• Kim Boshuisen, Monique M J van Schooneveld, Cuno S P M Uiterwaal, J Helen Cross, Sue Harrison, Tilman Polster, Marion Daehn, Sarina Djimjadi, Dilek Yalnizoglu, Guzide Turanli, Robert Sassen, Christian Hoppe, Stefan Kuczaty, Carmen Barba, Philippe Kahane, Susanne Schubert-Bast, Gitta Reuner, Thomas Bast, Karl Strobl, Hans Mayer, Anne de Saint-Martin, Caroline Seegmuller, Agathe Laurent, Alexis Arzimanoglou, Kees P J Braun, and TimeToStop cognitive outcome study group.
• Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
• Ann. Neurol. 2015 Jul 1;78(1):104-14.

ObjectiveAntiepileptic 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.MethodsWe 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.ResultsMean 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).InterpretationStart 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.© 2015 American Neurological Association.

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