Abstracts

Phenobarbital is widely used for the treatment of neonatal seizures, but is effective in only about one-third to one-half of neonates with seizures. Second line treatments such as phenytoin or benzodiazepines have also been of limited effectiveness. In addition, in animal studies, all of these drugs increase neuronal death. Levetiracetam (LEV) potentially represents an alternative option because of its novel mechanism of action and favorable pharmacological profile. However, little is know about the effects of LEV in neonates with seizures. The purpose of this work is to characterize the safety and efficacy of levetiracetam in neonates with seizures., The effectiveness of LEV was studied retrospectively in a group of neonates with EEG confirmed seizures. Patients were identified from a database of EEGs done in the neonatal intensive care unit at Cincinnati Children[apos]s Hospital Medical Center and associated hospitals over the past 18 months. Neonates were included if they had electrographic seizures (with or without clinical correlate) on an initial EEG and in whom LEV was used within the first 52 weeks post-conceptual age. Gestational age, post-conceptual age at seizure onset and at time of initiation of LEV, seizure frequency as determined from serial EEGs and clinical course, etiology of seizures, concomitant antiepileptic therapies, dose of LEV, and side effects associated with LEV therapy were recorded., Five neonates met the entry criteria. The average gestational age was 34 weeks (SD 7.1) with the average post-conceptual age at seizure onset being 39.2 weeks. The etiologies included malformations of cortical development (2), prematurity with intracranial hemorrhage (2) and unknown (1). The median seizure frequency at the time of the initial EEG was 24 per day (range 1-48). All infants were initially treated with and maintained on Phenobarbital. Following initiation of phenobarbital therapy, the median seizure frequency was 7.5 per day (range 1-48). Levetiracetam therapy was initiated at an average postconceptual age of 41.2 weeks (SD 5.3). Doses of LEV were titrated to effect and ranged from 24 to 72 mg/kg/d. No treatment-related side effects were seen even at the highest LEV dose. During LEV therapy, the median seizure frequency was 1 seizure per day (range 0.3-24). One neonate became seizure free and another had over a 75% reduction in seizure frequency; two infants had a 50-75% reduction in seizure frequency and there was no response to LEV in the remaining infant. In addition to infants that met entry criteria, another 4 infants were treated with LEV within the first 6 months of life. In these infants, levetiracetam doses ranged from 25-86 mg/kg/d. No treatment related side effects were reported., Levetiracetam was well tolerated in neonates, even at high doses. Seizure frequency was reduced in all but one neonate and one infant became seizure-free. Levetiracetam should be considered in the treatment of neonatal seizures., (Supported by UCB Pharma.)