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Criteria for the Diagnosis of Neurosyphilis in Cerebrospinal Fluid: Relationships With Intrathecal Immunoglobulin Synthesis and Blood–Cerebrospinal Fluid Barrier Dysfunction

Levchik, Nadezhda MD, PhD*; Ponomareva, Marina MS*; Surganova, Vera MD, PhD; Zilberberg, Natalia MD, PhD; Kungurov, Nikolai MD, PhD

doi: 10.1097/OLQ.0000000000000049
Original Study

Background The origin of cerebrospinal fluid (CSF) syphilis antibodies (intrathecal or blood-derived) is in doubt. Little is known about CSF test behavior under the condition of physiological or disturbed functioning of blood-CSF barrier (BCB) and intrathecal immunoglobulin (Ig) production.

Methods We collected 126 serum/CSF pairs from patients with serological evidence of syphilis. We explored the relationships between the established facts of intrathecal Ig synthesis and/or BCB dysfunction and the results of CSF diagnostic tests: the Treponema pallidum hemagglutination (TPHA) test, the fluorescent treponemal antibody absorption (FTA-Abs) test, the Venereal Disease Research Laboratory (VDRL) test, and white blood cell counts. We checked the criteria used either to support or refute the diagnosis of neurosyphilis.

Results Reactive CSF-VDRL tests, elevated CSF–white blood cell counts, and elevated CSF-TPHA titers/indices were associated with the signs of intrathecal Ig synthesis, whereas nonreactive CSF–fluorescent treponemal antibody absorption, nonreactive CSF-TPHA tests, and CSF-TPHA titers from 1:4 to 1:160 were associated with cases where the intrathecal synthesis was not detected. There were some peculiarities of the tests toward BCB dysfunction.

Most of reactive CSF-VDRL test samples and CSF samples with pleocytosis were also meeting at least 1 of the CSF-TPHA titer/indices-based criteria. T. pallidum hemagglutination indices were in no better conformity with the facts of intrathecal immune response than CSF-TPHA titers.

Conclusions Our findings have shown that all the examined criteria for the diagnosis of neurosyphilis in CSF are different assessment tools of intrathecal humoral immune activity and support the hypothesis that high CSF treponemal-specific antibody titers are a consequence of inflammatory pathology of the central nervous system.

Current criteria for the diagnosis of neurosyphilis in cerebrospinal fluid, including treponemal-specific antibody titers and indices, are different assessment tools of intrathecal immunoglobulin synthesis with some differences toward blood–cerebrospinal fluid barrier dysfunction.

From the Departments of *Laboratory Medicine, †Venereology, and ‡Science, Urals Institute of Dermatovenereology and Immunopathology, Yekaterinburg, Russia

Conflict of interest: None declared.

Funding: None declared.

Correspondence: Nadezhda Levchik, MD, PhD, Department of Laboratory Medicine, Urals Institute of Dermatovenereology and Immunopathology, Shcherbakova 8, 620076 Yekaterinburg, Russia. E-mail:

Received for publication April 26, 2013, and accepted September 20, 2013.

© Copyright 2013 American Sexually Transmitted Diseases Association