Anoxia-ischemia: A mechanism of seizure termination in ictal asystole

Cerebral anoxia–ischemia (CAI) is a potent inhibi-torofcerebralhyperactivityandapotentialmech-anism of seizure self-termination. Prolonged ictalasystole (IA) invariably leads to CAI and has beenimplicated as a potential cause of sudden unex-plained death in epilepsy (SUDEP). IA was seen ineight consecutive patients (0.12% of all patientsmonitored). Ten of their seizures with IA had evi-dence of CAI on electroencephalography (EEG),manifested by bilateral hypersynchronous slowing(BHS), and were compared to 18 seizures withoutsigns of CAI. The ictal EEG pattern resolved in all10 CAI events with onset of the BHS. The periodfrom IA onset to seizure end was reduced ineventswithBHScomparedtoeventswithoutBHS(10.5 s vs. 28.3 s, respectively; p = 0.005), and thetotal seizure duration tended to be shorter.Anoxia–ischemia as a result of IA may representan effective endogenous mechanism for seizuretermination and may explain why the hearts ofpatients with ictal asystole reported to date in theliteratureresumedbeatingspontaneously.KEY WORDS:Ictalasystole,Seizuretermination,Suddenunexplaineddeathinepilepsy,SUDEP.A variety of mechanisms contribute to seizure termina-tion (Lado & Moshe, 2008). Energy depletion can abolishexcitatory synaptic activity and terminates hypersynchro-nousneuronalfiring.Cerebralhypoxiaandischemia seemto play a crucial role in self-regulatory seizure cessationbased on various animal models. Failure of seizure inhibi-tion leads to seizure prolongation and status epilepticus.On the other hand, over-regulation of cerebral inhibitionduringseizure termination might playan important role insudden unexplained death in epilepsy (SUDEP) (McLean&Wimalaratna,2007).Ictalasystole(IA)isthoughttobetriggeredbyepilepticactivation of autonomic centers in the brain, and has beenimplicated as a potential cause of SUDEP (Britton et al.,2006). Animaldata havedemonstrated that epileptic auto-nomic activation can be synchronized with cardiac neuraldischarges, and that persistent stimulation can lead to bra-dycardia and permanent cessation of the heart (Oppenhei-mer et al., 1991). In patients with IA, longer periods ofcardiac arrest invariably lead to cerebral anoxia–ischemia(CAI) as indicated by apredictable sequence of electroen-cephalography (EEG)changes(Schuele et al., 2007). Thisstudyinvestigates the effectsof CAI on the electrographicseizure activity during prolonged asystolic events com-pared to control seizures, which occurred in the samepatient population without electrographic evidence ofCAI.