Original articleLevetiracetam vs. sulthiame in benign epilepsy with centrotemporal spikes in childhood: A double-blinded, randomized, controlled trial (German HEAD Study)
Introduction
Benign epilepsy with centrotemporal spikes is the most common partial epilepsy in childhood accounting for 15–20% of all cases of epilepsy in this age group.1 It has been placed recently within epilepsy syndromes of unknown etiology of the latest ILAE classification of epileptic syndromes.2 The most characteristic seizure types are unilateral sensorimotor seizures of the oropharynx most commonly occurring during sleep. Generalized tonic-clonic seizures occur in up to 44% of cases.3 The typical EEG pattern consists of sharp waves occurring mainly over the centrotemporal region with marked increase in frequency during light sleep with genetic linkage to chromosome 15q14.4, 5 BECTS is commonly classified as a benign condition with complete remission of seizures in adolescents in the vast majority of cases. However, neuropsychological dysfunction and behavioral abnormalities are encountered in a considerable number of patients.6, 7 Controversy exists about whether or not and when to start antiepileptic drug therapy in patients with BECTS.1, 8 In addition, there are considerable geographic differences regarding which specific AED is used. While sulthiame appears to be the most commonly drug used in some Middle-European countries as Germany and Austria,9 valproic acid was defined more appropriate in others10 and carbamazepine/oxcarbazepine are the drugs of choice in the US followed by gabapentin, lamotrigine and levetiracetam.11
Sulthiame has been shown to reduce both seizure frequency and the number of interictal epileptic discharges in the EEG in a randomized placebo-controlled trial.12, 13 Recently, concerns have been raised about sulthiame impairing cognitive functions in patients with BECTS though the study population was low.14 Levetiracetam has not yet been investigated in randomized controlled trials on patients with BECTS, though data have shown efficacy and tolerability in both partial and generalized epilepsies in childhood.15, 16
The aim of the present study was to investigate efficacy, tolerability and safety of levetiracetam and sulthiame in a double-blinded, randomized head-to-head approach in patients with BECTS.
Section snippets
Study design and study population
This randomized, double-blinded, controlled trial was conducted over a period of 26 months between July 2006 (first patient in) and September 2008 (last patient out) involving 47 German centers (EudraCT No. 2005-004468-22). This study was initially planned as a non-inferiority trial of LEV compared to STM. The study was performed in accordance with the Declaration of Helsinki and its recent amendments. The ethical review boards of each study center approved the study design. All patients and/or
Patient recruitment
A total of 83 patients were screened for eligibility to enter the study. 44 patients were finally recruited within a recruitment period of 18 months between July 2006 and February 2008. The remaining subjects (n = 39) screened did not enter the study for the following reasons: parents refused consent to participate (n = 17, 43.6%), patients did not meet the inclusion criteria (n = 12, 30.8%), other reasons (n = 10, 25.6%, Fig. 2). There were no differences in the recruitment rates between
Discussion
In this randomized-controlled trial the efficacy of levetiracetam and sulthiame in patients with benign epilepsy with centrotemporal spikes was compared. The primary goal was analysis for non-inferiority of LEV treatment in BECTS compared to STM. However, the number of patients included in the study was too low to allow for such analysis. Given the small number of patients, efficacy of LEV and STM to avoid seizures within the observational period of 24 weeks did not differ significantly.
Disclosure related to contents of this article
We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with these guidelines.
I.B. received speaker fees from UCB Pharma, Eisai, Novartis and Desitin.
M. B. received travel imbursement from UCB Pharma.
T. B. received fees for presentations and participations on advisory boards from UCB Pharma, Eisai and Desitin.
B.-A. N. received fees for presentations and advisory board meetings from UCB Pharma, Eisai and Desitin
K.-J.
Funding
UCB Pharma SA, Brussels, Belgium, funded partly this study.
Acknowledgments
We thank the members of the advisory board of the study CE Elger (Bonn, Germany), UH Mansmann (Munich, Germany) and BJ Steinhoff (Kehl-Kork, Germany). We thank Dr. Jan Rémi (Department of Neurology, University of Munich) for carefully reviewing the manuscript.
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