 A bit about the Brain Foundation. For those of you who are new or who don't know much about us, our primary goal at the Brain Foundation is to fund high quality Australian research into brain diseases, disorders and injuries with the ultimate goal of improving patient outcomes. Secondly, we provide medically reviewed resources about brain conditions that anyone can use to learn more about a particular disorder. So this includes the articles on our website and also resources like this webinar and the other content that we've been sharing throughout Brain Awareness Week. And lastly, we raise awareness about the impact of brain diseases and advocate for patients. So just to make sure everyone's in the right place tonight, who is this webinar for? This is for anyone who is interested in improving their brain health. If you would like to learn more about cerebrovascular diseases such as stroke or aneurysm. And thirdly, if you want to ask a brain researcher about the link between health, lifestyle and cerebrovascular disease and submit questions tonight, you can send them in the chat, which everyone's already using. And then there's also the Q&A function, which you should also see in the bottom part of the webinar. And you can send your questions directly to the panelists to make sure that we don't miss them. And now I'd like to introduce tonight's speaker, Dr Matilda Balby. Dr Balby is a neuroscientist within the Queensland Brain Institute at the University of Queensland. And she leads a lab which aims to make an impact on the field of stroke recovery and other diseases by using a combination of imaging techniques, brain stimulation and individually tailored recovery models. And she actually received a Brain Foundation research grant last year to investigate a debilitating complication of aneurysm rupture, which occurs in about a quarter of patients. So we're really looking forward to learning more through her research and are really excited that she can be here to speak to us tonight. So without further ado, let's start the presentation. Good afternoon, everybody. Before starting, I'd like to acknowledge the traditional owners and custodianship of the land on which we meet today. I'd like to pay my respects to their ancestors and their descendants who continue cultural and spiritual connections to the country. I'd like to recognise their valuable contributions to Australia and the global society. Hello and welcome to this webinar on cerebrovascular health as part of the 2024 Brain Awareness Week. My name is Matilde Balby and I am a group leader at the Queensland Brain Institute at the University of Queensland in Brisbane. Today we are going to talk about cerebrovascular health, what it means and what are the key components of cerebrovascular health. I'm going to talk about factors influencing cerebrovascular health and I'm going to give you some examples of cerebrovascular diseases specifically on stroke, which is what we study in my lab. In the last part of the talk, I'm going to quickly talk about my research on cerebrovascular health and I will finish off with a few basic tips for promoting cerebrovascular health. So let's start with what is cerebrovascular health? Well, cerebrovascular health refers to the overall well-being and functioning of the blood vessels that supply the brain with oxygen and nutrients. The term cerebrovascular specifically refers to the blood vessels in the brain, including arteries and veins. Maintaining good cerebrovascular health is essential for optimal brain functioning and for preventing neurological disorders. But why? Why is this so crucial? Well, first of all, because the brain has a very high basal metabolic demand. It uses up to 20% of the body energy in terms of oxygen consumption while accounting for only 2% of the total body mass. However, the brain can store a very limited amount of energy substrates, which makes the brain a very hungry organ. To satisfy this hunger, the brain requires a continuous delivery of glucose and oxygen throughout the bloodstream. Therefore, the brain needs a very tight regulation of cerebral blood flow, as any imbalance between metabolism and blood flow quickly affects brain function. To irrigate the brain, blood is delivered throughout the cerebrovascular. From the brain surface, arteries and veins are generally defined as piled arteries or piled veins. And then as they descend into the brain, they get smaller and they change their cellular composition. So penetrating arteries will be characterized by a thicker layer of endotelium cells, for example, compared to parenchyoma arteries, which are deeper into the brain. Capillaries are the deeper, you see them here, are the smaller and deeper part of the vascular tree. So the intricate relationship between brain activity and the blood flow regulation involves many cell types. These cell types form what is called the neurovascular unit. We typically hear about the neurons, which are the cell types we all concentrate the most when we think about diseases. But there are lots of other cells that play a key role in maintaining brain's function. And that includes supporting cells, such as astrocytes, which have many, many functions in the brain, including unrolling waste clearance from the brain. Mycrolidia are another example. They are the brain's resident in themselves, and they also play an important role in keeping the brain healthy. So as you can see in this schematic right here, the cells that form the neurovascular unit are all either directly or indirectly contacting each other, and they are contacting brain vasculatures. So this communication and this interaction between cell types is essential for a physiological neurovascular coupling. Now, the neurovascular coupling is a crucial mechanism that is needed to match the high energy demand of the brain with a supply in energy substrates from the blood stream. And all the signaling within cells in the neurovascular unit is responsible for activity dependent changes in the cerebral blood flow. So an increase in brain activity needs to correspond to an increase in blood supply, and this process needs to be finely tuned. The factors that contribute to cerebrovascular health can be classified as modifiable and non-modifiable risk factors. Modifiable risk factors, I want you to think about them as something that you can control, and those include high blood pressure or hypertension, which can damage the arteries. So over time, high blood pressure can weaken and narrow blood vessels and increase the risk of stroke or other cerebrovascular events. So managing hypertension through lifestyle changes, such as maintaining a healthy diet, regular exercise and stress reduction may significantly reduce the risk of cerebrovascular diseases. So regular monitoring and control of blood pressure levels are essential for OB rule cerebrovascular health. High levels of cholesterol, particularly low density lipoprotein cholesterol, can contribute to the formation of plaques in the blood vessels leading to atherosclerosis. So atherosclerosis can restrict blood flow and can increase the risk of stroke. Also in these cases, managing cholesterol levels through lifestyle changes, such as adopting a healthy diet, which is low in saturated and trans fats, regular exercise, weight management can significantly help reduce the risk of cerebrovascular diseases. Chronic elevated blood sugar levels as seen in conditions such as diabetes can damage the walls of our blood vessels and that's throughout the entire body, including vessels in the brain. We can manage diabetes through lifestyle. We can maintain a healthy diet, regular exercise and blood sugar monitoring. This can be accompanied with medications and this is essential for reducing the risk of cerebrovascular diseases. Additionally, it's important to control for other risk factors associated with diabetes such as high blood pressure and high cholesterol levels and that's very, very important. I mentioned already more than once the importance of a healthy lifestyle. So choosing and managing lifestyle factors such as regular physical activity, a balanced diet, maintaining a healthy weight and avoiding smoking, drinking, significantly contributes to cerebrovascular health. Non-modifiable risk factors for cerebrovascular diseases are those factors that cannot be changed or controlled. These include age. So the risk of cerebrovascular diseases increases with age, with older adults being at a higher risk. These age-related increases in risk is mainly attributed to factors such as the cumulative effects of chronic conditions decrease the elasticity of blood vessels and age-related changes in brain vasculatures. Sex is also a factor. Men have a higher risk of stroke compared to women, although women's risk increases after menopause. Having a family history of stroke or cerebrovascular diseases also increased the one's risk. In obesity, certain ethnic groups such as African Americans, Hispanics and Native Americans are higher risk of stroke compared to others. And several factors can contribute to these parties, including differences in the prevalence of traditional stroke risk factors such as hypertension, diabetes and obesity among certain ethnic groups. For example, African Americans have a higher rate of hypertension and diabetes compared to Caucasians, which contributes to their increased risk of stroke. Additionally, this is something to consider. Social economic factors, access to healthcare and cultural influences may also play a role in stroke risk disparities among different ethnic groups. There is another component I need to mention that's genetic factors, which may also contribute to differences in risk among different ethnic groups. Now, while these risk factors cannot be changed, it is important for individuals to be aware of that and to focus on the modifiable risk factors to reduce the overall risk. Now, let's switch gears and let's look at numbers. When we look at the top five causes in Australia, we see ischemic heart diseases being right on top and that's a condition where the blood flow to the heart is reduced to the narrowing of coronary arteries. Dementia and Alzheimer's disease is a condition characterized by progressive cognitive decline and memory loss. And then cerebrovascular diseases are the third leading cause of that in Australia. And that's followed by lung cancer and chronic obstructive pulmonary diseases, a condition affecting the lungs. Now, when we specifically look at the numbers for stroke, we can see that one, I mean, stroke is one of the main examples of cerebrovascular conditions. So every 19 minutes, an Australian will suffer a stroke and more than 40,000 Australians are already living with the effects of a stroke. Regional Australians are 17% more likely to suffer a stroke. But why? What's happening? What causes a stroke and what are their effects? So a stroke occurs when an artery leading to the brain or within the brain is blocked or damaged. And this leads to brain damage. And that damage is specific to the function of that part of the brain. Now, blood flow can be interrupted either by a blood clot, and in this case, we speak of an ischemic stroke, or a burst vessels that leads to a hemorrhagic stroke. Following stroke, we can distinguish between a stroke core, which is an area where the damage is irreversible. And within the core, cell debt occurs very fast. The area that surrounds the ischemic stroke is instead called penumbra. And the penumbra is considered an at-risk area, because over the course of the days following stroke, there is an increased, there is an increased likelihood that cell debt will occur. However, this process may be reversed, maybe in the cell debt may be interrupted if blood flow is promptly restored. And this area may still be rescued. So this is the target area for intervention. And I will get back to that when I'm going to tell you a bit more about the research that we do in my lab. So the effects of a stroke can vary widely, depending on factors such as the type of stroke, the area of the brain affected, and the severity of the injury. Stroke can cause weakness or paralysis on one side of the body, and that's known as hemiparesis. And these can affect mobility, balance, and coordination. Stroke can impair the ability to speak, understand language, or produce coherent speech condition that is known as aphasia. And it can also affect reading and writing abilities. Stroke can lead to cognitive deficits, such as difficulties with memory, attention, problem solving, and reasoning. And some individuals may even experience changes in the personality or behavior. Stroke can cause sensory deficit, such as numbness, tingling, or loss of sensation on one side of the body, and can also affect vision, resulting in visual field cuts or loss in some patients, double vision, or visual perception problems. Stroke can impair the ability to swallow safely, leading to choking, aspiration, or difficulties eating and drinking. Stroke survivors may experience more changes such as depression, anxiety, irritability, and emotional ability. And coping with the physical and emotional challenges of a stroke can also lead to stress and adjustment difficulties. So it's not easy. And many stroke survivors also experience fatigue, which can significantly impact the daily functioning and quality of life overall. Stroke can affect activities of daily living, such as stressing, body and grooming, feeding. It may also impact participation in the social and recreational activities. So overall, the effects of stroke can be profound. And they may require long-term rehabilitation and support to basically maximize recovering quality of life. Now, rehabilitation strategies may include physical therapy, occupational therapy, speech therapy, cognitive therapy, cognitive therapy, and also psychological support. Now, early intervention and ongoing care are a crucial step for optimizing outcomes and promoting independence and well-being for stroke survivors. And it is exactly on this acute time frame that myself and researchers in my lab focus our efforts. So now I'm quickly going to give you an idea of what we work on in the lab and what is that we're doing to understand how we can use rehabilitation. So in the lab, we use animal models to measure things that we couldn't measure in human patients. We develop new strategies for rehabilitation after stroke, such as direct brain stimulation, and we use cranial windows and advanced microscopy techniques to observe the responses of neurons and blood vessels in real time. Now, the type of brain stimulation that I use focuses on reactivating homeostatic mechanisms that play a role in maintaining a healthy equilibrium under normal conditions. And by starting treatment as early as possible after stroke and seizing controls for these mechanisms, we have now shown that we can mitigate some of the damage and improve the outcome. So using a specific type of brain stimulation at a specific frequency, we have shown the neuroprotective effects of our intervention and that was in acute phase after stroke. What we actually show is that our stimulation improves cerebral blood flow in the penumbra, which is our target area. It reduces the occurrence of spreading depolarizing waves, which is an event known to occur after stroke that basically correlates with the worst outcome. And it finally improves motor performance. More recently, we have tried to understand the mechanism behind these neuroprotective effects that we saw. And we showed that our stimulation restores the ability of the brain to establish functional connections between the neurons that are in the same region, but also neurons that are across different brain regions. And this is a phenomenon called functional synaptic plasticity. So I hope I have convinced you by modulating brain activity, the modulating brain activity may serve as a potential target for neuroprotection against stroke. And having the possibility of exploring these mechanisms is essential to then translate these findings in the human, in the clinical setting. So I like to finish this presentation with a few tips for maintaining a good neurovascular health. That includes minimizing the lifestyle risk factors that I mentioned before. So exercise regularly, eat healthy and balanced diet, drinking moderation or abstain from drinking, if you can, and lose more link. From my own research, I would recommend always getting a good sleep. Now, one of the most important functions of sleep is to flush out some of the bio products of neural activity and replenish the extracellular fluid in the brain. If you're starting point is already out of the balance, the outcome after stroke can be much worse. So sleep is actually neuroprotective before stroke and can make a huge difference later on. Finally, stress is a big risk factors for high blood pressure. So do your best to improve your work-life balance and meditation is also highly recommended. So find meditation techniques that appeal to you. And last but not least, socialize. Humans are social animals and building stronger connection is fantastic for our neurological well-being. So spend time with friends and family because even if they pee to you, they can at least call an ambulance when you need it. And if you want to know more about our research, please reach out. I'm always happy to talk more about what we do in the lab. And for the moment, I thank you for the attention and I look forward to hearing your questions in the second part of the webinar. Thank you. Well, thank you so much for that Matilde. That was a really great presentation. I hope everyone enjoyed that and yeah, I'm looking forward to getting into the questions. I just had a couple of things that I wanted to ask first just based on your presentation because you mentioned that there were the two types of stroke or the two, I guess, like areas of damage in stroke, the penumbra and the part that has the irreversible damage. Just for context, how do you identify how much has been damaged? Is that an MRI or do you need to do surgery or is there some other like test or symptoms that you can measure? How do you tell what the extent of the damage is? So definitely one of the first things that you do when you get to the hospital is imaging, brain imaging that will be able to determine the location and the size of your stroke of your damage. We like to define things when we, in our research, for a very important reason and you did mention that when you talked about the damage, the irreversible core, the damage in the core, within the core and the penumbra which surrounds the strongly, heavily damaged area. And this is our target of intervention. We usually, with our intervention, target the penumbra because this is the region that we can still rescue. So it's very, very important to immediately, at least as soon as possible, determine where the stroke is and how much is damaged. Yeah, of course. And is there anything that predicts where the damage happens in the brain? Is there anything connected or is it just random where the stroke occurs? Okay, yeah. So I'm getting into some of these questions and we have one here from Pam. You spoke about high blood pressure as a risk factor, but is there anything about low blood pressure and stroke? Yeah, definitely. So I mean, it is a less common cause of a stroke, but if you think that low blood pressure is any way, will any way determine less blood for the brain, it can be associated with damage, but it's definitely a less common cause. Still harmful, but less common that high blood pressure. Okay, that makes sense, yeah. And then we have an anonymous question here asking, after a CVA, is that another term for stroke? Okay. So this person has asked after a CVA, what are the recovery time frames? Do you continue to see improvements? Is it just in that like that short acute phase that you spoke about, or can you see improvements here two, three years afterwards? So definitely, I mean, recovery time is very different for everyone. Some people can take weeks, months, years. There is still, I mean, improvements can continue over time, even for years, but for many people it's the first six months is where the quickest improvement occurs. So you will see the difference in terms of improvements within the first six months, then then it's everything slowed down a tiny bit. But anyway, it's very different from person to person. That's why it's very important to continue therapy. Obviously that depends on where the stroke occurred, so the kind of therapy that you are going to be doing. But it's very, very important to continue therapy and to really have a positive attitude even towards that. Yeah, no, of course. It makes a huge difference. Yeah, that's good to know then. And we have a question here from Carl asking, what are some potential activities that we can do to promote the brain stimulation and the strengthening of connections, whether that's in general or in that really important recovery phase? So for example, during the recovery phase, I would definitely follow what speech pathologies the physiotherapists will recommend to do. It really depends on the kind of brain region that has been affected. This is something that, I mean, we're speaking of the recovery phase, right? What you can do before something that follows within what I've been discussing in the presentation like lifestyle, activity, healthy diet, those are things that help the brain a lot. And in the last part of the presentation, I did mention something that is extremely interesting about the ability of the brain to wash out all products of metabolism. And that helps a lot the brain to prevent neurodegeneration. But in the phase post stroke, it really depends on the kind of therapy that you will have to follow. And that's something that depends on the brain region affected. Okay, right. And in terms of the research that you're doing about the brain stimulation, what is, do you know anything about like the time frame of the research outcomes? Like obviously, it's a really exciting prospect being able to stimulate that kind of neuroplasticity and everything. But what's kind of the timeframe on when we might start to see clinical trials or like what stage of the research are we at currently? So right now, we are conducting preclinical studies. So we are still at the phase where we use animal models. And the research has shown a lot of promises when targeting the acute phase after stroke. Right now, next step will be to try to expand a tiny bit the window intervention. So trying with our stimulation a tiny bit later on after the occurrence of a stroke, just because it's much more realistic that any sort of intervention will occur at a later stage after the occurrence of a stroke. So once we add the desired piece of the puzzle, I think that will put us in a very good position to try to then go for clinical trials. The kind of stimulations that we are trying are also we are trying to be very close to trans to something that is translatable. So we're trying sensory stimulations because that would be easy to translate from my animal models to humans. So we're not there yet, but we're getting very close. Yeah, that's really exciting. I can't wait to learn more about that. And we have this is slightly, I guess, a different topic. And I'm not really sure what the response might be here. But we have a question here from Wendy, sorry, from Leanne, asking, how do you tell the difference between MS stroke and dementia brain lesions? And there's also Ingrid sent a message saying no question, but an interesting and challenging history, mentioning, you know, aneurysm, sleep apnea, absence epilepsy, and so all these different kind of conditions. And I was wondering, like, how do you identify the difference between them in imaging and are they connected to each other? Like, can MS make you more likely to have a stroke or something like that? How are they connected? If at all? Okay, so there are different tests and different imaging techniques that we'll be able to tell if you have MS, if you have a stroke. And for things like Alzheimer, that's a bit more tricky. Those are usually post more analysis that will tell you more about that. But MS is can be diagnosed. I think there is, I think it does, especially if it happens in one person with multiple conditions, I will tend to think that there is some genetic components that can play a role here. I think there is a case report of patients having closed sclerosis. And that was correlated with the occurrence of aneurysm rupture. But again, I think it has to do with some genetics components that play a key role, as I mentioned, in cerebrovascular health. There was another part of your question, I think. No, it was a very complicated question. I think you covered it off. And I think you also just answered Dorothy's question, because she has just asked if stroke is a genetic condition. And it can be, is that... There can be a genetic component. Yeah. Okay. Great. And the next question is from an anonymous attendee. And they've asked if rational vein occlusions are similar to a stroke? Or are they a precursor to stroke? Or are they something completely separate? Well, if you think that stroke is defined as an obstruction in an artery that leads to a shortage of blood to a specific brain region, that's very similar to what happens to a retinal occlusion. Right. It is a visual field. It's something a tiny bit more complex. And it has... It represents a lot of the characteristics that, if you think in terms of connections of blood vessels and supplying different parts of the eye, it is something that it's a tiny bit outside of my field of study. But definitely those are... So I'm not 100% sure about the correlation between having some retinal occlusion and occlusion, if there is any correlation. Yeah. Okay. Yeah. No, I thought that when I was thinking retinal, I was like, oh, I don't know if this is... But thank you anyway for that answer. So we have another answer here, a question here from anonymous again, asking what the difference between a stroke and a brain aneurysm is. Because I think I often hear, personally, it's used interchangeably a lot, but they are different, aren't they? So an aneurysm is a subtype of stroke, basically. It's a type of stroke. You can distinguish... A stroke is an occlusion. It's a shortage of blood to a brain area. And that can be in the form of ischemia, which is a clot in a blood vessel, or an aneurysm, which is the rupture of a vessel. They both lead to a reduction in blood flow in a specific area. But an aneurysm is a subtype of stroke. Mm-hmm. But the aneurysm, if it's not ruptured yet, if it's just intact, then it's kind of... Yeah, is that... The rupture of an aneurysm leads to an hemorrhage, a blood hemorrhage, right? But there is still like a site where the blood... I mean, it basically forms like a... It's still a point where there is no flow. Mm-hmm. Okay. Yeah, that makes sense. And then we have a question... Next, we have a question from Sarah, asking if a person adopts a healthy lifestyle, could they possibly reverse the atherosclerotic plaques which might have formed in an unhealthy lifestyle? Like, let's say you're drinking and smoking and then you turn your life around and adopt all these healthy habits. Can you reverse the damage, possibly? So, this is a tricky one. It definitely helps. It depends on the on the stage of the atherosclerotic plaques that we are talking about. Lifestyle alone... I mean, maybe combined with the therapy, you can definitely have positive effects, but it depends on which stage we're talking about. I cannot give you a definite answer because you need to have an assessment of the state you are at, but it definitely... It definitely helps. I mean, I guess it's always going to be like beneficial to make those lifestyle changes regardless of, you know, what stage you're at or anything. Absolutely. Yeah, it's never going to be detrimental. Absolutely. Yeah. Okay, and then another one about risk factors here. Andy has said that they usually take 100 milligrams of caffeine every morning and they've asked how this affects their cerebrovascular health. Is there really any caffeine? I'm not sure about any research on caffeine. Specifically, at least I'm not aware of. Oh, okay. Sure. Yeah, it's definitely a stimulator. I mean, I don't know. I'm not a coffee drinker so I don't know how much 100 milligram of caffeine will... I think 100 milligrams is about a cup of coffee, I think, from memory. I could be wrong, but... I would say that excess is a problem. I'm not sure a cup of coffee can be defined as something that is excessive drinking, but yeah, I'm not 100% sure about how that would be affecting your cerebrovascular health. Again, the healthy lifestyle is the key, but I don't see a cup of coffee as an excess. Okay, great. That's good then. And next question we have from Anonymous is asking about your research. The stimulation that you're talking about, is it electrical or sensory stimulation? We do both. We do both. Yeah, we do both in my lab. And we are trying to, as I mentioned before, we're trying to find the translatable forms of stimulation. Sensory, it's something that it's a new avenue. Electrical stimulation is something that we are exploring. It is done in stroke patients already, but what we are targeting, the key what we are doing is really to explore frequency-specific types of stimulation. And we are trying to adapt the kind of stimulations that we are doing. We try to target it to ongoing brain activity so that each individual will get a specific type of treatment. We are really trying to get to the point where we will have individualized forms of stimulation. Instead of having what is commonly done as this one-size-fits-all kind of approach, we are really trying to understand how brain activity of each individual can be affected by stroke and how our intervention can be modulated according to the need of a specific person. Yeah, that's amazing. Personalized treatments are such an exciting area in neurological research in general, but yeah, that's great to hear. We have a question here about sleep. You mentioned that sleep is neuroprotective. Are there any other options that are available to assist those who have non-modifiable risks present? If someone has a bunch of non-modifiable risk factors, will it still be worth improving the sleep? Absolutely, especially for people that have non-modifiable risk factors, try to as I mentioned before, unfortunately there is not much you can do for those factors, but try to improve the rest. Try to help yourself with sleeping, health lifestyle. It's still something extremely important. Block pressure is something very, very important. Okay, that's good then. So all of those other lifestyle and factors and behaviors, if anyone's worried about their non-modifiable risk factors, yeah, that's great to know that you can still engage in all of those other habits and yeah. I have another question here from Miriam and this is, I guess, more of a personal question. She's actually mentioned that she has had a stroke and her left side is affected and while we can't, I guess, answer for her specific situation because obviously you're not her doctor, but in general, if someone loses like motor function in one side of their body after a stroke, is there anything that can be done with rehabilitation or possibly with your research with the electrical sensory stimulation? So in terms of rehabilitation, this is something that it has been shown, it has improved a lot motor function, so this is something that you need to, it may be hard at the very beginning, but please continue physical rehabilitation. Obviously try to talk, you could mean my research specifically, we're not there yet where we can be tested in humans, but there are forms of stimulation that can be used, but you need to talk to your doctor and you need to ask what is available in your area, in your hospital. Okay, that's great, thank you. Then we have, Lelita has followed up actually on the sleep that we were talking about earlier and she's said in terms of sleep assisting with bioproducts, sorry, I'm trying to get rid of. What was the other benefit, she's mentioned replenishing extracellular fluid, can you please elaborate a bit on what that actually means? Yeah, absolutely. So it's exactly what you mentioned, extracellular fluid and clearing of the brain is a process that naturally occurs when we sleep and it's like getting rid of all waste that we accumulate in the brain and recent findings, recent studies have shown that this can be on the long run malfunctioning of clearing, waste clearing from our brain, brain can lead to neurodegeneration. Imaging like your brain being full of waste products that accelerates things like plaques for missions and amyloid even. So there are very interesting studies on Alzheimer's disease and the effects of lymphatic clearance in the brain and the effect that that has on pathologies like Alzheimer. So this is the key. No, that makes sense. Thank you. And now a couple more questions before we wrap up. I have one here from Patrick has mentioned a couple of times that he has a disease called caracil, which I believe is a type of cerebrovascular no small vessel disease. It's a very, it's a very dear form of disease to me because I did my PhD on carazil. One is the dominant is a dominant type of small vessel disease. The carazil is the recessive form. They are both genetic forms of small vessel diseases. It definitely, it definitely needs greater recognition. I totally agree with you. You may be misdiagnosed. That's what I'm trying to say. There are, I mean, also in this case, it's very important that you talk to the neurologist about specific tests that can be used to distinguish and imaging brain imaging. But you are right that it can be misdiagnosed with MS. And I, I unfortunately cannot really comment on on that much more than than saying that there is a lot of research that we are trying to conduct specifically on these rare forms of small vessel diseases. Yeah, of course. No, thank you. I understand that you can't give any like specific advice, but but that's really interesting to hear that that was part of your thesis. And another question here in the last few minutes. What have we got here? Sorry, I'm just going through the through the Q&A here. Yeah. And if I can add something while you find another question, because I'm reading follow up. Yeah, there are no other, I mean, it's a genetic form, it's a genetic form. For caracil and caracil, it's a genetic component. Those are genes alteration in certain genes that cause the cause of the disease. So that that's why Oh, right. follow up question. Great. Thank you. And I guess to wrap up, I've seen a few questions come through that have mentioned migraine and stroke risk. And I've heard a couple of things about this in the past. Do you know anything about the relation here or yeah, I guess if there is a connection between migraine and stroke? Yeah, I mean, there is a lot of research trying to find correlation between migraine and certain kinds of migraines with stroke. So there is there is a lot of research ongoing at the moment. Okay. Great. And I guess is there anything else that you wanted to touch on or talk about just in the last couple of minutes here, anything that you feel like we haven't talked about yet in the Q&A time that you wanted to address? I'm not I'm not sure. I think I did mention that maybe something that did not come up in the in the questions. But I did mention during the presentation is the effects of sex. So how stroke can affect many women differently. With obviously, women being less affected doing the before menopause, because of some hormones that are that are protective, estrogen is protective. But then after menopause, that's more or less the same sort of more or less the same than they may after. And that's something that did not come up during the questions. But it's something I think very interesting. Sex differences is something very, yeah, very interesting that I think your research needs to be explored more. Yeah, this is something that, yeah, maybe yeah, be interesting for people to hear. But yeah. Yeah, we actually, I'm sorry to keep going, but we talked about this as well in Monday's webinar about dementia respectors. And Karen mentioned that it's similar with dementia, how the drop in estrogen can also like increase risk of dementia. And she mentioned that like possibly something to do with HRT, I guess, like being studied to see if that would help reduce people's risk of dementia. Is there any similar research happening with stroke? I am not aware of it, but it's definitely something interesting to explore. And as I mentioned, there needs to be done much more on that field. And it's really interesting to hear that for other conditions as the same and then highlights the importance of uncovering more in the space. Yeah. Yeah, definitely. Well, hopefully all of the research can kind of, I guess, like inform each other. Absolutely. Well, thank you so much for your time, Matilda. It was really great. And I think we had a really interesting and I learned a lot during this Q&A. So I hope everyone else feels the same. And yeah, thank you so much for being part of Frone Awareness Week. Thanks. Yeah. Hope you enjoy the rest of your week.