Comprehensive CSF Analysis for Suspected CNS Infections and Malignancy
A comprehensive cerebrospinal fluid (CSF) analysis for suspected CNS infections or malignancy should include standard measurements, microbiological studies, and specialized tests based on clinical presentation, with PCR testing for HSV-1/2, VZV, and enteroviruses as core components for all patients with suspected encephalitis.
Standard CSF Collection and Analysis
Collection Requirements
- Collect at least 20 cc of fluid when possible 1
- Freeze 5-10 cc for potential additional testing 1
- Transport in sterile container at room temperature within 2 hours 2
Basic CSF Parameters (Required for All Cases)
- Opening pressure measurement 1
- Cell count with differential (WBC, RBC) 1
- Protein level 1
- Glucose level (with simultaneous serum glucose) 1
- CSF:serum glucose ratio 3
- CSF lactate (values <2 mmol/L help rule out bacterial disease) 1
Microbiological Testing
Standard Microbiology (All Suspected Infections)
- Gram stain and bacterial culture 1
- Cryptococcal antigen and/or India ink staining 1
- VDRL for syphilis 1
Viral Testing
- PCR for HSV-1/2, VZV, and enteroviruses (identifies 90% of known viral cases) 1
- Consider EBV PCR, especially in immunocompromised patients 1
- Consider additional viral PCR based on clinical presentation:
Bacterial Testing Beyond Standard Culture
- Consider PCR for S. pneumoniae and N. meningitidis if recent antibiotic use 1
- Acid-fast bacillus staining and culture for M. tuberculosis (if suspected) 1
- Consider specialized bacterial PCR based on clinical presentation 1
Fungal Testing
- Culture on Sabouraud Dextrose Agar and Potato Dextrose Agar for fungal isolation 2
- For suspected Aspergillus, culture at both 30°C and 37°C for 72 hours 2
Immunological and Specialized Testing
Immunological Markers
- Oligoclonal bands and IgG index 1
- Consider virus-specific IgM in CSF for certain viral agents 1
- Paired CSF and serum antibody testing for suspected pathogens 1
Malignancy Evaluation
- Cytology for malignant cells 1
- Consider large-volume CSF cytology if leptomeningeal carcinomatosis suspected 3
- Flow cytometry in patients with hematologic malignancies 1
Testing Based on Clinical Scenarios
Immunocompromised Patients
- Standard viral PCR plus EBV and CMV PCR 1
- Cryptococcal antigen testing 1
- Consider JC/BK virus PCR 1
- Toxoplasma gondii antibody testing and PCR if positive 1
Suspected Autoimmune Encephalitis
Travel or Exposure History
- Specific testing based on geographic exposure:
Interpretation Considerations
Traumatic Tap Adjustment
- Subtract 1 white cell for every 700 red blood cells 1
- Note that blood-stained CSF in HSV encephalitis may reflect hemorrhagic pathophysiology 1
Special Considerations
- Acellular CSF may still indicate infection in immunocompromised patients 1
- High CSF lactate may indicate bacterial infection or metabolic disorder 1
- Lymphocytic pleocytosis is typical of viral infections but can occur in TB, listeriosis, and partially treated bacterial meningitis 1
Practical Algorithm
First-line testing (all suspected CNS infections):
- Basic CSF parameters + Gram stain and culture + Cryptococcal antigen
- PCR for HSV-1/2, VZV, and enteroviruses
Second-line testing (based on clinical presentation):
- Immunocompromised: Add EBV/CMV PCR, fungal testing
- Suspected TB: Add acid-fast staining, TB culture/PCR
- Suspected malignancy: Add cytology, flow cytometry
- Suspected autoimmune: Add antibody testing, oligoclonal bands
Third-line testing (special circumstances):
- Specific exposures: Add targeted testing for relevant pathogens
- Unusual presentations: Consider rare pathogens based on epidemiology
By following this comprehensive approach to CSF analysis, clinicians can maximize diagnostic yield while prioritizing tests most likely to impact patient outcomes in terms of morbidity, mortality, and quality of life.