Biomarkers May Help Diagnose Concussion – MedPage Today
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Two biomarkers may help better diagnose mild traumatic brain injury (mTBI), although one appears to be better than the other, researchers found.
In a study of patients treated at a level 1 trauma center, glial fibrillary acidic protein (GFAP) beat out ubiquitin C-terminal hydrolase L1 (UCH-L1) for detecting TBI, CT lesions, and neurosurgical intervention, Linda Papa, MD, of Orlando Regional Medical Center, and colleagues reported online in JAMA Neurology.
Combining the two were better than GFAP alone at some time points, but these differences weren’t statistically significant, they reported.
“GFAP appears to detect mTBI and traumatic intracranial lesions on CT and predict neurosurgical intervention consistently over 7 days after injury, whereas the utility of UCH-L1 seems to be more limited to the earliest time points after injury,” they wrote.
Mild TBI can be a challenge to diagnose because the symptoms can overlap with other conditions, such as delirium and intoxication. Thus there remains a need for predictive biomarkers for TBI, the researchers said.
Much research has focused on GFAP, a structural protein expressed almost exclusively in astrocytes and released on disintegration of the cytoskeleton, and UCH-L1, a marker of neuronal injury found in high abundance in neurons. Some work has suggested that combining these two markers could improve accuracy.
So Papa and colleagues looked at 1,831 samples from 584 patients treated at their trauma center, and found striking differences in the temporal profiles of these two markers following mTBI.
Although both were detectable within an hour of the injury, GFAP peaked at 20 hours and slowly declined, while UCH-L1 peaked at 8 hours and fell over 48 hours.
They found that GFAP was better than UCH-L1 at distinguishing patients with clinically diagnosed mTBI from trauma controls within 7 days of injury (AUC 0.73 to 0.94 versus AUC 0.30 to 0.67).
They also saw a slight advantage for GFAP in detecting intracranial lesions on CT (AUC 0.80 to 0.97 versus 0.31 to 0.77) and in distinguishing patients with versus without neurosurgical intervention (AUC 0.91 to 1.00 versus 0.50 to 0.92).
In an accompanying editorial, Tanya Bogoslovsky, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, of the Uniformed Services University, said careful design and consistency of data collection “enables their study to bring new insights into the diagnostic accuracy of these two biomarkers.”
“The early rise of UCH-L1 can be useful for detecting mTBI in hyperacute settings and may be suitable for development of point-of-care testing,” they wrote. “The longer half-life of GFAP and its ability to detect CT lesions within 7 days after injury make it useful in subacute settings, when the diagnosis of mTBI with persistent symptoms incurred after concussion can be a particular challenge.”
Julian Bailes, MD, of NorthShore University HealthSystem, who was not involved in the study, said these biomarker screens could be implemented soon, but that it’s unlikely doctors would skip doing a CT scan give its “benefit and relative cost effectiveness, despite radiation concerns, of ‘seeing’ the anatomical structures.”
“As with all systemic or peripheral blood samples, the lack of direct visualization of the brain and skull may be a drawback,” Bailes told MedPage Today. “However, this is an exciting field of study for the future ability to measure the brain’s response with a biomarker.”
In a second study in JAMA Neurology, Jonathan Coles, PhD, of Cambridge University, and colleagues looked at a new PET tracer to get a better understanding of whether cerebral ischemia and hypoxia have distinct pathophysiologic mechanisms in TBI.
They assessed 10 patients who had severe or moderate TBI within 8 days of their injury and compared them with two cohorts of 10 healthy volunteers.
The researchers used both oxygen 15-labeled (15O) and fluorine 18-labeled fluoromisonidazole ([18F]FMISO) to assess ischemia and hypoxia. The 15O PET is more commonly used; [18F]FMISO is a newer PET tracer that undergoes irreversible selective bioreduction within hypoxic cells. It has been used to detect cerebral ischemia in stroke, and could help confirm earlier findings in TBI.
Coles and colleagues found that hypoxia and ischemia both occur in the post-TBI brain, but they don’t necessarily overlap. For instance, tissue hypoxia after TBI isn’t confined to regions with structural abnormality, and can occur in the absence of conventional ischemia.
They said this physiologic signature is “consistent with microvascular ischemia and is a target for novel neuroprotective strategies.”
In an accompanying editorial, Paul Vespa, MD, of the University of California Los Angeles, suggests that hypoxia may be unrelated to cerebral blood flow and may be related to other mechanisms, such as diffusion barrier to oxygen into edematous tissue, a lack of oxygen diffusion into the tissue despite adequate blood flow, or a host of other possibilities.
He added that the study is “hypothesis generating and should stimulate additional studies to explain brain hypoxia.”
Bailes added that the findings should “lead to greater appreciation of the role of hypoxia, and its relationship to cerebral blood flow and ischemia, especially in areas remote from the radiographic injury, and when not necessarily correlated with elevated intracranial pressure.”
The biomarker study was supported by the NINDS.
Papa reported being an unpaid scientific consultant for Banyan Biomarkers but has not received stock or royalties from the company and did not benefit financially from the publication.
The hypoxia study was supported by several governmental and philanthropic agencies. The authors disclosed no financial relationships with industry.
The editorialists on both studies disclosed no financial relationships with industry.
Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College
Biomarkers May Help Diagnose Concussion – MedPage Today