Brainstem Damage in Epilepsy May Be Biomarker for Increased SUDEP Risk

Patients who died from suspected SUDEP had extensive damage to areas of the mid-brain and brainstem that control autonomic function.
The following article is part of live conference coverage from the 2017 American Epilepsy Society Annual Meeting in Washington, DC. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AES 2017.

WASHINGTON, DC – Epilepsy-related brainstem damage on magnetic resonance imaging (MRI) may be a potential biomarker for increased risk of sudden unexplained death in epilepsy (SUDEP), according to findings presented at the 2017 American Epilepsy Society Annual Meeting, December 1-5, 2017 in Washington, DC.

Previous evidence from animal and MRI studies in humans suggest a breakdown of the central autonomic system in SUDEP, which can adversely affect breathing and heart rate variability. Structural damage in the brainstem has been previously observed in patients who died from suspected SUDEP.

In order to better understand the role of brainstem damage in SUDEP risk, researchers studied 2 populations of patients with epilepsy: an autonomic population comprised of 18 patients with focal epilepsy and 11 controls who had available heart rate variability measurements and 3 tesla MRI; and 27 patients with epilepsy who had MRI data available 1-10 years before their SUDEP-related death. Deformation-based morphometry of the brainstem was used to create profile similarity maps from Jacobian determinant maps that were characterized by graph analysis regions with excessive expansion (sigExcROIs).

MRI data revealed mild damage in the mesencephalon in patients in the autonomic group. The total sigExcROIs counts in the autonomic population were negatively correlated with heart rate variability (r= -.37; P =.03). They also noted that sigExcROIs counts in the periventricular gray/medulla oblongata autonomic nuclei were responsible for most of the heart rate variability-associated variation (r/r2= -0.82/0.67; P2 =-.60, P =.001). In the SUDEP population, more extensive damage was identified in the mesencephalon, as well as the medulla oblongata.

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“We suspect that if areas of the brain involved in breathing and heart rate are damaged, people who have epilepsy may no longer be able to control these functions properly during a situation of heightened demand, such as a seizure,” said co-author Alica Goldman, MD, PhD, MS, of Baylor College of Medicine in Houston, in a statement.

“Being able to identify people who may be at risk would be significant,” said lead author Susanne Mueller, MD, of the University of California, San Francisco. “While we are a long way from being able to use MRI as a biomarker, this is the first evidence that brainstem damage, one of the mechanisms that has been shown to cause SUDEP in animals, could also play a role in people with epilepsy.”

The researchers noted that the findings need to be repeated in larger, prospective studies using standardized imaging protocol before being employed as a clinical biomarker in this population.

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Mueller SG, Nei M, Bateman L, et al. Evidence for brainstem network disruption in focal epilepsy and sudden unexplained death in epilepsy: a first validation study. Presented at: 2017 American Epilepsy Society Annual Meeting. December 1-5, 2017; Washington, DC. Abstract 3.205.