What are the guidelines for cerebrospinal fluid (CSF) analysis and interpretation?

Guidelines for Cerebrospinal Fluid (CSF) Analysis and Interpretation

CSF analysis should include cell counts with differential, glucose and protein concentrations, Gram stain, and bacterial cultures as the standard panel for all suspected central nervous system infections, with additional specialized tests determined by clinical context. 1

Standard CSF Analysis Components

Basic CSF Parameters

• Normal CSF contains fewer than 5 white blood cells (WBCs) per mm³, predominantly lymphocytes 2
• Normal CSF protein is typically less than 220 mg/dL, with elevated levels suggesting infection or inflammation 1
• Normal CSF glucose should be greater than 35 mg/dL with a CSF-to-blood glucose ratio greater than 0.23; lower values suggest bacterial infection 1
• CSF opening pressure should be measured when clinically indicated, with normal pressure excluding meningitis in immunologically normal hosts 1

Cell Count and Differential

• Cell count with differential is essential for all CSF analyses 1
• Bacterial meningitis typically presents with 2,000 total WBCs/μL or 1,180 neutrophils/μL 1
• Viral meningitis typically shows mild to moderate lymphocytic pleocytosis (5-1000 cells/μL) 1
• Correction for traumatic lumbar puncture: subtract 1 WBC for every 700 RBCs/μL in traumatic taps 2

Biochemical Analysis

• Protein and glucose measurements should be performed on all CSF samples 1
• CSF lactate may help distinguish bacterial from viral meningitis, with higher levels in bacterial infection 1
• CSF albumin-to-serum albumin ratio (Qalb) is preferred over total protein measurement for assessing blood-brain barrier integrity 3

Specialized CSF Testing Based on Clinical Context

Infectious Disease Evaluation

• For suspected bacterial meningitis: Gram stain, culture, and antimicrobial susceptibility testing 1
• For suspected viral encephalitis/meningitis: PCR for herpes simplex virus, enterovirus, and other viruses based on epidemiology 1
• For immunocompromised patients: additional testing for cryptococcal antigen, fungal stains/cultures, acid-fast bacilli, and PCR for opportunistic pathogens (CMV, JC virus, West Nile virus) 1
• For suspected neurosyphilis: CSF VDRL or RPR testing 1

Subarachnoid Hemorrhage

• Xanthochromia assessment and RBC count for suspected subarachnoid hemorrhage, especially when presentation is delayed beyond 6 hours after symptom onset 4
• Bilirubin detection for CT-negative intrathecal bleeding 3

Demyelinating and Neurodegenerative Disorders

• For suspected multiple sclerosis: oligoclonal bands, IgG index, and IgG synthesis rate 1
• For suspected Alzheimer's disease: Aβ42 and tau/phosphorylated tau (p-tau) profiles when diagnostic uncertainty remains after structural imaging 1
• CSF biomarkers for AD are more useful in early or atypical presentations when diagnostic confidence is intermediate 1

Malignancy

• Cytological examination for suspected leptomeningeal metastases 4
• Large-volume CSF cytology may be required for optimal diagnostic yield 4

Timing and Handling of CSF Samples

• CSF should be analyzed immediately after collection to prevent cellular degradation 3
• If storage is needed, CSF should be divided into 3-4 sterile tubes (minimum 12 mL total) 3
• For research purposes, CSF should be processed within 30-60 minutes of collection 1
• CSF for cell count should be examined promptly as cells begin to lyse within 1-2 hours 2

Special Considerations for Patients with Intracranial Devices

• For patients with ventriculostomy catheters who develop fever or signs of meningitis, the catheter should be removed and the tip cultured 1
• In patients with shunt systems or Ommaya reservoirs, CSF should be obtained from the reservoir 1
• When CSF flow to the subarachnoid space is obstructed, consider obtaining samples from both the device and lumbar space 1

Interpretation Challenges and Pitfalls

• CSF findings may be normal early in the course of certain CNS infections, particularly viral encephalitis 2
• The presence of a normal opening pressure, fewer than 5 WBCs/μL, and normal protein concentration essentially excludes meningitis in immunocompetent hosts 1
• Interpretation of AD CSF biomarkers requires consideration of pretest probability, age, clinical presentation, and possibility of multiple pathologies 1
• False-positive results on imaging studies (CT, MRI, PET) may occur due to immune deficiency-related lymphoid hyperplasia or opportunistic infections in immunocompromised patients 1

Algorithm for CSF Analysis in Different Clinical Scenarios

1. Suspected bacterial meningitis:

   • Perform CT before lumbar puncture if focal neurologic signs, papilledema, or altered consciousness 1
   • Start empiric antibiotics before lumbar puncture if delayed 1
   • Analyze CSF for cell count, glucose, protein, Gram stain, and culture 1

2. Suspected viral encephalitis/meningitis:

   • Analyze CSF for cell count, glucose, protein, and PCR for suspected viral pathogens 1
   • Consider repeat lumbar puncture if initial CSF is normal but clinical suspicion remains high 2

3. Suspected neurodegenerative disorder:

   • Obtain CSF for Aβ42 and tau/p-tau profiles when diagnostic uncertainty remains after structural imaging 1
   • Interpret results in context of clinical presentation and other biomarkers 1

4. Patients with intracranial devices:

   • Obtain CSF from the device reservoir when infection is suspected 1
   • Remove and culture ventriculostomy catheters if signs of meningitis develop 1