Feb. 7, 2023

#86: Demystifying inflammatory brain disease. With Dr Sam Long

#86: Demystifying inflammatory brain disease. With Dr Sam Long
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Season 1

Who loves neurology?! That little blob of skull-jelly and all the wires that come off it can be very confusing and very intimidating, even more so when we start talking about the encephalitis/meningitis complex of diseases that we encounter in our veterinary patients. To help us make sense of the different immune-mediated neurological diseases we’re joined by specialist veterinary neurologist Dr Sam Long. Dr Sam gives us a clear plan for getting to a diagnosis, including how to make sense of serology testing and how to use some new diagnostic tools available to us. He also shares his tips on a practical treatment plan, even if you don’t manage to confirm a diagnosis. 

Dr Long underwent his residency and specialist training in Glasgow in the UK.  Following his specialist training he undertook a PhD in canine brain cancer before moving to the United States to take up a position as head of the Section of Neurology at the University of Pennsylvania’s Veterinary Hospital.  In 2008 Dr Long returned to Melbourne to establish the University of Melbourne Veterinary Hospital’s first-ever Neurology clinical service and specialist training programme. In 2017 he established Melbourne’s first private referral neurology service and in 2020 moved his service to the Veterinary Referral Hospital in Dandenong.  His research interests are in the field of brain tumours, canine epilepsy, canine spinal cord trauma and canine degenerative myelopathy.  He supervises resident and registrar training and has authored more than 30 papers and multiple book chapters on veterinary neurology. 

This episode is supported by the SVS Pathology Network. Contact their veterinary pathologists to discuss a diagnostic plan for your neurology cases at:

QML/TML Vetnostics (QLD & Tas): 1300 838 765 vetnostics@qml.com.au

Vetnostics (NSW & ACT): 02 9006 7468 enquiries@vetnostics.com.au

ASAP Laboratory (VIC): 1300 838 522 admin@asaplab.com.au

Vetpath (WA): 08 9317 0777 admin@vetpath.com.au

 

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Is it the case?Eager?I don't know what's wrong with this patient.Got to be neurological.Send it to a neurologist.Absolutely.Yes.Anything with depression or Tremors, which can include shivering apparently or a strange posture or anything that comes and goes kind of by default half the time ends up in urology.
So how many of those do you end up sitting back to medicine or surgery or something?Oh no.Usually by the time they get to me they've been through everyone else.So I have nowhere else to send me and then you put them on parades and hope for the best.Yeah, but I've got a good reason why.
Who loves neurology and you look at that concert list.And you see, under reason for visit acting strange, or circling to one side or seizures, do you go or do you go?Hey, that sounds like a fun challenge.
So why is that?Here's what I think.When we get that feeling, it's often a case of lack of clarity.I'm unclear on how to approach this case and clear on what my steps are and unclear on what to advise the I'd generally the type of people who come vets like to do this stuff, right?
We don't like that.Feeling of, I don't know what I'm doing here.So let's get some clarity on this topic, the inflammatory brain diseases, the GM, he's and mu 0 is and steroid.Responsive meningitis has and whatever else.Just the list of names is confusing.
In this episode, we have specialist veteran in neurologist, dr.Sam long, from the veteran e, referral Hospital in Melbourne to help us, make sense of which diseases, what?And to teach us what to be on the lookout for to make sure we don't miss the inflammatory brain diseases.In the consult room, Sam gives us a clear plan for getting to a diagnosis.
Including how to make sense of serology tasting for infectious brain disease as well as some new Tools in our lab testing tool box.And of course, how to treat these diseases, once we do have a diagnosis or even if we don't manage to get to final diagnosis because of finances or whatever else.
Now quick clarification on something, you'll hear us talk about serology testing, you know, the IGG and IGM panels for Tock 7eo and Elk at crypto and all of those funky kind of things.And you'll also hear us, Talk about the new, or at least new to me, neurology PCR panels, which I was thrilled to learn about because goodness knows we can use all the help we can get for these cases.
If you haven't heard of them yet, they are now PCR.Tests, available for the common infectious organisms, that can affect the nervous system, and that we need to rule out.When we chasing a diagnosis for near a disease.If you're in Australia, you can get these Downs at whichever of the labs that are part of the SPs pathology Network you're using.
So that's with gnostics The red path ASAP laboratory and qml with gnostics.Depending on where you are.You have heard us talk about them in previous episodes as a financial supporter of the podcast and they are currently supporting this episode as well which is convenient because I needed some clarification.
So as earlier in the episode deciding whether to send Bloods for serology or CSF for PCR or maybe sending both is still the tricky decision.Even if you're a neurologist each test has pros and cons.And Each test adds value and has limitations.
So I spoke to a pathologist friends at the SBS pathology Network which for me here in Queensland is qml with gnostics and the takeaway from that conversation was that as a practicing with, you don't need to know and remember all of the ins and outs.You just need to remember the phone number of your SVS, pathology Network, pathologist when you get that narrows case make a diagnostic plan.
But before you start sticking needles into spinal cords, or sending Bloods or whatever, Hop on the phone to your pathologist to talk through the case they smarter than you and they very nice.Okay.Let's get to it, dr.Sam long.And the inflammatory brain diseases.
I'll save.Thank you so much for joining us on the way.It felt to talk neurology because novel, or GP B.Love, Brian cases, right?Absolutely, isn't it?Their favorite specialization it?Why is it so intimidating?Do you think Sam?I don't know.
I think I wonder if it's because there's a lot of anatomy, you know, when we sort of teach students in that school, there's a hell of a lot of, you know, forebrain midbrain brainstem proprioceptive Pathways murder neurons, upper motor, neuron There's a lot of terminology in a lot of anatomy and I think that gets a bit daunting to people I know the time, but it's not that hard.
I mean, I'm a neurologist.I wouldn't be doing it if it were, if it was really hard.So our topic for today.So when I Was preparing for this, I I realized we could, you can go so vast and it's a veteran neurology.So, should we try and focus on?
I don't know.Do we call it the inflammatory neurological diseases, 10, sifl lightest type syndromes.Does that make?Sense.Is that is it a good thing to group together?Sure.Do you want to include the I'm going to use this word and I hate myself for doing it.Do you want to include the meningitis story as well?
Yeah, definitely.It is there any other kind?Well I think it's useful because the word meningitis gets thrown around like almost nothing else, really buy all sorts of vets and I think it's worth reminding people of a couple of things.
Number one I'm going to turn To the lecturer.When we talk literally about all of the artists has whether it's Encephalitis, whether it's meningitis, whether it's myelitis, literally, what we're talking about is inflammation, so inflammatory cells coming and infiltrating and an organ or tissue and causing a response that's driven by the immune system meningitis.
Just means that that inflammatory reaction is within the meninges.So the outer layer of either the brain or the spinal cord, both of them are covered with men in.Geez, we use this word very commonly because many drivers is a really relatively common in pretty well, understood conditioning people.
But there is a major difference between the human and the veterinary world.So less than 2% of all meningitis, cases in dogs, particularly are infectious and the vast majority of men, and I've seen people is infectious either viral or bacterial.
Meningococcal, and all of those conditions.So when we talk about meningitis we do it but it's it's much much more common that when we see many jobs in our patient patients it's going to be as part of an immune-mediated disease or an autoimmune disease.
Well less than 2%.Yeah.Very very uncommon C infection.I mean as a general rule infection in the CNS of dogs and cats is pretty rare, it's much more.Commonly you're going to have other drivers of information.And mostly that means autoimmune disease.
What mean with yet a disease just which is one of the, you know, one of the occasions where we're a little bit different.People compared with dogs and cats, infections much, much more common for us than it is for dogs and cats.One of the first things were, but I normally try and start, when I tackle the topic is to make sure we don't miss it, but you get it on the radar off the radar when we see something.
So, when we zooming in on these Let's call them.These immune mediated or inflammatory related brain diseases, are they things?That will move it up on the d-list compared to a tumor or epilepsy, or a neurotoxin or something like that?Or is it kind of Ulster?
Same potential presentation.It can be enormously variable so I guess it's probably worth signing off by making sure.We know what we're talking about.So when for me as a neurologist, the inflammatory diseases that I think of, when I'm thinking of immune-mediated disease.
So we'll leave the infections aside for now.But when I'm thinking of immune-mediated disease in the brain or the spinal cord dogs and cats, the things that I would consider would be most commonly would be mu 0, so meningoencephalitis of Unknown Origin.Yeah, I would consider a couple of other quirky things like cerebellar or corticosteroids responsive Tremor.
Syndrome is probably the best name for what we want to called Shake a dog disease or white Harry Shaker disease or idiopathic terrible itís.And then, I would include SRM a, or corticosteroid responsive meningitis, arteritis.Those would probably be my big three when you're thinking of non-infectious immune-mediated disease in Brandon's bunker Dawson cat.
Or what about gme going along?Yeah.Okay.So mu 0 is this basket term too many guns, have lightest of Unknown Origin is now this huge basket term for what includes both gme and all of the breed Associated Encephalitis.
So you probably come across Pug.Encephalitis Yorkshire, Terrier Encephalitis Maltese tear into flames, Chihuahua, and have lights, all these sorts of things within that basket.I sort of I do think about the two groups as separate, but you can't be absolutely sure from an MRI and CSF.
Tap, which one is, which the only way you can tell for sure is to have a bit of the brain under a microscope in front of you and both of them were use the same drugs to treat and they both Both within that sort of basket but the gme and all of the others tend to end up having the same survival times with the treatments that we use, which is why we put them all into one big basket.
So gme we've known about since the 60s and 70s, 1960s and 70s and in the very, very early days, there was some discussion about it being a form of cancer, probably lymphoma related.
You have a look at dogs with gme and you have a look at that their brains under the microscope, they have these this amazing immune response which is so full of lymphocytes and mononuclear cells, plasma cells, and macrophages and those cells are so busy that you often have a huge ton of mitotic figures on the on the microscope field in front of you.
So it really can look a lot like a tumor in some in some respect and Once Upon a Time, the gme used to be called inflammatory reticular system, there the other end of this funny condition called reticular sis was called me, a plastic meticulous and that was then reclassified as b-cell lymphoma.
So, there are some bits of gme that, in the past, we've wondered about, whether it could be a type of tumor, but we think it probably isn't, and then all of the other diseases which we've seen probably some from the 1980s onwards.
When pug Encephalitis was first identified, those forms of encephalitis.Look, much more the inflammation.When you look at these brains histologically is much quieter.It's more like these, our brains, where great big areas have just died and been wiped out, and you're left with holes in the brain and a much quieter immune response around the edges.
And that's the same.Whether you're looking at the plugs or the chihuahuas, or the Maltese areas or the Orcs Chariot, you know, it's a necrotizing process that the immune response is there but the end result is is death of the tissue.So you end up with sort of lakes of food and when you look at those guys on Mi you see you know holds effectively that are just full of fluid not much in the way of contrast uptake.
Usually not much in the way of swelling or huge numbers of of inflammatory cells coming into the brain and making it bigger on one side.A to the other whereas Jamie sometimes is much more.Some gme cases look like they have come to long.You look at them on Emma and yet you put you put all of these dogs on, you know, corticosteroids plus one of a number of other immuno modulatory drugs and they all get better.
And they all lived for about the same amount of time.And what about your what?Because you're differentiated steroid responses mean engine itself latest are traitors from the embryos.How's that different pathologically Management and everything else.So SRM a is that when neurologists get together they use all of the letters and SRM is the one that we tend to pull out for these guys.
So that the classic picture is a young large breed dog with neck pain and pyrexia, you know, the Labradors golden retrievers wine Runners and similar sort of largely dogs.Essentially what you're working up is a Pyrex your of Unknown Origin with neck pain initially and those guys you put in Into the MRI, you find nothing.
So it's not quite true.You find almost nothing in the spinal cord.Sometimes you'll find a bit of information, interestingly within the muscle for reasons, we don't really understand and you put those dogs on immunosuppressive doses of steroids but you can get them off immunosuppressive just of steroids and cure them effectively.
So mu 0 cases tend to be smaller breeds.And tend to be older.The SR May tend to be large breed dogs and younger.Mostly presenting just with neck pain and parity, I occasionally some neurological deficits, not much.
So those guys look like they have spinal cord disease where the muo cases again, mostly look like the head brain disease.That's really useful.So when we say steroid response of the immune rose up, also steroid responsive but not as response.Yeah.So that mu woes I sort of think of them a little bit like treating cancer.
We think we can put them into remission for long periods of time.Yeah, but almost always they're going to come back eventually and ultimately will kill the animal.Most of the time these days we get several years before that happens but probably a fatal disease.
All right, that helps a lot in terms of better Genesis.Do we understand?Is it simply autoimmune disease?Like and I am ha or a whatever it may be but except instead of red blood cells, the immune system starts bullying them.The system.
Yeah, essentially.And and the honest answer is, no, we don't know.There have been some people that have done some pretty extensive hunting for infectious triggers or causes.So it's a weave pretty consistently failed to find any evidence of infectious causes.
None of this is very conclusive and doesn't get us very much further than the fact that it's a, basically, an immune system attack on the brain.Presumably, there's a genetic component just because we see it much more.Only in some breeds and some types of dog.
I would say as in small dogs is because small breeds rather than large breeds of dogs increasingly, you know, we expect to see mu 0 in just about any small breed of dog, they stage.And so there must be something about the genetics that make you a pug or a Maltese or Chihuahua.
That makes it more likely that you're going to get this inflammatory response but we don't know what it is.It's certainly not a single Gene.That's the problem.It's going to be a multi-generational.Genacore polygenic in nature if it is.So I just had a thought that bugs do ours and what these are so stupid.
They actually allergic to their own brains that mean that you can't be a real pain to kill your brain cells or so back to that initial consult the small dog that comes in with narrow signs.
Other things that are going to take it off the DD list for us like age or present presenting signs or harvest can say generally doesn't happen in in old dogs, but on Tuesday, I sort of fourteen-year-old Yorkshire Terrier that looks like he's got it.
So, not necessarily the thing that makes me really think of mu 0 classically would be a, what we would talk about, as multifocal localization.So, you know, as neurologist would pretty simple types.And we generally start, when we see our patients with this, basic assumption, that there is only one problem in one part of the nervous system and you explain all of you.
When we localize things with our neuro exam, you explain all of the abnormalities and and and the normal stuff with this one, lesion in one part of the brain or spinal cord, sort of idea.But with these guys we generally or often will see things that are Not just in one place often you'll see a symmetric sign.
So changes for instance in the left for brain toward signs, that suggest you've got a problem in the left for brain and also the right stimulus system or rightful brain and and also maybe something else going on the left side of the brain tumor.
And so by and large that the kind of the classic presentation, you know, the one that you never actually see but that's in all the textbooks is one of multifocal.Aziz, that's a symmetric.So that's probably the strongest, give away.
The other thing, I would say it's a little bit of a, sort of a pretty subtle thing with the general theme for the MU 0 cases is that they're almost always in training.So it's almost always just brain disease, even though we're talking about multifocal disease and pretty much exclusively the necrotizing group, The Pub Chihuahua, Maltese Yorkshire, terrier group of diseases.
Those guys end up having their lesions restricted to the brain.Where in gme you can have a lesion just in the sponge or in the brain.And this from do, these guys, normally seizure like a sea during dog, it is on your list of DD.
Yes, it is.And, you know, the deal with seizures in general when I'm talking to the resident or to the unassisted.I say, you know, when you see seizures that is just an indication.Now that you've got a problem in the forebrain, if you see seizures, that's just sign that the full range unhappy of that.
If there's this enormous list of differentials that can cause seizures with in the forebrain and one of those things is inflammatory disease and in particular, mu R and then we mentioned the S.There s rma's are often painful when I year Encephalitis.
I think of pain do the Jimmy's and these sort of the muh 8.Present with neck pain or spinal pain or anything, or not really, no, usually not the other.I mean, a couple of other things that are generally fit the pattern, but an exclusive would be something that's been progressing for a little while so something that that it hasn't.
You know, the dog hasn't been normal yesterday and is suddenly abnormal today.Usually, these are conditions that progress over a few days or a week or a few weeks as always exceptions to every rule, but that's the general pain.Not Usually painful but occasionally because there are no pain receptors or nerve endings within the brain or the spinal cord itself, you don't feel pain because of the problem with in your brain, you feel pain.
If you've got something like hydrocephalus that's expanding your through glamour, brain enough to squash your meninges SRM, a is painful because you have inflammation within the meninges, but if the inflammation is just in the brain or the spinal cord generally speaking In non-painful.
Okay?So, these are going to be small breed dogs that see during or circling or having weird behavioral changes or less.So, come things would be cortical blindness.So loss of vision in one eye that is not accompanied by a change.
In PL are so if the pupil is still responsive to light on both sides, but your Menace response is absent on one side, for instance, in the animals, not seem then that would indicate that it's for brain causing blindness rather than an ocular or cranial nerve to so clean.
The usual for brain science.Circling hemiparesis cortico said, proprioceptive deficits on the side opposite, the lesion getting stuck in Corners.Head pressing or that's of stuff seizures, plus or minus stuff going on in the hindbrain as well.To cerebellar signs or cranial nerve.
Deficits were associated with the brain stem, that sort of thing.So are we at Chasing a diagnosis for them, usually you need some sort of Imaging and sadly a Mars is both the most expensive and the best CT is it's not at all.
Uncommon for you to miss some of these lesions if you're looking for them on CT, where Mr. Is going to show you what the lesions are and probably some extent going to help you sort out.Whether it's Jamie or necrotizing enterocolitis if you'll, if you care that much about which ones which Based on since we treat them both the same, you may not be that trust that NCS have tapped.
So doing a month after a quick break to plug our clinical podcasts.So we talked about the clarity around our cases at the start of this episode and about how feeling unclear can affect how you feel about work, and that's the goal with our clinical podcasts, more clarity on more things presented in a format that you'll actually use, and it's easy to you a clinical podcast, our conversations with Specialists, where I ask all the questions that I've struggled with or being confused about or garden stuck on or seen others get stuck on over my career, these are not lectures and they not the definitive guide on any one topic they had to fill in the gaps and get some real and practical advice from people who are the best in their field that you can use today in your next case, and the ultimate goal with these is not just to know more, it's to understand more And to feel better because it feels great to be just a little bit better than you were yesterday.
Go and try it for free and VV n dot super cast.com.So in the the GP clinic on the emergency clinic, you have your nearest case, it's showing all these signs from what you said to him.In less than 2% are going to be infectious.
Trying to think of it, your initial workup before I send it to Sam.What should I be doing?So it's always a good thing to make sure you've done blood work.There are a couple of things you can do if it is a patient where SRM a is on the list then CRP is often very very high.
So it's a a marker.It's not terribly specific, so a whole bunch of other things.Will also makes you happy high but it's one more thing that adds to the and one of the other things you can do is go some way towards ruling out.The Infectious causes of information by looking for serology, for nice, for a Toxoplasma checked for crypto as well.
Do an elk at.So if you say serology, I something crossed my radar.The other day that there's now potentially PC artists for these things because it used to be you, I'd say in these seizure panels of going.Yeah, I'm getting nothing back.It's got to be for 500 bucks for the results or even words I get a result but it's that iffy.
Yeah.Has been exposed in the past, but rather you are, that means nothing.So, are we changing his anything new?Yeah.So there is this, this PCR panel that you can run and it looks for in dogs Toxoplasma.These for a distemper and just Romulus, and in cat, looks for Toxoplasma, cryptococcus actually cooked, Cox's Onkyo anglin's.
Well, so couple things.Number one, Whatever test, you run.Ideally its best run on CSF because if you're finding, either DNA of the organism that you're looking for or antibodies in your CSF, then then that means that whatever you're looking for and have found is being made in The central nervous system slight, caveat on that if you do a CSF tap and get a ton of blood, then that will doesn't quite apply because could be leakage from the systemic circulation.
But by and large, you know, things like antibodies and DNA of organisms that you pick up in on a clean CR CSF, tap have to have been made within the central nervous system.And you would think that if you're looking for DNA of an organism with PCI, given how in Credibly sensitive.
The technology is if you find the DNA in the central nervous system, it's absolutely got to be the case that the infection is there.And if you don't find it, equally that the infection isn't there, in my experience, neither of those two things is absolutely bulletproof.
It's a couple of things.If you've got a little bit of DNA of an orgasm, that's buried deep within the print convert issue, it might never get to a Surface where CSF is flowing and therefore allow it to be picked up by OPC are even though.Whatever it is you know what is, what is it?
1 ml of a substance in an Olympic-sized swimming pool containing.DNA is sufficient for you to be able to detected on PCR as a general rule but that still will see false negatives and we'll also see false positives.
So just because you've got DNA of an orgasm in your central nervous system doesn't mean that the organism is alive or causing.Infection.So in an Ideal World with clients for whom money is not a particularly big problem that you'll your safest bet is actually to combine both serology and PCR panels on your CSF and profile.
So serology, I'm taking for antibodies pci's.Checking for DNA of the organism in my head, surely, you're going to be more reliably picking up DNA than antibodies or not necessarily you would think so wouldn't you?You but I don't think that's necessarily the case.
I think you've got to put all of these things.You've got to add everything up, together.You've got to put the PCR results.Together with what you've seen on the MRI and the CSF.Cell count looks like and all that sort of thing.But I'm looking for a shortcut, you're not giving me any shortcuts this.All right, we're not very good at dealing with shortcuts.
Yeah, it can be quite frustrating sometimes.So let's say, is you say I in an Ideal World to going to ask before.To you.Is it worth sending blood for serology and PCR or do you just go?Look this is go for CSF if you can it's a useful thing to do because if I mean if you do get a screamingly high titer too.
Nice for or toxin, for instance?Then you can say, oh, well this this may well be the case that that we've got my answer again putting it into context with everything else you're on your exam and whether that fits with what the patient's doing.So on so forth, but yeah.
Yeah, if you get a toxo tighter of one in 1048 or even probably one in 512, you can say, okay, that's that's a real number anything lower than then I tend to think of as a little bit equivocal some people you know the lab most Labs will probably say a tighter of other one in 64 is suspicious.
I like to see greater than one in five hundred and twelve to be certain of an active infection.IGM and IGG infected up the other side of the.Or the other issue is that when you're looking to titers against in particular, the protozoal diseases, toxic only a spora IGG and IGM.
The labs will sort of give you often this little guide to whether one is high and the other is not high and whether that means it's an active infection or a recent previous infection or just previous exposure.I tend to put more weight on on absolute numbers.
And then how do we interpret the PC?Ours is a positive, a positive.If I get here, get back crypto.Yeah, this crypto in the blood.So the PCR on blood may not be terribly helpful surrounded, she's probably much more useful.I would have said so I tend to reserve PCR for just looking at CSF samples.
And the point of this, you know if we're talking about the mus in general, what we're looking for is to find none of these, you know you want to say that there is no.No infection going on.So you want all the all of your PC as ideally to be - I've certainly had cases where everything else really fits with them.
You are the one of the PCR results has come back as being positive live said, are you absolutely sure.And if you talk to the lab and you get them to rerun the sample, that is it's worth rechecking.If you, if it doesn't fit, if you've gone positive result and the animal has its a three-year-old pug.
Is full brain signs and some evidence of asymmetry and you really, really are suspicious.And then we won double-check the positive PCR, it's more likely to be a false positive.All right, so let's say you've got the client in that are the don't have all the money in the world and it's that sort of Narrows case.
Is it something you'd leave off?Leave out of your work up.Yeah, I think so.I would probably if they've got the money I do serology.Then you're left with a best-guess scenario which is where things can little bit tricky.So you've got, you've got a little bit of okay, well mu 0 is top of our differential list, because again, the breeds right the ages, right?
And it's a multifocal intracranial localization, but you still not entirely.Sure.Then all you can do is say, look, I think it is but I can't be absolutely sure the gamble.Is that what you're needing to do?
To treat with immunosuppression.And if there is an infection there, even though it's unlikely, things could go south very quickly.I'll often do the halfway house is to start with anti-inflammatory just as a prednisolone with clindamycin at the same time and then if you get to the point where there's some signs of improvement and you know that there's, you know, you can't get any further, diagnostic e, then you can say, okay, well we're going to take this Gamble and as long as as the owners are on side and your and you've scared them as much as you can with the consequences of immunosuppression in an animal that hasn't had a complete diagnosis.
It's all he can do because the alternative is, you know, if it is Mu 0, it's going to be very rapidly fatal if you don't do anything.Yeah.All right let's talk about the Glide then that can go further.So we've done serology in-house.
We've done full blades for bloodsworth.It.Yeah.Looking for liver issues.It's like that.Yeah, suddenly.I mean, there's some of these cases will only just present with full brain signs or with teachers, so, certainly for blades.And if there's any indication that, that there's liver disease, you know, bonus tolerance, tests, also useful.
Okay?So we've done all those than serology, they -.So next step is CSF or Imaging.I much prefer to do imaging plus CS F.If the CSF is Vindicated, the reason being that it's not that uncommon.
I mean, CSF Taps occasionally a very risky in a dangerous thing to do.If you've got some cause of raised intracranial pressure and you haven't identified that because if you've got, you know, let's say it's an obstructive hydrocephalus that you haven't picked up and there's there's a huge amount of pressure within scold.
You do a CSF tap and what physiologically, what you're doing is releasing the pressure on the outside of the skull.Setting up this pressure.Differential high pressure within the skull low pressure outside the skull and in an attempt to equalize the pressure.The brain is going to try and leave the skull which is never a good idea when your brain tries to leave your Scholars and know.
So so you can get fatal trends for aminal herniation in those situations.So if at all possible, I will do the Imaging first.Make sure there isn't raised intracranial pressure or something else.That raises the risk of CSF Taps.
And then when I'm happy, I'll do the CSF tab in an ideal world.Is the combination of those two things that gives you your diagnosis.Okay, but you're not going to pick up that pressure clinically, it's going to be an Imaging, know it's, there are few things that can help.
So in general animals that are really, really dull than can be an indicator of high intricate Impressions.It's just not a terribly specific.Helpful neurological training and some of the time, if you do a fun dick exam, you may see papilledema.
So swelling of the optic nerve that can be a useful Hallmark of raised intracranial pressure And not a guarantees the problem.So you sometimes you can be surprised and find a patient that has been walking around as though nothing's wrong.
Has tons of swelling going on and you end up going.Oh, I'm very glad we did the MRI.We're not going to do the CSF tap on this.So I'm just trying to picture a scenario over the the end only that can't go for Imaging or you stuck in the middle of the country where there's no Imaging available.
Is it worth doing a CSF?Tap is it with drooling out things?If you have the technical skills.Yeah if you've got enough.So if the skills are there and your And it's all you've gotten and the owners are happy to take the risk.
Then that's better.It's probably better than doing nothing.Probably.But you you do have to warn them that this, you know, you could do the CSF tap and that could be the end of everything.If if that's the case and you've missed it in general, you know, if the animal is relatively bright and and is looking like, it's not tremendously sick.
That's a terribly vague thing to say, I know it.But, you know, that the ones that have raised intracranial, Will often, and they will often look like there's something seriously wrong with them.And if that's not the case, then you can say to people look like they're absolutely definite risk, that things can go terribly wrong, but the option is to do immunosuppression blindly, but otherwise your alternative is again.
Best guess, you know, we've we rule out the infections of in can and then we start with anti-inflammatory just as prednisone and condom.Bison, give us a week or so, to cover everything and if there's some improvement, then you could say, okay, let's try an expression.
That's the best you can do and that's night, okay?The scenario of taking a serious if Deb when you're not in a specialist Centre or not right next to the lab I've heard before that.It doesn't transport.Well doesn't hold well as a sample is it worth doing at all?
Like what are you going to learn from a sample?That's going to take two days to get to the lab from Alice Springs or Yeah, if you're a long way away from a lamb then probably not worth doing it, there are kind of ways that you can can.Look at CSF, samples yourself.
If you have a hummus, I am and you're good at, you know, if you're familiar with it and you're good at using it, you can take a drop of CSF and put if you've got a you know, a good counter and you put a microscope slide on it and you put the right amount of CSF in.
If you're a million miles away from from a good lab, it's Lee worth figuring out how to do those things and acquire those skills, but otherwise, it needs to be really at a lab within probably 12 hours.Does that does the same hold true for the PCR.
You mentioned, sending says, if for PCR, PC has a pretty stable, you can get DNA out of paraffin embedded tissue and still work, but that's okay.So you can still send it off for that.You can look in hours for inflammatory cells and then send it off for that.That's right.Okay, so anti-inflammatory doses of breads, What do you classify as an anti-inflammatory dose of bread?
Yeah, I'm probably a little bit higher than most for dogs point.Two five, two five, two point, five milligrams, per kilogram twice a day initially and then tapering off if you're not going any higher, my immunosuppressive does for dog would be one Mig TIG be ID for a cat.
Double that in large Stones.I'll often calculate the dose per meter squared rather than milligrams per kilogram because big Dogs tend to do, you know, they have much, they just don't seem to tolerate steroids nearly as well as fold up.
Still both big and small dogs tolerate steroids better than people do that.And then when you get to immunosuppressive doses of of corticosteroids the other important thing is you need to add in something else as well.So my usual recipe will be to start in Nespresso just of steroids and then add something your options are Cyclosporine or Science Center Ivan aside, or azathioprine, or make sure in late or left in mind, which one do you use?
It really is unusually.What we do is we use one of them until it stops working and then we move on to the next and then to the next.And then to the next cyclosporine is probably the easiest, you know, it's twice daily, it's all templates.You can give it home, you can write it as a script.
If you do write script, you want to make sure it's the micro-emulsion that you get the equivalent of them, the oil.And the other thing about cyclosporine is that when you are using it, we would commonly use it at a 5 mg per kg B ID dose and you ideally run a trough serum level a week after you start because some dogs at then 5 milligrams per kilogram, dose will have a serum level of over 800, whatever is micrograms per milliliter and you only I need it to be about about 250.
So for some of those dogs you can drop the do significant, some dogs, you started 505 Mig TIG be Hardy and they'll have a serum level of three or four hundred so you don't need to change the dose.But in some dogs, you can drop the dose from there.The site is for, in side effects are most common one rgi related to vomiting and diarrhea but generally it's pretty safe and it's pretty easy in the UK depending on where you are.
Ooh are you know the UK in the state's a lot of neurologists will reach to cytosine arrived in a side as your first extra in munis precedent but that's a little bit more tedious because you've got to give it as an infusion.Really should treated like a cytotoxic agent that you're given as part of chemotherapy and it's a it's just a little bit more painful waste you know our protocols traditionally we've done, you know one dose every three weeks which is an infusion over 12 hours away.
As base every three weeks, three Doses.And then every four weeks before their asses and then every five weeks for five doses.There's been some suggestion that was paid rather you catered.Suggest you can just do a single infusion at the beginning and and it's almost as good as doing the whole other rigmarole.
But I think our experiences that sadly probably isn't and then at the same time as you're doing all of this, your you've started your stare.Droids at and immunosuppressive dose and do that for six weeks and then you tape it by half every six weeks until it's off.
Is that for the embryos or does the same hold true for there is the steroid responses and enjoy.So for the MU has we use you know prednisolone plus and for the ass rma's prednisone on its own, it's fine.So same protocol.
Temporary got better outcome.Yeah.Curative rather than remission.Okay.Is it categorically going to be six weeks later?Six weekly reduction or do monitor response to monitor CRP at all?Yeah, so for the SRM a, there is paper out there.
That says, actually, what you can do is, is taper in response to the CRP but not all of them will have an elevated CRP at the beginning, so you don't always get to you CRP to guide you all tapering there are, you know, again a couple of earlier Studies have suggested that you can look at CSF.
Cell counts and tab that way for the to bit painful and expensive.To do a CSF type of, every six weeks.And similarly, that early, you know, definitive diagnostic tools was to look at some, I GA levels for then CSF and again, to taper in response to IGN levels but you're back into the same problem.
You really don't want to be knocking out and doing CSF, that silly six weeks.Okay, so we kind of thinking 26-week, sleep cycles and if they if you taper and Get worse than you.Bang up again to the previous.Yeah, pretty much stay.There are some dogs where we have to do it every eight weeks.
There's a study out of North Carolina in the past couple of weeks, it's yes, maybe you don't need to do it quite so, you know, this, the six weeks is maybe a little bit of Overkill, but I generally have found that that six-week number, it gives you the most reliable response and does it for both the drugs for the embryos that you've got a steroid blasts for the MU owes you leave your second.
And immunosuppressant going for as long as you can and the likelihood is that it eventually will stop working speed like you know, lymphoma protocols, you know, once they're in remission, you you keep going but then at some point the cancer cells seem to become resistant and the same with the inflammatory cells in the MU are they seem to become resistant?
We think two things especially the interesting thing is that the median survival times for there have been a bunch of papers.Now looking at All of these individually scientific sites for entire being AZT mycophenolate.And all of them, when you put them all in a row, have roughly similar survival times of a pattern again on average about 20, odd years, two to three years in the order of some 1,200 odds days but because it's an average, you just don't know what each individual dog in front of you is going to do some of those.
It'll be six months before they stop responding to the psyche, sporting have to use something else.And some dogs, it'll be three years.Generally, if this little you start and cyclosporine and you get six months or three months, they do worse and you drop it to as a fire brain or something.
Do they generally respond or do they respond to less the second round?That's also good question.I would.So I just to sort of clarify.The other thing I'll do is Bump The Pride back up to immunosuppressive doses at the same time and then start the weaned all over again.
So it's probably the combination of the two that shows Improvement.And my own kind of personal feeling is that the necrotizing enterocolitis cases tend to respond slightly less well than the GM.He's you don't get quite back to where you were with each successive changer, if that makes sense.
Kind of makes sense.If you've got holes in your brain, I'm going to really going to plug the holes with breads.Are you.That's right.There's a little bit less, you can rescue.That's a really insightful.That's clarified a lot of things.As for me, I am I missing anything Sam.I'm sure I'm missing a lot but that's, uh, that's a good stab we've covered.
I would have said we've covered.Most of the important stuff I reckon and very briefly these conditions, they're not thinking cats, right?I don't think so again my personal feeling versus the evidence, there are a couple of terms out there that have diagnosed muo in cats but I think it's almost certainly a fundamentally different disease.
And I just don't think we've we certainly don't see it in the same sort of numbers.And I think it probably fundamentally is something else to catch them.Like, humans will likely go to be infectious or something else.Probably.Yeah, marvelous em.
Thank you so much for that.Thank you for your time.Which every night.

Dr Sam Long