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OBJECTIVE: Neurosyphilis commonly presents with cognitive impairment, and penicillin remains the treatment of choice. However, despite a rapid increase in syphilis incidence, the effect of penicillin on long-term cognitive outcomes has not previously been evaluated. We therefore aimed to assess the effect of penicillin on cognitive function in neurosyphilis. METHODS: We performed a systematic review of all studies of neurosyphilis, where cognitive function was assessed objectively both before and after penicillin therapy for at least one patient. Where Mini-Mental State Examination (MMSE) scores were taken, we performed a paired-samples t test to assess the change in cognitive function and aimed to correlate this with change in serological titers. RESULTS: Nine studies met inclusion criteria. The one cohort study reported a nonsignificant overall improvement in MMSE, while amalgamation of case reports produced a significant improvement (P=.02) in MMSE after treatment. However, follow-up duration was inadequate, and data were insufficient to correlate changes in cognitive function with serological markers. CONCLUSIONS: Despite evidence of short-term improvement, there are insufficient data to support the long-term benefit of penicillin therapy on cognitive function in neurosyphilis.

Original publication




Journal article


Gen Hosp Psychiatry

Publication Date





49 - 52


Cognition, Mini-Mental State Examination, Neurosyphilis, Penicillin, Cognition Disorders, Humans, Neurosyphilis, Penicillins