Executive Summary: State-of-the-Art Review: Neurosyphilis (2024)

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WHAT IS THIS CLINICAL REVIEW ABOUT?

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. While we did not focus on ocular and otic syphilis, which are entities distinct from neurosyphilis, we have included some information about these diagnoses to highlight relevant distinctions with neurosyphilis. We begin by describing the epidemiology of syphilis in the United States, highlighting populations that are markedly affected by this infection, and attempting 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 cerebrospinal fluid (CSF) examination indications and the performance characteristics of different CSF assays, including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers are briefly considered, as is the role of imaging. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G (BPG) to supplement intravenous penicillin. We conclude by reviewing follow-up recommendations, prevention strategies, and the importance of shared decision-making around management.

WHAT ARE THE MAIN DIAGNOSTIC, MANAGEMENT, AND TREATMENT CHALLENGES?

There are many gray areas in the diagnosis and management of neurosyphilis. These include when to perform a CSF examination-including the role of CSF examinations in persons with HIV, how to interpret CSF parameters, treatment options in those unable or unwilling to receive intravenous penicillin, and the role of enhanced intramuscular BPG therapy to supplement intravenous penicillin therapy. We also address the challenges presented to providers and patients by treatment non-response.

HOW DO YOU SET EXPECTATIONS AND ENGAGE IN SHARED DECISION-MAKING?

We normalize syphilis testing in a bid to reduce the stigma associated with a diagnosis of a sexually transmitted infection. There is a dearth of robust data to support many of the management strategies that providers currently offer, which are often based on decades of clinical experience rather than controlled experimental data. Thus, acknowledging these grey areas and guiding patients with candor about diagnostic, treatment, and prognostic uncertainties is at the core of shared decision-making. Ensuring that expectations are discussed at diagnosis is key, as this ensures that patients and their families are aware that neurological deficits may not resolve even after appropriate treatment. We discuss the pros and cons of potential management approaches, the potential harms of under- and over-investigation and treatment, and ensure patients remain at the center of decision-making.

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Author notes

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.

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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