The Journal of Neurotrauma - 2

EXPERT PANEL DISCUSSION
have been working hard and publishing about
various types of devices and technology intended as
objective biomarkers for concussion and traumatic
brain injury.
In this conversation, we will look at some of the
key questions related to TBI biomarkers. Five of
the leading experts in biomarker analysis and TBI
clinical care are on this panel, so I want to try to
understand things from your perspectives, and
learn from your wealth of clinical experience. What
is the most promising direction we should be
heading in regarding the objective diagnosis of
concussion?
We currently have diagnostic tools that are used
in the field to evaluate patients suspected of having
a concussion. In the Military, the MACE/MACE 2
have been used since 2008 to evaluate Service
Members suspected of having had a concussion,
and the SCAT has been used to evaluate athletes.2
Is there really a need for a more objective diagnostic biomarker in your view?
Dr. Bazarian: I think so. Now, I come at this from an
emergency medicine standpoint. These tools can be
useful, but they are difficult to apply to a lot of the
patients who end up coming into the emergency department with what may be a concussion because they
are under the influence of alcohol or other substances,
making the responses to these questions or the evaluation of their memories suspect.
We also have trouble using them with patients who
may have early dementia or may have pre-injury
problems with memory or language, or even in kids
who are pre-verbal. There is a whole host of conditions
where, although these tools are great, and they have
gotten us a long way in Military and athletic settings,
they are hard to apply on a population basis.
Probably others can speak to this with more authority, but with Military cohorts, I know that there are
ways to game the MACE and to memorize the answers
to some of these questions ahead of time. Both tools
include a possibility of getting around them and appear
that you are not concussed if you have the inclination.
Dr. Marion: Sure. So, Dr. Manley, what are your
thoughts about this?
Dr. Manley: I tend to agree with Dr. Bazarian. If we
think about how we deal with other diseases, certainly
if somebody comes in with chest pain to rule out a
heart attack, we are going to have questions that apply
to that scenario. Of course, there is no standard questionnaire like the MACE or the SCAT for chest pain,
but there is a set of diagnostic questions that someone
like Dr. Bazarian would ask a patient in the emergency
department.
2

And yet, what we have found is that the ability to
have a blood-based biomarker can accelerate that
process for evaluating chest pain and can actually cut
through some of the confounding that one might have
with something like indigestion presenting as chest
pain.
I think what Dr. Bazarian is saying is that there are
many confounders in the average patients that come to
our hospital that may not exist in an athlete and may
not exist in a soldier, although there is confounding in
those populations, as well. I think that as with anything
in medicine, we find that to make a diagnosis is actually a constellation of factors. To simply rely upon an
assessment tool, I think, precludes the diagnosis of
some diseases and severity of conditions, and maybe
overestimates the diagnosis in others.
So the ability to have a test that objectively tells us
whether or not there has been some effect or impact on
the brain is critical. We know that people, for example,
can have troponin leaks and still not have profound or
irreversible cardiac damage, is critical. And then we
see people who have very high levels of troponin who
actually do have significant heart attacks.
So again, we are trying to look at the diagnosis of a
problem, and even small levels of some of these proteins may lead us to a diagnosis. But I think we need to
be very careful distinguishing diagnosis from prognosis because sometimes people mix those two. I believe that a tool like a blood-based biomarker will be
additive to things like the MACE and the SCAT, and
in the particularly challenging environments that we
have in emergency departments across our country,
these will actually facilitate and accelerate triage and
diagnosis of these patients.
Dr. Marion: What I am hearing is that you are
concerned about the reliability of your clinical
evaluation of that patient in the emergency department, maybe because of the presence of drugs
or alcohol.
Ava Puccio, you have been in the emergency
department a lot evaluating these patients. What
are your thoughts? Are the MACE and the SCAT2
not likely to be effective enough?
Dr. Puccio: I agree with both Dr. Manley and Dr.
Bazarian. Yes, it is difficult to evaluate these patients
in the emergency department given how busy it is and
considering how many patients are coming in at a
certain period of time. To apply one of these measures
at a one-on-one basis to a patient is not really feasible
and is less likely to happen at that initial evaluation.
You are not going to have the time.
I also agree with Dr. Bazarian that there are the
confounding factors of a patient coming in under the
influence of drugs or alcohol. Also, a lot of patients
ª 2020 by MARY ANN LIEBERT, INC.

The Journal of Neurotrauma

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