A new technique that uses deep brain stimulation tailored to each patient has exceeded researchers’ expectations in treating cognitive impairment caused by moderate to severe traumatic brain injury.
In 2001, Gina Arata was in her final semester of college and planning to enter law school when she suffered a traumatic brain injury in a car accident. The injury affected her concentration and she struggled with her job sorting mail.
“I couldn’t remember anything,” said Arata, who lives in Modesto with her parents. “My left leg dropped and I was tripping over things a lot. I was always getting into car accidents. And I didn’t have a filter, so I got angry easily.”
Her parents learned about the research being done at Stanford University and contacted them. Arata was accepted as a participant. In 2018, doctors surgically implanted the device deep into her brain, then carefully adjusted the device’s electrical activity to stimulate networks that had been suppressed by the damage.
She noticed the difference right away. When she was asked to list items in the produce section of a grocery store, she could rattle off the fruits and vegetables. The researcher then turned off the device, but she was unable to name it.
“Since the implant, I have never gotten a speeding ticket,” Arata said. “I don’t trip anymore. I remember how much money is in my bank account. I couldn’t read, but after I got the implant, I bought books. Where the crayfish sing, I loved it and remembered it. And I’m not that impatient. ”
Breakthrough in brain injury treatment
An experimental deep brain stimulation device has helped Arata and four others regain varying degrees of cognitive abilities they had lost due to brain injuries years earlier. This new technology, developed by researchers at Stanford Medicine and collaborators at other institutions, is the first to show promise for long-term disability from moderate to severe traumatic brain injury.
The results of the clinical trial were published in a journal on December 4th. natural medicine.
Living with Traumatic Brain Injury
More than 5 million Americans live with the lasting effects of moderate to severe traumatic brain injury: difficulty concentrating, remembering, and making decisions. Many recover to the point where they can live independently, but their disability prevents them from returning to school, work, or resuming a social life.
“Generally, there are very few treatments for these patients,” says Jamie Henderson, MD, professor of neurosurgery and co-senior author of the study.
However, the fact that these patients recovered from coma and regained a significant amount of cognitive function suggests that attention and alertness, the brain’s ability to stay awake, pay attention to conversations, and focus on tasks, supports the brain’s ability to stay awake, pay attention to conversations, and focus on tasks. It suggests that the system was relatively ineffective. Saved.
Understanding and targeting the brain
These systems connect the thalamus, a relay station deep in the brain, to points throughout the cortex, the outer layer of the brain that controls higher cognitive functions.
“In these patients, those pathways are mostly intact, but they’re all downregulated,” said Henderson, the John Bloom Robert and Ruth Halperin Professor. “It’s as if the lights went dim and there wasn’t enough power to turn them back on.”
In particular, an area called the centrolateral nucleus of the thalamus acts as a hub that controls various aspects of consciousness.
“The central lateral nucleus is optimized to drive things over a wide range, but its vulnerability is greater when there is multifocal damage, because it can be attacked from almost anywhere in the brain. That’s what we tend to be hit with,” said Dr. Nicholas Schiff. He is a professor at Weill Cornell Medicine and co-senior author of the study.
The researchers hoped that by precisely electrically stimulating the central nucleus and its connections, these pathways could be reactivated and the lights could turn on again.
clinical trial success
For this study, researchers recruited five participants who had persistent cognitive impairment for two years or more after a moderate to severe traumatic brain injury. They range in age from 22 to 60 years old and were injured between 3 and 18 years ago.
The challenge was to precisely place the stimulation device in the appropriate area, which varies from person to person. Their brains were originally shaped differently, and the damage led to further modifications.
“So we’ve developed a number of tools to more precisely define what that area is,” Henderson said. The researchers created a virtual model of each brain, allowing them to determine the location and level of stimulation that activated the central lateral nucleus.
Based on these models, Henderson surgically implanted the device in five participants.
“It’s important to target the area accurately,” he said. “If you miss your target by even a few millimeters, you are outside the effective zone.”
pioneering moment
After a two-week titration phase to optimize stimulation, participants spent 90 days with the device on for 12 hours per day.
Their progress was measured by a standard test of mental processing speed called the Trail Making Test, in which participants draw lines connecting jumbled letters and numbers.
“This is a very sensitive test of exactly what we’re looking at: focus, concentration, planning and the ability to do this in a time-sensitive way,” Henderson said. .
At the end of the 90-day treatment period, participants’ test speeds improved by an average of 32%, far exceeding the researchers’ goal of 10%.
“The only surprising thing is that it worked exactly as we predicted, which is not necessarily a given,” Henderson said.
Impact on participants’ lives
Improvements in daily life were evident for participants and their families. They resumed activities that seemed impossible, such as reading books, watching TV shows, playing video games, and completing homework. They felt less tired and were able to get through the day without napping.
This treatment was so effective that the researchers struggled to complete the final part of the study. They had planned a blind exit phase in which half of the participants would be randomly selected and their devices would be turned off. Two of his patients did not want to take advantage of the opportunity and declined. Of his three participants in the withdrawal phase, one had his device randomly turned off. After her three weeks without stimulation, that participant’s trail-making test performance was 34% slower than her.
Advances in brain injury treatment
This clinical trial is the first to target this region of the brain in patients with moderate to severe traumatic brain injury, offering hope to many patients whose recovery has stalled.
“This is a pioneering moment,” Schiff said. “Our goal now is to take systematic steps to make this a cure. This is enough signal for us to make every effort.”
Reference: “Deep Thalamic Brain Stimulation in Traumatic Brain Injury: A Phase 1 Randomized Feasibility Study” Nicholas D. Schiff, Joseph T. Giacino, Christopher R. Butson, Eun Young Choi, Jonathan L. Baker, Kyle P O’ Sullivan, Andrew P. Janson, Michael Bergin, Helen M. Bronte-Stewart, Jason Chua, Laurel DeGeorge, Sreya Dikmen, Adam Fogerty, Linda M. Garber, Mark Krell, Jose Maldonado, Matthew Radovan, Sudin A. Shah, Jason Hsu, Nancy Temkin, Thomas Trudias, Jonathan D. Victor, Abigail Waters, Stephanie A. Kolakowski-Hayner, Joseph J. Fins , Andre G. Machado, Brian K. Rutt, Jamie M. Henderson, December 4, 2023, natural medicine.
DOI: 10.1038/s41591-023-02638-4
Weill Cornell Medicine, Spalding Rehabilitation Hospital in Boston, Harvard Medical School, University of Utah; University of FloridaVanderbilt University, University of WashingtonUniversity of Bordeaux, and Cleveland Clinic also contributed to this research.
This research was supported by funding from the National Institutes of Health BRAIN Initiative and a grant from the Center for Translational Sciences at Weill Cornell Medical College. Surgical implants were provided by Medtronic.