CSF Analysis: Cell Count and Differential
Cell count and differential on cerebrospinal fluid is a core component of standard CSF analysis, routinely performed as part of the initial diagnostic workup for suspected central nervous system infections, inflammatory conditions, and other neurological disorders. 1, 2
What This Test Includes
CSF cell count and differential is part of the essential testing panel that should be performed on all patients undergoing lumbar puncture for suspected CNS disease. The test specifically measures:
- Total white blood cell (WBC) count - quantifies the number of inflammatory cells present 2, 3
- Differential cell count - identifies the specific types of white blood cells (neutrophils, lymphocytes, monocytes, eosinophils) and their proportions 1, 2
- Red blood cell (RBC) count - helps distinguish traumatic tap from pathologic hemorrhage 1, 3
Clinical Significance and Interpretation
The cell count and differential provides critical diagnostic information that helps differentiate between major categories of CNS disease:
Bacterial Meningitis
- Typically shows ≥2,000 WBCs/μL or ≥1,180 neutrophils/μL with neutrophilic predominance 2
- Persistent neutrophilic pleocytosis can occur with West Nile virus encephalitis 1
- Early in disease course, polymorphonuclear cell predominance may be seen even in viral infections 1
Viral Infections
- Characterized by lymphocytic pleocytosis (5-1,000 cells/μL) with mononuclear cell predominance 1, 2
- Mild mononuclear pleocytosis is typical 1
Autoimmune Encephalitis
- Shows mild to moderate lymphocytic pleocytosis (commonly 20-200 cells but can reach 900 cells) 1
- Routine CSF studies may be normal in some patients, which does not exclude the diagnosis 1
Guillain-Barré Syndrome
- Classic finding is albumino-cytological dissociation (elevated protein with normal cell count) 1
- Marked pleocytosis (>50 cells/μL) suggests alternative diagnoses such as leptomeningeal malignancy or infectious/inflammatory polyradiculitis 1
- Mild pleocytosis (10-50 cells/μL) is compatible with GBS but should prompt consideration of infectious causes 1
Integration with Comprehensive CSF Analysis
Cell count and differential is always performed alongside other essential CSF tests:
- Opening pressure - critical for detecting elevated intracranial pressure 2
- Protein concentration - normal <220 mg/dL; elevated in infection/inflammation 2
- Glucose level and CSF/serum glucose ratio - normal glucose >35 mg/dL with ratio >0.23; lower values suggest bacterial infection 2
- Gram stain and bacterial culture - for organism identification 1, 2
- Additional specialized testing based on clinical suspicion (PCR for viruses, oligoclonal bands, cytology, etc.) 1, 2
Critical Technical Considerations
Timing is essential: Process CSF within 30 minutes to prevent cellular degradation that can lead to falsely low cell counts 2. Delayed processing beyond 30 minutes is a common cause of inaccurate results 2.
Volume requirements: Collect at least 5 mL of CSF for standard testing, with 8-10 mL required for comprehensive panels 2. Insufficient volume is a leading cause of false-negative results 2.
Sample handling: The first tube collected has the highest contamination risk and should not be sent for microbiology studies 2. Hemorrhagic contamination interferes with test interpretation 2.