Treatment of Syphilis-Related Stroke in Young Patients
Young patients with stroke caused by neurosyphilis must be treated with intravenous aqueous crystalline penicillin G 18-24 million units per day (administered as 3-4 million units every 4 hours or continuous infusion) for 10-14 days. 1
Critical Initial Steps
When a young patient presents with stroke, neurosyphilis should be strongly suspected if:
- Absence of traditional vascular risk factors (hypertension, diabetes, hyperlipidemia) 2, 3
- Cryptogenic stroke without clear etiology on standard workup 3
- HIV coinfection (present in approximately one-third of cases) 4, 5
- History of high-risk sexual behavior or multiple partners 4
Diagnostic Confirmation Required Before Treatment
CSF examination is mandatory to confirm neurosyphilis before initiating treatment: 6
- CSF VDRL (specific but less sensitive)
- CSF cell count (elevated white blood cells suggest active infection) 3
- CSF protein (typically elevated)
- Serum treponemal and nontreponemal tests (RPR/VDRL) 2
The CDC explicitly states that patients with neurologic manifestations including stroke require prompt CSF examination. 6
Definitive Treatment Regimen
The only acceptable treatment for neurosyphilis causing stroke is:
- Aqueous crystalline penicillin G 18-24 million units per day IV for 10-14 days 1
- Administered as 3-4 million units every 4 hours OR continuous infusion 1
This regimen applies regardless of HIV status, though HIV-positive patients require more frequent follow-up (every 3 months versus every 6 months). 1
Management of Penicillin Allergy
Penicillin desensitization is required if the patient has a documented penicillin allergy, as no proven alternatives exist for neurosyphilis. 6, 1
However, if desensitization is not feasible:
- Ceftriaxone has been used in case reports (2g IV daily for 14 days), though this is not FDA-approved and requires close monitoring 6, 2
- One case report documented successful treatment with ceftriaxone in a penicillin-allergic patient with neurosyphilis-related stroke 2
- The CDC states that data are insufficient regarding ceftriaxone, and if used, close serologic and CSF follow-up are mandatory 6
Critical Pitfalls to Avoid
Do not use benzathine penicillin G for neurosyphilis—this formulation does not achieve adequate CSF concentrations and is only appropriate for early/late latent syphilis without neurologic involvement. 1
Do not delay treatment while awaiting confirmatory tests if clinical suspicion is high, as untreated neurosyphilis carries a significantly higher risk of recurrent stroke compared to other vascular risk factors. 2
Do not assume stroke is solely due to traditional risk factors in young patients—even those with diabetes or other comorbidities may have neurosyphilis as the primary or contributing cause. 2, 3
Post-Treatment Monitoring
Following completion of IV penicillin therapy:
- Repeat CSF examination at 6 months to document treatment response 6
- CSF should show declining cell counts and protein levels 6
- If CSF remains abnormal or worsens, retreatment is required 6
- Quantitative nontreponemal titers (RPR/VDRL) should be checked at 6,12, and 24 months 6
- Treatment failure is defined as failure of titers to decline fourfold within 12-24 months 1
HIV Testing Mandatory
All patients with syphilis must be tested for HIV, as coinfection is common and affects follow-up intensity. 6, 4 HIV-positive patients require serologic monitoring every 3 months rather than every 6 months. 1
Why This Matters for Stroke Prevention
Meningovascular syphilis causes inflammatory arteritis of cerebral vessels, leading to vascular occlusion and infarction. 2 The condition is frequently underdiagnosed—only 19% of neurosyphilis-related strokes are correctly identified initially. 2 Early diagnosis and treatment with IV penicillin are essential to prevent recurrent strokes, as well as progression to dementia and other neurologic complications. 2, 3