- Christina M Marra, MD
Christina M Marra, MD
- Professor of Neurology, Adjunct Professor of Medicine (Infectious Diseases)
- University of Washington School of Medicine
- Section Editors
- Francisco González-Scarano, MD
Francisco González-Scarano, MD
- Section Editor — Multiple Sclerosis; Neurovirology & NeuroAIDS
- John P. Howe, III, MD, Distinguished Chair in Health Policy
- The University of Texas Health Science Center at San Antonio
- John G Bartlett, MD
John G Bartlett, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — HIV; Pulmonary Infections
- Professor Emeritus
- Johns Hopkins University School of Medicine
The term "neurosyphilis" refers to infection of the central nervous system (CNS) by Treponema pallidum, subspecies pallidum (hereafter termed T. pallidum). Neurosyphilis can occur at any time after initial infection.
Early in the course of syphilis, the most common forms of neurosyphilis involve the cerebrospinal fluid, meninges, and vasculature (asymptomatic meningitis, symptomatic meningitis, and meningovascular disease). Late in disease, the most common forms involve the brain and spinal cord parenchyma (general paralysis of the insane and tabes dorsalis). Each form has characteristic clinical findings, but in some cases there is overlap between these findings.
This topic will review the pathogenesis, epidemiology, clinical findings, diagnosis, and treatment of neurosyphilis. Other aspects of syphilis are discussed separately. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients" and "Syphilis: Treatment and monitoring" and "Epidemiology, clinical presentation, and diagnosis of syphilis in the HIV-infected patient".)
Neurosyphilis begins with invasion of the cerebrospinal fluid (CSF), a process that probably occurs shortly after acquisition of T. pallidum infection. The organism can be identified in the CSF from approximately one-quarter of untreated patients with early syphilis [1,2]. Specific strains of T. pallidum may be more likely to cause neurosyphilis .
Unlike other bacteria that can infect the CSF, invasion of CSF with T. pallidum does not always result in persistent infection, as spontaneous resolution may occur in some cases without an inflammatory response. In other cases, spontaneous resolution may occur after a transient meningitis (figure 1).
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- Marra C, Sahi S, Tantalo L, et al. Enhanced molecular typing of treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis 2010; 202:1380.
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- Marra CM, Castro CD, Kuller L, et al. Mechanisms of clearance of Treponema pallidum from the CSF in a nonhuman primate model. Neurology 1998; 51:957.
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- Taylor MM, Aynalem G, Olea LM, et al. A consequence of the syphilis epidemic among men who have sex with men (MSM): neurosyphilis in Los Angeles, 2001-2004. Sex Transm Dis 2008; 35:430.
- Poliseli R, Vidal JE, Penalva De Oliveira AC, Hernandez AV. Neurosyphilis in HIV-infected patients: clinical manifestations, serum venereal disease research laboratory titers, and associated factors to symptomatic neurosyphilis. Sex Transm Dis 2008; 35:425.
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- Oliver S, Sahi SK, Tantalo LC, et al. Molecular Typing of Treponema pallidum in Ocular Syphilis. Sex Transm Dis 2016; 43:524.
- Yimtae K, Srirompotong S, Lertsukprasert K. Otosyphilis: a review of 85 cases. Otolaryngol Head Neck Surg 2007; 136:67.
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- Hicdonmez T, Utku U, Turgut N, et al. Reversible postictal MRI change mimicking structural lesion. Clin Neurol Neurosurg 2003; 105:288.
- Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
- 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.
- Libois A, De Wit S, Poll B, et al. HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis 2007; 34:141.
- Ghanem KG, Moore RD, Rompalo AM, et al. Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS 2008; 22:1145.
- Marra CM, Sahi SK, Tantalo LC, et al. Toll-like receptor polymorphisms are associated with increased neurosyphilis risk. Sex Transm Dis 2014; 41:440.
- Janier M, Hegyi V, Dupin N, et al. 2014 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol 2014; 28:1581.
- Larsen SA, Hambie EA, Wobig GH, Kennedy EJ. Cerebrospinal fluid serologic test for syphilis: treponemal and nontreponemal tests. In: Advances in sexually transmitted diseases, Morisset R, Kurstak E. (Eds), VNU Science Press, Utrecht 1986. p.157-162.
- Izzat NN, Bartruff JK, Glicksman JM, et al. Validity of the VDRL test on cerebrospinal fluid contaminated by blood. Br J Vener Dis 1971; 47:162.
- Marra CM, Tantalo LC, Maxwell CL, et al. The rapid plasma reagin test cannot replace the venereal disease research laboratory test for neurosyphilis diagnosis. Sex Transm Dis 2012; 39:453.
- Harding AS, Ghanem KG. The performance of cerebrospinal fluid treponemal-specific antibody tests in neurosyphilis: a systematic review. Sex Transm Dis 2012; 39:291.
- 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.
- Marra CM, Maxwell CL, Tantalo LC, et al. Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. Clin Infect Dis 2008; 47:893.
- Marra CM, Maxwell CL, Collier AC, et al. Interpreting cerebrospinal fluid pleocytosis in HIV in the era of potent antiretroviral therapy. BMC Infect Dis 2007; 7:37.
- Marra CM, Tantalo LC, Sahi SK, et al. CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV-infected patients with syphilis. Sex Transm Dis 2010; 37:283.
- Mothapo KM, Verbeek MM, van der Velden LB, et al. Has CXCL13 an added value in diagnosis of neurosyphilis? J Clin Microbiol 2015; 53:1693.
- 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.
- Yim CW, Flynn NM, Fitzgerald FT. Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis. Antimicrob Agents Chemother 1985; 28:347.
- Punia V, Rayi A, Sivaraju A. Stroke after Initiating IV Penicillin for Neurosyphilis: A Possible Jarisch-Herxheimer Reaction. Case Rep Neurol Med 2014; 2014:548179.
- Davis LE, Oyer R, Beckham JD, Tyler KL. Elevated CSF cytokines in the Jarisch-Herxheimer reaction of general paresis. JAMA Neurol 2013; 70:1060.
- CLINICAL MANIFESTATIONS
- Early neurosyphilis
- - Asymptomatic neurosyphilis
- - Symptomatic meningitis
- - Ocular syphilis
- - Otosyphilis
- - Meningovascular syphilis
- Late neurosyphilis
- - General paresis
- - Tabes dorsalis
- Atypical neurosyphilis
- Unknown syphilis history
- Known syphilis
- Spinal fluid examination
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS
- Epidemiology and clinical manifestations
- Diagnosis summary
- Treatment summary