Syphilis, caused by the bacterium Treponema pallidum , is able to invade the central nervous system early in the course of infection. As many as 40% of patients will have neuroinvasion of syphilis but most will not exhibit symptoms of neurosyphilis. Early neurosyphilis typically occurs within the first years of infection and can manifest as meningitis (symptomatic or asymptomatic), otosyphilis, ocular syphilis, and meningovascular syphilis. Later phase syphilis (usually one to two decades after initial infection) can result in the syndromes of tabes dorsalis and general paresis.
Symptomatic meningitis can present with headache, neck stiffness, photophobia, and confusion. Multiple cranial neuropathies may occur. Otosyphilis and ocular syphilis may occur independently or in conjunction with meningitis. Symptoms of otosyphilis include hearing loss, tinnitus, and vertigo. Vision loss secondary to uveitis, chorioretinitis, or optic nerve involvement may occur with ocular syphilis.
Meningovascular syphilis represents an infectious arteritis typically affecting the medium to large arteries and leading to cerebral or spinal cord infarction. It may occur early after primary infection or years later. Involvement may be limited to the intracranial vessels, with the middle cerebral artery often preferentially involved, or may affect extracranial vessels as well, including the aorta and its branches. Diagnosis is with computed tomography or magnetic resonance angiography.
In tabes dorsalis, syphilitic infection damages the dorsal columns of the spinal cord and dorsal roots of the spinal nerves. Findings include impaired vibration and proprioception in lower extremities causing an ataxic gait and positive Romberg sign, shooting pain in the legs and abdomen, bladder dysfunction, areflexia in lower extremities, and Argyll Robertson pupils (constrict to accommodation but not to light).
General paresis manifests as progressive dementia, personality change, and other psychiatric symptoms including depression, delusions, and hallucinations. Other neurologic deficits may include dysarthria, tremor, hyperreflexia, and Argyll Robertson pupils.
Diagnosis of syphilis is made using two types of tests: (1) non-treponemal serum screening tests, such as the rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) test; and (2) treponemal-specific tests such as the fluorescent treponemal antibody absorption test (FTA-ABS), T. pallidum particle agglutination assay (TP-PA), and microhemagglutination test for antibodies to T. pallidum (MHA-TP). Non-treponemal tests have lower sensitivity for late forms of syphilis, and are more likely to produce false-positive results, but have the advantage of providing a semiquantitative titer that correlates with infectious activity. Treponemal-specific tests are more sensitive for later forms of syphilis, and will remain positive for life once infection has occurred. Thus patients previously treated for syphilis with a positive treponemal test may or may not have active infection; evaluation of the non-treponemal test titer can help with this determination. The classic testing pathway is to perform the non-treponemal test first with positive results confirmed using a treponemal assay. More recently with advances in laboratory instrumentation, a reversed testing protocol has been introduced in some institutions starting with the treponemal-specific assay and, in positive subjects, subsequently testing the non-treponemal assay.
Patients with positive syphilis testing and suspected neurosyphilis should undergo lumbar puncture to assess for central nervous system infectious activity. Human immunodeficiency virus (HIV) testing should also be performed as up to 40% of people with syphilis are coinfected with HIV. In the absence of HIV infection, an elevated cerebrospinal fluid (CSF) protein (> 45 mg/dL) OR pleocytosis (white blood cells, WBC > 5 cells/mm 3 ) OR a positive CSF VDRL indicates possible neurosyphilis and is an indication for treatment.
Interpretation of CSF studies in patients with HIV infection is challenging as HIV infection itself may cause elevated protein and mononuclear pleocytosis. If CSF WBC are ≤ 5 cells/mm 3 and the CSF VDRL is negative, neurosyphilis can be reliably excluded. If the CSF VDRL is positive OR WBC > 20 cells/mm 3 are present, the patient should be treated for neurosyphilis. In cases with intermediate pleocytosis, consultation with an infectious disease expert is reasonable to decide on treatment.
Treatment of neurosyphilis is more intensive than that for patients with syphilis not affecting the nervous system. Patients with penicillin allergy should undergo penicillin desensitization followed by treatment with penicillin. Efficacy of non-penicillin treatment for treatment of neurosyphilis is limited.
Monitoring includes repeat lumbar puncture at 6, 12, and 24 months posttreatment. Re-treatment should be considered if the CSF WBC count has not normalized by 6 months, the CSF VDRL has not become negative or decreased fourfold by 12 months, or CSF abnormalities persist at 24 months.