What is the recommended treatment for neurosyphilis?

Neurosyphilis Treatment and Management

The recommended first-line treatment for neurosyphilis is aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units IV every 4 hours or by continuous infusion, for 10-14 days. 1, 2, 3

Diagnosis and Clinical Presentation

Neurosyphilis can occur at any stage of syphilis infection and presents with various neurological manifestations:

• Common presentations:

  • Cognitive dysfunction
  • Motor or sensory deficits
  • Cranial nerve palsies
  • Meningitis symptoms
  • Ophthalmic or auditory symptoms
  • Seizures
  • Stroke-like symptoms

• Diagnostic criteria:

  • Reactive serum treponemal tests
  • Neurologic manifestations consistent with neurosyphilis
  • CSF abnormalities (pleocytosis, elevated protein, positive CSF-VDRL)

Treatment Regimens

First-Line Treatment

• Aqueous crystalline penicillin G: 18-24 million units per day, administered as 3-4 million units IV every 4 hours or by continuous infusion, for 10-14 days 1, 2, 3

Alternative Regimens

• Procaine penicillin: 2.4 million units IM once daily PLUS probenecid 500 mg orally four times a day, both for 10-14 days 1, 2

• For penicillin-allergic patients: Ceftriaxone 2 g daily either IM or IV for 10-14 days (note: possibility of cross-reactivity exists) 1, 2

• Additional therapy: Benzathine penicillin G 2.4 million units IM once per week for up to 3 weeks after completion of neurosyphilis treatment to provide comparable total duration of therapy to that used for late syphilis 1, 2

Follow-Up Protocol

• CSF examination: Repeat every 6 months until the cell count normalizes 1, 2

  • CSF cell count (pleocytosis) is the most sensitive measure of treatment effectiveness
  • CSF-VDRL and protein normalize more slowly than cell count

• Retreatment indications: 1, 2

  • If CSF cell count has not decreased after 6 months
  • If CSF cell count or protein is not normal after 2 years
  • If clinical symptoms persist or recur

• Serological monitoring: Follow serum RPR titers for 12-24 months; a fourfold decrease indicates good response 1, 2

Special Considerations

HIV Co-infection

• HIV-infected patients may have poorer serological and CSF responses to treatment 1, 4
• The same treatment regimens are recommended for HIV-infected patients 1
• All persons with syphilis should be tested for HIV 1, 2
• HIV-infected patients may have unusual serologic responses, including higher titers or delayed seroreactivity 1

Ocular/Otic Syphilis

• Patients with syphilitic eye disease should be managed according to neurosyphilis recommendations in collaboration with an ophthalmologist 1, 2
• Systemic steroids are often used as adjunctive therapy for otologic syphilis, though benefit is unproven 1, 2

Treatment Pitfalls and Caveats

1. Inadequate dosing: Low-dose penicillin regimens may not achieve treponemicidal concentrations in the CNS 5

2. Incomplete follow-up: Failure to monitor CSF normalization may miss treatment failures 1, 2

3. Penicillin allergy management: Consider skin testing and desensitization for patients with penicillin allergy when ceftriaxone is contraindicated 1

4. Treatment failure in HIV: Higher rates of treatment failure may occur in HIV-infected patients, requiring closer monitoring 4

5. Serofast state: 15-20% of patients may remain "serofast" with low, unchanging titers after successful treatment, which does not necessarily represent treatment failure 1

6. Jarisch-Herxheimer reaction: Patients should be monitored for this acute febrile reaction that can occur within 24 hours of treatment initiation

Remember that neurosyphilis treatment requires careful monitoring and follow-up to ensure eradication of the infection and resolution of neurological symptoms.