Abstracts

Rationale:
Sudden Unexpected Death in Epilepsy (SUDEP) is the leading cause of death in patients with treatment-resistant epilepsy. Seizure-induced central apneas that occur during and after a seizure appear critically important in the pathophysiology of SUDEP. Although it has been repeatedly established that seizure spread to and electrical stimulation of the amygdala can induce apnea, in these studies, breathing resumed when the stimulation or seizure activity ended. To date, no known mechanism has been found to explain the persistent loss of breathing after either nonfatal seizures or seizures that lead to SUDEP.
Method:
We studied 28 intractable pediatric and adult epilepsy patients undergoing intracranial electroencephalography (iEEG). We recorded respiration during seizures and electrical stimulation mapping. Stimulation consisted of focal bipolar biphasic electrical stimulation using adjacent electrode contact pairs at 50 Hz.
Results:
In the 28 patients, amygdala stimulation induced apnea at the previously identified amygdala inhibition of respiration (AIR) site in humans. In 5 out of 28 patients, amygdala stimulation or amygdala stimulation evoked seizure resulted in apneas lasting long after the stimulation or seizure stopped. In one patient, amygdala stimulation resulted in persistent apneas lasting two minutes beyond the end of stimulation. In another patient, apneas lasted up to 16 minutes after the amygdala stimulation induced seizure ended. This site was relatively specific to the amygdala as no other site elicited apnea or apneas after stimulation ended. A machine learning algorithm indicated the sites of stimulation that induced persistent apneas overlaps with the amygdala inhibition of respiration (AIR) site.
Conclusion:
Our results provide a mechanism linking seizure activity in the amygdala to postictal dysregulation of breathing and the apnea that occurs after seizures terminate. Continued breathing dysregulation after amygdala stimulation or seizure activity may be a biomarker for SUDEP risk. Finally, this site in the amygdala in certain individuals at high risk of SUDEP may be a target for treatment to prevent SUDEP.
Funding:
:Support was provided by the University of Iowa Neurosurgery Department, the National Institute of Neurological Disorders and Stroke Grant 5-K12NS080223, the Congress of Neurological Surgeons Getch Scholar Award (B.J.D), and the Iowa Neuroscience Institute Carver Trust. G.I.H. was also supported in part by National Institute of Health training grant T32 GM067795.