Standard CSF Testing Panel
When sending cerebrospinal fluid to the laboratory, order a core panel consisting of: opening pressure, cell count with differential, glucose (with simultaneous serum glucose), protein, Gram stain, and bacterial culture—this foundational set identifies the vast majority of clinically significant pathology and guides all subsequent specialized testing. 1
Essential Core Tests (Order on Every Sample)
Opening pressure: Critical for detecting elevated intracranial pressure and guiding management 2
Cell count with differential: Distinguishes bacterial meningitis (typically ≥2,000 WBCs/μL or ≥1,180 neutrophils/μL) from viral infections (lymphocytic pleocytosis, 5-1,000 cells/μL) 1
Glucose with simultaneous serum glucose: Normal CSF glucose is >35 mg/dL with CSF-to-blood ratio >0.23; ratios <0.36 have 92.9% sensitivity and specificity for bacterial meningitis 1, 3
Protein: Normal is <220 mg/dL; elevations indicate infection or inflammation 1
Gram stain and bacterial culture with sensitivities: Despite limited sensitivity of Gram stain, these remain critical for organism identification and antibiotic guidance 1, 4
Reserve sample (2 mL minimum): Store frozen for future virological or specialized testing as clinical picture evolves 2
Volume Requirements
Collect at least 5 mL total for standard testing; 8-10 mL if specialized panels are anticipated 1
First tube has highest contamination risk—do not send for microbiology studies 1
Larger volumes (5-10 mL) increase sensitivity for mycobacterial and fungal cultures 1
Process within 30 minutes to prevent cellular degradation; if impossible, fix with ethanol/Carbowax (1:1 ratio) 1
Specialized Testing Based on Clinical Context
For Suspected Viral Encephalitis (All Patients)
HSV-1, HSV-2, and VZV PCR: Identifies 90% of viral encephalitis cases when combined with enterovirus testing 2
Enterovirus and parechovirus PCR: Essential components of initial viral workup 2
For Immunocompromised Patients
Cryptococcal antigen, fungal stains and cultures 1
Acid-fast bacillus smears and mycobacterial cultures (6 mL) 2, 1
PCR for CMV, HHV-6/7, HIV, JC virus, West Nile virus, adenovirus 2, 1
Toxoplasma gondii serology and/or PCR 2
For Specific Clinical Presentations
Psychotic features or movement disorders: Anti-NMDAR antibody (serum and CSF), rabies testing 2
Respiratory symptoms: Mycoplasma pneumoniae serology and throat PCR; if positive, add CSF PCR 2
Temporal lobe findings on imaging: VGKC antibodies (serum and CSF), HHV-6/7 PCR 2
CSF protein >100 mg/dL or glucose <2/3 peripheral glucose with subacute onset: Mycobacterium tuberculosis testing 2
Suspected neurosyphilis: CSF VDRL or RPR 1
Suspected malignancy: Cytologic examination with large-volume CSF (minimum 5 mL) 1
Demyelinating disorders: Oligoclonal bands, IgG index, IgG synthesis rate 1, 5
Critical Pitfalls to Avoid
Never delay antibiotics for imaging or LP results if bacterial meningitis is suspected—start empirical therapy immediately after blood cultures 1, 4
Insufficient volume is a leading cause of false-negative results—collect adequate amounts upfront 1
Delayed processing beyond 30 minutes causes cellular degradation and invalidates cell counts 1
In immunocompromised patients, normal cell count and glucose do not exclude infection—maintain high suspicion until cultures finalize 1, 6
If initial LP is non-diagnostic, repeat at 24-48 hours—particularly important for HSV encephalitis where initial CSF may be normal in 5-10% of adults 2
PCR multiplex panels add substantial value in patients already on antibiotics—particularly for Streptococcus pneumoniae detection 7