Testing Rhinorrhea for CSF
β2-transferrin analysis is the definitive laboratory test to confirm that nasal fluid is cerebrospinal fluid and should be performed first when CSF rhinorrhea is suspected. 1, 2
Primary Diagnostic Test
β2-transferrin testing is the most reliable laboratory test to confirm CSF leak, with near 100% specificity and high sensitivity. 3, 1
β2-transferrin is a desialated form of transferrin uniquely found only in CSF, perilymph, and aqueous/vitreous humor—it is not present in nasal secretions, saliva, tears, or serum under normal conditions. 4, 5
The test is performed using immunofixation electrophoresis on high-resolution agarose gels, which can detect β2-transferrin at concentrations as low as 2.5 mg/L. 5
Clinical studies demonstrate that β2-transferrin testing allows patients with negative results to avoid unnecessary invasive investigations, as surgical exploration in β2-transferrin negative patients consistently shows no CSF leak. 6
Alternative Confirmatory Test
β-trace protein immunoblot is an alternative confirmatory test with comparable sensitivity and specificity to β2-transferrin analysis. 4, 7
β-trace protein testing may be particularly useful when rapid results are needed, as newer immunoblot methods provide fast and reliable detection. 7
DTPA cisternography should be reserved only for cases where insufficient fluid volume can be collected for β2-transferrin testing, with sensitivity of 76-100% and specificity of 100%. 1
Tests to Avoid
Glucose oxidase testing (glucose detection) is NOT recommended as it has poor diagnostic sensitivity and specificity. 4
Glucose testing produces false-negative results with bacterial contamination and false-positive results in diabetic patients, making it unreliable for CSF leak confirmation. 4
Clinical Algorithm
Collect nasal fluid sample when rhinorrhea is present and send for β2-transferrin analysis as the first-line diagnostic test. 1, 2
If β2-transferrin is positive, CSF leak is confirmed and high-resolution CT (HRCT) of the paranasal sinuses should be performed for anatomic localization of the skull base defect. 1, 8
If β2-transferrin is negative, CSF leak is effectively ruled out and invasive imaging studies like CT cisternography can be avoided. 6
Important Caveats
The patient must have active rhinorrhea at the time of sample collection—if the leak is intermittent, multiple samples may need to be collected during episodes of drainage. 3
β2-transferrin testing typically requires several days for processing, which may delay diagnosis but should not delay empiric treatment if clinical suspicion for CSF leak with meningitis is high. 9
In emergency situations with suspected meningitis and CSF rhinorrhea, do not delay antibiotic therapy while awaiting β2-transferrin results. 8