- 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 Gonzalez-Scarano, MD
Francisco Gonzalez-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
- Section Editor — 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. 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 (CSF), 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 "Pathophysiology, transmission, and natural history of syphilis" and "Pathogenesis, clinical manifestations, and treatment of early syphilis" and "Pathogenesis, clinical manifestations, and treatment of late syphilis" 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]. Although investigators in the first half of the 20th century did not believe that there were "neurotropic strains" of T. pallidum, a study conducted in the antibiotic era suggested that strain variability may affect the characteristics of the infection .
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.
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- Tantalo LC, Lukehart SA, Marra CM. Treponema pallidum strain-specific differences in neuroinvasion and clinical phenotype in a rabbit model. J Infect Dis 2005; 191:75.
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- 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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- 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.
- Ghanem KG, Moore RD, Rompalo AM, et al. Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms. Clin Infect Dis 2009; 48:816.
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- 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.
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- 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
- SUMMARY AND RECOMMENDATIONS
- Epidemiology and clinical manifestations
- Diagnosis summary
- Treatment summary