B-280 Sensitivity and Specificity of Beta-2 Transferrin Gel Electrophoresis With Immunofixation for Evaluating Nasal Cerebrospinal Fluid Leaks
Authors: Zari H , Juras A , Chen C , Veasey K , Craig J , Carey J L , Cook B C 
Published: September 2023

Abstract

Background
Cerebrospinal fluid (CSF) rhinorrhea usually presents as unilateral clear thin nasal drainage, is caused by a direct communication from the subarachnoid space to the sinonasal cavities and can lead to intracranial infection, pneumocephalus, or death. Diagnosing CSF rhinorrhea can be challenging. While the gold standard for CSF leak confirmation is surgical exploration, testing nasal fluid for beta-2 transferrin (B2Tf) via agarose gel electrophoresis followed by immunofixation (AGEI) remains the initial non-invasive CSF confirmatory test of choice. However, AGEI requires subjective interpretation of immune-stained protein bands. Multiple studies have reported high sensitivity and specificity of B2Tf AGEI (90–100%), but other studies have shown wider ranges from 70–100%. Due to small sample sizes and methodologic differences between studies, comparing results between studies is problematic. The purpose of this study was to assess the sensitivity and specificity of B2Tf AGEI in confirming or excluding CSF rhinorrhea in patients with unilateral clear thin nasal drainage, and to determine the inter-reviewer variability of AGEI interpretation.

Methods
This was a retrospective observational study of patients who had B2Tf AGEI performed on their unilateral clear nasal drainage from 2020 through 2022. A pathologist and four trained medical laboratory scientists conducted visual reviews of archived gels and their results were compared to the documented CSF rhinorrhea status. Results were also compared to the original test results documented in patients’ charts. Sensitivity and specificity, and inter-reviewer agreement were assessed for B2Tf AGEI confirming or excluding CSF rhinorrhea. The gold standard for confirming CSF rhinorrhea was surgical exploration. The gold standard for excluding CSF rhinorrhea included either negative surgical exploration or rhinorrhea resolution after medical therapy aimed at treating rhinitis or rhinosinusitis.

Results
Sensitivity and specificity varied for the five reviewers and documented test results, with sensitivities ranging from 65.0 to 86.0% (mean ± SD, 73.0 ± 5.7) and specificities from 61.4 to 88.6% (84.1 ± 11.0). The false positive rate was 8.7%, and false negative rate was 13.9%. Sensitivity and specificity for the documented test results ranging from 57.1 to 82.1% (mean ± SD, 72.1, 9.3) and specificities from 75.0 to 97.26% (91.6 ± 9.4). The abilities of the reviewers to reliability identify a CSF leak was moderate, with kappa statistics ranging from 0.313 to 0.646 (weighted average 62.2, 4.0). Two of the four reviewers demonstrated substantial to almost perfect agreement to the expert reviewer, with the other two demonstrating moderate agreement.

Conclusions
B2Tf AGEI demonstrated lower sensitivity and specificity than some previous reports, however this study had a larger sample size and very well-defined clinical standards for CSF and non-CSF rhinorrhea. While false results were present in 9 to 14% of cases, the test is non-invasive, and is helpful in stratifying patients into those more or less likely to have CSF rhinorrhea. There was also substantial inter-reviewer variability, highlighting the challenges of subjective interpretation of this testing modality. Larger prospective studies would be helpful to more accurately determine the diagnostic accuracy of B2Tf AGEI, as well as explore practices to help limit inter-reviewer variability.