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Neurosyphilis: Knowledge Gaps and Controversies

Tuddenham, Susan, MD, MPH; Ghanem, Khalil, G., MD, PhD

Sexually Transmitted Diseases: March 2018 - Volume 45 - Issue 3 - p 147–151
doi: 10.1097/OLQ.0000000000000723

After reaching a nadir at the turn of the century, syphilis rates in the United States have increased since 2000. Treponema pallidum may disseminate to the central nervous system within hours to days after inoculation. In this review, we focus on knowledge gaps and areas of controversy in neurosyphilis epidemiology, diagnosis, and management. Modern estimates of the prevalence of neurosyphilis are hindered by the lack of consistent reporting data and are based on relatively small retrospective cohort studies. The various diagnostic modalities for neurosyphilis have significant limitations. Although several novel biomarkers for neurosyphilis have been evaluated, none to date have found a place in clinical practice. The role of a cerebrospinal fluid examination in patients without neurological symptoms continues to be an area of controversy, whereas the data for the use of antibiotic regimens other than intravenous aqueous or intramuscular procaine penicillin for the treatment of neurosyphilis are limited. As syphilis incidence continues to increase unabated in many countries around the world, it is critical to address these gaps of knowledge.

In this article we review knowledge gaps and controversies in the epidemiology, diagnosis, and management of neurosyphilis.

From the Johns Hopkins University School of Medicine, Baltimore, MD

(For further references please see "Supplementary References",

Conflicts of Interest and Sources of Funding: None declared.

Correspondence: Khalil Ghanem, MD, PhD, JHUBMC, ID Division 5200 Eastern Ave, MFL Center Tower, Suite 378 Baltimore, MD 21224. E-mail:

Received for publication May 24, 2017, and accepted August 29, 2017.

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