Scientists devise breakthrough test for mild brain injuries

It happens all the time in sports—someone receives a blow to the head during a game and assures team trainers all is well: “Put me back in, Coach.” Except the player may have suffered a concussion, also known as a mild traumatic brain injury. Most people spontaneously recover, but about 15 percent continue to have post-concussive symptoms more than a year after their injury—symptoms that may not have even been present when the injury occurred.

“Caregivers see a seemingly innocuous injury on the soccer field, and the player winds up suffering from headaches and failing out of school,” says Damon Kuehl, M.D., an emergency medicine physician at Carilion Clinic and an associate professor at the Virginia Tech Carilion School of Medicine. “Yet someone who may have been knocked completely unconscious gets up, and an hour later is seemingly fine and has no ill effects—ever.

“The way I describe it is providers need a proverbial crystal ball to deliver quicker, more definitive diagnoses so we can get patients the care they need more quickly,” Dr. Kuehl adds. “The problem is we don’t have great tools right now for diagnosing mild traumatic brain injuries at the initial point of care.” It’s the concussion conundrum—how do you diagnose an injury that often has no signs or symptoms? It could be that the solution is small enough to fit in your pocket.

Game Plan

Work started in 2018 when Virginia Tech scientists—including principal investigators Michael Friedlander, Ph.D., executive director of the Fralin Biomedical Research Institute at VTC, and Stephen LaConte, Ph.D., an associate professor at the institute—won a $500,000 competitive grant to speed the development of a multi-modality system to aid in the diagnosis and management of mild traumatic brain injury. The effort involved BRAINBox Solutions, an early-stage startup biotech company that was developing a multi-modality concussion test to administer directly at the point of care.

“While our research was under way, the U.S. Food and Drug Administration granted ‘Breakthrough Device’ designation for the new diagnostic approach from BRAINBox Solutions,” says Dr. Friedlander, who also serves as Virginia Tech’s vice president for health sciences and technology. “The FDA recognized how important it was to accelerate this effort and to be able to accurately and rapidly diagnose mild traumatic brain injury in patients, especially those at greatest risk, including young people, athletes, soldiers, and the elderly.”

The device uses a biochemical test called an immunoassay that measures the presence of molecules in a solution. A small patient blood sample is placed in a container not much larger than a USB drive. The test hunts for specific proteins that have leaked from injury-damaged cells in the brain, entered cerebrospinal fluid, and from there crossed the blood-brain barrier. The proteins serve as biomarkers that can be measured at the point of care through an artificial intelligence–driven algorithm that integrates data from all the test’s components, which also includes validated neuropsychiatric testing. Cognitive assessments are included as well to determine the result of the biological and functional impact of the injury.

“This is a game changer,” says Donna Edmonds, a former critical care nurse and chief executive officer of BRAINBox Solutions. “The brain is extremely complex, and to understand what is going on during a head injury, it takes a multi-biomarker, multi-modality approach. Our method includes a test using a sample of whole blood placed on a cartridge or analyzed in a hospital-based laboratory. The point-of-care test will be plugged into a handheld device, and within about 30 minutes, you have a result.”

As part of a specific site sub-study, Dr. LaConte is deploying sophisticated structural and functional brain imaging technologies on patient volunteers in conjunction with Dr. Kuehl’s clinical assessments and venous blood draws to evaluate BRAINBox’s blood-based biomarker assay.

The objective of the research is to determine whether BRAINBox Solutions’ test is as accurate as clinical assessments and to demonstrate when to use magnetic resonance imaging. “Ultimately, the goal is to reveal what the brain is doing functionally in the context of results from neurocognitive and behavioral testing,”Dr. Friedlander says. “The profile of blood-borne biomarkers in combination with functional testing that reflect the injury and restoration processes under way in the brain provides a very promising approach to the process in its earliest stages, before the later manifestations occur at the level of behavior and cognition.

“When integrated with a battery of neuropsychological tests and through standardization across multiple sites,” Dr. Friedlander adds, “this approach offers an exciting new opportunity for the development of a true point-of-care objective assessment for diagnosing mild traumatic brain injury and providing a scientifically valid approach for personalized care for the patient.”

A Health Problem for All Ages

Just about everyone knows the Hollywood version of the concussion test. Someone gets cracked in the head and a helpful friend rushes to that person’s side, anxiously asking, “How many fingers am I holding up?” If the answer to the question is close to the mark—as it always is—the injured party jumps back into the fray. In real life, the script is not that much different. People really are eager to get back into the game, or to school or work.

After all, “mild traumatic brain injury” suggests the injury is, indeed, mild. Right? Not always. The potential side effects of concussions can be life-changing. The Centers for Disease Control and Prevention has concluded that concussions can affect memory, reasoning, sight, communication, and understanding. And multiple mild traumatic brain injuries have been linked to a range of mental health issues, including depression, anxiety, personality changes, and aggression. As a clinical condition, concussion has been recognized for more than 2,000 years, dating back to Hippocrates, who watched classical wrestlers lose their senses after receiving head blows. The father of modern medicine concluded that “no head injury is too trivial to ignore.”

The warning was visionary, but not necessarily heeded. And as a research subject, concussion hasn’t kept pace. In the 16th century, physicians coined the term commotio cerebri, referring to the shaking of the brain to describe the loss of mental function that concussion can cause. The development of the microscope in the 17th century allowed scientists to reveal the differences in brain tissue of deceased patients who have had concussions compared with those who have had severe brain trauma.

By John Pastor