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Hope for patients with traumatic brain injury

Ken Budd , Special to AAMCNews
October 24, 2019

Groundbreaking research at academic medical centers has led to new treatments for the millions of athletes, veterans, and car accident victims suffering from the debilitating effects of head trauma.

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Every year, more than 1.7 million people suffer a traumatic brain injury (TBI), most of them from falls and car accidents. About 288,000 of those people are hospitalized, and 50,000 of them die. Now, imagine that every potential TBI victim receives an injection as soon as they arrive at the emergency department. The injection not only prevents brain inflammation, but it dramatically reduces the odds of long-term effects.  

It sounds futuristic, but that treatment could be closer than you think. On July 4, 2019, the Journal of Cerebral Blood Flow and Metabolism published research from the University of Texas Health Science Center at San Antonio (UT Health San Antonio) on an experimental TBI treatment. The idea? Brain inflammation can affect electrical currents in nerve cells and lead to seizures (about 40% of mice suffered a seizure within one week of a TBI and many experienced seizures for years, UT Health San Antonio’s research found). The injection activates proteins that can stop that abnormal electrical activity, with impressive results: The treatment reduced brain damage in mice almost to levels of mice without TBI.

“We’re stopping the entire process right from the start,” says Mark Shapiro, PhD, a UT Health San Antonio professor of cellular and integrative physiology and the study’s senior author.

Academic centers like UT Health San Antonio are at the forefront of much-needed research on TBI.

From research into sports-related head trauma to a better understanding of patients who end up in a coma or with long-term disabilities, biomedical researchers around the country are working to help prevent and treat the third leading cause of death and disability in the United States.

Insights on sports-related head injuries

As the U.S. women’s soccer team was competing in the Women’s World Cup in France, some ex-players were making news in Boston. On June 27, soccer legends Brandi Chastain and Michelle Akers announced their participation in Boston University’s (BU) Soccer, Head Impacts, and Neurological Effects (SHINE) study, which will study 20 former female soccer players to determine if headers cause chronic traumatic encephalopathy (CTE). For BU, it’s the latest in a series of groundbreaking CTE projects. The university’s CTE Center maintains the world’s largest tissue repository for research on TBI with more than 600 brains, over 325 of which have CTE. Researchers are using the brain bank for a variety of projects, such as developing a diagnostic test for CTE (which is also a goal for a BU program called DIAGNOSE CTE).

“We have a vast trove of information that’s come from this work,” says Lee Goldstein, an associate professor at BU’s School of Medicine and College of Engineering, and a senior investigator at its Alzheimer’s Disease Center and CTE Center. In 2018, a BU School of Medicine study in the journal Brain found “strong casual evidence linking head impact to TBI and early CTE, independent of concussion,” according to Goldstein. “Once it gets triggered, [CTE] progresses through the brain even if you don’t have subsequent injury. This is a bad, bad disease.”

More recently, researchers at BU, Arizona State University, Mayo Clinic, and Banner Health used an experimental brain scan to detect tau proteins in the brains of NFL players living with CTE. The study, published in May 2019 in the New England Journal of Medicine, showed that the 26 players had significantly higher tau levels than those without symptoms or who hadn’t played contact sports. More research is needed, the study leaders say, to determine if positron emission tomography (PET) scans can be used to diagnose CTE.      

Communicating with coma patients

Determining if a coma patient is conscious seems easy, right? Yet the error rate for detecting consciousness is 30-40%, says Joseph Giacino, PhD, program director and principal investigator for the Spaulding-Harvard Traumatic Brain Injury Model System.

Over the past 15 years, Giacino and his team have used functional magnetic resonance imaging (fMRI) to determine consciousness. A person with a coma is put in a scanner and instructed to perform a mental task, such as thinking of the word “truck.” When they do, the language areas of their brain light up. The same thing happens for motor function if you ask someone to think about raising their right hand.     

“You might have a patient with no evidence of conscious behavior, no speech, no movement, nothing,” says Giacino, lead author of the coma recovery scale-revised, which helps diagnose, assess, and treat coma patients. “But then you put them in the scanner and say, ‘I want you to imagine walking around the rooms of your house, I want you to imagine playing tennis, I want you to imagine saying the word truck,’ and then we look for these functional signatures in the brain. We know now that between 15 and 30% of people who don’t show behavioral signs of conscious awareness actually perform these tasks in a scanner. That’s a big deal.”

Spaulding-Harvard is part of the Traumatic Brain Injury Model Systems (TBIMS) program, which was created in 1987 and includes 16 academic centers, from Indiana University to the University of Washington. Requirements for the “model systems,” as they’re called, include enrolling at least 35 people a year with moderate to severe TBI for the national database, which is run by the TBIMS National Data and Statistical Center and contains information on close to 16,000 individuals.     

TBIMS members also must conduct research and participate in at least one collaborative study with others in the system. Research topics include:

  • Drug treatments for headaches, irritability, and aggression.
  • Interventions to address postinjury substance abuse; decrease caregiver and patient fatigue, distress, and sleep disorders; and improve psychological well-being.
  • Cognitive interventions to improve processing speed, memory, and attention.

An additional focus is developing new diagnostic and prognostic tools for TBI. Giacino is enthusiastic about using biomarkers to predict TBI patient outcomes. Biomarkers and imaging are also helping doctors create more specific subcategories of TBI, which could lead to better treatments. “This idea of phenotyping traumatic brain injury has taken off in a big way and will likely change the complexion of the field,” he says. But one of the critical, most “super important findings” of the last 5-10 years, he says, is that brain injury is not a static event. Some people continue to show improvement over five years and beyond. Others plateau and stay about the same. Roughly 40-50% of people decline. “Brain injury is a chronic health condition,” he says. “And it needs to be managed that way.”

Studying older vets

In October 2019, David Cifu, MD, was awarded a five-year, $50 million grant — the Long-term Impact of Mild Brain Injury Consortium (LIMBIC) — to continue the Chronic Effects of NeuroTrauma Consortium (CENC). Cifu, associate dean of innovation and system integration at Virginia Commonwealth University (VCU) and professor and chairman of VCU’s Department of Physical Medicine and Rehabilitation, will use the money to expand the CENC, which was launched in 2013 to address the long-term effects, refine the diagnostic assessment, and identify innovative therapeutic interventions for combat-related mild TBI. CENC has published more than 70 peer-reviewed papers, delivered 150 presentations, and completed 11 studies, with contributions from more than 70 researchers in 30 universities. Among its findings: Veterans and service members who experienced TBI, regardless of its severity, have significantly higher risks for neurodegeneration — including Alzheimer’s and Parkinson’s disease — as well as chronic pain, suicide, and mental illness.

In one CENC study, which is being expanded in LIMBIC, roughly one third of subjects were experiencing significant symptoms up to seven years after their TBI. The CENC has also found that subjects who suffered three or more head injuries were more likely to experience continuing problems than those who didn’t. “That doesn’t mean they were incapacitated or disabled,” he says. “These people were still working. They still have family lives. But they had a burden of symptoms, such as headaches. Some had difficulty with day-to-day memory.”

With the new five-year grant, the CENC will study the long-term effects of TBI. More than 1,700 current service members and Iraq and Afghanistan veterans are participating in a longitudinal study across eight sites. The CENC plans to increase the number of participants to at least 3,000 and add veterans from other conflicts, including Vietnam and the first Gulf War, as well as active-duty Navy SEALs and Special Forces who were exposed to blasts during training activities and covert operations.

As for the future, clinical research is underway for a variety of new treatments, says Cifu, from medications to specialized therapies, which should benefit the roughly 10% of individuals who don’t show progress after normal treatments. “These studies are highly promising and are likely to generate innovative treatments in the next five years,” he says. Among the most intriguing is implanting microchips into the brain: The chips would receive signals from neurons and improve motor function in people with brain injuries or even control robotic limbs. A prototype unveiled by Elon Musk and his startup Neuralink in July 2019 would use a hearing aid-like device that communicates with the chip and sends data via Bluetooth to a smart phone or other device that runs the necessary software.

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