Dear colleagues, good evening and good morning to you, depending on what continent you're dialling in from, as scientific communication manager for Purina Europe and Middle East, I have the honour on behalf of Purina UK to welcome you to this next webinar in Purina series. We had wonderful feedback from everyone in the series of talk. And as usual, Purina supports what is best in science innovation.
So without further ado, with great privilege, I give the floor to the great speaker, most knowledgeable, engaging, and charismatic neurologist and neurosurgeon of Royal Viterina College, Professor Holger Volk. I'm sure everyone will enjoy this lecture very much. Thank you for the fantastic introduction.
Yeah, I hope, I hope I can actually, the bars of set very high, so I'll hopefully be able to meet those expectations. And I want to also welcome you wherever you are. One thing of the webinars, even if it's the morning, you can kick back and drink some wine, or if it's evening, obviously, you deserve your wine.
And I hope you find, a lot of things very interesting. Some of them you hopefully you get to say to your normal life. So, but before we start, I Just want to do a call, because a lot of stuff we are talking about today comes actually from ideas from owners, breeders, and you vets as vets, telling us what you want to do next.
And actually, our diet try came from, mainly owners as an idea, because they always told me that diets have a major influence, and then we were looking into this. And we are Continuous doing research on this, and I'm really looking forward to see your patients. We are at the moment, doing what they call the lifetime trial.
We're looking for dogs without cluster seizures or status of replica. So dogs which have a, a normal seizure history, which don't have those, more challenging seizures, called cluster seizures, where you have 2 or more seizures in a day. And they have to be, older than 6 months.
They can already have a full workup, clinical neuro exam and an MRI and so on, but we also can do everything for free. The only, probably bar for the owners to overcome is that they have to adhere to the protocol. The owners will get, free food up to a year, And there's no restriction on drugs, in any form, but they have to be obviously for a certain period of time, normally 3 to 6 months, without a big change.
But if you have any questions, please, navigate those owners to our survey, or fill it in, yourself or write, as an email, and I put you in touch with our clinication centre. Thank you for listening. And let's talk, I start with the talk.
So I first want to talk about beauty. Beauty is obviously a beautiful dog, and I, I'm sure some of you might have heard, some of my talks before, and I often present her and talk about how unpredictable, uncontrollable seizure activities are. But today, I actually want to talk to you about something else.
Because the two things what alsoome Beauty taught me, and one of the is cognitive dysfunction, and also that she had some, food intolerances. And somehow, as you might realise, she also had idiopathic appety, right? So she had a combination of different behaviour abnormalities, plus had a dietary, limitations.
And, and, you know, when owners told me about that you can Actually change the diet and it influences, the seizure control. I was, and the behaviour. I was a little bit sceptical in the beginning, but then I recall about beauty.
But to be honest, I'm a vet, so I have the worst compliance of all. And we, we probably, are not the best, dog owners. I mean, I'm sure you're all amazing, but, as you know, I'm, I'm, it's always more difficult to look after your own pet.
So when you look into this, then you find tonnes of research, obviously in, in rodents, but also in people. People, and rodents have shown that there's an interlink between the, gut microbuilder and the gut and the behaviour. There's also some very interesting papers out now in docs, which also shows this interlink, which are mainly in the Area of, fear and anxiety, and also, attention deficit hyperactivity disorders, or ADHD, as well has been linked quite closely in this good, understanding that there might be a link.
Even more interestingly, that, people who had anxiety disorders, they, those, people, they gave their, faeces that they know, the microbial. And they were implanted in, rodents, and they could, germ-free rodents, they could exactly replicate these type of behaviour changes as well. So there's definitely an interlink.
And it kind of makes sense because if you think about it in, in more depth, that these bacteria, they probably try to influence our behaviour, to also influence their survival, and to also communicate between each other. We have seen also, that the information not only gets transmitted over, the vagal nerve, but also over the bloodstream. People have seen that when you, for example, get antibiotics, there's a, a case series that some patients respond to certain, antibiotics better, and have done better seizure control, for example.
The, the other thing is what people have seen is that, when you have a change in stress, that also your behaviour changes. And we all know this as well. And people have seen that there are some influences and there's also a big debate how good probing prebos are, but there's definitely good evidence, especially about ketogenic diet in people, that it can influence, ADHD behaviour, and seizure control and some of the behaviours.
So a lot, obviously in this first slide, and probably a nice summary before we start digging into the detail. So, as I said, you know, I often talk about beauty, because, a seizure is even if you are medically trained, is something quite awful to watch. And I think one of the main things for us, why it's so stressful is because it happens at any time, so it's unpredictable.
We, we don't like unpredictable events. And it's, it feels uncontrollable. Yes, we know we have, drugs as a vet, but as an owner, you're totally, frustrated.
And that's why, we often recommend people to give, have rectal diazepam at home. It might not make such a huge difference for that individual, pet. However, the owner feels more under control and able to do something and help that pet.
And we talk a lot about this in more detail. When we, did a study and, and looking at how stressful is a seizure event, we found that, in dogs, obviously, when you have a seizure, you get a spike, which was significant after 40 minutes, and in humans, it looks like they see a seizure in dog. And then they are stressed for the 1st 20 minutes and then they, they calm down a little bit.
We did another study just recently, where we looked at, chronic stress, and, it's, it's just submitted, so you have to come to another webinar, but it's really cool data. And Rowena Packer, who's an absolutely amazing researcher in, in our group, she, she was leading on this, and she has shown that it looks like that when you have, because of the chronic stress, you get itchy, adrenal fatigue. So there's definitely potentially some influences also for the, gut brain axis.
We all know that epilepsy has a huge impact. It's the most common chronic neurological disease. We know that when you're diagnosed as a dog with epilepsy, you have around 2.5 years to live, but a nice study from there from, Copenhagen.
We know that it has an impact in behaviour changes. We know, show you some very recent data. It's also changes in cognitive function in some dogs.
And we do obviously know that it has a, quality of life impact, not only for the dog, but also for the owner. When you look at what, actually, impacts that quality of life, Annette investment did an amazing study, where she, she looked at which factors. And there's no surprise that owners obviously, as our proxy to evaluate the quality of Li feel that high seizure frequency of that patch receiving, I mean polypharmacy, so the third antimileptic drug was the main factors which at the end could hold the multivariate statistic analysis and came out significant.
Which, which is totally understandable. However, what I thought was very surprising to me was that the owner's quality of life, and the owner's quality of life is mainly impacted by sedation attacks, and that was something I was totally surprised about because I thought it's, you know, it's a typical thing, living in an English house. Carpets, dog is urinating and da da da, that I thought that the, the polyuria, the polyphagia, that they're on a walk and they're constantly looking for food is the main one.
However, that was not the case. And then I, I had a very good chat to, Robert Farco, who's a fantastic first opinion practitioner. And, and she always puts me straight.
And, and she said, oh yeah, you know, when you measure any side effects, it's normally the side effects which the owner witnesses constantly. So what they constantly see, what they see at every moment of their life, that's the one which probably impacts their own perception about it and their own quality of life as well. And That, and no surprise there, sedation and ataxia, are saying this, saying this, and we just finished another trial and, and we also did a g analysis study where we could show that owners has a certain level of ataxia dog has to have before owners are actually noticing it, which is really interesting.
We, we know, and this is, is one of the mains of this talk is that you, as a first opinion practitioner have an unbelievable important role. Because the owners come to you to get this reassurance. The method showed very nicely that this link between you and the dog is, is, and the owner is really important, and that can actually improve, not only them feeling more under control, give them back control, but actually also, with the epilepsy management, because we know that there's also a big placebo effect, and, and.
To improving seizure control if the owner, is more on board. It's also called the cost and effect that the owner actually went there on trial, for example, they are giving the medication, and I'll show you this how important that is. But 85% of owners actually come to you, right?
They are going to, the, the media, and, and social medias, but, mainly they are trying to get the information from you. So as better you are informed, as better you can act. I won't go through this extensive list, but as you know, we, wrote a couple of consensus statements.
And in one of the consensus statements, which are freely downloadable, from the web, when you go to the BMC that research or you Google, IBTF, and I think this is a very nice checklist to have at your practise if you don't have that, just to make sure that the owners are really informed about, all the eventualities. Then I just want to talk a couple of sentences about why I think this is so important. When you look at good clinical practise, we often focus and you hear a lot in the media, a lot in the bad press at the moment, and if you come to BSAVA, please come to a talk I give there.
We talk about evidence-based medicine, yeah. And evidence-based investment is essential. We need to create more, we need to do more studies, we need to critique ourselves more.
There's no question about it. However, I wouldn't underestimate how important clinical practises is because the clinical practise, I, at the end of the day, you're reading glasses of the evidence, and you're reading glasses of, the pet who is in front of you. So you are putting the evidence into practise.
But the one thing I think we have ignored for quite a while, and, is the owner. And I show you there's some amazing data, which I couldn't believe, which, we are still working on, publishing at the moment, didn't have enough time in the last couple of years, but it's, it's absolutely amazing. And I think understanding the value and the qualities of the owners and how they translate this information, in for their pet is really essential.
What disease process, doesn't matter if it's epilepsy or something else. And again, from Robin, a very good example, is she had a, a receptionist who has an epileptic dog. And if she feels there's a compliance issue, then she actually goes, to the receptionist and ask her to speak to them.
And often, and there's enough research out there in human medicine that as more lay people give another lay person, the background and the information as better it's, listened to. I mean, you know, here, people don't wear white coats, but those with white coat effected, a lot of owners would never challenge the doctor and never ask again. I know that this might be the times in the past, but no, I'm just joking.
So I think the, the way, what we have to think about is how do we create a bigger synergy, and I think actually you as a first edia practitioners do a lot better than any referral clinician. And this is the thing that I wanted to show you. This is the shocking results from this very nice, BET math student project.
She found that only 1 in 5 people are 100% compliant, and she did it to, in, two ways of the study. So it's, it's actually confirmed. One was survey-based, so just that.
And the other one was to get actually to practises and look at the prescribing regime, and look how often people actually came back to get tablets. And when you just look at This gap, it's phenomenal. It's absolutely phenomenal.
And, only 33% had a compliance rate over 80%. So it's very similar to NSAID, antimicrobials and so on. So I, I thought that epilepsy, that it would be different because people are worried about the seizures, but it looks like there's a huge compliance issue.
So as better education, as better, medication. So that is to say. Also, interestingly, if you're a referral clinician, you might not see these patients so much because we normally see the ones which are on multiple medications, and that was the one which was significantly, significant influencer.
Obviously, we, we have an app for, for tracking procedures, which then the owner can also, actually explore and we are still working on the updated version. I know it was promising for a while, has been a bit of a challenge with the app developer at the moment, saying this, that the reason why we developed this was also that the owners have a a reminder, so not only obviously collecting data and having questionnaire and, and information, but also having a, a reminder, which, helps them to remind them on the medication. And the next version will have a, a, a, a rather large reminder.
So just because of the research we've done. Don't worry, I won't speak about spaghetti. I just wanted to put this on there for all our RBC students, which I hold very fondly.
but we will talk about diets in a second. What I will talk about is about, this metaphor, which also I love, and I like to show, it's from Lennox in the books. And what they, they, Kind of Explained a seizure or the seizure threshold by a flood, yeah, and a riverbed.
So if you think about a river, being the combination of multiple streams coming together. And, what you can see here, there are obviously genetic factors, there are, disease factors, there are stress factors. There's a lot of other factors, which are here, shown as, as streams which are coming together.
And if there's too much water in any of them, then the, the water bed will, overspill, will go and then have a, have a flood, right? And as a, as an example, they gave seizure thresholds. So you can actually reverse this by reversing these factors which might influence us, but also you can increase the seizure threshold.
So actually, increase the, the, the borders. Of the river bed, to make sure by driven drugs, diets, and so on, which then will make it less likely. And this is also very nice to explain because we know that we are, when we're giving medication or any, intervention, we are not treating the disease.
We are just, changing the seizure threshold, making it less likely for the animal to seizure. Idiopathic epilepsy is not one disease, and, as in people, whatever medication, whatever, management option you will try, you will have some dogs which will, or cats will will respond amazingly, some which kind of mediocre and. Won't respond at all.
And that's the reason is quite simple because it's it just tells you that idiopathic epilepsy, there might be, multiple genetic factors that there might be some structural lesions you can't see. There's a lot of possibilities why an animal might, might seizure. And this is just highlighted again in this chart where you can see this is from my old mentor where I did my PhD for Russia.
It's amazing, . Researcher, one of the most sighted people in the world. And he showed it as a kind of a two hit model that you had a, you know, seizure, head trauma, or whatever, that will then, there will be failure to repair.
There might be no consequences, or you have a genetic background, which then push you, pushes you over, you Kick start the epileptic genesis. And at the moment, we have no medication really to stop the epileppogenesis. We have no medication to disease modify or reverse the drug resistance.
So, actually, the spontaneous seizures are the one main ones which we are changing by changing the seizure threshold. And that's why we came up with this new approach that we, we actually look into how can we combine, the different modalities and also put them into better synergy. So you have not the side effects, which I mentioned before, because at the end of the day, our ultimate aim is unfortunately, with epilepsy, Rarely will cure, unless you find a structural region, which you can, remove, successfully.
But even then, you might have to keep them lifelong on epileptic drugs. But you are the main aim is therefore always quality of life, right? And they, if you look at this, is the environment, are there any trigger factors?
Are there any new behaviour comorbidity, how cognition? What stand from a management point of view, is there an underlying cause we can define target directly plus anti epileptic drugs, brain development, epilepsy treatment, epilepsy characters, malnutrition. And then the other thing is, obviously, you know, which, which is again came when we launched the epilepsy app, is, which, which I really didn't grasp until this lady, who had herself epilepsy, she spoke about it.
And a lot of the concepts I explained to you come also from, from, from her experience, because she told us, you know, when she was 16 years of age, she obviously went to the doctor and they gave her all these drugs, and, nothing was really working until she found the one doctor who listened to her. Looked at her lifestyle, looked at her nutrition, looked at every part, and also the anti-epileptic drugs. And then, when she was 30, she was, then seizure-free.
So it took them a long time to figure out, we don't have this time as, as that. But the other thing, what she was telling me is she said, you know, the seizure itself, yes, it's awful. Yes, you know, I'm, I'm aching and, and so on and so on.
However, that's just a moment in my life. Actually, what's a lot more challenging for me is, and she She, the main side effect, what she found the most challenging was the cognitive, effect of the drugs she was taking. So she was more forgetful now and, and, and couldn't remember things.
And, and so she said, look, hold on, I live, I might have a seizure every 3 months, every half a year. However, I live every second, of my life with those side effects and with the comorbidities of epilepsy. And that got me really started.
And I, I have to say, we, I think we have ignored, these facts. And when you look at what, what people tell you, what else is epilepsy, for, they had a lot of words, which are something you probably would have never associated with it, right? They have, they, like autism, ADHD, stress, lethargy, obviously, that makes more sense.
Memory loss is probably something new for you than fear, confusion, anxiety, boss, medication. So there's a lot of words which, are associated that for, for people. And no surprise, right?
The one which is the kind of the hard fact, and, and then there are some more softer facts. But nowadays, we shouldn't talk about this because political. But the hard fact that seizure activity, the generalised tonic seizure is a bit different for focal seizures.
Someone can identify that owners can identify this, and, you can measure it. The behaviour comorbidities are a lot more challenging to measure, and we're just working on improving how we can measure them better. So there is, it's been known for, for a long time.
Hippocrates already saw that, there is a bi-directional relationship between melancholics become epileptics and vice versa. This has also been shown over the history by psychiatrists and epileptologists. They have shown that, if you are having a, for example, depression, anxiety, you're more likely to get epilepsy and vice versa.
If you have epilepsy, you're more likely to get depression and anxiety. So the classic one was, you know, melancholics become epileptics and epileptics become me melancholics. And, and if you think about this, and in the beginning you're like, oh, why, why this makes no sense.
But actually when you think about this in the next level, you, it actually makes totally sense because the brain rather complex structure, and I'm sure your brain is more complex than mine. However, one of, one of the things is it probably has only a limited way of expressing pathology, expressing itself. And if you look at these pathways, they often play a role in both diseases.
So if you have a change, for example, in, in, in serotonin, you might also affect your epilepsy. And people have shown that when you improve, you fear and anxiety and epileptic patient, you might also improve their seizure control, and vice versa. When you look at our dogs, we find that, in a study from Nadia Shihab, was one of our first residents, very proud of, and really amazingly a fantastic neurologist.
And she, she found in her study that in drug, naive patient, the main ones are fear and anxiety, defensive aggression, and abnormal perception. Which, which come up because obviously drugs will influence your behaviour as well. And at least, I mean, nearly all of them, you know, if you think about it, 3 out of 4 dogs had behaviour changes which were changed, doesn't mean always politically, but at least statistically.
And when you look at what, what did change, it's mainly the interference with unfamiliar objects, unfamiliar dogs, or unfamiliar people, which is the one thing which affects these dogs. And I think it's something you need to think about when you speak to these owners that they are aware about this, and that this might be normal. It doesn't mean that it's, a good thing, but just something if, if you identified, you can also work against it.
Then, Louisa Devizio has done a very nice study. She has really nicely categorised these, Lakota Roman yodels, and she found that prior of them starting medication, the drachmae dogs, had a higher likeli of fear and anxiety and no perception. You didn't find offensive aggression, but again, she could, confirm, some of these results.
And then a really interesting study from, Taya Join up from Tinden housing key. And, I had a great pleasure to, to be her, to do her bible for her PhD. And, and, and one of the really nice things on this study is, it shows you very nicely, the interplay between behaviour change and also epilepsy.
So they got, they have a gene defect, they have what is called a benign childhood epilepsy. And they can actually grow out of the epilepsy, so they stopped having seizures. And she followed them up, and looked at their behaviour when they were 5 to 6 years old, and were then, found that they had a change in their impulsivity and they were more hyperactive and in their attention span, right?
So again, she came to a conclusion that this might be ADHD and that was really interesting because at the same time, Rubina Packer said, Hey, hey, you know, I think these dogs, this is not just fear and anxiety. I think there's more to it, right? And she, she, thought it might be ADHD like behaviour.
And, and then Tia's paper came out and it felt a bit more, secure to make a statement about this. But we also found that, a certain medium change my diet, improved some of these behaviour factors and, also was actually taking a little bit more at the end of the talk about that. When you look at the drugs we are giving, they obviously have an influence, no, no surprise there.
We know that some dogs rea rather straightly to the perbrate fido bar, and there's a number evidence about, primidone, which actually is angiogenic, . In some dogs, we do know that, the traitan can do the opposite. It can, there's, what in humans, it's called Capra rage.
I've not really seen that. I've seen some overreactive dogs on Capra, but I've never seen that they have this really this rage, what they describe. When you look at the drug.
Which might have actually the best, aylytic properties is pregaba gabapentin, they might actually improve, this, aspect. However, you have to be careful when you combine them with phenobar. They can enhance the, side effect levels of phenobarb and you can see more sedation.
When you look at the study from Dewey, that's, you could very nice to demonstrate that. The other thing is, there's a new drug on the, on the blog, so, it's not so new anymore, called Ibitone. And, this, this drug, there are some evidence when you look at the older papers, where, Lisa found that in those beagles where he tested it, he, he could see that some of the dogs improved also their behaviour profile.
They were less, fearful, looking. And, Ravida and I, we wanted to prove this, we're still collecting shells and dots for that study, to do a longitudinal, study which, which is still not finished. We did a, a cross-sectional one where we just asked the survey, and we couldn't find an effect.
However, things, Danny Mills, he did a study where he shown that especially noise phobia type, related problems, that giving to might have an, an effect and there has been just, licence, change, for, for reperto because of another firework study. Well, I told you about beauty. We come up a couple of times in this talk, and here she is, still beautiful.
I hope you agree. We call it also the whites, and I hope people will say the same about me because I've definitely, I've become whiter and wiser, hopefully as well. But you see that she is obviously not 100% with us, right?
And so when you think about this, so what is the role of cognitive function in dogs with advocacy? And that's a really interesting one, because people, it, it, it's, it's probably far from the truth that people who have epilepsy are not as highly intelligent. That's, that's not true.
However, what has been shown is that if they have already Some form of cognitive impairment, right? You, for example, you age, and you, unfortunately, we do cognitive, get worse, then it might aggravate it. So the idea is actually that it aggravates, cognitive impairment.
That's, that's one of the, hypothesis at the moment. We, we looked at this as well. We did a, a huge question of study.
We had 45,000 dogs in gold. We aimed it for adult dogs because we didn't want to buy it for epilepsy patients. And when you look at that, what it did influence tradeability, it was, dogs obviously being older than aged dogs, or older than 12 years in our study, and dogs with idiopathic epilepsy.
So they were slower to learn new tricks. They, they were slower to, respond to, to punishment, returns with call off lead, and so on. And the most interesting thing is, that the dogs, did a lot better if they had a positive reinforcement.
They had obviously more exposure to reward-based methods and also more trade. These dogs. There were some drugs which were associated, polytherapy, again, in humans, often as soon you start polytherapy, that's why they often recommend to stay first with one drug before you add too many drugs straight away.
So these are mide and potassium bromide, where, associate with the poorer ability. The other thing what we did is we looked at, canine cognitive instruction scores. So, when you're normally over 8 years of age, as a dog, you have a higher likely of getting a canine cognitive struction.
And, we wanted to see how is it in dogs actually being younger. I mean, are they probably just ageing faster, so to speak? Yeah?
And that's why also the graph can be explained by this because, one of the things I told you at the beginning of the talk is that when you're diagnosed with epilepsy, you have 2.5 years to live after that. And so we didn't have a lot of old dogs.
So the modelling actually for the older dogs was not as accurate, but for the younger dogs, you can see the the wide variety for this canine cognitive dysfunction score. When you're over 50, they would score you as having clinical relevant canococcal dysfunction. And when you look at these dogs in this model, that we had 4000 dogs involved and 286 dogs with epilepsy, and epilepsy diagnosis that model, age, weight, so lighter dogs at a higher risk and training history.
Yeah. So, what you guys are doing, you know, you're very dedicated. It's, it's already evening, and you're still learning.
So that's a good thing. At least we can save some neurons today. The other thing is what people have shown is that it's, very much, what is, can, what I modify it when you have epilepsy apart from drugs, obviously, is, just a seizure.
So it's, it's more seizure than your patient is, it's more likely it will not only not respond to treatment, more Likely will also have comorbidities. And these are probably the ones which we especially focus our attention to when we modify all these other factors and also incorporate these other factors. So the history of cluster seizures, a high seizure frequency, where the two things which, did model quite strongly with a cane and cogitive dysfunctions go over 50.
And the other thing is we wanted to develop a test where we, looked at kind of a bedside test for, doing our clinical trials. And, we used, one from a, a Spanish group. And, and what we did there is we, is a food rewarded based test, and what we found is probably to keep it simple, we found that Working memory was OK, but the spatial memory was, affected.
That makes very much sense in dogs because we know that you have temporal region. This is the area where you, it has to go through when you create a memory, but also for the retrieval of the memory, which is often affected epilepsy, high epiderogenic, area, is affected in destalks. And this is just a highlight this.
We, we don't have a lot of follow-up studies in dogs because often we only have one MRI scan, and you can see very nicely that the dogs, 2 years later, they can actually change the area of, of these, peripheral node and the, and the hippocampus amygdala areas the limbic system. Again, and the limbic system, obviously, as you realise, has also an influence on behaviour. So, if we think about this, so how can we actually reverse this?
Because on the one hand, I can tell you there's an influences of changing the likely of seizures, but we can obviously change, also, the side, to the borders of the waterbed to, increase this in some form to stop having the animal having seizures. And we came up with this more comprehensive or holistic approach, which the side of the fences then. So thinking about, first of all, is there a potential trigger?
Do we know that the animal always reacts to certain changes in lifestyle, reducing these stress factors, anti-alptic drugs are and will be always the cornerstone and the main foundation of, of our management, but then also thinking about, how does nutrition influences this and hopefully get epilepsy control. Let's start, and I, I will do this very fast because the beginning is all about drugs, but just to highlight you know importance about drugs and what the, specialist out there say. So let's say you had poppy had 4 seizures in the last 3 months, in the last month, sorry, and had a physical interectne exam, bloods and neurons were unremarkable.
What would you do? Most of you, you know, would think, OK, this is a dog, has no interactal changes, has actually a very high chance. And 11 study predicted 97% chance of having idiopathic epilepsy, others would say, over 90 or 85% chance.
So it's a very solid answer to say, yes, let's start treatment. Which one would you use if you are, in the UK, or in Europe, as you might realise, sorry, typical starting like an English person say, then you would go either yarbital in to if you are suspected epilepsy and there's no indication of clusters. And you have seen, obviously, these faces before, there might be an epileptologist, a neurologist in your area.
We have this big task because we're working at the moment I'm just reviving it, a lot of activities. We are doing one for cats now, the consensus statements, and we also do one for stars of elective justice seizures, and some common data elements and so on and EEG, so it's a lot more activity to come. And first one was we came up with 7 consensus statements, which we have published a video online, and, go and, and feel free to actually have a look at that.
Then also we had an ACIM one where I was, had the great pleasure to be co-chair with Michael Goodell, who's, absolutely amazing and done an amazing job in creating this, a bit, probably a little bit more practical than the European version, but the European version is also very good. It just gives you more of the European aspect, of it. And then, I want to also thank, Super Marios, and I have sent him a lot in, in different talks.
And it's, it's a reason why you should never put any, pictures on your Facebook profile, because people might steal it. But Marius has done an amazing job, because he has actually, was one of the main reasons why we're able to come to a consensus because we did a, systematic review, about the Antibiptic drugs out there and found that there's good evidence for phenobarto taroma a bit less and then leviracetam as an adult, there was some evidence. There is, however, there's been a bit of a change, at the moment, and leviterracetam from a study from Eparent looked like to be not as effective in first line treatment.
It's different for add-on and for cluster and, . From a side effect profile we wrote another paper, where we have done this, and found that levitrasetam is the safest that we would be told that about the potassium pro, when you look at all the side effects, and we have also done one for cats, you also find it. And, but now, just about, obviously, popping the dog, what, what came out in the IVTF and ACIM was that if you have an animal presented with starts lapticus or just the seizures, start treating it.
If there are severe proictal signs, if you identify a structural lesion, we'd also, highly recommend it because we know that these animals are more likely to get cluster seizures asicles, and you don't want to get there in that situation. And I always, always change the way you do things when there's an increase in seizure frequency or severity. I would, however, also say that epilepsy can be a waxing weighing disease.
So, often it's good to have a 3 month, cycle, obviously, if the dog sudden start clustering, then you need to intervent first. Yeah. Most owners will tolerate 22 seizures or less in a 6-month period.
That's why we said if you have 2 or more isolated seizures in the 6 month, you should probably start treating. When you look at the level of evidence for monotherapy, then from the AFIM where we use two factors, we, this is using not only scientific evidence but also clinical expertise. Then again, the bar in the bride and then no so is a might then pione, we said no.
When, from a consensus, like I said, the European one is, also taking into account the cascade regulation, then, you start a dog with fiddlearb when the recurrent single generalised epileptic seizures, cluster seizures or any other epilepsy type, inittoin is only licenced for recurring single generalised epileptic seizures and potassium at all. But you know that's all. And there's no question that we obviously want to balance the nicity and tolerability and when we talk about diet, that's also one of the possibilities that it actually can help to improve the tolerability because you don't need as much drugs.
The way that you checkinar, most people know this as well. And, and this becomes actually a bit more important, in future talks that we give you because they will tell you a little bit more about how diets can actually influence alsoinobarb levels, in the long run. But, it's the other way around, as you think.
and, and I come to this data. But normally, you would check after 40 days. And the reason for that is quite simple because Finobarb is, is probably one of the most potent liver enzyme inducers.
And, it takes, so the half-life is, depending which literature, a day, if you give it every, you give it every, 12 hours, then normally after a couple of days, you should be very easy in your steady state. However, you, you still check, obviously after 14 days. And the reason is, 12 days or 10 days.
The reason is because your liver enzyme activity starts increasing and the liver enzyme activity when it increases also metabolises, in a field up faster. And that's why you take it after the peak, which is normally 7 days, . There's also a debate.
I was about to peak of trough debate, and I wouldn't go into this, when do you take actually the er concentrations, Jacque Panderre has done that study with Raque Montero, where they showed that if you take 10 milligrammes or more, then you need to do this. There's a difference between pet. But actually very more practical.
If you know that there's, a dog which always succeed before the next dose is given, or you have any, any any suspicion that there might be an effect of that, then I would do a peak and trough in that more difficult to control patient. With inittoin, obviously, you don't check your serum concentrations. It has a longer effect or it's assumed to have a longer effect in the brain than the than the serum half-life.
So, let's talk a little bit more. This is kind of the basic, what you do, and I just want to highlight how important drugs are in this, in this disease process. Let's talk a bit more about the other factors.
So what's the role of diets? And, and like I said before, you know, every breeder thought I gave, and I gave quite a few in my life, they always blamed the diet. And I thought like, yeah, yeah, yeah.
And then there were a lot of people on the online, you know, social medias where they also, they describe it, they say, look, when I change this and this. And I said, OK, that's, that's interesting. And we do know.
That with certain diets, your phytogra absorption changes, especially when you have a high fat diet, they can actually change. We also know that, yobarb actually has an influence in your, in, in the gut function, in the microbuilder function. So there's also this interlink, it changes the microbuilder which are present, which is also interesting.
But the one, we, we, you know, which we all know is that owners probably will not tell you about it, and that's why we did this one study here from Ben Berg, who's currently a PhD student. And he said, OK, who is actually giving diet of supplements? You have to be always careful because obviously, when you do these questionnaires, you get probably a bias.
However, saying this, you had nearly 70% of the owners, who, who, who are gay. So 2 out of 3, owners did change the diet when the dog started to have epilepsy. And they either change the diet completely or they added dietary supplements.
And if you think about your own personal life, a lot of people do this and actually what we found is that people who change their diets or eat have take dietary supplements, they also will do the same. For the dogs. And then we asked them for the reasons why did you do it.
And they said, you know, it was a reduction of seizure frequency, I felt, protection of the dog, from the effects of the side effects of the anti-epileptic drugs, and to reduce the seizures severity. What I think, what I found really interesting was that owners already recognised that these animals might have cognitive problems and also behavioural problems. And that's what the reason why they gave, these compounds.
They might be actually ahead of us, in a lot of things, and I think the observation should not be, under, underrecognized. And, and just to mention it again. So it's, it's really, important, what, what you tell them, they wouldn't, wouldn't do this if, if, if you would not, recommend it or, or do the opposite.
So you have, like I said before, you're probably one of the most important links, between success and not success, in the epilepsy management. And When you look at what, what are they changing, then very clearly, things like fats and oils are always very popular. And when you look there, it's the coconut oils and MCT oils, but I, I think you have to be careful with coconut oils, because they also chain fat assets, but MCT oils, we talk about this a little bit more in detailed data, are very safe.
At least what we know until today. People also give, omega 3 fatty acid oils and there's some evidence that they can improve in the right combination and the right, the right, the, the right mix of omega 3 fatty acids. So, we all know that potassium bromide is a salt, right?
We all know that it gets confused, bromide gets confused with chloride in, not only in the blood, in the, in the, in the body, but also in your, biochemistry analysis. You get a pseudohyperchloremia when you have a dog or Some bromide. So the machine picks up the bromide ions instead of chloride ions.
The idea is that instead of 21 chloride ion going into this, into the cell, into the neurons, you have 2 or 3, chlo bromide ions going in and making it less likely to fire. So that's the, all the reasons. Where we know that the dietary supplementation, with salt will also attract your bromide levels at the end of the day, right?
Because the body confuses bromide with chloride. So we do know that, you know, if, if the dog has a change in diet, then the bromide levels will also change. Quite vividly, and if people, for example, you have those stocks which had a potassium boma because the owners didn't stop the loading dose, you can actually treat it with putting them on sodium chloride drip, increasing diabetes, and then they will, improve significantly.
We, the one thing I was not aware was what people actually are feeding, right? So I'm sure, you know, when you want, I mean, we all know this, right, when you want to show someone appreciation. When you take someone out, if it's someone you really, you know, would like to have a more long-term relationship with, you would only take them out for a nice dinner, right?
You will serve them food because you show your appreciation over, over, if you show your caring. When you go home, you know, your parents are like, Oh, don't you like it? Because at the end of the day, when you don't eat everything, then they feel not loved as much, right?
Because they show they're caring for you with their, with their food, right? And the same actually happens to dog owners and, and I, and I, I never thought about this until we did the diet. My wife is a, is a dermatologist here.
He constantly tells me that I have to ask my dietary questions differently, and I, I have noticed, I'm, I'm, I'm getting better. But what we found out was that, owners were telling, yeah, it's the standard diet, and they tell you the standard diet. However, what they don't tell you, like in a dermatology consult, they don't tell you all the other stuff they give, and they give a lot of other stuff.
And when we did the diet trial, they, we really had to work with some owners, and some owners actually dropped out, because they were not able, felt able to not give stuff from the table, in these stocks. So, obviously, it's a salt, like I said, and if you modify the diet, you will also modify the salt content in the diet, you will also modify the brant concentrations. So let's talk a little bit more about, the diet trial and medium shade because of the diet trial and a little bit how we started.
And I give a BSAVA talk, and the BSAV talk was about canine cognitive dysfunction, and I looked at all the evidence, and I found a really interesting paper where they looked at, and shown that the brain works better on ketone bodies, and you actually have And we, we know this now that, a neuron is 4 to 6 times more efficient on, on a, on a ketone than it's on sugar, which I found very surprising. And so I looked into this a little bit more. And then you'll find actually that, especially in the ageing brain, you are more, dependent on these ketone bodies.
And the, the, the glucose, is important for the supporting cells, and you always need some, blood sugar. However, your brain actually will. Incredibly well, on a ketogenic diet, and it gets more, more clarity.
And if you ever tried one of the, you know, Atkins or try to slim with California, you will have some clarity, and, and that's one of, 11 of the reasons. There are some side effects, you get a headache and then you get your proof. So I was looking at this a bit more.
And then interestingly, the I mean, Matthew Walker is an amazing epileptologist. He, he did this very interesting study, and he had this poster at, at a conference in New York where he, talked many about barphoric acid, which also is a medium shape fatty acid. And he, he looked at different factors, different, fatty acids, which could also have a similar effect.
And so I got very interested in these medium chain glycerides, which are between C8 and C12. And at the same time, we obviously want to look into what effect does the diet have because owners were always telling us. So we, we organised and, we're able to get this, this trial, sponsored, using a randomised trial, medium change was right.
And let me talk to you a little bit through the study design. So it was a 6 month perspective, trial. We were all, I mean it's a double blinded, but at the end of the day, the person who did statistics was all blinded.
So we, we try to be as, as as, as unbiased as possible. All these doctors that have idiopathic epilepsy, a tier 2 diagnosis means that they also had advanced imaging, and we had to have at least one antipileptic drugs, and I show you the second most multiple antipileptic. Drugs.
They had to have at least 3 seizures in the last 3 months because we wanted to have it, 3 months, 3 months to have enough seizure frequency to pick up, the difference, and they were blocked randomised either starting, on a placebo diet and then, switched after 3 months to enriched and medium traded diet, or vice versa. When you look at the dogs, we included at the end, for analysis were 21 dogs, 6 were females, 150 males, like I said, all dogs see finobarb, potassium bromide, and most of them 18. We just, you know, Pitton just came on the market, and we just had one dog with had an add-on, and then 4 dogs that, and some of them had it as a, as a cult, treatment, quite a big variety of breeds.
It was not just one specific breed. When you look at the effect, you can see that there was a significant effect in seizure frequency reduction. I think one of the things, highlighted here in, in blue are all the dogs which, which reduced.
There, none of these trials, and we had some dogs and I show you in the seconds, which had a lot of seizures. They had like nearly one seizure a day. They would have to have all the dogs are always improving.
However, for some dogs, it really made a huge difference because 3 dogs became, completely seizure-free, and the owners were really keen to continue. There were 7 dogs in addition, who were, had more than 50% reduction. And, and so, think about it, half of them obviously did a really good response.
When you look at the, on the top, you see the total number of seizures in the placebo and then during the MCT period, you can see that the effect was, immediately, which also makes sense because the, medium trade have a high ketogenic yield. So they automatically, I mean, very rapidly change your, your level of PHP, bedroxybutyrate. And the effect was long lasting.
When you look at the, summary and conclusions, we found that quite a lot of talks did improve, but remained, like I said, 14% became seizure-free, and half were classical, responders, that means more than 50% reduction. Really interestingly, yes, they had an increase in beta hydroxy puttorate levels. But the one thing, it was not like a massive, but I don't think that this is, really necessary to have to be, massive in, in different of meaning with that that they are truly ketogenic.
Yeah. I think it's really important that it's, it's more focused on giving MCTs and rather causing a ketosis. But I'm not a nutritionist, so this is my interpretation.
Interestingly, there was no effect on the antideileptic drug serum levels, between, the most phases. And we have just done a, a, a supplementary trial with MCTs and we could replicate these, data, not as, as good, but also we see an improvement, in those dogs. And, what I said earlier about Finobarb, we could see that phenobarb serum concentration that goes slightly down in that trunk.
Because we just use an add on oil, and that might be the reason for that. saying this, it was not significant, it was significant, but it was not, clinically significant because these dogs, also actually improved even at a lower field up concentration, at a better improvement, in their seizure control when, when they were on MC MCT supplementation. Sorry about this.
I started like, I hope, I hope you don't feel this, but, my, my children are both in a nursery, and, they definitely have quite some bacteria culture going on there and bring a lot of bug so. So, very interesting, as I said to you before, is that we are not only interested in the seizure control, but also in other factors. And what was really interesting that, in this, in this first study, and we could actually, and we'll show you more, but as I publish it so I don't want to go too, too much detail, but there's some really improvement, also in the comorbidities, side of things.
and in this study, we could show that in the chasing behaviour and a properties as mentioned before. Just a couple of, backgrounds. When you think about an epileptic dog, there's one way of finding out the epileptic focus, and this is PET scan, and you use glucose, for that, which is, which you can ready to trace.
And when you actually in the epileptic focus, in the time of the seizure, you have a lot of activity, you need a lot of glucose. But in the, in between, it's actually the opposite. Yeah, it's kind of a cool.
One of the ideas would be that, is it perhaps that especially in the intermediate, period, that these might even work better like the aged brain, like these areas actually work better on ketone bodies, than, than the normal brain. We also, looked into this a bit more detail, and there's a nice study from Matthew Walker. We have shown that there might be actually a direct effect on certain medium-term universal, and he found certain C10s, which is, They are still working, on, on, on, on identifying a couple more, but they, have already painted in some, some C10s, but it's a direct effect on the APA receptor.
That's another hypothesis. There's also another hypothesis, which has been shown by some nice study where the C8, actually, Change, the concentration of, of freely available viic acid by, by pushing these, away from the element and also by, changing the serotonin metabolism. And that could also explain why some of these, drugs might affect the behaviour as all seizure control.
We, we just published, recently a study, and I, I don't want to bore you too much, but it was quite an interesting one because, T, T, my, my postdoc, he came to my office and said, Oh, I found C17. And I was like, Wow, that's really interesting. And, and the reality is, I, I really didn't get it.
And then he said, however, there should not be C. So, and there's not some other studies out which, which found the same. As you might remember from your biochemistry, is you always have, you know, equal numbers.
So you see 16, C 1820, and so on. You should not have odd numbers, right? So, the interesting thing and one of the hypotheses we had is that it was alpha oxygenation.
And, the idea is that this then gets broken down to rehaptin, which also showed antibusant effect and also might be an evidence of the mitochondrial function. Has been improved, which will replicate other things I said earlier. So taking this all together, how I could show you that epilepsy is far more than just simple seizure disorder, and probably needs also a bit more, complex toolkit to really look at all the aspects and improve the quality of life.
I want to thank, everyone in my group, all the funding buddies, who always make these research available. We have a lot, going on, and as a good and final, I will be leaving the UK. I will go back to the vet school in Hanover, where we also will very soon start, continuing all the research.
I will continue, obviously, being active at the REC, but, we'll go back, and take a chair at the Hanover. We will also do some of these studies like the Life in Hanover. Hopefully soon.
I will also want to thank, beauty, and don't forget, there's a lifestyle trial if you have an epileptic dog, which doesn't have cluster seizures, Zoolepticus is older than 6 months, please send them to us. We really need to do this trial. We want to really look at the long-term effects, and in a controlled way.
These studies are not possible. Thank you for listening, and I'm long looking forward to answer all your questions.
