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‘It’s a long road ahead, but we have a road’

New trial reveals potential of Deep Brain Stimulation for brain injury survivors, even years after TBI

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Deep Brain Stimulation (DBS) has been found to improve cognition after brain injury, even years after a person sustained their TBI – giving hope that the intervention could help to change the reality for survivors. 

Five people who had life-changing, seemingly irreversible cognitive deficits following moderate to severe traumatic brain injuries showed substantial improvements in their cognition and quality of life after receiving an experimental form of deep brain stimulation (DBS) in a phase 1 clinical trial. 

The trial – led by investigators at Weill Cornell Medicine, Stanford University, the Cleveland Clinic, Harvard Medical School and the University of Utah – paves the way for larger clinical trials of the DBS technique and offer hope that cognitive deficits associated with disability following traumatic brain injury (TBI) may be treatable, even many years after the injury.

The DBS stimulation, administered for 12 hours a day, targeted the thalamus region of the brain. After three months of treatment, all the participants scored higher on a standard test of executive function that involves mental control, with the improvements ranging from 15 to 55 per cent.

The participants also markedly improved on secondary measures of attention and other executive functions. 

Several of the participants and their family members reported substantial quality of life gains, including improvements in the ability to work and to participate in social activities, according to a report describing participant and family perspectives from the trial.

“These participants had experienced brain injury years to decades before, and it was thought that whatever recovery process was possible had already played out, so we were surprised and pleased to see how much they improved,” said study co-senior author Dr. Nicholas Schiff, of Weill Cornell Medicine.

“Our aim now is to expand this trial, to confirm the effectiveness of our DBS technique, and to see how broadly it can be applied to TBI patients with chronic cognitive deficits,” said study co-senior author Dr. Jaimie Henderson, at Stanford University School of Medicine.

Chronic consequences after TBI typically involve memory, attention and other cognitive deficits along with related personality changes, which together impair the individuals’ social relationships, ability to work and overall ability to function independently. 

Traditionally, researchers have assumed that these problems stem from irreversible brain cell loss and are therefore untreatable.

However, Dr Schiff’s work has shown that activity in a specific brain circuit, which the investigators termed the ‘mesocircuit,’ underlies deficits in attention, planning and other abilities known as executive cognitive functions, after TBI, and that such functions may be at least partially recoverable. 

The central thalamus brain region normally serves as a kind of energy regulator for this cognitive circuit. Though this region is generally damaged by a TBI, stimulating it via DBS may restore its activity, and thus reactivate the cognitive circuits it serves.

“Basically, our idea has been to overdrive this part of the thalamus to restore brain function, much as a cardiac pacemaker works to restore heart function,” Dr Schiff said.

In a 2007 study, Dr. Schiff and colleagues showed that DBS targeting the central thalamus markedly improved measures of cognition and behaviour in a person with severe TBI who had been in a minimally conscious state for six years. That success, and related preclinical research, led to the new study.

The participants in the new study, four men and one woman, had regained independence in daily function, but cognitive deficits involving executive functions, stemming from TBIs three to 18 years prior, prevented return to pre-injury levels of work, academic study and social activities.

“Despite decades of costly research, we have barely moved the needle in preventing or reducing TBI-related disability. Our results, although preliminary, suggest that DBS may improve cognitive function well into the chronic phase of recovery,” said Dr. Joseph Giacino, a neuropsychologist who helped design the trial, and served as co-first author of the 2007 study. 

Neurosurgeon Dr Andre Machado, chairman of the Neurological Institute at Cleveland Clinic, who previously worked with Dr Schiff on DBS studies of minimally conscious participants, also helped develop the surgical procedure in the new study.

“Targeting very specific parts of the brain after a devastating injury is complex, as each person is affected in different ways by the trauma,” said Dr Machado.

“The success of this study is the fruit of multi-institutional, professional collaboration and the combination of many teams to address a gap in healthcare. This is how good science happens.”

Starting two to three months after implantation surgery, the study team tested the DBS in each participant, fine-tuning the stimulation signal and checking for side effects.

Following the fine-tuning and safety-check period, the five participants were treated by DBS for twelve hours a day, the signals being switched off at night. 

The primary measure of efficacy was the change in the participant’s score, from before surgery to after the 90-day treatment window, on a standard executive function test called the trail-making test part B (TMT-B). The researchers’ pre-set threshold for a clinically meaningful improvement was a ten per cent increase in the TMT-B score.

Even now, several years after the study was completed, all five participants still have their DBS implants, some with new batteries, Dr. Henderson said.

To the researchers, the findings indicate that thalamus-targeted DBS has the potential to meaningfully boost cognitive function and quality of life for many people with moderate to severe TBI.

They now plan a phase 2 clinical trial, with 25 to 50 participants, to optimise the treatment, to confirm its safety and efficacy and to understand better the type of patient with TBI that is best suited for it. If that trial goes well, a larger and more conclusive, phase 3 study would follow.

“There’s a long road ahead, but at least we have a road,” Dr Schiff said.

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