Findings of a study published in The Lancet Neurology journal have confirmed the effectiveness of a high sensitivity blood test that might help doctors in ruling out traumatic intracranial injuries like contusion and hemorrhage before resorting to CT (computed tomography) scanning.
The large, multicentre observational trial was conducted by Jeffrey Bazarian, the University of Rochester School of Medicine in Rochester, New York, U.S., and colleagues to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.
TBI occurs when an external force such as a bump or blow to the head disrupts the normal function of the brain. Leading causes include falls, motor vehicle accidents, and assaults. An estimated 54-60 million people worldwide suffer a TBI every year. In the USA, TBI is responsible for more than 2.5 million visits to the emergency department every year, most of which involve milder TBIs like a concussion.
The novel blood test was administered within 12 hours of a suspected traumatic brain injury (TBI), and measured levels of two biomarker proteins which are released into the bloodstream following a brain injury.
Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analyzable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries.
- The blood test correctly identified 99.6% of patients who did not have a traumatic intracranial injury on head CT scans among over 1,900 adults (mostly with mild TBI) presenting to the emergency department.
- For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931–0·995) and an NPV of 0·996 (0·987–0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.
- The blood test was able to predict which patients did not have a brain injury visible on CT scan with very high accuracy, even among those with a GCS less than 15.
Current practice for mild TBI involves a series of checklists of symptoms and signs–known as clinical decision rules–that a treating physician will look for to decide whether a CT scan is necessary. One of the most important clinical guides for determining the need for a CT scan is the patient’s initial level of alertness–measured using the Glasgow Coma Scale score (GCS)–with some guidelines recommending a head CT for anyone with a less than perfect GCS score of 15.
“Based on the results of this multicentre study, routine use of the new biomarker test in emergency departments could reduce head CT scans by a third in acutely head injured patients thought to be in need of CT scanning, avoiding unnecessary CT-associated costs and radiation exposure, with a very low false-negative rate”, says Dr. Bazarian.
“Our results suggest that patients with mild TBI (initial GCS of 14 or 15) who have no other indication for a CT (such as a focal neurologic deficit), and who have a negative test can safely avoid a CT scan. Those patients with a positive test have a 10% chance of an intracranial lesion and most clinicians would get a CT scan of their head to determine if an intracranial injury exists, and define it further. The extent to which these biomarker results can be applied to patients presenting with more severe injury, that is in those with a GCS less than 14, requires further confirmation.”
Based on early, unpublished results of the study, the US Food and Drug Administration has approved the commercial use of this blood-based brain biomarker test, making it the first clinically approved test of its kind in North America.
Currently, doctors use CT scans to detect traumatic intracranial injuries, usually bleeding, which sometimes require immediate neurosurgery. Over 20 million head CT scans are performed each year in the US alone. However, CT scans reveal such injuries in less than 10% of those with milder head injuries, which make up three-quarters of all TBIs, and there is concern about the high radiation dose associated with CT scans of the head which can increase the risk of cancer.
Previous research has highlighted the potential of blood-based brain injury biomarkers to predict patients at high risk of intracranial injuries and in need of CT scanning. S100B is a well-accepted biomarker for TBI and is already in clinical use in Europe. Two other proteins–ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP)–have also emerged as promising predictors of head CT results in small studies.
To provide more evidence, the researchers conducted a prospective study of 1959 adults (aged 18 or over) attending emergency departments between December 2012 and March 2014 with suspected TBIs at 22 sites in the USA and Europe. The ALERT-TBI study directly compared the results of the new biomarker test combining UCH-L1 and GFAP with head CT scan results.
Participants had a Glasgow Coma Scale score ranging from 9-15, and the majority (98%) had a mild TBI, with a score of 14-15 (GCS scores range from 3 [deep coma] to 15 [full consciousness]). All participants received a head CT as part of standard emergency care and had blood samples taken within 12 hours of injury.
“Further research to determine the extent to which the biomarker test complements decision rules, and as well as its impact on health care costs and patient throughput, will be key to understanding the test’s usefulness in clinical practice,” concluded the authors.
For further information log on to https://doi.org/10.1016/S1474-4422(18)30231-X