Mayfield Foundation helps UC Researchers Earn $4.7M to Study Secondary Injury after TBI

CINCINNATI -- Seed money provided by the Mayfield Education & Research Foundation helped researchers in the University of Cincinnati (UC) Department of Neurosurgery gather the data they needed to earn a $4.7 million grant from the Psychological Health/Traumatic Brain Injury Research Program at the United States Department of Defense.

The grant will enable UC and five other academic institutions to use new monitoring techniques to study the wave of secondary injury that follows an initial blow to the head. Secondary injury occurs in the form of damaging, seizure-like waves that spread slowly through the brain following a traumatic brain injury (TBI). The team will investigate less invasive techniques to monitor these waves of electrical disturbance – called spreading depolarizations or "brain tsunamis" – which are associated with worse outcomes in patients.

Jed Hartings, PhD, Research Associate Professor in the Department of Neurosurgery and a former major in the U.S. Army Medical Service Corps, is the study's principal investigator.

Besides UC, study sites comprise Baylor College of Medicine, Massachusetts General Hospital / Harvard University, the University of California San Francisco, the University of Pittsburgh and the University of Miami. The study is a collaboration with TRACK-TBI, a national effort to improve understanding and classifications of TBI.

Preliminary research that led to the award was published in the journal Annals of Neurology in 2014 and highlighted in the journal Nature Reviews. The preliminary research, which involved a small sample of patients, also was funded by the U.S. Army's Psychological Health and Traumatic Brain Injury Research Program.

TBI research

In the new study, Dr. Hartings and his colleagues aim to measure brain tsunamis in two ways in nearly 200 patients treated at the UC Medical Center at UC Health. They will place one set of monitoring electrodes directly on the brain during surgery, and the second set on the scalp. Scalp electrodes produce an electroencephalograph, or EEG, recording. Previously, spreading depolarizations could only be detected through the insertion of surgical leads onto the patient's brain.

"The invasive recordings will allow us to interpret the non-invasive scalp (EEG) recordings and confirm whether or not spreading depolarizations are occurring," Dr. Hartings says. "This will allow us to develop the criteria we need to recognize brain tsunamis that occur in patients who have a brain injury but do not require surgery."

If successful, the researchers will have opened a new "window" into the brain for the 85 to 90 percent of patients who have suffered a head injury but are not candidates for surgery and intracranial monitoring.

"Knowledge of whether spreading depolarizations are occurring in these patients would revolutionize neurotrauma care by allowing clinicians to administer treatment selectively and to adjust therapeutic intensity according to its ability to block the depolarizations," Dr. Hartings says.

If the researchers confirm their ability to diagnose brain tsunamis through EEG monitoring, they hope to determine whether the tsunamis occur in all TBI patients or only in a subset of patients. They also seek to determine whether the tsunamis are associated with increased morbidity and mortality in TBI patients who do not require surgery.

Results of the study could make EEG an important diagnostic tool in the treatment of all intensive care patients following neurotrauma. Furthermore, the monitoring could be extended to individuals who have suffered a stroke.

"Spreading depolarizations occur in 80 to 90 percent of people who suffer a severe stroke," Dr. Hartings says. "The damage they cause in stroke patients is similar to the damage caused in neurotrauma patients."

The discovery that depolarizations could be viewed through scalp EEG was not made sooner because of historical conventions in how scalp EEG data is reviewed. Continuous EEG is typically studied in small 10-second segments, which allows detection of abnormal brain waves, such as epileptic spikes, which last fractions of a second. The changes associated with spreading depolarizations, on the other hand, develop over tens of minutes. In the Annals of Neurology study, the researchers reported on spreading depolarizations that lasted from 10 minutes to several hours.

When EEG data is time-compressed so that hours of recordings are presented on a single screen, a depression in the amplitude of brainwaves comes into focus. Dr. Hartings has likened the phenomenon to the Nazca Lines, the famous geoglyphs in the desert of southern Peru. The Nazca lines suggest nothing up close; but when seen at a distance from surrounding foothills or an airplane, images of artistry emerge.

Bringing noninvasive brain monitoring to the patient's bedside is a primary objective of Dr. Hartings's research, which has played a leading role worldwide in the understanding of spreading depolarizations in acute neurologic injury. Dr. Hartings and his team characterized the phenomenon in TBI and laid the foundation for understanding its destructive nature in research published in Lancet Neurology and Brain in 2011.