Research Highlights of the Decade: Part One Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI): A powerful research initiative to address TBI in the United States

In recent years, researchers and clinicians have made significant progress in their understanding of traumatic brain injury (TBI). TBI is a serious public health concern, contributing to one-third of injury-related deaths in the United States and costing the country an estimated $76 billion each year. Experts agree that TBI represents a devastating burden on affected individuals and on the nation’s health care system—yet these recent scientific advances have not been translated into reliable and effective treatments for this common, life-threatening injury.

In one of the most impactful TBI research efforts in this last decade, researchers in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study have focused on developing safe, effective treatments and drugs to improve the lives of individuals affected by TBI. Funded by the National Institute of Neurological Disorders and Stroke (NINDS), this collaborative study supports public-private partnerships at 18 research sites across the United States. TRACK-TBI has enrolled and collected data from 3,684 TBI patients to date, far surpassing the study’s original goal of 3,000 participants. These data are uploaded to an online repository for public access, enabling scientists around the nation to conduct diverse, high-quality, large-sample research studies that contribute to our growing knowledge of TBI.

The ultimate goal of TRACK-TBI is to identify and develop new diagnostic and prognostic tools for use in successful clinical trials. With hope, these trials will result in reliable, innovative methods for preventing, diagnosing, and treating TBI among the millions of individuals who sustain head injuries each year.

Below, we summarize three published research studies from TRACK-TBI that have significantly advanced clinical application in TBI over the last decade. Encompassing multiple populations, injuries, tools, and outcomes, these studies highlight the diversity and flexibility of TRACK-TBI research.

The impact of previous traumatic brain injury on health and functioning: a TRACK-TBI study

While some individuals find that the negative after-effects of their TBI resolve within days or weeks following injury, others suffer long-term issues and deficits. The factors that influence the duration of these issues and longer-term outcomes are not well understood, however past research indicates that the trajectory could be influenced by a history of previous TBI. The goal of this TRACK-TBI study was to determine whether a prior history of TBI had an impact on the outcomes of a current TBI in a population of patients who were admitted to the emergency department for head injury.

Subjects were individuals who were admitted to the emergency department of TRACK-TBI-participating trauma hospitals and had head injuries severe enough to require a CT scan. These individuals provided information about their injury history so that the researchers could group them based on any previous history of TBI with loss of consciousness (LOC), a common measure of TBI severity. The researchers also collected information about the severity of their current TBI. Over the six months after the current injury, they continued to assess the participants’ cognitive, psychological, and psychosocial outcomes, as well as their overall satisfaction with life.

The researchers found several differences between the populations. Individuals who reported having a previous injury were more likely to have co-occurring health complaints, such as musculoskeletal pain, neurological issues, developmental disabilities, and gastrointestinal problems. They were more likely to have been treated for psychological conditions such as anxiety and depression, and were also more likely to have been unemployed at the time of their current injury. According to the results of their six-month follow up, individuals with a previous TBI were more likely to experience more severe mood, post-traumatic stress, and post-concussive symptoms. They were also more likely to report poor satisfaction with life, impaired information processing speed, and poorer verbal learning than those who reported no previous TBI.

Prior to this study, the majority of research on outcomes for individuals with multiple TBIs focused primarily on special groups, such as athletes, who were likely to have multiple head injuries in quick succession. The findings of this study are important because they suggest that, even in cases where there is a long gap between head injuries, the long-term consequences of TBI can be cumulative.

Development of a prediction model for post-concussive symptoms following mild traumatic brain injury: a TRACK-TBI pilot study

Though some individuals who suffer mild traumatic brain injury (mTBI) recover fully within the weeks following their injury, many others experience long-term symptoms, collectively referred to as post-concussive syndrome (PCS). PCS can significantly impact day-to day-living, but it can be difficult to determine who is susceptible for developing this condition. The goal of this study was to create a statistical model to determine what factors may contribute to the likelihood of developing PCS after experiencing mTBI.

The participants in this TRACK-TBI study were individuals who had suffered mTBI, some of whom reported PCS. The researchers compared different demographic factors (such as age, gender, years of education, prior history of TBI, and pre-injury psychiatric conditions) and injury details (such as occurrence of loss of consciousness, post-traumatic amnesia, or extracranial injury) to determine if any of those factors were predictive of developing PCS. To determine which individuals suffered PCS, the researchers used scores from the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), a self-report questionnaire that helps quantify the presence and severity of a variety of post-concussive symptoms. The researchers then used RPQ scores from individuals with PCS at six months post-injury to understand whether different factors predicted the likelihood that different types of symptoms would develop.

Data from a total of 277 patients were included in this study. The researchers found that the presence of emotional, physical, and emotional symptoms were predicted by years of education, pre-injury psychiatric disorders, and prior TBI. They also found that gender, pre-injury migraine or headache, and loss of consciousness or post-traumatic amnesia as a result of injury predicted the occurrence of symptoms from at least one symptom category.

Overall, the results of this study are important because they lay groundwork for determining who is at risk for developing PCS following a TBI. However, the researchers acknowledge that this is a preliminary study, and the results could only be applied to about one fifth of their study population. They acknowledge that future research with larger study populations could expand and further validate the findings from this study.

Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study

Diagnosing a mild traumatic brain injury (mTBI) is not always straightforward. Although CT scans or MRIs are often conducted in the emergency department, these imaging tools may or may not reveal abnormalities—even when an mTBI has been confirmed using other assessment methods. As a result, clinicians and researchers are seeking more definitive ways to diagnose mTBI. Recent diagnostic methods include biomarkers, molecules found in the blood following injury that can indicate the presence of certain injuries or diseases. Biomarkers are used to assess the presence of many different conditions, and they may be helpful a helpful tool for diagnosing mTBI when used alone or in combination with other diagnostic techniques.

This TRACK-TBI study sought to determine whether the presence of a biomarker called glial fibrillary acidic protein (GFAP) could be used to help confirm the results of imaging techniques such as CT and MRI scans if taken within 24 hours following injury. Researchers recruited patients who were brought to the emergency department for head injury and had CT scans that indicated normal findings. Some of the subjects had normal MRI scans, and others had abnormal MRI scans. Importantly, despite their varying neuroimaging results, all of the patients included in this study had suffered an mTBI according to their score on the Glasgow Coma Scale, a commonly used measure of head injury severity. Data from these patients were compared with control groups who either had experienced a non-TBI trauma or had no physical trauma at all. The goal of the study was to determine whether GFAP could be used to confirm the MRI findings.

The researchers found that GFAP concentration was higher in patients who had abnormal MRI findings than those who had normal MRI findings. They also found that these results were dose-dependent: the lower the concentration of GFAP in the blood, the more likely they were to find negative MRI findings. In other words, low concentrations of GFAP correlated with normal (negative) MRI findings, and higher concentrations of GFAP correlated with abnormal (positive) MRI findings. Overall, the researchers concluded that GFAP could be used to confirm MRI results. This finding is important because it helps rule out the possibility of false-negative MRI results, and allow doctors to make decisions about future treatments, such as whether follow-up MRIs are needed after an mTBI.

Citations

1. About TRACK-TBI. Brain and Spinal Injury Center, University of California, San Francisco. 2014. Retrieved from: https://tracktbi.ucsf.edu/transforming-research-and-clinical-knowledge-tbi

2. Dams-O'Connor K, Spielman L, Singh A. et al. (2013). The impact of previous traumatic brain injury on health and functioning: a TRACK-TBI study. Journal of Neurotrauma, 30(24):2014-2020.

3. Cnossen MC, Winkler EA, Yue JK, et al. (2017). Development of a prediction model for post-concussive symptoms following mild traumatic brain injury: a TRACK-TBI pilot study. Journal of Neurotrauma, 34(16):2396-2409.

4. Yue JK, Yuh EL, Korley FK, et al. (2019). Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study. The Lancet Neurology, 18(10):953-961.

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