Neurosyphilis: Knowledge Gaps and Controversies

Abstract

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.

Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis

“…Compared with noninflammatory neurological diseases, the CSF sTREM2 levels increased in patients with MS and other inflammatory diseases, corroborating that sTREM2 reflects the neuroinflammatory process of the CNS (9). CSF RPR had an high diagnostic value in NS and was positively correlated with the inflammatory activity of the disease (15,17,18,23). More patients in the late-NS group had positive CSF RPR, indicating persistent infection of treponema pallidum in the brain, which could cause and maintain neuroinflammation and tissue damage (24).…”

“…We recorded the medical history, neurological symptoms and signs, and serum and CSF laboratory testing results. According to the guidelines of NS in the USA, Europe and related literatures (14)(15)(16)(17)(18), the criteria for the diagnosis of NS in our study included positive syphilis serologies and one or more of the followings: (a) positive CSF rapid plasma regain (RPR); (b) positive CSF Treponema pallidum particle agglutination (TPPA) and fluorescent treponemal antibody absorption (FTA-ABS), with increased CSF protein (>45 mg/dl) or white blood cells (WBC) (> 5/µl) in absence of other known causes of these abnormalities. All of the enrolled patients were HIV negative.…”

Clinical and Laboratory Characteristics of Symptomatic and Asymptomatic Neurosyphilis in HIV-Negative Patients: A Retrospective Study of 264 Cases

“…The European also recommend CSF RPR as the diagnosis of neurosyphilis for its high specificity [5]. In contrast, the CSF treponemal antibody tests are more sensitive and relatively nonspecific eliminating neurosyphilis as a diagnostic possibility [6]. In our study, the CSF RPR and the CSF treponema pallidum particle agglutination (TPPA)/fluorescent treponemal antibody absorption (FTA-ABS) were used for the diagnosis of neurosyphilis.…”

Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat

“…The ability of spirochetes to infiltrate the brain and cause disease has been well documented in the case of Treponema palladium , the causative agent of syphilis and associated neuropsychiatric disorders (Tuddenham and Ghanem, 2018). Less well-understood is how another spirochete, B. burgdorferi , the causative agent of Lyme disease, impacts the CNS.…”