How do you interpret a CSF (Cerebrospinal Fluid) study?

How to Interpret a CSF Study

Interpret CSF studies systematically by first assessing basic parameters (opening pressure, cell count, protein, glucose), then applying disease-specific biomarker patterns, while always considering the clinical context including age, comorbidities, and timing of disease.

Immediate Assessment Parameters

Opening Pressure

• Normal range: 6-25 cmH₂O (population mean ~18 cmH₂O) 1
• Elevated pressure suggests: increased intracranial pressure, meningitis, or subarachnoid hemorrhage 2
• Critical caveat: Pressure can sometimes be normal despite significant pathology 3

Cell Count and Differential

• Perform cytological staining whenever pleocytosis is found 4
• Bacterial meningitis: Elevated white blood cells with neutrophil predominance 2
• Viral meningitis: Lymphocytic pleocytosis 2
• Fungal/TB meningitis: Lymphocytic pleocytosis with elevated protein 4
• Always evaluate cellular morphology to rule out leptomeningeal metastases 4

Protein and Glucose

• Use albumin CSF/serum ratio (Qalb) rather than total protein alone 4
• Adjust normal upper limits for patient age 4
• Elevated Qalb occurs in: bacterial/cryptococcal/tuberculous meningitis, leptomeningeal metastases, acute/chronic demyelinating polyneuropathies 4
• CSF glucose should be approximately 2/3 of serum glucose 1
• Pathologically decreased CSF/serum glucose ratio indicates: bacterial or fungal meningitis, or leptomeningeal metastases 4

Lactate

• Increased lactate concentration indicates bacterial or fungal meningitis or leptomeningeal metastases 4
• Use as adjunctive test to differentiate bacterial from viral meningitis 2

Disease-Specific Interpretation Algorithms

For Suspected Alzheimer's Disease/Cognitive Impairment

Primary Biomarkers 5:

• Measure: Aβ1-42, total tau, and phosphorylated tau (p-tau)
• Use laboratory-specific cut-off points validated by BIOMARKAPD consortium recommendations 5

Interpretation Pattern 5:

1. AD Pattern (High Probability):

   • Decreased Aβ1-42 AND elevated tau AND elevated p-tau
   • Action: Offer cholinesterase inhibitors/memantine, counseling, clinical trial enrollment 5
   • Prognosis: 54% 3-year risk of progression to dementia in MCI patients 5

2. Conflicting Results:

   • Decreased Aβ1-42 but normal tau/p-tau: AD still possible but less likely 5
   • Elevated tau/p-tau but normal Aβ1-42: Consider other neurodegenerative disorders 5
   • Action: Check CSF cell count, albumin quotient, consider measuring Aβ1-40, add imaging biomarkers 5

3. Normal Pattern:

   • All three biomarkers normal: AD unlikely as cause 5
   • Prognosis: 14% 3-year risk of progression in MCI patients 5

4. Gray Zone (Near Cut-offs):

   • Analytical variability ~10% creates uncertainty zone 5
   • Action: Repeat analysis or add imaging biomarker 5

Critical Interpretation Caveats 5:

• Use same cut-off points regardless of APOE genotype 5
• Do not adjust for age, as age-related Aβ decreases reflect actual amyloid accumulation 5
• APOE ε4 carriers may have low CSF Aβ1-42 without clinical AD symptoms 5

For Suspected Infectious Meningitis

Bacterial Meningitis Pattern 2:

• High WBC count with neutrophil predominance
• Elevated protein
• Low CSF:serum glucose ratio
• Elevated lactate
• Obtain CSF culture immediately for organism identification and antibiotic sensitivities 2

Viral Meningitis Pattern 2:

• Lymphocytic pleocytosis
• Normal to mildly elevated protein
• Normal glucose
• Use PCR testing to identify specific viral pathogens 2

Immunocompromised Patients 2:

• Consider TB, neurosyphilis, fungal, or parasitic causes
• Perform panbacterial and panfungal examinations when relevant 6

For Suspected Subarachnoid Hemorrhage

Diagnostic Criteria 2:

• Elevated red blood cell count
• Xanthochromia (bilirubin detection) is characteristic 2, 4
• CSF analysis required if CT negative and >6 hours from symptom onset 2

For Inflammatory/Autoimmune Conditions

Multiple Sclerosis Pattern 4:

• Intrathecal IgG synthesis demonstrated by isoelectric focusing with specific staining 4
• Oligoclonal bands present in CSF but not serum

Neurosyphilis 5:

• Positive treponemal serology
• CSF VDRL is insensitive but specific 5
• Mononuclear pleocytosis and elevated protein 5
• Lumbar puncture mandatory for neurologic/ocular symptoms or late latent syphilis 5

Context-Dependent Interpretation Factors

Age-Related Considerations

• Adjust normal ranges for patient age, particularly for albumin ratio 4
• Co-pathology is common in patients 80s-90s, complicating interpretation 5
• CSF inflammatory markers may show nonlinear or U-shaped trajectories with aging 7

Inflammatory Marker Interpretation 5, 7

• Never interpret single inflammatory markers in isolation 7
• Consider network-based approach with multiple markers 7
• Blood inflammatory markers are insufficient proxies for neuroinflammation without CNS validation 5
• Pro-inflammatory markers have pleiotropic, context-dependent functions 7
• Parenchymal glia secretome may be insufficiently captured by bulk CSF assays 7

Comorbidity Impact 5

• Migraine, systemic lupus erythematosus, normal pressure hydrocephalus can alter inflammatory profiles 5
• Different neurodegenerative diseases may show distinct CSF inflammatory signatures 5
• Chronic health conditions exacerbate inflammatory pathways 5

Technical and Timing Considerations

Sample Handling 4, 8

• Analyze CSF immediately after collection 4
• If storage needed: partition ≥2 mL into 3-4 sterile tubes 4
• Optimize all preanalytic factors to ensure valid results 8

Contraindications to Lumbar Puncture 5

• Increased intracranial pressure
• Coagulopathy (including current anticoagulant use)
• Skin infection at injection site
• Weigh risk of stopping anticoagulation against benefit of biomarker information 5

Common Complications 5

• Transient back pain
• Post-LP headache

Practical Clinical Algorithm

1. Obtain clinical context first: Age, symptom timeline, comorbidities, medication history
2. Assess basic parameters: Pressure, cells, protein, glucose, lactate
3. Apply disease-specific biomarker patterns based on clinical suspicion
4. Interpret results within gray zones cautiously - consider repeat testing or additional biomarkers
5. Integrate with imaging and clinical findings - CSF alone is rarely definitive 2, 9
6. Consider co-pathologies and confounders in elderly or complex patients 5, 7