What is neurosyphilis (infection of the central nervous system caused by Treponema pallidum)?

From the Guidelines

Neurosyphilis should be treated with high-dose intravenous penicillin G, specifically 18-24 million units daily, administered as 3-4 million units every 4 hours for 10-14 days, as recommended by the most recent guidelines 1. The diagnosis of neurosyphilis is established by examination of the cerebrospinal fluid (CSF), which may indicate mild mononuclear pleocytosis, normal or mildly elevated protein concentration, or a reactive CSF-VDRL 1.

Key Considerations

• Patients with clinical evidence of neurologic involvement, such as cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of meningitis, should undergo a CSF examination 1.
• Syphilitic uveitis or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis 1.
• Patients who have neurosyphilis or syphilitic eye disease should be treated with the recommended regimen for neurosyphilis, and those with eye disease should be managed in collaboration with an ophthalmologist 1.

Treatment Regimens

• The recommended regimen for neurosyphilis is aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion, for 10-14 days 1.
• An alternative regimen is procaine penicillin 2.4 million units IM once daily, plus probenecid 500 mg orally four times a day, both for 10-14 days, if compliance with therapy can be ensured 1.

Follow-Up

• Patients should undergo regular follow-up with cerebrospinal fluid examinations at 6-month intervals until cell count normalizes and serologic tests show improvement 1.
• If CSF pleocytosis was present initially, a CSF examination should be performed to assess treatment response 1.

From the Research

Definition and Diagnosis of Neurosyphilis

• Neurosyphilis is defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid 2.
• The diagnosis of neurosyphilis depends on serologic tests and cerebrospinal fluid (CSF) examination, which can be complicated by the suboptimal sensitivity and specificity of these tests, particularly among patients coinfected with HIV 3.
• CSF examination should be performed to evaluate for neurosyphilis in all patients with positive serum syphilis serology and neurologic, ophthalmic, or tertiary disease, or in those who have failed therapy, and in HIV-infected patients with late latent syphilis or syphilis of unknown duration 3.

Treatment of Neurosyphilis

• Intravenous penicillin G is the recommended treatment for all forms of neurosyphilis and for syphilitic eye disease 3.
• An outpatient alternative, if adherence can be assured, is intramuscular benzathine penicillin with oral probenecid 3.
• Newer drugs that penetrate CSF, such as ceftriaxone or azithromycin, have not yet been adequately tested for neurosyphilis 3.
• Oral doxycycline may be an effective and safe alternative regimen to intravenous or intramuscular penicillin for the treatment of neurosyphilis in HIV-infected patients 4.

Management and Follow-up of Neurosyphilis

• Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms 5.
• If CSF pleocytosis is evident at initial CSF examination, these examinations should be repeated every 6 months until the cell count is normal 5.
• HIV-infected persons with syphilis of any stages whose RPR titers are ≥ 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis 5.
• The burden of neurosyphilis and its clinical significance in the antibiotic era are important considerations in the management of syphilis 6.