2. INTRODUCTION
Syphilis incidence continues to increase.
T. pallidum may disseminate to the central nervous system within hours to days after inoculation.
Neurologic manifestations of syphilis may occur during any stage of the infection.
2015 CDC Sexually Transmitted Diseases Surveillance. https://www.cdc.gov/std/stats15/syphilis.htm.
Collart P, Franceschini P, Durel P. Experimental rabbit syphilis. The British journal of venereal diseases. 1971;47(6):389-400.
4. EPIDEMIOLOGY
Early neurosyphilis, which manifests as meningeal or meningovascular involvement of the central
nervous system, was rare
Late neurosyphilis (or tertiary neurosyphilis) was more common.
The onslaught of HIV corresponded with increasing numbers of reported neurosyphilis cases-
particularly early neurosyphilis
Tuddenham S, Ghanem KG. Neurosyphilis: Knowledge Gaps and Controversies. Sexually transmitted diseases. 2018 Mar 1;45(3):147-51.
Centers for Disease C, Prevention. Symptomatic early neurosyphilis among HIV-positive men who have sex with men--four cities, United States, January 2002-June 2004. MMWR. Morbidity and mortality weekly report. 2007;56(25):625-628.
Flood JM, Weinstock HS, Guroy ME, et al. Neurosyphilis during the AIDS epidemic, San Francisco, 1985-1992. The Journal of infectious diseases. 1998;177(4):931-940.
Ghanem KG, Moore RD, Rompalo AM, et al. Neurosyphilis in a clinical cohort of HIV-1-infected patients. Aids. 2008;22(10):1145-1151.
5. DIAGNOSIS
Challenging
No gold standard tests
Clinical and CSF findings
Tuddenham S, Ghanem KG. Neurosyphilis: Knowledge Gaps and Controversies. Sexually transmitted diseases. 2018 Mar 1;45(3):147-51.
6. SIGNS & SYMPTOMS
Gliatto M, Caroff S. Neurosyphilis: A History and Clinical Review. Psychiatr Ann. 2001; 31: 153-161.
7. CSF VDRL
The most common test used to diagnose neurosyphilis.
Highly specific in the absence of gross blood contamination.
50-60 % sensitivity.
False positive: meningeal carcinomatosis, spinal cord tumor, trypanosomiasis, and cerebral malaria.
(occurred in patients without serological evidence of syphilis)
Diagnosis of neurosyphilis:
- Neurological symptoms, serological evidence of syphilis, with positive CSF VDRL.
- Neurological symptoms, serological evidence of syphilis, with CSF pleocytosis and no alternate diagnosis.
Tuddenham S, Ghanem KG. Neurosyphilis: Knowledge Gaps and Controversies. Sexually transmitted diseases. 2018 Mar 1;45(3):147-51.
8. CSF TREPONEMAL TESTS
Highly sensitive 83.3% to 100%,
CDC 2015 STD Treatment Guidelines, “Neurosyphilis is highly unlikely with a negative CSF FTA-ABS test,
especially among patients with nonspecific neurologic signs and symptoms.”
In patients with serologic evidence of syphilis and a high clinical probability of neurosyphilis, a
nonreactive CSF treponemal antibody test may not rule out neurosyphilis.
Workowski KA, Bolan GA, Centers for Disease C, et al. Sexually transmitted diseases treatment guidelines, 2015. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2015;64(RR-03):1-137.
Harding AS, Ghanem KG. The performance of cerebrospinal fluid treponemal-specific antibody tests in neurosyphilis: a systematic review. Sexually transmitted diseases. 2012;39(4):291-297.
Guarner J, Jost H, Pillay A, et al. Evaluation of treponemal serum tests performed on cerebrospinal fluid for diagnosis of neurosyphilis. American journal of clinical pathology. 2015;143(4):479-484.Ho EL, Marra CM. Treponemal tests for neurosyphilis--less accurate than what we thought? Sexually transmitted diseases. 2012;39(4):298-299.
9. CSF PLEOCYTOSIS
> 5 cells / mL in non HIV patients
> 10 cells / mL in HIV patients receiving ART
> 20 cells/ mL in HIV patients without ART
Pleocytosis while non-specific is a sensitive marker for neurosyphilis. (except in tabes dorsalis)
The CSF cell count appears to correlate with disease activity and is typically the first parameter to
improve following therapy.
Merritt A, Solomon. Neurosyphilis. Oxford University Press; 1946.
Marra CM, Maxwell CL, Tantalo L, et al. Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter? Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
2004;38(7):1001-1006.
Tuddenham S, Ghanem KG. Neurosyphilis: Knowledge Gaps and Controversies. Sexually transmitted diseases. 2018 Mar 1;45(3):147-51.
10. CSF EXAMINATION INDICATION
Serological evidence of syphilis who have neurological signs and/or symptoms.
Asymptomatic persons with syphilis whose serological titers do not decline four-fold following stage-
appropriate therapy.
Workowski KA, Bolan GA, Centers for Disease C, et al. Sexually transmitted diseases treatment guidelines, 2015. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2015;64(RR-03):1-137.
11. SEROFAST
Patients who do not achieve a four-fold decline in nontreponemal serological titers within a specified
period of time (12 months in early syphilis and 24 months in late syphilis) following appropriate stage-
directed therapy.
Patients who achieve a fourfold decline in non treponemal titer but do not completely revert from
reactive to nonreactive.
Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. Jama. 2014;312(18):1905-1917.
12. TREATMENY
Aqueous crystalline penicillin G 18–24 million units per day, administered as 3–4 million units IV every 4
hours or continuous infusion, for 10–14 days.
Alternative:
Intravenous ceftriaxone for 10 to 14 days, 2 gram daily.
Procaine penicillin 2.4 million units IM once daily PLUS Probenecid 500 mg orally four times a day, both
for 10–14 days.
Amoxicillin (3.0 g) and probenecid (0.5 g) administered twice daily for 15 days.
Doxycycline 200 mg twice a day for 28 days for neurosyphilis patients allergic to penicillin.
Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. Centers for Disease Control and Prevention; 2010.
Shann S, Wilson J. Treatment of neurosyphilis with ceftriaxone. Sexually transmitted infections. 2003 Oct 1;79(5):415-6.
Berger JR, Dean D. Neurosyphilis. InHandbook of clinical neurology 2014 Jan 1 (Vol. 121, pp. 1461-1472). Elsevier.
13. SUMMARY
Reliable estimates of the prevalence of neurosyphilis in the modern era are lacking and because there
are no gold standard tests, and much of the data comes from the pre-antibiotic era.
Diagnosis of neurosyphilis is challenging and a source of controversy.
The management of serofast patients is controversial, and complicated by differing definitions.
Finally, the efficacy of antibiotics other than IV penicillin in the treatment neurosyphilis is not well
established
