Abstracts

Summary: Over the past 20 years, there is increasing evidence that anticonvulsant medications - while largely effective in controlling seizures in both infants and children - carry unique age-dependent risks to the developing brain. Specifically, anticonvulsants that block voltage-gated sodium channels, N-methyl-D-aspartate receptors, and enhance GABAergic transmission have been shown to induce dose-dependent apoptotic neurodegeneration in the brains of rat pups. Even certain newer anticonvulsants are not without such risks, if administered in combination therapy. Thus, early post-natal exposure to anticonvulsants might cause neuronal injury, and may contribute to later neurocognitive deficits. More recently, investigators have shown that fetal exposure to anticonvulsants can disrupt the normal architecture of seizure-prone structures such as the hippocampus, yielding neuronal loss and dispersion. This finding adds to the already well-described somatic malformations such as cleft lip and palate, or more generally, the fetal anticonvulsant syndrome. While certain anticonvulsants are already known to cause such problems, there are emerging new data that raise heightened concerns for fetal drug exposure with this class of broadly-prescribed medications. Taken together, whether during gestation or the neonatal period, existing anticonvulsants may pose a significant risk to normal brain integrity and development. The practical implications of these experimental and clinical findings constitute the core rationale of this investigators’ workshop. Dr. Chrysanthy Ikonomidou (Children's Hospital, Dresden, Germany) will review the experimental data supporting early postnatal anticonvulsant-induced neuronal apoptosis, and Dr. Richard Finnell (Texas A&M Health Science Center, Houston, Texas, USA ) will evaluate the adverse effects of fetal anticonvulsant exposure to normal brain development. In an integrative fashion, Dr. Kimford Meador (University of Florida, Gainesville, Florida, USA) will summarize the clinical data addressing the adverse effects of prenatal and early post-natal exposure to anticonvulsants. Whether these research findings should influence the standard medical management of pregnant women with epilepsy and of very young neonates/infants remains uncertain, and should constitute grounds for lively debate and further inquiry.