{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:42:43Z","timestamp":1792154563054,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["MCNT2\u20102023\u201012377646"],"award-info":[{"award-number":["MCNT2\u20102023\u201012377646"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to evaluate the efficacy and safety of adjunctive, highly purified Cannabidiol (Epidiolex\u00ae) in individuals with drug\u2010resistant epilepsy (DRE) due to genetically determined typical Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We recruited subjects with genetically confirmed typical RTT and CDD with drug\u2010resistant seizures who received add\u2010on treatment with highly purified Cannabidiol (CBD) through a national collaboration group. CBD treatment was titrated from 5 to 20\u2009mg\/kg\/day; concurrent antiseizure medications (ASMs) could have been adjusted as clinically indicated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We enrolled 27 subjects (26 females), carrying a\n                      <jats:italic>MECP2<\/jats:italic>\n                      genetic variant (14 subjects, 51.9%) or a\n                      <jats:italic>CDKL5<\/jats:italic>\n                      genetic variant (13 subjects, 48.1%). Median age [IRQ] of individuals was 10.5 [7.9, 18.5] years. The median dose of CBD [IRQ] at last follow\u2010up was 15 [11.12, 18.8] mg\/kg\/day, in association with a mean of 3 ASMs (range 2\u20134). The median duration of treatment was 14 [8.5, 20] months. Although not reaching a significant statistical effect, CBD reduced the incidence of seizures with respect to the baseline in 18\/27 (66.6%) subjects, with 7 (25.9%) showing a seizure reduction &gt;75%, and 11 (40.7%) &gt;50%. The most relevant adverse events were somnolence seen in 3 subjects, irritability\/agitation in 2 subjects, loss of appetite in 2 subjects, and insomnia in 1 individual. Caregivers reported an improvement in attention and reactivity in 12 subjects (44.4%), in sleep quality in 5 subjects (18.5%), and in motor aspects in 3 patients (11.1%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>CBD resulted effective in reducing seizure frequency in 66.6% of the study sample, regardless of the pathogenic variant; side effects were mild, and caregivers reported an improvement in behavioral and motor features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>This study explored the use of highly purified Cannabidiol (CBD, Epidiolex\u00ae) as an add\u2010on therapy for individuals with drug\u2010resistant epilepsy due to Rett Syndrome (RTT) or CDKL5 Deficiency Disorder (CDD). Twenty\u2010seven participants received CBD alongside their usual ASMs. After a median treatment duration of 14\u2009months, 66.6% experienced fewer seizures, with some showing over 75% reduction. Side effects were generally mild, mainly sleepiness or irritability. Notably, caregivers reported improvements in attention, responsiveness, sleep, and motor function. While results were not statistically significant, they suggest CBD may benefit seizure control and quality of life in RTT and CDD patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70078","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T12:53:37Z","timestamp":1750510417000},"page":"1111-1119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Is highly purified cannabidiol a treatment opportunity for drug\u2010resistant epilepsy in subjects with typical Rett syndrome and\n                    <scp>CDKL5<\/scp>\n                    deficiency disorder?"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-4663","authenticated-orcid":false,"given":"Aglaia","family":"Vignoli","sequence":"first","affiliation":[{"name":"Childhood and Adolescence Neuropsychiatry Unit Grande Ospedale Metropolitano Niguarda  Milan Italy"},{"name":"Health Sciences Department Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Prato","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry IRCCS Istituto Giannina Gaslini, Full Member of European Reference Network EpiCARE  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Alfei","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Buzzi Children's Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Bagnasco","sequence":"additional","affiliation":[{"name":"Division of Child Neuropsychiatry Martini Hospital  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Danieli","sequence":"additional","affiliation":[{"name":"Epilepsy Unit IRCCS E. Medea Scientific Institute  Conegliano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Celario","sequence":"additional","affiliation":[{"name":"Department of Child Neurology and Psychiatry IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-2398","authenticated-orcid":false,"given":"Jacopo","family":"Favaro","sequence":"additional","affiliation":[{"name":"Department of Women's and Child's Health University of Padua  Padova Italy"},{"name":"Paediatric Neurology and Neurophysiology Unit \u2013 University Hospital of Padua  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Matricardi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Chieti  Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2444-8761","authenticated-orcid":false,"given":"Francesca Felicia","family":"Operto","sequence":"additional","affiliation":[{"name":"Department of Science of Health School of Medicine University Magna Greacia of Catanzaro  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Orsini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, University Hospital of Pisa Azienda Ospedaliero Universitaria Pisana  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide Paolo","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Center, School of Medicine and Surgery University of Milano\u2010Bicocca  Italy"},{"name":"Clinical Research and Innovation Unit Grande Ospedale Metropolitano Niguarda  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pietrafusa","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy and Movement Disorders Unit Bambino Ges\u00f9 Children's Hospital IRCCS, Full Member of European Reference Network EpiCARE  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Health Sciences Department Universit\u00e0 degli Studi di Milano  Milan Italy"},{"name":"Child Neurology Unit, Epilepsy Center San Paolo Hospital, Member of European Reference Network EpiCARE  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Manfredini","sequence":"additional","affiliation":[{"name":"Paediatric Chronic Pain and Palliative Care Service IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Balletto","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry IRCCS Istituto Giannina Gaslini, Full Member of European Reference Network EpiCARE  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Epilepsy Unit IRCCS E. Medea Scientific Institute  Conegliano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Canevini","sequence":"additional","affiliation":[{"name":"Health Sciences Department Universit\u00e0 degli Studi di Milano  Milan Italy"},{"name":"Child Neurology Unit, Epilepsy Center San Paolo Hospital, Member of European Reference Network EpiCARE  Milan 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":"Department of Child Neurology and Psychiatry IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia 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