{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:07:43Z","timestamp":1790521663283,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T00:00:00Z","timestamp":1435017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006117","name":"Epilepsiefonds","doi-asserted-by":"publisher","award":["08-10"],"award-info":[{"award-number":["08-10"]}],"id":[{"id":"10.13039\/501100006117","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED withdrawal does not majorly influence long\u2010term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative intelligence quotient (IQ), and change in IQ (delta IQ) following pediatric epilepsy surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected IQ scores of children from the TTS cohort with both pre\u2010 and postoperative neuropsychological assessments (NPAs; n\u2009=\u2009301) and analyzed whether reduction of AEDs prior to the latest NPA was related to postoperative IQ and delta IQ, using linear regression analyses. Factors previously identified as independently relating to (delta) IQ, and currently identified predictors of (delta) IQ, were considered possible confounders and used for adjustment. Additionally, we adjusted for a compound propensity score that contained previously identified determinants of timing of AED withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean interval to the latest NPA was 19.8\u2009\u00b1\u200918.9 months. Reduction of AEDs at the latest NPA significantly improved postoperative IQ and delta IQ (adjusted regression coefficient [RC]\u2009=\u20093.4, 95% confidence interval [CI]\u2009=\u20090.6\u20136.2, <jats:italic>p<\/jats:italic>\u2009=\u20090.018 and RC\u2009=\u20094.5, 95% CI\u2009=\u20091.7\u20137.4, <jats:italic>p<\/jats:italic>\u2009=\u20090.002), as did complete withdrawal (RC\u2009=\u20094.8, 95% CI\u2009=\u20091.4\u20138.3, <jats:italic>p<\/jats:italic>\u2009=\u20090.006 and RC\u2009=\u20095.1, 95% CI\u2009=\u20091.5\u20138.7, <jats:italic>p<\/jats:italic>\u2009=\u20090.006). AED reduction also predicted \u226510\u2010point IQ increase (<jats:italic>p<\/jats:italic>\u2009=\u20090.019). The higher the number of AEDs reduced, the higher was the IQ (gain) after surgery (RC\u2009=\u20092.2, 95% CI\u2009=\u20090.6\u20133.7, <jats:italic>p<\/jats:italic>\u2009=\u20090.007 and RC\u2009=\u20092.6, 95% CI\u2009=\u20091.0\u20134.2, <jats:italic>p<\/jats:italic>\u2009=\u20090.001, IQ points per AED reduced).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Start of AED withdrawal, number of AEDs reduced, and complete AED withdrawal were associated with improved postoperative IQ scores and gain in IQ, independent of other determinants of cognitive outcome. Ann Neurol 2015;78:104\u2013114<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24427","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T05:18:56Z","timestamp":1429593536000},"page":"104-114","source":"Crossref","is-referenced-by-count":117,"title":["Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery"],"prefix":"10.1002","volume":"78","author":[{"given":"Kim","family":"Boshuisen","sequence":"first","affiliation":[{"name":"Department of Child Neurology Brain Center Rudolf Magnus, University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique M. J.","family":"van Schooneveld","sequence":"additional","affiliation":[{"name":"Department of Child Psychology University Medical Center Utrecht  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuno S. P. M.","family":"Uiterwaal","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Helen","family":"Cross","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences University College London Institute of Child Health, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London and Young Epilepsy  Lingfield United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Harrison","sequence":"additional","affiliation":[{"name":"Neuroscience Department University College London Institute of Child Health and Great Ormond Street Hospital for Children National Health Service Trust  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Polster","sequence":"additional","affiliation":[{"name":"Bethel Epilepsy Center  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Daehn","sequence":"additional","affiliation":[{"name":"Bethel Epilepsy Center  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Djimjadi","sequence":"additional","affiliation":[{"name":"Bethel Epilepsy Center  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"Yalnizoglu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hacettepe University Children's Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guzide","family":"Turanli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hacettepe University Children's Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sassen","sequence":"additional","affiliation":[{"name":"University of Bonn Medical Center  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hoppe","sequence":"additional","affiliation":[{"name":"University of Bonn Medical Center  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kuczaty","sequence":"additional","affiliation":[{"name":"University of Bonn Medical Center  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Barba","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit A. Meyer Children's Hospital\u2013University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Kahane","sequence":"additional","affiliation":[{"name":"Neurology Department Michallon Hospital, Grenoble Alpes University  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Schubert\u2010Bast","sequence":"additional","affiliation":[{"name":"University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitta","family":"Reuner","sequence":"additional","affiliation":[{"name":"University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bast","sequence":"additional","affiliation":[{"name":"University Children's Hospital  Heidelberg Germany"},{"name":"Kork Epilepsy Center  Kehl Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Strobl","sequence":"additional","affiliation":[{"name":"Kork Epilepsy Center  Kehl Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Mayer","sequence":"additional","affiliation":[{"name":"Kork Epilepsy Center  Kehl Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"de Saint\u2010Martin","sequence":"additional","affiliation":[{"name":"Strasbourg University Hospital  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Seegmuller","sequence":"additional","affiliation":[{"name":"Strasbourg University Hospital  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Laurent","sequence":"additional","affiliation":[{"name":"Department of Epilepsy Sleep, and Pediatric Neurophysiology, Woman Mother Child Hospital, University Hospitals of Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Arzimanoglou","sequence":"additional","affiliation":[{"name":"Department of Epilepsy Sleep, and Pediatric Neurophysiology, Woman Mother Child Hospital, University Hospitals of Lyon Lyon France"},{"name":"Brain Dynamics and Cognition Team Lyon Neuroscience Research Center  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees P. 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