The Journal of Neurotrauma - 7

EXPERT PANEL DISCUSSION
Dr. Marion: You did not mention exosomes?
Dr. Gill: In our labs we have looked at exosomes for
inflammation specifically, because we know that
when we see IL-6 or something that is more proinflammatory in the blood, it is indicative of being
more prognostic. But what we really want to do is
focus in on the central inflammation, which we know
is much more related to that.
We have seen, especially in some of our CENC
studies, that IL-6 and central inflammation relates to
having these chronic symptoms, and is also linked
with NfL activity. And so that is really the promise
of exosomes: being able to use peripheral blood, not
to go more centrally, to understand the central
mechanisms of tau as well as inflammation. We have
a series of studies that seem to be pretty promising to
give us much more prognostic evaluations.
Dr. Marion: Dr. Puccio, what about microRNA?
Dr. Puccio: I do not think we are as far along in the
microRNA arena yet, although we are exploring a little
more. It will come.
We need to see a lot more assays performed. Unfortunately, some of those are expensive. That is one of
the things that also needs to be considered when
evaluating any of these assessments. So, as you mentioned, EEG. With EEG, there is additional technician
and clinician time of placement and cost associated
with other assays that we mentioned. It's the same
thing with microRNA. Right now, that is not an easy,
quick return on your money.
Dr. Marion: Dr. Manley, if a point-of-care testing
device were available - i-STAT, for example -
would this blood-based biomarker analysis technology be useful to you even if it only indicated that
the CT was abnormal, but it did not tell you much
about whether or not there was a concussion?
Dr. Manley: Yes, because this is going to help with
our triage. As you know, the single biggest driver for
TBI patient admission to the hospital these days is
abnormalities on a head CT. We often think about
these blood-based biomarkers for a population where
we cannot see what we would call obvious trauma that
would suggest a significant brain injury.
And something that Dr. Bazarian alluded to earlier is
that we are seeing an increasing age in our population
with traumatic brain injury, and people with these
more significant injuries tend to stay silent for a longer
period of time. If you go to your emergency department, if you are not comatose when you show up, you
are likely to end up on a waiting list to be able to get a
head CT. If you look at the average time at most level 1
ª 2020 by MARY ANN LIEBERT, INC.

trauma centers from the time a head CT is ordered for a
patient who is not comatose or in extremis, it can be
several hours.
We have all had the experience where a patient
actually declines within that period of time, suggesting that had we known earlier that they had the
kind of injury that would merit a head CT, we could
have intervened from a neurosurgical perspective
earlier. These biomarkers are not only for the milder
forms of injury, but they are also there for the more
significant forms of injury, which can go undetected.
This goes back to the notion of these different devices for diagnosis. Many of them are very good,
whether we are talking about eye tracking or some of
the EEG technology that is out there. I think what it
comes down to is, what will clinicians actually use?
And I think the idea of having a point-of-care device
would accelerate things because it is something that we
as clinicians are comfortable with, which is a blood test
- we order blood tests for everything. There are at least
120 blood tests at our disposal. This is not to say that
these other tools that have been developed to diagnose
TBI are not great tools and they do not do what they say
they are going to do, because they do. It is what actually
fits into the practical clinical workflow that clinicians
are used to doing, and are already doing daily in the care
of patients.
Patients are much more comfortable going to a
lab out in their community and getting a blood
draw for a test. As Dr. Gill brought up, what are the
subacute and chronic effects of these kinds of injuries? I think her work and the work of others is
beginning to demonstrate that there may be value in
these blood-based biomarkers after the initial event.
The notion of being able to just go get a blood test to
see, for example, what your neurofilament light (NFL) is doing over time, because we see that this marker
goes up over time, whereas these other markers are
going down, and that may be a marker of long-term
degeneration.
I think it is a very exciting time. I think that on one
hand, we have got some very practical things that we
are seeing acutely that we can do, and a lot of promise
for other things that we may find in the future.
Dr. Marion: One of the things that I think is also
going to be very important is that this technology
be usable in a remote environment. In the Military
that is an important requirement. Military conflicts are frequently in austere environments and
combat medics and corpsmen need to be able to
do a lot of the assessment and acute care of TBI
patients. A portable, or point-of-care, technology
for the early determination of whether or not a
patient has a surgical intracranial mass lesion
would be very useful.
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