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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.

There are four clinical types of neurosyphilis:

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. 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.

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.

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.

Symptoms and signs

Symptoms of neurosyphilis include:[2]

  • Abnormal gait
  • Blindness
  • Confusion
  • Dementia
  • Depression
  • Headache
  • Incontinence
  • Irritability
  • Numbness in the toes, feet, or legs
  • Poor concentration
  • Seizures
  • Neck stiffness
  • Tremors
  • Visual disturbances. There may be the sign of Argyll Robertson pupils, which are bilateral small pupils that constrict when the patient focuses on a near object, but do not constrict when exposed to bright light.
  • Muscle weakness

Upon further diagnostic workup, the following signs may be present:

  • Abnormal reflexes
  • Muscle atrophy
  • Muscle contractions

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


In addition to evaluation of any symptoms and signs, various blood tests can be done:[2]

  • Venereal Disease Research Laboratory test (VDRL)
  • Fluorescent treponemal antibody absorption (FTA-ABS)
  • Rapid plasma reagin (RPR)
  • Treponema pallidum particle agglutination assay (TPPA)

Also, it is important to test the cerebrospinal fluid for signs of syphilis.[2]

Additional tests to look for problems with the nervous system may include:[2]


Penicillin is used to treat neurosyphilis. Two examples of penicillin therapies include:[2]

  • Injection into a vein several times a day for 10 - 14 days.
  • One daily intramuscular injection and oral probenecid 4 times a day, both for 10 - 14 days.

Follow-up blood tests are generally performed at 3, 6, 12, 24, and 36 months to make sure the infection is gone.[2] Lumbar punctures for CSF fluid analysis are generally performed every 6 months.

See also


  1. Richard B. Jamess, MD, PhD (2002). Syphilis- Sexually Transmitted Infections, 2006.. Sexually transmitted diseases treatment guidelines.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Cite error: Invalid <ref> tag; no text was provided for refs named pubmedhealth

Further reading

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