Laboratory Testing for CSF Leak Diagnosis
β2-transferrin testing is the definitive laboratory test to confirm cerebrospinal fluid leak, with near 100% specificity and high sensitivity. 1
Primary Laboratory Test
β2-transferrin (beta-2-transferrin) is the gold standard laboratory test for confirming that fluid collected from the nose or ear is cerebrospinal fluid rather than other body secretions. 1
This test works by detecting β2-transferrin, an asialotransferrin glycoprotein uniquely produced by neuraminidase activity in the brain and found only in CSF and perilymph—it is absent in all other body secretions including blood, nasal mucus, and tears. 2, 3
The American College of Radiology recommends obtaining laboratory confirmation with β2-transferrin before proceeding to imaging studies like HRCT. 4
Alternative Laboratory Test
β-trace protein is an alternative laboratory marker with comparable sensitivity and specificity to β2-transferrin for CSF leak detection. 5
β2-transferrin remains more commonly used in clinical practice due to wider availability and established testing protocols. 5
Clinical Algorithm for Laboratory Testing
Collect fluid specimen from the nose (rhinorrhea) or ear (otorrhea) when active leakage is present—at least 0.5-1 mL is typically needed for β2-transferrin analysis. 2
If β2-transferrin is positive, CSF leak is confirmed and you should proceed directly to high-resolution CT imaging for anatomic localization of the leak site. 4, 1
If β2-transferrin is negative but clinical suspicion remains high, the patient can avoid unnecessary invasive investigations—however, consider repeat testing during active leakage episodes for intermittent leaks. 2, 3
When Laboratory Testing Cannot Be Performed
DTPA radionuclide cisternography is reserved specifically for cases where insufficient fluid volume can be collected for β2-transferrin testing, achieving 76-100% sensitivity and 100% specificity for confirming CSF leak presence. 1
This nuclear medicine study requires lumbar puncture with intrathecal administration of indium-111 labeled DTPA, making it more invasive than simple fluid collection for β2-transferrin. 4
Important Clinical Considerations
β2-transferrin testing has demonstrated 96.2% sensitivity and 97.1% specificity in clinical validation studies, with the ability to detect CSF even when mixed with blood or other secretions. 6
The test requires 70 minutes to several hours for results using immunofixation electrophoresis methods, which is significantly faster than older electrophoresis-based techniques but still not immediate point-of-care testing. 6, 3
False negatives can occur if fluid is collected during periods when an intermittent leak is inactive—clinical correlation is essential, and negative results should be interpreted cautiously if symptoms strongly suggest CSF leak. 3
The β2-transferrin assay almost matches the sensitivity of more invasive procedures like intrathecal fluorescein application and surgical exploration, making it the appropriate first-line screening method. 3