children under eight years of age, in pregnant women, and in patients allergic to doxycycline,
amoxicillin 500 mg three times daily or cefuroxime axetil 500 mg twice daily are
probably as effective, though less well studied. In those with parenchymal CNS involvement,
or those who fail these oral regimens, intravenous ceftriaxone (2 g daily), cefotaxime (2 g
three times daily), or penicillin 24 million units daily, all for two to four weeks, are highly
effective (12).
Neurosyphilis
Transmitted primarily by sexual contact, syphilis typically begins with an asymptomatic skin
lesion at the site of inoculation, the chancre. Spirochetes disseminate quite early in infection,
with seeding of the neuraxis in about 40% of individuals (15). Almost all of these patients
develop meningitis, which can be variably symptomatic. However, virtually all develop CSF
changes including a lymphocytic pleocytosis, modest elevation of protein, and minimal
changes in glucose. In most, nonspecific “reaginic” (anti-cardiolipin) antibodies are detectable
in the CSF; treatment success can be monitored by measuring the decline in these antibodies as
well as in the cell count.
Parenchymal CNS involvement is grouped into three syndromes. Meningovascular
syphilis tends to occur on average seven years after initial infection and results from
inflammatory damage to the blood vessels in the subarachnoid space. This causes a series of
primarily small-artery strokes, often somewhat slowly evolving, typically accompanied by
chronic headaches from the meningitis. One to two decades after disease onset other patients
will develop “general paresis of the insane,” a more diffuse picture thought to result from a
combination of chronic hydrocephalus and parenchymal gummas. Finally, some patients will
develop tabes dorsalis two to three decades after initial infection—primarily a disorder of the
dorsal roots (which cross through the chronically inflamed subarachnoid space). These same
patients often develop parenchymal inflammation in the midbrain causing Argyll Robertson
pupils.
Diagnosis is primarily serologic, using both reaginic antibody tests such as the rapid plasma
reagent (RPR) and venereal disease research laboratory (VDRL) assays and more specific tests
such as the fluorescent treponemal antibody (FTA) and more recently ELISA technology.
Treatment when the CNS parenchyma is involved is typically with parenteral penicillin,
typically 18 to 24 million units daily for 10 to 14 days. Oral doxycycline (200 mg daily for four
weeks) is recommended and used as an alternative in penicillin-allergic patients, despite a
paucity of supportive studies.
Listeria
Listeriais a widely prevalent organism that only rarely causes human disease. Infection most
often occurs by exposure to contaminated food, most often dairy products. The organism is
ingested by, and survives within, a number of types of cells. It seems particularly able to invade
the placenta and the CNS, probably hiding intracellularly within trafficking monocytes (16).
Initial symptoms are primarily gastrointestinal. Infections are particularly problematic in
pregnant women (causing miscarriages) and newborns (causing disseminated infection).
Neurologic involvement takes several forms, most typically meningitis, being the commonest
cause of bacterial meningitis in the immunocompromised and the second most common in
healthy adults over age 50. The clinical picture of this meningitis is often more indolent than in
other meningitides; patients appear less ill and the time course is more protracted. A subset of
patients—often younger and otherwise healthy—develops a brainstem encephalitis, or
rhombencephalitis, with cranial nerve and long tract signs (ataxia, paresis) referable to this
anatomic segment of the CNS (17).
MR imaging can demonstrate microabscesses, particularly in the brainstem. Diagnosis is
typically by culture of blood or CSF. The organism is very sensitive to ampicillin and penicillin,
but perhaps because of its intracellular location, slow to respond. Consequently, gentamicin is
often added for synergy and treatment is typically prolonged. Meningitis is typically treated
for three weeks; rhombencephalitis for six.
158 Halperin