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NIH-Funded Study Links Seizure Activity in the Amygdala to SUDEP

Researchers hypothesize that the seizure activity in the amygdala causes breathing failure in patients with postictal apnea, leading to SUDEP.

In a recent press release by the National Institutes of Health (NIH), the organization announced the results of a study published by the National Institute of Neurological Disorders and Stroke (NINDS), revealing that seizure activity in the amygdala could be linked to sudden unexpected death in epilepsy (SUDEP).

The article was published in the Journal of Clinical Investigation Insights by researchers at the University of Iowa in Iowa City.

The researchers noted that one of the primary causes of SUDEP is a loss of breathing after a seizure ends, called postictal apnea. The NIH release describes this concept as a loss of “air hunger.” According to the release, the primal urge to breathe is compromised in postictal apnea, preventing the brain from detecting and responding to elevated carbon dioxide levels. Some theories suggest that a loss of air hunger also contributes to sudden infant death syndrome (SIDS).

Investigators recruited 20 patients with uncontrolled epilepsy, including 12 adults and 8 children. Each patient attempted to control their medication through medication but eventually opted to undergo intracranial electroencephalography (iEEG).

Intracranial electroencephalography is an approach that uses electrodes implanted into the skull to record electrical activity and locate seizure origins. In this investigation, scientists provided direct electrical stimulation to areas of the forebrain to assess breathing response and apnea.

Approximately 25% of the participants developed postictal apnea, indicating that uncontrolled seizures may trigger the condition and cause SUDEP. Researchers determined that postictal apnea-related seizures originate in the amygdala.

Beyond that general insight, researchers conducted an additional evaluation to determine the subregion involved in SUDEP. Using functional magnetic resonance imaging (fMRI) and electrical stimulation, the researchers identified a connection between the amygdala and the brainstem that typically detects changes in carbon dioxide levels and controls breathing.

“Taken together, the findings suggest that seizure activity in a subregion of the amygdala can suppress breathing and air hunger for prolonged periods of time following seizure. This is likely controlled via connections with the brainstem and other brain sites involved in sensing signals from the body. Additional studies are needed to confirm the role of the amygdala in breathing suppression and its involvement in SUDEP,” concluded the NIH release.

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