Neurology Exam Prep: Neurosyphilis Overview

Introduction to Neurosyphilis

  • Hosts: Harry and Aaron Bauer, an attending at Yale School of Medicine in neuroimmunology.
  • Topic Overview: Discussion on neurosyphilis, epidemiology, pathophysiology, systemic and neurologic presentations, diagnostic testing, and therapy.

Epidemiology of Syphilis

  • Increasing Rates: Notable rise in primary and secondary syphilis cases in the US over the last 20 years.
    • 2017 Data: Estimated 9.5 cases per 100,000, with 3.5% developing neurosyphilis.
  • Demographic Trends:
    • Higher incidence in males (approximately 86% of cases in 2018).
    • Doubling of rates in women from 2014 to 2018.
  • Congenital Syphilis: Increased cases due to rising rates in the general population.
  • Coinfection with HIV: Approximately 42% of syphilis cases also involve HIV.

Pathophysiology of Syphilis

  • Causative Agent: Treponema pallidum, a spirochete.
  • Transmission: Occurs via sexual contact and vertical transmission (from mother to child).
  • Disease Course: Manifestations result from a local inflammatory response due to spirochete replication.

Stages of Syphilis

Early Syphilis
  • Definition: Infection duration less than 1 year (CDC) or 2 years (WHO).
  • Primary Syphilis:
    • Symptoms: Painless chancre (typically genital) and regional lymphadenopathy.
    • Onset: 3 weeks after exposure.
  • Secondary Syphilis:
    • Symptoms: Flu-like symptoms, mucosal lesions (e.g., alopecia, hepatitis), and a characteristic rash on palms and soles.
    • Onset: 6-8 weeks post-exposure.
Tertiary Syphilis
  • Latency: Asymptomatic phase between secondary and tertiary.
  • Symptoms: Severe cardiovascular involvement (aneurysms, aortic valve insufficiency), gummas (granulomatous lesions), and neurological complications.
  • Neurologic Sequelae: Tabes dorsalis and general paresis are significant concerns.

Neurologic Presentations of Syphilis

Early Neurologic Involvement
  • Meningeal Involvement:
    • Symptoms: Headache, meningismus, possible cranial nerve palsies.
    • CSF Findings: Pleocytosis.
  • Meningovascular Syphilis:
    • Symptoms: Focal neurologic deficits and possible strokes.
Late Neurologic Involvement
  • Tabes Dorsalis:
    • Symptoms: Poor proprioception, ataxia, lightning-like leg pain, and paraparesis.
    • CSF Findings: Mild chronic pleocytosis.
  • General Paresis:
    • Symptoms: Progressive dementia, psychiatric syndromes (personality changes, manic delusions), tremors, dysarthria.
  • Argyle Robinson Pupils: Nonreactive to light but constrict with accommodation—seen in both tabes dorsalis and general paresis.

Diagnostic Testing for Syphilis

  • Testing Categories:
    • Nontreponemal Tests: VDRL, RPR (positive early, decline in late).
    • Treponemal Tests: FTA-ABS (positive throughout disease).
  • Diagnosis Algorithm:
    1. Positive Serum Treponemal Test: If negative with no symptoms, not neurosyphilis.
    2. If Symptoms Present: Perform lumbar puncture.
    3. CSF Test: Send for VDRL; if positive, confirms neurosyphilis.
    4. Nonreactive VDRL: Assess CSF pleocytosis and protein; if present, proceed to CSF Treponemal test for confirmation.

Treatment of Neurosyphilis

  • First-Line Treatment: Aqueous penicillin G (18-24 million units/day, IV).
  • Monitoring: Track serum nontreponemal titers and CSF pleocytosis; treatment duration typically 10-14 days.
  • Alternative Treatments: Limited efficacy with alternatives (e.g., ceftriaxone) if allergic to penicillin, but penicillin remains the preferred drug.
  • Post-Treatment Considerations: Monitor for titers decline (4-fold reduction expected). Completion of treatment does not always reverse neurological symptoms.

Conclusion

  • Key Takeaways: Understanding the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and treatment of neurosyphilis are essential for effective management and improved patient outcomes.