Good evening Wana Sara Watades. Hello everyone. Thank you so much for coming on the webinar.

We're very fortunate tonight to have Fabio Stabbi who's gonna be talking about interactive epilepsy, top tips for first opinion practitioners. Fabio qualified from Padua and has a PhD in neurology. In 2008, he moved to the UK to work as a resident at the Animal Health Trust, and he's also a diplomat of the European College of Veterinary Neurology and an RCBS specialist.

He's now working at Southfield's veterinary specialist. Has authored papers and chapters in various Textbooks and in journals, I, I'm really looking forward to hearing what Fabio has to say about a really big problem in first opinion practise, the epileptic patients. So Fabio, thrilled to have you on, it's over to you.

Thank you so much, Anthony, for the kind introduction and thank you to webinar vet for this opportunity and to the Tool for sponsoring this webinar as well. I really, really appreciate it. And this is because, well, first of all, I have a chance to talk about one of my favourite subject and also, I have a chance to talk about something that when I was working as a general practitioner, scared me and scared me big time because when you have patients seizuring, It affects you.

It doesn't only affect the client and the patient, but I find myself as well when I see animal in hospital seizure and it's, it's not a nice thing and I just feel very, very strongly for this. So, After a little chatting discussion how to introduce the subject, what I decided to do is to just do a few slides about the diagnosis of epilepsy and treatment of epilepsy. But then, we took the most asked question by practitioner to, the, the talking or ask the ESPA scheme, which is a The service that the talking on offer and asking and answering to practitioner question about the use of phenobarbiton during epilepsy.

So, so said, let's dive in, in, again, one of my favourite subjects. Epilepsy is such a massive, interesting topic for me because first of all, it can be caused by many, many different conditions of intracranial disease of any sort, tumour, inflammation, infection, infants to metabolic disease, think of a young dog with a portosystemic shunt or an old dog with an insulinoma, for example. And of course the It's a massive, massive big chapter of idiopathic epilepsy, which is the most chronic neurological condition.

Dog is a lifelong condition. Dogs that we are able to take off medication are very, very, very few. And the other most interesting part is that the treatment of the disease is tailored to each patient.

So, yes, you could have a protocol to follow, but then you need to mould your treatment around your patient. The treatment of epileptic seizure, is based on first of all, dandelion cause. Clearly, if it is in jeopathic epilepsy, we are gonna think of some treatment whether, the dog is having seizure because of an intracranial lesion, we need to consider additional treatment.

The presence of any previous or concurrent illnesses, but a medication we can't use in the presence of kidney disease, for example, or liver disease, and of course it's based on an accurate diagnosis and the closer we can get to that, the better for our treatment and the outcome of our treatment. We differentiate EPA decision in three big groups. One is called reactive metabolic or toxic seizures.

Again, think of metabolic disorder as we said just a second ago like demiant or insulinoma or even toxicity, metaldehyde, for example. . Symptomatic or structural epilepsy, which is epilepsy caused by a disease sitting in the brain and on the bottom left, you see the MRI the transsection of, of the brain of a chihuahua with this massive or hydro massive hydrocephalus.

You see all this content of water in the brain squashing the brain from within. And the middle picture here was a little western and white area. You see the symmetry between this side of the brain and this side of the brain, very, very suggestive images of an inflammatory infectious process like the inflammatory like GME.

And the last image here, you have a mid line section of the brain of a old Labrador with this tumour that was a meningioma. Once we are able to rule out all the reactive and symptomatic cause of seizure when we are left with the diagnosis of idiopathic epilepsy. The full list of investigation for idiopathic epilepsy does not only involve a collection of a full history, a physical and neurological examination, which should be normal in between seizures, but also include full blood analysis, and this includes haematologists set on biochemistry.

We always suggest to perform pre and postparia bile acid in order to make 100% sure the liver function is normal in those patients and also a thyroid panel. And this is mainly because some antiyactive medication might interfere with thyroid panel reading after you start the treatment. Should your patient have been travelling abroad, in the case of we are very lucky, we don't have that many infectious central nervous system disease that could be linked to epilepsy.

However, Involves animals that have been travelling abroad or are fed on a raw meat diet and this is massive right now, performs some infectious disease started just to make sure that there is nothing associated with it. For your analysis as well should be part of your, of your screening and involve animals which are elderly starts showing a seizure later on in life or very, very early in life, so younger than 6 months, then I have done ultrasound, access of the chest will complete your investigations. Not all our clients are fortunate enough to have full insurance, but should we really get to the bottom of the reason for the epilepsy happening, then performing imaging of the brain via MRI ideally, completely with the cerebrospinner three collection analysis would be the most important step that, you know, that we complete fully your, your diagnostic workup, we will have a better idea of what is going on in their brain.

A latentencephalography, well, that would be brilliant. Being able to perform a latent encephalography is not that easy, even nowadays in referral practise is not that, that common. But that would be what really would confirm the presence of a pla spike.

The treatment of epileptic seizure has been ideally to eradicate seizure. Who doesn't wish for that. But every time we talk to clients, we need to be a little bit more with feet on our ground, control seizures probably more likely than eradicate them at all.

Ideally decrease the frequency and the number of seizure, decrease the severity of the seizure and the postal sign. There are dogs that become aggressive or become, for example, blind after a seizure, decreasing both parties sign, significantly improved quality of life in our patient and for our clients as well. And of course, we need to make sure that we need to minimise side effects on the antiyactive medication.

It would be great to have an animal that has less seizure if possible with the minimal side effects. No one wants a zombie, totally zoned out dogs seizure-free. So when do we start the treatment?

In 2015, the International Veterinary Epilepsy Task Force came up with a great plan on when to start the treatment, a clear, straightforward guideline. And what we suggested is to start the treatment if a dog is, experiencing one, more than 1 seizure every 6 months. And probably a lot of you might think, well, that is a bit radical.

Come on, we can wait a bit longer. Now, the decision to do one seizure over 6 months is because, after reviewing a lot of literature about epilepsy, it was actually found that the more a dog seizure without medication, they treated the seizure to control later on in life. So I think it makes sense to start antiepileptic treatment at this point.

Clearly, if a dog is is very cluster as a seizure status epilepticus is a neurological emergency, we need to start an antipyretic treatment immediately. If there is a structure called for epilepsy, if there is a tumour or an inflammation that is perpetuating seizures, then, well, we need to start with or antipyretic treatment, even if you, remove that tumour is unlikely, then then epileptic seizure will stop. If there are, as we said before, severe or dangerous postdictal events, or seizure frequency is increasing in severity and infrequency over time.

Of course, the last point is always valid, but as someone they just cannot cope with doing nothing, . As opposite but our owner vet just say no, we're not gonna give any medication to our dogs and it's our job at least advising on what would be the best course of action. So at this point, let's dive in through the question that they are most commonly asked to the aspect about epilepsy.

And one is how can we establish if there is a brain lesion. With minimal equipment. And this is a very, very valid question, not only because there are a lot of dogs out there that are not insured, but also because in this pandemic period, we've not been able to possibly have a further and go ahead with further investigation.

So what can we do? Well, first of all, the history is rather important. Is the dog experiencing epilepsy when he's younger than 6 months?

That maybe make us think there is something in the brain or metabolically wrong with that dog and probably we need to chase the reason down pretty soon, or is the dog experiencing the first age after 6 or 7 years of age, that makes possible intracranial lesion most likely. Is there any abnormality at the neurological examination and is the seizure presentation potentially helping us in determining whether there is a brain lesion? These are all questions we would like to answer in the next slide.

Well, first of all, there has been a study looking at the clinical reasoning for canine epilepsy and what the researcher have done have looked at neurological abnormality in the with brain disease. And what they found is that between 47 and 55% of Dogs with neurological deficit have a brain lesion, OK. So 47% of dogs with a lateralized lesion will have a symmetrical neurological deficit.

55% of dogs with symmetrical brain lesion will have a symmetrical neurological deficits. Or that would have that are not normal in between seizure are 16.5 times more likely to have a brain lesion.

Another important information to keep in mind is that even if you have a normal neurological examination in between seizure, this does not completely rule out that that patient might have a brain disease. And this is because there are clearly clinically silent regions in our, in, in the brain of the dogs, like the olfactory lab, frontal and piriform lobes. Where dogs could have disease, structural disease, we're talking about tumours or inflammation or developmental abnormality and potentially not show any neurological abnormalities and just experience seizures.

And therefore what the same study found is that the 23% of dog with stre epilepsy, so with a disease in the brain that perpetrate seizure, had a normal neurological examination in between seizures. The first sign of structural epilepsy is actually seizure in 76% of dogs, which is a rather large number. And though they actually have a disease in the most frontal part of the brain, are more likely to develop epileptic seizure compared to dogs developing tumours somewhere else in the brain.

Can the manifestation of seizure help us? Well, it's not really a very good predictive variable. 77% of idiopathic epileptic dogs will suffer generalised seizures.

79% of those with brain lesion will suffer epileptic. Seizure and there was an old myth suggested that maybe they have a focal onset epilepsy are more likely to have a brain disease. Well, this was proven wrong by another study which showed that 93% of the brain tumour will have generalised seizures.

So let's go down to our neurological examination. Neurological examination could be a complex examination to perform. However, I want to break it down and try to show you what we actually can do quickly in practise in order to at least have an idea if a dog will have or not a brain disease.

We divide the neurological examination in two parts, the hands-off examination during which we look and observe a dog, we checkmentation, posture, and gait. And this is something you can very, very quickly do while the dog is coming into your consult room from, from the waiting room, for example. Is the dog behaving normal?

Is it circling? Is it turning toward one side? Does the head toward one side?

Is the dog behaving normally, normally for you or not? Is the dog hexic? Is he falling over?

Only to a question that will take just a few seconds to maximum minutes to answer to. And of the hands on examination instead, we start with a poster reaction. Now you see one of my colleagues here, Guillaume, doing a poster reaction in this dog, he's turning his feet upside down.

When you do this test, you need to support the dog and you will see that this dog has neurological deficit, a proed deficit on almost all the limbs. Another thing to consider, this dog has Has abnormal posture. All the feet are spreading out outside the centre of the body.

And we don't have the sounds here, but you would have heard the dog here constantly whinging and crying. I know, she's a beela, yet it is not an excuse that would suggest an abnormal mentation. And as you can appreciate, this little lady has receptors on her legs.

Well, the spinal reflex is, is probably not something that will help us much in investigating the brain. The spinal reflex assess the reflex arc that goes from the pore straight into the spinal cord and all the way back. So it's something that probably we can skip if you need to do a quick neurological examination.

Whereas for the cranial nerve. Parts is something that we probably need to check and particularly what I would suggest to do is to check, first of all that your dog can blink and there's a normal facial sensation as Guillaume is doing here, and then immediately after before the menace response. Now you will notice in this dog that initially it seems like she has a normal menace response in that right eye.

However, do not get fooled by the fact that dogs can actually blink spontaneously without responding to a manna's response. So this dog, before she was blinking spontaneously in the right eye, but then after trialling the manner response, she stopped blinking and you can see the manna response is absent on both eyes. Another important part would be checking, palpating the head and the spine of, of these patients.

Some dogs with intracranial lesion might have discomfort vision of the head, and they can also have discomfortation of the neck. And this is because increasing intracranial pressure will potentially cause secondary effect on the cervical spinal cord, which might manifest with, with neck pain. So if we look back at our dog, she had an abnormal mutation, and you have to trust me here.

She has an abnormal posture. The legs were totally spread out to the body. You need to trust me on the fact that she was attacking and the poster reaction were delayed on all legs.

She also had decreasement response bilaterally and she had some discomfort with palpation of the neck. And B suggested diffuse bilateral forebrain lesion. So, Get acquainted with this little test.

Properception will take a minute to check. Mena response, facial sensation will not take long at all, and that could already give you a good indication of whether that patient might or might not have an intracranial lesion. The second most common question is what antipytic medication can we choose as a first line monotherapy to treat seizures?

Well, in the UK we are lucky enough to have two medication licenced as a first line antipyretic treatment, and these are phenobarbital, epiphan orbital inexion. We can use potassium bromide as a first line antihylactic treatment involves patients that cannot receive E2 medication and therefore, generally patients that have liver disease. As far as phenobarbital goes, well, the first answer we need to ask ourselves is, is liver function of the patient normal?

And this is because phenobarbital is heavily metabolised by the liver. We make sure that the patient can support the medication. And therefore, performing haematology, a full set on biochemistry and the lay stimulation test is really essential.

If you have a possibility in-house to perform ammonia, that will increase the confidence level that you have in the fact that the liver is completely normal. The other medication is Epito. Imitone is licenced for reduction of seizure frequency or generalised seizures in idiopathic epileptic dogs, and EMA suggests after careful evaluation of alternative treatment options.

Should not be used if a dog has cluster seizures and status epilepticus. The same thing cannot be said with phenobarbital actually phenobarbital can be used really well in these situations. So if we compare the two medication, the main question when deciding whether to use noobarbital is, is liver function normal?

As far as the epittoin goes, we need to ask ourselves, is liver function normal? Is renal function normal? Unfortunately, bioin cannot be used, renal function isn't normal, cannot be used also if cardiac function isn't normal.

We need to be Sure that the dog is suffering hepatic epilepsy and that ideallype generalised tonic chronic seizure, we need to make sure that there is no cluster seizure status epilepticus. As far as dosing goes, when using phenobarbital, we suggest to use it 2.5 to 3 milligrammes per kilogramme every 12 hours.

And this can raise a little bit of confusion. The product is licenced for use at initial dosage of 2 to 5 milligrammes per kilogramme a day, divided into two equal dosages, which means 1 to 2.5 milligrammes per kilogramme every 12 hours.

Now, using it at a higher dosages to start with, as it is recommended by many neurologists and by the International veterinary Epilepsy Task Force is not enough licence used. It's just the fact that it needs to be modulated based on epileptic seizure occurrence and on side effects. So, the licence for initial dosage of up to 2.5 milligramme per kilogramme every 12 hours, but best does not have to limit the dosage you use on your patient.

As far as for, as far as Epitoin goes, then the initial dosage is between 10 to 20 milligrammes per kilogramme every 12 hours. And out there, there is enough literature to suggest that if you use an epittoin, start it immediately at 20 milligrammes per kilogramme every 12 hours because it's unlikely to significantly work at a lower dosages. Should your patient don't respond to 20 milligrammes per kilogramme every 12 hours, just go to a maximum dosage of 30 milligrammes per kilogramme every 12 hours.

Then if you still don't have any response, we need to consider switching to another medication. And the comparison between phenobarbital and emittoin is It's not particularly investigative, there are just a few people out there. The last one being a study I, performed in 2019 or published in 2019.

In our study, what we did was to evaluate the phenomenology of seizures, so whether the dogs were having single seizure or cluster or tacticles, and the frequency of seizure in dogs that were not receiving any medication and the I started either on meitone or obarbital. So, in, in, in order to do the study, all dogs will start to between 10 and 20 milligramme per kilogramme and maxed out 30 milligrammes per kg every 12 hours according to client request and according to the manifestation of seizures. Instead, if a client was choosing phenobarbital, we were starting the patient on a dosage between 2.5 and 3 milligrammes per kilogramme every 12 hours, and depending on phenobarbitals level and seizure occurrence, we then modulating the treatment.

We managed to recruit 31 patients in the yin group and 30 in the phenobarbital group. Without wanting it, actually, the dog that was starting on phenobarbital was experienced his seizure for a longer time, almost the double of the time compared to the dogs, but instead we're starting on phytoin. And also without wanting it, the dog that's wearing the phenobarbital group actually experienced a higher frequency of seizures, compared to the dog that ended up in the epittoin group.

Interestingly, the seizure frequency after treatment significantly decreased more in the phenobarbital group. So the dogs that were in the eno phenobarbital group experience way less seizure compared to the one in the, in the pitoin group. But the results that was more shocking is that 21 dogs starting on maybe over 31 experienced cluster of seizures, whereas only 11 dogs over 30 starting on phenobarbiton experienced cluster of seizure, and this was a significant difference between the two groups.

If dogs were experienced cluster in the epitone group were experienced after 4 months more or less, whereas in the dog experience the cluster, often aboutbiton were experienced almost after 18 months. Also, an interesting result is that in the meytoin group, 7 dogs actually experienced unacceptable adverse effect in the first month of treatment, that brought the client to request change to another medication. And we didn't have any of the dogs in the phenobarbital group experienced such severe side effects.

I then follow this patient through time up to 3 years after we starting the anti-active treatment. And 25 out of 31 dogs, so 80% of the dogs starting on epidoin had to have medication discontinued, and none of the dogs starting arbitton had to have medi medication discontinued. So just to summarise, trust theheia developed significantly more frequently and earlier in life in dog starting Olitoin.

And baby seizure frequency was significantly lower in your in the partic aid dog starting on phenobarbium, even if 4 dog were actually the dog washesing more before the treatment. An acceptable adverse effect which included aggression. And ataxia were more frequently noticing the epidorin group.

And theepitone group had significantly higher discontinuation of the medication. A 3 year follow up. And we know how important following these dogs for a long time because in the literature, in the veteran litre, we have a lot of studies following dogs for weeks to a few months, but at the end of the day, we are treating this animal for life.

After 3 years, which is when my follow-up stopped, 80% of dogs on immipito had to be changed to phenobarbiton, and none of the dog on phenobarbiton had the treatment interrupted. The other question that comes up fairly often is when you have a dog on phenobarbital epiphen, you will find that there are raised liver enzyme. Should we be worried about this?

Well, we know that the treatment with phenobarbital will cause laboratory changes. And these changes can be either expected changes or adverse effects. In the expected changes, what you can have is that ALT, ALP, GGT might increase.

The triglyceride as well could be increased and the albumin level. Tend to creep down with the treatment of obarbital. So, you would add that between 1 month and 3 months, the abdoin will start or will continue to creep down slightly in specific cases.

And that might raise the question, should I really be worried about liver function here? Well, the right answer would be perform a balllay stimulation test. Penobarbiton is a very potent inducer of his own metabolism and therefore, with time, it is normal to have increment ALB for example.

And liver enzymes. This does not really correlate to liver disease. The formal a stimulation test, if a stimulation test is normal, then, the liver is actually working fine and that should not make you decide to change or stop the treatment.

Another thing to consider is that because phenobarbiton accelerate metabolism, T4, 3, T4 may creep down as well, making the The diagnosis of possible hypothyroidism more challenging in this patient. TSH well can creep slightly up, making things a little bit more complicated. And then there are phenobarbiton adverse effects that can be noticed in laboratory changes.

So if, for example, you have increased ALTLP, GGT and you decide to perform correctly a bilayer test and this is increased. And at the same time you have decreased urea and albumin, then yes, we have some kind of liver disease. Whether the liver disease has developed because of the phenobarbital or is there another concomitant disorder is difficult to say.

What we know is that hepatotoxicity associated with phenobarbium is really uncommon if phenobarbium serum level is lower than 35 milligrammes per litre at a trough. Troughle is collected just before the administration is due. So if we keep the phenobarbital lower than 35 milligramme per litre trough, it's unlikely that we're going to cause issue unless there is a sort of idiosyncratic reaction or there is another condition developing in your patient.

Another laboratory changes which is an adverse reaction is a form of blood dysplasia, which are an idiosyncratic adverse effect of phenobar because so you can have anaemia, you can have pancytopenia, you can have thrombocytopenia or only decreased white blood cells. And this is being reported in a very low percentage of cases going from 0.6% to 6% of all cases.

And it's, again, it's totally syncratic, so it's not related to the length of treatment, it's not related to the dosage of the medication and it's not related to the serum level of medication. It can just happen. Thankfully, is a reaction that just goes back to normal once you stop the treatment and change to another anti medication.

So not a life-threatening condition if it's in time. Hyperbominemia could be developing with phenobarbiton, as we said before, at the beginning of treatment, the albumin could creep down. Why can a patient be hypoalbuminemic?

Well, first of all, lack of assumption in the diet would be a good thing to question your client about is actually without not producing albumin, then we need to check liver function for an abdominal ultrasound. Or is your patient losing protein somehow? So is a protein losing enteropathy?

Does your patient have vomiting or diarrhoea? Can we measure cobalamine folate in the blood to check whether gastric absorb gut absorption is normal or not? And it might be worth performing abdominal ultrasound as well.

Another reason for increased discretion is protein losing nephropathy. So perform urinalysis, again, perform abdominal ultrasound and if required, consider culture and sensitivity in the urine. Clearly, if a dog or your patient is losing protein through the skin because severe skin disease, you would have already seen probably you don't need to perform any kind of investigation, such as what I've suggested here.

Another big hit question is when should we perform phenobarbital blood testing? Well, first of all, when performing phenobarbium blood testing, do it on a fast, on a fast sample. And this is because, we know the dog on yobarbitton will be probably more polyphagic and for this reason, we tend to have a little bit of lipemia compared to more to, to the other dogs in the general population.

And we know the triglyceride, higher than 11.3 millimo per litre will falsely elevated your phenobarbital serum level. So if you have a lipi sample with high triglyceride, then just question yourself, is phenobarbital really reliable, not should we start this patient for a longer time instead of submitting the sample.

Another important information to keep in mind is do not use serum separator tubes and check whether your nurses are using serum separ tubes. The gel in the same separator tube binds the phenobarbital, and that means that in your sample, phenobarbital will be falsely decreased. Another interesting subject that came out in, in a research study presented at the conference of European neurologists last year, is the difference between phenobarbium serum concentration using different machine.

So the catalyst of IDEX is now a available machine in many practises. And the study presented ACN compared the same sample of the same blood sample of the neglected dogs and measured phenobarbital with catalyst, the Xidex and with a laboratory emulide, which is the normal standard machine that any lab would have. And very interestingly, all the sample down with the catalyst were significantly higher compared to the same sample done by the Emulite machine.

And therefore, if you do have a catalyst and you measure you feel a barbita level with the catalyst and the result is of a scale, before deciding to change or reduce the dosage in that dog, please check again and send it to a lab. Make sure that it's not a false increase results. Now, this is just a It is a chapter that was presented at the symposium, but I found several cases while working in referral that actually had this issue.

So I would really urge you if you have the, this machine and you have very, very high phenobarbital level, double check them before changing your treatment. Another very tricky question is, is the time of collection of the blood important when we check phenobarbital level? But the answer is that it's not really relevant if you have a stable patient and your patient is a phenobarbiton at a dosage lower than 5 milligrammes per kilogramme every 12 hours.

In most patients, checking whenever is convenient for you, checking whenever convenient for your client. We know though that the hepa toxicity caused by phenobarbiitton is associated with phenobarbitos concentration higher than 35 milligrammes per litre at a trough. So just before the administration is due.

So in that case, if you need to choose one time to always measure phenobarbi, measure it a trough. If you measure it after 4 hours from menstruation, for example, then you're measuring the higher level of phenobarbital, and that, you know, potentially could make you take decision in that patient, which is not probably ideal. So check it the trough.

Make sure the trough is at a safe level. It's probably the easiest bet. The concentration of phenobarbium involves patients that receive phenobarbital level higher than 5 millik every 12 hours or in a patient that, for example, does not have a satisfactory seizure control, then I think it would be an idea to measure both the peak and trough level of phenobarbiton.

The peak again is at maximum concentration of the 4 hour from administration, and the trough instead is at the lower end here, so just before the next administration is due. And I would recommend you to do it in this situation. So whether, whether you have an unsatisfactory epi control or seriouside effects, or in case your dog, your, your patient is having anything about it at higher dosages.

And this is because potentially, you can have a really, really large fluctuation between the two concentrations. So the peak and the trough can fluctuate very, very significantly over the course of the day. And if this actually happened, what you can actually do is calculating based on those two results, how quickly your patient is eliminating the phenobarbiton, and this is called elimination half-life.

Once you have these two results and you can calculate ammunition half-life, then potentially you can changeobarbium to 3 times a day, so administration every 8 hours in order to flatten that curve and give you less fluctuation between the level of peak and trophenobarbium, leading to hopefully a better success in treating those epileptic seizures. Now, this is probably not very common, but I've seen it and I've done a case series, published a case series on the record about the administration of phenobarbital every 8 hours. And what I've done, I've collected a total of 10 dogs, and not not a lot, but it's probably not a very common condition.

I have collected 10 dogs in which I measured phenobarbital at the peak in the trough level, and they all show that they're getting, they were getting rid of philobarbitum very, very quickly. So lower than 20 hours, the normal elimination half-life of phenobarbitum should really be between 50 and 80 hours. And in these patients, I adjusted the dosage every 8 hours and the results we had were very, very, very good.

I mean, in 9 dogs, seizure frequency improved. Significantly, and 8 of these had actually experienced the longest time seizure-free they ever had. In one dog, we didn't have any significant improvement in seizure frequency.

However, the client said that the clinic assigned the side effects of the treatment were much alleviated, leading to a better quality of life. So something to bear in mind that might help your patient and experiences less side effects. But as a general rule, as a routine monitoring phenobarbiton, we always recommend never to use separator, serum separator tubes, only measure it on starved or fasted samples.

Measure it 2 to 3 weeks after the beginning of the treatment or after any change in oral dosage. 2 to 3 weeks is the time where the concentration in the blood should not significantly fluctuate. If a patient is stable, then continue measuring it every 3 to 6 months.

6 months is absolutely fine. If a client is particularly worried, do it every, every 3 months. But also, every 6 months at least, performing haematology, serum biochemistry, and lay stimulation tests.

It's just good practise for any patient or human on a chronic treatment. If there is an increase in seizure frequency or if a patient experience too much side effects, measure your phenobarbital serum ladder. And that brings us to the following very, very common question, which is, if serumbabito phenol level is in within the concentration range, but the dog is still seizuring, what should we do?

Well, the first thing I would ask is, are we sure that the dog is experiencing the epileptic seizure or can be something else? Now, this is a video provided to me by a client. This is a young Labrador.

3 years old, my new tread starting having these episodes, all these epileptic seizures. Well, the first thing to ask is how long do they last? Epiattic seizure uncommonly lasts less than 5 minutes if it lasts longer than the steptoce because we need to be seriously worried.

And this dog doesn't seem particularly out of it mentally despite all his body fully affected by what is happening. Well, this is a typical example of what is called labral dyskinesia, which is not epileptic seizure, it is a movement disorder which is unlikely to respond to any kind of epileptic, antiepileptic treatment. To make things complicated, Labrador are also very prone to verypatic epilepsy, and dogs with this full body dyskinesia can also have patic epilepsy.

So it's not a very straightforward black or white answer, but investigate, get a video of this patient if your client can do it because that can give you much more information on what you're actually treating. The other thing to ask ourselves is, are we administering the antipin medication at the correct initial dosage? Well, again, if you're using phenobarbiton, use it between 2.5 to 3 milligrammes per kilogramme every 12 hours.

And if the concentration is between 20 and 30 milligramme per litre, which is the suggested target range, then we need to ask ourselves, can we increase the dosage? And I generally use this formula which is very, very useful. So if you have the phenobarbital level of your patient, which is the actual phenobarbital level, and you want to increase to a different level, so a desired higher phenobarbital level, but you can divide them, multiply by the total daily dosage of phenobarbital, and then you will find the correct dosage of phenobarbital you need to give your patient to achieve a desired level.

So let's go for an example. So this is our alpha, 2 years old menu thread, 10 kilogrammes just to make it easy. Epileptic dogs receiving phenobarbiter of 30 milligrammes per kilogramme every 12 hour, which is a total dosage of 30 milligrammes twice daily.

And his phenobarbi concentration is 20 milligrammes per litre. And we want to increase it. And let's say we want to increase it to 30 milligrammes per litre.

So we said this receipt is, is actual phenobarbital level is 20 milligramme per litre and he is receiving 60 milligrammes a day, so 30 milligrammes every 12 hours. And let's say we want to increase the level to 30 milligrammes per litre, that means that we need to give that dog 90 milligrammes of inarbi a day or 45 milligrammes every 12 hours in order to achieve our desired concentration. It's a very simple calculation to do in practise.

I always use it when I need to increase phenobarbital level in my patients. Once we increase your fobarbital concentration, just remember to maintain your trough level lower than 35 milligramme per litre. What should we do in case of an accidental phenobarbital overdose?

Well, we know that dogs that are on phenobarbital are polyphaggic and frequently, it happened actually surprisingly frequently, and we are asked, the dog has ingested morphinobar than it should, what should we actually do? Then if we can get to know if it is a real overdose, then we can get to know how many tablets actually the patient has eaten that he shouldn't have, then we can check against the load inphenobarbitone dosage. And we know that if for example, you need to quickly bring phenobarbi to a level higher in the, in the serumol patient, you can give 12 to 24 milligrammes per kilogramme in 24 hours.

So, If we can, let's check how many milligrammes per kilogramme that patient has ingested accidentally. Because if it's just a loading dose, then probably let's just check the sernophenobarbital concentration, check haematology, and sero biochemistry to make sure nothing wrong is happening. And then because it takes 2 to 3 weeks for phenobarbital to to, to reach a new steady states.

Check again everything in 3 weeks just to make sure that there is not a delay process. If instead we are absolutely sure it is an overdose, the ingestion of phenobarbital has been high enough to be seriously dangerous, then we need to consider administering hemetic if we are in time or activated charcoal, potentially a gastric lavage. And then check again serophenobarbital concentration, check your rheumatology and serum biochemistry.

Start IV fluid for the patient, maintaining under checks, constant checks, and again, after 3 weeks, check the IUinobarbital concentration and full blood with the stimulation test to make sure that the liver is coping with the accidental overdose. Another very, very tricky question is, can we take a patient off aarbital? Well, I must confess my experience is rather scary.

I probably have done it in 4 patients and I have regretted in all 4 of them, and I clearly remember one, that actually belonged to a colleague, a Labrador. He managed to be seizure-free for 2 years and my colleague said, look, It's been for 2 years. Let's take it off it.

And we've done it very, very, very gently and very slowly and unfortunately, after reducing of 50%, the dog experience rebound epileptic seizure, which is extremely difficult to control. And now the dog is actually on 3 different epileptic medication with acceptable epileptic seizure frequency, and that always makes me wonder. Should have just been more strong and say no, we're not doing it or not, and that is a very, very tricky decision to make.

What is actually published in the literature. Well, there is not much really. There is a study published in 2015 on the anti-ractic seizure medication withdrawal in dog with epilepsy.

These, these colleagues, check the medical record of 138 patients and only in 11 dogs, the antibiotic treatment was withdrawn, so 80%, 8% of all the dogs were reviewed. Mostly were on phenobarbiton. And unfortunately, 2/3 of the dog had severe rebound epileptic seizures.

Some dogs, so 36%, remain seizure-free, which is fantastic, but a lot of dogs, experience the current of epileptic seizures. We really don't know what this is. The reason why there is withdrawal seizure can be either a current of the original epilepsy, and this is called like a rebound phenomenon.

And our possibility is that dogs have developed resistance after the dislociliation of the medication. And it's not really possible to determine which of the two is the reason for the severe rebound of epileptic seizure, but we know this is a phenomenon that can happen and can be very, very tricky to get a hold off with antipyactive medication. What instead should we do if we need to add a second line antiplatic medication?

Well, we have several options. The first thing I would ask is Before starting a second medication, have I used the first one at its full potential? Adding a medication is adding job on the owner's shoulder and that potentially can really jeopardise the compliance of the client.

And therefore, if we need to, fine, but first of all, let's check if phenobarb can use at its full potential. Have we checked that the phenobarbital concentration is at the higher target range than the trough? Is it possible phenobarbital is metabolised too quickly with the patient benefit of phenobarbiton every 8 hours?

Let's check the phenobarbiton peak and trough level. If a dog is in pitoin. If I increase the dosage of pione to the maximum allows of 30 milligramme per kg every 12 hours.

Well, if the answer is yes, I've checked all this, and there is no doubt we need to start a second lineactive medication. One possibility is using potassium bromide at 150 milligrammes per kilo every, every 8 hours. But potassium bromide takes a long time, so Freeman to achieve the steady state.

Can the patient wait for 3 months in order to have a steady controlled anaesthesia? If the answer is yes, great. If not, then we can load the patient on potassium bromide by giving 100 milligrammes per kilogramme a day, divided in multiple dosages, and then continue your treatment at 15 to 20 milligrammes per kilogramme every 12 hours.

Now, veloin can cause severe side effects, including vomiting, diarrhoea, potassium bromide is salt, and, therefore you have a lot of gas intestinal irritation. Because of the loading dosage you give, it's likely that dog would be also very, very sedated and whenever they say very sedated, I mean sometimes I need to wake them up to go out for a walk or wake them up to feed them. So, that that can be significant.

And our possibilities use levetiracetam, which can be administered at the loading dose of 60 milligrammes per kilogramme IV and then continue at 20 to 30 milligrammes per kilogramme every 8 hours. But you can see how that will increase a job for a client. About levetiracetam, there has been some publication, a systemic review on antipileptic medication efficacy, show that actually there is a fair evidence of recommending leveteracan as an adjunctive treatment.

But the consensus statement on seizure management of American College of Internal Medicine, for example, reviewed our publication and said, actually, Leviterac is really not recommended but is a low evidence of recommendation for uses of monotherapy. Instead, it's a Ione therapy to phenobarbital or potassium bromide or pito then has a moderate recommendation. The publication about levetiracetam do not unfortunately contain a lot of, of patients.

A retrospective study published in 2015, included 29 dogs starting on maintenance, levi treatment, instead, 23 dogs starting on past treatment, so treatment given only during cluster seizures. And 2/3, 2/3 of the dog had a 50% reduction in epileptic seizure frequency. The first study reporting the use of levetiracel in dog yobarbiton or phenobarbital and potassium bromide and having not really good epileptic control.

Reported 8 dogs receiving levetiracetam and 5 of his dogs were classified as responders, and this is a frequency decrease of 60%. So we're not talking about many dogs, but it seems to be helping. However, an American study, a very interesting study done on 22 dogs, which were having already phenobarbital and potassium bromide, were either start, well actually where they all started on levitiracum to start with for 4 weeks.

Then the treatment was stopped and they were given a placebo, so just. An empty pill for further few weeks. So it's not 4 weeks, it's 16 weeks.

And very interestingly, what they showed is that, yes, the dog had levitracetam had some improvement in seizure frequency. However, when you compare the time when the dog was receiving levetiracetam and the time when the dog was receiving the empty pill, there was no difference in in reduction of seizure activity. So it was not a significant benefit in using levetiracetam over placebo.

And this is probably likely due to the fact that epilepsy or idiopathic epilepsy is a waxing and waning condition, but a moment or period in life in which deteriorates and period of life in which smokequiescent. However, this is a very interesting, very, very well-prommed study. But as you see, taking decision on patient, we need to maintain on, on, on antibiotic treatment for life based on study.

On few dogs or last a few weeks, it's probably not always the correct thing to do, but that's what we have and what we have to start reasoning about the treatment. Last question, how is the best way to manage status epilepticus? Well, Epitic seizure can happen as a late event or as a cluster seizures or stage of epileus, both of which are emergency treatments or emergency manifestation.

Clusteresthesia is more than one eptic decision in 24 hours. Stteplaticus is a continuous hetic seizure longer than 2 minutes or 2 or more seizures or a cluster seizure without complete recovery or consciousness in between seizures. The clinical manifestation can be severe, and the most common type of seizure is a generalised tonic chronic seizure.

However, epileptic seizure after a period of time become self-sustaining, and unfortunately, you lose the most severe, Manifestation, muscular manifestation in what is called electromechanical dissociation. So you have animals that from generalised tonic chronic manifestation convulsions, they start developing very, very subtle twitches and the alternation. And this is an example of a young bulldog in the Statusticus that was keep having this focal little seizure that we were not able to stop.

On the right side of the skin, you see a dorsal image of the brain of this dog, an MRI scan. You see the brain, you see a, a normal brain should be this grey colour and you see that in the middle of the brain here, this area of the cortex is extremely white, suggesting that there is a significant damage, hypoxic damage to that part of the brain, unfortunately. So really, we need to stop that epileptic seizure as soon as we can.

Mortality in the dog with cluster seizures is up to 25%, so we need to really make sure we get the stop epileptic disease as soon as we can. How do we treat classic seizure status of that? Well, first of all, I said before, we need to understand what causes it.

Is it idiopathic epilepsy or is that dog, for example, being exposed to any toxic? Is there any concurrent illnesses? And then we need to get control on that seizure and stabilise any kind of secondary systemic effect.

As an emergency treatment, first thing to ask ourselves is, is there a liver disease or not? Well, if there is a liver disease, the best shot we have is probably levetiracetam. Again, we load the 60 milligramme per kilogramme slowly IV.

And then we continue on 20 milligrammes per kilogramme every 8 hours. Rare are a situation in which you need to do a cost direct infusion of the levetiracetam, but if you have the do to start with would be 5 milligrammes per kilogramme hourly and that you decrease it ideally every 2 hours. Of course, we need to show constant monitoring for, for this kind of patients.

Instead, if liver this is not suspecting, then my first choice would be going down with diazepam, either viruses, IV or perectum or 0.5 to 1 milligramme per kilogramme, and generally we go up to 3 times in 24 hour, mainly because if your patient has not responded to 3 bolus of diazepam, it's very unlikely it's going to respond to the 4th. We need to think outside the box and go to another anti-reactive medication.

So the core, you can consider a CRI of the Azepam diluted in dextrozole sine. Ittazepam is not an option, but you can use midazolam. Bizazolam can be used at 0.07 or 0.22 milligramme per kilogramme IVO AM.

And again, you can easily use the CRI of midazolam 0.3 to 0.9 milligramme per kilogramme hourly.

But another thing to consider is using phenobarbiton. If your patient, for example, is not on a first line treatment, then load that patient on phenobarbitton. You can give 180 milligrammes per kilogramme, ideally divided in multiple dosages over 24 to 48 hours.

You can even go up to 20 to 24 milligrammes per kilogramme divided in multiple dosages over 24 to 48 hours. In patients that are already on phenobarbital, you can do what is called a mini loading, so using 12 to 15 milligrammes per kilogramme, dividing multiple doses over 24 to 48 hours. And that, the aim of the loading is to bring up quickly, so over 24 or 48 hours, the phenobarbital serum level.

Penobarbital will take 30 minutes to set an antipplectic response. And in animals that are poorly responsive to, to benzodiazepine, statin phenobarbital is actually a very good option in at the same time of administration of diazepa Emidazole. Propofol, well, we, we hope never to get to this point, but if we have to, then policies of 1 milligramme, 1 to 3 milligramme per kilogramme IVO2 effect is the way forward to start with and then we continue on a CRI of 1 to 3 milligrammes per kilogramme hourly.

In this patient, we need to monitor ventilation and prepare to intubate and ventilate in case you have significant respiratory depression. And then you continue decreasing the CRI by 25% every 2 hours. Ideally, the aim of your CRI, especially if you use rool, is to have, is to have an awake animal which is seizure-free with the minimal dosage of infusion.

We don't really want a flat animal. We just need to give that much medication enough to keep it seizure-free. The other thing to consider is, is it an old patient that could potentially you found having some kind of neurological deficit?

Is it possible that that patient has an intracranial lesion and potentially bringing down the intracranial pressure, which very likely will be increased, would be another part of your treatment. And you can assess whether there is an increase in tranial pressure, if an animal is storal coma. If a pupil diameter is abnormal, for example, and isochoic.

If there is no response to light. If a dog has bradycardia and has arteria hypertension, then unfortunately, the situation is pretty bad, but that is a clear indication of increasing the kind of pressure. In most patients then using Manitol.

0.5, even up to 2, just 1.5 grammes per kilogramme would be a possibility.

Use it slowly over 20 minutes bonuses and don't use it in patients with a hypovolemic or hypenatrimic. So it's good practise to always do some blood tests before and check electrolytes for these patients. And our possibility, if you don't have a monitor, then you can use hypertonic saline, so solo 7%.

Again, we need to monitor electrolytes frequently, continue fluidapine, and we need to actually make sure that those patients don't have treatment potassium bromide. And this is because giving diuretic or sodium chloride, we actually eliminate the bromide very, very, very quickly from the system of the patient. And I think I have completed my part of the presentation and I pass over to Felicity from the talking and then I will be available for questions.

Thank you very much. Thanks Fabio and thanks Felicity is going to speak to us and obviously thank you Bet Quin for making this possible. It's been absolutely fantastic.

Felicity Bford is tech services manager at Better Quin, and he's gonna talk us through just some of the the product line and so on. So over to you, Felicity. Hi, Anthony, thank you very much.

I'd like to start just by saying a massive thank you to Fabio, for fantastic and informative webinar. I've actually had the pleasure of hearing Fabio speak on many occasions now, and I always really enjoy myself. But I also always manage to come away learning something new every time.

So, absolutely amazing. Thank you. I'm just going to talk to you guys really briefly, a little bit aboutetta Quin and Epiphan.

So you may already be aware that, Beta Quinn produce Epiphan. Which is the market leading treatment in the UK for canine epilepsy. And not only is it available in tablets, so 30 milligramme and 60 milligramme tablets, we're also the only UK licenced phenobarbital, which is available as a solution, which is fantastic for your smaller dogs, and also if you want to really finely tune your, your dosage.

The technical team at Vettaquinol, have over 20 years of experience in the field of canine epilepsy. So we're well aware of how tricky it can be to manage. And as a result, we always strive to support vets in managing this challenging condition in as many ways as we can.

So one way we do that is, is obviously by sponsoring webinars like tonight. We've also produced our latest resource for, for first opinion vets, is our online platform, which is Epilife.uk, which you can see on the screen currently.

And on this site, you can find information on Epiphan. The latest research, including Fabio's lovely study, which he discussed earlier. We also have pet owner support materials and also some interactive case studies, which you can work your way through, to help hone your clinical skills.

And tonight's webinar will also be made available on the Epilife platform in the new year. So I won't take up any more of your time because I'm pretty sure everyone's itching to ask some questions. So I am going to pop myself back onto mute and hand you back over to Fabio and Anthony.

Thanks so much, Felicity. Fascinating to see where everybody is listening in from. So we've got Eng in Singapore.

I do pop in the the box where you're listening in from, that would be quite nice just to, to see where everybody is listening in from. So from into the chat box and then any questions, put in the question and answer. So we've got Meggie in Portugal, Essex, Canada.

London, Kent, Germany, Sweden, Horsham. Wexford, Romania, Gothenburg, hell, Sweden, Isle of Man, Denmark, Switzerland, Bulgaria, Edinburgh, Galway, Llja, Greece, Chile, Slovenia, and in USA, Vienna, Poland, Germany, Italy, Norfolk. Always lovely down in Norfolk.

Thessaloniki, Milton Keynes, Czech Republic, Ireland, New Zealand, early in the morning for you, Melanie, so well done for getting up so early. And theitha in Malawi, so welcome everyone. Thanks everyone for letting us know where you're listening in from and Fabio, thank you so much for a fab webinar and obviously for Betta Queal for making it possible.

You're, you're happy to stick around for a couple of questions, aren't you? Of course, of course, very, very happy to, and thank you so much. It's, it's amazing seeing all these people from all over the world, isn't it?

Yeah, no, it's great. We've got Joo from Portugal and he said, I have a case. Obviously I know it's difficult to To help completely, but maybe just a little bit of advice.

Female beagle with epilepsy from 2 years old, not very responsive to medication, phenobarbital, gabapentin, hepatoin. After 15 months ago, she had a crisis with cluster seizuring and developed a meningoencephalitis, was in a coma for about 26 hours and slowly recovered mental state. But she lost sense of smell, hearing and partial vision.

And stop having seizures until about 2 weeks ago. So she's obviously started them, client can't afford imaging or CSF analysis. How would you manage such a case?

Well, first of all, I will check that your phenobarbital level are within the range, so make sure that you can push them as high as you possibly can. Gabapentin, there are two studies out there looking to gabapentin and anti, antitic medication, and unfortunately, results were not great. Again, unfortunately, we're talking about a handful of cases.

And you know, study with very difficult medi very different medication, very different protocols. So it's always very difficult to take a decision on this. However, possibly gabapent is not the best anti-lactic treatment we can use.

Iittoin, have you increased up to 30 milligrammes per kilogramme in 12 hours? Probably you have, but if you haven't, just make, make sure that you, you go that way. The fact that this dog developed mening encephalitis then might suggest that maybe she would benefit of some form of steroidal treatments.

So I would probably consider if we can't really afford anything else, maybe give her some anti-inflammatory dosage of steroids and see where we are going from there. Very interesting actually, Antony, if you don't mind, There are some considerations also in human whether treatment with steroids, especially during clusters that toreticus might help stopping reverberating inflammatory circuit of the brain, so potentially why not. As somebody, a wise man once said, Fabio, I never let a dog die without the benefit of steroids.

I couldn't agree more. Yeah, we've also got just a question of how long should we fast the dog before phenobarb testing. 12 hours, probably, this is what I generally suggest.

If after 12 hours you have still a very, very light in sample. Then, consider starting the patient, particularly for a little bit longer and explain the client that you know we are wasting money if you don't have a very reliable results in that blood sample, but generally no to be fair, I'm a man. If you ask to start my dog for more than 12 hours, I will already be a bit upset, but there you go.

If I need to do it and save money, I would do it so that everything would. And as far as the tube goes, just use the normal plain tube even if you need to keep it in the fridge overnight and send it the day after it's fine. How, how big a problem do you think it is of people sending them in on the serum gel tubes and therefore getting a an an abnormal results, is that a problem that the labs tell you is quite common or is it an occasional thing that bats get wrong?

. It's generally, it, it's generally not even coming from, from the labs. A lot of, practises, I know it's less common these days compared to the past. We're spinning down with the gel separating tube, the sample, and that unfortunately we break down compar of Narbiton or most of Narbiton.

So in that case is I would just say just put in a plain tube and send it. I always say, Fabbio, that if you learn one thing from a webinar and you take that into practise, then that's been worthwhile going to the webinar. So if anybody's picked up on that, that, not, not to use gel tubes, then it's well worth just for that for coming to the webinar.

So thank you for that great tip, one of many. . Veronica is asking, do you decrease the dosage of phenobarb when you change to 3 times daily?

Do you split it up over the, the 3 doses? How does that work? Veronica, you are asking the question that I was dreading when I submitted my study.

And this is because there is no guideline in the veteran literature. You can look through any book or any study. No one tells you what to do.

What you are told is you can give it 3 times a day. So it was very much a learning experience for me. And if I have the time and if you don't mind and Antony, I tell you what I've done.

Initially, I had a dove that was, let's say on arbium 30 milligrammes twice a day, and I started to give you 30 milligrammes 3 times a day. I checked the ladle that was sky high through the roof and therefore it decreased the dosage. The following case.

I had a dog with 30 milligrammes per kilogramme twice a day, which means it was only 60 milligrammes. I cut the dosage in three different administrations. So 20 milligramme 3 times a day, but dogs arrive in cluster because the the dos were too low, so.

Right now, every time I need to do it, I go right in the middle. Yeah. And as you say, you, you measure the dose and obviously you, you look at the clinical improvement of the dog or, or, or not.

Yes, always, and then you recheck your barbital level after 3 weeks. But in such a situation, do not be afraid of asking a specialist. Just get in touch with someone.

I'm pretty sure everyone will be happy to help. They're not very easy situations. Yeah, they are .

Scary cases, the sort of status epileptic as doctors. This is the next question from Sophie, who said, What dosage do we use safely intravenously with a cluster patient or status epilepticus. My book says 12 milligrammes, I presume per kilogrammes, and she said, it seems very high.

Yeah, it is very high, but what I would really suggest you do is give bonuses, instead of giving a, a, a bolus of 12 milligramme, give bonuses of 3 milligrammes per kilogramme. OK, and repeat it up to 6 times a day. So you reach a total total dosage in 24 hours of 18 milligrammes per kilogramme.

That is a very, very safe loading phenobarbital dosage. Yeah, yeah. Another question this one from Elidi, could you repeat the dosage about Keppra, please?

Yes, sure. So if you need to administer Keppra for the first time in a patient that, for example, is in cluster, you can safely give 60 milligrammes per kilogramme once. And then you follow the administration with anything between 20 to 30 milligrammes per kilogramme every 8 hours.

Keppra is a very, very safe antipyin medication, very, very safe. I think, Anthony, toxic dosages have been reported up to 1200 milligrammes per kilogramme, and I think the toxicity was sedation and ataxia. So it's a very safe antipptic medication.

Fantastic. We've got a question which I think Jessica, we've answered, you were asking about the sample for checking levels have to be run straight away. I think you, you said Fabio that it's quite right to leave them until the next morning to run.

Yeah, brilliant. So that's that one Jessica, hopefully answered for you. Fair, can diazepam be used subcutaneously?

Well, what I will suggest to you is if you need the choice, if you need to choose between interreal or IV, go interacttal because the absorption of diazepam interrectal is ever so quick. It's very, very similar and comparable to IV. You don't need to inject anything under the skin.

It's just extremely, extremely quick. So my preference would be not even subcut, but IV. Now, I don't know where this attendee lives, so I'm not sure what product they have.

I never had to give it subcutaneous to any patient, to be fair. Yeah, no, great, great answer. Thank you for that, Fabio.

A couple of people, Melena and Samuel asking about CBD oil. Any thoughts? That is a very massive chapter nowadays, isn't it?

It seems like CDB are amazing for everything. So what we know from, recent study is that CDB, CBD, sorry, are not harmful. So every time I'm approached by a client and asked about it, I would say they're not harmful.

That they actually help is still under question. There are some study that that showing that maybe actually there could be a good addition, but I don't think there is enough proven peer reviewed scientific study suggesting or pushing any vet to say, let's go with it because we're amazing. So I think it's a little bit too early.

Fantastic. I've got Anne asking a question. I, I have to ask Anne's question because she's an ex-student colleague of mine, so I would be in trouble when I next see her if I don't do that.

Is there a link between central diabetes inscipidus and epilepsy? I have a patient or a colleague 6 years old, who I've recently diagnosed with CDI that has just started fitting. Interesting one.

What, what were your thoughts? . If there is a link, I would be worried that the link is a structural disease of the brain and that it could be something affecting the hypothalamus of that dog.

That would be my main worry. A link between idiopathic epilepsy that I'm not aware of. So my worry if such a patient would be, am I actually dealing with an endocardial lesion?

Some sort of space occupying lesions to affect other areas as well it's not. Sorry about that and over over to you with that one, As somebody anonymously said do steroids have a role if you suspect the space occupying intraccranial lesion. I think you have we, yes, yes, absolutely.

Yeah, yeah. I mean, steroids can decrease very, very quickly and very well. Any kind of edoema surrounding a suspected space occupying lesion, potentially maybe also shrink a little bit in the volume of the lesion itself, so why not?

I'm, I'm all for it. And Siobhann is just asking, did she understand properly when you said, did you say that if epilepsy is not treated early, it is more likely to be refractory to treatment? What I said was that A recent study, what was found is that the longer a patient with left seizure, maybe the More tricky would be to control, so.

Potentially, yes, I think, I think it would be more on the aggressive side idea. I would say yes, I would treat earlier rather than later. That's great.

We've got Anna asking you a great question. In animals with persistent hypercholesterolemia due to phenobarbital, what type of treatment do you use? So one possibility is check on the diet and change the diet of a patient.

Check and make sure that there is not polyphagia and over feeding of any sort. Checking whether there is any kind of concomitant conditions so we probably food lands and check for any other reason for it. But apart from that, I wouldn't start any other treatment against the hypercholesterolemia.

OK, great. And Net is asking the question, Felicity, you're, you're having it far too easy, so I'm gonna pull you in here. Anne is asking, is Epiphan available in the Netherlands?

Sorry there, I was just on mute. No, to my understanding, yeah, I'm afraid it isn't licenced er over in the, the Netherlands. Epifan's only licenced in the UK and Canada.

OK, thanks. Thank you, Felicity. Catherine's asking another question that's really interesting, and I think with my dermatology ha on I I I'm, I like this one as well.

Are hypoallergenic diets useful for reducing seizure frequency and I don't know just as a sort of addendum to that question, Fabio, have you had much experience using the Purina diet which supposedly helps to reduce seizures as well. Yes, so, Yes, hypologenic diet can definitely be useful. Do they really reduce epileptic seizure?

I have my doubts. There has been, a study published by the Royal Veterinary College on the use of a diet with, would say, amino acid, in, which is the Purina diet, . So in this study, they showed that some dog had experienced a decrease in seizure frequency, .

I'm going to be very honest. I've used it a few times in some patients, and none of my clients were satisfied by the diet or we didn't have any kind of, feeling that was helping the dog whatsoever. So none of my patients unfortunately, we continued it for that reason.

OK, fantastic. We have, I think 2 more questions, . A is asking for a 4 month old puppy.

If an anti-seizure drug is absolutely needed, which drug would you choose for long term use initially? Would it be levetirootem or potassium bride? Right, so if it's such a young puppy, my question would be, is it seing because there is a congenital liver disease like a postsystemic shunt?

Is it seizing because it has a congenital intracranial disease. So I would probably, if we don't have the money to investigate it, I would lean on the safe side and I will use levetiracetam. For The initial period at least in order to check how the response is.

If a dog either relapses, then I would add potassium bromide or I would just switch completely to potassium bromide and use levity acid to stop any kind of clusters. Fantastic. I think a final question from Rasa, which is what about Topiramates instead of Lebo as a third line adult.

No, it's definitely a good options. There are not many studies out there about the pyramids, and it's not very, very commonly used, here in the UK where I work. I've been using it a few times, with good results, to be fair, but it's definitely a valid option, absolutely.

Fabulo, that's been absolutely splendid. It, it's such an important area, you know, it's a a really worrying area, isn't it, when we get dogs coming in for the clients and, and obviously also for ourselves as well and I, you know, there's been some fabulous tips in there for, for us, so I've really enjoyed the webinar and unfortunately, Fabio, the, the, the problem with with webinars is that you can't hear the tumultuous applause. But I've had so many positive comments in the questions and answers in the chat that you should feel assured that we have thoroughly enjoyed the talk.

Thank you so much. It's been really great. Thank you.

And, and thank you so much, Felicity, and obviously Betauinol for making it possible, you know, in this difficult year, it's been great that you know, webinar that we've be able to help people to still. Get their CEOs in, but also, you know, to, to keep up to date and just become better vets, which is what CPD is all about. So thank you so much, Beta Quinol, that's been so kind of you and obviously fab, fabulous talk and I will tell you the story about the fish and Padua another time.

Yes, thank you very much. Thank you for, for this opportunity. It was great, absolutely great.

Thank you, Grazi Berra. Good night buche. We will see you all soon.

Take care.