Tertiary syphilis
ICD-10 A52 · ICD-11 1A62.Z

Treatment of Tertiary Syphilis in Neurosyphilis: Positive Serology with Neurological Symptoms

When tertiary syphilis presents alongside neurological involvement — confirmed by positive syphilis serology and clinical features of neurosyphilis — a specific, structured treatment approach is required. This protocol covers that scenario.

Clinical scenario — Neurosyphilis Positive syphilis serology accompanied by symptoms suggestive of neurological involvement, such as cognitive dysfunction, motor or sensory deficits, cranial nerve dysfunction, or signs and symptoms of meningitis or stroke. Every patient meeting this profile warrants a thorough neurological examination.
Treatment approach (partial overview) Management involves a multi-week course of antibiotic therapy, with corticosteroid cover initiated before antibiotics begin. Multiple antibiotic regimen options exist and are selected according to clinical circumstances. The complete protocol — including all regimen choices, routes, and the steroid schedule — is available via the link below.
Treatment goals: A measurable decrease in cerebrospinal fluid white blood cell count and CSF protein level, assessed by follow-up CSF examination performed 6 weeks to 6 months after completing treatment.
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References

Every patient with a positive serological test for syphilis and symptoms suggestive of neurological involvement (such as cognitive dysfunction, motor or sensory deficits, cranial nerve dysfunction or symptoms/signs of meningitis or stroke) should have a thorough neurological examination.

Procaine penicillin 1.8–2.4 MU IM OD PLUS probenecid 500 mg PO QDS for 14 days: 1C.

Benzylpenicillin 10.8–14.4 g OD, given as 1.8–2.4 g IV every 4 h for 14 days: 1C.

Ceftriaxone 2 g IM or IV for 10–14 days: 2D.

Doxycycline 200 mg PO BD for 28 days: 2D.

Amoxycillin 2 g PO TDS PLUS probenecid 500 mg PO QDS for 28 days: 2D.

Steroids should be given with all anti-treponemal antibiotics for neurosyphilis; 40–60 mg prednisolone OD for 3 days starting 24 h before the antibiotics.

Follow-up examination of CSF should be performed 6 weeks to 6 months after treatment of neurosyphilis to monitor the decrease in white blood cell count and protein level: 2D.

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