“It was a literal moving target,” Dr. Henderson said.
In the beginning, investigators used microelectrode recording to “listen” to individual neurons to see which ones weren’t firing correctly.
When that method failed to offer the precise information needed for electrode placement, the investigators switched to neuroimaging, which allowed them to complete the surgery more quickly and accurately.
Participants remained in the hospital 1-2 days after surgery. They returned for postoperative imaging 30 days after surgery and were randomly assigned to different schedules for a 14-day titration period to optimize DBS stimulation.
The primary outcome was a 10% improvement on part B of the trail-making test, a neuropsychological test that measures executive functioning.
After 90 days of 12-hour daily DBS treatments, participants’ scores increased 15%–52% (average 32%) from baseline. Participants also reported an average of 33% decline in fatigue, one of the most common side effects of msTBI, and an average 80% improvement in attention.
The main safety risk during the 3- to-4-hour procedure is bleeding, which didn’t affect any of the participants in this study. One participant developed a surgical site infection, but all other side effects were mild.
After the 90-day treatment period, the study plan called for patients to be randomly assigned to a blinded withdrawal of treatment, with the DBS turned off for 21 days. Two of the patients declined to be randomized. DBS was turned off in one participant while the other two continued as normal.
After 3 weeks, the patient whose DBS was turned off showed a 34% decline on cognitive tests. The device was reactivated after the study and that participant has since reported improvements.
The DBS devices continue to function in all participants. Although their performance is not being measured as part of the study, anecdotal reports indicate sustained improvement in executive functioning.
“The brain injury causes this global down-regulation of brain function and what we think that this is doing is turning that back up again,” Dr. Henderson said. “At a very simplistic level, what we’re trying to do is turn the lights back up after the dimmer switch is switched down from the injury.”
New Hope
TBI patients are usually treated aggressively during the first year, when significant improvements are most likely, but there are few therapeutic options beyond that time, said neurologist Javier Cardenas, MD, who commented on the findings for this article.
“Many providers throw their hands up after a year in terms of intervention and then we’re always looking at potential declines over time,” said Dr. Cardenas, director of the Concussion and Brain Injury Center at the Rockefeller Neuroscience Institution, West Virginia University, Morgantown. “Most people plateau and don’t decline but we’re always worried about a secondary decline in traumatic brain injury.”Surgery is usually only employed immediately following the brain injury. The notion of surgery as a therapeutic option years after the initial assault on the brain is novel, said Jimmy Yang, MD, assistant professor of neurologic surgery at Ohio State University College of Medicine, Columbus, who commented on the findings for this article.
“While deep brain stimulation surgery in clinical practice is specifically tailored to each patient we treat, this study goes a step further by integrating research tools that have not yet made it to the clinical realm,” Dr. Yang said. “As a result, while these methods are not commonly used in clinical care, the overall strategy highlights how research advances are linked to clinical advances.”
Investigators are working to secure funding for a larger phase 2 trial.
“With millions of people affected by traumatic brain injury but without effective therapies, this study brings hope that options are on the horizon to help these patients,” Dr. Yang said.
The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic. Dr. Henderson and Dr. Schiff are listed as inventors on several patent applications for the experimental DBS therapy described in the study. Dr. Cardenas and Dr. Yang report no relevant financial relationships.
A version of this article first appeared on Medscape.com .