 2

Traumatic Tap Correction

• Subtract 1 white cell for every 7000 RBCs/μL in CSF
• Subtract 0.1 g/dL protein for every 100 RBCs 2

Pitfalls to Avoid

1. Delaying antimicrobial therapy: If bacterial meningitis is suspected and LP is delayed, start empiric antibiotics after blood cultures 2

2. Relying solely on CSF cell count: Normal CSF cell count occurs in approximately 5-10% of adults with proven HSV encephalitis, and even more frequently in immunocompromised patients 2

3. Misinterpreting bacterial antigen tests: False positives and negatives occur; a negative test does not rule out infection 2

4. Overlooking autoimmune causes: Consider autoimmune encephalitis in patients with subacute presentation, especially with normal or inconclusive infectious workup 1

5. Failing to repeat testing: Consider repeat LP and HSV PCR 3-7 days later if initial tests are negative but clinical suspicion remains high 2

By systematically analyzing CSF parameters and integrating results with clinical presentation, clinicians can effectively diagnose CNS infections and initiate appropriate treatment to improve patient outcomes.