Current Neurology and Neuroscience Reports

, Volume 4, Issue 6, pp 435–440 | Cite as


  • Christina M. Marra


Treponema pallidum, the bacterium that causes syphilis, invades the central nervous system early in the course of disease but causes persistent infection in only a subset of infected persons. Individuals with persistent infection or asymptomatic meningitis are at risk for developing symptomatic neurosyphilis if they are not treated with a drug regimen that achieves sufficient drug levels in cerebrospinal fluid to kill the organism. In this article, recent studies that address the risk, diagnosis, and management of neurosyphilis are discussed within the context of a brief review. Particular attention is given to current controversies. In the developed world, these issues are particularly relevant to persons who are infected with HIV.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Golden MR, Marra CM, Holmes KK: Update on syphilis: resurgence of an old problem. JAMA 2003, 290:1510–1514. Concise review that includes information gleaned in the era before antibiotics.PubMedCrossRefGoogle Scholar
  2. 2.
    World Health Organization Department of HIV/AIDS: Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates. http:// Accessed on July 7, 2004.Google Scholar
  3. 3.
    World Health Organization: The World Health Report 2004—changing history. Accessed on July 7, 2004.Google Scholar
  4. 4.
    Primary and secondary syphilis—United States, 1999. MMWR Morb Mortal Wkly Rep 2001, 50:113–117.Google Scholar
  5. 5.
    Primary and secondary syphilis—United States, 2000–2001. MMWR Morb Mortal Wkly Rep 2002, 51:971–973.Google Scholar
  6. 6.
    Notice to readers: final 2002 reports of notifiable diseases. MMWR Morb Mortal Wkly Rep 2003, 52:741–750.Google Scholar
  7. 7.
    Primary and secondary syphilis—United States, 2002. iaMMWR Morb Mortal Wkly Rep 2003, 52:1117–1120.Google Scholar
  8. 8.
    Kahn RH, Heffelfinger JD, Berman SM: Syphilis outbreaks among men who have sex with men: a public health trend of concern. Sex Transm Dis 2002, 29:285–287.PubMedCrossRefGoogle Scholar
  9. 9.
    Weir E, Fisman D, Fishman D: Syphilis: have we dropped the ball? Can Med Assoc J 2002, 167:1267–1268.Google Scholar
  10. 10.
    Ashton M, Sopwith W, Clark P, et al.: An outbreak no longer: factors contributing to the return of syphilis in Greater Manchester. Sex Transm Infect 2003, 79:291–293.PubMedCrossRefGoogle Scholar
  11. 11.
    Berry CD, Hooton TM, Collier AC, Lukehart SA: Neurologic relapse after benzathine penicillin therapy for secondary syphilis in a patient with HIV infection. N Engl J Med 1987, 316:1587–1589.PubMedCrossRefGoogle Scholar
  12. 12.
    Musher DM: Syphilis, neurosyphilis, penicillin, and AIDS. J Infect Dis 1991, 163:1201–1206.PubMedGoogle Scholar
  13. 13.
    Moore J: Studies in asymptomatic neurosyphilis II. The classification, treatment, and prognosis of early asymptomatic neurosyphilis. Bull Johns Hopkins Hosp 1922, 33:231–246.Google Scholar
  14. 14.
    Ravaut P: Le liquide céphalo-rachidien des syphiliques en période secondaire. Ann Dermatol Syphiligr 1903, 4:537–554.Google Scholar
  15. 15.
    Wile UJ, Stokes JH: A study of the spinal fluid with reference to involvement of the nervous system in secondary syphilis. J Cutan Dis 1914, 32:607–623.Google Scholar
  16. 16.
    Fildes P, Parnell RJ, Maitland HB: The occurrence of unsuspected involvement of the central nervous system in unselected cases of syphilis. Brain 1918, 41:255–301.CrossRefGoogle Scholar
  17. 17.
    Mills CH: Routine examination of the cerebrospinal fluid in syphilis: its value in regard to more accurate knowledge, prognosis and treatment. BMJ 1927, 2:527–532.CrossRefPubMedGoogle Scholar
  18. 18.
    Merritt HH, Adams RD, Solomon HC: Neurosyphilis. New York: Oxford; 1946Google Scholar
  19. 19.
    Lukehart SA, Hook EW III, 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.PubMedGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 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. The results of this large study show that treatment for non-neurologic syphilis and syphilis stage does not influence the likelihood of CSF abnormalities due to syphilis. In contrast, high serum RPR titer (≥1:32) is a strong predictor of such abnormalities. Further, it shows that HIV-induced immunosuppression increases the likelihood of neurosyphilis.PubMedCrossRefGoogle Scholar
  22. 22.
    Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines 2002. MMWR Morb Mortal Wkly Rep 2002, 51:18–30.Google Scholar
  23. 23.
    Tramont EC: Persistence of Treponema pallidum following penicillin G therapy. Report of two cases. JAMA 1976, 236:2206–2207.PubMedCrossRefGoogle Scholar
  24. 24.
    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. This study shows that compared with HIV-uninfected patients, CSF-VDRL reactivity is less likely to normalize after neurosyphilis treatment in HIV-infected individuals. These results suggest that HIV-infected individuals might require more intensive therapy for neurosyphilis than those who are not HIV infected.PubMedCrossRefGoogle Scholar
  25. 25.
    Hart G: Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986, 104:368–376.PubMedGoogle Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Marra CM, Tantalo LC, Maxwell CL, et al.: Alternative cerebrospinal fluid tests to diagnose neurosyphilis in HIV-infected individuals. Neurology 2004, 63:85–88.PubMedGoogle Scholar
  28. 28.
    Razavi-Encha F, Fleury-Feith J, Gherardi R, Bernaudin JF: Cytologic features of cerebrospinal fluid in Lyme disease. Acta Cytol 1987, 31:439–440.PubMedGoogle Scholar
  29. 29.
    Sindern E, Malin JP: Phenotypic analysis of cerebrospinal fluid cells over the course of Lyme meningoradiculitis. Acta Cytol 1995, 39:73–75.PubMedGoogle Scholar
  30. 30.
    Cepok S, Zhou D, Vogel F, et al.: The immune response at onset and during recovery from Borrelia burgdorferi meningoradiculitis. Arch Neurol 2003, 60:849–855.PubMedCrossRefGoogle Scholar
  31. 31.
    Bash S, Hathout GM, Cohen S: Mesiotemporal T2-weighted hyperintensity: neurosyphilis mimicking herpes encephalitis. Am J Neuroradiol 2001, 22:314–316. Review of neuroimaging abnormalities in neurosyphilis.PubMedGoogle Scholar
  32. 32.
    Brightbill TC, Ihmeidan IH, Post MJ, et al.: Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings. Am J Neuroradiol 1995, 16:703–711.PubMedGoogle Scholar
  33. 33.
    Denays R, Collier A, Rubinstein M, Atsama P: A 51-year-old woman with disorientation and amnesia. Lancet 1999, 354:1786.PubMedCrossRefGoogle Scholar
  34. 34.
    Silberstein P, Lawrence R, Pryor D, Shnier R: A case of neurosyphilis with a florid Jarisch-Herxheimer reaction. J Clin Neurosci 2002, 9:689–690.PubMedCrossRefGoogle Scholar
  35. 35.
    Lauria G, Erbetta A, Pareyson D, Sghirlanzoni A: Parenchymatous neurosyphilis. Neurol Sci 2001, 22:281–282.PubMedCrossRefGoogle Scholar
  36. 36.
    Szilak I, Marty F, Helft J, Soeiro R: Neurosyphilis presenting as herpes simplex encephalitis. Clin Infect Dis 2001, 32:1108–1109.PubMedCrossRefGoogle Scholar
  37. 37.
    Ances BM, Shellhaus R, Brown MJ, et al.: Neurosyphilis and status epilepticus: case report and literature review. Epilepsy Res 2004, 59:67–70.PubMedCrossRefGoogle Scholar
  38. 38.
    Berbel-Garcia A, Porta-Etessam J, Martinez-Salio A, et al.: Magnetic resonance image-reversible findings in a patient with general paresis. Sex Transm Dis 2004, 31:350–352.PubMedCrossRefGoogle Scholar
  39. 39.
    Marano E, Briganti F, Tortora F, et al.: Neurosyphilis with complex partial status epilepticus and mesiotemporal MRI abnormalities mimicking herpes simplex encephalitis. J Neurol Neurosurg Psychiatry 2004, 75:833.PubMedCrossRefGoogle Scholar
  40. 40.
    Marra CM, Boutin P, McArthur JC, et al.: A pilot study evaluating ceftriaxone and penicillin g as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis 2000, 30:540–544.PubMedCrossRefGoogle Scholar
  41. 41.
    Smith NH, Musher DM, Huang DB, et al.: Response of HIVinfected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin. Int J STD AIDS 2004, 15:328–332.PubMedCrossRefGoogle Scholar
  42. 42.
    Hook EW 3rd, Stephens J, Ennis DM: Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis. Ann Intern Med 1999, 131:434–437.PubMedGoogle Scholar
  43. 43.
    Hook EW 3rd, Martin DH, Stephens J, et al.: A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis 2002, 29:486–490.PubMedCrossRefGoogle Scholar
  44. 44.
    Lukehart SA, Godornes C, Molini BJ, et al.: Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 2004, 351:154–158. A mutation that confers resistance to azithromycin was identified in 11% to 88% of T. pallidum isolates from different geographic locations. The results suggest that azithromycin should not be used for routine treatment of syphilis.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Christina M. Marra
    • 1
  1. 1.Harborview Medical Center, NeurologyUniversity of Washington School of MedicineSeattleUSA

Personalised recommendations