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  • • Central nervous system (CNS) or ophthalmic signs or symptoms of CNS syphilis (neurosyphilitic syndromes).
  • • Serologic evidence of syphilis infection (positive results on nontreponemal and treponemal tests).
  • • One of the following findings: positive cerebrospinal fluid (CSF) Venereal Disease Research Laboratories (VDRL) test result, CSF protein concentration greater than 40 mg/dL, or CSF white blood cell (WBC) count greater than 5 mononuclear cells per microliter.

Approximately 7% of patients with primary and secondary syphilis, if untreated, develop some form of symptomatic neurosyphilis. In 1990, the number of cases of primary and secondary syphilis reported to the US Centers for Disease Control and Prevention (CDC) peaked at over 50,000. By 1996, the incidence had fallen dramatically, and in 1997, fewer than 10,000 cases were reported. Many counties, however, report an incidence of more than 4 cases per 100,000 population. As of 2006, cases of primary and secondary syphilis are again increasing in the United States, particularly in populations of men having sex with men, thus increasing the risk pool for neurosyphilis.

The nervous system is affected early in syphilis, and 10–25% of patients have CSF abnormalities at the time of the development of the secondary stage. CSF inflammation eventually occurs in approximately one-third of patients with syphilis, with the peak of CSF abnormalities seen 12–18 months after the primary infection. Of patients with CSF inflammation, 30% will develop some form of neurosyphilis. In those with normal CSF examination findings 5 years after the primary infection, the risk of neurosyphilis is approximately 1%. Each of the clinical forms of neurosyphilis is a manifestation of this inflammatory response that continues, in reaction to Treponema pallidum invasion, over decades (see Figure 20–1).

Figure 20–1.

The interval between primary syphilis infection and symptomatic neurosyphilis. (Reproduced, with permission, from Simon RP. Neurosyphilis. Arch Neurol 1985;42:602.)

There has been some experimental evidence regarding treponemal strain specificity and neuroinvasion. The sheath proteins of T pallidum have conserved and variable regions that differ between strains. Strain-specific differences in neuroinvasion in rabbits have been demonstrated, and the possibility that these proteins may explain T pallidum tropism is being studied.

Neurosyphilis can occur in both early and later stages of syphilis. Prevention of neurosyphilis can be primary—through the prevention of sexual exposure and syphilis infection—or secondary—through treatment in early stages to prevent the progression of syphilis.

Symptoms and Signs

The inflammatory process in the subarachnoid space produces the classic spectrum of presentation, which comprises acute syphilitic meningitis, arteritis (meningovascular syphilis), meningoencephalitis (syphilitic dementia, general paresis), and dorsal root ganglionopathy (tabes dorsalis). These entities may overlap; however, relatively pure forms predominate, demonstrating a characteristic time course and presentation following the initial primary infection (see Figure 20–1).

Acute syphilitic meningitis is the earliest symptomatic subtype and often accompanies the rash of ...

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