Researchers at the University of Iowa have made a significant discovery in understanding the leading cause of death in patients with severe epilepsy – sudden unexpected death in epilepsy (SUDEP). Supported by the National Institutes of Health (NIH), the research team identified that seizure activity in the amygdala region of the brain may be associated with breathing failure following a seizure in individuals with uncontrolled epilepsy.
SUDEP is believed to be caused by the loss of breathing, known as postictal apnea, that occurs after a seizure. The study found that individuals who experience postictal apnea do not feel the primal urge to breathe or a sense of alarm, suggesting that the brain fails to detect and respond to rising carbon dioxide levels in the blood during the apnea.
To investigate this, the researchers enrolled 12 adults and eight children with uncontrolled epilepsy and conducted intracranial electroencephalography (iEEG) procedures. They induced seizures and examined the forebrain control of breathing and apnea. The study revealed that seizures originating in the amygdala, a region associated with processing emotion and fear, can lead to postictal apnea. Furthermore, the team identified the specific subregion of the amygdala involved in prolonged breathing loss.
Using electrical stimulation and functional MRI, the researchers discovered novel connections between the amygdala and the brainstem, the region critical for sensing changes in blood carbon dioxide levels and controlling breathing. These findings suggest that seizure activity in the amygdala subregion can suppress breathing and the urge to breathe for extended periods following a seizure, controlled through connections with other brain sites responsible for sensing bodily signals.
The study increases understanding of SUDEP and may contribute to the development of preventative treatments and the identification of individuals who are at a higher risk. The research received partial funding from the National Institute of Neurological Disorders and Stroke (NINDS), a division of NIH.
Further investigation is required to fully confirm the role of the amygdala in breathing suppression and its involvement in SUDEP.
– Harmata, GIS, Rhone AE, et al. “Failure to breathe persists without air hunger or alarm following amygdala seizures.” Oct 3, 2023. JCI Insight. DOI: https://doi.org/10.1172/jci.insight.172423
– NINDS (R01 NS113764, K08 NS112573 01, 5K12NS080223), the National Institute on Drug Abuse (R01DA052953), and the National Institute of General Medical Sciences (T32 GM067795)
– Congress of Neurological Surgeons, Oxford University Hospitals NHS Trust, University of Oxford, Roy J. Carver Charitable Trust, and the U.S. Department of Veterans Affairs
– Seizure: A sudden, uncontrolled electrical disturbance in the brain that can cause changes in behavior, movements, and consciousness.
– Amygdala: A region in the brain involved in processing emotions and fear.
– Sudden Unexpected Death in Epilepsy (SUDEP): The leading cause of death in individuals with severe epilepsy, often attributed to breathing failure following a seizure.
– Postictal apnea: Loss of breathing that occurs after a seizure ends.
– Intracranial Electroencephalography (iEEG): A procedure that involves placing electrodes inside the skull to record electrical activity from the brain.
– Functional MRI (fMRI): A technique that measures brain activity by detecting changes in blood oxygen levels.
– Carbon Dioxide (CO2): A waste product produced by the body’s metabolism, high levels of which can affect breathing and oxygen levels in the blood.
– NINDS (National Institute of Neurological Disorders and Stroke)
– NIH (National Institutes of Health)