Alternatives to the Cerebrospinal Fluid Venereal Disease Research Laboratory Test for Neurosyphilis Diagnosis.

Abstract

The diagnosis of neurosyphilis relies in large part on the cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test, which is diagnostically specific but not sensitive. We determined the sensitivity and specificity of 3 CSF tests in addition to the CSF-VDRL in participants with syphilis enrolled in a research study: detection of Treponema pallidum ribosomal RNA, T. pallidum particle agglutination titer, and chemokine (C-X-C motif) ligand 13 (CXCL13) concentration. Neurosyphilis was defined as asymptomatic or symptomatic meningitis: CSF white blood cells >10/μL without or with neurological symptoms, including new vision or hearing loss. Cerebrospinal fluid-VDRL, CSF T. pallidum ribosomal RNA detection, and CSF T. pallidum particle agglutination titer ≥1:640 were specific (89%-96%) but not sensitive (12%-48%). In contrast, diagnostic sensitivity of CSF-CXCL13 thresholds established from receiver operating characteristic curves using the Youden index was 78% to 83% and specificity was 76% to 81%. In individuals with nonreactive CSF-VDRL, neurosyphilis diagnosis could be confirmed by CSF-CXCL13 concentration in 69% to 75%. Further studies of CSF-CXCL13 should include CSF samples from multiple cohorts and countries and should use standard neurosyphilis definitions to establish uniform thresholds for diagnosis.