Vague Symptoms, Serious Infection: 5 Points on Neurosyphilis

Syphilis cases in the United States grew by nearly 80% between 2018 and 2022. Neurosyphilis, resulting from invasion of the central nervous system by Treponema pallidum, can cause irreversible vision loss, hearing loss, and paralysis. Five essential points summarize recognition, diagnosis, and treatment.1. Neurosyphilis Occurs at Any StageNeurosyphilis can develop shortly after infection or at any stage, often with vague neurologic or ophthalmologic complaints. Consider it for unexplained headache, visual symptoms, or cognitive changes, particularly with prior untreated syphilis, human immunodeficiency virus (HIV) infection, substance use, social instability, or incomplete sexually transmitted infection treatment.2. The Early SymptomsHeadaches and visual disturbances often serve as early indicators. Headache in meningovascular disease may reflect chronic meningitis and cerebral vasculitis, sometimes with focal deficits from infarction. Visual involvement ranges from transient blurring to irreversible blindness.3. A Combo of Diagnostic TestsPair a nontreponemal test (RPR) with a confirmatory treponemal test (Treponema pallidum particle agglutination). A reactive RPR indicates active or recent infection, and its titer can be monitored to assess treatment response. Treponemal antibodies typically stay positive for life. A reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory test is the gold standard despite limited sensitivity. Test all patients with newly diagnosed syphilis for HIV.4. The Mainstay of TreatmentThe 2021 CDC guidelines recommend aqueous crystalline penicillin G, 3-4 million units every 4 hours (18-24 million units daily), by intravenous (IV) or continuous infusion.Duration: Both 10- and 14-day courses are acceptable. The 14-day course is preferred with HIV coinfection, severe, late, or atypical disease, or poor follow-up.Alternatives: Procaine penicillin G plus probenecid is acceptable only when adherence is assured. For severe penicillin allergy, desensitization is preferred. Ceftriaxone is a possible alternative but not equivalent to penicillin.Not effective: Doxycycline and azithromycin, due to poor CSF penetration.5. Corticosteroid Evidence LimitedSteroids are sometimes used to reduce the Jarisch-Herxheimer reaction, based on limited data and expert opinion. They may benefit ocular syphilis, otosyphilis (evidence largely anecdotal), or meningeal disease at high risk of the reaction.Bottom LineEarly recognition and prompt IV penicillin G, with regimen length tailored to patient risk, prevent permanent neurologic and visual damage.This article is based on a recent Medscape article titled " Diagnostic Challenges and Clinical Insights of Resurgent Neurosyphilis" and was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.