Traumatic brain injury (TBI) occurs when an external force to the body or head alters brain function. There are approximately 2-4 million new incidents of TBI in the United States annually, and 30-50 million cases globally. Additionally, the Centers for Disease Control (CDC) estimate that about 5 million Americans live with the sequelae of TBI. Data suggests a recent increase in disability rates for TBI-associated injuries in the military, and severe long-term effects for professional athletes. Furthermore, TBI increases the lifetime risk for neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease. TBI has a substantial medical and personal financial burden as well. The direct and indirect costs of medical diagnosis and treatment, in combination with lost productivity for mild TBI, may be greater than $60 billion annually.
There is much variability in the severity, diagnosis, and even nomenclature used. TBI may also be called mTBI (mild traumatic brain injury), minor closed head injury, or concussion, among other terms. The diagnostic criteria, classification, and management of TBI is fragmented in medical specialties and even professional medical societies. Without a standardized diagnostic process that is universally accepted and applied, there is risk of missing patients affected with TBI, which may lead to suboptimal patient care. Some providers may use The Glasgow Coma Scale (GCS) as a screening tool, which applies a point value to varying symptoms. The more responsive a patient is, the higher the score. Thus, a lower score is suggestive of greater severity. A GCS score of 3-8 is severe; 9-12 is moderate; and 13-15 is mild. A full TBI workup is difficult to perform in the field and usually occurs in the traditional clinical setting of a doctor’s office or emergency room visit. Brain imaging in the form of a computerized tomography (CT) scan or magnetic resonance imaging (MRI) may be used to determine severity of a head injury. These imaging technologies are useful for fractures, hematomas, and brain edema. However, most CT scans and MRIs demonstrate unremarkable findings for those with mTBI, and do not rule out the risk for long-term adverse effects.
Although TBI may be accidental and affects people of all ages, it may occur more commonly in specific settings such as the military, first responders, and recreational/collegiate/professional contact sports participants. Many of these head injuries occur in a “field” environment, and there is no access to a medical facility. Sporting events may have medical professionals available to screen players for injuries, including TBI. For example, the National Football League (NFL) has instituted a sideline protocol for evaluating players for a TBI or concussion, which was updated in 2018. It is important that injured players are removed from the game so they can receive proper medical care; conversely, it is crucial that those who do not have traumatic injury can continue to participate. Even among healthcare providers who are trained to screen for TBI, there is some variability in the diagnosis and ruling out TBI, especially where symptoms are mild and unpredictable.
ImPACT, an FDA cleared medical device, can be used to assess traumatic brain injury, which is marketed to healthcare institutions, schools, and sports organizations. It consists of an online questionnaire that is administered in the beginning of a sports season, employment period, etc., and when someone is injured. The baseline answers are compared with the answers provided at the time of injury. The questionnaire takes about 25 minutes to complete and is designed to measure and compare neurocognitive function, memory, attention span, non-verbal problem solving, reaction time, etc. The proprietary software algorithm creates a customized health report which will aid clinicians in patient care. Although this online questionnaire format creates some standardization for the diagnosis of TBI, researchers are trying to create a screening test using biological markers in a clinical lab setting.
A brain injury may cause a combination of tissue deformation, axonal shearing, contusion, necrosis, and blood-brain barrier disruption. Biomarkers can be released into the cerebrospinal fluid and bloodstream after a head injury. Therefore, different biomarkers are being researched to create a TBI blood test that would allow for standardization in a point of care setting. Ubiquitin C-terminal hydrolsase-L1 (UCH-L1) is a protein that may be found in the cytoplasm of a nerve cell. Multiple independent studies have demonstrated UCH-L1 serum levels are correlated with severe TBI and may have clinical utility in prognosis. Glial fibrillary acidic protein (GFAP) also stands out among biomarkers studied as being extremely reliable. Similar to UCH-L1, GFAP may be indicative of TBI severity.
There is a great need for a precise, accurate, and rapid test that can be performed in the field, outside of the traditional medical setting for point of care. To that end, Abbot has commercialized a blood test that is performed on their handheld i-STAT™ Alinity™ platform. If an individual is suspected of having a concussion, this test can be run quickly and efficiently with a high degree of accuracy. Furthermore, the FDA recently provided 510(K) clearance for this technology. Results are typically available within 15 minutes. The i-STAT Alinity TBI plasma test measures GFAP and UCH-L1 simultaneously. Currently, a blood specimen needs to be spun in a centrifuge and the test is performed on the separated plasma. To alleviate the need for centrifuging, which may hamper field testing, Abbot is researching a similar test to be performed on a whole blood specimen. The implementation of a biomarker-based test may reduce the need for unnecessary CT and MRI scans for diagnosis, thus saving healthcare millions of dollars.
TBI poses a significant healthcare burden, while the diagnosis of such injuries can be subjective, depending on the methodology and the clinician performing the assessment. Professional medical society guidelines may differ in their recommendations. Fortunately, the FDA recently approved a biomarker-based test, which has the potential to streamline the assessment and save considerable time and money. This test will likely be improved with further research, with the intent of having a reliable, precise, rapid test that can be performed at point of care. It has the capability of becoming particularly useful in contact sports, the military, and first responders; especially if the test can be validated on whole blood. Hopefully, biomarker-based testing will be widely accepted after clinical utility is demonstrated, which may assist clinicians in the diagnosis and ruling out of TBI in a field setting.
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Abbot Hand-held i-Stat test – https://www.pointofcare.abbott/us/en/offerings/istat/istat-test-cartridges
CDC Glasgow Coma Scale – https://www.cdc.gov/masstrauma/resources/gcs.pdf
ImPACT Questionnaire-based testing – https://impactconcussion.com/
Insights / March 10, 2019 / by beaconlbs
MagnaCare Announces Collaboration with BeaconLBS to Help Physicians Select Laboratory Tests that Can Improve Patient Care and Reduce Costs
MagnaCare, a leader in health plan management services, announced today that it has entered into an agreement with BeaconLBS.