Rapid, accurate and non-invasive detection of cerebrospinal fluid leakage using combined determination of β-trace protein in secretion and serum

Background: p-Trace protein (Btp) has been proposed as a valuable marker of cerebrospinal fluid (CSF) leakage overcoming the drawbacks of beta-2-transferrin (B-2Tr) determination. However, there is still controversy about the appropriate cut-offs to be used (range 0.35-6 mg/L). The aim of the study was to evaluate cut-offs of Btp determination for detection CSF leakage. Further, we assessed whether the Btp secretion to serum ratio (Btp-sec/ser-ratio) would add diagnostic value. Methods: Prospective study in patients with suspected CSF leakage. Quantitative determination of Btp in secretion and serum (Dade-Behring) and qualitative measurement of B-2-Tr in secretion and serum. Results were assessed in view of clinical data. Cut-offs and diagnostic characteristics were determined by ROC analysis. Results: A total of 176 samples, were assessed originating from 105 patients. In 43 samples CSF leakage could be confirmed. Sensitivity of B-2-Tr was 84% specificity amounted to 100%. The area under the curve (AUC) for Btp-measurement in secretion was 0.98. At a cut-off of 0.68 mg/L, sensitivity was 100% and specificity 91%. At a cut-off of 1.11 mg/L, the specificity was 100% with a sensitivity of 93%. The Btp-sec/ser-ratio has an AUC of 0.99. Combining a 0.68 mg/L cut-off in secretion with a Btp-sec/ser-ratio cut-off of 4.9 reveals a sensitivity of 99% and a specificity of 100%. Conclusions: Btp is a rapid and accurate marker for the presence of CSF leakage. Combining measurement of Btp in secretion together with determination of the Btp-sec/ser-ratio enhances the diagnostic characteristics of the Btp assay. Determination of Btp in both serum and secretion is thus recommended. (C) 2004 Elsevier B.V. All rights reserved.