Study Reveals Association Between Amygdala Region and Persistent Breathing Loss Following Seizures

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In a recently published study, investigators have identified a part of the brain that may be associated with breathing failure following a seizure in patients with severe epilepsy that cannot be managed with treatment.

Brian Dlouhy, MD, associate professor of neurosurgery and pediatrics at the University of Iowa

Brian Dlouhy, MD

Newly published in the journal of JCI insight, findings from a study showed that stimulation in a specific area of the amygdala brain region produced a persistent loss of breathing that continued following the end of a seizure among patients with epilepsy.1 These findings provide new insights into the mechanisms that underlie the probable cause of sudden unexpected death in epilepsy (SUDEP) which may help uncover preventative treatments and identify those most at risk of it.2

In the study, investigators observed that seizures that originated in the amygdala caused postictal apnea and identified a distinct region in the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss continuing well after stimulation. Among 20 participants, 5 patients developed postictal apnea following the stimulation of the amygdala region. According to the authors, this suggested that some individuals with uncontrolled seizures may be more prone to the condition than other patients with epilepsy.1

Clinical Takeaways

  • The study pinpoints a specific amygdala area linked to persistent breathing loss after seizures, offering insights into the mechanisms of sudden unexpected death in epilepsy.
  • Uncontrolled seizures may lead to varying susceptibility to postictal apnea, emphasizing personalized risk assessment in patients with epilepsy.
  • Findings highlight impaired CO2 chemosensitivity during postictal apnea, suggesting the amygdala as a potential target for prevention strategies.

"The importance of our latest work is immense. As you may know, the majority of SUDEP cases are due to loss of breathing that occurs after a seizure ends (postictally)," senior author Brian Dlouhy, MD, associate professor of neurosurgery and pediatrics at the University of Iowa, told NeurologyLive®. We have now identified a focal site in the amygdala that not only causes ictal apnea but also persistent and prolonged postictal apnea following amygdala seizures. We also identify novel connections between this site and the brainstem critical for chemosensation using novel intraoperative experiments and electrical stimulation concurrent with blood-oxygen-level-dependent (BOLD) functional MRI (fMRI)."

READ MORE: Intermittent Use of Midazolam Shows Continued Favorable Profile in Seizure Clusters

Investigators enrolled 12 adults and 8 children with epilepsy that could not be managed with medications, and who also were undergoing intracranial electroencephalography (iEEG) to control their seizures. Seizures were induced in the participants by the researchers using direct electrical stimulation under medical supervision to assess forebrain control of breathing and apnea. The authors then used a technique combining electrical stimulation with fMRI to recognize any connections between the amygdala site and the brainstem region that could be critical for sensing changes in blood CO2 levels and breathing control.

“These new findings are a critical step in developing our understanding of what causes SUDEP and in the development of ways in which to identify those individuals at highest risk and ways to prevent SUDEP,” 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, said in a statement.2

In the patients who experienced postictal apnea with the stimulation, the persistent apnea was resistant to rising CO2 levels and “air hunger” failed to occur. Based on this finding, the authors suggested that postictal apnea impaired CO2 chemosensitivity among the patients. Additionally, investigators observed that amygdala stimulation altered BOLD activity in the pons and medulla and in the ventral insula when combining electrical stimulation with functional MRI. Overall, the authors noted that additional research is required to confirm these results on the role of the amygdala in breathing suppression and its involvement in SUDEP.3

"We have identified a focal site in the amygdala that is critical for postictal apnea and possibly SUDEP. We may be able to identify patients at highest risk of SUDEP and we may now have a potential therapeutic target to prevent SUDEP," Dlouhy, also a member of the Iowa Neuroscience Institute, told. "With this work along with some upcoming and potentially groundbreaking discoveries we will be submitting soon for publication, we believe we are at the precipice for understanding amygdala's role in all of breathing, SUDEP, and interoception/fear/anxiety, and possibly a future clinical trial for SUDEP in epilepsy patients at the highest risk of SUDEP."

REFERENCES
1. Harmata GI, Rhone AE, Kovach CK, et al. Failure to breathe persists without air hunger or alarm following amygdala seizures. JCI Insight. 2023;e172423. doi:10.1172/jci.insight.172423
2. Brain regions identified that may play a role in Sudden Unexpected Death in Epilepsy. News Release. University of Iowa. Published October 3, 2023. Accessed November 21, 2023. https://medicine.uiowa.edu/content/brain-regions-identified-may-play-role-sudden-unexpected-death-epilepsy
3. Small study identifies brain region associated with breathing failure following seizures. News Release. National Institutes of Health. Published October 3, 2023. Accessed November 21, 2023. https://www.nih.gov/news-events/news-releases/small-study-identifies-brain-region-associated-breathing-failure-following-seizures
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