- • 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
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).
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.
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 ...