Abstracts

Rationale: Acute unexpected deaths occur frequently in Dravet syndrome (DS). DS model mice, SCN1AR1407X /- mutant mice, suffer from recurrent spontaneous seizures and 40% of them die within 3 months after birth. SCN1A is reported to be expressed in heart, mainly in sinoatrial node and Purkinje fibers. Thus, we postulate and test the hypothesis that death in DS is related to the channelopathy which commonly affect central nervous system and cardiac conduction system. Methods: Simultaneous ECG and EEG monitoring were performed in SCN1AR1407X /- mutant mice: subdural EEG electrodes and two subcutaneous ECG electrodes were implanted in freely roaming mice. Clinical symptoms were recorded by video-monitoring system. We examined effects of hyperthermia in induction of seizures, and applied atropine pretreatment to evaluate the influence of parasympathetic nerve activities on heart. Results: Ictal deaths were captured in 6 mutant mice; one in spontaneous seizure, and 5 in hyperthermia-induced seizures. In a spontaneous seizure, bradyarrhythmia occured 2.5 sec later after seizure onset, eventually leading to death. In hyperthermia-induced seizures, tachycardia was observed at the beginning of seizures, and thereafter intermittent bradyarrhythmia appeared associated with paroxysmal discharges and characteristic ST changes on EEG (Fig). The intervals from seizure onset to death were 3.0 to 6.5 min (mean 4.7 min). Parasympathetic nerve blockage by atropine pretreatment completely prevented bradyarrhythmia but ST changes remained. Conclusions: Ictal death in mutant mice occurs following ictal bradyarrhythmia and characteristic ST wave form change, suggesting that common abnormalities of sodium channel exist both in brain and heart. Such phenomena may occur in patients with DS.