Neurosyphilis – A Complete Patient‑Friendly Guide

Overview

Neurosyphilis is an infection of the central nervous system (CNS) that occurs when the bacterium Treponema pallidum (the cause of syphilis) spreads from the bloodstream to the brain, spinal cord, or meninges. It can develop at any stage of syphilis—primary, secondary, latent, or tertiary—but most commonly appears years after the initial infection if untreated.

• Who it affects: Anyone who acquires syphilis is at risk, but certain groups have higher rates:
  • Men who have sex with men (MSM)
  • People living with HIV
  • Individuals with multiple sexual partners or inconsistent condom use
• Prevalence: In the United States, syphilis cases rose 71 % from 2019 to 2022, reaching 2.4 cases per 100,000 people (CDC, 2023). Neurosyphilis occurs in roughly 5–10 % of untreated syphilis cases, though exact numbers are difficult to capture because symptoms can mimic other neurologic disorders.

Symptoms

Neurosyphilis presents with a wide spectrum of neurologic and psychiatric manifestations. The clinical picture depends on which part of the CNS is involved.

Early (or meningeal) Neurosyphilis

• Headache – often dull, persistent, and worsens with movement.
• Neck stiffness (meningismus) – may be mistaken for meningitis.
• Fever and malaise.
• Photophobia (sensitivity to light).
• Gait disturbances – unsteady walking, vertigo.

Parenchymal (or general paresis) Neurosyphilis

• Cognitive decline – memory loss, difficulty concentrating, “brain fog.”
• Personality changes – irritability, depression, mania, or psychosis.
• Speech problems – slurred or unintelligible speech (dysarthria).
• Motor deficits – weakness, tremor, or spasticity.
• Seizures – focal or generalized.

Vascular Neurosyphilis (Syphilitic Myelitis/Stroke‑like)

• Acute or sub‑acute stroke symptoms – sudden weakness, facial droop, visual field loss.
• Headache with focal neurologic signs.
• Transient ischemic attacks (mini‑strokes) — often recurrent.

Spinal (tabes dorsalis) Neurosyphilis

• Lightning‑like pains in the legs or trunk (positive Romberg sign).
• Loss of proprioception – difficulty knowing the position of limbs, leading to unsteady gait.
• Urinary incontinence or retention.
• Sexual dysfunction.

Other possible manifestations

• Optic neuritis – vision loss or blurred vision.
• Hearing loss or tinnitus.
• Peripheral neuropathy – tingling, numbness.
• Neuropsychiatric symptoms that mimic Alzheimer’s disease or Parkinson’s disease.

Causes and Risk Factors

Neurosyphilis is caused by the same spirochete that causes all stages of syphilis: Treponema pallidum. The organism can cross the blood‑brain barrier during any stage of infection, especially when the immune system is compromised.

Primary cause

• Unprotected sexual contact with an infected person (vaginal, anal, or oral). The bacterium enters through mucous membranes or minor skin abrasions.

Risk factors that increase the likelihood of CNS involvement

• HIV co‑infection: HIV reduces immune surveillance, allowing spirochetes to disseminate more easily (CDC, 2022).
• Late or untreated syphilis: The longer the infection remains untreated, the higher the chance of CNS spread.
• Alcoholism & drug use: May impair judgment leading to risky sexual behavior and weaken immunity.
• Pregnancy: Congenital syphilis can affect the fetal CNS, but maternal neurosyphilis is rare.
• Age: Older adults may have atypical presentations and slower clearance of the bacterium.

Diagnosis

Because symptoms overlap with many neurologic diseases, a combination of serologic testing, cerebrospinal fluid (CSF) analysis, and imaging is required.

1. Serologic tests for syphilis

• Nontreponemal tests: VDRL (Venereal Disease Research Laboratory) and RPR (Rapid Plasma Reagin). Useful for screening and monitoring treatment response.
• Treponemal tests: FTA‑ABS (Fluorescent Treponemal Antibody‑Absorption) and TP‑PA (Treponema pallidum particle agglutination). Confirmatory, remain positive for life.

2. Cerebrospinal fluid (CSF) examination

All patients with suspected neurosyphilis should undergo a lumbar puncture.

• CSF VDRL: The only test with high specificity for neurosyphilis; a positive result confirms the diagnosis.
• CSF cell count: Elevated white blood cells (typically lymphocytic pleocytosis).
• Protein: Increased CSF protein (>45 mg/dL) is common.
• CSF FTA‑ABS: Very sensitive but less specific; used when VDRL is negative but suspicion remains high.

3. Neuroimaging

• MRI of brain and spine: May show meningeal enhancement, cortical atrophy, infarcts, or spinal cord signal changes in tabes dorsalis.
• CT scan: Useful in emergency settings to rule out hemorrhage or large infarcts.

4. Additional tests

• Electroencephalogram (EEG) – can detect seizures or diffuse slowing in general paresis.
• Neuropsychological testing – helps quantify cognitive deficits.

Key point: A normal serum VDRL does not rule out neurosyphilis if the patient has high clinical suspicion; CSF testing is essential.

Treatment Options

The cornerstone of therapy is intravenous penicillin, which achieves bactericidal concentrations in the CSF.

1. First‑line antimicrobial therapy

• Aqueous crystalline penicillin G 18–24 million units per day, administered as 3–4 million units IV every 4 hours for 10‑14 days (CDC Treatment Guidelines, 2021).
• Alternative for penicillin‑allergic patients: Desensitization** followed by penicillin (preferred) or, if impossible, IV ceftriaxone 2 g daily for 10‑14 days (supported by limited data).

2. Follow‑up CSF testing

• Repeat lumbar puncture at 6‑month intervals until CSF cell count normalizes (<5 cells/µL) and VDRL becomes non‑reactive.
• Persistent abnormalities after 2 years may indicate treatment failure or reinfection.

3. Adjunctive therapies

• Antiepileptic drugs for seizure control (e.g., levetiracetam, carbamazepine).
• Physical and occupational therapy for gait and motor deficits.
• Cognitive rehabilitation for memory/attention problems.

4. Lifestyle and supportive measures

• Avoid alcohol and recreational drugs that can worsen neurologic function.
• Maintain a balanced diet rich in B‑vitamins and omega‑3 fatty acids to support nerve health.
• Adhere to scheduled follow‑up appointments; missing doses of penicillin can lead to relapse.

Living with Neurosyphilis

Even after successful treatment, many patients experience lingering neurologic deficits. A multidisciplinary approach helps maximise quality of life.

• Medication adherence: Set daily alarms or use a pill‑box.
• Regular neurologic check‑ups: Every 6‑12 months for the first two years, then annually.
• Therapies:
  • Physical therapy for balance and strength.
  • Speech‑language therapy if dysarthria persists.
  • Neuropsychology or counseling for mood disorders.
• Safety modifications: Install grab bars, use non‑slip mats, and ensure adequate lighting to prevent falls.
• Support networks: Connect with local or online groups for people with syphilis or chronic neurological conditions.
• Sexual health: Notify all recent partners, use condoms consistently, and undergo repeat testing until both serology and CSF are cleared.

Prevention

The best strategy is to prevent the initial syphilis infection and to treat it promptly before CNS spread.

• Safe sexual practices: Use latex or polyurethane condoms for every sexual act; consider dental dams for oral contact.
• Regular screening: At least yearly for sexually active adults, and every 3–6 months for MSM, people living with HIV, or those with multiple partners (CDC, 2023).
• Partner notification: Encourage recent partners to get tested and treated.
• Vaccinations: While no vaccine exists for syphilis, staying up‑to‑date on hepatitis B and HPV vaccines reduces overall STI risk.
• Prompt treatment of primary/secondary syphilis: A single IM dose of benzathine penicillin G (2.4 million units) eradicates the organism before it can reach the CNS.

Complications

If left untreated, neurosyphilis can cause irreversible damage.

• Permanent cognitive impairment: Dementia‑like syndrome, loss of independence.
• Motor dysfunction: Spastic paresis, ataxia, or permanent paralysis.
• Visual loss: Optic atrophy or retinal vasculitis.
• Hearing loss: Sensorineural deafness.
• Stroke: Recurrent syphilitic vasculitis leads to ischemic events.
• Psychiatric illness: Chronic psychosis or severe depression that may require long‑term psychiatric care.
• Congenital infection: In pregnant women, untreated syphilis can lead to stillbirth, neonatal death, or severe neurologic deficits in the newborn.

When to Seek Emergency Care

References

• Centers for Disease Control and Prevention. Syphilis – CDC Fact Sheet. 2023.
• Mayo Clinic. Syphilis: Symptoms & Causes. Updated 2022.
• World Health Organization. Syphilis Fact Sheet. 2022.
• National Institutes of Health. Neurosyphilis. In: StatPearls, 2024.
• Cleveland Clinic. Syphilis Overview. 2023.
• CDC. Sexually Transmitted Infections Treatment Guidelines – Syphilis. 2021.