Abstracts

Rationale: Neonatal seizures occur with a frequency of around 1.5/1000 newborns. At present, phenobarbital (PHB) is the treatment of choice in children not responding to pyridoxine and pyridoxal phosphate. However, PHB has been found to induce neuronal apoptosis in rats. In addition, the known risk of cognitive side effects of PHB in infants and toddlers should be considered. In children >4 years of age, levetiracetam (LEV) is an effective and well-tolerated antiepileptic drug (AED). Furthermore, LEV has not been found to increase apoptosis in animal models. Therefore, as LEV may be an alternative treatment in neonatal seizures, we initiated a prospective, open, single centre, proof-of-principle pilot study.Methods: The study was approved by the local ethics committee. 6 consecutive newborns and premature babies (>2000 g and >30 weeks gestation) with neonatal seizures were enrolled after exclusion of hypoglycaemia, hypomagnesaemia and pyridoxine dependency. Patients who had already received >2 doses of PHB or other AEDs were excluded. LEV was administered orally and the dose was increased by 10 mg/kg/day over 3 days. In case of persisting seizures, additional therapy with PHB in single doses was allowed during titration. The endpoint was the need for additional AED(s) (PHB or others) after day 3.Results: All 6 patients treated with oral LEV (30-50 mg/kg/day) became seizure-free within 6 days. 4 received PHB on days 1-3, 1 had an additional dose of PHB on day 4, and 1 did not receive any other medication. Seizures recurred within the following months in 3/6 patients. One of these has had drug-resistant epilepsy from age 3 months; LEV was stopped and various drugs were applied without success. After 6-8 months follow-up, the remaining 5/6 children are seizure-free, 2 without any medication (LEV stopped after 3 and 6 months). In one patient, sulthiame (SLT) was combined with LEV because of an EEG-worsening at age 4 months and the patient stayed seizure-free. In another patient, LEV was stopped at 6 months and seizures relapsed after 1 week; SLT monotherapy was initiated at age 7 months and the patient became seizure-free. Finally, LEV was replaced by carbamazepine monotherapy in a child with seizure relapse at 5 months of age. No severe adverse events were observed. Drowsiness was reported in 1 child. Conclusions: Oral administration of LEV in the treatment of neonatal seizures was well tolerated and rapidly effective in these 6 consecutive patients. Results from our small patient group indicate that LEV may be an alternative therapeutic option in neonates suffering from seizures.