Two SMU researchers have potentially identified the events that occur during Sudden Unexpected Death in Epilepsy (SUDEP), bringing researchers closer to a medical solution.
SUDEP occurs abruptly and often at night in epilepsy patients, said Kelsey Paulhus, postdoctoral researcher and SMU PhD graduate.
“It’s not like they fell and hit their head,” Paulhus said. “So there’s kind of this big black box surrounding what happens.”
Paulhus embarked on her research project last year with Edward Glasscock, an SMU biology professor who has extensively researched epilepsy and SUDEP. She used transgenic mice to model epilepsy in Glasscock’s lab on campus. Less than a month after Paulhus and Glasscock published their article in the journal Brain Communications, SMU received its Carnegie Research One (R1) title, distinguishing it as a top research university nationally. Epilepsy is one of the most common neurological disorders in the United States and will cause sudden death in a subset of the people it affects, Paulhus said.
The condition is more common in the U.S. than many realize, said Yukthi Kadari, program associate for the Epilepsy Foundation Texas.
“Because of its prevalence and potential impact on daily life, raising awareness about epilepsy is crucial to reducing stigma, improving treatment options and ensuring that those affected receive the support they need,” Kadari stated in an email.
Paulhus led a study investigating the role of KCNA1, a gene that encodes the Kv1.1 potassium channel, in epilepsy-related mechanisms. Kv1.1 helps regulate neuronal excitability in the brain, and mutations in KCNA1 are a well-established genetic cause of epilepsy in humans, as noted in SMU’s press release about the study.
“There were many projects that led up to mine, but in this specific project, we deleted this one gene in a very specific brain circuit—the corticolimbic circuit—because this circuit plays a crucial role in regulating both heart and lung function, which are two organs that, along with the brain, we think ultimately fail during a terminal seizure,” Paulhus stated in an email.
By selectively removing KCNA1, the researchers created a mouse model that spontaneously develops seizures, mirroring the uncontrolled seizure activity seen in people with epilepsy.
“We identified this potential pattern of events that goes on when somebody dies from a seizure, but then on top of that, because we were just disrupting this gene in a particular part of the brain and not leaving it intact anywhere else, it was giving us an idea of the underlying anatomy that could be driving things,” Glasscock said.
Paulhus and Glasscock then observed the mice as they experienced the effects of the gene’s removal, including death.
“I think the real power in this study is that we were able to capture a SUDEP event while monitoring brain, heart and lung activity simultaneously,” Paulhus said. “Respiration seems to be what fails first.”
The mice without the KCNA1 gene also died earlier than normal, much like human epilepsy patients who die from SUDEP.
“We see that they have short lifespans, so they start dying pretty early,” Paulhus said. “Mice can live for several years, but these are dying in 25 to 40 days.”
Paulhus’ research will have broader impacts on the study of epilepsy, bringing researchers closer to a solution for SUDEP by identifying a set of biological events and the brain region in which they occur.
“The brain has billions of synapses, and we’ve narrowed it down to a circuit,” Paulhus said. “It is a big step towards knowing more about something that we’ve known very little about.”
