(Kim et al. 2018) SUDEP is believed to be caused by cardiorespiratory arrest (or the stopping of the heart and breathing). However, it is not clear whether heart rate slows and stops, causing respirations to stop, or vice versa. Because SCN1A is expressed in heart tissue as well as brain tissue, scientists have hypothesized that SUDEP may be a cardiac issue, but mouse models have suggested evidence for both arguments. In this study, the authors examined breathing near generalized seizures (“peri-ictal,” including before, during, and after a seizure) in human patients and found significant alterations in breathing. To further characterize this breathing, they looked at one female patient with DS who had extensive monitoring during 3 generalized tonic clonic seizures. They recorded respirations, measured the lung volume based on chest rise and falls, and performed transcutaneal CO2 testing, which measures the concentration of carbon dioxide in the arteries, similar to the O2 measurement of a pulse oximeter. The patient had definite respiratory alterations and was found face down in bed due to probable SUDEP three years later.

The authors also looked at mice with Scn1a mutations who exhibit a high rate of SUDEP. Two mice who were monitored extensively were found to have normal breathing before the fatal seizure, then complete apnea that continued after the seizure, as well as a heart rate that decreased during the seizure and eventually slowed further after the 4- minute seizure, suggesting respiratory arrest was a key player in their death. Looking at the non-fatal seizures in these mice that preceded the fatal seizure, bradycardia did not occur without apnea or decreased breathing.

Kim Y, Bravo E, Thirnbeck CK, Smith-Mellecker LA, Kim SH, Gehlbach BK, Laux LC, Nordli DR Jr, Richerson GB. Severe peri-ictal respiratory dysfunction is common in Dravet syndrome. J Clin Invest. 2018 Jan 11. pii: 94999. doi: 10.1172/JCI94999. [Epub ahead of print] PubMed PMID: 29329111.