Abstracts

Summary: Experimental data provide strong evidence that seizures early in life produce long-lasting alterations with cognitive impairment and increased risk of developing epilepsy. However, clinical studies suggest that long-term outcome correlate best with etiology rather than with the presence of seizures or their duration. Controversies persist whether seizures per se are injurious to the neonatal brain. Benign Familial Neonatal Seizures (BNFS) is a genetically determined neonatal seizure disorder in which affected newborns experience partial or generalized seizures occurring many times daily. Mutations in neuron-specific KCNQ2 and KCNQ3 potassium channels have been found associated with BNFS. Through a mechanism of loss of function, these mutations induce a reduction of K+current leading to neuronal hyperexcitability. While newborns with BNFS may suffer from multiple episodes of seizure activity, this syndrome is usually not associated with any neurodevelopmental sequelae. Mouse models of human BFNS seem to parallel this benign neurocognitive profile. The workshop is intended to discuss the dilemma with new insights from clinical and basic research on BFNS. Tim Benke will show the morphological and molecular changes associated with neonatal seizures. Maria Roberta Cilio will discuss the unique clinical and electrophysiological presentation of BFNS, their genetic background and the emerging genotype-phenotype correlations. Maurizio Taglialatela will present the cellular and developmental basis of neuronal excitability and seizure discharges in BNFS individuals. Finally Nanda Singh will expose studies on mouse models of human KCNQ2 and KCNQ3 mutations. Dr. Gregory Holmes will be the discussant.