OK, let's get started. Welcome to this lecture on the causes of confusion and circling in docs. We're gonna use some case presentations to help us understand how we can, differentiate between the possible causes of brain disease in dogs.
We're gonna go with a, 11 point plan to start with a review of something that you do probably in practise on a daily basis. But we're just gonna articulate here so that we can understand how we're working our way through some of these cases. We deal first with the who are you?
Why are you here and what's been going on? Questions And that is the signalman and the age can really help us here. The presenting complaint.
And so the as we'll talk about the speed of the onset, the potential progression, there may the potential asymmetry that that's present, the potential pain that's present those things, factors which can help us understand what could be going on. And then the history we wanna know. Has the, dog had any other illnesses recently?
Anything which could suggest a more chronic, ongoing disease or something related to something systemically that may have been ignored based on AAA perceived acute onset. So these are very important factors. We then do the physical exam, neuro exam.
Talk about that a bit more in a second, with the aims of trying ultimately to localise the lesion and and this session being on confusion and circling points really to intracranial disease for brain disease. And that's what we're gonna be focusing on re really today. A differential diagnosis is narrowed down using some of the factors that we've mentioned here.
And we'll continue to mention throughout this session age lateralization potential presence of, pain or multifocal disease. If we're thinking about brain disease, most often it's not painful, But we have neck pain as well. Maybe there's a multifocal component to it, and then the onset Is it acute?
This is chronic is a It's static. These factors will go over in our cases and show you how they help understand what is most likely diagnostic plan, will often determine what tests are gonna be most appropriate and most helpful in an individual case based on what the disease is. That is suspected.
So if we have neoplasia for instance, as a suspect we might wanna do thorax and abdomen imaging to see. Could it have come from somewhere else? Could that be, an easier way to look at a multifocal disease?
Treatment plan? We look at treating forreal, and we'll go through this in some of our cases. What's possible in these cases?
And prognosis. Obviously, this is important to the owner, and we'll communicate that, all wrapped up once we've gone through these steps. But prognosis is often determined by the neurological exam as well as the underlying disease that we suspect is is causing the clinical signs.
So we look at really this 11 point plan as, a jigsaw puzzle. We're looking at piecing everything together to try to come up with. Where is the disease?
What could it be? How do we then treat it? And what could the prognosis be?
So the aims of our neurological exam are really is it a neurologic problem? And as you'll see from some of these videos, that can be quite easy to determine in some cases, in some cases, it's tough. Where's the disease itself?
We wanna look for in the brain and out of the brain. Most of the time, that's our an atomic diagnosis, because the differentials for an intracranial disease obviously very different from a spinal disease. And then what could it be?
This is really important. And we'll use those factors to try and narrow down the differential diagnosis. That will all really determine what tests we think are gonna be most helpful.
So we'll use the signal. And as we said most commonly, the age occasionally breed will help. Very rarely.
Gender. Very rarely. Co coloration.
We use sign to help us. We use a presenting complaint. Onset.
Was it rapid or slow? Has the disease got worse? Has it remained the same as it was at the time of onset?
Did anything set this off? So, is there trauma involved? Is the potential for toxins?
Has there been any ongoing therapy? Any systemic diseases, that we need to know about, regardless of how insignificant they may feel, based on the severity of the of the presentation. History always going to be important here in terms of knowing, underlying conditions that the the patient has, as well as any Anything else that the patient has suffered from in the past.
All of these things help us narrow down the disease process. So we'll we'll start with our first case and show you how we put this together. It is a bit of AAA jigsaw puzzle, as we said.
So let's look at some of these pieces. 12 year old poodle mix. We've got an older dog, a sudden collapse this morning and was seen to be confused and then circle.
The owners were a bit unsure about the visual state of the patient, and I thought maybe maybe the dog's blind. Hadn't really seen this before. There was no evidence of trauma, no access to toxins, predominantly an indoor dog.
No. Previous, systemic health issues. Either.
This is a healthy dog. And when we saw the dog, as you'll see, it was, ambulatory on presentation. So let's look at this, snippet of a video and look at a stream of consciousness.
So here we see this dog. We've got a collapse going on. That was our primary complaint.
He is able to stand. There's a slight turn to the right here. We can see, let's get the dog out.
Let's see what he can do with minimal support. We've got him walking, so this is good. Maybe a slight stiff gait, But we've got a circle here, so we've got a circle to the right.
He seems maybe a bit quiet or gonna ask for input from the owner on that. So this turn to the right circle to the right is important. We're not really sure whether there's any ataxia.
There's a little bit of weakness. But you can see that up there. A little bit of ataxia.
Now he's getting stuck under furniture, so his problem solving skills are not great. So we've got this asymmetry going on, marked by the circling. We've got some confusion, some potential dullness that we'll confirm with the the owner.
Is this normal for the dog? Seems not being a little bit of a taxi there. This is day one, remember?
Now, let's look a little bit more. We're gonna just look at some postural testing here. We do a hopping.
We can see on the left. The dog's failing on the right. Oh, looks great.
So here we're trying to hop the dog. And on the left a bit of a failure, to do anything but on the right. Looks very dainty.
That looks great. OK, so marked asymmetry on the left. We've got postural reaction deficits.
And remember this dark circles to the right. Now top 15 reasons. Why people, or one of the top 15 reasons why people hate neurology is it seems that everything crosses over.
So that is, a potential confusion in this case. But let's just talk about something here before we move on. When we talk about, the neurologic signs we've seen, we're gonna say that this dog has a bit of a curvature to its right and circles to the right.
Oh, so a bit of a curvature to the right circles to the right. Let me get rid of this pen. That's not working out too well for me right now.
And so that usually tells us when you circle to the right, you turn to the right. That usually tells us that we have a right sided lesion. Let's move this video on a little bit more and see if that I can annotate that it's trying to be clever, not work it out for me.
So right, Sided circling. Let's stop you here. OK, so right.
Sided circling, tends to imply that you've got a right sided lesion. Right? So here, we've got confusion, depression, So we've got an intracranial lesion.
So we're thinking about a right sided intracranial lesion. Now look at this. Here on the left side, we've got deficits, imp proprioception.
It's postural reaction. And this is one of the big three things that crosses over. It's really only three things you need to worry about that crosses over.
One of them is proprioception. So a left sided proprioceptive deficit often implies then a left sided neck problem or a right sided brain lesion. Same in the pelvic limbs, Right?
Left sided. Proprioceptive problem means left sided, spinal or right sided brain. That's one of the things that crosses over.
The other thing that crosses over is a visual field. So a left eye problem would mean a right brain problem if it's a central disease. And the other thing is facial awareness.
So if we were to pinch the lip, then if it was a decreased response, it would point to a contralateral thing. So only three things there that do cross over. And so we've got now indication of an intracranial disease in this patient and, an asymmetric intracranial disease.
And that's important, because when we've got, an asymmetric disease, we think about three major possible causes in the absence of trauma. And those are vascular disease, inflammatory disease and neoplasia three big causes of asymmetry in the brain. Let's go through this vitamin D list here.
These are the differentials of brain disease. And as we've talked about, there are some characters touristic which can help out, narrow down this list. So vascular disease, certain onset asymmetric nonprogressive inflammatory disease can be certain onset, usually less so, and is progressive.
Can be multifocal often presents with asymmetry. Toxicity is a symmetric disease. Trauma nonprogressive.
Hopefully, there's some history can be asymmetric anomalous disease. This means are you a young dog with a structural abnormality? Most commonly, hydrocephalus could be symmetric or asymmetric.
But youth really tends to rule that out metabolic disease. Usually you're very sick with this. You do have some systemic health issues.
Eating, drinking, weight loss, diarrhoea, vomiting, that sort of thing. And it's symmetrical. Right?
So if you have a liver disease, for instance, you've got a symmetrical disease. liver dysfunction is not going to affect the left more than the right, So we'll rule that out. In any case, that's got asymmetry.
There is no idiopathic asymmetric diseases. Idiopathic is an odd one, right? For neurologic disease, we think, Well, that means you haven't found anything, and many times we don't find anything.
So shouldn't most things be considered idiopathic? Really? Idiopathic means a specific disease that might have a genetic underpinning.
And so this is epilepsy, vestibular disease, hornets, facial pais. So, some specific things. There is no idiopathic circling or confusion, dementia, that sort of thing.
So, we're gonna go No, on that neoplasia. Well, would be an older dog, which we've got, unlikely to be a very sudden onset, as in this case, so seems that we'll put that at the bottom of the list. It's always on the list.
Could be asymmetric. Most of the time is, so on the list, but just lower Nutritional fell off the map for a while, but now people feel that they can feed their dogs raw meat and bones. It's back on the map, but most of the time again, it's a symmetrical condition.
Degenerative disease. As we'll mention at the end of this, session. Cognitive dysfunction syndrome is the main thing we think of in older dogs.
There's no asymmetric, disease dysfunction present, with degenerative disease. It's usually a very symmetric thing. Young dogs can get degenerative disease as well, if they're born missing an enzyme in their brain.
A lysosomal storage diseases are an example. It's rare. Multiple members of the litter may be affected.
And it's progressive over a sort of few month period starting maybe 36 months of age. So when we look at our dog old dog per acute onset, asymmetric and so we think asymmetric certainly could be vascular could be inflammatory. Could be neoplasia.
It's an old dog. Could be neoplasia. Less likely inflammatory but possible.
Could be vascular, but the per acute nature makes us think vascular is certainly top of the list here. So what do we mean by vascular? Let's just clarify a couple of things.
Cerebrovascular disease means you've got disease of your blood vessels. And as we all age, we all have cerebrovascular disease to a certain degree. Now, in humans, if you smoke, you don't exercise.
You eat big Macs. you drink too much. The these sort of things.
Then you have more cerebral vascular disease than someone who doesn't. Doesn't mean that you'll have any signs of it if that's cerebrovascular disease. So blood vessel disease, a build up of plaque, for instance, within these blood vessels supplying the brain.
If this blood vessel disease creates an obstruction, or a leakage of the blood vessel, then that's a cerebrovascular accident commonly referred to as a stroke occasionally in cats. This is referred to as feline ischemic encephalopathy. But it's not really a specific disease.
It is a, umbrella term for vascular disease of the brain. Classically, this is acute nonprogressive and asymmetric. Now, we don't know if it's nonprogressive in this dog time.
Therefore will be a good diagnostic test, because if this dog goes on to progress over the next few days. Then it tends to rule down a vascular cause. Now two major types of cerebrovascular disease most common.
80% of cases in dogs and humans are vessel occlusion. So a plaque type build up. That's thrombosis.
Or something around the body breaks off and blocks a blood vessel. That's an embolus known for people. Atrial fibrillation can cause a clot formation in your or atrium, and a piece can break off cause a stroke.
Neoplasia parasites, infection. All of these things can do this. That's vessel occlusion.
Vessel rupture. 20% of cases dogs and humans. This is haemorrhage.
This is your subarachnoid haemorrhage. You might have heard of people with aneurysms where they have a bursting blood vessel, less common, but, possible to have, haemorrhage in both humans and dogs, causing an acute problem. Now, this can have some slight progression over 24 hours as the hematoma reaches its maximum size and local pressure stops again any bigger?
So we've got two types of stroke. Ischemic stroke is a blockage of the blood vessel. Could be large, territorial or small, as they're called lacuna.
So tiny, versus hemorrhagic intrarenal. Most common. So inside of the brain.
A hematoma versus saracho. This is more common in people, but the bleed location can determine the clinical signs. So your clinical signs are not, specific for a bleed, or ischemia.
The clinical signs are determined by where that bleed is so for brain signs. Cerebellar signs brain stem C will be seen if the lesion is in any of those places. Now, we've got a dog who has four brain signs confusion, depression circling, maybe visual deficits, on an acute basis, ataxia.
But most of the time, short brain signs don't cause really any gait abnormalities. After the 1st 24 hours, you will see a dog with a normal gait. So clinical signs don't help us with is this, a vascular disease?
But their onset and progression and lateralization do help us. OK, what do we know about stroke in dogs? Well can happen to any dog, but, median age is eight.
So we've got an older patient. A couple of breeds we see that are overrepresented cavalier, King Charles and the Greyhounds potentially related to, underlying platelet abnormalities and blood vessel structure abnormalities, respectively. And this is an interesting thing that, some of these dogs that present to us with with, stroke may have a history of possible transient ischemic attacks.
These are cases that have a sudden onset of neurologic dysfunction and over a few hours get better. And there's nothing really that that commonly does that besides vascular disease. So if you have an owner, swear that a dog had a head tilt or swear that he collapsed, and then you see a normal dog.
Then you start to think, Well, could this older dog be having transient ischaemic attacks? In which case, as we'll talk about you could work them up for underlying causes. Once they have one of these events, we know that a third of them will have recurrent events based on their underlying predispositions.
And there is a, 20% or so mortality rate not really related to the stroke, but related to its associated quality of life perceptions. Many times there will be improvement. But sim owners, may not be happy with the level of improvement or the time, obviously the cost that it may be associated with.
So about these predispositions, I And that's what we we should say. They are associated diseases. Predispositions Not necessarily, definitively linked.
Because these are older patients that may have these concurrent diseases. Now, in up to 50% or so of cases, these may be healthy dogs. So all the money in the world you'll find nothing but other things that we find that could be linked to the cause may just be associated or concurrent incidental findings.
Chronic kidney disease that can cause a hypercoagulable state cushings that can cause hypercoagulable state, infection somewhere so that a septic emboli might cause this hypothyroidism, can cause atherosclerosis or plaque build up, tumour somewhere else. Parasites. can cause this as well either direct migration or, interference with the coagulation cascade diabetes.
But look at this cardiogenic. No real proof that cardiac disease in dogs causes, or is associated with strokes. Not to say it isn't but no real proof at this stage.
Hypothyroidism is worth looking for therefore diabetes. So we'll we'll look at these things and say, Well, how should this determine how we work the patient up? Most of the time, we're looking for underlying health issues.
Maybe these are the cause. So maybe if we look at focusing on them, we could reduce that recurrence rate. When we briefly talk about haemorrhage, this is, slightly different from, ischemia.
So we've got a blood vessel leakage or burst, in people arterial hypertension. So we should always look for blood pressure issues. This is a possibility, less common in dogs than in people.
Vascular malformations. So you're born with some type of arteriovenous malformation. Not so common Aneurysm is not so common in dogs.
Neoplasia is coagulopathy is. And so we look at these two things, as possible causes of haemorrhage. An underlying inflammation in the brain might cause a bleed.
And sometimes infarctions So the ischemic disease that we've just been talking about can actually cause damage to the brain, and then they they leak a little bit. Clinically, these can look the same ischemia. Haemorrhage.
Apart from the fact as we mentioned, that haemorrhage can have some progression associated with it over 24 hours as the hematoma gets bigger. So how do we diagnose these cases? Unfortunately, definitive diagnosis is always a bit elusive, but imaging can help you, MRI much better than CT for these conditions.
I in this case, we see a very well defined lesion here. It happens to be in the cordate nucleus, which happens to be, in an area predisposed to stroke. But you can't look at these images and say, Well, that's definitely a stroke.
And that's not a tumour or inflammation. And that's the problem with MRI. It's suggestive, but it isn't unfortunately, as specific as you would like it to be.
A CS F type may help rule out inflammation and would be relatively normal with, stroke relatively normal with brain tumour. So that could help. but it isn't anything again.
That's definitive. Now, there is something in some of the larger MRI, machines that, can be performed That gets you a little closer to a diagnosis. You may have heard of this, but this is called MRI Diffusion weighted imaging.
Now, the idea here looks very complicated. The idea here is that if you've had a stroke, you've got an area of your brain that has an in. And so you've got a piece of dead tissue.
And in that dead tissue, therefore, you have water that's trapped. Now, your sodium potassium pumps aren't working anymore. And so you get swelling of the cells.
Now, this diffusion weighted imaging can detect that as a very specific area of water in the brain. And what's called an E An apparent diffusion coefficient or a DC, then shows up as a lack of diffusion. Right, Because normally, water is diffusing F, completely around the brain from cell to cell, and in and out of cells.
But here, we've got a very specific wench. So a well defined area of, lack of diffusion. Really?
So, this this is a fancy technique which can get you closer to saying, Yeah, this is a stroke. And this is what we see in our dog. We see a very well defined region of, ischemia here.
So that gets us a bit closer in our dog. Now, what would we do? No time.
As we said, would be one test that I would employ in this dog. If the owner says, Hey, I can't afford an MRI or CS F I don't really feel comfortable with that in my older dog. What would we do?
We certainly would look at what happens in the next few days. Supportive care, and let's see if the dog can improve. And if it does, then that's very supportive of a vascular disease.
When your other two major differentials are inflammation and tumour, which are not gonna get better on their own, things we could do to help us look for underlying conditions. Blood pressure assessment, cholesterol assessments and triglycerides. D dias D diers seem to, correlate with the with the potential of a stroke, showing a hypercoagulable situation a bit more so than antithrombin three and thrombo elastography.
If any of you have access to that, we do do endocrine evaluations, mostly for hypothyroidism and diabetes. Cushions is also worth looking for. If there is some clinical suspicion, renal evaluation, or or a function that, at least is is worth looking at cardiac evaluation.
Maybe less so. And faecal analysis, particularly for nios Strongylus as this interferes with your coagulation cascade. So it certainly can, cause a hyper, a hypocoagulable.
So you may have a a bleeding going on. There is no specific treatment for, dogs with strokes. And so supportive care is what we will look at.
And often they will make a fairly dramatic improvement over the first week or two. And that improvement will continue for, up to three months. Now, there's a potential that some of these dogs will have a seizure focus because of the damage in their brains.
So we'll warn the owners that a complete recovery might not occur and they may have seizures for life. So that's an unknown specific care, Really. This is focused on a an attempt to reduce the recurrence.
And so if you have high blood pressure, maybe we consider amlodipine. If you have high cholesterol, maybe we consider statins. Unless there there's an associated cushions, or hyperthyroidism that we could target.
If you have a hypercoagulable state, then we might consider aspirin or clopidogrel. And so these are things which might help. There is no evidence that they do reduce the rate of recurrence because there is no evidence that what you find has actually caused the stroke.
They're all associations. And so we look to see if we can improve the dog's overall health. Now, one of the big three, causes of an asymmetrical presentation is stroke.
What about the other? So let's look at this guy here. A young now female spade springer spaniel with this contortion that is called Pleo tous fancy name that says we've got a whole body turn head, neck, body.
Now this dog has an eight day history of depression. And this body term, it's an outside dog. It's not vaccinated.
There's some dietary indiscretion. So a few things to consider again. Let's look at this case and see with a stream of consciousness what we're thinking about so overall.
Well, this doesn't look good. We've got a body contortion. So your turn to one side usually indicates that we've got more muscle tone on one side than another.
This end indicates either brain or spinal disease, not that specific, but with depression with any confusion, do we start to think Well, maybe this is a brain thing. We'll get the owners to input. But this makes me worried that you've got some brain disease going on again.
Turn to the left. Maybe it's more left sided. Don't worry about Is it left or right?
No owner really is too worried about about that. It's the asymmetry itself that is important here. So we've got this body turn.
Let's do some postural reaction testing. He's turned to the left and on the right. It's got reduced, positioning on the left.
It's pretty rapid at turning so very similar to the last case here. So we are looking really just to to establish that there's a neurologic issue which we think there is anyway, reduced, knuckling or proceed, placing on the right. Pretty good on the left.
So very asymmetric here. So we like this. The A is very helpful.
We think the depression puts this in the dog's brain. We check the dog's neck for any pain. There is none.
So we're thinking a very asymmetric brain disease. Now it's a younger dog with some progression of of disease. So what are we thinking about again?
Asymmetry. Right. So your big three are gonna be vascular.
So let's just talk about a second about these Big three vascular. Yeah, but this is a more chronic situation, right? Younger dog doesn't mean it's impossible, but more chronic situation.
So with some progression, So I'm gonna say, Yeah, it doesn't quite fit. Inflammatory. Younger dog will definitely on the list.
And there's some progression. Yeah. So you are a possibility.
Toxicity? It's always possible. And this dog's an outdoor dog.
Dietary indiscretion. Who knows? But it's asymmetric, so no trauma, maybe can't rule it out if it's an outdoor dog, but there is some progression.
So we're gonna go? No. No physical signs of the trauma.
Anomalous disease, As we said, Really? That's hydrocephalus. Bit old for that now.
No physical signs of it. Can't rule it out. If it's secondary to an underlying condition, we're gonna go.
No, no metabolic problems because you're asymmetric, right? No idiopathic cause of this. Because you're asymmetric.
Remember, Idiopathic is epilepsy. Vestibular facial, Breus, hornet neoplasia. Well, that's possible.
You're a young dog, so that wouldn't be good. Not good at any age, I suppose. But, not not good to be thinking about any young dog, so we'll put you a bit lower on the list.
Nutritional. You're asymmetric. So no degenerative.
Well, you're not a puppy with a enzyme deficiency or an older dog with cognitive dysfunction. So we're gonna go? No.
So we're gonna probably say that you are inflammatory. Can't rule out neoplasia. And now how would we How do we work this up?
Now, there are some systemic signs that, we could be looking for If you have inflammatory disease, we'll talk about this in a second. But if we're gonna look in the brain again, we come to advanced imaging and CS F tap. But again, advanced imaging is non-specific.
Here we see some white splodges in the brain, on various sequences, and these suggest a multifocal disease predominantly one sided. So we've got some asymmetry. Multifocal tends to say that could be inflammation, But you can't rule out that this isn't tumour lymphoma, for instance, And so non-specific.
And that's important because this is an expensive test, and that can sometimes irritate the owners because they would expect a more definitive diagnosis. Now, with CS F in our patient. We have a high white cell count, normally less than five.
We've got 42 protein. This indicates you've got a break in the blood brain barrier. We've got 27.
Should have less than 20. So there's something on fire in the brain. Probably not surprised.
Based on what you've seen clinically, on cytology, there's a bunch of neutrophils. So we've got some, active process going on eosinophils. Well, that could mean parasite.
It could mean protozoal disease, fungal disease. It could mean immune mediated disease and in some cases, cancer. And so, really, although you'll read in textbooks, there are some specific patterns of CS F cytology that are seen with with individual diseases.
There's a massive overlap. And so unfortunately, most of the time, CS F is just a supportive test again. Non-specific.
Unless we see organisms in the CS F, it's rare that we can say what it indicates. And so what we've got here is, a case of brain fire. Right.
So you've got high white cell count active disease, with some chronicity going on with the macrophages non-specific with the MRI multifocal disease. MM. Gives us a bit more confidence that this is in inflammation.
We mean by inflammation. This is important to have this perspective. If we're gonna, try to work this patient up, we need to have some perspective.
As what could the cause be now, in dogs, when we say inflammation, 20% is infectious. Whereas in cats Sorry about this. Whereas in cats, 99% is infectious disease F IP toxo crypto.
The big guys here with some bacteria thrown in infectious disease, less common in dogs. Overall, as a cause of inflammation, we've got viral disease, like Rabies. If you live in this sort of endemic areas to stemper if they're not vaccinated, in dogs, bacterial disease, if you are, bitten or if you have ear or nasal disease that could have made its way in or if your septic protozoal disease is possible.
Fungal disease again depends where you live. But as perilla cryptococcus always a possibility anywhere in the world, just less likely in some regions, like the UK. And then 80% of dogs have this, sterile or immune mediated disease that's often breed associated, and we're gonna get into it for a second.
And that's meningitis of unknown aetiology or origin. Very rare in cats, occasionally parasitic migration. So when we talk about inflammation, we think Let's rule out infection.
If this is the case, probably have some systemic signs of this. Maybe you've got some predispositions to this geographically or health wise. But most of the time you are immune mediated, particularly if you're of the right breed and you're a young patient.
Let's get into that a little bit in a second. So if we think about inflammation, what do we do? We can do a minimum database to try to improve our confidence.
We wanna obviously history and, look at as you are you Have you been in contact or in a region where there's some infectious disease? Concern. Physical exams can help us with you.
Any systemic problems as a fundic exam can? Maybe if you've got chorioretinitis, you've got some systemic inflammation. It is, after all, the window to the brain so you could see potential extension of inflammation into the retina.
From the optic nerve haematology serum chemistry. Now important to say that they could be normal even if you have raging inflammation in the brain, cos it's locked in the brain, so just cos it's normal doesn't rule out inflammation. But if it's abnormal, well, this may be a systemic disease, which points more to infection than immune mediated disease.
Most immune mediated diseases of the brain do not have blood changes. Your analysis. Same type of deal.
You're looking for systemic components of this disease. If you think maybe there's metabolic problem, then maybe we do bile acids. In most cases where we have asymmetry, that's not on the list.
Thorax and abdominal imaging. Again, you're looking for whether there's a systemic component here. Infectious disease.
TTI, at least, is a bit of an issue, right, because, most of the time we're perform performing them on serum rather than CS F. They, can indicate just exposure, particularly with proto, however, for instance, just exposure rather than active disease, and you may need to do pair tighter. So there's an expense.
There's a lack of sensitivity, going on, and even with PC R, where we'd expect to find an answer if it's there. Sometimes it's negative, and so not as sensitive as we would like it to be. So we often can't wait for these pair tits and need to make treatment decisions before they come back.
We'll talk about that in a second. Other tests that may help us. Well, skull radiographs know because, it's rare that, with an inflammatory disease, you'll see any involvement of the skull, and it's expensive to be performing.
Orthogonal skull radiographs, multiple view skull radiographs under anaesthesia CT and MRI. That's gonna be helpful. to a degree, as we've said but remain non-specific in most cases.
CS F analysis. Same thing. They're all pieces of the jigsaw, right?
EEG rarely performed. Some academic institutes will have this. It's non-specific can help you say that at least you have a brain abnormality and then tissue biopsy, right?
We think nothing if you have a liver problem or relatively nothing. If you have a liver problem or an abdominal problem, let's say of saying Well, the next step may be to get a sample. But if you have a brain disease, we're not thinking that the next reasonable step is to get a sample of the brain.
Obviously, it's expensive, but it's, gonna be associated with some morbidity. And so there's a risk here and imagine getting a biopsy back that says could be inflammation. Can't rule out lymphoma.
Or maybe you just hit the edge of the lesion. Well, so we're always playing this game with our hands tied behind our backs here. We're having to guess because we haven't got any pathology to help us.
And these tests or pieces of the jigsaw which improve the, which improve the level of confidence. But don't definitively diagnose that disease. CS F ana analysis.
I'm not sure whether that picture is small, but, just to add a little bit to it, it's expensive because it requires anaesthesia bit of technical experience. But more problematic is that it requires an immediate laboratory analysis. We are taking CS F from around the nervous system so it could be reflective of an underlying inflammatory disease.
but there's no real glucose levels in the CS F, which could support, cells living outside of the system for more than 30 minutes. And so to preserve it. If you haven't got a lab on site which most of us don't.
Then we need to add, some heter starch at 1 to 1, or autologous serum at sort of, 1 to 10 roughly, and then store in the fridge or cold pack overnight for delivery to the lab. And these are ways to try to preserve your cell counts. If you're gonna add anything to it, you need to separate the CS F because adding something to it may affect your protein levels.
So, non-specific but can be quite sensitive for inflammation. CT scan again. Non-specific not as good as MRI, but you could see concurrent osteomyelitis as we see here, suggestive of, a bacterial disease, for instance.
You can see with contrast, areas that light up, particularly with an abscess and so conscious enhancement can help. Not such great imaging of what we call the cordial phosphor or the back of the skull, cos you've got really thick bone all the way around it, and this interferes with your bean. And so we get a bit of a disturbed image in this region.
So and this is unfortunately where a lot of information likes to live MRI, obviously great soft tissue detail. However, as we said, and as well as being not specific, it's not as sensitive as you would like. CS F is considered the gold standard, and sometimes that can be normal in these inflammatory diseases.
MRI, though considered only to be about three quarters as sensitive as CS F, so you could have a completely normal MRI yet still have inflammation in the brain. I suppose that rules out a mass such as a tumour or a a lesion such as a stroke. So let's talk a little bit about what this is.
This immune mediated disease that we're thinking about is most common in dogs in cats. So meningitis of unknown aetiology or origin, is the latest term or acronym. That's that's preferred.
No infectious agents have been identified, loves the brain and the cervical spine less so, thy LL thesr area. This is an umbrella term for a bunch of diseases that can only be diagnosed on pathology. Granulomatous meningoencephalitis, NEC izing, mening, sophis, necrotizing Leuco, encephalitis, steroid, responsive meningitis, arthritis and what has been termed as little white shakers in the past.
And now idiopathic tremors and these are all immune mediated usually require pathology to be definitive. So we make a guess about their, presence based on, clinical signs and these clinical signs Is that, that that you are a young, purebred dog most of the time. And by young, I mean, average age is two or three, and that you have asymmetry to your neurological exam and progression of the neurologic deficits.
These are things which make us think, OK, you could have this rule out infection, and we get as close as we can to say you have MUO. Unfortunately, a lot of treatments have been documented in the this, set of conditions. They're all immunosuppressive and range from steroids alone, through to combination therapies.
Cytosine Arab aside is often used. Cyclosporin can be used so you can see here There's variable studies which are, you can go back and and and look at the specifics of, But there's pulled out of these studies with all of these treatments. That are, potential.
There are some need to know facts and the need to know, facts for meningitis of unknown origin are here. A third of these cases will die in the first month, regardless of what you do. So that's important to let the owners know a third will need these immunosuppressant medications for life, and it may just not be one.
Maybe they need 23, maybe even four. They all work in slightly different ways. They have different cost implications.
They have side effects which need to be you need to be aware of. And so these medications are gonna come at, a financial and a, physical cost. A third of these patients, though, can be weaned off medications.
However, half of them will relapse within about seven months. Overall survival time is about 2 to 3 years. Median survival time, About 2 to 3 years.
Those that are alive at six months. A third of them will have persistent neurologic deficits so important to warn the owners You may have seizures. You may have deficits which you think impact the quality of life of the dog, negatively associated with survival.
The fact that you're a pug. The fact that you have seizures on presentation or the fact that you have perrey are not good signs. And if you don't have seizures on presentation, of course, will develop seizures after presentation along with treatment.
So these are our need to know it's not a good set of diseases. We need to get them through the first month. They may be on medication for life, and those medications may cause some significant, la, adverse effects.
So this is our kind of flow chart for how we deal with these many of these, meningitis cases, of unknown origin. These immune mediated cases will attack, purebreds. And many of them, are small breed purebreds.
And so we see a lot of them in the small white fluffy. And so this is a bit of a, flow flow representation of what we could consider. We might see a young patient with asymmetric, progressive signs, and we think, Yeah, you could have inflammation.
Maybe the owners are not keen on doing further tests. And so if we have some time on our hands, I know this is a bit cheesy, but time on our hands because the dog's not severely affected, we could say, Well, I don't know. You're not infectious, so I'm gonna go with antibiotics as well as anti-inflammatory steroids.
It seems odd if you think there's an infectious disease, but what will kill these patients is the inflammation. So we go with this approach and potentially that helps. And if that is the case, we'll stop your anti-inflammatory steroids and continue with antibiotics for about three weeks.
We often use broad spectrum combination antibiotics cos we're not sure what's going on. So maybe clindamycin maybe, fluoroquinolones. We're looking for combinations to deal with the potential infectious.
Now, if you use this approach and the dog is no better in the first few days to week, then we could always change the antibiotics. But it may be time to consider that you have a ticking time bomb on your hands again cheesy. But, a more severe situation where now we need to accept that 80% of cases need immunosuppressive treatment will often start with immunosuppressive steroids, at quite a high dose, so at least two milligrammes per kilogramme per day, for at least two weeks.
And if that improves the case then you can look at weaning this case down, stepping it down. As we said, Some cases you'll get off the meds. Some cases you won't.
But if that doesn't work, then we may need to look at adding a second drug. Cytosine is often used as a second drug, but as we said, well, other immunosuppressants have been documented to have a degree of success. We also need to warn the owners that if it's not working potentially, this is bad news.
Don't wanna offend anyone here. But this is just to remind us that we have a situation where this could be fatal in the first month. Maybe it's not inflammation.
Maybe it's actually a neoplasia. And so we're warning the owners that a failure to respond is not good now. And the dog you saw at the start, actually turns out to be good news, that we used, immunosuppressive steroids in this case, and we saw a fairly dramatic improvement.
This dog is not normal. It's very anxious. And, seem to be, have some visual issues as well.
So not completely mentally normal, either. But five days later, immunosuppressive steroids. And, the dog did well for two or three years, and then we lost a follow up.
So, this is, an example of how that that, medication flow chart flow diagram can be used when you're not certain what's going on because you're not without a biopsy. You do not know what these patients have. OK, so our last case here is an alter Dalmatian.
Progressive change in behaviour over the last three weeks. Started to get trapped on the furniture, hide in the corners, barking at the wall. Previous history was hit by a car a couple of years ago, but seemed to be stable since then.
It's been an outdoor dog. Hasn't been vaccinated for a few years, but otherwise happy, healthy. So brief snippet of, this patient and we can see that it is ambulatory.
That's good. Heads for corners, paces, maybe not as aware of his environment as he should be. This went on all day, so there was a compulsive activity here, and then again, heads for corners would occasionally get trapped in these corners.
Mentally seems a little bit dull and then we'd have, like, periodic short term collapsing like this. So we thought, OK, this is supportive of brain dysfunction. There was a tendency to go more to the right in this patient, and there were again proprioceptive deficits.
That were asymmetric. So we thought, OK, asymmetric for brain disease. You see the theme here.
So this time we've got an older dog. It's chronic, it's progressive. And so we're gonna go for neoplasia is really top of the list, right?
With progression, we'll rule out vascular. We can't rule out inflammation, so it's a possibility. It's an older dog, less likely, but it's on the list.
Can't rule it out. Toxicity is asymmetric. No history of trauma is progressive.
Too old for hydrocephalus. It's asymmetric, so it's not me, not metabolic. There's no idiopathic causes of circling.
The dog was on a decent diet, but it's asymmetric, so it's not nutritional and not degenerative. Because there's a symmetry to the exam. And it's not a young dog who's missing an enzyme.
It's too rapid for cognitive dysfunction as we'll go over right at the end of this session. So we put neoplasia on the top of the list for this guy. What do we know about it?
What? What? What?
What is gonna help us make this Or break this as a possible case of neoplasia? Well, we know there is an older dog disease. Median age of nine.
Cats can be a little younger, especially if they have a lymphoma. But we have some breed predispositions. The brachiocephalic brachycephalic are predisposed to glial cell tumours.
These are tumours within the brain, tumours of the cells of the, brain. And these two are right up on the list boxes. Boston terriers and the dolichocephalic are are sort of golden retrievers.
German shepherds. Dobermans are kind of overrepresented to be predisposed for meningioma. These are tumours of the packaging of the brain.
Slightly better brain tumour to have, if you are gonna choose one as it's slow growing. And it's outside of the brain itself rather than, of the cells of the brain. Diagnosis is very similar to before CS FT.
Maybe some slight non-specific changes, but, really, we're doing this to rule out inflammation. CT scan and MRI may show us that we've got a mass lesion. Doesn't say that's not inflammation in both these cases.
Here, we've got AC T on the left. An MRI on the right. Can't rule out the inflammation, but the mass nature of it makes you think, Well, this could be a, a tumour.
So non-specific. Even if you think it's a tumour, you cannot say what type. Really?
I mean, is if we If I tell you, this is a tumour. Is that a glioma? So a tumour of the cells of the brain.
Is it a lymphoma? Is it a metastasis? So it's very difficult to to know.
They just add a degree of remembering that biopsy is the only way to to get close to definitive. And that's going to be expensive and has some morbidity. And in brain tumour case, if you're going to do biopsy one, why not do surgery?
At the time, you're there to try and resect it. So you've got some considerations that the owner, they need to be discussed with the owner treatment options, are split into, you know, paliative or conservative, and, we'll talk about that in a second versus definitive, Which really, is surgical debulking in radiation therapy? Chemotherapy.
Not that helpful in dogs. for brain tumours. The the the therapy that is is used is not really successful.
And in people, it's the third, adjunctive type of therapy. So it's added on top of surgery or added on top of radiation. Because there is no chemotherapy for brain tumours that is uniformly successful.
New therapies such as radiosurgery. So an advance on radiation therapy, gene therapy immunotherapy are breaking through, and so there is more success. But overall, there is no cure.
And, the, survival times are as follows. If we use palliative treatment with steroids anti-inflammatory doses, you'll take away a lot of edoema reduces some of the pressure in there. You can add diuretics, to that such as, frusemide Lasix.
Sometimes acetazolamide you can add to that as well as anti convulsant. If there are seizures going on, in the background. But you've really got about a three month survival time in these patients, if that's what the cause is and you're going with with just this palliative approach Surgery, gives you a bit of a better, success with meningioma.
There's more success. So maybe nine months in dogs, maybe a couple of years or more in cats. If you've got a glioma surgery made by you six months, and so this is tumours of the cells of the brain.
So, a more serious situation. Radiation therapy. When used alone may buy you a year with the various types of brain tumour, Not a guarantee.
And as we know, when combined with surgery can buy you maybe a couple of years or so, so an expensive way to, treat these patients, but be more aggressive, so radiation can help it. It's obviously a tricky situation because you need to know what type of tumour to be able to give the owner the most accurate advice about treatment and prognosis. And rarely is this absolutely possible.
So we wanna finish with this, cognitive dysfunction syndrome. It's not talked about a lot. It is a cause of brain disease.
Confusion in dogs, also in cats, but will not cause specific neurologic dysfunction, so it will not cause Proceed deficits or, asymmetric blindness, for instance. So what is it? Well, we see it in many animals.
Most of them are older. So over eight. And it's been noted that in dogs, about 30% of patients over the age of 11 will have this.
70% of patients over the age of 50 will have this, clinical signs are used to suspect it, and the acronym of Disa is used where patients with chronic disorientation, interaction, changes or interaction with the owners. Other people sleep changes. They'll often be up at night and sleep in the day to some sort of reversal of their normal sleep house training loss.
They may have anxiety and an overall general activity decrease. These things make you suspicious that you have brain disease, and maybe it's cognitive dysfunction syndrome. You have to really look at ruling other things out.
There is no definitive test, but MRI can show you that you have brain atrophy as you get older. This cognitive dysfunction syndrome is similar, not identical, but similar to Alzheimer's in people. Here's a normal dog on the top.
Normal, healthy brain, lots of, white and Grey Mass are here. And then here's a dog with cognitive dysfunction syndrome where we've got atrophy of the brain, and hopefully you can appreciate there's more white here. This is all fluid around the brain.
The ventricles are bigger. Third ventricle is bigger. Here, this is brain atrophy.
And so, it's an exclusion diagnosis. MRI can help with behavioural questionnaires have been set up to again make you a little bit more confident that you have this. You're ruling out other diseases, and much like Alzheimer's.
The sooner you diagnose this, the better. And prevention is better than treatment. You know, we often feel well, our older relatives, older pets, maybe they just want a bit of a break from life.
So, turn on the afternoon shows and put them in a rocking chair. Well, that's not great, cos you need to maintain mental stimulation. Right?
So this is what has been proven to, delay the onset, delay the progression of these brain degenerative S, diseases. In addition, to dietary antioxidant use. Medium chain triglycerides have been used.
So there are some, commercial diets that contain these, brain diet from hills and, neuro care from Purina. I don't work for either, so I'm not promoting it. But medium chain triglycerides are in them.
B vitamins, fish oil. So many of these have been used, and we do often get a nutritionist to help us in an individual case. Come up with dietary suggestions that can take away, they, or should I say, more accurately can can, delay the inevitable with these cases medications or selegiline or Ranil?
Anapril. This is an inhibitor of the monoamine oxidase B pathway, which increases dopamine and catecholamine. So it will boost your brain, and reduces free radicals.
So has been shown again to help delay the, progression. Anything that you see in the patient most of the time is kind of a permanent change. Unfortunately, LEVES has been shown as an anti convulsant to have some effect on improving your mitochondrial function.
And in in so potentially, maybe an improved medication that helps patients with Alzheimer's and therefore dogs with cognitive dysfunction, so kind of watch this space on that drug anxiolytics many of these patients will have increased anxiety. Antidepressants, again, potentially, can go hand in hand, and then melatonin sleep. Wake cycles can be improved by the addition of this.
So just a brief summary to end with on that when we're comparing older dogs with brain disease, we need to keep an eye, an eye open for the potential of cognitive dysfunction syndrome. All right, so that is the end of this session. I really appreciate, your patients.
I'd be happy to take any questions by email. That you have, this QR code enters you into a free educational website that we run for, neurology. Please, feel free to, have a look around.
All right. Thank you very much.