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The Glasgow Neurosociety
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in association with SI, or Surgical Neurology International, and SI Digital are happy to present
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the abstracts and discussion of the 10th anniversary Glasgow Neurosociety meeting held in November of 2022 in Glasgow, Scotland.
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Hassan Ishmael is president of the Glasgow Neurosociety at that time. He's from the Wolfson School of Medicine at the University of Glasgow in Scotland and the United Kingdom
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Faculty commentators are Likith L. Akhandi, who's the consultant neurosurgeon at the Queen Elizabeth University Hospital in Glasgow
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And Amy Davidson, a neurologist, also at the University of Glasgow, also at the Institute of Infection, Immunity, and Inflammation in Glasgow, Scotland.
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Other Glasgow neuro hosts were Alidith Middleton, Vice President of Glasgow neuro,
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and Edica Choudry, another Vice President of Glasgow neuro. And that concludes our third panel discussion, too We are looking at the effect of Xanthine oxidase inhibitors on post-stroke cognitive
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status, a post-hoc analysis of the
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CELO first randomized controlled trial, presented by Sally Wong, Union Wong. Go ahead, Sally, over to you.
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Everyone, so I'm Sally Wong. I'm one of four of your medical students from the
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University of Glasgow. And today, I'm very excited to present my project and as has another statement title. Um, so just a short background, like as you know, um,
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the ischemic stroke and transition ischemic attack has a very, is a high risk for collective impairment in the long run. And it has been shown that about 30 will eventually progress to vascular
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dementia. And unfortunately, we don't have a very good management plan for vascular dementia compared to Alzheimer's disease. Even though Alzheimer's disease also helps certain vascular components
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to it. So it will be quite interesting to know what's the
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pattern mechanisms behind the cognitive impairments of the stroke. And so to know if there is any targets we could pharmacologically a target to. And so my project is to know whether a alprinol,
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which is a xanthinoxidus in vision, is
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going to reduce the level of of the stream re-accid level in the body. and which eventually may lead to improvement in the cognitive impairment in the long run. So to understand the aim of project,
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we must first understand the data's research done on this. So eventually the serum uric acid level has been found to be recorded in the science of cardiovascular diseases and as well as the cognitive
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impairment
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From our research, literature research, we found that many of us have shown a correlation between high level of serum uric acids and increased risk of cognitive impairments, but there are different
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results in different literatures and this creates a very equivocal conclusion to it conclusion to it. For example, some of them found there is a U-shaped relationship where very low level of sumeric
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acid has also been found to contribute to any sort of cardiovascular disorders and so forth. And the core in among all these mechanisms is the xanthine and oxidase. So xanthine and oxidase is an
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enzyme which degrades purine, which is
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a sort of metabolite from any cellular breakdown. And it creates purine into serum uric acid, so uric acid level. We measure the uric acid as an indirect, a predictor to the level of xanthine
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oxidase inside the body. As the xanthine oxidase releases the free oxygen radicals during the process. And this contributes to oxidative stress and as you all know, the inflammatory pathways,
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leads to worsening of ischemia and it's also one of the major components in atherosclerosis and all of which has been shown to cause a major increase in vascular dementia. However, the serum drug
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acid itself has been shown to be protective against Alzheimer's disease and Parkinson's disease, so that's an interesting real. And so the use of alprenal as a drug to show if the sun find oxidized
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level reduction will improve cognitive is
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a
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first trial as far as we know. And we just compared between two groups. So one group received alprenal and viola group received the control. And both groups they have been, the patients have been
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selected based on their recent. ischemic stroke diagnosis or transient ischemic stroke. And the results have been compared, but unfortunately it's found that there is no significant difference
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between the two groups. Although we also did like a sort of a regression analysis to see if there is any baseline variables that may be associated with worsening cognition within the populations in
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the study And we have found that the high level of white matter hyperintensities and diabetes have been shown to results in worse than in their
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cognitive test throughout the two years of a study. And this is very interesting because it actually agrees to the previous studies that have found that white matter hyperintensities, aka, which is
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a component of a small vessel stroke, is a major risk factor in cognitive impairment. And so this list of conclusions that maybe a new direction in the future research could lead to looking at the
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effect of santhine oxidase and sumeric acid specifically in the small vessel stroke and therefore to see whether this actually improved cognitive impairment in the long term. Thank you.
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Thank you very much for that. That was really great and really interesting and I think it's very important that we present, even if you don't see a positive response, I think it's really important
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that we present all these trials and I think about it because it's how we move things forward. So you talked about the kind of U-shaped curve and how the levels low or high. Do you think that would
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have some relevance on the fact that you didn't see a response? Could you be that you were pushing people too low or you're reaching them at the wrong point or putting them into the wrong point of
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the curve, I guess? Yeah, that's one of the downside of a project actually because we did not measure the sumo rig acid level throughout the entire project. I think we only measured it at a start
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as a baseline and as you know, the baseline would be high because of recent stroke. But whether We should have targeted like. each individual's ceramic acid level and a dosage. It is something
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which we have thought about. As I've mentioned, the US.
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shape relationship has been found that a low serum acid level, actually it's a risk factor within itself. And this has been shown in one of us study by OPTCHF, which has shown that people with low
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level of serum regacid do not benefits from the
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alopreneal treatment. And whereas people with high baseline, high
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serum regacid level, actually benefits more. So yeah, definitely it is something to be considered in a future project to have a regular measurement of serum regacid level. Excellent, thank you
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for that really thoughtful answer. Do you think, the timing after the stroke would be important for interventions like this, like, are we given this day one, you know, reload them with aspirin
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and give all appearance or is it something that, you know, that we do down the line? Where do you see these kind of these therapies fitting in in the, in the, where do you think they have more
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use, I guess? Yeah. So
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I suppose because we don't really have a previous research to compare to what we use of our signals, it's very hard to decide on the timeline itself. I
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suppose we should need to understand the petal physiology. The xanthan oxidase is part of the oxidative stress in pathways. And within the stroke, it's most likely to be like the head injury, like
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a sedentary damage to the head, to the brain. I mean, and
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I don't think it should be understood like after we've been like a long duration after the first event of stroke. In our project, the patients received their first dose after one month, but you'll
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be interested to see whether giving the drugs at the first instance will make a difference, and whether giving the drugs, let's say at three months give a different result So I suppose with more
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projects and more research could be done to see whether the timeline is important in
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terms of lowering the urate level in the body.
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And so what would be, how would you take this on next? What would be your next move? So personally, I suppose the most important thing here is to acknowledge whether the serum rig acid itself has
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definitive role being played in the cognitive impairment always there are other factors because given the multiplicity of cognitive impairment, it is definitely a multifactorial pathology. And one
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of the interesting film field I've been discussing with my colleagues is to look at a bigger population range using the genetic testing and using the biobanks so seeing if whether there are other
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factors which we could take into considerations in terms of cognitive impairments in the stroke population and to see if there are more easy targets to put in a simple ways for management of vascular
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stroke and vascular dementia Great, thank you very much.
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Thank you, very, very interesting, Salisa.
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So, my question is, as the study been, I've heard of a couple of studies for using alloperable for head injuries. So, the biochemical mechanism is pretty similar in terms. So, as they've been
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work done on head injury outcomes in a similar way, once
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you say, I've got another question after this. So, what is your understanding about this particular aspect in head injury and the cognitive outcome from following head injuries?
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Head injury has very well researched mechanisms. It has a primary and secondary brain injuries I suppose you mean by the secondary injuries there is a wider.
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inflammatory process going on. So xanthin oxidase itself being the enzyme which is used to degrade appearing. So I suppose during the secondary head injuries, like wide range ischemia. It
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is a significant role in it. Unfortunately, I haven't read too much about the role of xanthin oxidase in head injury, although it will
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be very interesting And given that we know one of the major pathology in the head injury is a so excited toxicity. And if we do a reverse thinking, maybe excited to see, could be one of pathology
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in ischemia stroke as well, since both leads to an ischemia of the brain tissue. And at the same - On the same line, we could also think about the role of sometimes oxidase in the brain injuries as
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well.
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Yeah, the other thing is the similarity of hypothermia.
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Is there any comparison or complementary treatment with hypothermia and all of perinol for either stroke or any other brain injuries?
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I suppose hypothermia is used to, as it comes to mechanisms to the
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inflammatory process. I know it's been used before in cardiovascular disease. So
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the thing we've done find oxidase, but it belongs to a family of enzymes called the zanphine, OXC,
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dehydrogenase, enzymes, and so when they normal pathology. my understanding is that xanphine oxidase exists as the xanphine dehydrogenism enzymes and this itself does not lead to any release of a
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reactive oxygen species and normally it does not contribute to the oxidative stress but some of research have found
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that the xanphine oxidase expression actually elevates during an ischemic process especially during the reperfusion ischemic process and leading to increasing oxidative stress and so in terms of a
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hypothermia i'm not really sure about this relationship with any sort of reperfusion ischemic sort of and mechanisms so i can't say
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No, no, I'm not expecting you to say the rest, but because there have been some studies done particularly in neonatal head injuries with a combination of alopiginal or amaputam. Anyway, thank you
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very much. That's a very interesting paper, so I was just wondering if you can broaden the horizons towards a more, you know, wider pathology like TBIs or one of them. Okay, thank you very much,
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Sally, well done
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Lovely, and Sally, any other comments or anything from your end? I know it was an amazing discussion. Thank you all so much. Thank you very much, and that concludes this panel discussion. We
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