September 9, 2025 • 46 mins
The quest to understand persistent brain symptoms after concussion has puzzled doctors and researchers for decades. What happens when the brain doesn't heal as expected? Why do some patients develop long-term problems while others recover completely?
Dr. Mavrudis, consultant neurologist and pioneering researcher, pulls back the curtain on these mysteries by revealing surprising connections between post-concussion syndrome, functional neurological disorders, and even long COVID. At the heart of his research is a revolutionary perspective: these seemingly different conditions share fundamental mechanisms related to neuroplasticity – the brain's ability to adapt and form new connections. When this process breaks down at the synaptic level, where neurons communicate, symptoms persist despite normal-appearing brain scans.
The conversation takes us deep into the cutting-edge world of brain biomarkers – molecular messengers that could revolutionize how we diagnose and treat concussions. Dr. Mavrudis explains how his team is developing cloud applications and machine learning algorithms to interpret patterns in these biomarkers, potentially allowing doctors to predict which patients will develop serious problems and tailor treatments accordingly. Particularly promising is his work on CGRP biomarkers for post-traumatic headaches, offering hope to many patients dissatisfied with current treatments.
But perhaps most refreshing is Dr. Mavrudis' holistic approach to treatment. Rather than reaching first for medications, he emphasizes behavioral therapies, appropriate exercise, stress management, and addressing cervical injuries that invariably accompany concussions. "The brain doesn't exist in isolation," he reminds us, highlighting how liver function, kidney health, and even gut activity significantly impact brain recovery.
Whether you're struggling with persistent symptoms after a concussion, caring for someone who is, or simply fascinated by the frontiers of neuroscience, this episode offers a roadmap to understanding the complex interconnections of brain injury and recovery.
Dr. Mavroudis: Website
LinkedIn: Profile
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Dr. Wolf's book Concussion Breakthrough: Discover the Missing Pieces of Concussion Recovery is now available on Amazon!
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Ioannis Mavroudis (00:00):
Yes, so the main question in the
neurodegenerative conditions iswhether a patient with mild
symptoms will develop the fullcondition.
For example, if we have apatient with mild cognitive
impairment, some of thesepatients will develop
Alzheimer's or other types ofdementia, but others will never
develop dementia.
(00:21):
It's really important.
It's really crucial now, in theera of these new therapeutic
methods you know the monoclonalantibodies that we develop,
these biomarkers.
There are some biomarkers thatare very sensitive and we can
use them to differentiate thesepatients.
Dr. Ayla Wolf (00:42):
Welcome to Life After Impact the concussion
recovery podcast.
I'm Dr Ayla Wolff and I will behosting today's episode, where
we help you navigate the oftenconfusing, frustrating and
overwhelming journey ofconcussion and brain injury
recovery.
This podcast is your go-toresource for actionable
information, whether you'redealing with a recent concussion
(01:03):
, struggling with postconcussion syndrome or just
feeling stuck in your healingprocess.
In each episode, we dive deepinto the symptoms, testing,
treatments and neurologicalinsights that can help you move
forward with clarity andconfidence.
We bring you leading experts inthe world of brain health,
functional neurology andrehabilitation to share their
(01:25):
wisdom and strategies.
So if you're feeling lost,hopeless or like no one
understands what you're goingthrough, know that you are not
alone.
This podcast can be your guideand partner in recovery, helping
you build a better life afterimpact.
Dr Mavroudis, thank you so muchfor joining Life After Impact
(01:47):
the concussion recovery podcast.
When I am doing a lot of myresearch on the internet on
brain injuries, your name keepscoming up as somebody who has
published a lot of research, butyou're also a clinician and a
consultant neurologist at theUniversity of Leeds, and I think
it's so important that thepeople that are doing research
(02:09):
also are working with patientswho have that experience of
hearing directly from patientswhat it is their struggles are,
because I think that thatinforms our research so much.
So welcome to the show.
Dr. Ioannis Mavroudis (02:23):
Thank you very much.
Thank you very much for thisinvitation.
Thank you for having me today.
It's my pleasure and honor todiscuss with you about
concussions, about braininjuries.
Dr. Ayla Wolf (02:36):
Yeah, tell us a little bit about your background
and how you ended up on thistrack.
Dr. Ioannis Mavroudis (02:41):
Yeah.
So I started medicine in Greecemany years ago, 20-26 years ago
, graduated in 2004,.
Then I did a PhD inneuromorphology and
neuropathology and I was alsofascinated by the brain.
You know, the brain has alwaysrepresented to me the ultimate
(03:01):
challenge, always represented tome the ultimate challenge.
Of course, there are othervital and important organs, like
the heart, like the lungs, eventhe kidneys, but the brain
remains a universe of mysteriesand I'd like to explore this
universe because the brain iswhat we actually are.
(03:24):
So the brain is the seat ofconsciousness, personality,
creativity, memory, anything.
Of course, meeting my mentor inmy PhD was very important,
crucial to my decision to studyneurology and neuropathology.
(03:44):
Then I did my neurology trainingin Greece the same time I
finished my PhD.
Then I came to the UK mainly tostudy neuropathology diagnostic
neuropathology, and to studybrain biopsies and muscle
biopsies.
And then I jumped back to thefield of clinical neurology when
(04:08):
I started seeing many rugbyplayers with traumatic brain
injuries and because most ofthese patients were undiagnosed
and they never get the treatmentand the attention they needed,
they required, that's how Idecided to shift my practice
(04:31):
mainly into this field.
So what I do now is I run apractice I mainly see patients
with traumatic brain injuriesmainly mild traumatic brain
injuries, and the cognitiveimpairment which is the
aftermath of that, and because Isee many things in common with
functional neurologicaldisorders.
(04:51):
That's why I also do afunctional neurological disorder
clinic, trying to find thingsthat are in common.
Dr. Ayla Wolf (04:59):
Yeah, and those functional neurological
disorders.
I mean those patients oftenhave seen so many doctors.
They've been told there'snothing wrong with you.
So I imagine you've heard a lotof stories and you've seen a
lot of frustrations with peoplethat have that diagnosis.
I'm curious what are youfinding as a commonality between
(05:20):
these patients?
Dr. Ioannis Mavroudis (05:22):
Yeah.
So we have recently publishedat least two or three papers
trying to explain thecommonalities between functional
neurological disorders andpost-concussion syndrome.
Of course, post-concussionsyndrome is not a term that
we're allowed to use becauseit's not in the ICD-11 anymore,
but it's a label that we caneasily use and can help us and
(05:44):
the patients to understand.
It's just a constellation ofdifferent symptoms.
So if we see a patient withfunctional cognitive disorder
and if we see a patient withpost-concussion syndrome, we
will notice the same things.
We will notice the samemechanisms and the same triggers
in their symptoms.
In their symptoms, both groupsof these patients will have the
(06:07):
same triggers, such as stress.
Both groups will have fatigue,which is one of the predominant
of the main symptoms, and we'vesuggested that there are many
(06:31):
things in common and possiblycommon mechanisms, which my
personal position is that thisis deep inside the brain and is
because of a change in theneuroplasticity and the ability
of the brain to adapt.
Dr. Ayla Wolf (06:40):
And does that come back to say mitochondrial
dysfunction, or is there someother mechanism that is
affecting the neuroplasticity?
Dr. Ioannis Mavroudis (06:51):
Yeah, the mitochondria play a very, very
important and viral role to howthe brain and how the neurons
work.
They provide the energy, andnot only the energy.
They do more things than that.
But I believe that the problemis mainly in the synapse, where
the neurons communicate whenthey send information.
(07:11):
So there are two differentmechanisms it's the long-term
depression and long-termpotentiation.
These are the two mechanismswhere the ability of the brain
relies on, and I believe thatthese mechanisms are disrupted
and this is why the brain inthese patients is not able to
(07:35):
adapt to the post-injury or thepost-FND diagnosis daily life.
And speaking of that, I foundmany things in common with the
prolonged, the persistent postsorry, the long COVID syndrome.
There are many things in commonand I believe that there are
(07:57):
similarities in the pathologicalmechanisms in this condition
too.
Dr. Ayla Wolf (08:03):
I know you had published a paper speaking to
the similarities and symptomsbetween post-concussion syndrome
and long COVID.
Bringing up long-termpotentiation brings me right
back to neurology 101.
So it comes back to the basics,right Of just understanding
synaptic neuroplasticity, howthe brain communicates.
(08:24):
And so you're seeing that thecommonality between a lot of
these persistent syndromes isthis idea of the synapses
struggling to communicate, whichbrings me to an interesting
paper that you also justpublished on microglial exosomes
.
And so what is the role of theimmune system in all of this?
(08:45):
And neuroinflammation?
Dr. Ioannis Mavroudi (08:48):
Absolutely , absolutely.
The role of microglia is veryimportant.
So the microglia arespecialized cells.
They're part of the immunesystem.
They're not part of the centralnervous system but they are
specialized.
They go into the centralnervous system very early in
their life and this is why theyare allowed to be there, because
(09:10):
we have the blood-brain barrier, so nothing from the blood can
cross this barrier under normalcircumstances.
These cells, they have the samerole as the protective cells
have in the blood.
So what they do?
They get activated when thereis inflammation.
(09:30):
But sometimes this inflammationcan cause damage and this
inflammation, because of theincreased demand of energy, can
affect the mitochondria, as yousaid before, and this can affect
how the brain works.
Because if there is lack ofenergy into the neuron, then
this long-term potentiation andthe overall neuroplasticity will
(09:55):
be affected and the neuronswill not be able to communicate
effectively yeah, and so in yourclinical practice, how are you
unraveling all this?
Dr. Ayla Wolf (10:08):
how are you addressing this uh mess of both
mitochondrial dysfunction uhmicroglial dysfunction, the
persistence of neuroinflammationaffecting uh neuroplasticity.
You know where do you jump into try to kind of fix all of
that yeah, this, this is noteasy, so.
Dr. Ioannis Mavroudis (10:24):
So, first of all, we need to focus on the
translational neuroscience, sowe need to translate the
research results and the resultsfrom the papers we do and
publish into the clinicalpractice.
This is not always easy, butit's something we need to do in
(10:45):
order to help our patients.
First step is to listen to thepatients, to understand the
needs, understand the symptoms,try to explain them based on the
basic knowledge we haveobtained from medical school and
from early years in ourtraining, and this way you're
able to send the patients to theright pathway recovery pathway
(11:11):
and treatment pathway.
Dr. Ayla Wolf (11:13):
And are you utilizing certain medications or
are you really focusing onlifestyle changes?
Diet when are you kind ofrecommending people start?
Dr. Ioannis Mavroudis (11:26):
Yes.
So to be honest I'm not a fanof medications.
I try not to give too manymedications to my patients.
So, for example, for fatigue inthe United States there are
some tablets that are prescribedhere in the UK and in my own
practice we try to avoid that.
We try mainly to help thepatients without any medication,
(11:50):
to advise them on the amount ofrest they need, the amount of
sleep they need.
I believe I'm a big believer ofbehavioral therapies and
neuropsychology.
I believe that neuropsychologycan help patients, both in
post-concussion syndrome andfunctional neurological
disorders, to to have a bettertreatment and a better outcome.
(12:17):
So we always try to advise onright exercise, right amount of
exercise, not too intenseexercise, low intensity.
40-45 minutes of walking orlight jogging in the morning is
the best exercise because thisway you're able to manage your
stress better.
Stress is not an ally in thiswar.
(12:40):
Then diet is very important.
You know the usual stuff,nothing special.
But we always try to advise thepatients to drink plenty of
fluids, to avoid alcohol oranything else that can harm the
brain, can cause more harm tothe brain, and to try lots of
(13:01):
antioxidants and things likethat, just the general healthy
stuff.
Of course we have specializeddieticians that will see the
patients.
In the end, if with thisgeneral advice on diet, if it's
not helpful, we have coachesthat can help the patients, can
(13:21):
give them the right exercises,the right programs that can help
them in the gym.
So we basically try to providea tailored program to each
patient.
If this doesn't work, we willrepeat some of the tests that we
do after three and six monthsand if there is no improvement
then we might try somemedications.
(13:42):
But to my experience, the onlymedications that can help are
very low doses ofantidepressants, just to fight
stress and to help the mood.
This is the only thing that hasplace in the treatment of these
conditions.
Dr. Ayla Wolf (14:01):
And you mentioned that one of your focuses is on
the cognitive symptoms thatpeople are describing.
Are you doing differentcognitive exercises or training
programs with people as well?
Dr. Ioannis Mavroudis (14:12):
Yes.
So, first of all, in terms ofdiagnosis, we don't do the usual
diagnostic tests such as theMOCA, the mini mental state
examination on the Addenbrookes,because these tests are not
sensitive for patients withtraumatic brain injuries.
I personally prefer to do acomputerized test, the impact
test, which is widely known andwidely accepted, and with this
(14:38):
test you can study differentaspects of the cognitive
functions.
We also do a test using virtualreality.
It's an eye-tracking testbecause the ocular movements are
very important in the recoveryof these patients.
(14:59):
These are the tests we do, andthen, in terms of recovery, we
use our own tests.
We have developed a couple ofvideo games that we try to use
in patients that love videogames.
These video games, they havesome cognitive challenges, they
have some eye-trackingchallenges, some cognitive
challenges, they have someeye-tracking challenges.
(15:21):
And then, of course, it's thegolden standard, the cognitive
behavioral therapy withexperienced neuropsychologists.
Dr. Ayla Wolf (15:26):
And you're seeing that with use of the virtual
reality, at least the people whocan handle that that that's
actually helping in terms ofsome of their ocular motor
symptoms as well as, maybe,things like reaction time and
other cognitive processes.
Dr. Ioannis Mavroudi (15:41):
Absolutely , absolutely.
This test is very usefulbecause, of course, you can
study the ocular movements, butat the same time, there are some
other parameters that you canstudy.
For example, there is thecervical element.
You ask the patient to do someneck movements, having the VR
(16:03):
set on their heads, and this wayyou can see if anything changes
, and this is an indication ofan injury to the cervical spine,
because there is no concussion,no traumatic brain injury
without cervical injury, as weknow.
And then there are somecognitive challenges as well.
So we have the saccade, thesaccade movements when we ask
(16:23):
the patient to follow a flashinglight, but at the same time, we
have the antisaccades, when weask the patient to look at the
opposite side, and this has acognitive element as well.
Dr. Ayla Wolf (16:34):
Yeah, yeah.
That's such a great window intothat prefrontal cortex and
impulse control.
I do that test at the bedsideand I often see people struggle
with it when they've hadconcussions.
Absolutely.
Dr. Ioannis Mavroudi (16:46):
Absolutely , absolutely.
Yeah, this is my favoritebedside test.
It's the vestibulocular test,which I always do, but in my
practice I prefer to do uh thevr test, which is a bit more
impressive, and, of course, it'suh something that you can video
and you can document everythingon the patient and you can
(17:10):
repeat that after three and sixmonths and uh using the same
standards you have.
You can have a goodunderstanding of the progress or
the changes.
Dr. Ayla Wolf (17:21):
Yeah, my mentor, dr Carrick, had published a
study on the.
He tested a lot of people'socular motor movements Olympians
in the 2024 Olympics.
His team went there and studiedthe eye movements of people
that were in high impact sports,like boxing, versus people who
were in sports that didn'tinvolve high impact, and they
(17:45):
were able to really showdifferences in eye movements and
the people that were performingthese high impact sports.
Even if they hadn't had thatconcussion diagnosis, they were
still kind of evidence of somedysfunction there.
So I love that the spotlight onthe importance of eye movements
is getting a lot more attention, which is great because it is a
(18:06):
window into so many parts ofthe brain, because eye movements
are so complex and they alsotake up a lot of cognitive
energy too, and so when peopleare struggling with their ocular
motor system, that can create alot of that brain fatigue that
we see symptomatically.
Dr. Ioannis Mavroudi (18:23):
Absolutely , absolutely.
And doing that, we're able tooffer vestibular rehabilitation
to help our patients, becausemost patients, you know, when
they come to see me or to seeone of my colleagues in clinic,
even five or six or seven yearsafter the injury, they've never
had the right test, they'venever had the chance to get the
right treatment.
Dr. Ayla Wolf (18:44):
Yeah, yep, absolutely.
And so, switching gears alittle bit, let's talk about
some of the blood biomarkerresearch, and it seems like
there's certain blood biomarkersthat are not quite so specific
to the brain exclusively, likeS100B is not exclusive to brain
(19:05):
injury, but still a marker ofbrain injury potentially, and so
there are some markers thatkind of are meaningful within
the first, you know, couple ofhours after an injury.
There are some pro-inflammatorymarkers that maybe can give an
indication of is this brainrecovering.
So I think it's very confusingfor the general person to say,
(19:25):
okay, we've got pro-inflammatoryand anti-inflammatory markers,
and then some of them areindicating this at this time
point or that at that time point.
This can be a very confusingtopic.
So let's maybe dive into thisblood biomarker research.
Dr. Ioannis Mavroudis (19:41):
You're absolutely right.
So, yes, I agree with you.
Most of these biomarkers arenot brain specific, but the
combination of all of them andconsidering the history of the
brain injury can help us tounderstand what's going on.
As you said, there are somebiomarkers that can help us to
understand about the healingprocess, about the inflammation.
(20:02):
Of course, we have the, thelight chain neurofilament light
chain biomarker, that it's amarker of disruption of actions
in the central nervous system.
Most of these biomarkers can beraised, even in general
injuries or orthopedic injuries.
(20:25):
What we try to do now is todevelop a kind of a cloud
application and a device tostudy these biomarkers as a
group and then to feed them intoan algorithm that will help us
to understand them better.
Of course, always, always,always working with the patient,
(20:50):
working with the history andtaking into account the
patient's experience and thepatient's side of things.
If we just take a set ofbiomarkers and you know they
might be raised, they might bedifferent to the normal range.
We'll never be able to make adiagnosis unless we have the
(21:12):
patient in front of us, unlesswe have a medical history,
unless we have a neurologicalexamination, unless we have a
medical history, unless we havea neurological examination.
I believe that in the nearfuture, probably in the next
five years, the biomarkers willbe able to help us with the
diagnosis, a more accuratediagnosis, because in most of
(21:41):
these cases, especially insports concussions and in the
medical legal setting you knowroad traffic accidents, things
like that accurate diagnosis isvery, very important.
So hopefully, with thesebiomarkers and doing
non-invasive testing like salivaswab because most of these
biomarkers now are taken fromblood or CSF, taking saliva swab
(22:01):
will make things even easierfor the patients.
I believe that the future is inthe exosomal biomarkers, which
is very sensitive in themicroRNAs.
So having a combination of allof these biomarkers will give us
what we need.
I had a meeting with anexcellent colleague of mine that
(22:22):
we've done a lot of researchtogether, professor Čobika.
He's a biochemist in Romaniaand we had the meeting and he
said that I always ask mystudents when I interview them
for their PhD, how manybiomarkers do we have for
(22:45):
neurological and psychiatricconditions?
And they always you know moststudents they will say they will
tell 10, 5, 20, 200.
And what is the right number?
Zero, we don't have any.
It's the combination of themand the combination of the
patient, the combination of thehistory and anything else that
(23:07):
can help us to understand thepatient and to have an accurate
diagnosis.
But we need to remember that inmedicine nothing is
deterministic.
It's always probabilistic.
So, even with the best evidence, the diagnosis is based on the
probability, on the balance ofprobabilities, and these
biomarkers can help us toincrease the probability of a
(23:30):
more accurate diagnosis.
Dr. Ayla Wolf (23:33):
Right, and I think at this point is it fair
to say too that in this kind ofpreliminary state that some of
these blood biomarkers, whentaken as a panel together, can
then inform, say, a doctor in anemergency department whether or
not they need to do a CT scan.
Dr. Ioannis Mavroudis (23:51):
Exactly exactly.
I agree with that, and this iswhere the research is mainly
focused to save patients fromgetting exposed to radiation and
, of course, to save money tothe health systems.
This can be very useful for theemergency physicians to decide
(24:11):
whether to do or not to do a CTscan, but, as I said, this alone
is not enough.
We always need to take intoaccount everything else, because
if we have a patient with aminor head injury and
significant neurologicalsymptoms, even if the biomarkers
are not raised, we definitelyneed to do a scan.
Dr. Ayla Wolf (24:31):
Yeah, absolutely.
And then I know, on the flipside of that, in certain people
maybe elderly people that havekidney failure some of these
biomarkers might also beelevated as a result of kidney
function or a loss of kidneyfunction.
So again, it's also taking intoaccount the age of the patient,
pre-existing conditions.
(24:52):
So sometimes these markers canbe elevated for other reasons
too.
Dr. Ioannis Mavroudis (24:58):
Exactly, exactly, exactly, yes, so yeah,
to my knowledge, in somecountries I think in France, I'm
not sure I think that in theStates as well, but you might
know better there are somepanels of biomarkers that are
used in the emergency settingmainly I think it's mainly three
biomarkers.
The problem is that can only beused in the first 72 hours in
(25:22):
the acute phase, and thesebiomarkers can help us with the
diagnosis but cannot help us,are not predictive of the
outcome, cannot help us yet withthe prognosis of these patients
.
Dr. Ayla Wolf (25:37):
Yeah, which brings me to my next question,
because you also are researchinga lot in the world of just
neurodegenerative disease and soyou're also studying biomarkers
in that context of trying tounderstand is there a way where
we can get a better handle ondoes somebody have a
neurodegenerative condition?
(25:58):
And so fill me in on kind ofwhere the research is on that in
terms of the biomarkers.
Dr. Ioannis Mavroudis (26:04):
Yes, so the main question in the
neurodegenerative conditions iswhether a patient with mild
symptoms will develop the fullcondition.
For example, if we have apatient with mild cognitive
impairment, some of thesepatients will develop
Alzheimer's or other types ofdementia, but others will never
develop dementia.
(26:25):
It's really important.
It's really crucial now, in theera of these new therapeutic
methods, the monoclonalantibodies, that we develop,
these biomarkers.
There are some biomarkers thatare very sensitive and we can
use them to differentiate thesepatients and to stratify the
(26:46):
patients that will most likelydevelop a condition and, on the
balance of probabilities, willnot develop the condition, and
to treat them differently.
Dr. Ayla Wolf (26:57):
Yeah, that sounds very cutting edge and that,
would you say at this point, isvery much still in the realm of
research, it's not yet beingkind of implemented.
Dr. Ioannis Mavroudis (27:07):
Yes, unfortunately, all these are
still in the very first steps,the very first stages, but there
are some of these biomarkersthat can help us.
For example, this is how wedeveloped all this theory about
the alpha-beta peptide and aboutthe tau protein in Alzheimer's
disease, and this has helped usto understand the
(27:31):
pathophysiology of the disease.
We're currently working on aproject on neurogranin.
Neurogranin is a very sensitivebiomarker.
It's a substance that can helpus to understand the synaptic
function.
We did a study a few years backthat showed us that it's a very
sensitive biomarker forAlzheimer's disease and using
(27:55):
that we can tell whether apatient will develop or will not
develop Alzheimer's.
And now we're working on thisbiomarker as a prognostic marker
for prolonged or severepost-concussion syndrome after a
concussion, and the results sofar are promising.
But we are in the very earlystages.
(28:17):
If you look at the basics,that's how I approach my
research.
I go back to the basics, I goback to my medical school books,
I go back to physiology, backto biochemistry and looking into
the details.
This is how I approach myresearch and how we design our
projects approach my researchand how we design our projects.
Dr. Ayla Wolf (28:47):
And I know that the microglia are involved in
synaptic pruning.
So, going back to this idea ofthe importance of the microglia
and this idea that they havedifferent functions, you know
that we're all talking about howthey can create a lot of
pro-inflammatory situations, butthey also play these very
important roles of surveillanceand synaptic pruning and taking
(29:07):
away synapses we don't need.
But if that gets upregulated,all of a sudden all these
synapses are dying.
And so are you also studyingthe microglia in the context of
blood sugar management and justthis idea of what we call type 3
diabetes in the brain, wherethe ability to regulate glucose
(29:29):
is affected, and then thatthrows everything else off and
kind of creates a state wherethese synapses are perhaps dying
at a greater rate than we wantthem to.
Dr. Ioannis Mavroudis (29:40):
Yeah, this is an excellent idea.
This is an excellent question.
Unfortunately, I don't do thistype of research myself, but a
colleague of mine is a very bigfan of this theory and he's
trying to establish a researchproject on this, which is very
important and sounds verypromising.
So hopefully this will besomething that we will be able
to talk about, maybe in a coupleof years.
Dr. Ayla Wolf (30:02):
Okay, and then what about this paper that you
recently published on themicroglial exosomes?
Talk a little bit about what anexosome is and what this study
is looking at.
Dr. Ioannis Mavroudis (30:14):
Yeah, the exosomes and the endosomes are
small vesicles that are releasedby the neurons and these can
contain different substances.
So in the exosomes we can findif we test the exosomes in the
(30:34):
saliva, for example, we can finddifferent markers, different
substances.
That will help us to have abetter understanding of what's
going on into the body and morespecifically, into the brain.
And studying the exosomes inpatients with post-concussion
(30:57):
syndrome and traumatic braininjuries, we're able to identify
a couple of substances.
Some of them are the microRNAssmall parts of RNAs that we can
study.
And in the exosomes you canalso find some other substances,
like some pieces of tau proteinand other biomarkers that you
(31:19):
can also study, and these arevery important.
Dr. Ayla Wolf (31:24):
Mm-hmm.
So these are kind of messengersthat are being released that
can create kind of a cascade ofevents, is that?
Dr. Ioannis Mavroudis (31:32):
fair to say Exactly, that's fair to say.
And some small portions of themwill also be released into the
bloodstream and into the saliva,and this is how we can capture
them and can study them.
Dr. Ayla Wolf (31:46):
Mm-hmm Got it, so that sounds like the future is
promising in terms of being ableto, hopefully in the near
future, have some better testingmethods to understand where
somebody is at on the scale of,say, neuroinflammation or if
they're having symptoms.
How worried do we need to bethat this might progress into
(32:07):
something more serious down theline?
Dr. Ioannis Mavroudis (32:10):
Exactly exactly.
I believe that in the nearfuture, we'll be able to offer
personalized medicine, tounderstand the patient and to
offer tailored treatment andtailored strategies for each one
of them, based on their needsand based on these biomarkers
and potentially more biomarkersthat will rise in the future.
Dr. Ayla Wolf (32:30):
Yeah Well, how exciting to be at the cutting
edge of all of that.
The other question I wanted toask you was on this when we talk
about the brain, much like wedo with medicine, everything
kind of becomes siloed, and sowe often talk about the brain as
this separate entity from therest of the body.
But in my practice, I pay a lotof attention to the health of
(32:54):
the liver and the kidneys andthe role of healthy liver and
kidney function on healthy brainfunction.
But I think this is somethingthat I don't really hear anybody
else talking about, and so I'mcurious if you have anything to
say in terms of how you look atthe you know, the totality of it
.
Dr. Ioannis Mavroudi (33:12):
Absolutely , absolutely.
Yeah, so the brain doesn'texist in isolation.
The brain always works andcollaborates with the other
organs.
The brain is the sender, butthe other organs are also vital.
We all know from our ownexperience that the liver
function, the kidney function,even the intestinal function and
(33:38):
the stomach are reallyimportant for the brain.
When I was a student sixth yearof medical school, the last
year, I was involved in aresearch that widened my
horizons on the understanding ofwhat you're talking about,
because it was a PhD project andthe guy that did that.
(34:00):
He worked on how somesubstances that we now
understand as orexins from thestomach can affect the brain,
can affect the hypothalamus andthis way can affect the whole
brain function.
So, yeah, all these organs arevery important and crucial.
So we know that we have thecondition which is called
(34:24):
hepatic encephalopathy.
If there is dysfunction to theliver and the energy that will
go to the brain is not enough,then we'll have dysfunction of
the brain and the patient willdevelop a kind of dementia-like
presentation.
Dr. Ayla Wolf (34:41):
Yeah, I remember when my grandmother ended up in
the hospital and she had aurinary tract infection, but
before they had diagnosed it itwas affecting her cognition.
She didn't know her own son'sname, and so there was this
brief moment in time where weall thought, oh no, she's going
downhill really fast andcognitively she was completely
(35:03):
delirious and all of a suddenthey said, oh no, she just has a
urinary tract infection.
And once they fixed that, allof a sudden her cognitive
faculties returned and it wassuch an acute thing to have.
Okay, a urinary tract infectioncan cause this severe type of
dementia symptoms that come.
(35:24):
Connection is vital.
And even if we don't have, likean extreme kidney failure, what
happens if the kidneys I feellike in our modern medicine the
kidneys have to be likepractically failing before
things start to show up on bloodwork or before we start to pay
attention to them?
And yet in our current day andage our kidneys are assaulted
(35:46):
with so many environmentaltoxins and chemicals and things
in the environment that I feellike they're having to work
overtime and yet we just don'treally pay attention to them as
much as we should.
Especially with COVID, welearned that that can create a
lot of inflammation in thekidneys and cause all kinds of
problems, and then you've gotdownstream consequences from
(36:08):
that.
So I, just with my backgroundin Chinese medicine, we always
pay very close attention tokidney function and so I just
see that that being another kindof avenue of you know, this
idea of integration and wetalked about the gut brain axis,
but I think we also need totalk a lot more about that role
of liver health and kidneyhealth and those impacts on the
(36:30):
brain if those aren't workingoptimally or subpar.
Dr. Ioannis Mavroudi (36:34):
Absolutely .
I could not agree more.
Yeah, yeah, as the ancientGreek used to say, it's the
golden min moderation.
Dr. Ayla Wolf (36:42):
Yes, absolutely.
Well, what are the nextprojects that you're working on?
Dr. Ioannis Mavroudis (36:48):
Yeah.
So the main study that we'vejust recently started is to work
on this cloud application andthis machine learning algorithm
on the diagnosis ofpost-concussion syndrome and
traumatic brain injuries, mainlythe concussions.
We try to standardize the panelthat we will use.
(37:09):
So we've identified through theliterature six or seven
biomarkers, to begin withIndistinguishably cortisol is
one of them.
Cortisol is a very versatilebiomarker and can be raised in
different conditions, but wefound that it's very sensitive
(37:32):
and can help in the prognosis ofdifferent symptoms, mainly
psychological symptoms, in thesepatients.
Then we have the CGRP biomarker.
The CGRP is the biomarker thatcan help us on the prognosis of
post-traumatic headaches.
So we've identified thesebiomarkers and we're trying to
(37:54):
do a clinical trial now and thisis the main project that I'm
very enthusiastic about.
Dr. Ayla Wolf (38:02):
Yeah, absolutely.
I see lots of patients withchronic post-traumatic headaches
.
I see lots of patients withchronic post-traumatic headaches
and many of them are givenmigraine medications but not the
CGRP antagonists.
Again, I think because of moneyand because of the insurance
model saying, well, let's givethem all these other medications
(38:23):
first and we have to prove thatthese don't work before you get
the better, more expensivedrugs.
Dr. Ioannis Mavroudis (38:29):
Exactly, exactly, exactly.
This is how the symptomssystems work, but they need to
be sustainable, so it'ssomething we need to follow.
Dr. Ayla Wolf (38:39):
Yeah, yeah.
Well, I'll be excited to seethat research since CGRP is one
of those things that is wellstudied in the migraine
literature, but we're stillreally trying to figure out why
patients with post-traumaticheadaches don't always respond
well to migraine medications.
Dr. Ioannis Mavroudis (38:59):
Yeah, because not all post-traumatic
headaches are migraines innature.
They're different mechanisms.
About 75% of the post-traumaticheadaches they have mixed
features of tension typeheadaches, some migraineous
features as well, cervicogenicheadache, and there was always
stress and psychologicalsymptoms.
(39:21):
Only 20% can be clearlymigraineous.
This is why just a smallpercentage of patients with
post-traumatic headaches willrespond well to migraine
medication.
But CGRP is something that canhelp in other types of headaches
as well, not only in themigraines.
Dr. Ayla Wolf (39:41):
Excellent, so tell me more about that.
You're seeing that even inthese mixed types of headaches
that CGRP is elevated.
Dr. Ioannis Mavroudis (39:51):
CGRP can be elevated and can be a very
good prognostic factor ofdeveloping post-traumatic
headache, independently of thesubtype of headache.
So some patients they mightdevelop tensio-type headaches,
others will develop migraineheadaches.
Other patients may developoccipital neuralgia or even
trigeminal neuralgia or veryrare types of headaches, and
(40:17):
this is a very, very sensitivebiomarker and giving these
patients anti-CGRP medicationcan make the difference.
Dr. Ayla Wolf (40:28):
Yeah, fascinating .
Well, I'm excited to see thatresearch because we definitely
need to help these people, moreso than we are.
There was a study that came outin 2020 that said that 87% of
people with post-traumaticheadaches were dissatisfied with
their current medical treatment, so we need to do better for
(40:48):
these people.
Dr. Ioannis Mavroudis (40:49):
Exactly exactly.
We need to do better and, again, we need a holistic approach.
Just giving medication will notalways help the patient.
We need to consider everything,to consider every other element
that can trigger the headache.
To my experience and theliterature, physiotherapy, neck
(41:11):
physiotherapy will always have apositive impact on these types
of headaches, the post-traumaticheadaches, independently of the
subtype of the headache,because most physicians will say
that, yeah, but this is amigraine headache, how neck
physiotherapy can help?
But there is always acervicogenic element in these
types of headaches Because, as Isaid before, there is always a
(41:36):
cervical spine injury when youhave a concussion.
And then managing stress isalso very important and avoiding
triggers.
This is something that wealways forget.
We forget to advise patients toavoid triggers and then most of
these patients, because theysuffer a lot from the headaches
(41:58):
and other symptoms, they tend tooveruse medication and this is
something else we need to alwayslook at and to be very careful
with these patients to advisethem not to overdo it with
medication, because evenparacetamol or ibuprofen
medications that you can easilybuy over the counter if you take
them long term, they can have avery negative impact on these
(42:20):
headaches.
Dr. Ayla Wolf (42:21):
Yeah, yeah, absolutely the medication
overuse headaches are a realeffect for sure, not to mention
their impact on the liver andthe kidneys.
Dr. Ioannis Mavroudi (42:31):
Absolutely , absolutely.
I agree, I agree yeah.
Dr. Ayla Wolf (42:34):
Yeah, wow, well, anything else that we haven't
talked about that you would liketo cover before we wrap up?
Dr. Ioannis Mavroudis (42:42):
No, I don't have anything else.
You know, I could talk forhours about the brain, about the
neuroplasticity and about theseconditions, but I don't have
anything else.
If you have any other questions, I'm happy to continue the
discussion.
Dr. Ayla Wolf (42:59):
Well, what are the things that you do for your
own brain health?
Dr. Ioannis Mavroudis (43:03):
Yeah, so I used to be an athlete.
I played basketball for manyyears.
I love basketball so I stilltry to play basketball with
friends at the university Notvery successful anymore and I
always try to do some exerciseand to follow a good, balanced
diet and avoid alcohol.
(43:24):
I avoid alcohol.
I tend to admit that I mightenjoy some spirits now and then
two, three times a year, butthat's it.
Dr. Ayla Wolf (43:38):
So very much in moderation.
Dr. Ioannis Mavroudis (43:39):
Exactly.
Dr. Ayla Wolf (43:46):
Yeah, Fabulous yeah, Having those basic pieces
in place.
Dr. Ioannis Mavroudis (43:47):
The exercise the diet, the sleep,
absolutely.
Dr. Ayla Wolf (43:50):
Wonderful.
Well, thank you so much foryour time, and I'd love to have
you back on the show here in alittle bit, once you have some
of these other research findingspublished, and I'd love to stay
on top of all of thiscutting-edge work that you're
doing, because it's so important.
Dr. Ioannis Mavroudis (44:05):
Thank you .
Thank you very much for havingme today.
I'm honored.
Thank you, thank you.
Dr. Ayla Wolf (44:08):
Thank you very much for having me today.
I'm honored.
Dr. Ioannis Mavroudis (44:09):
Thank you , thank you.
Dr. Ayla Wolf (44:11):
Where can people find you?
I know you've got some YouTubechannels out there or
information.
Dr. Ioannis Mavroudis (44:17):
Yeah, so unfortunately I cannot work on
my YouTube channels because ofmy other commitments, but they
can find me on LinkedIn and I'malways happy to respond to any
messages or any queries.
Dr. Ayla Wolf (44:30):
Okay, fabulous.
Well, I can put that in theshow notes there.
Dr. Ioannis Mavroudis (44:34):
Wonderful .
Dr. Ayla Wolf (44:35):
Thank you so much for your time, Dr Mavroudis.
Dr. Ioannis Mavroudis (44:38):
Thank you .
Thank you very much.
Dr. Ayla Wolf (44:43):
Medical Disclaimer.
Disclaimer this video orpodcast is for general
informational purposes only anddoes not constitute the practice
of medicine or otherprofessional health care
services, including the givingof medical advice.
No doctor patient relationshipis formed.
The use of this information andmaterials included is at the
(45:03):
user's own risk.
The content of this video orpodcast is not intended to be a
substitute for medical advice,diagnosis or treatment, and
consumers of this informationshould seek the advice of a
medical professional for any andall health-related issues.
A link to our full medicaldisclaimer is available in the
notes.
Yes, so the main question in the
neurodegenerative conditions iswhether a patient with mild
symptoms will develop the fullcondition.
For example, if we have apatient with mild cognitive
impairment, some of thesepatients will develop
Alzheimer's or other types ofdementia, but others will never
develop dementia.
(00:21):
It's really important.
It's really crucial now, in theera of these new therapeutic
methods you know the monoclonalantibodies that we develop,
these biomarkers.
There are some biomarkers thatare very sensitive and we can
use them to differentiate thesepatients.
Dr. Ayla Wolf (00:42):
Welcome to Life After Impact the concussion
recovery podcast.
I'm Dr Ayla Wolff and I will behosting today's episode, where
we help you navigate the oftenconfusing, frustrating and
overwhelming journey ofconcussion and brain injury
recovery.
This podcast is your go-toresource for actionable
information, whether you'redealing with a recent concussion
(01:03):
, struggling with postconcussion syndrome or just
feeling stuck in your healingprocess.
In each episode, we dive deepinto the symptoms, testing,
treatments and neurologicalinsights that can help you move
forward with clarity andconfidence.
We bring you leading experts inthe world of brain health,
functional neurology andrehabilitation to share their
(01:25):
wisdom and strategies.
So if you're feeling lost,hopeless or like no one
understands what you're goingthrough, know that you are not
alone.
This podcast can be your guideand partner in recovery, helping
you build a better life afterimpact.
Dr Mavroudis, thank you so muchfor joining Life After Impact
(01:47):
the concussion recovery podcast.
When I am doing a lot of myresearch on the internet on
brain injuries, your name keepscoming up as somebody who has
published a lot of research, butyou're also a clinician and a
consultant neurologist at theUniversity of Leeds, and I think
it's so important that thepeople that are doing research
(02:09):
also are working with patientswho have that experience of
hearing directly from patientswhat it is their struggles are,
because I think that thatinforms our research so much.
So welcome to the show.
Dr. Ioannis Mavroudis (02:23):
Thank you very much.
Thank you very much for thisinvitation.
Thank you for having me today.
It's my pleasure and honor todiscuss with you about
concussions, about braininjuries.
Dr. Ayla Wolf (02:36):
Yeah, tell us a little bit about your background
and how you ended up on thistrack.
Dr. Ioannis Mavroudis (02:41):
Yeah.
So I started medicine in Greecemany years ago, 20-26 years ago
, graduated in 2004,.
Then I did a PhD inneuromorphology and
neuropathology and I was alsofascinated by the brain.
You know, the brain has alwaysrepresented to me the ultimate
(03:01):
challenge, always represented tome the ultimate challenge.
Of course, there are othervital and important organs, like
the heart, like the lungs, eventhe kidneys, but the brain
remains a universe of mysteriesand I'd like to explore this
universe because the brain iswhat we actually are.
(03:24):
So the brain is the seat ofconsciousness, personality,
creativity, memory, anything.
Of course, meeting my mentor inmy PhD was very important,
crucial to my decision to studyneurology and neuropathology.
(03:44):
Then I did my neurology trainingin Greece the same time I
finished my PhD.
Then I came to the UK mainly tostudy neuropathology diagnostic
neuropathology, and to studybrain biopsies and muscle
biopsies.
And then I jumped back to thefield of clinical neurology when
(04:08):
I started seeing many rugbyplayers with traumatic brain
injuries and because most ofthese patients were undiagnosed
and they never get the treatmentand the attention they needed,
they required, that's how Idecided to shift my practice
(04:31):
mainly into this field.
So what I do now is I run apractice I mainly see patients
with traumatic brain injuriesmainly mild traumatic brain
injuries, and the cognitiveimpairment which is the
aftermath of that, and because Isee many things in common with
functional neurologicaldisorders.
(04:51):
That's why I also do afunctional neurological disorder
clinic, trying to find thingsthat are in common.
Dr. Ayla Wolf (04:59):
Yeah, and those functional neurological
disorders.
I mean those patients oftenhave seen so many doctors.
They've been told there'snothing wrong with you.
So I imagine you've heard a lotof stories and you've seen a
lot of frustrations with peoplethat have that diagnosis.
I'm curious what are youfinding as a commonality between
(05:20):
these patients?
Dr. Ioannis Mavroudis (05:22):
Yeah.
So we have recently publishedat least two or three papers
trying to explain thecommonalities between functional
neurological disorders andpost-concussion syndrome.
Of course, post-concussionsyndrome is not a term that
we're allowed to use becauseit's not in the ICD-11 anymore,
but it's a label that we caneasily use and can help us and
(05:44):
the patients to understand.
It's just a constellation ofdifferent symptoms.
So if we see a patient withfunctional cognitive disorder
and if we see a patient withpost-concussion syndrome, we
will notice the same things.
We will notice the samemechanisms and the same triggers
in their symptoms.
In their symptoms, both groupsof these patients will have the
(06:07):
same triggers, such as stress.
Both groups will have fatigue,which is one of the predominant
of the main symptoms, and we'vesuggested that there are many
(06:31):
things in common and possiblycommon mechanisms, which my
personal position is that thisis deep inside the brain and is
because of a change in theneuroplasticity and the ability
of the brain to adapt.
Dr. Ayla Wolf (06:40):
And does that come back to say mitochondrial
dysfunction, or is there someother mechanism that is
affecting the neuroplasticity?
Dr. Ioannis Mavroudis (06:51):
Yeah, the mitochondria play a very, very
important and viral role to howthe brain and how the neurons
work.
They provide the energy, andnot only the energy.
They do more things than that.
But I believe that the problemis mainly in the synapse, where
the neurons communicate whenthey send information.
(07:11):
So there are two differentmechanisms it's the long-term
depression and long-termpotentiation.
These are the two mechanismswhere the ability of the brain
relies on, and I believe thatthese mechanisms are disrupted
and this is why the brain inthese patients is not able to
(07:35):
adapt to the post-injury or thepost-FND diagnosis daily life.
And speaking of that, I foundmany things in common with the
prolonged, the persistent postsorry, the long COVID syndrome.
There are many things in commonand I believe that there are
(07:57):
similarities in the pathologicalmechanisms in this condition
too.
Dr. Ayla Wolf (08:03):
I know you had published a paper speaking to
the similarities and symptomsbetween post-concussion syndrome
and long COVID.
Bringing up long-termpotentiation brings me right
back to neurology 101.
So it comes back to the basics,right Of just understanding
synaptic neuroplasticity, howthe brain communicates.
(08:24):
And so you're seeing that thecommonality between a lot of
these persistent syndromes isthis idea of the synapses
struggling to communicate, whichbrings me to an interesting
paper that you also justpublished on microglial exosomes
.
And so what is the role of theimmune system in all of this?
(08:45):
And neuroinflammation?
Dr. Ioannis Mavroudi (08:48):
Absolutely , absolutely.
The role of microglia is veryimportant.
So the microglia arespecialized cells.
They're part of the immunesystem.
They're not part of the centralnervous system but they are
specialized.
They go into the centralnervous system very early in
their life and this is why theyare allowed to be there, because
(09:10):
we have the blood-brain barrier, so nothing from the blood can
cross this barrier under normalcircumstances.
These cells, they have the samerole as the protective cells
have in the blood.
So what they do?
They get activated when thereis inflammation.
(09:30):
But sometimes this inflammationcan cause damage and this
inflammation, because of theincreased demand of energy, can
affect the mitochondria, as yousaid before, and this can affect
how the brain works.
Because if there is lack ofenergy into the neuron, then
this long-term potentiation andthe overall neuroplasticity will
(09:55):
be affected and the neuronswill not be able to communicate
effectively yeah, and so in yourclinical practice, how are you
unraveling all this?
Dr. Ayla Wolf (10:08):
how are you addressing this uh mess of both
mitochondrial dysfunction uhmicroglial dysfunction, the
persistence of neuroinflammationaffecting uh neuroplasticity.
You know where do you jump into try to kind of fix all of
that yeah, this, this is noteasy, so.
Dr. Ioannis Mavroudis (10:24):
So, first of all, we need to focus on the
translational neuroscience, sowe need to translate the
research results and the resultsfrom the papers we do and
publish into the clinicalpractice.
This is not always easy, butit's something we need to do in
(10:45):
order to help our patients.
First step is to listen to thepatients, to understand the
needs, understand the symptoms,try to explain them based on the
basic knowledge we haveobtained from medical school and
from early years in ourtraining, and this way you're
able to send the patients to theright pathway recovery pathway
(11:11):
and treatment pathway.
Dr. Ayla Wolf (11:13):
And are you utilizing certain medications or
are you really focusing onlifestyle changes?
Diet when are you kind ofrecommending people start?
Dr. Ioannis Mavroudis (11:26):
Yes.
So to be honest I'm not a fanof medications.
I try not to give too manymedications to my patients.
So, for example, for fatigue inthe United States there are
some tablets that are prescribedhere in the UK and in my own
practice we try to avoid that.
We try mainly to help thepatients without any medication,
(11:50):
to advise them on the amount ofrest they need, the amount of
sleep they need.
I believe I'm a big believer ofbehavioral therapies and
neuropsychology.
I believe that neuropsychologycan help patients, both in
post-concussion syndrome andfunctional neurological
disorders, to to have a bettertreatment and a better outcome.
(12:17):
So we always try to advise onright exercise, right amount of
exercise, not too intenseexercise, low intensity.
40-45 minutes of walking orlight jogging in the morning is
the best exercise because thisway you're able to manage your
stress better.
Stress is not an ally in thiswar.
(12:40):
Then diet is very important.
You know the usual stuff,nothing special.
But we always try to advise thepatients to drink plenty of
fluids, to avoid alcohol oranything else that can harm the
brain, can cause more harm tothe brain, and to try lots of
(13:01):
antioxidants and things likethat, just the general healthy
stuff.
Of course we have specializeddieticians that will see the
patients.
In the end, if with thisgeneral advice on diet, if it's
not helpful, we have coachesthat can help the patients, can
(13:21):
give them the right exercises,the right programs that can help
them in the gym.
So we basically try to providea tailored program to each
patient.
If this doesn't work, we willrepeat some of the tests that we
do after three and six monthsand if there is no improvement
then we might try somemedications.
(13:42):
But to my experience, the onlymedications that can help are
very low doses ofantidepressants, just to fight
stress and to help the mood.
This is the only thing that hasplace in the treatment of these
conditions.
Dr. Ayla Wolf (14:01):
And you mentioned that one of your focuses is on
the cognitive symptoms thatpeople are describing.
Are you doing differentcognitive exercises or training
programs with people as well?
Dr. Ioannis Mavroudis (14:12):
Yes.
So, first of all, in terms ofdiagnosis, we don't do the usual
diagnostic tests such as theMOCA, the mini mental state
examination on the Addenbrookes,because these tests are not
sensitive for patients withtraumatic brain injuries.
I personally prefer to do acomputerized test, the impact
test, which is widely known andwidely accepted, and with this
(14:38):
test you can study differentaspects of the cognitive
functions.
We also do a test using virtualreality.
It's an eye-tracking testbecause the ocular movements are
very important in the recoveryof these patients.
(14:59):
These are the tests we do, andthen, in terms of recovery, we
use our own tests.
We have developed a couple ofvideo games that we try to use
in patients that love videogames.
These video games, they havesome cognitive challenges, they
have some eye-trackingchallenges, some cognitive
challenges, they have someeye-tracking challenges.
(15:21):
And then, of course, it's thegolden standard, the cognitive
behavioral therapy withexperienced neuropsychologists.
Dr. Ayla Wolf (15:26):
And you're seeing that with use of the virtual
reality, at least the people whocan handle that that that's
actually helping in terms ofsome of their ocular motor
symptoms as well as, maybe,things like reaction time and
other cognitive processes.
Dr. Ioannis Mavroudi (15:41):
Absolutely , absolutely.
This test is very usefulbecause, of course, you can
study the ocular movements, butat the same time, there are some
other parameters that you canstudy.
For example, there is thecervical element.
You ask the patient to do someneck movements, having the VR
(16:03):
set on their heads, and this wayyou can see if anything changes
, and this is an indication ofan injury to the cervical spine,
because there is no concussion,no traumatic brain injury
without cervical injury, as weknow.
And then there are somecognitive challenges as well.
So we have the saccade, thesaccade movements when we ask
(16:23):
the patient to follow a flashinglight, but at the same time, we
have the antisaccades, when weask the patient to look at the
opposite side, and this has acognitive element as well.
Dr. Ayla Wolf (16:34):
Yeah, yeah.
That's such a great window intothat prefrontal cortex and
impulse control.
I do that test at the bedsideand I often see people struggle
with it when they've hadconcussions.
Absolutely.
Dr. Ioannis Mavroudi (16:46):
Absolutely , absolutely.
Yeah, this is my favoritebedside test.
It's the vestibulocular test,which I always do, but in my
practice I prefer to do uh thevr test, which is a bit more
impressive, and, of course, it'suh something that you can video
and you can document everythingon the patient and you can
(17:10):
repeat that after three and sixmonths and uh using the same
standards you have.
You can have a goodunderstanding of the progress or
the changes.
Dr. Ayla Wolf (17:21):
Yeah, my mentor, dr Carrick, had published a
study on the.
He tested a lot of people'socular motor movements Olympians
in the 2024 Olympics.
His team went there and studiedthe eye movements of people
that were in high impact sports,like boxing, versus people who
were in sports that didn'tinvolve high impact, and they
(17:45):
were able to really showdifferences in eye movements and
the people that were performingthese high impact sports.
Even if they hadn't had thatconcussion diagnosis, they were
still kind of evidence of somedysfunction there.
So I love that the spotlight onthe importance of eye movements
is getting a lot more attention, which is great because it is a
(18:06):
window into so many parts ofthe brain, because eye movements
are so complex and they alsotake up a lot of cognitive
energy too, and so when peopleare struggling with their ocular
motor system, that can create alot of that brain fatigue that
we see symptomatically.
Dr. Ioannis Mavroudi (18:23):
Absolutely , absolutely.
And doing that, we're able tooffer vestibular rehabilitation
to help our patients, becausemost patients, you know, when
they come to see me or to seeone of my colleagues in clinic,
even five or six or seven yearsafter the injury, they've never
had the right test, they'venever had the chance to get the
right treatment.
Dr. Ayla Wolf (18:44):
Yeah, yep, absolutely.
And so, switching gears alittle bit, let's talk about
some of the blood biomarkerresearch, and it seems like
there's certain blood biomarkersthat are not quite so specific
to the brain exclusively, likeS100B is not exclusive to brain
(19:05):
injury, but still a marker ofbrain injury potentially, and so
there are some markers thatkind of are meaningful within
the first, you know, couple ofhours after an injury.
There are some pro-inflammatorymarkers that maybe can give an
indication of is this brainrecovering.
So I think it's very confusingfor the general person to say,
(19:25):
okay, we've got pro-inflammatoryand anti-inflammatory markers,
and then some of them areindicating this at this time
point or that at that time point.
This can be a very confusingtopic.
So let's maybe dive into thisblood biomarker research.
Dr. Ioannis Mavroudis (19:41):
You're absolutely right.
So, yes, I agree with you.
Most of these biomarkers arenot brain specific, but the
combination of all of them andconsidering the history of the
brain injury can help us tounderstand what's going on.
As you said, there are somebiomarkers that can help us to
understand about the healingprocess, about the inflammation.
(20:02):
Of course, we have the, thelight chain neurofilament light
chain biomarker, that it's amarker of disruption of actions
in the central nervous system.
Most of these biomarkers can beraised, even in general
injuries or orthopedic injuries.
(20:25):
What we try to do now is todevelop a kind of a cloud
application and a device tostudy these biomarkers as a
group and then to feed them intoan algorithm that will help us
to understand them better.
Of course, always, always,always working with the patient,
(20:50):
working with the history andtaking into account the
patient's experience and thepatient's side of things.
If we just take a set ofbiomarkers and you know they
might be raised, they might bedifferent to the normal range.
We'll never be able to make adiagnosis unless we have the
(21:12):
patient in front of us, unlesswe have a medical history,
unless we have a neurologicalexamination, unless we have a
medical history, unless we havea neurological examination.
I believe that in the nearfuture, probably in the next
five years, the biomarkers willbe able to help us with the
diagnosis, a more accuratediagnosis, because in most of
(21:41):
these cases, especially insports concussions and in the
medical legal setting you knowroad traffic accidents, things
like that accurate diagnosis isvery, very important.
So hopefully, with thesebiomarkers and doing
non-invasive testing like salivaswab because most of these
biomarkers now are taken fromblood or CSF, taking saliva swab
(22:01):
will make things even easierfor the patients.
I believe that the future is inthe exosomal biomarkers, which
is very sensitive in themicroRNAs.
So having a combination of allof these biomarkers will give us
what we need.
I had a meeting with anexcellent colleague of mine that
(22:22):
we've done a lot of researchtogether, professor Čobika.
He's a biochemist in Romaniaand we had the meeting and he
said that I always ask mystudents when I interview them
for their PhD, how manybiomarkers do we have for
(22:45):
neurological and psychiatricconditions?
And they always you know moststudents they will say they will
tell 10, 5, 20, 200.
And what is the right number?
Zero, we don't have any.
It's the combination of themand the combination of the
patient, the combination of thehistory and anything else that
(23:07):
can help us to understand thepatient and to have an accurate
diagnosis.
But we need to remember that inmedicine nothing is
deterministic.
It's always probabilistic.
So, even with the best evidence, the diagnosis is based on the
probability, on the balance ofprobabilities, and these
biomarkers can help us toincrease the probability of a
(23:30):
more accurate diagnosis.
Dr. Ayla Wolf (23:33):
Right, and I think at this point is it fair
to say too that in this kind ofpreliminary state that some of
these blood biomarkers, whentaken as a panel together, can
then inform, say, a doctor in anemergency department whether or
not they need to do a CT scan.
Dr. Ioannis Mavroudis (23:51):
Exactly exactly.
I agree with that, and this iswhere the research is mainly
focused to save patients fromgetting exposed to radiation and
, of course, to save money tothe health systems.
This can be very useful for theemergency physicians to decide
(24:11):
whether to do or not to do a CTscan, but, as I said, this alone
is not enough.
We always need to take intoaccount everything else, because
if we have a patient with aminor head injury and
significant neurologicalsymptoms, even if the biomarkers
are not raised, we definitelyneed to do a scan.
Dr. Ayla Wolf (24:31):
Yeah, absolutely.
And then I know, on the flipside of that, in certain people
maybe elderly people that havekidney failure some of these
biomarkers might also beelevated as a result of kidney
function or a loss of kidneyfunction.
So again, it's also taking intoaccount the age of the patient,
pre-existing conditions.
(24:52):
So sometimes these markers canbe elevated for other reasons
too.
Dr. Ioannis Mavroudis (24:58):
Exactly, exactly, exactly, yes, so yeah,
to my knowledge, in somecountries I think in France, I'm
not sure I think that in theStates as well, but you might
know better there are somepanels of biomarkers that are
used in the emergency settingmainly I think it's mainly three
biomarkers.
The problem is that can only beused in the first 72 hours in
(25:22):
the acute phase, and thesebiomarkers can help us with the
diagnosis but cannot help us,are not predictive of the
outcome, cannot help us yet withthe prognosis of these patients
.
Dr. Ayla Wolf (25:37):
Yeah, which brings me to my next question,
because you also are researchinga lot in the world of just
neurodegenerative disease and soyou're also studying biomarkers
in that context of trying tounderstand is there a way where
we can get a better handle ondoes somebody have a
neurodegenerative condition?
(25:58):
And so fill me in on kind ofwhere the research is on that in
terms of the biomarkers.
Dr. Ioannis Mavroudis (26:04):
Yes, so the main question in the
neurodegenerative conditions iswhether a patient with mild
symptoms will develop the fullcondition.
For example, if we have apatient with mild cognitive
impairment, some of thesepatients will develop
Alzheimer's or other types ofdementia, but others will never
develop dementia.
(26:25):
It's really important.
It's really crucial now, in theera of these new therapeutic
methods, the monoclonalantibodies, that we develop,
these biomarkers.
There are some biomarkers thatare very sensitive and we can
use them to differentiate thesepatients and to stratify the
(26:46):
patients that will most likelydevelop a condition and, on the
balance of probabilities, willnot develop the condition, and
to treat them differently.
Dr. Ayla Wolf (26:57):
Yeah, that sounds very cutting edge and that,
would you say at this point, isvery much still in the realm of
research, it's not yet beingkind of implemented.
Dr. Ioannis Mavroudis (27:07):
Yes, unfortunately, all these are
still in the very first steps,the very first stages, but there
are some of these biomarkersthat can help us.
For example, this is how wedeveloped all this theory about
the alpha-beta peptide and aboutthe tau protein in Alzheimer's
disease, and this has helped usto understand the
(27:31):
pathophysiology of the disease.
We're currently working on aproject on neurogranin.
Neurogranin is a very sensitivebiomarker.
It's a substance that can helpus to understand the synaptic
function.
We did a study a few years backthat showed us that it's a very
sensitive biomarker forAlzheimer's disease and using
(27:55):
that we can tell whether apatient will develop or will not
develop Alzheimer's.
And now we're working on thisbiomarker as a prognostic marker
for prolonged or severepost-concussion syndrome after a
concussion, and the results sofar are promising.
But we are in the very earlystages.
(28:17):
If you look at the basics,that's how I approach my
research.
I go back to the basics, I goback to my medical school books,
I go back to physiology, backto biochemistry and looking into
the details.
This is how I approach myresearch and how we design our
projects approach my researchand how we design our projects.
Dr. Ayla Wolf (28:47):
And I know that the microglia are involved in
synaptic pruning.
So, going back to this idea ofthe importance of the microglia
and this idea that they havedifferent functions, you know
that we're all talking about howthey can create a lot of
pro-inflammatory situations, butthey also play these very
important roles of surveillanceand synaptic pruning and taking
(29:07):
away synapses we don't need.
But if that gets upregulated,all of a sudden all these
synapses are dying.
And so are you also studyingthe microglia in the context of
blood sugar management and justthis idea of what we call type 3
diabetes in the brain, wherethe ability to regulate glucose
(29:29):
is affected, and then thatthrows everything else off and
kind of creates a state wherethese synapses are perhaps dying
at a greater rate than we wantthem to.
Dr. Ioannis Mavroudis (29:40):
Yeah, this is an excellent idea.
This is an excellent question.
Unfortunately, I don't do thistype of research myself, but a
colleague of mine is a very bigfan of this theory and he's
trying to establish a researchproject on this, which is very
important and sounds verypromising.
So hopefully this will besomething that we will be able
to talk about, maybe in a coupleof years.
Dr. Ayla Wolf (30:02):
Okay, and then what about this paper that you
recently published on themicroglial exosomes?
Talk a little bit about what anexosome is and what this study
is looking at.
Dr. Ioannis Mavroudis (30:14):
Yeah, the exosomes and the endosomes are
small vesicles that are releasedby the neurons and these can
contain different substances.
So in the exosomes we can findif we test the exosomes in the
(30:34):
saliva, for example, we can finddifferent markers, different
substances.
That will help us to have abetter understanding of what's
going on into the body and morespecifically, into the brain.
And studying the exosomes inpatients with post-concussion
(30:57):
syndrome and traumatic braininjuries, we're able to identify
a couple of substances.
Some of them are the microRNAssmall parts of RNAs that we can
study.
And in the exosomes you canalso find some other substances,
like some pieces of tau proteinand other biomarkers that you
(31:19):
can also study, and these arevery important.
Dr. Ayla Wolf (31:24):
Mm-hmm.
So these are kind of messengersthat are being released that
can create kind of a cascade ofevents, is that?
Dr. Ioannis Mavroudis (31:32):
fair to say Exactly, that's fair to say.
And some small portions of themwill also be released into the
bloodstream and into the saliva,and this is how we can capture
them and can study them.
Dr. Ayla Wolf (31:46):
Mm-hmm Got it, so that sounds like the future is
promising in terms of being ableto, hopefully in the near
future, have some better testingmethods to understand where
somebody is at on the scale of,say, neuroinflammation or if
they're having symptoms.
How worried do we need to bethat this might progress into
(32:07):
something more serious down theline?
Dr. Ioannis Mavroudis (32:10):
Exactly exactly.
I believe that in the nearfuture, we'll be able to offer
personalized medicine, tounderstand the patient and to
offer tailored treatment andtailored strategies for each one
of them, based on their needsand based on these biomarkers
and potentially more biomarkersthat will rise in the future.
Dr. Ayla Wolf (32:30):
Yeah Well, how exciting to be at the cutting
edge of all of that.
The other question I wanted toask you was on this when we talk
about the brain, much like wedo with medicine, everything
kind of becomes siloed, and sowe often talk about the brain as
this separate entity from therest of the body.
But in my practice, I pay a lotof attention to the health of
(32:54):
the liver and the kidneys andthe role of healthy liver and
kidney function on healthy brainfunction.
But I think this is somethingthat I don't really hear anybody
else talking about, and so I'mcurious if you have anything to
say in terms of how you look atthe you know, the totality of it
.
Dr. Ioannis Mavroudi (33:12):
Absolutely , absolutely.
Yeah, so the brain doesn'texist in isolation.
The brain always works andcollaborates with the other
organs.
The brain is the sender, butthe other organs are also vital.
We all know from our ownexperience that the liver
function, the kidney function,even the intestinal function and
(33:38):
the stomach are reallyimportant for the brain.
When I was a student sixth yearof medical school, the last
year, I was involved in aresearch that widened my
horizons on the understanding ofwhat you're talking about,
because it was a PhD project andthe guy that did that.
(34:00):
He worked on how somesubstances that we now
understand as orexins from thestomach can affect the brain,
can affect the hypothalamus andthis way can affect the whole
brain function.
So, yeah, all these organs arevery important and crucial.
So we know that we have thecondition which is called
(34:24):
hepatic encephalopathy.
If there is dysfunction to theliver and the energy that will
go to the brain is not enough,then we'll have dysfunction of
the brain and the patient willdevelop a kind of dementia-like
presentation.
Dr. Ayla Wolf (34:41):
Yeah, I remember when my grandmother ended up in
the hospital and she had aurinary tract infection, but
before they had diagnosed it itwas affecting her cognition.
She didn't know her own son'sname, and so there was this
brief moment in time where weall thought, oh no, she's going
downhill really fast andcognitively she was completely
(35:03):
delirious and all of a suddenthey said, oh no, she just has a
urinary tract infection.
And once they fixed that, allof a sudden her cognitive
faculties returned and it wassuch an acute thing to have.
Okay, a urinary tract infectioncan cause this severe type of
dementia symptoms that come.
(35:24):
Connection is vital.
And even if we don't have, likean extreme kidney failure, what
happens if the kidneys I feellike in our modern medicine the
kidneys have to be likepractically failing before
things start to show up on bloodwork or before we start to pay
attention to them?
And yet in our current day andage our kidneys are assaulted
(35:46):
with so many environmentaltoxins and chemicals and things
in the environment that I feellike they're having to work
overtime and yet we just don'treally pay attention to them as
much as we should.
Especially with COVID, welearned that that can create a
lot of inflammation in thekidneys and cause all kinds of
problems, and then you've gotdownstream consequences from
(36:08):
that.
So I, just with my backgroundin Chinese medicine, we always
pay very close attention tokidney function and so I just
see that that being another kindof avenue of you know, this
idea of integration and wetalked about the gut brain axis,
but I think we also need totalk a lot more about that role
of liver health and kidneyhealth and those impacts on the
(36:30):
brain if those aren't workingoptimally or subpar.
Dr. Ioannis Mavroudi (36:34):
Absolutely .
I could not agree more.
Yeah, yeah, as the ancientGreek used to say, it's the
golden min moderation.
Dr. Ayla Wolf (36:42):
Yes, absolutely.
Well, what are the nextprojects that you're working on?
Dr. Ioannis Mavroudis (36:48):
Yeah.
So the main study that we'vejust recently started is to work
on this cloud application andthis machine learning algorithm
on the diagnosis ofpost-concussion syndrome and
traumatic brain injuries, mainlythe concussions.
We try to standardize the panelthat we will use.
(37:09):
So we've identified through theliterature six or seven
biomarkers, to begin withIndistinguishably cortisol is
one of them.
Cortisol is a very versatilebiomarker and can be raised in
different conditions, but wefound that it's very sensitive
(37:32):
and can help in the prognosis ofdifferent symptoms, mainly
psychological symptoms, in thesepatients.
Then we have the CGRP biomarker.
The CGRP is the biomarker thatcan help us on the prognosis of
post-traumatic headaches.
So we've identified thesebiomarkers and we're trying to
(37:54):
do a clinical trial now and thisis the main project that I'm
very enthusiastic about.
Dr. Ayla Wolf (38:02):
Yeah, absolutely.
I see lots of patients withchronic post-traumatic headaches
.
I see lots of patients withchronic post-traumatic headaches
and many of them are givenmigraine medications but not the
CGRP antagonists.
Again, I think because of moneyand because of the insurance
model saying, well, let's givethem all these other medications
(38:23):
first and we have to prove thatthese don't work before you get
the better, more expensivedrugs.
Dr. Ioannis Mavroudis (38:29):
Exactly, exactly, exactly.
This is how the symptomssystems work, but they need to
be sustainable, so it'ssomething we need to follow.
Dr. Ayla Wolf (38:39):
Yeah, yeah.
Well, I'll be excited to seethat research since CGRP is one
of those things that is wellstudied in the migraine
literature, but we're stillreally trying to figure out why
patients with post-traumaticheadaches don't always respond
well to migraine medications.
Dr. Ioannis Mavroudis (38:59):
Yeah, because not all post-traumatic
headaches are migraines innature.
They're different mechanisms.
About 75% of the post-traumaticheadaches they have mixed
features of tension typeheadaches, some migraineous
features as well, cervicogenicheadache, and there was always
stress and psychologicalsymptoms.
(39:21):
Only 20% can be clearlymigraineous.
This is why just a smallpercentage of patients with
post-traumatic headaches willrespond well to migraine
medication.
But CGRP is something that canhelp in other types of headaches
as well, not only in themigraines.
Dr. Ayla Wolf (39:41):
Excellent, so tell me more about that.
You're seeing that even inthese mixed types of headaches
that CGRP is elevated.
Dr. Ioannis Mavroudis (39:51):
CGRP can be elevated and can be a very
good prognostic factor ofdeveloping post-traumatic
headache, independently of thesubtype of headache.
So some patients they mightdevelop tensio-type headaches,
others will develop migraineheadaches.
Other patients may developoccipital neuralgia or even
trigeminal neuralgia or veryrare types of headaches, and
(40:17):
this is a very, very sensitivebiomarker and giving these
patients anti-CGRP medicationcan make the difference.
Dr. Ayla Wolf (40:28):
Yeah, fascinating .
Well, I'm excited to see thatresearch because we definitely
need to help these people, moreso than we are.
There was a study that came outin 2020 that said that 87% of
people with post-traumaticheadaches were dissatisfied with
their current medical treatment, so we need to do better for
(40:48):
these people.
Dr. Ioannis Mavroudis (40:49):
Exactly exactly.
We need to do better and, again, we need a holistic approach.
Just giving medication will notalways help the patient.
We need to consider everything,to consider every other element
that can trigger the headache.
To my experience and theliterature, physiotherapy, neck
(41:11):
physiotherapy will always have apositive impact on these types
of headaches, the post-traumaticheadaches, independently of the
subtype of the headache,because most physicians will say
that, yeah, but this is amigraine headache, how neck
physiotherapy can help?
But there is always acervicogenic element in these
types of headaches Because, as Isaid before, there is always a
(41:36):
cervical spine injury when youhave a concussion.
And then managing stress isalso very important and avoiding
triggers.
This is something that wealways forget.
We forget to advise patients toavoid triggers and then most of
these patients, because theysuffer a lot from the headaches
(41:58):
and other symptoms, they tend tooveruse medication and this is
something else we need to alwayslook at and to be very careful
with these patients to advisethem not to overdo it with
medication, because evenparacetamol or ibuprofen
medications that you can easilybuy over the counter if you take
them long term, they can have avery negative impact on these
(42:20):
headaches.
Dr. Ayla Wolf (42:21):
Yeah, yeah, absolutely the medication
overuse headaches are a realeffect for sure, not to mention
their impact on the liver andthe kidneys.
Dr. Ioannis Mavroudi (42:31):
Absolutely , absolutely.
I agree, I agree yeah.
Dr. Ayla Wolf (42:34):
Yeah, wow, well, anything else that we haven't
talked about that you would liketo cover before we wrap up?
Dr. Ioannis Mavroudis (42:42):
No, I don't have anything else.
You know, I could talk forhours about the brain, about the
neuroplasticity and about theseconditions, but I don't have
anything else.
If you have any other questions, I'm happy to continue the
discussion.
Dr. Ayla Wolf (42:59):
Well, what are the things that you do for your
own brain health?
Dr. Ioannis Mavroudis (43:03):
Yeah, so I used to be an athlete.
I played basketball for manyyears.
I love basketball so I stilltry to play basketball with
friends at the university Notvery successful anymore and I
always try to do some exerciseand to follow a good, balanced
diet and avoid alcohol.
(43:24):
I avoid alcohol.
I tend to admit that I mightenjoy some spirits now and then
two, three times a year, butthat's it.
Dr. Ayla Wolf (43:38):
So very much in moderation.
Dr. Ioannis Mavroudis (43:39):
Exactly.
Dr. Ayla Wolf (43:46):
Yeah, Fabulous yeah, Having those basic pieces
in place.
Dr. Ioannis Mavroudis (43:47):
The exercise the diet, the sleep,
absolutely.
Dr. Ayla Wolf (43:50):
Wonderful.
Well, thank you so much foryour time, and I'd love to have
you back on the show here in alittle bit, once you have some
of these other research findingspublished, and I'd love to stay
on top of all of thiscutting-edge work that you're
doing, because it's so important.
Dr. Ioannis Mavroudis (44:05):
Thank you .
Thank you very much for havingme today.
I'm honored.
Thank you, thank you.
Dr. Ayla Wolf (44:08):
Thank you very much for having me today.
I'm honored.
Dr. Ioannis Mavroudis (44:09):
Thank you , thank you.
Dr. Ayla Wolf (44:11):
Where can people find you?
I know you've got some YouTubechannels out there or
information.
Dr. Ioannis Mavroudis (44:17):
Yeah, so unfortunately I cannot work on
my YouTube channels because ofmy other commitments, but they
can find me on LinkedIn and I'malways happy to respond to any
messages or any queries.
Dr. Ayla Wolf (44:30):
Okay, fabulous.
Well, I can put that in theshow notes there.
Dr. Ioannis Mavroudis (44:34):
Wonderful .
Dr. Ayla Wolf (44:35):
Thank you so much for your time, Dr Mavroudis.
Dr. Ioannis Mavroudis (44:38):
Thank you .
Thank you very much.
Dr. Ayla Wolf (44:43):
Medical Disclaimer.
Disclaimer this video orpodcast is for general
informational purposes only anddoes not constitute the practice
of medicine or otherprofessional health care
services, including the givingof medical advice.
No doctor patient relationshipis formed.
The use of this information andmaterials included is at the
(45:03):
user's own risk.
The content of this video orpodcast is not intended to be a
substitute for medical advice,diagnosis or treatment, and
consumers of this informationshould seek the advice of a
medical professional for any andall health-related issues.
A link to our full medicaldisclaimer is available in the
notes.
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