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Review
. 2024 May 15;78(5):e57-e68.
doi: 10.1093/cid/ciad437.

State-of-the-Art Review: Neurosyphilis

Matthew M Hamill  1 , Khalil G Ghanem  1 , Susan Tuddenham  1
Affiliations
Review

State-of-the-Art Review: Neurosyphilis

Matthew M Hamill et al. Clin Infect Dis. .

Abstract

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin.

Keywords: Treponema pallidum; cerebrospinal fluid; lumbar puncture; neurosyphilis; syphilis.

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Conflict of interest statement

Potential conflicts of interest. M. M. H. reports royalties from UpToDate, consulting fees from GSK, and writing fees from DynaMed. K. G. G. reports royalties from UpToDate. S. T. reports serving as a consultant for Biofire Diagnostics, Roche Molecular Diagnostics, and Luca Biologics; royalties from UpToDate; speaker honoraria from Roche Molecular Diagnostics and Medscape/WebMD; an unpaid role as a board member for the American Sexually Transmitted Diseases Association; and receipt of donated test kits to institution from Hologic. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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