Should the Traditional Algorithm for Syphilis Screening be Abandoned? Neurosyphilis Presenting as Limbic Encephalitis: A Prozone False-Negative RPR Missed by an RPR-Only Initial Screen.

Introduction: Neurosyphilis is a treatable mimic of viral and autoimmune limbic encephalitis. The prozone phenomenon-antibody excess preventing the antigen-antibody lattice-can render an undiluted non-treponemal test such as the rapid plasma reagin (RPR) test falsely negative, with reactivity restored on dilution. Case description: A 37-year-old man presented with seizures and rapidly progressive limbic encephalitis; Brain magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery sequences showed hyperintensities in the amygdalae, periventricular regions, left insula and left putamen. On admission, the possibility of a sexually transmitted infection was considered, but only an RPR was requested, and it was negative. When the encephalitis failed to respond to empirical antiviral, antibacterial and corticosteroid therapy, a Discussion: With an RPR-only screen, the non-treponemal/treponemal discordance that typically signals a prozone never arose, so the false negative was accepted at face value; the delay reflected the prozone compounded by the initial testing strategy. Because empirical ceftriaxone active against Conclusion: When syphilis is suspected, a negative undiluted RPR does not exclude it; pairing a treponemal test with the RPR-or adopting a treponemal-first screening strategy-guards against prozone-related false negatives. LEARNING POINTS: When a sexually transmitted infection is being considered, obtain a careful, respectful sexual history and request non-treponemal and treponemal tests together; a rapid plasma reagin -only screen cannot reveal the non-treponemal/treponemal discordance that signals a prozone false negative. A treponemal-first (reverse-sequence) algorithm avoids this particular pitfall.A negative undiluted RPR does not exclude syphilis: the prozone phenomenon occurs even at low-to-moderate titres and in human immunodeficiency virus-negative patients, so serial dilution should be requested when clinical suspicion is high.Neurosyphilis is a treatable mimic of limbic encephalitis; outcome depends on prompt effective therapy, and including a treponemal-active agent (e.g. ceftriaxone) in empirical meningoencephalitis coverage may limit harm from diagnostic delay.