Volume 78, Issue 1 pp. 104-114

Research Article

Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery

Kim Boshuisen MD,

Kim Boshuisen MD

Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands

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Monique M. J. van Schooneveld MSc,

Monique M. J. van Schooneveld MSc

Department of Child Psychology, University Medical Center Utrecht, the Netherlands

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Cuno S. P. M. Uiterwaal MD, PhD,

Cuno S. P. M. Uiterwaal MD, PhD

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands

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J. Helen Cross MD, PhD,

J. Helen Cross MD, PhD

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

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Sue Harrison MSc,

Sue Harrison MSc

Neuroscience Department, University College London Institute of Child Health and Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom

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Tilman Polster MD,

Tilman Polster MD

Bethel Epilepsy Center, Bielefeld, Germany

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Marion Daehn MSc,

Marion Daehn MSc

Bethel Epilepsy Center, Bielefeld, Germany

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Sarina Djimjadi MSc,

Sarina Djimjadi MSc

Bethel Epilepsy Center, Bielefeld, Germany

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Dilek Yalnizoglu MD,

Dilek Yalnizoglu MD

Department of Pediatric Neurology, Hacettepe University Children's Hospital, Ankara, Turkey

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Guzide Turanli MD,

Guzide Turanli MD

Department of Pediatric Neurology, Hacettepe University Children's Hospital, Ankara, Turkey

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Robert Sassen MD,

Robert Sassen MD

University of Bonn Medical Center, Bonn, Germany

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Christian Hoppe MSc, PhD,

Christian Hoppe MSc, PhD

University of Bonn Medical Center, Bonn, Germany

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Stefan Kuczaty MD,

Stefan Kuczaty MD

University of Bonn Medical Center, Bonn, Germany

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Carmen Barba MD, PhD,

Carmen Barba MD, PhD

Pediatric Neurology Unit, A. Meyer Children's Hospital–University of Florence, Florence, Italy

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Philippe Kahane MD, PhD,

Philippe Kahane MD, PhD

Neurology Department, Michallon Hospital, Grenoble Alpes University, Grenoble, France

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Susanne Schubert-Bast MD,

Susanne Schubert-Bast MD

University Children's Hospital, Heidelberg, Germany

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Gitta Reuner MSc, PhD,

Gitta Reuner MSc, PhD

University Children's Hospital, Heidelberg, Germany

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Thomas Bast MD, PhD,

Thomas Bast MD, PhD

University Children's Hospital, Heidelberg, Germany

Kork Epilepsy Center, Kehl, Germany

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Karl Strobl MD,

Karl Strobl MD

Kork Epilepsy Center, Kehl, Germany

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Hans Mayer PhD,

Hans Mayer PhD

Kork Epilepsy Center, Kehl, Germany

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Anne de Saint-Martin MD,

Anne de Saint-Martin MD

Strasbourg University Hospital, Strasbourg, France

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Caroline Seegmuller MD,

Caroline Seegmuller MD

Strasbourg University Hospital, Strasbourg, France

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Agathe Laurent MSc,

Agathe Laurent MSc

Department of Epilepsy, Sleep, and Pediatric Neurophysiology, Woman Mother Child Hospital, University Hospitals of Lyon, Lyon, France

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Alexis Arzimanoglou MD, PhD,

Alexis Arzimanoglou MD, PhD

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

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Kees P. J. Braun MD, PhD,

Corresponding Author

Kees P. J. Braun MD, PhD

Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands

Address correspondence to Prof. Dr. Braun, Department of (Child) Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands, Room KC.03.063.0, PO Box 85090, 3508 AB Utrecht, the Netherlands. E-mail: [email protected]Search for more papers by this author

for the TimeToStop cognitive outcome study group,

for the TimeToStop cognitive outcome study group

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Kim Boshuisen MD,

Kim Boshuisen MD

Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands

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Monique M. J. van Schooneveld MSc,

Monique M. J. van Schooneveld MSc

Department of Child Psychology, University Medical Center Utrecht, the Netherlands

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Cuno S. P. M. Uiterwaal MD, PhD,

Cuno S. P. M. Uiterwaal MD, PhD

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands

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J. Helen Cross MD, PhD,

J. Helen Cross MD, PhD

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Sue Harrison MSc,

Sue Harrison MSc

Neuroscience Department, University College London Institute of Child Health and Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom

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Tilman Polster MD,

Tilman Polster MD

Bethel Epilepsy Center, Bielefeld, Germany

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Marion Daehn MSc,

Marion Daehn MSc

Bethel Epilepsy Center, Bielefeld, Germany

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Sarina Djimjadi MSc,

Sarina Djimjadi MSc

Bethel Epilepsy Center, Bielefeld, Germany

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Dilek Yalnizoglu MD,

Dilek Yalnizoglu MD

Department of Pediatric Neurology, Hacettepe University Children's Hospital, Ankara, Turkey

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Guzide Turanli MD,

Guzide Turanli MD

Department of Pediatric Neurology, Hacettepe University Children's Hospital, Ankara, Turkey

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Robert Sassen MD,

Robert Sassen MD

University of Bonn Medical Center, Bonn, Germany

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Christian Hoppe MSc, PhD,

Christian Hoppe MSc, PhD

University of Bonn Medical Center, Bonn, Germany

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Stefan Kuczaty MD,

Stefan Kuczaty MD

University of Bonn Medical Center, Bonn, Germany

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Carmen Barba MD, PhD,

Carmen Barba MD, PhD

Pediatric Neurology Unit, A. Meyer Children's Hospital–University of Florence, Florence, Italy

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Philippe Kahane MD, PhD,

Philippe Kahane MD, PhD

Neurology Department, Michallon Hospital, Grenoble Alpes University, Grenoble, France

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Susanne Schubert-Bast MD,

Susanne Schubert-Bast MD

University Children's Hospital, Heidelberg, Germany

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Gitta Reuner MSc, PhD,

Gitta Reuner MSc, PhD

University Children's Hospital, Heidelberg, Germany

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Thomas Bast MD, PhD,

Thomas Bast MD, PhD

University Children's Hospital, Heidelberg, Germany

Kork Epilepsy Center, Kehl, Germany

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Karl Strobl MD,

Karl Strobl MD

Kork Epilepsy Center, Kehl, Germany

Search for more papers by this author

Hans Mayer PhD,

Hans Mayer PhD

Kork Epilepsy Center, Kehl, Germany

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Anne de Saint-Martin MD,

Anne de Saint-Martin MD

Strasbourg University Hospital, Strasbourg, France

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Caroline Seegmuller MD,

Caroline Seegmuller MD

Strasbourg University Hospital, Strasbourg, France

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Agathe Laurent MSc,

Agathe Laurent MSc

Department of Epilepsy, Sleep, and Pediatric Neurophysiology, Woman Mother Child Hospital, University Hospitals of Lyon, Lyon, France

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Alexis Arzimanoglou MD, PhD,

Alexis Arzimanoglou MD, PhD

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

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Kees P. J. Braun MD, PhD,

Corresponding Author

Kees P. J. Braun MD, PhD

Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands

for the TimeToStop cognitive outcome study group,

for the TimeToStop cognitive outcome study group

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First published: 21 April 2015

https://doi.org/10.1002/ana.24427

Citations: 105

Members of the TimeToStop cognitive outcome study group are available as an online supplementary file.

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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. Ann Neurol 2015;78:104–114

Supporting Information

References

1 Shields WD. Catastrophic epilepsy in childhood. Epilepsia 2000; 41(suppl 2): S2–S6.
10.1111/j.1528-1157.2000.tb01518.x
PubMed Web of Science® Google Scholar
2 Cross JH. Epilepsy surgery in childhood. Epilepsia 2002; 43(suppl 3): 65–70.
10.1046/j.1528-1157.43.s.3.6.x
PubMed Web of Science® Google Scholar
3 Van Schooneveld MM, Braun KP. Cognitive outcome after epilepsy surgery in children. Brain Dev 2013; 35: 721–729.
10.1016/j.braindev.2013.01.011
PubMed Web of Science® Google Scholar
4 Kaindl AM, Asimiadou S, Manthey D, et al. Antiepileptic drugs and the developing brain. Cell Mol Life Sci 2006; 63: 399–413.
10.1007/s00018-005-5348-0
CAS PubMed Web of Science® Google Scholar
5 Ikonomidou C, Turski L. Antiepileptic drugs and brain development. Epilepsy Res 2010; 88: 11–22.
10.1016/j.eplepsyres.2009.09.019
CAS PubMed Web of Science® Google Scholar
6 Loring DW, Meador KJ. Cognitive side effects of antiepileptic drugs in children. Neurology 2004; 62: 872–877.
10.1212/01.WNL.0000115653.82763.07
CAS PubMed Web of Science® Google Scholar
7 Meador KJ. Cognitive outcomes and predictive factors in epilepsy. Neurology 2002; 58(8 suppl 5): S21–S26.
10.1212/WNL.58.8_suppl_5.S21
PubMed Web of Science® Google Scholar
8 Mula M, Trimble MR. Antiepileptic drug-induced cognitive adverse effects: potential mechanisms and contributing factors. CNS Drugs 2009; 23: 121–137.
10.2165/00023210-200923020-00003
CAS PubMed Web of Science® Google Scholar
9 Braun KP, Schmidt D. Stopping antiepileptic drugs in seizure-free patients. Curr Opin Neurol 2014; 27: 219–226.
10.1097/WCO.0000000000000075
CAS PubMed Web of Science® Google Scholar
10 Lossius MI, Hessen E, Mowinckel P, et al. Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study). Epilepsia 2008; 49: 455–463.
10.1111/j.1528-1167.2007.01323.x
PubMed Web of Science® Google Scholar
11 Hessen E, Lossius MI, Reinvang I, Gjerstad L. Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy. Epilepsia 2006; 47: 2038–2045.
10.1111/j.1528-1167.2006.00805.x
CAS PubMed Web of Science® Google Scholar
12 Aldenkamp AP, Alpherts WC, Blennow G, et al. Withdrawal of antiepileptic medication in children—effects on cognitive function: the Multicenter Holmfrid Study. Neurology 1993; 43: 41–50.
10.1212/WNL.43.1_Part_1.41
PubMed Web of Science® Google Scholar
13 Aldenkamp AP, Alpherts WC, Sandstedt P, et al. Antiepileptic drug-related cognitive complaints in seizure-free children with epilepsy before and after drug discontinuation. Epilepsia 1998; 39: 1070–1074.
10.1111/j.1528-1157.1998.tb01292.x
CAS PubMed Web of Science® Google Scholar
14 van Schooneveld MM, van Erp N, Boshuisen K, et al. Withdrawal of antiepileptic drugs improves psychomotor speed after childhood epilepsy surgery. Epilepsy Res 2013; 107: 200–203.
10.1016/j.eplepsyres.2013.08.004
CAS PubMed Web of Science® Google Scholar
15 Hallbook T, Tideman P, Rosen I, et al. Epilepsy surgery in children with drug-resistant epilepsy, a long-term follow-up. Acta Neurol Scand 2013; 128: 414–421.
10.1111/ane.12154
CAS PubMed Web of Science® Google Scholar
16 Meekes J, Braams O, Braun KP, et al. Verbal memory after epilepsy surgery in childhood. Epilepsy Res 2013; 107: 146–155.
10.1016/j.eplepsyres.2013.08.017
PubMed Web of Science® Google Scholar
17 Skirrow C, Cross JH, Cormack F, et al. Long-term intellectual outcome after temporal lobe surgery in childhood. Neurology 2011; 76: 1330–1337.
10.1212/WNL.0b013e31821527f0
CAS PubMed Web of Science® Google Scholar
18 Boshuisen K, Arzimanoglou A, Cross JH, et al. Timing of antiepileptic drug withdrawal and long-term seizure outcome after paediatric epilepsy surgery (TimeToStop): a retrospective observational study. Lancet Neurol 2012; 11: 784–791.
10.1016/S1474-4422(12)70165-5
CAS PubMed Web of Science® Google Scholar
19 Boshuisen K, Schmidt D, Uiterwaal CS, et al. Time to relapse after epilepsy surgery in children: AED withdrawal policies are a contributing factor. Epileptic Disord 2014; 16: 305–311.
10.1684/epd.2014.0681
PubMed Web of Science® Google Scholar
20 Spencer S, Huh L. Outcomes of epilepsy surgery in adults and children. Lancet Neurol 2008; 7: 525–537.
10.1016/S1474-4422(08)70109-1
PubMed Web of Science® Google Scholar
21 Prayson BE, Prayson RA, Kubu CS, et al. Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy. Epilepsy Behav 2013; 28: 426–431.
10.1016/j.yebeh.2013.05.040
PubMed Web of Science® Google Scholar
22 Hessen E, Lossius MI, Gjerstad L. Antiepileptic monotherapy significantly impairs normative scores on common tests of executive functions. Acta Neurol Scand 2009; 119: 194–198.
10.1111/j.1600-0404.2008.01109.x
CAS PubMed Web of Science® Google Scholar
23 Helmstaedter C, Witt JA. Do antiepileptic drug changes affect cognitive outcome after epilepsy surgery? Epilepsia 2014; 55(suppl 2):175 (abstract p540).
PubMed Google Scholar
24 Ortinski P, Meador KJ. Cognitive side effects of antiepileptic drugs. Epilepsy Behav 2004; 5(suppl 1): S60–S65.
10.1016/j.yebeh.2003.11.008
PubMed Web of Science® Google Scholar
25 Sarco DP, Bourgeois BF. The safety and tolerability of newer antiepileptic drugs in children and adolescents. CNS Drugs 2010; 24: 399–430.
10.2165/11310980-000000000-00000
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume78, Issue1

July 2015

Pages 104-114

Filename	Description
ana24427-sup-0001-suppinfo.docx13.9 KB	Supplementary Information
ana24427-sup-0001-supptbls.docx24.7 KB	Supplementary Tables

Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery

Abstract

Objective

Methods

Results

Interpretation

Supporting Information

References

Citing Literature

References

Information

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Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery

Abstract

Objective

Methods

Results

Interpretation

Supporting Information

References

Citing Literature

References

Related

Information