{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:49:39Z","timestamp":1791370179873,"version":"4.3.1"},"reference-count":11,"publisher":"SMC Media","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Introduction: Neurosyphilis is a treatable mimic of viral and autoimmune limbic encephalitis. The prozone phenomenon\u2014antibody excess preventing the antigen\u2013antibody lattice\u2014can 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 Treponema pallidum haemagglutination assay was added; it was positive, and serially diluted serum yielded a reactive RPR (endpoint titre 1:32), revealing a prozone false negative. Cerebrospinal fluid studies confirmed neurosyphilis, and the patient recovered fully after penicillin. 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 T. pallidum had been started on admission, effective treatment was not delayed. Conclusion: When syphilis is suspected, a negative undiluted RPR does not exclude it; pairing a treponemal test with the RPR\u2014or adopting a treponemal-first screening strategy\u2014guards against prozone-related false negatives.<\/jats:p>","DOI":"10.12890\/2026_007473","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:32:52Z","timestamp":1790598772000},"source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.12890","volume":"13","author":[{"given":"Hidenori","family":"Sanayama","sequence":"first","affiliation":[{"name":"Division of General Medicine, Department of Comprehensive Medicine 1, Jichi Medical University Saitama Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Comprehensive Medicine 1, Jichi Medical University Saitama Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Fykuchi","sequence":"additional","affiliation":[{"name":"Division of General Medicine, Department of Comprehensive Medicine 1, Jichi Medical University Saitama Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10397","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"10.12890\/2026_007473_ref1","doi-asserted-by":"crossref","unstructured":"Komori A, Mori H, Xie W, Valenti S, Naito T. Rapid resurgence of syphilis in Japan after the COVID-19 pandemic: A descriptive study. PLoS One. 2024;19(3):e0298288. doi: 10.1371\/journal.pone.0298288.","DOI":"10.1371\/journal.pone.0298288"},{"key":"10.12890\/2026_007473_ref2","doi-asserted-by":"crossref","unstructured":"Ropper AH. Neurosyphilis. N Engl J Med. 2019;381(14):1358-1363. doi: 10.1056\/NEJMra1906228. Erratum in: N Engl J Med. 2019;381(18):1789. doi: 10.1056\/NEJMx190030. Erratum in: N Engl J Med. 2023;389(19):1828. doi: 10.1056\/NEJMx230008.","DOI":"10.1056\/NEJMra1906228"},{"key":"10.12890\/2026_007473_ref3","doi-asserted-by":"crossref","unstructured":"Fujimoto H, Imaizumi T, Nishimura Y, Miura Y, Ayabe M, Shoji H, et al. Neurosyphilis showing transient global amnesia-like attacks and magnetic resonance imaging abnormalities mainly in the limbic system. 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MMWR Recomm Rep. 2024;73(1):1-32. doi: 10.15585\/mmwr.rr7301a1.","DOI":"10.15585\/mmwr.rr7301a1"},{"key":"10.12890\/2026_007473_ref7","doi-asserted-by":"crossref","unstructured":"Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. doi: 10.15585\/mmwr.rr7004a1. Erratum in: MMWR Morb Mortal Wkly Rep. 2023;72(4):107-108. doi: 10.15585\/mmwr.mm7204a5.","DOI":"10.15585\/mmwr.mm7204a5"},{"key":"10.12890\/2026_007473_ref8","doi-asserted-by":"crossref","unstructured":"Liu LL, Lin LR, Tong ML, Zhang HL, Huang SJ, Chen YY, et al. Incidence and risk factors for the prozone phenomenon in serologic testing for syphilis in a large cohort. Clin Infect Dis. 2014;59(3):384-9. doi: 10.1093\/cid\/ciu325.","DOI":"10.1093\/cid\/ciu325"},{"key":"10.12890\/2026_007473_ref9","doi-asserted-by":"crossref","unstructured":"Liao H, Zhang Y, Yue W. Case Report: A Case Report of Neurosyphilis Mimicking Limbic Encephalitis. Front Neurol. 2022;13:862175. doi: 10.3389\/fneur.2022.862175.","DOI":"10.3389\/fneur.2022.862175"},{"key":"10.12890\/2026_007473_ref10","doi-asserted-by":"crossref","unstructured":"Bettuzzi T, Jourdes A, Robineau O, Alcaraz I, Manda V, Molina JM, et al. Ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis in France: a retrospective multicentre study. Lancet Infect Dis. 2021;21(10):1441-1447. doi: 10.1016\/S1473-3099(20)30857-4. Erratum in: Lancet Infect Dis. 2021;21(10):e302. doi: 10.1016\/S1473-3099(21)00477-1.","DOI":"10.1016\/S1473-3099(21)00477-1"},{"key":"10.12890\/2026_007473_ref11","unstructured":"Cantor A, Nelson HD, Daeges M, Pappas M. Screening for Syphilis in Nonpregnant Adolescents and Adults: Systematic Review to Update the 2004 U.S. Preventive Services Task Force Recommendation [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Jun. 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