{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:20:39Z","timestamp":1792016439116,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["Grant No: 602391\u20132; w\u200aw\u200aw\u200a.epistop\u200a.eu"],"award-info":[{"award-number":["Grant No: 602391\u20132; w\u200aw\u200aw\u200a.epistop\u200a.eu"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open\u2010label trial (OLT). Subjects were followed until 2\u2009years of age. The primary endpoint was the time to first clinical seizure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty\u2010seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment [RCT: 364\u2009days (95% confidence interval [CI] =\u2009223\u2013535) vs 124\u2009days (95% CI = 33\u2013149); OLT: 426\u2009days (95% CI = 258\u2013628) vs 106\u2009days (95% CI = 11\u2013149)]. At 24\u2009months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.032), drug\u2010resistant epilepsy (OR = 0.23,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.022), and infantile spasms (OR = 0,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). No adverse events related to preventive treatment were noted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2021;89:304\u2013314<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25956","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T13:55:47Z","timestamp":1605189347000},"page":"304-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":255,"title":["Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the\n                    <scp>EPISTOP<\/scp>\n                    Trial"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-250X","authenticated-orcid":false,"given":"Katarzyna","family":"Kotulska","sequence":"first","affiliation":[{"name":"Department of Neurology and Epileptology The Children's Memorial Health Institute  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Curatolo","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Systems Medicine Department Tor Vergata University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Weschke","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Charit\u00e9 University Medicine Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Riney","sequence":"additional","affiliation":[{"name":"Neurosciences Unit Queensland Children's Hospital  South Brisbane QLD Australia"},{"name":"School of Medicine University of Queensland  St Lucia QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Brain Center University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Feucht","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Krsek","sequence":"additional","affiliation":[{"name":"Motol University Hospital, Charles University  Prague 5 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Nabbout","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Necker\u2010 Enfants Malades Hospital University Paris Descartes, Imagine Institute  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit\u2010UZ Brussel  Brussels Belgium"},{"name":"Neurogenetics Research Group Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Wojdan","sequence":"additional","affiliation":[{"name":"Transition Technologies  Warsaw Poland"},{"name":"Warsaw University of Technology, Institute of Heat Engineering  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Sijko","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology The Children's Memorial Health Institute  Warsaw Poland"},{"name":"Transition Technologies  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagoda","family":"G\u0142owacka\u2010Walas","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology The Children's Memorial Health Institute  Warsaw Poland"},{"name":"Warsaw University of Technology, The Faculty of Electronics and Information Technology  Warsaw 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