{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:01:03Z","timestamp":1790748063938,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Rett syndrome (RTT) is a severe neurodevelopmental disorder frequently associated with drug\u2010resistant epilepsy, autonomic dysfunction, respiratory abnormalities, sleep disturbances, and behavioral impairment. Fenfluramine has shown efficacy in developmental and epileptic encephalopathies and may provide broader therapeutic benefits through modulation of serotonergic and sigma\u20101 receptor pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a prospective, open\u2010label, single\u2010center study to evaluate the efficacy, safety, and tolerability of adjunctive fenfluramine in patients with classic RTT carrying pathogenic\n                      <jats:italic>MECP2<\/jats:italic>\n                      variants. Clinical assessments were performed at baseline and after 3 and 6\u2009months of treatment. Outcomes included seizure frequency; clinician\u2010reported measures of RTT severity, including the Clinical Global Impression\u2013Improvement (CGI\u2010I) scale, Clinical Severity Scale (CSS), and Motor Behavior Assessment (MBA); caregiver\u2010reported measures, including the Rett Syndrome Behavior Questionnaire (RSBQ), Sleep Disturbance Scale for Children (SDSC), the EQ\u20105D\u20105L quality of life scale; and neurophysiological measures using auditory evoked potentials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight patients with classic RTT and drug\u2010resistant epilepsy were included. Median age was 12\u2009years (range, 6\u201317\u2009years), and the median number of previously failed antiseizure medications was 5 (range, 2\u201310). All patients achieved a &gt;50% reduction in seizure frequency. Significant improvements were observed in clinician\u2010reported outcomes, including CGI\u2010I, CSS, and MBA scores, and in caregiver\u2010reported behavioral symptoms assessed with the RSBQ at 3 and 6\u2009months (\u22127 and \u22129, respectively). Sleep disturbances improved markedly, with normalization of SDSC scores in all patients by month 6. Respiratory dysfunction, including hyperventilation\u2010related symptoms, improved during follow\u2010up. Neurophysiological assessments showed improved attentional and auditory discrimination processing in a subset of patients. Adverse events occurred in 71% of patients, most commonly somnolence; no patient discontinued treatment because of tolerability issues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Fenfluramine was associated with clinically meaningful improvements across several symptom domains in patients with RTT, including seizures, respiratory dysfunction, behavior, sleep, and overall disease severity, with an acceptable safety profile. Further evaluation of fenfluramine as a potential multisymptomatic treatment strategy in RTT in prospective controlled studies is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Rett syndrome is a rare genetic disorder with complex symptoms that affect many aspects of daily life. In this study, fenfluramine was associated with improvements in seizures and several other important symptoms, including behavior, sleep, breathing, and clinical severity. The treatment was generally well tolerated. These results support further studies to determine whether fenfluramine could become a treatment for multiple symptoms of Rett syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70355","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:50:56Z","timestamp":1790747456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fenfluramine in Rett syndrome: A multidimensional clinical study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0247-9187","authenticated-orcid":false,"given":"Elena","family":"Gonzalez\u2010Alguacil","sequence":"first","affiliation":[{"name":"Pediatric Neurology Department Hospital Infantil Universitario Ni\u00f1o Jes\u00fas  Madrid Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid 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