Kim Boshuisen1, Monique M J van Schooneveld2, Cuno S P M Uiterwaal3, J Helen Cross4, Sue Harrison5, Tilman Polster6, Marion Daehn6, Sarina Djimjadi6, Dilek Yalnizoglu7, Guzide Turanli7, Robert Sassen8, Christian Hoppe8, Stefan Kuczaty8, Carmen Barba9, Philippe Kahane10, Susanne Schubert-Bast11, Gitta Reuner11, Thomas Bast11,12, Karl Strobl12, Hans Mayer12, Anne de Saint-Martin13, Caroline Seegmuller13, Agathe Laurent14, Alexis Arzimanoglou14,15, Kees P J Braun1. 1. Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. 2. Department of Child Psychology, University Medical Center Utrecht, the Netherlands. 3. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 4. 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. 5. Neuroscience Department, University College London Institute of Child Health and Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom. 6. Bethel Epilepsy Center, Bielefeld, Germany. 7. Department of Pediatric Neurology, Hacettepe University Children's Hospital, Ankara, Turkey. 8. University of Bonn Medical Center, Bonn, Germany. 9. Pediatric Neurology Unit, A. Meyer Children's Hospital-University of Florence, Florence, Italy. 10. Neurology Department, Michallon Hospital, Grenoble Alpes University, Grenoble, France. 11. University Children's Hospital, Heidelberg, Germany. 12. Kork Epilepsy Center, Kehl, Germany. 13. Strasbourg University Hospital, Strasbourg, France. 14. Department of Epilepsy, Sleep, and Pediatric Neurophysiology, Woman Mother Child Hospital, University Hospitals of Lyon, Lyon, France. 15. Brain Dynamics and Cognition Team, Lyon Neuroscience Research Center, Lyon, France.
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). INTERPRETATION: 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.
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). INTERPRETATION: 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: Manish N Shah; Anish Mitra; Manu S Goyal; Abraham Z Snyder; Jing Zhang; Joshua S Shimony; David D Limbrick; Marcus E Raichle; Matthew D Smyth Journal: Childs Nerv Syst Date: 2018-03-06 Impact factor: 1.475
Authors: Barbora Benova; Anezka Belohlavkova; Petr Jezdik; Alena Jahodová; Martin Kudr; Vladimir Komarek; Vilem Novak; Petr Liby; Robert Lesko; Michal Tichý; Martin Kyncl; Josef Zamecnik; Pavel Krsek; Alice Maulisova Journal: PeerJ Date: 2019-10-08 Impact factor: 2.984
Authors: Samuel W Terman; Carole E Aubert; Chloe E Hill; Donovan T Maust; John P Betjemann; Cynthia M Boyd; James F Burke Journal: Epilepsy Behav Date: 2020-07-03 Impact factor: 2.937