New Frontiers in Concussion Research with Dr. Ioannis Mavroudis | E34

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

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Chapters

• 0:00 Understanding Neurodegenerative Conditions
• 6:42 Dr. Mavrudis' Journey in Neurology
• 11:18 Commonalities in Neurological Disorders
• 21:29 Neuroinflammation and Microglial Function
• 26:57 Treatment Approaches Without Medication
• 35:09 Cognitive Testing and Rehabilitation
• 42:04 Blood Biomarkers in Brain Injury
• 47:56 Future Research and Whole-Body Approach

Transcript

Dr. Ioannis Mavroudis: 0:00

Yes, so the main question in the neurodegenerative conditions is whether a patient with mild symptoms will develop the full condition. For example, if we have a patient with mild cognitive impairment, some of these patients will develop Alzheimer's or other types of dementia, but others will never develop dementia. It's really important. It's really crucial now, in the era of these new therapeutic methods you know the monoclonal antibodies that we develop, these biomarkers. There are some biomarkers that are very sensitive and we can use them to differentiate these patients.

Dr. Ayla Wolf: 0:42

Welcome to Life After Impact the concussion recovery podcast. I'm Dr Ayla Wolff and I will be hosting today's episode, where we help you navigate the often confusing, frustrating and overwhelming journey of concussion and brain injury recovery. This podcast is your go-to resource for actionable information, whether you're dealing with a recent concussion, struggling with post concussion syndrome or just feeling stuck in your healing process. In each episode, we dive deep into the symptoms, testing, treatments and neurological insights that can help you move forward with clarity and confidence. We bring you leading experts in the world of brain health, functional neurology and rehabilitation to share their wisdom and strategies.

Dr. Ayla Wolf: 1:27

So if you're feeling lost, hopeless or like no one understands what you're going through, know that you are not alone. This podcast can be your guide and partner in recovery, helping you build a better life after impact. Dr Mavroudis, thank you so much for joining Life After Impact the concussion recovery podcast. When I am doing a lot of my research on the internet on brain injuries, your name keeps coming up as somebody who has published a lot of research, but you're also a clinician and a consultant neurologist at the University of Leeds, and I think it's so important that the people that are doing research also are working with patients who have that experience of hearing directly from patients what it is their struggles are, because I think that that informs our research so much. So welcome to the show.

Dr. Ioannis Mavroudis: 2:23

Thank you very much. Thank you very much for this invitation. Thank you for having me today. It's my pleasure and honor to discuss with you about concussions, about brain injuries.

Dr. Ayla Wolf: 2:36

Yeah, tell us a little bit about your background and how you ended up on this track.

Dr. Ioannis Mavroudis: 2:41

Yeah. So I started medicine in Greece many years ago, 20-26 years ago, graduated in 2004,. Then I did a PhD in neuromorphology and neuropathology and I was also fascinated by the brain. You know, the brain has always represented to me the ultimate challenge, always represented to me the ultimate challenge. Of course, there are other vital and important organs, like the heart, like the lungs, even the kidneys, but the brain remains a universe of mysteries and I'd like to explore this universe because the brain is what we actually are. So the brain is the seat of consciousness, personality, creativity, memory, anything. Of course, meeting my mentor in my PhD was very important, crucial to my decision to study neurology and neuropathology.

Dr. Ioannis Mavroudis: 3:44

Then I did my neurology training in Greece the same time I finished my PhD. Then I came to the UK mainly to study neuropathology diagnostic neuropathology, and to study brain biopsies and muscle biopsies. And then I jumped back to the field of clinical neurology when I started seeing many rugby players with traumatic brain injuries and because most of these patients were undiagnosed and they never get the treatment and the attention they needed, they required, that's how I decided to shift my practice mainly into this field. So what I do now is I run a practice I mainly see patients with traumatic brain injuries mainly mild traumatic brain injuries, and the cognitive impairment which is the aftermath of that, and because I see many things in common with functional neurological disorders. That's why I also do a functional neurological disorder clinic, trying to find things that are in common.

Dr. Ayla Wolf: 4:59

Yeah, and those functional neurological disorders. I mean those patients often have seen so many doctors. They've been told there's nothing wrong with you. So I imagine you've heard a lot of stories and you've seen a lot of frustrations with people that have that diagnosis. I'm curious what are you finding as a commonality between these patients?

Dr. Ioannis Mavroudis: 5:22

Yeah. So we have recently published at least two or three papers trying to explain the commonalities between functional neurological disorders and post-concussion syndrome. Of course, post-concussion syndrome is not a term that we're allowed to use because it's not in the ICD-11 anymore, but it's a label that we can easily use and can help us and the patients to understand. It's just a constellation of different symptoms. So if we see a patient with functional cognitive disorder and if we see a patient with post-concussion syndrome, we will notice the same things. We will notice the same mechanisms and the same triggers in their symptoms. In their symptoms, both groups of these patients will have the same triggers, such as stress. Both groups will have fatigue, which is one of the predominant of the main symptoms, and we've suggested that there are many things in common and possibly common mechanisms, which my personal position is that this is deep inside the brain and is because of a change in the neuroplasticity and the ability of the brain to adapt.

Dr. Ayla Wolf: 6:40

And does that come back to say mitochondrial dysfunction, or is there some other mechanism that is affecting the neuroplasticity?

Dr. Ioannis Mavroudis: 6:51

Yeah, the mitochondria play a very, very important and viral role to how the brain and how the neurons work. They provide the energy, and not only the energy. They do more things than that. But I believe that the problem is mainly in the synapse, where the neurons communicate when they send information. So there are two different mechanisms it's the long-term depression and long-term potentiation. These are the two mechanisms where the ability of the brain relies on, and I believe that these mechanisms are disrupted and this is why the brain in these patients is not able to adapt to the post-injury or the post-FND diagnosis daily life. And speaking of that, I found many things in common with the prolonged, the persistent post sorry, the long COVID syndrome. There are many things in common and I believe that there are similarities in the pathological mechanisms in this condition too.

Dr. Ayla Wolf: 8:03

I know you had published a paper speaking to the similarities and symptoms between post-concussion syndrome and long COVID. Bringing up long-term potentiation brings me right back to neurology 101. So it comes back to the basics, right Of just understanding synaptic neuroplasticity, how the brain communicates.

Dr. Ayla Wolf: 8:24

And so you're seeing that the commonality between a lot of these persistent syndromes is this idea of the synapses struggling to communicate, which brings me to an interesting paper that you also just published on microglial exosomes. And so what is the role of the immune system in all of this? And neuroinflammation?

Dr. Ioannis Mavroudis: 8:48

Absolutely, absolutely. The role of microglia is very important. So the microglia are specialized cells. They're part of the immune system. They're not part of the central nervous system but they are specialized. They go into the central nervous system very early in their life and this is why they are allowed to be there, because we have the blood-brain barrier, so nothing from the blood can cross this barrier under normal circumstances. These cells, they have the same role as the protective cells have in the blood. So what they do? They get activated when there is inflammation. But sometimes this inflammation can cause damage and this inflammation, because of the increased demand of energy, can affect the mitochondria, as you said before, and this can affect how the brain works. Because if there is lack of energy into the neuron, then this long-term potentiation and the overall neuroplasticity will be affected and the neurons will not be able to communicate effectively yeah, and so in your clinical practice, how are you unraveling all this?

Dr. Ayla Wolf: 10:08

how are you addressing this uh mess of both mitochondrial dysfunction uh microglial dysfunction, the persistence of neuroinflammation affecting uh neuroplasticity. You know where do you jump in to try to kind of fix all of that yeah, this, this is not easy, so.

Dr. Ioannis Mavroudis: 10:24

So, first of all, we need to focus on the translational neuroscience, so we need to translate the research results and the results from the papers we do and publish into the clinical practice. This is not always easy, but it's something we need to do in order to help our patients. First step is to listen to the patients, to understand the needs, understand the symptoms, try to explain them based on the basic knowledge we have obtained from medical school and from early years in our training, and this way you're able to send the patients to the right pathway recovery pathway and treatment pathway.

Dr. Ayla Wolf: 11:13

And are you utilizing certain medications or are you really focusing on lifestyle changes? Diet when are you kind of recommending people start?

Dr. Ioannis Mavroudis: 11:26

Yes. So to be honest I'm not a fan of medications. I try not to give too many medications to my patients. So, for example, for fatigue in the United States there are some tablets that are prescribed here in the UK and in my own practice we try to avoid that. We try mainly to help the patients without any medication, to advise them on the amount of rest they need, the amount of sleep they need.

Dr. Ioannis Mavroudis: 11:58

I believe I'm a big believer of behavioral therapies and neuropsychology. I believe that neuropsychology can help patients, both in post-concussion syndrome and functional neurological disorders, to to have a better treatment and a better outcome. So we always try to advise on right exercise, right amount of exercise, not too intense exercise, low intensity. 40-45 minutes of walking or light jogging in the morning is the best exercise because this way you're able to manage your stress better. Stress is not an ally in this war.

Dr. Ioannis Mavroudis: 12:40

Then diet is very important. You know the usual stuff, nothing special. But we always try to advise the patients to drink plenty of fluids, to avoid alcohol or anything else that can harm the brain, can cause more harm to the brain, and to try lots of antioxidants and things like that, just the general healthy stuff. Of course we have specialized dieticians that will see the patients. In the end, if with this general advice on diet, if it's not helpful, we have coaches that can help the patients, can give them the right exercises, the right programs that can help them in the gym. So we basically try to provide a tailored program to each patient. If this doesn't work, we will repeat some of the tests that we do after three and six months and if there is no improvement then we might try some medications. But to my experience, the only medications that can help are very low doses of antidepressants, just to fight stress and to help the mood. This is the only thing that has place in the treatment of these conditions.

Dr. Ayla Wolf: 14:01

And you mentioned that one of your focuses is on the cognitive symptoms that people are describing. Are you doing different cognitive exercises or training programs with people as well?

Dr. Ioannis Mavroudis: 14:12

Yes. So, first of all, in terms of diagnosis, we don't do the usual diagnostic tests such as the MOCA, the mini mental state examination on the Addenbrookes, because these tests are not sensitive for patients with traumatic brain injuries. I personally prefer to do a computerized test, the impact test, which is widely known and widely accepted, and with this test you can study different aspects of the cognitive functions. We also do a test using virtual reality. It's an eye-tracking test because the ocular movements are very important in the recovery of these patients. These are the tests we do, and then, in terms of recovery, we use our own tests. We have developed a couple of video games that we try to use in patients that love video games. These video games, they have some cognitive challenges, they have some eye-tracking challenges, some cognitive challenges, they have some eye-tracking challenges. And then, of course, it's the golden standard, the cognitive behavioral therapy with experienced neuropsychologists.

Dr. Ayla Wolf: 15:26

And you're seeing that with use of the virtual reality, at least the people who can handle that that that's actually helping in terms of some of their ocular motor symptoms as well as, maybe, things like reaction time and other cognitive processes.

Dr. Ioannis Mavroudis: 15:41

Absolutely, absolutely. This test is very useful because, of course, you can study the ocular movements, but at the same time, there are some other parameters that you can study. For example, there is the cervical element. You ask the patient to do some neck movements, having the VR set on their heads, and this way you can see if anything changes, and this is an indication of an injury to the cervical spine, because there is no concussion, no traumatic brain injury without cervical injury, as we know. And then there are some cognitive challenges as well. So we have the saccade, the saccade movements when we ask the patient to follow a flashing light, but at the same time, we have the antisaccades, when we ask the patient to look at the opposite side, and this has a cognitive element as well.

Dr. Ayla Wolf: 16:34

Yeah, yeah. That's such a great window into that prefrontal cortex and impulse control. I do that test at the bedside and I often see people struggle with it when they've had concussions. Absolutely.

Dr. Ioannis Mavroudis: 16:46

Absolutely, absolutely. Yeah, this is my favorite bedside test. It's the vestibulocular test, which I always do, but in my practice I prefer to do uh the vr test, which is a bit more impressive, and, of course, it's uh something that you can video and you can document everything on the patient and you can repeat that after three and six months and uh using the same standards you have. You can have a good understanding 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's ocular motor movements Olympians in the 2024 Olympics. His team went there and studied the eye movements of people that were in high impact sports, like boxing, versus people who were in sports that didn't involve high impact, and they were able to really show differences in eye movements and the people that were performing these high impact sports. Even if they hadn't had that concussion diagnosis, they were still kind of evidence of some dysfunction there. So I love that the spotlight on the importance of eye movements is getting a lot more attention, which is great because it is a window into so many parts of the brain, because eye movements are so complex and they also take up a lot of cognitive energy too, and so when people are struggling with their ocular motor system, that can create a lot of that brain fatigue that we see symptomatically.

Dr. Ioannis Mavroudis: 18:23

Absolutely, absolutely. And doing that, we're able to offer vestibular rehabilitation to help our patients, because most patients, you know, when they come to see me or to see one of my colleagues in clinic, even five or six or seven years after the injury, they've never had the right test, they've never had the chance to get the right treatment.

Dr. Ayla Wolf: 19:54

Yeah, yep, absolutely. And so, switching gears a little bit, let's talk about some of the blood biomarker research, and it seems like there's certain blood biomarkers that are not quite so specific to the brain exclusively, like S100B is not exclusive to brain injury, but still a marker of brain injury potentially, and so there are some markers that kind of are meaningful within the first, you know, couple of hours after an injury. There are some pro-inflammatory markers that maybe can give an indication of is this brain recovering. So I think it's very confusing for the general person to say, okay, we've got pro-inflammatory and anti-inflammatory markers, and then some of them are indicating this at this time point or that at that time point. This can be a very confusing topic. So let's maybe dive into this blood biomarker research.

Dr. Ioannis Mavroudis: 20:51

You're absolutely right. So, yes, I agree with you. Most of these biomarkers are not brain specific, but the combination of all of them and considering the history of the brain injury can help us to understand what's going on. As you said, there are some biomarkers that can help us to understand about the healing process, about the inflammation. Of course, we have the, the light chain neurofilament light chain biomarker, that it's a marker of disruption of actions in the central nervous system. Most of these biomarkers can be raised, even in general injuries or orthopedic injuries.

Dr. Ioannis Mavroudis: 21:35

What we try to do now is to develop a kind of a cloud application and a device to study these biomarkers as a group and then to feed them into an algorithm that will help us to understand them better. Of course, always, always, always working with the patient, working with the history and taking into account the patient's experience and the patient's side of things. If we just take a set of biomarkers and you know they might be raised, they might be different to the normal range. We'll never be able to make a diagnosis unless we have the patient in front of us, unless we have a medical history, unless we have a neurological examination, unless we have a medical history, unless we have a neurological examination. I believe that in the near future, probably in the next five years, the biomarkers will be able to help us with the diagnosis, a more accurate diagnosis, because in most of these cases, especially in sports concussions and in the medical legal setting you know road traffic accidents, things like that accurate diagnosis is very, very important. So hopefully, with these biomarkers and doing non-invasive testing like saliva swab because most of these biomarkers now are taken from blood or CSF, taking saliva swab will make things even easier for the patients. I believe that the future is in the exosomal biomarkers, which is very sensitive in the microRNAs. So having a combination of all of these biomarkers will give us what we need.

Dr. Ioannis Mavroudis: 23:29

I had a meeting with an excellent colleague of mine that we've done a lot of research together, professor Čobika. He's a biochemist in Romania and we had the meeting and he said that I always ask my students when I interview them for their PhD, how many biomarkers do we have for neurological and psychiatric conditions? And they always you know most students 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 them and the combination of the patient, the combination of the history and anything else that can help us to understand the patient and to have an accurate diagnosis. But we need to remember that in medicine nothing is deterministic. It's always probabilistic. So, even with the best evidence, the diagnosis is based on the probability, on the balance of probabilities, and these biomarkers can help us to increase the probability of a more accurate diagnosis.

Dr. Ayla Wolf: 24:43

Right, and I think at this point is it fair to say too that in this kind of preliminary state that some of these blood biomarkers, when taken as a panel together, can then inform, say, a doctor in an emergency department whether or not they need to do a CT scan.

Dr. Ioannis Mavroudis: 25:01

Exactly exactly. I agree with that, and this is where the research is mainly focused to save patients from getting exposed to radiation and, of course, to save money to the health systems. This can be very useful for the emergency physicians to decide whether to do or not to do a CT scan, but, as I said, this alone is not enough. We always need to take into account everything else, because if we have a patient with a minor head injury and significant neurological symptoms, even if the biomarkers are not raised, we definitely need to do a scan.

Dr. Ayla Wolf: 25:41

Yeah, absolutely. And then I know, on the flip side of that, in certain people maybe elderly people that have kidney failure some of these biomarkers might also be elevated as a result of kidney function or a loss of kidney function. So again, it's also taking into account the age of the patient, pre-existing conditions. So sometimes these markers can be elevated for other reasons too.

Dr. Ioannis Mavroudis: 26:08

Exactly, exactly, exactly, yes, so yeah, to my knowledge, in some countries I think in France, I'm not sure I think that in the States as well, but you might know better there are some panels of biomarkers that are used in the emergency setting mainly I think it's mainly three biomarkers. The problem is that can only be used in the first 72 hours in the acute phase, and these biomarkers can help us with the diagnosis but cannot help us, are not predictive of the outcome, cannot help us yet with the prognosis of these patients.

Dr. Ayla Wolf: 26:48

Yeah, which brings me to my next question, because you also are researching a lot in the world of just neurodegenerative disease and so you're also studying biomarkers in that context of trying to understand is there a way where we can get a better handle on does somebody have a neurodegenerative condition? And so fill me in on kind of where the research is on that in terms of the biomarkers.

Dr. Ioannis Mavroudis: 27:14

Yes, so the main question in the neurodegenerative conditions is whether a patient with mild symptoms will develop the full condition. For example, if we have a patient with mild cognitive impairment, some of these patients will develop Alzheimer's or other types of dementia, but others will never develop dementia. It's really important. It's really crucial now, in the era of these new therapeutic methods, the monoclonal antibodies, that we develop, these biomarkers. There are some biomarkers that are very sensitive and we can use them to differentiate these patients and to stratify the patients that will most likely develop a condition and, on the balance of probabilities, will not develop the condition, and to treat them differently.

Dr. Ayla Wolf: 28:08

Yeah, that sounds very cutting edge and that, would you say at this point, is very much still in the realm of research, it's not yet being kind of implemented.

Dr. Ioannis Mavroudis: 28:17

Yes, unfortunately, all these are still in the very first steps, the very first stages, but there are some of these biomarkers that can help us. For example, this is how we developed all this theory about the alpha-beta peptide and about the tau protein in Alzheimer's disease, and this has helped us to understand the pathophysiology of the disease. We're currently working on a project on neurogranin. Neurogranin is a very sensitive biomarker. It's a substance that can help us to understand the synaptic function. We did a study a few years back that showed us that it's a very sensitive biomarker for Alzheimer's disease and using that we can tell whether a patient will develop or will not develop Alzheimer's. And now we're working on this biomarker as a prognostic marker for prolonged or severe post-concussion syndrome after a concussion, and the results so far are promising.

Dr. Ioannis Mavroudis: 29:24

But we are in the very early stages. If you look at the basics, that's how I approach my research. I go back to the basics, I go back to my medical school books, I go back to physiology, back to biochemistry and looking into the details. This is how I approach my research and how we design our projects approach my research and how we design our projects.

Dr. Ayla Wolf: 29:57

And I know that the microglia are involved in synaptic pruning. So, going back to this idea of the importance of the microglia and this idea that they have different functions, you know that we're all talking about how they can create a lot of pro-inflammatory situations, but they also play these very important roles of surveillance and synaptic pruning and taking 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 studying the microglia in the context of blood sugar management and just this idea of what we call type 3 diabetes in the brain, where the ability to regulate glucose is affected, and then that throws everything else off and kind of creates a state where these synapses are perhaps dying at a greater rate than we want them to.

Dr. Ioannis Mavroudis: 30:50

Yeah, this is an excellent idea. This is an excellent question. Unfortunately, I don't do this type of research myself, but a colleague of mine is a very big fan of this theory and he's trying to establish a research project on this, which is very important and sounds very promising. So hopefully this will be something that we will be able to talk about, maybe in a couple of years.

Dr. Ayla Wolf: 31:12

Okay, and then what about this paper that you recently published on the microglial exosomes? Talk a little bit about what an exosome is and what this study is looking at.

Dr. Ioannis Mavroudis: 31:24

Yeah, the exosomes and the endosomes are small vesicles that are released by the neurons and these can contain different substances. So in the exosomes we can find if we test the exosomes in the saliva, for example, we can find different markers, different substances. That will help us to have a better understanding of what's going on into the body and more specifically, into the brain. And studying the exosomes in patients with post-concussion syndrome and traumatic brain injuries, we're able to identify a couple of substances. Some of them are the microRNAs small parts of RNAs that we can study. And in the exosomes you can also find some other substances, like some pieces of tau protein and other biomarkers that you can also study, and these are very important.

Dr. Ayla Wolf: 32:34

Mm-hmm. So these are kind of messengers that are being released that can create kind of a cascade of events, is that?

Dr. Ioannis Mavroudis: 32:42

fair to say Exactly, that's fair to say. And some small portions of them will 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: 32:56

Mm-hmm Got it, so that sounds like the future is promising in terms of being able to, hopefully in the near future, have some better testing methods to understand where somebody is at on the scale of, say, neuroinflammation or if they're having symptoms. How worried do we need to be that this might progress into something more serious down the line?

Dr. Ioannis Mavroudis: 33:20

Exactly exactly. I believe that in the near future, we'll be able to offer personalized medicine, to understand the patient and to offer tailored treatment and tailored strategies for each one of them, based on their needs and based on these biomarkers and potentially more biomarkers that will rise in the future.

Dr. Ayla Wolf: 33:40

Yeah Well, how exciting to be at the cutting edge of all of that. The other question I wanted to ask you was on this when we talk about the brain, much like we do with medicine, everything kind of becomes siloed, and so we often talk about the brain as this separate entity from the rest of the body. But in my practice, I pay a lot of attention to the health of the liver and the kidneys and the role of healthy liver and kidney function on healthy brain function. But I think this is something that I don't really hear anybody else talking about, and so I'm curious if you have anything to say in terms of how you look at the you know, the totality of it.

Dr. Ioannis Mavroudis: 34:22

Absolutely, absolutely. Yeah, so the brain doesn't exist in isolation. The brain always works and collaborates with the other organs. The brain is the sender, but the other organs are also vital. We all know from our own experience that the liver function, the kidney function, even the intestinal function and the stomach are really important for the brain. When I was a student sixth year of medical school, the last year, I was involved in a research that widened my horizons on the understanding of what you're talking about, because it was a PhD project and the guy that did that. He worked on how some substances that we now understand as orexins from the stomach can affect the brain, can affect the hypothalamus and this way can affect the whole brain function. So, yeah, all these organs are very important and crucial. So we know that we have the condition which is called hepatic encephalopathy. If there is dysfunction to the liver and the energy that will go to the brain is not enough, then we'll have dysfunction of the brain and the patient will develop a kind of dementia-like presentation.

Dr. Ayla Wolf: 35:52

Yeah, I remember when my grandmother ended up in the hospital and she had a urinary tract infection, but before they had diagnosed it it was affecting her cognition. She didn't know her own son's name, and so there was this brief moment in time where we all thought, oh no, she's going downhill really fast and cognitively she was completely delirious and all of a sudden they said, oh no, she just has a urinary tract infection. And once they fixed that, all of a sudden her cognitive faculties returned and it was such an acute thing to have. Okay, a urinary tract infection can cause this severe type of dementia symptoms that come. Connection is vital.

Dr. Ayla Wolf: 36:37

And even if we don't have, like an extreme kidney failure, what happens if the kidneys I feel like in our modern medicine the kidneys have to be like practically failing before things start to show up on blood work or before we start to pay attention to them?

Dr. Ayla Wolf: 36:51

And yet in our current day and age our kidneys are assaulted with so many environmental toxins and chemicals and things in the environment that I feel like they're having to work overtime and yet we just don't really pay attention to them as much as we should. Especially with COVID, we learned that that can create a lot of inflammation in the kidneys and cause all kinds of problems, and then you've got downstream consequences from that. So I, just with my background in Chinese medicine, we always pay very close attention to kidney function and so I just see that that being another kind of avenue of you know, this idea of integration and we talked about the gut brain axis, but I think we also need to talk a lot more about that role of liver health and kidney health and those impacts on the brain if those aren't working optimally or subpar.

Dr. Ioannis Mavroudis: 37:44

Absolutely. I could not agree more. Yeah, yeah, as the ancient Greek used to say, it's the golden min moderation.

Dr. Ayla Wolf: 37:52

Yes, absolutely. Well, what are the next projects that you're working on?

Dr. Ioannis Mavroudis: 37:58

Yeah. So the main study that we've just recently started is to work on this cloud application and this machine learning algorithm on the diagnosis of post-concussion syndrome and traumatic brain injuries, mainly the concussions. We try to standardize the panel that we will use. So we've identified through the literature six or seven biomarkers, to begin with Indistinguishably cortisol is one of them. Cortisol is a very versatile biomarker and can be raised in different conditions, but we found that it's very sensitive and can help in the prognosis of different symptoms, mainly psychological symptoms, in these patients. Then we have the CGRP biomarker. The CGRP is the biomarker that can help us on the prognosis of post-traumatic headaches. So we've identified these biomarkers and we're trying to do a clinical trial now and this is the main project that I'm very enthusiastic about.

Dr. Ayla Wolf: 39:12

Yeah, absolutely. I see lots of patients with chronic post-traumatic headaches. I see lots of patients with chronic post-traumatic headaches and many of them are given migraine medications but not the CGRP antagonists. Again, I think because of money and because of the insurance model saying, well, let's give them all these other medications first and we have to prove that these don't work before you get the better, more expensive drugs.

Dr. Ioannis Mavroudis: 39:39

Exactly, exactly, exactly. This is how the symptoms systems work, but they need to be sustainable, so it's something we need to follow.

Dr. Ayla Wolf: 39:49

Yeah, yeah. Well, I'll be excited to see that research since CGRP is one of those things that is well studied in the migraine literature, but we're still really trying to figure out why patients with post-traumatic headaches don't always respond well to migraine medications.

Dr. Ioannis Mavroudis: 40:09

Yeah, because not all post-traumatic headaches are migraines in nature. They're different mechanisms. About 75% of the post-traumatic headaches they have mixed features of tension type headaches, some migraineous features as well, cervicogenic headache, and there was always stress and psychological symptoms. Only 20% can be clearly migraineous. This is why just a small percentage of patients with post-traumatic headaches will respond well to migraine medication. But CGRP is something that can help in other types of headaches as well, not only in the migraines.

Dr. Ayla Wolf: 40:51

Excellent, so tell me more about that. You're seeing that even in these mixed types of headaches that CGRP is elevated.

Dr. Ioannis Mavroudis: 41:01

CGRP can be elevated and can be a very good prognostic factor of developing post-traumatic headache, independently of the subtype of headache. So some patients they might develop tensio-type headaches, others will develop migraine headaches. Other patients may develop occipital neuralgia or even trigeminal neuralgia or very rare types of headaches, and this is a very, very sensitive biomarker and giving these patients anti-CGRP medication can make the difference.

Dr. Ayla Wolf: 41:38

Yeah, fascinating. Well, I'm excited to see that research because we definitely need to help these people, more so than we are. There was a study that came out in 2020 that said that 87% of people with post-traumatic headaches were dissatisfied with their current medical treatment, so we need to do better for these people.

Dr. Ioannis Mavroudis: 41:59

Exactly exactly. We need to do better and, again, we need a holistic approach. Just giving medication will not always help the patient. We need to consider everything, to consider every other element that can trigger the headache.

Dr. Ioannis Mavroudis: 42:17

To my experience and the literature, physiotherapy, neck physiotherapy will always have a positive impact on these types of headaches, the post-traumatic headaches, independently of the subtype of the headache, because most physicians will say that, yeah, but this is a migraine headache, how neck physiotherapy can help? But there is always a cervicogenic element in these types of headaches Because, as I said before, there is always a cervical spine injury when you have a concussion. And then managing stress is also very important and avoiding triggers. This is something that we always forget. We forget to advise patients to avoid triggers and then most of these patients, because they suffer a lot from the headaches and other symptoms, they tend to overuse medication and this is something else we need to always look at and to be very careful with these patients to advise them not to overdo it with medication, because even paracetamol or ibuprofen medications that you can easily buy over the counter if you take them long term, they can have a very negative impact on these headaches.

Dr. Ayla Wolf: 43:31

Yeah, yeah, absolutely the medication overuse headaches are a real effect for sure, not to mention their impact on the liver and the kidneys.

Dr. Ioannis Mavroudis: 43:41

Absolutely, absolutely. I agree, I agree yeah.

Dr. Ayla Wolf: 43:44

Yeah, wow, well, anything else that we haven't talked about that you would like to cover before we wrap up?

Dr. Ioannis Mavroudis: 43:52

No, I don't have anything else. You know, I could talk for hours about the brain, about the neuroplasticity and about these conditions, but I don't have anything else. If you have any other questions, I'm happy to continue the discussion.

Dr. Ayla Wolf: 44:09

Well, what are the things that you do for your own brain health?

Dr. Ioannis Mavroudis: 44:14

Yeah, so I used to be an athlete. I played basketball for many years. I love basketball so I still try to play basketball with friends at the university Not very successful anymore and I always try to do some exercise and to follow a good, balanced diet and avoid alcohol. I avoid alcohol. I tend to admit that I might enjoy some spirits now and then two, three times a year, but that's it.

Dr. Ayla Wolf: 44:48

So very much in moderation.

Dr. Ioannis Mavroudis: 44:50

Exactly.

Dr. Ayla Wolf: 44:56

Yeah, Fabulous yeah, Having those basic pieces in place.

Dr. Ioannis Mavroudis: 44:57

The exercise the diet, the sleep, absolutely.

Dr. Ayla Wolf: 45:00

Wonderful. Well, thank you so much for your time, and I'd love to have you back on the show here in a little bit, once you have some of these other research findings published, and I'd love to stay on top of all of this cutting-edge work that you're doing, because it's so important.

Dr. Ioannis Mavroudis: 45:15

Thank you. Thank you very much for having me today. I'm honored. Thank you, thank you.

Dr. Ayla Wolf: 45:18

Thank you very much for having me today. I'm honored.

Dr. Ioannis Mavroudis: 45:20

Thank you, thank you.

Dr. Ayla Wolf: 45:21

Where can people find you? I know you've got some YouTube channels out there or information.

Dr. Ioannis Mavroudis: 45:28

Yeah, so unfortunately I cannot work on my YouTube channels because of my other commitments, but they can find me on LinkedIn and I'm always happy to respond to any messages or any queries.

Dr. Ayla Wolf: 45:40

Okay, fabulous. Well, I can put that in the show notes there.

Dr. Ioannis Mavroudis: 45:44

Wonderful.

Dr. Ayla Wolf: 45:45

Thank you so much for your time, Dr Mavroudis.

Dr. Ioannis Mavroudis: 45:48

Thank you. Thank you very much.

Dr. Ayla Wolf: 45:53

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