December 23, 2024

Brain’s Breathing Block: Deciphering Unexplained Epilepsy Deaths

Current research offers fresh insights into the causes of SUDEP (Sudden Unexpected Death in Epilepsy). The research study identified a particular area in the amygdala that, when promoted, can cause prolonged apnea, even after a seizure concludes. This cutting-edge discovery, combined with innovative brain imaging techniques, may lead to enhanced understanding and possible preventive treatments for SUDEP.
Research study discovers amygdala area is connected to consistent loss of breathing after seizure.
New findings might take researchers an action better to understanding what triggers SUDEP– Sudden Unexpected Death in Epilepsy– a uncommon but deadly problem of epilepsy.
There have to do with 3,000 deaths from SUDEP each year in the U.S. The greatest threat factor is epilepsy that is not well controlled with medication or surgery, however the precise cause of SUDEP is not known. Increasing proof suggests that loss of breathing, or apnea, that continues after a seizure is a major cause of SUDEP.

Current research uses fresh insights into the causes of SUDEP (Sudden Unexpected Death in Epilepsy). This groundbreaking discovery, integrated with ingenious brain imaging methods, might lead to enhanced understanding and prospective preventive treatments for SUDEP.
There are about 3,000 deaths from SUDEP each year in the U.S. The biggest risk element is epilepsy that is not well controlled with medication or surgical treatment, however the exact cause of SUDEP is not known. Increasing proof suggests that loss of breathing, or apnea, that persists after a seizure is a major cause of SUDEP.

Development Findings
In the brand-new research study, University of Iowa neuroscientists discovered that stimulating a particular location of the amygdala brain area provokes prolonged loss of breathing that continues even after a seizure has ended.
Scientist recognized a website in the amygdala crucial to breathing loss following a seizure. The purple and blue area represents a likelihood map of the region linked to relentless apnea, based on data from 20 subjects with uncontrolled epilepsy. Credit: Dlouhy lab, University of Iowa
” This is the first study to determine a website in the brain that can trigger persistent apnea after the seizure ends,” states Brian Dlouhy, MD, UI associate professor of neurosurgery and pediatrics, and senior author on the brand-new research study released online on Octoctober 3 in JCI Insight. “We believe this carefully looks like the apnea that takes place and has been monitored in SUDEP cases reported in the literature, suggesting that this focal location of the amygdala underlies consistent apnea that can lead to death.”
The research study offers new insight into the systems that underlie this possible cause of SUDEP.
” These new findings are a crucial action in establishing our understanding of what causes SUDEP and in the advancement of methods which to determine those individuals at greatest risk and methods to prevent SUDEP,” states Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, which contributed funding for the study.
A Deeper Look Into Brain Mechanisms
The UI research study group, consisting of lead authors Gail Harmata, PhD, a postdoctoral research fellow, and Ariane Rhone, PhD, a research researcher, used numerous methods to study the brain systems linked to this loss of breathing. Particularly, they studied 20 patients, both kids and grownups, who were getting ready for epilepsy surgical treatment. The clients who got involved in the study had intracranial electroencephalography (iEEG) electrodes implanted in their brain to help prepare their surgeries.
Brian Dlouhy, MD, neurosurgeon with University of Iowa Health Care, performs a minimally intrusive procedure to deal with epilepsy. Credit: University of Iowa Health Care
Combining intracranial recordings from these electrodes with practical MRI brain imaging permitted the researchers to map the effect of stimulation at many amygdala sites, causing the recognition of the new focal website in the amygdala.
The study recommends that not every patient is at threat for this phenomenon; only five of the patients established extended apnea following amygdala stimulation. In addition, the specific place within the amygdala was also essential. Even within the very same client, stimulating one part of the amygdala triggered just short-lived loss of breathing while promoting a different location led to relentless apnea after the stimulation stopped.
Revelations From New Brain Imaging Technique
The group also utilized a new method, called electrical stimulation concurrent with practical MRI, to trace the brain networks associated with the consistent post-seizure apnea.
Remarkably, during the experiment the patients were entirely unaware that they had actually stopped breathing. They did not experience the normal sensations of breathlessness or “air hunger” that should have triggered deep breaths.
” Not only did the stimulation of these specific amygdala sites persistently hinder breathing, it likewise persistently prevented the typical alarm that you would receive from not breathing and the normal air hunger that you must experience from elevated co2 levels,” explains Dlouhy, who also belongs to the Iowa Neuroscience Institute.
” This unique method enables us to take a look at causal results from stimulating one site in the brain to see what else it is doing at other websites. It enables us to look at circuitry,” he includes.
The brain circuitry revealed through the experiments revealed that stimulation of the amygdala lowered the activity of websites in the brainstem, a crucial area for managing breathing and noticing carbon dioxide levels. Elevated levels of co2 that build up when breathing stops typically prompt deep breathing. The fact that the focal amygdala stimulation obstructed this normal response recommends that chemo-sensing is disrupted in these patients. The research studies likewise showed modified activity in another brain region called the insula, which is associated with air appetite.
” These brand-new findings are a critical action in developing our understanding of what causes SUDEP and in the advancement of methods which to determine those people at greatest danger and methods to avoid SUDEP.”
— Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke
Dlouhy is excited by the new findings and hopes that they will lead to an increased understanding of SUDEP that may eventually enable doctors to identify patients who are at threat and even result in scientific trials of treatments to avoid SUDEP from taking place.
” Were homing in on more of a focused target in the amygdala, which is essential if we wish to translate this to a preventative or healing method,” he states.
Recommendation: “Failure to breathe persists without air appetite or alarm following amygdala seizures” by Gail I.S. Harmata, Ariane E. Rhone, Christopher K. Kovach, Sukhbinder Kumar, Md Rakibul Mowla, Rup K. Sainju, Yasunori Nagahama, Hiroyuki Oya, Brian K. Gehlbach, Michael A. Ciliberto, Rashmi N. Mueller, Hiroto Kawasaki, Kyle T.S. Pattinson, Kristina Simonyan, Paul W. Davenport, Matthew A. Howard III, Mitchell Steinschneider, Aubrey C. Chan, George B. Richerson, John A. Wemmie and Brian J. Dlouhy, 3 October 2023, JCI Insight.DOI: 10.1172/ jci.insight.172423.
In addition to Dlouhy, Rhone, and Harmata, the research group consisted of UI researchers Christopher Kovach; Sukhbinder Kumar; Md Rakibul Mowla; Rup Sainju; Yasunori Nagahama; Hiroyuki Oya; Brian Gehlbach; Michael Ciliberto; Rashmi Mueller; Hiroto Kawasaki; Matthew Howard III; Aubrey Chan; George Richerson; and John Wemmie. Researchers at University of Oxford, Harvard Medical School, University of Florida, and Albert Einstein College of Medicine in New York were likewise part of the team.