All right. Today we're gonna be talking about seizure management and cats and dogs. I'm Doctor Missy Carpentier.
I'm a neurologist in Minnesota. I currently work at an own Minnesota Veterinary neurology. So the purpose of today's talk is to really look into more of the management side of seizures, though, of course, we'll run through everything that kind of gets you to the management overall.
So, we'll go through the signalment and history of the cases that are presenting the physical and neurologic examination and what you may be looking for. We'll go through Localization, because that is key, so that you can actually make an accurate list of differentials for your patients. And then, of course, we'll go through anti-epileptic drugs, because that's gonna be the most helpful and beneficial because I know it can be a little taxing on general practitioners trying to figure out which one they should be using, and remembering all the side effects, as well as the monitoring that potentially goes with it.
So when we start, we're talking about the signalment of our patients. So signalment in history, so for our signalment and for canines and felines, when they're less than one year of age and they're presenting for seizures, you definitely want to make sure you're doing a thorough evaluation and workup. So less than a year of age, we're worried about things like what are systemic shunts, as well as other congenital abnormalities, whether or not it's within directly the brain, such as morencephaly or hydrocephalus, we're worried about inflammatory brain disease, and we're also worried about different degenerative conditions that can happen, such as lysosomal storage diseases.
Now, if they're greater than 5 years of age, again, we kind of want to broaden our horizons and they'd be thinking about things like inflammatory brain disease, potentially neoplasia, CVA stands for cerebrovascular accidents, or could they also have a degenerative condition occurring? So if you have a dog presenting between 1 and 5 years of age, that is the prime age for idiopathic epilepsy when these dogs are going to present. And then if you have a feline, just know that we used to always think cats with seizures, it was kind of bad news, but epilepsy of unknown cause actually makes up 25 to 50% of the cases.
And this is, we call it epilepsy of unknown cause because we of course don't see as many purebred cats, and so we don't call it idiopathic or genetic epilepsy, but this can be any age of cat. So you always want to work up a cat that has seizures, if you're able to with a more advanced diagnostics, however, if not, just know that. Up to usually I say about 25% or a quarter of them will actually have epilepsy of unknown cause, and you'll manage them similar as you would a dog with idiopathic epilepsy.
So other key kind of clues that you're gonna be looking for is the breed, when they're coming in, right? So border collies, Labrador retrievers, Australian shepherds, those are your poster children for idiopathic epilepsy, definitely have also added in, you know, other dogs as well to this, and one of those is the French bulldog. Initially, many, many years ago, anytime I saw a French bulldog that was having seizures, it would be inflammatory brain disease until proven otherwise, but now they are definitely becoming a breed that we see quite commonly for idiopathic epilepsy.
And then if I have a pug come in, let's say with seizures, then for me I'm gonna be more worried about inflammatory brain disease. So there's certain breeds that you're gonna see, they're gonna kind of move idiopathic epilepsy higher on your list, and then there's other breeds that are gonna come in that will make your list a little bit longer and maybe put you put idiopathic epilepsy lower on that list. So the history I would say is honestly gonna be one of the most important parts, because you're gonna be able to gain so much information from the owners to really already start making your list of differentials and knowing what it potentially could or could not be.
So you want to have the owners describe the actual event that they're talking about that is a seizure. We see many. Patients, and I'm sure you guys have too when the owners bring them in and they say, my dog just had a seizure, my dog is having seizures, and they'll show you a video of something and it is not.
Maybe they are vestibular, maybe they have neck pain, or maybe they're an idiopathic head tremor. So you just want to make sure you're getting that accurate history, and better yet, everybody has a phone on them now. So if you're able to actually get a video, that will absolutely be helpful.
And you want to go through with the owner, the different stages that we can see. So we have the pre-ecty icy and the post ecty stages. So for that pre-icy stage is what we consider a symptom.
So sometimes what they can have is this apprehensive behaviour, they can be pacing, they can be agitated. And it's very common that they're seeking out the owners. I have many owners that know when their dog is about to have a seizure, even not immediately.
It can be that day at some points because their dog starts just being snuggle bugs, not wanting to leave their side. My own personal dog would seek out my husband, and that would be the only time that she would. Seek out my husband over me.
So there's definitely certain key things that you can be looking for to know if they're gonna have a seizure. And important with this too, because if some dogs are able or start to show these signs, well, in advance of the seizure, it actually can be helpful because you can start instituting kind of what we call cluster buster therapy at this point to try to prevent a seizure from occurring. Now the seizure itself, there's many different types that we can see in dogs and cats.
You can have tonic clonic seizures, you can have clonic tonic, pure tonic, atonic, myoclonic, oral facial, which is a huge one in our kitties. Petite mal seizures are very questionable in the animals. I think a lot of the times we call something a petite mal seizure, and it's actually gonna be a focal seizure, so.
Petite mal seizures are managed very differently in people, so I would kind of, if you have that in vocabulary, you can probably just Get rid of it and just put in focal, just because that's likely what we're dealing with. With focal seizures, we're gonna dive into those in a little bit here, but you're always looking for lateralization with those seizures, whether it is facial lateralization or forelimb. And then fly biting, we'll also discuss this as well, because is it a focal seizure vers is it sensory versus an OCD component versus is it GI disease.
And so we'll touch base on that one as well in a little bit. But Regardless, the type of seizure is gonna tell you, you know, what you may be listening or looking for with the owners. So with a oral facial seizure, they're not usually gonna lose consciousness, but with a tonic clonic or usually a pure tonic, those ones you're gonna definitely be looking to ask the owners, OK, were they conscious or not?
And then what sort of seizure, of course, so then you can classify it. Was it tonic then clonic, was it an oral facial? You wanna ask about autonomic dysfunction.
So was there urination, defecation, salivation, then you want to know the length of the seizures. Most seizures last less than 2 minutes. So if you have an owner that's coming in and they say my dog had a 10 minute seizure, definitely kind of push them to tell you.
Exactly what was happening during that time, because one, they might be confusing some of the pre-ey and post-epy with that seizure, 2, if it was truly a 10 minute seizure, then we need to get on that and treat that immediately, cause that's unfortunately very dangerous. And then the other thing is gonna be If it was that long as well, is it, is it something else? So if it really was 10 minutes, this dog was acting quote unquote off, well, maybe it wasn't a seizure or maybe it was something else that was going on.
Owners also, when their pet is having a seizure, I, I can personally say that I probably said my dog's first seizure lasted for 10 minutes, and it was probably 30 seconds, but it was the longest 30 seconds of my life. So just take that into, into note as well. You want to know about the time of day?
Is it early in the morning, when they're sleeping, and is there any activity associated with it? Because our one of our other big differentials for these is gonna be, it could potentially be a sinkable episode. If they're sleeping or resting, a lot less likely, and that's more classic for our seizures, but if they're running around in the backyard, backyard, excuse me, and then fall over, then definitely would have more of a sinkable or cardiac events higher on your list, and they can look very similar, so it can be very difficult to tell the difference between the two, and so that's why even if you have a video of a dog with, you know, a singable episode and they are You know, clonic in it, it can be very difficult to say, OK, is this a seizure or syncope, and that's why that history leading up to the event is very, very important.
Now the post dicty period, what we're gonna be looking for is, do they have altered mutation? It can last for hours, normally it'll be hours, but there are some animals that will actually, you know, have it for days. Are they confused, disoriented?
Unfortunately, we'll see a lot of dogs that have aggression as well postticly, they can be blind. Restless pacing, ataxic, and they can be polyphagic and polydipsic. If you think about it, they just used up so much energy if they just had a tonic-clonic seizure.
All of their glucose stores are, are now pretty much gone, so they need to replenish them is the best way to think about it. And so you'll also want to listen to these signs because This can be a key where if you're not sure what the owner is describing as a seizure or not, you can then look for the pre or post icy state because if there's post icy tendencies with these episodes, then you're more likely gonna lead towards, OK, I don't know for sure if this episode was a seizure or, you know, not because it's so atypical. Could absolutely be atypical epileptic activity, but then you add posting to it, post it signs into it.
Yeah, afterwards, they're off for a couple hours. They're, you know, just kind of pacing, wandering. They want to eat a lot and drink a lot, then you'd be more concerned that it was truly a seizure.
And in that post-y, you know, state, here is a dog who's Post it after experiencing a seizure, and he's just so a little twitchy, you know, just very disoriented, how you could tell he's not really sure what's going on. He also was having difficulties seeing, you can't really note that in here, but you can tell he's just kind of laying there like what just happened? He's trying to get his wits about him again.
Now other pertinent information that you want to be looking for is the age of seizure onset. You wanna be finding out how many seizures, so the total seizures, the seizure frequency, the length of seizure, the toxin exposure, if there is any, behaviour between seizures, history of trauma, and then AEDs currently being administered and have the red blood levels or improvement, cause it's not uncommon owners with seizures, you're gonna see a pet who was previously, you know, managed with somebody else and they've now moved and now you have this patient and you're kind of taking them over. So just make sure you go through these questions.
The history of trauma one is definitely one that, I try to just remind people to ask about, cause if you have a 2 year old dog, you know, he's healthy, coming in for seizures, it's a trauma is not gonna be something that's gonna be high on your list. However, you could ask because it trauma at any prior stage. Whether they were, you know, bit on the head as a puppy by the larger dog in the home or the neighbour or some sort of trauma that happened cause they can present with seizures after the fact, seizures after the head trauma, even years later.
So focal seizures. So when you're seeing a focal seizure, it's an abnormal excessive neuronal discharge in specific regions of the brain. And we also used to always consider this to be unfortunately associated with the sinister cause, because we would think it would be a very specific area of the brain, therefore, usually it's going to be unfortunately a mass or severe inflammation or something along those lines, but that's been disproven and it's very common that we will see dogs and cats with focal seizures.
So when you have these, you wanna know what part of the body is involved. Is it the face which is most common, oops, sorry guys. Oh my video doesn't wanna.
Other one doesn't want to work, so we won't be able to start this one for some reason, but is it a limb? Is it and how is their mentation? A lot of times, of course, these dogs are conscious and Able to, you know, look around, but they are usually fearful, and we'll kind of dive into focal seizures and fear in a second here, especially the research they're doing in human medicine.
And then are they lateralized? They should be lateralized with the focal seizure, so that's also something that can be really helpful to you when you're looking at these patients and it's always some facial twitching on the right side, you know, that they're associated with, then that'll be really helpful. Now, here's a video of a cat.
Who's having a very classic focal seizure. This is very commonly how they will present. You can see that that right forelimb is involved, and you can also see that, I'm gonna play it again for you guys, when you're watching the face, that right ear will also twitch back and the right side of the face was actually grimacing backwards as well.
So this is a very classic. Kitty focal seizure that they will present with. And focal seizures can occur in three ways.
So they can be isolated events, so it's the focal seizure, and that's kind of facial twitching, and then it's done. They can have focal seizure with impaired awareness, where they are conscious, but they're not 100%. Your concerns that they may be going into losing some form of consciousness and whether or not they're just, you know, really Confused by what's occurring, but we actually believe they are starting to have a little bit of impaired awareness with these types of focal seizures.
That could be very difficult for us to know and for us to be able to determine. And they can have focal progressing to a generalised seizure, and this is the most common type of epilepsy that is actually observed in dogs. They'll start with a focal and then go into a full tonic-clonic.
It's gonna be very commonly what we'll see whether it starts with facial twitching and then it extends to a forelimb and then we go into a full tonic-clonic seizure. Now focal seizures and fear. So approximately 15% of human patients experience fear during an aura.
So there is an association between anxiety and epilepsy, and it's becoming an increasing focus point. So paroxysms of sudden stereotypical behaviour occurring 80% of dogs with focal epilepsy and are interpreted by owners as fear or anxiety. So many publications out there are discussing seizure-related fear or anxiety.
They're really scarce in bed met. It's becoming a huge, huge topic in the human, medical field, and so it's interesting to see how it's gonna Transpire in the veterinary medicine because definitely I have some dogs who are just anxious and fearful and they are the ones that, you know, absolutely they have seizures and are they related in some in some regard. So they have found that paroxysmal behaviour abnormalities and fear in bull terriers, .
Occur with bull terriers that have focal seizures with impaired awareness. They've also seen juvenile onset focal epilepsy. As well, and then if we've had with an increase in reports of innerectal fear and anxiety related behaviour occurring in dogs after IE diagnosis.
So new research is not far away. I think since COVID and the behavioural changes that we've been seeing in our pets as well. I don't know if that has, you know, a role, but I definitely see more patients and more owners asking, you know, my dog is just always anxious, my dog seems fearful as we're treating their idiopathic epilepsy, and so we start to look at, do we need to try to manage these behaviours because could they be associated or driving or contributing to the seizures that they're having in some way.
Now, oral facial seizures are very commonly in what you're gonna be seeing in kitties. So they're gonna have oral facial motor signs, so sometimes they can be almost chewing, they're gonna be salivating. Usually it will be laterally dominant, so you're We're gonna see one side of the mouth seems to be more active than the other, and the hypersalivation is huge.
And so with our kitties, whenever we have oral facial seizures, we want to be thinking about a condition that's called feline limbic encephalitis. Which is also hippocampal necrosis complex. So what happens is this is actually an immune-mediated disease where antibodies are formed against voltage-gated potassium channels.
And so what happens is they have these secondary to that, the oral facial seizures. And what's really important to know with this is because it's an immune media in origin, we need to, of course, be managing the seizures with anti-seizure medications, but these kitty. Also needs some form of immunomodulation.
And so whether, most commonly we'll use steroids, but other medications can also be used. But it's important if you have a kitty with oral facial seizures. If they're not, owners aren't able to do a full workup.
You start them on anti-seizure medications and they're not improving. It could potentially be feline limbic encephalitis, and therefore, you may want to add in a low dose of steroids, anti-inflammatory dose. Usually don't have to go too crazy high with immune-mediated.
Just so that we're able to know, you know, to help control in case this is present, you're able to get control over the underlying pathology. This is a study that came out really describing this. It was back in 2011 about complex partial cluster seizures in cats, with oral facial seizures, and it's just really nice because it is just describing the first clinical presentation of these cats and So what they were presenting with and so all the icy signs that they can have as well as the interectile and postectile signs, and then the abnormalities at the first clinical presentation.
So we don't need to run through all of these and it is there for you guys to evaluate if needed or if interested. Now fly biting seizures are kind of a big topic of discussion, so this is a dog who presented. For fly biting seizures.
And you can see the dog is just literally looking and trying to bite and grasp anything in the air. Now, fly biting seizures themselves in regards to their underlying pathology. Is, is it a seizure?
And then there absolutely are epileptic fly biting seizures, but I think more commonly what their fly biting is secondary to is GI disease. And so whenever I have these cases, I will, and their neurologic exam is otherwise unremarkable. I what I'll talk to the owner about is treating usually GI disease first because it's so much more common that they're suffering from reflux or something along those lines that's making them do the fly biting than true seizures.
That dog that was shown on the previous slide had a pretty significant meningitis, and so we know that dog was having actual epileptic fly biting activity. However, whenever I have these cases, I always look at their GI first. And so with the gastrointestinal disease, multiple studies evaluating fly biting and other stereo.
Typical behaviours, they're able to relate the behaviours to underlying GI disease. So whether it's esophagitis, GERD, gastritis, if anybody's ever had esophagitis, it is so painful that it makes sense that these dogs are just, you know, so uncomfortable and they're trying to figure out, you know, what exactly is going on. So usually if you're looking at GI disease treatment, a lot of times what we'll discuss doing is an elimination diet and then starting omeprazole and a low dose of prednisone.
That of course is making sure that there's no, you know, true ulcerative lesions. But usually that'll be kind of the first steps in what we do, and then, of course, you can add in sucralfate, famotidine, metoclopramide if needed. But the elimination diet is oftentimes what we'll start with just to see if that will help.
Adding a little omeprazole never hurts either. But usually we'll do that to see whether or not we're able to eliminate or significantly decrease the fly biting episodes. So usually we'll treat for GI disease first.
Ideally, you're gonna treat for 2 to 4 weeks of treatment. If no improvement, then you can definitely consider starting an anti-epileptic drug. If the patient has a history of other types of seizures, then of course, I'm gonna be focusing on seizure control as well, but it's also not wrong to treat for GI disease in case there's something else going on, just because fly biting seizures.
Are definitely pretty rare of all the seizures that we see, and it's more common that they're gonna be secondary to GI disease. So we just, of course, want to make sure that we're treating the right underlying pathology. Now other conditions that owners can say, you know, is potentially is this a seizure activity the owners can think is congenital vestibular dog.
So you're gonna see what this dog here, he was presented for. Inducible seizures, and then when we saw him, we found that, OK, he's actually having vestibular episodes, and he was a congenital vestibular pup, super adorable and cute, and so that was not seizures, and we used to always think that vestibular disease is, you know, or vestibular signs is its own facet And then there have been cases though that made us question, could they actually be seizure activity. So just to make sure that we make seizure control a little more complicated, we have actually found the study just came out recently about clinical features and outcomes of 10 dogs with suspected idiopathic vestibular epilepsy.
So these dogs were presenting with an acute onset of vestibullary ataxia, with lateral drifting, rolling head tilt, and horizontal nystagmus, and then the signs of the vestibular disease lasted less than one minute to a maximum duration of one hour, and it had an abrupt ending with immediate return to normalcy, and the dogs appear responsive to the owner's voice, and pugs were overrepresented in this study. So I think it's important where if you have an owner presents a dog with, you know, these vestibular disease or you see a video of this cute onset of vestibular signs that is better, it only lasts less than a minute, and they have that abrupt ending and then they recover quickly, the dogs appear responsive, then I would have this higher on my list too as a potential vestibular epilepsy patient. That is new, that's coming out.
So just something to keep in the back of your mind too. If it's, you see a patient that keeps having these vestibular episodes, maybe it's a younger dog, it doesn't seem like this dog can keep, you know, it doesn't fit with anything that classically is gonna cause vestibular disease cause that's usually not gonna just come and go immediately in less than a minute, then me thinking about vestibular epilepsy. Syncope is just kind of a reminder that we definitely want to have this on our list of differentials for what these episodes could be, because I think one of the hardest things is actually knowing are our patients having seizures or not.
And so just remember that this is something that when you see these episodes, you're first gonna say the biggest question of course is, is this a seizure or not, and always having syncope in the back of your mind. So The physical and neurologic exam, if the patient's presenting for seizures, you already know the forebrain is involved. That is where our seizure activity is going to be driven from.
But now we need to find out if any other areas of the nervous system are involved. You're gonna do your standard physical exam. You're not just gonna jump right to your neuro exam, and you want to be looking for things in young dogs, are they pretty small?
You know, do they look like they're kind of a quote unquote poor doer? Having poor growth, in which case then we definitely wanna be looking at their liver to see do they have a poor systemic shunt, or are there other findings that have you concerned? Is there a dome shaped skull, in which case we're more worried about hydrocephalus, so making sure you're doing that full physical exam as well.
And then you're gonna be doing your neurologic examination because you want to be able to neuro localise these patients. So, like I said, you already know in their seizure activity, regardless of the underlying pathology that it is being driven from the forebrain, OK? And then we need to know, are there other areas involved because if we have other areas of the nervous system involved, other areas of the.
Brain or potentially are myelopathic, so say a C1 C5 versus a C62 myelopathy, then we're gonna push this patient into more of the multifocal neuro localization, which is going to change definitely our treatment plan as well as our of course, first and foremost, our list of differentials that we're gonna be having for this patient. So differentials that you can have, the way that you're gonna come up with your differentials is of course neuro localising. So you need to know if you are going to be solely neuro localising to the forebrain, or then are you gonna be having a multifocal neural localization.
That's really what you're gonna be looking for in these in these cases. Cause you already have the forebrain, you already have the brain involved. So then the biggest thing is, are there other areas of the nervous system involved?
And it's necessary to do this so that you're coming up with your most accurate list of differentials. And so this is a list of some differentials. It's not an exhaustive list that you can have using our damn V scheme.
Just so that you know you can go through this list and have it so that you can have certain differentials on your minds, and then you always want to be making sure you're making this list and you can of course order it, put it in order of highest to lowest for what you're thinking is going on, but that's a good list that you guys can have. There, because we also wanna be remembering that, you know, if we're not gonna be able to do full diagnostics on these patients, it's good that we're able to have this list so it worst case scenario, we're able to at least treat for the treatable, treat for the most likely. So on that neuro exam for just kind of some little information I call it the tidbits, some things that can throw you off, is that if you have a patient that's presenting to you within 24 hours of having a seizure, don't be alarmed if there are some mild behaviour changes, if there's inconsistent menace, if they're a toxic, but it's the signs should be improving.
So there are some dogs that can have some pretty significant postdictal signs and so The main thing you're gonna be looking for is improvement and that they're not getting worse. And so overall, what you're gonna be looking for is any evidence of other neurologic deficits, right? So for brain dysfunction, other things you might be looking for, circling, a head turn, CP deficits, cranial nerve deficits.
So these are things that you're seeing the patient, let's say, hasn't had a seizure in a week or so, but they're showing these signs. Well then we're gonna be worried about there's something more going on in the forebrain. Than just likely idiopathic or genetic epilepsy.
We're gonna be concerned for actual structural disease. Now, if there's any evidence of spinal hyperesthesia, you're immediately gonna start worrying about inflammatory disease of the nervous system, because that would involve, that would be our multifocal neuro. Localization.
And one of the big things that we would be worried about would be inflammatory disease. So our meningoencephalitities of unknown aetiology versus there can be infectious ideologies as well. But you definitely would want to have this on your list for your patients that present for seizures with spinal hyperesthesia.
So, here's an example of a four-brain dog, very classically, what you will see. So this dog presented to us for seizures. However, he also He was doing this pretty much endlessly, right?
He just is gonna walk until he finds something that stops him, and then if that bar wasn't there, he'd be turning to the left and taking these wide aimless circles. And so this is very classic for a forebrain dog. And then for another example, we have our multifocal.
And so this kitty right here, unfortunately had a multifocal neuro localization, very much so was weaker on the left side. I always call that my, the sexy leg, because those slick floors actually can help you. So this four friends, actually had a CNS lymphoma and So he had many different lesions throughout both the brain as well as the spinal cord, but his presentation was seizures with these neurologic deficits as well.
So, diagnostics that you're gonna wanna be doing for these patients. So these patients come in, you've done your evaluation, you have your list of differentials, and so commonly what we'll talk about based on, of course, what your list of differentials are, is doing a CBC and chemistry profile, some form of a liver function test, whether or not that's bile acids or ammonia, so that you're. To make sure your liver is functioning appropriately, plus or minus thoracic radiographs based on what you're finding with your patient.
Same with an ultrasound. And then, of course, the gold standard is gonna be doing an MRI and spinal tap. For those of you that have not seen a spinal tap, this is me obtaining spinal fluid from a dog.
Of course, they're under anaesthesia because no dog in their right mind is going to do what this dog is doing without it. Very commonly we'll do AOTAs, or what we call high taps, to be able to obtain the CSF, especially in our seizure patients. And so we're just gonna slowly advance the spinal needle and then you will see that we're gonna collect.
Approximately 20 drops of spinal fluid. The spinal fluid should be looking nice and clear. It should look like water.
Basically, it's even if you have inflammation going on in the nervous system, unless there's more than 500 cells per microliter in that sample, it's still gonna look normal, so you always, always, always are gonna be submitting the spinal fluid. So, you have your list and then you're trying to decide when do we start an antiepileptic drug. So the 2015 ACIM consensus discusses when we should do so.
So if there's an identifiable structural lesion presents, so you've imaged these patients, they've only had one seizure, but you're finding they have a, unfortunately, they have a brain tumour or they have inflammatory disease, or they had a cerebrovascular accident, that's definitely when you want to start them, or if they have a history of prior brain disease or TBI. So even if they had a TBI a year or two ago, they present to you for seizures, you definitely want to get them started, even if they've only had one seizure. So if they have acute repetitive seizures or status epilepticus, which is that icy period for greater than 5 minutes or 3 or more generalised seizures within a 24 hour period, and then kind of the biggest baseline and the one most commonly that I find people wanting to know is when do I start for those, you know, patients that aren't you know, luckily aren't having the status epileptica, so the cluster seizures.
My kind of cutoff is gonna be if there's two or more seizure events within a 6 month period. That's when we want to start anti-seizure medications. .
And then if there's prolonged severe, unusual postecttal periods, I also will start anti-seizure medications, especially in those dogs that are really aggressive. After the fact, that's a state though when you really, really want to have a heart to heart discussion with the owners because even starting these dog on anti-seizure medications, you're not gonna be able to stop that postnatal period. It's going to happen.
And if they're really aggressive, you, of course, want to make sure that both the owner and and the family members are safe as well as other animals in the house. So that's having a heart to heart. I definitely, you can mitigate those signs, but you're not able to completely get rid of them.
And so I don't want people thinking that, oh yeah, well, sorry I'm on meds and they're not going to be aggressive anymore. You definitely want to continue to be, you know, being as safe as possible. So, for epilepsy, approximately 0.5 to 5% of all dogs evaluated at veterinary referral hospitals are being evaluated due to epilepsy.
And so 25 to 30%, so a quarter of those dogs are gonna be refractory, and commonly we're gonna see that in our Australian shepherds, border cos, collies, Belgian Shepherds, and then on the rise, definitely our Labrador retrievers and French bulldogs, they're becoming a little bit of our trouble children as well. And there is an associated 25% mortality rate in dogs with cluster seizures and status epileptics. That's why it's so important that we get these dogs, or attempt to get these dogs under control as best we can.
No, anti-epileptic drugs, so we're looking for when we're starting an AED is of course we wanna be looking at getting seizure control, but the other kind of main component to this is the side effects of the medications because of course, we want these animals still to be able to have a great quality of life and if they're just a Talking zombie, but not having seizures, well, is that really fair to them? And is that fair for the owners? A lot of owners aren't gonna be satisfied with that.
And if the owner isn't satisfied, you're not gonna be able to do your best to control the seizures. So, definitely paying attention to, you know, how the owner is feeling the pet is doing with the medications because you don't want to have kind of a frustrated. Owner because then a lot of times they're just gonna want to stop giving the medications and we don't want to do that.
So you just got to find that happy medium, and so are the happy middle grounds. And so when we are starting an anti-epileptic drug, there's two main ways that our drugs are gonna work. Option one that we can do, or the one type is that we can increase inhibition, or the other option is we can decrease excitation.
So here is an example. Of, or a chart, excuse me, of the most common medications, anti-epileptic drugs that we use and how they work. So if they're working in increasing inhibition, they're working on our GABA receptors, our SVA2 receptors and pre-synaptic calcium channels, versus if they're decreasing excitation, then they're usually going to be working on our voltage-gated sodium channel.
And our glutamate receptors. So here is just a chart I think it's really helpful to have for you guys. Because a lot of times if I am starting medications, I like to try to think about how one medication works and maybe then, can I add in a second that works differently.
If I need to be adding in a second, clearly, I don't have great control. And so is it beneficial then to try to start a medication that works. In a different avenue, which maybe would be able to help our overall control for that patient.
So phenobarbital, the method of action, is it decreases seizure onset via enhanced sca receptor activated chloride conductance. It also works by decreasing seizure spread via reducing the current through the calcium channels and therefore reducing glutamate mediated excitation. So, reminder, when we're starting this, it's the majority of it is metabolised by the liver.
A third is excreted unchanged in the urine, and it's rapidly absorbed within 2 hours with max plasma concentrations in 48 hours. So the doses that we're usually gonna be starting with in dogs, you want to be starting at 2 to 3 makes per keg by mouth every 12 hours. Cats 1 to 2 makes per keg by mouth every 12 to 24 hours.
So some cats can actually handle this well every 24 hours, which a lot of owners like cause they can have a little difficult time killing their cats, though in really severe seizure cases, I find that they'll still need it every 12 hours, but that's just something to keep in mind. And of course, we're gonna be adjusting the dose based on seizure control, the drug level, and side effects. Now, you can load these medications as well in really severe cases.
I don't commonly load them unless they are really severe in hospital, . Having cluster seizures, mainly because the side effects that they can experience can be pretty significant, and owners can get really discouraged, but it is an option that you can for sure do is load them basically it's a 16 make per cake dose that you're gonna give to them over 24 hours. So most commonly what people will do is do a 6 make per cake dose and kind of IV or orally and divide it up through those 24 hours, so every 4 hours or so.
So you can definitely do that. I just saw a lot of owners, I think, have a hard time with the side effects. So side effects that you can see would be behavioural.
You can have hyper excitability, they can be restless, or more commonly they can be sedate, PUPD, polyphagia, mild ataxia, immune-mediated neutropenia, thrombocytopenia, or anaemia, and this is reversible and normally you're gonna see this within the 1st 6 months of dosing. I hadn't had one of these cases in, gosh, probably 7 years, and I just recently had one, so it is important to remember that you need to be checking blood work on these patients. They can have idiosyncratic hepatic reactions, and these are rare, so this is different than the kind of long term pheno.
Effects on the liver that we think about. And so what can happen is if we have a rap, we'll have a rapid elevation in ALT and your bile acids, and so again that's different than the long term hepatic side effects and so those that's when you're gonna be with these idiosyncratic reactions, we're gonna be stopping the phenome immediately. Superficial necrotizing dermatitis is very rare, is erythema multiforme, but if owners report their dog is starting to get skin lesions when they're on phenobarbital, you definitely wanna be looking at it and addressing it.
To make sure it's not one of those potential conditions. Now, long term complications, physical dependence, functional tolerance, and hepatotoxicity. It's definitely gonna be, of course, the big one as well.
So usually depending on what lab you use, they can go up to 30 is the high end, 35 is the high end, 40 is the high end. We find that dogs that are have a phenobarbital level greater than 35 are long term are at the highest risk of potentially developing hepatotoxicity later down the line. If the level suddenly jumps with no changes in dosing, you want to confirm the results and then you wanna start looking at the liver cause that patient may be starting to have a difficult time metabolising the phenobarbital, because that is the earliest indicator that the liver is starting to have a hard time.
You may not have elevations in liver enzymes and no other signs. So if all of a sudden that level jumps and you confirm the doc hasn't gotten any extra doses, there's no confusion on the dosing, then you need to start backing it down. Monitoring.
So usually kind of in general, what I'll do is 2 to 3 weeks after starting phenobarbital, I will check a phenobarbital level and I'll do a CBC and liver profile. And cats, I'll wait 2 to 4 weeks after starting and usually closer to that 4 week time period because they take a little. Longer to get up to therapeutic levels.
Same with them, CBC and liver profile. And then anytime you change the dose, you want to be checking a phenobarb level 2 weeks later. So every 2 weeks after a dose change, and then kind of chronically, I like to get a level every 6 months.
And for monitoring, the most important Avenue or kind of The timeline for this is that you just want to keep the timing consistent for when you're getting that phenobarbital level. A lot of people will advocate that it's gonna be first thing in the morning prior to dosing, to keep it consistent, but for a lot of people that means that it's gonna be a 50 a.m.
Blood draw, and I don't know very many people that are gonna want to do that, so it just isn't realistic. And a true sample is suggested. However, comparing samples from the same or very similar sample collection times is most important.
And in regards to peak control samples, it's really necessary only for animals in which a shorter half-life is expected. So you may need a shorter dosing interval, maybe necessary to maintain appropriate drug concentrations throughout that dosing interval. So that's the only time that I end up doing, .
You know, peak and control, peak and trough, depending on where you are and how you want to say it, level at that point. So the main thing, phenobarbital levels just try to make it consistent for long term, say, OK, this dog usually has a phenobarb level around 10 a.m.
Or or what have you, you just try to keep it around the same time. The therapeutic range that we're looking for is gonna be for dogs, 20 to 40. Is what we talk about as the therapeutic range, but I personally don't like to go above 35, unless I have a really severe case and owners are kind of on board for having the level a little higher understanding the risks to try to get better seizure control.
And cats 10 to 20 is the recommended therapeutic range. I definitely have had cats where I've had to go higher on this dose, and they tend to handle it OK, but that's usually what you're kind of looking for getting. And one thing to look forward to is if all of a sudden you have a 20% drop in your level, usually you wanna be talking to the owners and say, hey, you know, do we, are we not giving the medications as we thought it's very common one owner thought.
You know, the other family member was giving the medication at night or what have you, and, you know, it just was a confusing, it was kind of a, a mishap and the dog wasn't actually getting their evening dose or something along those lines. So you just wanna make sure that you're talking to them if you do have a significant drop in the level. So phenobarbital, other things to know is that it can decrease total T4 and free T4 and increase TCH.
So phenobarb very commonly will make it look like you have a hypothyroid patient even if you don't truly. It does not affect ACTH or your low dose de suppression test, and your ALP will elevate most commonly in dogs, and your ALT most commonly in cats. So if I have a dog on phenobarbital, I expect that ALP to go up.
If it isn't up, it almost makes me more suspicious than when it is up. So just know that that that is very common and it's expected that it's going to occur. So potassium bromide, this has been around for a while.
It is a great anti-seizure medication, so it decreases seizure onset via enhanced GAA activated chloride conduct conductance, excuse me. So bromide replaces chloride in that extracellular space, and the chloride channel is more permeable to bromide over chloride, OK. So excretion wise, it is renal, but what we want to note is that if we have increased chloride in the diet, we're gonna have increased elimination of bromide.
So I don't necessarily Kind of change an animal's diet, but this is important to know that if there is a diet change, it definitely can change the excretion level of that bromide, and so we need to be following up with repeating bromide levels. So the dose is gonna be 40 to 60 Ms per pig PO in dogs only. So kitties do not get potassium bromide due to bronchial asthma and pancreatitis that they can develop.
So potassium bromide is only for your dogs. You can divide it into BID dosing to decrease the GI side effects, and that is something that I commonly do. So I take that 40 to 60 make per cake dose and I divide that daily dose into divided by 2 so that they're getting that dose over every 12 hours.
And then loading, you can also do 400 to 600 makes per keg over 5 to 7 days. So say you're gonna do 100 makes per keg every 24 hours over 5 days. I do not commonly low potassium bromide because the side effects are pretty significant and owners usually get very dissatisfied pretty quickly with the medication and then they don't want to continue it.
And then again, potassium bromide is not for cats. So biggest side effects, you're giving these patients a salt, so they're gonna be PUPD, lethargy, mild ataxia. I find my larger breed or giant breed dogs are definitely will become more atoxic with potassium bromide than my smaller breeds, pancreatitis GI intolerance, and some animals will become aggressive.
So monitoring for potassium bromide every 2.5 to 3 months after starting the medication. And you may need to adjust this if you did end up loading, you may need to check it sooner, but 2 to 3 months after any dose change or diet change, you also want to be monitoring the bromide level.
So sample time anytime during the dosing interval, it's potassium bromide stays around for a long time, so it doesn't matter when you take the sample, and I recommend checking it every 6 to 12 months long term. And for monotherapy, you're looking at a level of 1 to 3 Ms per mL. If you have them with phenobarbital, usually will shoot for like a slightly lower level of 1.5 to 2.5 mg per mL, mainly because usually with potassium bromide, excuse me, usually with phenobarbital, you're gonna be able to have a slightly lower dose that's going to be needed.
So, and then also to help mitigate some of the side effects we can have from both of these medications together. Other tidbits you can have if you need to decrease the levels rapidly, give IV sodium chloride cause it will have them excreting that bromide pretty quickly. If you have increased chloride in the diet, increased elimination of bromide, so just remember that if you have high salt diet, they're going to be eliminating more of that bromide.
So again, I don't necessarily dictate their diet, but I stress the importance of keeping their diet consistent, and if they need to change that diet, totally fine. We just need to make sure we're rechecking that level in 3 months. So levetiracetam, how levetiracetam works is it binds the synaptic vesicle to A, so it's the SVA2 protein on the presynaptic terminal, and it modulates synaptic vesicle fusion and neurotransmitter release, most importantly are glutamate.
And so mice with no SVA2 are epileptics, and so we know this plays a role. There's many, many other theories out there with how levetiracetam works, that. It just keeps kind of going around and around in a circle and how it works.
So there's many theories out there, but the biggest way that it works is we believe that how its effect on the SVA to pre-synaptic terminal. So it is also rely excreted. So levetiracetam, the dose, the kind of minimum dose that you want to be looking at for regular levetiracetam is 20m per kg PO every 8 hours.
So remembering that regular needs to be given every 8, and then in regards to extended release. 30 mg per kg PO every 12 hours. If already on phenobarbital, you do need to increase the dose.
So this is because of the induction of the serum hydrolases, but it doesn't have anything to do with the cytochrome P450 system that we always think about with phenobarbital, and it doesn't inhibit or induce hepatic enzymes. It just has to do to what happens with the serum hydrolases. So with in regards to the dose of levetiracetam, it is extremely safe.
So I know many other neurologists, including myself, and many patients that will be on doses up to 60 to 80 makes per kg. To 8 or 12 depending on if they're on regular or extended release. So it is very safe, and that's also one of the reasons that we love it so much.
Side effects are minimal, so some owners report sedation and GI upset, but it's extremely uncommon, but definitely sedation is gonna be one of the main ones that we're gonna see based on that dosing that we're using, the higher the dose, and usually we'll start to see more of these side effects. So monitoring that's reported is that what's important to know with levitracism is that the steady state for this drug never truly occurs for dogs, and it may not in cats because the drug does not accumulate with each dose. So it makes testing really complicated cause there's a large degree of fluctuation of the drug concentration during the dosing interval.
So if you do choose to monitor, they do recommend a peak in trough level when levetiracetam is started, so you can determine your patient's half life. Two weeks after starting or discontinuing phenobarbital, as you do want to also check a level if you're choosing to do so, because phenobarbital decreases the half life of levetiracetam, and the proposed levels are 5 to 45. Now, I'll be very honest that I don't commonly evaluate these levels due to the large degree of fluctuation that can be present in one, you know, obtaining levels in the same day.
The cost of the test and the safety margin of levetiracetam, like it's so safe that patients are handling it well. I really don't, I don't worry too much, . About whether or not I have I maxed out this drug in regards to where the level is at.
Now definitely if I have a patient on 80 mg per kg of regular levetiracetam, TID, and they still don't have seizure control, I'm gonna be looking for another anti-seizure medication because then that clearly is not cutting it, it's not gonna do much more if I keep going up. So I say I kind of max out each drug, but I usually won't go much higher than 80 makes per kg on Keppra because you're not gonna get much more benefit, just more side effects. So other tidbits with status patients or cluster seizures, patients you can do intravenous or rectal administration.
You're gonna use your the usually it will be a 40 meg per dose of the parental formula, and patients commonly defecate. They extend a release capsules, so important to owners to know, and you can't split the extended release tablets for maintenance dosing. You can split them if you want to make the tablets immediate release.
So sometimes what we'll do in our cluster buster protocols, so you, when you break them, you take away that extended release formulation, they become immediate release, and then portosystemic shunt puppy is I still will recommend that these puppies are started on levetiracetam 24 hours prior to surgical intervention. Zenniimide is method of action. It's gonna decrease our seizure onset via enhanced sodium channel inactivation, and it decreases the seizure spread via reducing the current through those pre-synaptic calcium channels.
Metabolism and excretion, some hepatic metabolism, and it is renal excretion, and it's mostly gonna be unchanged. So your dose for zinniimide, 5 to 10 makes per kg every 12 hours by itself. If you are giving it with phenobarbital, you do need to go a little higher, so 10 to 12 makes per kg PO every 12 hours.
Side effects, it is a sulfonamide base, so we don't want to give this to our doies and any dog with a pre-existing sulfa drug hypersensitivity shouldn't be prescribed. You do wanna watch for sulphur reactions that can occur, so sedation, dry eye, ataxia, inappotence and vomiting. You can have a metabolic acidosis due to renal tubular acidosis, so you do wanna watch your chloride and bicarb with these patients.
They can have a hepatopathy, and it's estimated to occur in less than 1% of dogs, and usually this is going to occur within the 1st 3 weeks of treatment. So if you have a patient who all of a sudden is you put on senisimide, you're 2 weeks in and they are really sick, then you definitely want to check what their liver is doing because they may be with some of the rare that get the hepatopathy from senisamide. People report psychosis, so you may see that your patients are a little more anxious.
And in cats, one of the biggest things I see is a decreased appetite for sure, so you wanna watch that with your kitties. Monitoring is another with varying opinions for monitoring. I will say that some people do it and believe in it, and others don't.
So if you are gonna do it, you want to aim for a level of 20 mcg per mL, usually 10 to 40 mcg per mL is gonna be that therapeutic range, and stable plasma concentrations occur within 3 to 4 days. So usually you can check these levels within a week or so. If you choose to monitor, usually we'll say 2 weeks after starting with a liver profile, I kind of keep it simple and think of it like phenobarbital, as well.
And then 2 weeks after any dose change, 2 weeks after starting or discontinuing phenobarbital, because phenobarbital decreases the half-life of theniamide and long term every 6 to 12 months. Again, if you are Wanting to measure. So sampling times, again, that trough sample suggestion is suggested, however, again comparing samples from the same time, or very similar sample collection times is most important, and then the same thing in regards to the peak and the trough samples are necessary only for animals in which a shorter half-life is expected.
And therefore, a shorter dosing interval may be necessary to maintain appropriate drug concentrations throughout it. So again, it's not something that we commonly do unless you're concerned that your patient may need to have it more frequently because they are metabolising it very quickly. We're currently looking into rectal administration, not for status, but potentially to initiate treatment if PO isn't available, and more than 70% of refractory dogs will respond well, as anisamide with an add-on, and it was 58% were in another study.
So definitely can be a very good medication to add in to your treatment plan. And pregabalin, this is a wonderful anti-seizure medication for our patients. It's not necessarily new, it's just finally generic.
So we have this cost effective option that's not breaking the bank for most owners. Also great for neuropathic pain, and there's currently lots of studies underway right now evaluating pregabalin, and the mechanism of action. It's modulation of excitatory neurotransmitter release via binding to the alpha 2 delta subunit of neuronal voltage-gated calcium channels.
Now, there's no demonstrated effects on gainnergic mechanisms, so we're not, we know that there is involvement there, but we don't know if it is involvement with seizure control. So, information from human studies is that pregabalin has a high rate of absorption, Time to maximal plasma concentration is 1 hour, steady state after 24 to 48 hours. It's renal excretion, and it's virtually unchanged in their urine.
Metabolise less than 2%, and there's no hepatic involvement. So our dose for our dogs and our kitties, 2 to 4 makes per keg every 12 hours in dogs, 1 to 2 makes per keg every 12 hours in cats. You can go up to every 8 hours in refractory cases, and I'll always start on the lower end of the dose and work your way up to help with sedation, especially in my kitties.
They get pretty, they can be pretty sedate with a pregabalin, so I'll usually start at a one make for a dose and work up if need be. For our kitties, there is a 20 mg per mL suspension available that makes that dosing really easy, so you can titrate it perfectly for them. Side effects sedation is the biggest weakness, ataxia, some report disorientation, polydipsia, and flatulence is also another one.
So monitoring is under investigation. You currently we currently use human serum concentration ranges, but we're not able to do this currently. Other tidbits is that neuropathic pain treatment, you can start at the lower end, so to make for keg POVID.
And in humans, it is licenced as an adjunctive therapy for focal and focal onset seizures that are evolved into bilateral tonic-clonic seizures, neuropathic pain and anxiety. So one thing to consider pregabalin for that I like to use it for is my focal seizures. I think it can be very beneficial in these patients.
So Pyramate is another medication that usually it's kind of gonna be your 3rd or 4th line drug. 5 to 10 makes for keg POBID. Side effects, sedation, and weight loss, are gonna be the main ones and usually they'll have they because they can have the weight losses from a decreased appetite.
So you just wanna make sure your patients are eating if they're taking this medication. Recent studies, elevations in liver enzymes, but those patients were also on phenobarbital, so not sure. Monitoring isn't established, and again, this is gonna be like the 4th or 5th drug that you're gonna add in.
So CBD, of course, a big topic of discussion, 20 to 30% of epileptic dogs are refractory to management with phenobarb and potassium bromide, and so there's more than 104 cabinoids that were identified as constituents of the cannabis sativa plants, and the two that are most abundant are, of course, our CBD, which is non-psychotropic, and then our THC, which is psychotropic, and is toxic to dogs. So we are looking at using, that's why we use CBD. And so can CBD be a safe alternative for epileptic management?
And so lots of studies have been conducted, are still occurring and are coming, and the biggest problem that we have is there's so many CBD options out there. The theme that all these papers are showing us that have been done thus far is that there is a reduction in seizure frequency, but responders are similar between the groups that are studied, so we need additional research to determine whether a higher dosage of CBD would be effective in reducing seizure seizure activity by more than 50%. And when owners ask, I just say we're currently researching and hopefully we will have some consistent information soon on efficacy as well as the effects that it potentially has on other anti-seizure medications, cause that's gonna be the big thing is we want to make sure we're giving our patient this medication.
Not only is it efficacious but it's safe to do so. So that's kind of my the review of seizure management in cats and dogs. So remember, Signalment in history is very vital to making your list of differentials.
You wanna make sure you're doing a full physical and neurologic examination to help prioritise some differentials that you're already gonna be thinking about. You want to neuro localise so then you can further prioritise those differentials. So you either have forebrain or multifocal, and then your anti-seizure drugs.
There's many different medications that You know, different neurologists have preferences for, there is no right or wrong in regards to which one do you use. I think every situation is very different. Most commonly we see that levetiracetam, phenobarbital, are gonna be used.
Kind of first line, but that being said, I also know many that will jump to anniamide first, or others that are comfortable going to pregabalin first, especially I like to do that for my focal seizures. So there isn't a right or wrong, and there's many options out there, so just use what you think is going to be best for your patients is overall the theme for, for this talk. And then if there are any questions, you guys can absolutely reach out to me.
My email address is at the bottom there, carpenter@mm veterinary neurology.com. Thank you very much.