Neurosyphilis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]

Overview

• Neurosyphilis refers to a site of infection involving the central nervous system (CNS).

• Neurosyphilis may occur at any stage of syphilis.

• Before the advent of antibiotics, it was typically seen in 25-35% of patients with syphilis.

• Neurosyphilis is now most common in patients with HIV infection. Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV pandemic. The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, have not been well characterized. Furthermore, the alteration of host immunosuppression by antiretroviral therapy in recent years has further complicated such characterization.

Clinical presentation: Four clinical types

• The late forms of neurosyphilis (tabes dorsalis and general paresis) are seen much less frequently since the advent of antibiotics.
• The most common manifestations today are asymptomatic or symptomatic meningitis.

1. Asymptomatic meningitis

• Asymptomatic neurosyphilis usually has no signs or symptoms and is diagnosed exclusively with the presence or absence of CSF abnormalities notably pleocytosis, elevated protein, decreased glucose.

2. Symptomatic meningitis

• develops within 6-months to several years of primary infection
• typical meningitis symptoms: headache, nausea, vomiting, photophobia
• Acute syphilitic meningitis usually occurs within the first year of infection; 10% of cases are diagnosed at the time of the secondary rash.
• Patients present with headache, meningeal irritation, and cranial nerve abnormalities, especially the optic nerve, facial nerve, and the vestibulocochlear nerve.
• Rarely, it affects the spine instead of the brain, causing focal muscle weakness or sensory loss.

3. Meningovascular syphilis

• Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary syphilis infection.

• Meningovascular syphilis can be associated with prodromal symptoms lasting weeks to months before focal deficits are identifiable.

• Prodromal symptoms include:

• unilateral numbness,
• paresthesias,
• upper or lower extremity weakness,
• headache,
• vertigo,
• insomnia, and
• psychiatric abnormalities such as personality changes.

• The focal deficits initially are intermittent or progress slowly over a few days.

• However, it can also present as an infectious arteritis and cause an ischemic stroke, an outcome more commonly seen in younger patients.

• Angiography may be able to demonstrate areas of narrowing in the blood vessels or total occlusion.

4. Parenchymatous neurosyphilis

• develops 15-20 years after primary infection
• argyll robertson pupil: small irregular pupil
• clinical presents as general paresis or tabes dorsalis with resultant ataxia

• General paresis, otherwise known as general paresis of the insane, is a severe manifestation of neurosyphilis.

• It is a chronic dementia which ultimately results in death in as little as 2-3 years.

• Patients generally have progressive personality changes, memory loss, and poor judgment.

• More rarely, they can have psychosis, depression, or mania.

• Imaging of the brain usually shows atrophy.

Diagnosis

• Clinical signs of neurosyphilis (i.e., cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities) warrant further investigation and treatment for neurosyphilis.

• Approximately 35% to 40% of persons with secondary syphilis have asymptomatic central nervous system (CNS) involvement, as demonstrated by any of these on cerebrospinal fluid (CSF) examination:

• An abnormal leukocyte cell count, protein level, or glucose level
• Demonstrated reactivity to Venereal Disease Research Laboratory (VDRL) antibody test

• Laboratory testing is helpful in supporting the diagnosis of neurosyphilis; however, no single test can be used to diagnose neurosyphilis in all instances.

CSF analysis

• Cerebrospinal fluid (CSF) abnormalities are common in persons with early syphilis.

• Diagnosed by finding high numbers of leukocytes in the CSF or abnormally high protein concentration in the setting of syphilis infection.

• VDRL in cerebrospinal fluid (CSF-VDRL), which is highly specific but insensitive, is the standard serologic test for CSF. Although some advocate using the FTA-ABS test to improve sensitivity.

• When reactive in the absence of substantial contamination of CSF with blood, it is considered diagnostic of neurosyphilis; however in early syphilis, it can be of unknown prognostic significance.

• Most other tests are both insensitive and nonspecific and must be interpreted in relation to other test results and the clinical assessment. Therefore, the laboratory diagnosis of neurosyphilis usually depends on various combinations of reactive serologic test results, CSF cell count or protein, and a reactive CSF-VDRL with or without clinical manifestations.

HIV Co-infection

• There is anecdotal evidence that the incidence of neurosyphilis is higher in HIV patients, and some have recommended that all HIV-positive patients with syphilis should have a lumbar puncture to look for asymptomatic neurosyphilis.

• Among persons with HIV infection, the CSF leukocyte count usually is elevated (>5 white blood cell count [WBC]/mm3); using a higher cutoff (>20 WBC/ mm3) might improve the specificity of neurosyphilis diagnosis.

• The CSF-VDRL might be non-reactive even when neurosyphilis is present.

• Therefore, additional evaluation using FTA-ABS testing on CSF can be considered. The CSF FTA-ABS test is less specific for neurosyphilis than the CSF-VDRL but is highly sensitive; neurosyphilis is highly unlikely with a negative CSF FTA-ABS test.

Treatment

• For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without positive CSF results, aqueous crystalline penicillin G is the treatment of choice.

• The recommended regimen is intravenous treatment every 4 hours or continuously for 10-14 days.

• If intravenous administration is not possible, then procaine penicillin is an alternative (administered daily with probenecid for two weeks). Procaine injections are painful, however, and patient compliance may be difficult to ensure.

• To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of benzathine penicillin G after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for neurosyphilis.

• No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. The only alternative that has been studied and shown to be effective is intramuscular ceftriaxone daily for 14 days.

Related chapters

• Syphilis
• Congenital syphilis

Resources

• UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV
• "A New Gold Standard For Syphilis?" Poster Presentation for European Academy of Dermatology and Venereology 2004 Spring Symposium
• Syphilis Pictures and Information
• Kipkeepers, Pox and Gleet Vendors: A Rapid History of Syphilis
• POX: Genius, Madness, and the Mysteries of Syphilis
• Syphilis Informational resource
• Secrets of the Dead (PBS): The Syphilis Enigma
• Syphilis and AIDS: Lessons from history
• "Syphilis fact sheet" from the Center for Disease Control
• The treatment of dementia paralytica by malaria inoculation (A Nobel Prize lecture, December 13, 1927)
• National Institute of Allergy and Infectious Diseases Factsheet
• New study blames Columbus for syphilis spread from Reuters Jan 15, 2008

References

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