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Neurosyphilis – What You Need to Know

November 25, 2019

Written by Vivian Lei

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Neurosyphilis has a diversity of presentations, and clinical recognition is key, especially in an era where the disease has become rare.

Why does this matter?
Prior to antibiotics, neurosyphilis was ubiquitous. Unfortunately, primary and secondary syphilis has been on the rise in the US for the past 2 decades. While still rare, neurosyphilis should not be overlooked.

Clinical presentation

  • Early neurosyphilis is usually asymptomatic with only CSF pleocytosis.

  • If symptomatic, syphilitic meningitis symptoms include headache, meningismus, photophobia, cranial nerve palsies, confusion, lethargy, and seizures.

  • Meningovascular syphilis is a form of CNS vasculitis which can cause strokes and progressive myelopathy and can occur early or late (typically between 1 and 10 years following primary infection).

  • Late neurosyphilis develops decades after primary infection and manifests with general paresis and tabes dorsalis.

    • General paresis includes a host of neuropsychiatric symptoms, including psychosis, depression, progressive dementia, personality change, manic delusions, and dysarthria.

    • Tabes dorsalis is characterized by gait ataxia with Romberg’s sign and Argyll Robertson pupils (pupillary constriction when focusing on a nearby objection but not when illuminated). Patients also develop lancinating pains in their limbs and abdomen as well as impaired proprioception.


Serum and CSF serologic tests are required for diagnosis of neurosyphilis but are imperfect. Laboratory tests are classified as nontreponemal (venereal disease research laboratory [VDRL] or rapid plasma reagin [RPR]) and treponemal (fluorescent treponemal-antibody absorption [FTA-ABS]).

  • Serum nontreponemal tests are reactive in almost all cases of early neurosyphilis but can become negative in late neurosyphilis due to waning titers. Serum treponemal tests remain reactive for life regardless of previous treatment.

  • CSF VDRL is only 30-70% sensitive for neurosyphilis but highly specific.

  • If CSF VDRL is negative in a patient with a neurosyphilitic syndrome, CSF treponemal tests should be conducted.

  • Testing for HIV is recommended for all patients with syphilis.


  • All forms of neurosyphilis are treated with parenteral penicillin.

  • In the US, the CDC recommends:

    • Aqueous crystalline penicillin G (3-4 million units IV every 4 hours or 18-24 million units every 24 hours as a continuous infusion) for 10-14 days

    • If adherence can be ensured, penicillin G procaine (2.4 million units IM daily) plus probenecid (500 mg orally 4 times a day) for 10-14 days is an option.

  • Patients with a penicillin allergy should receive skin testing and desensitization.

  • Limited evidence suggests ceftriaxone, tetracycline, or doxycycline may be effective as well.

Neurosyphilis. N Engl J Med. 2019 Oct 3;381(14):1358-1363. doi: 10.1056/NEJMra1906228.

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Reviewed by Clay Smith

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