{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T05:04:34Z","timestamp":1785042274001,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004744","name":"Innoviris","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004744","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Benzodiazepines (BZDs) are the recommended first\u2010line treatment in early status epilepticus (SE). At least 30% of episodes are resistant, leading to established SE. Chronic BZD use may induce pharmacological tolerance. We hypothesized that chronic exposure to BZDs may reduce their efficacy as first\u2010line treatment in early SE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective case\u2013control study included SE episodes from 2010 to 2023 at a tertiary center in Brussels. Postanoxic and Alcohol\u2010 or BZD withdrawal\u2010related SE episodes were excluded, as well as those in which BZDs were not used as first\u2010line treatment. Chronic BZD use was defined as a daily use for at least 6\u2009months. Chronic BZD users (cases) were matched 1:1 with nonusers (controls) for age, sex, etiology, and semiology. Univariable and multivariable comparisons were performed. The primary outcome was evolution of early SE to established SE, defined as the use of second\u2010line treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ninety\u2010eight cases and 98 controls were included and matched. Chronic use of BZDs was associated with more frequent need for second\u2010line treatment or evolution to established SE (85% vs. 64%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.022). Established SE (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009146) was also associated with longer in\u2010hospital stay (15 vs. 5\u2009days,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001) and more complications (Complications Burden Index: 1 vs. 2.5,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001). After adjusting for both timing and dose of first\u2010line treatment, multivariable analysis confirmed chronic BZD use as an independent risk factor for established SE (odds ratio\u2009=\u20093.34, 95% confidence interval\u2009=\u20091.66\u20137.03,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.001). Among chronic users, no association was observed between modalities of BZD chronic use (dose, half\u2010life time, duration) and the establishment or refractoriness of SE episodes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Chronic BZD use is associated with a higher rate of second\u2010line treatment administration in SE, suggesting greater resistance to acute BZD administration. This association should be considered when managing early SE. Chronic BZD use should be considered with extreme caution in patients with epilepsy at risk of SE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70111","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:50:27Z","timestamp":1768974627000},"page":"2190-2200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Response of early status epilepticus to benzodiazepines in chronic benzodiazepine users: A case\u2013control study"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-3947","authenticated-orcid":false,"given":"Charlotte","family":"Damien","sequence":"first","affiliation":[{"name":"Neurology Department, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Laboratory of Experimental Neurology Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Neurology Department, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Torcida","sequence":"additional","affiliation":[{"name":"Neurology Department, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Laboratory of Experimental Neurology Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"De Maeseneire","sequence":"additional","affiliation":[{"name":"Neurology Department, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Legros","sequence":"additional","affiliation":[{"name":"Neurology Department, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Depondt","sequence":"additional","affiliation":[{"name":"Neurology Department, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Gaspard","sequence":"additional","affiliation":[{"name":"Neurology Department, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Laboratory of Experimental Neurology Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Neurology Department Yale University School of 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