Assessing cerebrospinal fluid rhinorrhea: A two-dimensional electrophoresis approach

Assessment of nasal cerebrospinal fluid (CSF) fistula commonly relies on th e determination of CSF markers in an aqueous rhinorrhea, such as the beta2- transferrin immunofixation assay. While generally reliable, false positive and false negative results have been reported for most of the laboratory te sts yet available. Based on the hypothesis that the simultaneous assessment of several CSF markers may yield an increased sensitivity and specificity, we used a proteomics, two-dimensional electrophoresis 2-DE based approach to study samples of nasal secretions obtained from 18 patients suspected of CSF rhinorrhea. Since CSF, nasal mucus and plasma may coexist in the nasal cavities, we first defined five specific markers for each of these biologi cal fluids (transferrin, prostaglandin-D synthase, transthyretin, and two u nknown trains of spots for CSF, immunoglobulin A (IgA) S-chain, lipocortin- 1, lipocalin-1, prolactine-inducible protein and palatal lung nasal epithel ium clone protein for mucus, haptoglobin alpha1/2- and beta -chains, fibrin ogen alpha-, beta- and gamma -chains for plasma). Gels from the rhinorrhea patients were then compared to these 2-DE reference maps to determine the p resence or absence of the defined markers, and clinical data were independe ntly compared to the results of the 2-DE study. In all cases, the biologica l fluid(s) anticipated to be present in the nasal secretions based on clini cal data were correctly identified by 2-DE. Moreover, an excellent correlat ion was found in nine patients who underwent extensive workup for suspected CSF rhinorrhea, since CSF was found by the 2-DE method in four patients in whom a CSF fistula was confirmed, whereas the test was negative in five pa tients in whom a CSF fistula was excluded. In the remaining patients, mucus , sometimes contamined with blood, was found to be the major component of t he nasal secretions, confirming that clear mucus may mimick CSF rhinorrhea. These preliminary results suggest that a 2-DE-based multimarker approach i s a valid, sensitive, and specific method to assess the presence of CSF in occult rhinorrhea.