The effect of levetiracetam on focal nocturnal epileptiform activity during sleep — A placebo-controlled double-blind cross-over study Pål Gunnar Larsson a, ⁎, Kristin A. Bakke b , Helge Bjørnæs b , Einar Heminghyt b , Elisif Rytter b , Line Brager-Larsen c , Ann-Sofie Eriksson b a Department of Neurosurgery, Oslo University Hospital, Norway b The National Center for Epilepsy, Oslo University Hospital, Norway c Vestre Viken Hospital Thrust, Drammen, Norway abstract article info Article history: Received 19 December 2011 Revised 28 January 2012 Accepted 27 February 2012 Available online 10 April 2012 Keywords: Electric Status Epilepticus during Sleep (ESES) Continuous Spike Wave during Slow Sleep (CSWS) EEG Levetiracetam Cognitive impairment Landau–Kleffner syndrome Autism spectrum disorder ADHD Spike index Electric Status Epilepticus during Sleep (ESES) occurs in children with and without epilepsy. It may be related to disturbances as autism spectrum disorder, attention-deficit hyperactivity disorder and acquired aphasia (Landau–Kleffner syndrome). Antiepileptic drug (AED) treatment has been reported in small studies without placebo control. This study was designed to assess AED effect in a placebo-controlled double-blind cross-over study. Levetiracetam (LEV) was chosen based on clinical evidence. Eighteen patients fulfilled the inclusion criteria. The mean spike index at baseline was 56, falling to a mean of 37 at the end of the LEV treatment pe- riod. Assessed with a 2-way ANOVA, there is a significant treatment effect (p b 0.0002). To the best of our knowledge, this is the first placebo-controlled double-blind cross-over study for any AED in patients with ESES. The effect of LEV is comparable with its effect in treatment of epileptic seizures. © 2012 Elsevier Inc. All rights reserved. 1. Introduction Nocturnal epileptiform activity significantly activated by sleep oc- curs in children with and without epilepsy. It is seen both in patients with idiopathic and symptomatic epilepsies [1,2]. ‘Electric Status Epilepticus induced by Sleep’ (ESES) was first reported in 1971 by Patry and coworkers [3], who described six children, five with epilep- sy and one with no epilepsy diagnosis. Two children, one with and one without epilepsy, never acquired speech, and one child with ep- ileptic seizures had very deficient language development. Two chil- dren experienced cognitive regression after 8 and 11 years of previous normal psychomotor development. Electric Status Epilepti- cus during Sleep was, in 1985, renamed to ‘Continuous Spike Wave during Slow Sleep’ (CSWS) [4]. CSWS has been related to two epilepsy syndromes: ‘Landau– Kleffner syndrome’ (LKS) [5] and ‘epilepsy with CSWS syndrome’ [6–8]. Originally, epileptiform activity during more than 85% of nonREM sleep time was required for labeling the activity as CSWS [4], but this is not part of the syndrome definition as proposed by the International League Against Epilepsy [6]. In clinical practice, the term CSWS, therefore, refers to patients with different electroclinical phenomena. Accordingly, Tassinari has proposed ESES as the name for EEG activity, and the term Penelope's syndrome to indicate the combination of deterioration of cognitive function and nocturnal epileptiform activity [9]. Hence, ESES is used here. The ESES activity has been associated with negative cognitive symptoms in many children. The above mentioned LKS was the first cognitive deficit recognized as being related to ESES, but autism spec- trum disorder (ASD) [10,11], attention-deficit hyperactive disorder (ADHD) [12] and other cognitive disturbances [13–15] have been reported in children with ESES. Children with epilepsy are at an increased risk for concomitant ADHD. The prevalence of ADHD in children with epilepsy is estimated to be between 14 and 38% [16,17]. Electroencephalography (EEG) has been reported to be abnormal in a larger proportion of children with ADHD, some also showing epileptiform activity. The reported preva- lence of epileptiform activity in children with ADHD ranges from 6.1% [18] to 30.1% [19,20]. Using video-polysomnography, a much higher prevalence of 53.1% has been found [12]. The latter patients were admitted due to sleep disturbances, which may, at least partly, Epilepsy & Behavior 24 (2012) 44–48 ⁎ Corresponding author at: Department of Neurosurgery, Oslo University Hospital, PO Box 4950, 0424 Nydalen, Norway. Fax: + 47 23074310. E-mail address: pal.gunnar.larsson@ous-hf.no (P.G. Larsson). 1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2012.02.024 Contents lists available at SciVerse ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh