Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy

Infantile and early childhood epileptic syndromes

In 1976, Ohtahara et al. described an epilepsy syndrome affecting very young infants with a suppression burst (SB) pattern on the EEG that frequently evolved into West syndrome and Lennox-Gastaut syndrome [1] and termed it “early infantile epileptic encephalopathy with suppression-burst” [2]. The eponym Ohtahara syndrome (OS) came into prominent use in the mid-1980s [3]. In 1978, early myoclonic encephalopathy (EME) was first described in neonates with erratic myoclonus and frequent focal seizures [4]. Numerous terms have been applied to this condition, including myoclonic epilepsy with neonatal onset, neonatal epileptic encephalopathy with periodic electroencephalogram bursts, and early myoclonic epileptic encephalopathy [5]. In 2001, the Task Force on Classification and Terminology of the International League Against Epilepsy recognizes two early-onset epileptic encephalopathies (EOEEs): early infantile epileptic encephalopathy (EIEE) (also called OS) and EME [6]. The term “epileptic encephalopathy” refers to conditions where the epileptic abnormalities themselves are believed to contribute to the progressive disturbance of cerebral function stipulating that early intervention may improve developmental outcome [6]. Nevertheless, several authors highlight that considering EOEEs as an epileptic encephalopathy is highly debatable because the neurological prognosis of these patients seems predominantly caused by the preexisting brain dysfunction [7-9]. Therefore, EOEEs are also called “catastrophic epilepsies” [10], “Genetic or acquired encephalopathies with epilepsy” [8], or “early-onset severe epilepsies with suppression burst” [9].SCOPUS: ch.binfo:eu-repo/semantics/publishe