Skip to main content

Advertisement

SpringerLink
Log in

Neurosyphilis: A current review

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Neurosyphilis continues to be a difficult diagnosis for clinicians. The decision to perform a lumbar puncture, interpretation of cerebrospinal fluid findings, clear diagnostic guidelines, establishment of definitive therapy (including alternatives to penicillins), and approach to the follow-up of patients with neurosyphilis are all areas that pose ongoing challenges to clinicians. Coinfection with HIV has also further complicated the already challenging arena of neurosyphilis presentation, diagnosis, and management. Clinicians must recognize the recent changes in the epidemiology of syphilis and know when to initiate appropriate screening. This article highlights the limitations and controversies related to neurosyphilis diagnosis and treatment, and current recommendations on management of patients with neurosyphilis, including those coinfected with HIV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Merritt HH, Adams RD, Solomon HC: Neurosyphilis. New York: Oxford University Press; 1946.

    Google Scholar 

  2. Centers for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention, Division of STDs: Sexually Transmitted Diseases Surveillance 2001. Atlanta, GA: Centers for Disease Control and Prevention; 2002.

    Google Scholar 

  3. Whiteside CM: Persistence of neurosyphilis despite multiple treatment regimens. Am J Med 1989, 87:225–227.

    Article  PubMed  CAS  Google Scholar 

  4. Musher DM, Hamill RJ, Baugh RE: Effect of human immunodeficiency virus infection on the course of syphilis and on the response to treatment. Ann Intern Med 1990, 113:872–881.

    PubMed  CAS  Google Scholar 

  5. Katz DA, Berger JR: Neurosyphilis in acquired immunodeficiency syndrome. Arch Neurol 1989, 46:895–898.

    PubMed  CAS  Google Scholar 

  6. Gordon SM, Eaton ME, George R, et al.: The response of symptomatic neurosyphilis to high dose intravenous penicillin G in patients with human immunodeficiency virus infection. N Engl J Med 1994, 331:1469–1473.

    Article  PubMed  CAS  Google Scholar 

  7. Brandt AM: Shadow on the land. In No Magic Bullet: A Social History of Venereal Disease in the United States Since 1880. New York: Oxford University Press; 1987.

    Google Scholar 

  8. Ciesielski CA: Sexually transmitted diseases in men who have sex with men: an epidemiologic review. Curr Infect Dis Rep 2003, 5:145–157.

    Article  PubMed  Google Scholar 

  9. Sexually transmitted diseases in men who have sex with men--New York City, 2001. MMWR Morb Mortal Wkly Rep 2002, 51:853–856.

  10. Transmission of primary and secondary syphilis by oral sex--Chicago, Illinois 1998–2002. MMWR Morb Mortal Wkly Rep 2004, 53:966–968.

  11. Lukehart SA, Hook EW 3rd, Baker-Zander SA, et al.: Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Ann Intern Med 1988, 109:855–862.

    PubMed  CAS  Google Scholar 

  12. Golden MR, Marra CM, Holmes KK: Update on syphilis: resurgence of an old problem. JAMA 2003, 290:1510–1514. This is a succinct recent overview of syphilis in the United States today.

    Article  PubMed  CAS  Google Scholar 

  13. Tramont EC: Syphilis in adults: from Christopher Columbus to Sir Alexander Fleming to AIDS. Clin Infect Dis 1995, 21:1361–1371.

    PubMed  CAS  Google Scholar 

  14. Tramont EC: Neurosyphilis. http://pier.acponline.org/ physicians/diseases/d777/d777.html. Accessed March 23, 2005.

  15. Ances BM, Shellhaus R, Brown MJ, et al.: Neurosyphilis and status epilepticus: case report and literature review. Epilepsy Res 2004, 59:67–70.

    Article  PubMed  Google Scholar 

  16. Jacquemin GL, Proulx P, Gilbert DA, et al.: Functional recovery from paraplegia caused by syphilitic meningomyelitis. J Spinal Cord Med 2002, 25:133–137.

    PubMed  Google Scholar 

  17. Becker GD: Late syphilitic hearing loss: a diagnostic and therapeutic dilemma. Laryngoscope 1979, 89:1273–1288.

    PubMed  CAS  Google Scholar 

  18. Rolfs RT, Joesoef MR, Hendershot EF, et al.: A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection: the Syphilis and HIV study group. N Engl J Med 1997, 337:307–314. This is the largest randomized prospective treatment trial for syphilis ever published. This article provides great insights into early syphilis infection and the effect it has on the CSF.

    Article  PubMed  CAS  Google Scholar 

  19. Rompalo AM, Joesoef MR, O’Donnell JA, et al.: Clinical manifestations of early syphilis by HIV status and gender: results of the Syphilis and HIV study. Sex Transm Dis 2001, 28:158–165. This study is a more detailed analysis of some of the results of Rolfs et al. [18••].

    Article  PubMed  CAS  Google Scholar 

  20. Sexually Transmitted Diseases Treatment Guidelines 2002: Centers for Disease Control & Prevention. MMWR Recomm Rep 2002, 51:1–78. Every clinician should have a copy of the most recent treatment guidelines. These are usually updated every 4 to 5 years.

  21. Marra CM, Maxwell CL, Smith SL, et al.: Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis 2004, 189:369–376. This is a very interesting study that looks further at what, if any, clinical data points may be helpful regarding the need for lumbar puncture in guiding clinicians who care for patients with syphilis.

    Article  PubMed  Google Scholar 

  22. van der Valk PGM, Kraai EJ, van Voorst Vadev PC, et al.: Penicillin concentrations in cerobrospinal fluid during repository treatment regimen for syphilis. Genitourin Med 1988, 64:223–225.

    PubMed  Google Scholar 

  23. Scheck DN, Hook EW 3rd: Neurosyphilis. Infect Dis Clin North Am 1994, 8:769–790.

    PubMed  CAS  Google Scholar 

  24. Chan DJ: Syphilis and HIV co-infection: when is lumbar puncture indicated? Curr HIV Res 2005, 3:95–98.

    Article  PubMed  CAS  Google Scholar 

  25. Norris SJ, Popee VP, Johnson RE, Larsen SA: Treponema and other host-associate spirochetes. In Manual of Clinical Microbiology, edn 8. Edited by Murray PR, Barron EJ, Jorgensen JH, et al. Washington, DC: ASM Press; 2003:955–971.

    Google Scholar 

  26. Larsen SA, Stiener BM, Rudolph AL: Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 1995, 8:1–21. Although this review is 10 years old, it is the best and most comprehensive in the literature, and well worth reviewing.

    PubMed  CAS  Google Scholar 

  27. Peter JB: Treponema pallidum. In Use and Interpretation of Laboratory Tests in Infectious Diseases, edn 6. Edited by Peter JB. Santa Monica, CA: Specialty Laboratories; 2000:256–257.

    Google Scholar 

  28. Participant Summary. G-C Syphilis Serology Survey. Chicago, IL: College of American Pathologists; 2004:1–17.

  29. Marra CM, Critchlow CW, Hook EW 3rd, et al.: Cerebrospinal fluid treponemal antibodies in untreated early syphilis. Arch Neurol 1995, 52:68–72.

    PubMed  CAS  Google Scholar 

  30. Luger AF, Schmidt BL, Kaulich M: Significance of laboratory findings for diagnosis of neurosyphilis. Int J STD AIDS 2000, 22:224–234.

    Article  Google Scholar 

  31. Grimpel EP, Sanchez PJ, Wendel GD, et al.: Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid. J Clin Microbiol 1991, 29:1711–1718.

    Google Scholar 

  32. Noordhoek DT, Wolters EC, De Jonge MEJ, van Embden JDA: Detection by polymerase chain reaction of Treponema pallidum DNA in cerebrospinal fluid from neurosyphilis patients before and after antibiotic therapy. J Clin Microbiol 1991, 29:1976–1984.

    PubMed  CAS  Google Scholar 

  33. Liu H, Rodes B, Chen CY, Steiner B: New tests for syphilis: rational design of a PCR method for detection of Treponema pallidum in clinical specimens using unique regions of the DNA polymerase 1 gene. J Clin Microbiol 2001, 39:1941–1946.

    Article  PubMed  CAS  Google Scholar 

  34. Collier AC, Marra CM, Coombs RW, et al.: Central nervous system manifestations in HIV and AIDS. J Acquir Immune Defic Syndr 1992, 5:229–241.

    PubMed  CAS  Google Scholar 

  35. Marshall DW, Brey RL, Cahill WT, et al.: Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus infection. Arch Neurol 1988, 45:954–958.

    PubMed  CAS  Google Scholar 

  36. Onoda Y: Therapeutic effect of oral doxycycline in syphilis. Br J Vener Dis 1979, 55:110–115.

    PubMed  CAS  Google Scholar 

  37. Yim CW, Flynn NM, Fitzgerald PT: Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis. Antimicrob Agents Chemother 1985, 28:347–348.

    PubMed  CAS  Google Scholar 

  38. Johnson RC, Bey RF, Wolgamot SJ: Comparison of the activities of ceftriaxone and penicillin against experimentally induced syphilis in rabbits. Antimicrob Agents Chemother 1982, 21:984–989.

    PubMed  CAS  Google Scholar 

  39. Marra CM, Slatter V, Tartaglione TA, et al.: Evaluation of aqueous penicillin G and ceftriaxone for experimental neurosyphilis [letter]. J Infect Dis 1992, 165:346–347.

    Google Scholar 

  40. Schofer H, Vogt HJ, Milbradt R: Ceftriaxone for treatment of primary and secondary syphilis. Chemotherapy 1989, 35:440–445.

    Google Scholar 

  41. Dowell ME, Ross PG, Musher DM, et al.: Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. Am J Med 1992, 93:481–488.

    Article  PubMed  CAS  Google Scholar 

  42. Marra CM, Boutin P, MCArthur JL, et al.: A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in HIV-infected individuals. Clin Infect Dis 2000, 30:540–544.

    Article  PubMed  CAS  Google Scholar 

  43. Smith NH, Musher DM, Huang DB, et al.: Response of HIV-infected patients with asymptomatic neurosyphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin. Int J STD AIDS 2004, 15:328–332.

    Article  PubMed  CAS  Google Scholar 

  44. Pao D, Goh BT, Bingham JS: Management issues in syphilis. Drugs 2002, 62:1447–1461. This is a good review of the current management of the various stages of syphilis. The authors are from the United Kingdom and present the European approach to syphilis in a comprehensive fashion.

    Article  PubMed  CAS  Google Scholar 

  45. Marra CM, Maxwell CL, Tantalo L, et al.: Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter? Clin Infect Dis 2004, 38:1001–1006.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Room 6303, NCB Mailstop 461, Hahnemann University Hospital, Broad and Vine Streets, 19102, Philadelphia, PA, USA

    Judith A. O’Donnell MD

Authors
  1. Judith A. O’Donnell MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher L. Emery MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Donnell, J.A., Emery, C.L. Neurosyphilis: A current review. Curr Infect Dis Rep 7, 277–284 (2005). https://doi.org/10.1007/s11908-005-0060-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-005-0060-7

Keywords

Search

Navigation