What test confirms if a nasal fluid is cerebrospinal fluid (CSF)?

Confirming Nasal Fluid is CSF

β2-transferrin testing is the definitive laboratory test to confirm that nasal fluid is cerebrospinal fluid, with near 100% specificity and high sensitivity. 1

Primary Diagnostic Test: β2-Transferrin Analysis

β2-transferrin is the gold standard biochemical marker because it is uniquely produced by neuraminidase activity in the brain and is found almost exclusively in CSF and perilymph—not in nasal secretions, tears, saliva, or serum. 2, 3, 4

Key Performance Characteristics:

• Sensitivity: Highly sensitive, detecting as little as 2.5 mg/L of β2-transferrin in fluid samples 2
• Specificity: Near 100% specificity for CSF 1, 3
• Sample requirements: Can detect CSF in as little as 1 microliter of pure CSF or 100 microliters (2 drops) of CSF per 1 mL of nasal secretion 5
• Stability: β2-transferrin remains detectable for up to 7 days at room temperature or refrigerated, even when exposed to nasal mucus 6

Testing Method:

• Immunofixation electrophoresis is the standard technique used to detect β2-transferrin 2, 3, 4
• The test identifies two transferrin bands in CSF (β1-transferrin and β2-transferrin), whereas other body fluids show only β1-transferrin 5

Important Caveats:

Potential Interfering Factors:

• Blood contamination can interfere with results and requires hemoglobin elimination using chromatography 5
• High protein content (>5 g/L) requires reduction with ammonium sulfate precipitation 5

Collection Considerations:

• Patients can collect nasal fluid at home if adequate volume cannot be obtained in clinic, as the protein remains stable for up to a week 6
• Negative β2-transferrin testing reliably excludes CSF leak, allowing patients to avoid unnecessary invasive investigations like CT cisternography 3

Alternative Confirmatory Test (When β2-Transferrin Testing Insufficient):

DTPA cisternography is reserved for cases where insufficient fluid can be collected for β2-transferrin testing. 1

• Performed by spinal injection of radiotracer with nasal pledget placement for 24-48 hours
• Sensitivity: 76-100% for confirming presence of CSF leak 1
• Specificity: 100% 1
• Limitation: Poor localization accuracy as pledgets and secretions move within the nasal cavity 1

Clinical Algorithm:

1. Collect nasal fluid sample (can be done at home over several days if needed) 6
2. Send for β2-transferrin analysis via immunofixation electrophoresis 2, 3
3. If positive: CSF leak confirmed—proceed to imaging (HRCT) for localization 1, 7
4. If negative: CSF leak excluded—avoid invasive testing 3
5. If insufficient fluid collected: Consider DTPA cisternography as alternative confirmatory test 1