Final moments: understanding the neurobiology of dying

A new study furthers research on "brain tsunamis" and provides insight into the neurobiology of dying. This innovative research received partial funding from the Mayfield Education & Research Foundation, the United States government, and Germany's Center for Stroke Research Berlin.

Researchers monitored a group of 9 patients who suffered devastating brain injuries caused by brain trauma or subarachnoid hemorrhage (bleeding after a brain aneurysm rupture). When the patients failed to respond to treatment in the intensive care unit, their families signed a Do Not Resuscitate (DNR) order and requested that their loved ones receive only comfort care.

Over the next moments, researchers studied the sequence of events in the brain and circulatory system using advanced methods to measure brain pressure, oxygen levels, and electrical activity. They found that brain electrical function stopped near the time of systemic circulatory arrest, as expected. However, it would take several more minutes until the final brain wave developed, a tsunami-like wave called a spreading depolarization.

"We know from animal studies that the toxic chemical and cellular changes that lead to brain death after circulatory arrest don't begin for several minutes, well after brain activity has stopped," says Jed Hartings, PhD, a lead author and Associate Professor in the Department of Neurosurgery at the University of Cincinnati. "These initiate spreading depolarizations, which begin the countdown to irreversible damage."

Evidence of terminal spreading depolarization was seen in most of the patients. These waves were once thought to develop only in some neurologic diseases, such as migraine with auras. This new study suggests that everyone will experience a brain tsunami at the end of life.

Spreading depolarizations in the dying process have not been observed previously because they can't be detected with normal clinical EEG methods. "If brain circulation can be restored quickly, the cellular changes of spreading depolarization may be reversible," Dr. Hartings says. "Therefore, our findings have potential for protecting the brain after survivable ischemic insults, such as stroke and cardiac arrest."

Prof. Jens Dreier, at the Center for Stroke Research Berlin, explains, "Our findings may also help fine-tune strategies for organ donation protocols. Death is typically declared between 2 and 10 minutes after circulatory arrest. But until the final tsunami-like wave occurs, the brain cells remain quite viable." The team's findings were published online last week in the journal Annals of Neurology.

Additional co-authors include Mayfield neurosurgeons Norberto Andaluz, MD, and Vincent DiNapoli, MD, PhD, as well as Sebastian Major, MD, Brandon Foreman, MD, Maren K. L. Winkler, MD, Eun-Jeung Kang, MD, Denny Milakara Coline L. Lemale, Jason M. Hinzman, PhD, Johannes Woitzik, MD, and Andrew Carlson, MD.

For immediate release:
February 28, 2018

Deborah Livingston
Development Director
Mayfield Education & Research Foundation

Phone: 513-569-5277