{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:20:01Z","timestamp":1756383601270,"version":"3.37.3"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T00:00:00Z","timestamp":1522972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001262","name":"Baily Thomas Charitable Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008771","name":"Tourette Association of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008771","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006662","name":"National Institute on Handicapped Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Tuberous sclerosis complex (<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>) is a multisystem genetic disorder caused by mutations in <jats:italic><jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>1<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>2<\/jats:italic>. Epilepsy occurs in 80%\u201090% of affected individuals during their lifetime, and up to one\u2010third of children with <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> will develop epileptic (infantile) spasms, for which vigabatrin has been shown to be particularly effective. Epilepsy severity and epileptic spasms are consistent markers of risk for the development of intellectual impairment in <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>. Although previous studies demonstrate a bimodal distribution of intellectual ability in <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>, recent findings suggest a unimodal distribution, which may reflect a change in <jats:styled-content style=\"fixed-case\">IQ<\/jats:styled-content> distribution over time. We compared 3 large historical <jats:styled-content style=\"fixed-case\">UK<\/jats:styled-content> cohorts of <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> (n = 331) that show varied distributions of intellectual ability, first ruling out differences in study methodology. Later\u2010born individuals had a higher frequency of reported spasms and higher likelihood of vigabatrin administration, but were less likely to have profound intellectual impairment, compared to the earlier\u2010born individuals. Our findings suggest that epileptic spasms went undetected in the older patients and therefore were not treated, leading to a higher occurrence of profound impairment, whereas the later born cohort had better access to treatment. These findings support the importance of early identification and treatment of seizures in <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/epi4.12111","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T15:46:38Z","timestamp":1520264798000},"page":"276-280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Secular changes in severity of intellectual disability in tuberous sclerosis complex: A reflection of improved identification and treatment of epileptic spasms?"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-9547","authenticated-orcid":false,"given":"Charlotte","family":"Tye","sequence":"first","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry and MRC Social Genetic &amp; Developmental Psychiatry Centre Institute of Psychiatry, Psychology &amp; Neuroscience King's College London London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura E.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics Institute of Medical Genetics Cardiff University School of Medicine Cardiff United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian R.","family":"Sampson","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics Institute of Medical Genetics Cardiff University School of Medicine Cardiff United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Lewis","sequence":"additional","affiliation":[{"name":"Mental Health and Learning Disabilities Division Anuerin Bevan University Health Board Newport United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finbar","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"Institute of Child Health University College London London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R. W.","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Cambridge Cambridge United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick F.","family":"Bolton","sequence":"additional","affiliation":[{"name":"Department of Child &amp; Adolescent Psychiatry and MRC Social Genetic &amp; Developmental Psychiatry Centre Institute of Psychiatry, Psychology &amp; Neuroscience King's College London London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02474.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12484"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738040190090601"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2017.02.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12484"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291715000264"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000280578.99900.96"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.012757"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.241"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291702007092"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2011.211995"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-004-0383-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2011.10.005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000280579.04974.c0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8335-5"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2011.08.037"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2009.03.003"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2015.09.013"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.04.009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2011.03.010"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.05.014"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fepi4.12111","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T07:29:54Z","timestamp":1694849394000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,6]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/epi4.12111"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12111","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"type":"print","value":"2470-9239"},{"type":"electronic","value":"2470-9239"}],"subject":[],"published":{"date-parts":[[2018,4,6]]},"assertion":[{"value":"2018-02-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}