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We are proud to partner with the American Epilepsy Society (AES) to attract the best and the brightest in the field. Since the 1960s, the Epilepsy Foundation has supported the careers of over 3,000 researchers.

EF/AES Junior Investigator Research Award

William Nobis MD, PhD
Vanderbilt University Medical Center
The Role of the Extended Amygdala in Respiratory Control and SUDEP

William Nobis MD PhD
 

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with uncontrolled seizures. Seizure-related apneas (cessation of breathing during a seizure) are being observed in epilepsy units where respiratory status is consistently monitored. When SUDEP has occurred in a healthcare setting, apnea has been observed prior to the terminal cardiac arrhythmias. This suggests that SUDEP might be a lethal combination of a seizure-related apnea along with impaired consciousness in the individual post-seizure.

In previous work, Dr. Nobis established that an area of the brain known as the extended amygdala causes apnea when stimulated. Dr. Nobis hypothesizes that this region or the parabrachial nucleus, another area implicated in respiratory control, may be activated during a seizure and thus cause the observed seizure-induced apneas. Using animal models that study SUDEP, he will test whether and how these brain regions are impacted during a seizure, and how this can impact respiratory control. Understanding this pathway and its role could open up new prevention strategies for those at high risk of SUDEP.

Alicia Guemez Gamboa PhD
Northwestern University
Uncovering Altered Connectivity in Epilepsy due to Somatic Mutations

Alicia Guemez Gamboa PhD
 

A somatic mutation is a genetic mutation that occurs as a cell divides in the developing body. If there is a genetic mutation that occurs during the division, this would be contained to the cell that the mutation occurred in and the other cells that this cell helped to create afterwards. There is evidence of somatic diversity in the brain, which means that specific brain cell populations have a genetic mutation in their DNA not associated with other brain cells or organs in the body. Some of these somatic mutations in the developing brain have been linked to focal cortical malformations associated with pediatric drug-resistant epilepsy.

To better understand how somatic mutations could impact epilepsy and brain circuits, Dr. Gamboa has created a mouse model that causes brain cell-specific genetic mutations that activate the mTOR pathway during cortical development. There are many studies that observe a frequent hyperactivation of mTOR signaling in epilepsy. For example, seizures associated with Tuberous Sclerosis, a rare genetic epilepsy syndrome, is treated by mTOR inhibitors. In this research proposal, she will explore how somatic mutations in the mTOR pathway in a contained population of neurons result in network abnormalities that lead to epilepsy. The disease mechanisms that arise from this research could lay the groundwork for new therapeutic approaches.

EF/AES Clinical Research and Training Fellow

Behnaz Esmaeili MD
Brigham and Women’s Hospital
Intracranial EEG Suppression and Heart Rate Variability in Epilepsy

Behnaz Esmaeili MD
 

SUDEP is the sudden, unexpected death of someone with epilepsy who was otherwise healthy. In SUDEP cases, no other cause of death is found when an autopsy is done. Each year, about 1 in 1,000 people with epilepsy die from SUDEP. The mechanism(s) of SUDEP are still under intense investigation by researchers in the U.S. and across the world.

The most consistent risk factor for SUDEP is frequent generalized tonic-clonic (GTC) seizures. Certain individuals experience a dramatic suppression of brain activity after a GTC seizure. This phenomenon is also linked to the altered state of consciousness post-seizure, which can last between 5 to 30 minutes. In addition to the change in brain activity, clinicians have also observed decreased heartrate variability in individuals post-seizure.

In a healthy heartbeat, you would experience healthy irregularities. For example, if you place a finger on your pulse, you would notice that your pulse can change based on how you breath (exhale versus inhale). These heart rate variabilities are dampened post-seizure. The question remains about whether the characteristics of the brain activity suppression and the decrease in heart rate variability post-seizure could be indicators of increased risk for SUDEP.

To answer this question, Dr. Esmaeili will be mining data from a data repository from the epilepsy monitoring unit of 5 major academic epilepsy centers to understand the range of characteristics of the brain activity and heart rate variability post-seizure. She will be observing whether there are any significant factors in either of these two measurements in confirmed SUDEP cases. This work could highlight physiological factors that indicate who is at higher risk of SUDEP.

Authored By: 
Sonya Dumanis PhD
Authored Date: 
10/2019
Reviewed By: 
Research Team
on: 
Thursday, October 31, 2019