The ‘Concussion Blood Test’ – Everything You Need to Know

The so-called concussion blood test may not replace the need for a head CT, but there are situations where is it more useful than not.

Last Updated: 30 March 2019

Concussion Blood Test Brain Trauma Indicator

By Jordan G. Roberts, PA-C

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The Concussion Blood Test Needs Assessment

Discovering a biomarker to identify a mild traumatic brain injury (mTBI) is the holy grail of concussion research. A so-called concussion blood test that can distinguish between concussed and non-concussed individuals, especially days to weeks later, would be a dream come true for clinicians and researchers alike. 

Because this remains such a public health concern and coupled with the fact that many states require certain practitioners to earn dedicated concussion CME each year, we thought we’d share an update on something near and dear to our brains.

Most concussion research to date has focused on sports-related concussion (SRC), which occurs most often in relatively young athletes. Sports-related concussion is a complex and often notoriously difficult diagnosis to make on the field or in the emergency department. Further complicating matters, the clinical presentation and evolution of the condition can vary greatly from patient to patient.

Because these patients are usually otherwise healthy and full of potential, the possibility of a permanent, devastating neurological outcome makes pediatric traumatic brain injury (TBI) a medico-legal landmine.

Concussion Medicolegal Issues

The initial investigation may consist of a head CT in the emergency department. However, expose too many young people to radiation, and someone might try to blame you for their cancer in 50 years. On the other hand, if you don’t scan the kid who dies of an epidural hematoma, it’ll haunt you forever. 

And don’t forget about your adult head trauma patients. This population is more likely to be injured at work, through violence, or other means different from your pediatric patients.

Fortunately, guidelines and algorithms such as the PECARN criteria exist to help clinicians make evidence-based medicine choices. Theoretically, this should reduce the use of CT scans in the pediatric emergency department. The downside (to some) is that many of these decision making tools still rely (somewhat) on clinical subjectivity.

However, in February of 2018, the US Food and Drug Administration (FDA) granted marketing approval to a new laboratory assay that uses a blood draw to ‘aid concussion evaluation.’

Some media outlets (who forgot to have a clinician double-check their headlines) quickly wrote all about the so-called concussion blood test. One might even think that this assay will dramatically reduce young athletes’ CT-induced radiation exposure.

It could change the workup in the emergency department. But when ‘to scan or not to scan’ is not your main decision point, it may not be as helpful. Also, you’ll get the results of the CT scan faster than the results of the current generation assay. I’ll explain that below.

Despite the issue of time sensitivity, many of us are wary about scanning young kids and their developing organs. Because we think radiation dosage is cumulative, too much gets a bad rap. Usually. And for good reason; treating pediatric radiation-deficiency has fallen out of favor lately

The Concussion Blood Test: The Brain Trauma Indicator

Developed by Banyan Biomarkers, Inc, it measures two proteins; Ubiquitin C-terminal Hydrolase-L1 (UCH-L1) and Glial Fibrillary Acidic Protein (GFAP). Scientists believe these biomarkers can be detected in the serum of patients with visible intracranial lesions on CT after a TBI. You may remember that patients with concussions don’t really have visible intracranial lesions.

So is this a concussion blood test or not?

Before we get there, remember the question we should always be asking ourselves first is “how does this change my management?”

Looking for great online CME?

What Is the Brain Trauma Indicator (BTI)?

It is the blood test developed by Banyan Biomarkers that is getting all the hype for being the first of its kind. It identifies the neural proteins Ubiquitin C-terminal Hydrolase-L1 (UCH-L1) and Glial Fibrillary Acidic Protein (GFAP) in the serum of adult patients with a traumatic brain injury.

And don’t try to tell me you don’t remember these from sleeping through neurology lectures! The UCH-L1 is found in high concentrations of neural tissue, comprising 1 to 5 percent of total neuronal protein. It functions to maintain axonal integrity, and is not found in high concentrations in other healthy tissue.

Defective UCH-L1 has also been implicated in neurodegenerative states, stroke, intracranial hemorrhage, high-grade glioma, pancreatic neuroendocrine tumors, and pediatric burn injuries.

GFAP is the main nanofilament found in astrocytes. It makes up a system that allows these cells to coordinate a response to central nervous system crises. Astrocytes take on this role in conditions such as stroke, neurodegeneration, and yes, CNS trauma.

These proteins escape the brain and head into the serum after a neurologic insult. This assay claims to measure the serum concentration of these molecules following a TBI. Although the catch is that you have to draw the sample within twelve hours of the injury. And then wait another three to four hours for the results. Longer if the lab is busy. But that isn’t too different from a lot of labs we order now. So what did the regulators say?

Concussion Blood Test
The Brain Trauma Indicator measures serum UCH-L1 and GFAP

The FDA Approval of the Brain Trauma Indicator

According to their press release on February 14, 2018, “the FDA today permitted marketing of the first blood test to evaluate mild traumatic brain injury (mTBI), commonly referred to as concussion, in adults.

Right off the bat we can see that this particular assay was not endorsed to be a part of the workup of sports-related concussions (SRC) in adolescents and younger children. 

In regards to the biomarkers, the FDA notes that “levels of these blood proteins after mTBI/concussion can help predict which patients may have intracranial lesions visible by CT scan and which won’t.”

The FDA also included this snippet below in their press release, which took me by surprise [emphasis mine]. Although it is a killer marketing move on the manufacturer’s part:

“These findings indicate that the test can reliably predict the absence of intracranial lesions and that health care professionals can incorporate this tool into the standard of care for patients to rule out the need for a CT scan in at least one-third of patients who are suspected of having mTBI.”

Standard of care, already? Slow down, there! We just met. And anyways, I’m not that kind of clinician. You at least have to buy me dinner and make me sit through a monotonous slide deck, first.

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Evidence For The Brain Trauma Indicator

The clinical trial results are pending as of this publication, so there isn’t much we can say with a lot of confidence at this point. Here’s some of the data that is available:

When measured up against head CT, the Brain Trauma Indicator correctly predicted the presence of intracranial lesions in 97.5 percent of cases.

It was also able to accurately identify those who did not have an intracranial lesion on a CT scan in 99.6 percent of cases.

Again, my only reference for this is the FDA press release, so be careful interpreting any results you haven’t personally verified. I’ll add more information as I get it.

Evidence Update (September 2018)

A study published in the Lancet in September 2018 reveals some interesting analysis about these two biomarkers. 

Researchers evaluated data from nearly 2,000 subjects aged 18 years and older presenting within twelve hours of a non-penetrating traumatic brain injury. Here’s what they found:

  • 125 (6%) had CT-detected intracranial injury
  • 8 (<1%) had neurosurgically manageable injuries
  • 1,288 (66%) had a positive UCH-L1 and GFAP test
  • 671 (34%) had a negative UCH and GFAP test
  • 3 (<1%) had a positive CT and negative blood test

This corresponds to a sensitivity of 97.6 percent and a negative predictive value of 99.6 percent. 

Of course, further studies are needed to determine how this study can best be clinically implemented.

By the way, for a brush-up on CT findings in patients with TBI as well as other neuroradiological principles, here’s some help. Fair warning – it’s not a beach read for most people. 

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PECARN for Pediatric Head Injury: A Clinical Decision-Making Tool

So, Do We Have A Concussion Blood Test?

Maybe.

When this test first came out, we would have flatly said no. However, as the evidence changes, so does our thinking.

This assay may have other value, too. It can help stratify adult patients into two groups: those who probably need a CT of the head anyway, and those who don’t.

However, it doesn’t tell you who has a concussion, who needs neurosurgery, and who might spend the rest of their life in the CT suite. Because only patients older than 18 years of age were included in this study, its use is limited in pediatrics. Therefore, this blood test won’t help diagnose or manage pediatric sports-related concussion in its current form.

However, it is a step in the right direction when it comes to brain trauma evaluation. It will be incredibly useful in resource-limited areas where the CT scanner is a three day journey rather than a three minute gurney ride down the hall. Like any tool, just be careful how you use and interpret it.

Concussion CME

Plus Other Concussion Resources for Physicians, PAs, & NPs

Clinicians from various specialties will be called on to care for patients with concussion.

From sports medicine to primary care, pediatrics, and emergency clinicians acutely to neurology, neurosurgery, and psychiatry in the long term, not to mention nursing, allied health, and others, the physicians, PAs, and NPs of these specialties have an interest in knowing what’s new.

Nobody “owns” concussion like some other conditions.

That’s why we have put together the best sports medicine CME for primary care providers, pediatrics CME, emergency medicine CME, neurology CME, neurosurgery CME reviews, psychiatry CME, and nursing CE to meet this need.

We also have an extensive collection of concussion resources, many free, including articles, clinical decision support tools, slide decks, and other innovative tools to help you provide the best care possible to patients with concussion. 

If you want to earn some CME and listen to smart people say funny things at the same time, you’ll want to subscribe to Hippo Education’s Primary Care Reviews and Perspectives. Check out episode 34 (aired in May of 2017) for my chapter on the non-sports concussion. By the way, sign up through our link above and get $25 off your subscription. 

If you enjoyed this post, sign up for our email list below so that you never miss another article like this. 

References

Bazarian JJ, Biberthaler P, Welch RD, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. The Lancet Neurology. 2018;17(9):782-789. doi:10.1016/s1474-4422(18)30231-x

Bishop P, Rocca D, Henley JM. Ubiquitin C-terminal hydrolase L1 (UCH-L1): structure, distribution and roles in brain function and dysfunction. Biochemical Journal. 2016;473(16):2453-2462. doi:10.1042/bcj20160082

Evaluation of Biomarkers of Traumatic Brain Injury  – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/record/NCT01426919?term=ALERT+TBI&rank=1.

GFAP glial fibrillary acidic protein [Homo sapiens (human)] – Gene – NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/gene/2670.

Hol EM, Pekny M. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Current Opinion in Cell Biology. 2015;32:121-130. doi:10.1016/j.ceb.2015.02.004

Moore MD, Finnerty B, Gray KD, et al. Decreased UCHL1 expression as a cytologic biomarker for aggressive behavior in pancreatic neuroendocrine tumors. Surgery. 2018;163(1):226-231. doi:10.1016/j.surg.2017.04.040

UCHL1 ubiquitin C-terminal hydrolase L1 [Homo sapiens (human)] – Gene – NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/gene/7345.

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