Neurosyphilis is the infection of the central nervous system in a patient with syphilis that can occur during any stage of the infection. Neurosyphilis can present with a wide spectrum of neuropsychiatric symptoms that are non-specific and can resemble many neurologic and psychiatric disorders (hence its historical name “The Great Imitator”).[1]

Prior to the discovery of Treponema pallidum (the spirochete bacterium responsible for syphilis) by Japanese bacteriologist Hideyo Noguchi in 1913, neurosyphilis was termed general paralysis of the insane (GPI), and erroneously thought to be caused by characterological flaws.[2] The identification of T. pallidum followed by the later discovery of penicillin and its use in the treatment of syphilis allowed for a curative treatment for GPI. Prior to this, GPI was fatal and it accounted for up to 30% of the primary diagnoses for patients in psychiatric hospitals.[3]

Enzyme Immunoassay (EIA) should be ordered as an initial screen for syphilis, followed by RPR if the EIA screen is reactive. If suspecting an early infection, then EIA should be repeated even in the presence of an initial negative screen.

A reactive RPR indicates can either indicate an old or new syphilis infection. The patient's history should then be evaluated to establish next steps and investigations. A reactive EIA, with a non-reactive RPR indicates a probable past infection. The natural history of RPR is that it will decrease even without treatment, and it may even become non‐reactive.

Serologic Tests for Syphilis

  • Treponemal tests (e.g. - EIA, TP-PA)
    • Highly specific for T. pallidum but remain for life
    • Positive tests need a non‐treponemal test to confirm active syphilis
  • Non‐treponemal tests (e.g. - RPR, VDRL)
    • Highly sensitive, but not specific to T. pallidum
    • False‐positive with IVDU, malaria, TB, and some autoimmune disorders
  • Direct methods
    • Darkfield microscopy
    • Direct fluorescent antibody (DFA)
    • Molecular testing
Case Reports
Interpretation Guidelines