An Update from the Center for SUDEP Research: November 2015

Epilepsy News From: Wednesday, November 18, 2015

What is the Center for SUDEP Research?

The Center for SUDEP Research

The Center for SUDEP Research (CSR) is a National Institute of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) funded consortium of basic science and clinical researchers from the U.S. and Europe, dedicating their time to the study of sudden unexpected death in epilepsy (SUDEP). Several of the principal investigators have published interesting new research on different aspects of the topic and are planning their second satellite meeting at the American Epilepsy Society meeting in December 2015. The meeting will include a review of ongoing research and a presentation for CSR Partners, a program involving nearly a dozen SUDEP advocacy groups.

An overview of the structure and function of the CSR; its priorities, goals, collaborations with academia, industry, and foundations; and its cutting edge research tools in development can be found in the special report on the Center, “Sudden unexpected death in epilepsy: Identifying risk and preventing mortality,” published in the November 2015 edition of the journal, Epilepsia.

What are CSR researchers doing?

CSR basic science researchers have reported this year on several important findings.

The laboratory of Dr. Jeffrey Noebels at Baylor College of Medicine discovered a causative mechanism for SUDEP in mice involving the sudden onset of “spreading depolarization,” an abnormal traveling wave of depression (slower than normal brain waves) that silences neurons in the brainstem which regulate breathing and the heartbeat. All seizures that trigger this wave resulted in immediate death, while mice recover normally from seizures when the wave was not present. Genes known to raise the risk of SUDEP, including SCN1A in Dravet Syndrome and KCNA1, were shown to lower the threshold for triggering this lethal post-seizure wave.   

Dr.  George Richerson’s laboratory at the University of Iowa is defining the key role of brainstem serotonin neurons in control of breathing, cardiovascular control, and other life-sustaining brain functions and is exploring how dysfunction of these neurons might contribute to SUDEP. His group reported that stimulation of the human amygdala triggers a brainstem-mediated respiratory arrest during and after seizures, revealing a mechanism of how lack of breathing and loss of consciousness in people with epilepsy could be fatal following seizures.

Drs. Jack Parent and Lori Isom at the University of Michigan published pioneering work on the use of patient-derived induced pluripotent stem cells to study SUDEP mechanisms, along with a new mouse model of SCN8A-Associated Epilepsy and SUDEP.

CSR clinical researchers, led by  Britta Wandschneider, investigated imaging biomarkers of SUDEP using a 3T MRI scanner in three patient groups: a healthy control group, a group at low risk for SUDEP, and a group at high risk for SUDEP. Very interestingly, the results showed consistent increased gray matter volume in two regions of the brain and decline in a third region of the brain in SUDEP and high risk patients. This suggests that it may be possible to identify high-risk patients through imaging. Another CSR researcher, Susanne Mueller had previously reported on MRI abnormalities in the brain centers that control breathing and circulation (the brainstem) in two SUDEP patients.

CSR neuropathology researchers also reported on SUDEP brain examinations and found macroscopic brain abnormalities in over half the cases. The authors found that close examination of such brains could potentially provide meaningful information on the SUDEP process, something the same researchers are attempting to do on more than 100 such brains collected by CSR investigators.

Reviewed Date

Wednesday, November 18, 2015

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