Diagnostic tools for neurosyphilis: a systematic review

Abstract

Purpose: Increasing incidences of syphilis highlight the preoccupation with the occurrence of neurosyphilis. This study aimed to understand the current diagnostic tools and their performance to detect neurosyphilis, including new technologies and the variety of existing methods.

Methods: We searched databases to select articles that reported neurosyphilis diagnostic methods and assessed their accuracy, presenting sensitivity and specificity values. Information was synthesized in tables. The risk of bias was examined using the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy recommendations.

Results: Fourteen studies were included. The main finding was a remarkable diversity of tests, which had varied purposes, techniques, and evaluation methodologies. There was no uniform criterion or gold standard to define neurosyphilis. The current basis for its diagnosis is clinical suspicion and cerebrospinal fluid analysis. There are new promising tests such as PCR tests and chemokine measurement assays.

Conclusions: The diagnosis of neurosyphilis is still a challenge, despite the variety of existing and developing tests. We believe that the multiplicity of reference standards adopted as criteria for diagnosis reveals the imprecision of the current definitions of neurosyphilis. An important next step for the scientific community is to create a universally accepted diagnostic definition for this disease.

Keywords: Accuracy; Cerebrospinal fluid; Diagnosis; Diagnostic tests; Neurosyphilis; Syphilis.

Fig. 1

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart, representing the selection of studies

Fig. 2

Methodological quality graph: proportions of low, unclear, and high risk of bias of the studies included in this review, according to the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy recommendations [13]

Fig. 3

Methodological quality summary for risk of bias for all studies. Based on the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy recommendations [13]

Fig. 4

Summary of the main clinical uses of diagnostic methods for neurosyphilis. CSF (cerebrospinal fluid); NS (neurosyphilis); VDRL (venereal disease research laboratory); RPR (rapid plasma reagin); FTA-ABS (fluorescent treponemal antibody absorption); CXCL (chemokine CXC ligand); MIF (macrophage migration inhibitory factor); sTREM2 (soluble triggering receptor expressed on myeloid cells 2); BACE1 (beta-site app-cleaving enzyme 1); IL-10 (interleukin 10)