title: Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery.
abstract: OBJECTIVE
  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-term 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.
  
  
  METHODS
  We collected IQ scores of children from the TTS cohort with both pre- and postoperative neuropsychological assessments (NPAs; n = 301) 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.
  
  
  RESULTS
  Mean interval to the latest NPA was 19.8 ± 18.9 months. Reduction of AEDs at the latest NPA significantly improved postoperative IQ and delta IQ (adjusted regression coefficient [RC] = 3.4, 95% confidence interval [CI] = 0.6-6.2, p = 0.018 and RC = 4.5, 95% CI = 1.7-7.4, p = 0.002), as did complete withdrawal (RC = 4.8, 95% CI = 1.4-8.3, p = 0.006 and RC = 5.1, 95% CI = 1.5-8.7, p = 0.006). AED reduction also predicted ≥ 10-point IQ increase (p = 0.019). The higher the number of AEDs reduced, the higher was the IQ (gain) after surgery (RC = 2.2, 95% CI = 0.6-3.7, p = 0.007 and RC = 2.6, 95% CI = 1.0-4.2, p = 0.001, IQ points per AED reduced).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Boshuisen
authors.affiliation: Department of Child Psychology, University Medical Center Utrecht, the Netherlands.
authors.forename: Monique M J
authors.initials: MM
authors.lastname: van Schooneveld
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Cuno S P M
authors.initials: CS
authors.lastname: Uiterwaal
authors.affiliation: 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.
authors.forename: J Helen
authors.initials: JH
authors.lastname: Cross
authors.affiliation: Neuroscience Department, University College London Institute of Child Health and Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom.
authors.forename: Sue
authors.initials: S
authors.lastname: Harrison
authors.affiliation: Bethel Epilepsy Center, Bielefeld, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Polster
authors.affiliation: Bethel Epilepsy Center, Bielefeld, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Daehn
authors.affiliation: Bethel Epilepsy Center, Bielefeld, Germany.
authors.forename: Sarina
authors.initials: S
authors.lastname: Djimjadi
authors.affiliation: Department of Pediatric Neurology, Hacettepe University Children's Hospital, Ankara, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Yalnizoglu
authors.affiliation: Department of Pediatric Neurology, Hacettepe University Children's Hospital, Ankara, Turkey.
authors.forename: Guzide
authors.initials: G
authors.lastname: Turanli
authors.affiliation: University of Bonn Medical Center, Bonn, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Sassen
authors.affiliation: University of Bonn Medical Center, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hoppe
authors.affiliation: University of Bonn Medical Center, Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kuczaty
authors.affiliation: Pediatric Neurology Unit, A. Meyer Children's Hospital-University of Florence, Florence, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Barba
authors.affiliation: Neurology Department, Michallon Hospital, Grenoble Alpes University, Grenoble, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kahane
authors.affiliation: University Children's Hospital, Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schubert-Bast
authors.affiliation: University Children's Hospital, Heidelberg, Germany.
authors.forename: Gitta
authors.initials: G
authors.lastname: Reuner
authors.affiliation: University Children's Hospital, Heidelberg, Germany.|Kork Epilepsy Center, Kehl, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bast
authors.affiliation: Kork Epilepsy Center, Kehl, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Strobl
authors.affiliation: Kork Epilepsy Center, Kehl, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Mayer
authors.affiliation: Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: de Saint-Martin
authors.affiliation: Strasbourg University Hospital, Strasbourg, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Seegmuller
authors.affiliation: Department of Epilepsy, Sleep, and Pediatric Neurophysiology, Woman Mother Child Hospital, University Hospitals of Lyon, Lyon, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Laurent
authors.affiliation: Department of Epilepsy, Sleep, and Pediatric Neurophysiology, Woman Mother Child Hospital, University Hospitals of Lyon, Lyon, France.|Brain Dynamics and Cognition Team, Lyon Neuroscience Research Center, Lyon, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Arzimanoglou
authors.affiliation: Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Kees P J
authors.initials: KP
authors.lastname: Braun
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000150:complications / Q000601:surgery*; D002648:Child; D003071:Cognition; D003072:Cognition Disorders / Q000139:chemically induced*; D015331:Cohort Studies; D004827:Epilepsy / Q000209:etiology / Q000628:therapy*; D005260:Female; D006801:Humans; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000601:surgery*; D009483:Neuropsychological Tests; D019635:Neurosurgical Procedures; D011184:Postoperative Period; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants