Clinical and genetic characteristics of epilepsy of infancy with migrating focal seizures in Chinese children.

OBJECTIVE: Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare and severe developmental epileptic encephalopathy. The aim of this study was to improve our understanding of EIMFS by using phenotype-genotype correlation. METHODS: We recruited, performed clinical genetic testing, and summarized the clinical features and genetic characteristics in five patients with EIMFS in China. RESULTS: The five recruited patients included 2 males and 3 females. The median age of seizure onset was 2 months (range, day 3 to 3 months). All patients exhibited the characteristics of clinically migrating focal motor (tonic or clonic) seizures. Typical migrating ictal electrical patterns were found in 1 patient; the remaining four patients presented with overlapping seizures with different areas of ictal onset in differing hemispheres. All the patients had the associated variants, including KCNT1, SCN1A, SCN2A, TBC1D24 and ALG1. All patients received two or more antiseizure medications, and 1 patient became seizure-free, 1 reported >75 % seizure reduction, 2 reported >50 % seizure reduction, and 1 patient showed no improvement. Varying degrees of psychomotor developmental delays were observed in all patients. CONCLUSIONS: The course of EIMFS could be related to the type of gene variant present, and different genes may have specific clinical features. Larger cohorts are required to elucidate such potential phenotype-genotype correlations.

Effects of acute cooling/rewarming on membrane potential and K(+) currents in rat ventricular myocytes / 生理学报

The effects of acute cooling/rewarming on cardiac K(+) currents and membrane potential were investigated. Membrane potential and current were assessed with whole-cell patch-clamp technique in current- and voltage-clamp modes. When the temperature of bath solution was decreased from 25 °C; to 4 °C, the transient outward current (I(to)) was completely abolished, the sustained outward K(+) current (I(ss)) at +60 mV and the inward rectifier K(+) current (I(K1)) at -120 mV were depressed by (48.5±14.1)% and (35.7±18.2)%, respectively, and the membrane potential became more positive. After the temperature of bath solution was raised from 4 °C; to 36 °C;, the membrane potential exhibited a transient hyperpolarization and then was maintained at a stable level. In some myocytes (36 out of 58), activation of the ATP-sensitive K(+) (K(ATP)) channels after rewarming was observed. The rewarming-induced change in the membrane potential was inhibited by the Na(+)/K(+)-ATPase inhibitor ouabain (100 μmol/L), and the rewarming-elicited activation of K(ATP) channels was inhibited by the protein kinase A inhibitor H-89 (100 μmol/L). Moreover, decrease of the temperature from 25 °C; to 4 °C; did not induce any significant change in cell volume when the cell membrane potential was clamped at 0 mV. However, significant cell shrinkage with spots was observed soon after rewarming-induced activation of K(ATP) channels. These data demonstrate that acute cooling/rewarming has a profound influence on the membrane potential and K(+) currents of ventricular myocytes, and suggest that activation of K(ATP) channels may play a role in cardiac cooling/rewarming injury.