LEV is a well-tolerated new AED that may effectively improve seizure control as an add-on drug in resistant epilepsy in childhood with good tolerability. However, neurologically handicapped children appear at increased risk for reversible neurocognitive side effects and have a poorer treatment response.

Since our last report on valproate (VPA)-related hepatotoxicity in 1988, 8 other children have died of VPA-associated liver failure in Germany and Switzerland. We compared the clinical course of these children with that of 6 children with a reversible outcome of severe hepatotoxicity related to VPA. Thirty-five percent of patients with fatal liver failure were normally developed, 23.5% were receiving VPA monotherapy, and 35.3% were aged < or = 2 years. The initial clinical symptoms of VPA-related hepatotoxicity were nausea, vomiting, apathy or coma, and increasing seizures in more than 50% of patients, in combination with febrile infections at onset of symptoms. As compared with the series of German patients reported in 1988, one third of the fatalities occurred after the first 6 months of therapy as compared with 6% in the 1988 series. Clinical symptoms and laboratory findings were the same in patients with reversible and with fatal outcome. Early or immediate withdrawal of VPA after the first signs of VPA-associated hepatotoxicity may be responsible for the increased number of children who recovered after VPA-related severe liver failure. The pathogenesis of liver failure during VPA treatment remains unknown; metabolic defects and cofactors such as polypharmacy or infections have become increasingly likely to contribute by depleting intracellular CoA. Worldwide, 132 patients have died of VPA-associated liver failure and/or pancreatitis. Because a group at risk for fatalities with VPA cannot be defined precisely, patients treated with VPA and their families must be made well aware of the clinical symptoms of hepatotoxicity such as apathy, vomiting, or increased seizure frequency, especially in the presence of febrile infections. Laboratory tests and clinical controls during the first 6 months of therapy should not be neglected.

In a retrospective study the results of therapy in 60 children with so-called benign partial epilepsies are reported. It has been shown that the assessment of the therapeutic effect has to include the EEG, especially in epilepsies with atypical course. Carbamazepine has no effect on the EEG, in epilepsies with atypical course (atypical benign partial epilepsy, Landau-Kleffner syndrome, epilepsy with continuous spikes and waves during slow sleep [CSWS]) carbamazepine usually has no effect either on the seizures or on the EEG, on the contrary, in some cases both may even get worse. In our experience, the drug of choice in all types of benign childhood epilepsy is sulthiame, if necessary in combination with clobazam. Other drugs previously administered, including carbamazepine, should be dropped quickly. If the treatment with sulthiame or sulthiame/clobazam in children with atypical course is not effective, ACTH-therapy should be considered as soon as possible. These results should be confirmed in a prospective randomized study.

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