{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:05:20Z","timestamp":1792591520667,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This real\u2010world, retrospective, multicenter study aims to investigate the effectiveness of highly purified cannabidiol (CBD) in a large cohort of patients with epilepsy of genetic etiology due to an identified monogenic cause. Additionally, we examine the potential relationship between specific genetic subgroups and treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study was conducted across 27 epilepsy centers and included patients with monogenic epileptic disorders (pathogenic or likely pathogenic variants) who were treated with highly purified CBD for at least 3\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 266 patients (135 females, 50.8%) with monogenic epilepsies were included with a median age at CBD initiation of 12\u2009years (interquartile range [IQR] =\u20097\u201319) and a median follow\u2010up duration of 17\u2009months (IQR\u2009=\u200912\u201324). Overall, 77 different monogenic epilepsies have been included, with the most common genes being\n                      <jats:italic>SCN1A<\/jats:italic>\n                      (32.3%),\n                      <jats:italic>TSC2<\/jats:italic>\n                      (13.5%),\n                      <jats:italic>CDKL5<\/jats:italic>\n                      , and\n                      <jats:italic>MECP2<\/jats:italic>\n                      (4.5% each). The mean seizure reduction at the last follow\u2010up was 38.6%, with 47.5% of patients achieving \u226550% seizure reduction and 7.4% achieving seizure freedom. The Clinical Global Impression scale indicated improvement in 65.8% of patients. The general linear mixed model revealed that a shorter maximum duration of seizure freedom before CBD initiation and a higher degree of intellectual disability were independently associated with lower CBD effectiveness. Conversely, no significant differences in seizure outcome were observed across different epilepsy syndromes (Lennox\u2013Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex epilepsy, and other developmental and epileptic encephalopathy), between approved indications and off\u2010label use, or between concomitant clobazam use or not.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This study supports CBD as a potential treatment for monogenic epilepsies beyond its licensed indications, demonstrating comparable effectiveness between approved and off\u2010label use and suggesting genetic subgroups with promising treatment responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18378","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T16:34:06Z","timestamp":1742920446000},"page":"2253-2267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real\u2010world study"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-555X","authenticated-orcid":false,"given":"Emanuele","family":"Cerulli Irelli","sequence":"first","affiliation":[{"name":"Department of Human Neurosciences Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Mazzeo","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0259-1046","authenticated-orcid":false,"given":"Roberto H.","family":"Caraballo","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. Garrahan\u201d  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Perulli","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Psychiatric Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-2087","authenticated-orcid":false,"given":"Patrick B.","family":"Moloney","sequence":"additional","affiliation":[{"name":"Department of Neurology Mater Misericordiae University Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-1292","authenticated-orcid":false,"given":"Javier","family":"Pe\u00f1a\u2010Ceballos","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marica","family":"Rubino","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive Sciences, and Odontostomatology Federico II University of Naples  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna M.","family":"Mieszczanek","sequence":"additional","affiliation":[{"name":"Danish Epilepsy Center  Dianalund Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Santangelo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Licchetta","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Delle Scienze Neurologiche di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5828-7070","authenticated-orcid":false,"given":"Valentina","family":"De Giorgis","sequence":"additional","affiliation":[{"name":"Brain and Behavioral Sciences Department University of Pavia  Pavia Italy"},{"name":"Department of Child Neurology and Psychiatry, Childhood and Adolescence Epilepsy Center Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Reyes Valenzuela","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P. 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