Hello, my name is Alex. I'm one of the neurologists at at Davies's Vets. And and this webinar is essentially looking at neuromuscular cases and and emergencies in in sort of clinical practise.

. So we'll have a brief introduction into those dogs that have neuromuscular disease. And then I thought, sort of the best way to go forward is then to have a few case examples. And so we'll look at how they presented, what they were like when they came to us, at the time of presentation, and then what diagnostics we did and what we came up with from a, a diagnosis point of view, and then how we go about, about treating them.

. And then hopefully that will give you a bit of a flavour as to the most common sort of neuromuscular cases that we see in in the referral setting. I'll try and go through what you know, you can do in the first opinion practise setting if if referral isn't an option and and then and then go from there. And so I guess the first thing to touch on in is that in, when we have a dog with a, a neuromuscular disorder, what we essentially see is, is a weakness rather than an ataxia.

So we often describe these dogs as being poetic and either paraporetic if it's just the back legs that are affected, or tetraporetic if it's all four limbs. And the same in, in cats obviously as well. And, and like I say, the main finding that we often sort of characterise as this sort of disease is this sort of generalised weakness.

It would be very unusual. You shouldn't really see any form of ataxia in a dog or cat with a neuromuscular disorder. It should just be paresis.

And so as part of your neurological assessment, one of the most important parts of the examination to ascertain whether your patient has a a neuromuscular disorder is whether they have present or absent reflexes. And so the main reflexes we check are the withdrawal reflexes and the the patellar reflexes in, in the hind limbs. And and if they are reduced or absent in all four limbs, then certainly we start to get worried about a problem affecting the, the neuromuscular system.

When we talk about the neuromuscular system, we're essentially talking about three components of it. You have the, the nerves, so the peripheral nerves that come away from the spinal cord and travel down your limbs. We have the muscles, where these nerves, sort of, synapse onto and that synapse itself, so the neuromuscular junction, might be affected if you.

Have something affecting the junction itself. And so when we talk about a problem affecting a dog's neuromuscular system, we essentially mean either the peripheral nerves, the actual muscle itself, or the junction in between the two. And so anything affecting one of those groups, is essentially a neuromuscular problem.

And when we talk about it in terms of how this works from a path of physiology point of view, you have your electrical activity that's transmitted down through your axon of your peripheral nerve. And this sort of electrical activity is passed along the cell membranes by sort of movement of sodium and potassium ions in and out of the cell, and it's also heavily influenced by by calcium. So if you have a disease that causes electrolyte disturbances, or either a hypernatremia or hypo er calcemia, then you will get a change in your neuromuscular junction and that might end up looking like a dog or cat with neuromuscular disease.

And then when your axon reaches the synaptic slick left in the synaptic junction, you get a release of acetylcholine that goes across to the receptors in the muscle, and then again, sort of modulated by calcium, you then get an action potential coursing through your muscle, which causes the contraction of, of that. And so again, a disturbance of that junction or a disturbance of the muscle and its receptors can also give you a patient with the disorder affecting their neuromuscular system. And when we have a, a dog that presents to us, with a generalised neuromuscular disease, I guess there's a few things that would come to the forefront of our minds in terms of differential diagnoses.

The first two are probably the most common reasons we see dogs come to us, to the referral clinic with a neuromuscular disease. The first is acute idiopathic polyradicular neuritis, and the second is, is myasthenia gravis. Now technically and in textbooks, you'll see that patients with botulism can present with a neuromuscular disease or a tick paralysis.

In reality, we never really see these in the UK it's quite rare to see them at all. And so whilst they should be on your list. Like I say, really, really unlikely.

But occasionally, it's always worth having in mind that, you know, a power neoplastic process can cause a polyneuropathy or, or even a junctionopathy. And so that's always worth bearing in mind with these, with these patients as we, as we go forward. And so I guess the most important thing is that when you do your neurological assessment and you localise the problem to the neuromuscular system.

That essentially means that we're not really dealing with a disease affecting the brain or the spinal cord, but obviously the peripheral nerves, the muscles or the junctions in between. And so straight away we know we don't need to do an MRI scan for these dogs. A lot of our diagnostics, is actually more to do with sort of blood work, and maybe some other forms of, of imaging.

And if you're then confident enough to diagnose these patients in, in practise. Actually, a lot of what we do in the referral setting are things that you could do in your own first opinion practise itself because you don't need to do an MRI scan with, with the majority of these patients. And so if I have a dog or cat that comes to me, I'm pretty convinced it has a problem affecting its neuromuscular system.

The first thing I do would be to do a full haematology and biochemistry and just make sure your biochemistry includes . Creating kinase. I often do, often do thyroid function tests and often do a complete urinalysis as the baseline.

If you have a myopathy, often your your CK will be up. Obviously it's important to check for electrolyte disturbances, particularly, you know, sodium, potassium or or calcium changes, and also it helps you to rule out any particular endocrin. That might give us a neuromuscular disease.

So that's the first thing I would do. The second thing, again, depending a little bit on how they present, it's worth checking for anti-accetylcholine receptor antibodies if you're suspicious of myasthenia gravis. And it's often worth just checking for toxoplasma and neospira, antibodies as well, although, like I say, pretty, pretty rare.

Often in these patients, we end up doing thoracic and abdominal imaging, primarily to rule out any neoplastic process, or a tumour in, in, in one of those cavities. It's also quite good to check for a megaroesophagus. Some of our neuromuscular diseases can also have a concurrent megaesophagus, so always worth checking.

And also because they're a bit more prone to getting aspiration pneumonia, it's quite good to check, as a baseline that we haven't got any signs of that at present. We'll come on to it a little bit more in a bit more detail later on, but often we do an Ehonium challenge test for dogs we suspect to have myasthenia gravis. And I guess, you know, the 1st 4 boxes of this diagnostic pathway are things that you could feasibly do in your own practise or own first opinion practise if you have the, the capability.

When we get down to route of doing electrodiagnostics, so often we do this under heavy sedation or or or general anaesthesia, particularly if you're doing nerve conduction studies. This is a bit more maybe something that we do at the referral setting, and we're checking other EMG or motor nerve conduction velocities or or repetitive nerve stimulations, . And occasionally we'll do nerve and biopsies following that to get us a bit more information from a diagnostic point of view.

Occasionally we we might do a spinal fluid tap on these patients, but, but like I say, it's not massively indicated in, in the majority of them. Fine. And so I thought the best sort of way to go forward from here would be to start with a few cases.

And like I said, the idea is to try to work through them as if they presented to them, them to you yourselves. And so we'll start with the signalment and the history, and then the neurological exam, where we localise, coming up with some differentials, and then the diagnostics, and then how we treat them and maybe have a little bit of a literature review about them. So our first case is Toby.

He's a 10 year old male neutered Yorkshire terrier, and he presented to me with quite an acute onset, but progressive weakness affecting all four of his limbs. And the only other thing that the the owner noticed was that he had a slight change in the the tone of his bark. .

And so this was him when he 1st, 1st came in. So you can see that he needs support to, to ambulate and my hand is under his, his chest there, and he got good, you know, voluntary movement in all four of his limbs. But you get this real sense that he's generally quite weak, quite poetic, not overtly attaxic.

He doesn't completely lose balance. It's just that he can't, you know, ambulate for himself. He hasn't got the strength to stand up or or stay ambulatory.

But when you support him and you have his hand under his chest, you know, he's got surprisingly good, postural reactions. He's got good paw placement in those thoracic climbs and good pare placement in those pelvic climbs. So the actual paw placement and hopping, responses are all pretty good, .

Compared to his, inability to, to ambulate. The owners never thought he was painful. They just saw this sort of progressive weakness over about 2 or 3 days prior to coming here.

You can see when we check his patella reflex, it's, it's present but, but, you know, quite, quite reduced. You can see a slight reflex there but but maybe not as brisk as we, we might expect. But most significantly, when we check his withdrawal reflex, he's just not able to pull his leg away from us.

Again, just that general weakness in that limb where he's not able to, to pull away. And you can see this in the thoracic limb as well, just not wanting to completely withdraw his leg up into his chest. Otherwise, the rest of his cranial nerve exam was normal, his mentation was appropriate, and there was no neck or, or back pain.

And so I guess my first question based on his neurological assessment is where would you neuro localise him to? And obviously, given the topic of this is is the neuromuscular system. It gives you a heavy clue.

But just to go through, I guess, other possibilities. So if we were to summarise his main abnormalities, he's non-ambulatory, tetraporetic, with reduced reflexes in all four limbs. But his posture erections are good, his cranial nerves are good, and there's no neck or back pain.

Now, for me, he localises to the neuromuscular system. Some people often we sent, get these cases sent to us and people are suspicious of a problem affecting the spinal cord. In the neck, so either a C1, C5 myopathy or a C6 T2 myelopathy.

And you can sort of see why people might think that the fact that all four limbs are affected and that the fact that he's not able to walk on all four legs. The biggest sort of giveaway sign as to why it's not either of these is the fact that A, he's not overtly attaxic, he's just primarily heretic. You might expect more of an ataxia with one or both of these.

Number 2. He doesn't have any ball placement deficits. Normally if I have a dog or cat with a C1, C5 myelopathy or a C62 myopathy, when I knuckle over their paws or check their hopping, you'd expect to, you know, to be slower or, or reduced.

And the third thing is that he has reduced reflexes in all four limbs. Now in a C1 and C5 myopathy, he should have normal reflexes in all four limbs. And in a C6T2 myelopathy, he might have reduced reflexes in his thoracic limbs, but his pelvic limbs should be perfectly normal, and you can see in his video that they were quite reduced.

So as soon as you have a tetrayretic dog that has reduced reflexes in all four limbs, particularly if their poor placement is normal, straight away think actually what we're dealing with is a neuromuscular problem. I put brain stem here again just because occasionally you can get brain stem conditions making a dog unable to ambulate, but you'd normally expect a reduced mentation, cranial nerve deficits, and also some partial deficits, and maybe even some ataxia. So again, not consistent with his exam, because his problem was affecting his neuromuscular system.

So if you were to try to summarise him as a case, he's a, a Yorkshire terrier with an acute sort of quite progressive, non-painful, a quite symmetrical disease affecting his neuromuscular system. And so in terms of the differentials, you'll see this list is similar to what we talked about at the beginning. So, top of the list for him would be either an acute idiopathic polyradicular neuritis or maybe a masasthenia gravis.

On the list, but really unlikely is a botulism or or a tick paralysis, and like I say, always worth having a perineoplastic process at the back of your minds for, for these cases. So in terms of how we, we work it up again, similar to what we discussed before. So we start with the haematology and biochemistry, including a CK, which was all perfectly normal, in his case.

We then do thyroid function tests, so T4, TSH again, quite normal. Then some thoracic radiographs and an abdominal ultrasound scan, and you can see from his thoracic radiographs above, pretty normal looking chest and his ultrasound scan was quite normal as well. We did send blood off to check for anti-astylcholine receptor antibodies.

A normal limit is less than 0.6 nanoms per litre, and you could see it was 0.04.

So a normal level of antibodies, so negative for that and so very unlikely to be myasthenia gravis. And then at this point, based on, you know, the quite unremarkable diagnostics so far, you could consider doing some electroagnostics and and a spinal fluid, tap. But based on the way he presented and his progression, and the so far pretty unremarkable test results, certainly the most likely disease that he has is this acute idiopathic polygradicar neuritis.

And this is probably the most common form of acute polyneuropathy that we see in dogs. And the way we diagnose it is typically really via a diagnosis of exclusion. It typically affects the back legs first, and then it sort of progresses to affect all four limbs.

And you'd normally expect the cranial nerves to be quite normal, but occasionally owners, and we see that these dogs can become, or have a dysphonia. So it's always worth checking and asking them about the tone of the bark or whether that's a, a change recently. And the other thing just to bear in mind is that on the thoracic radiographs compared to other.

Neuromuscular diseases, we don't normally expect to see a megaesophagus. So if you did have a megaesophagus, then maybe you'd start to think maybe about something else is is going on. And with this condition, it's always worth just telling owners that a recurrence of the disease is, is possible.

And in terms of how we treated. Well, sorry, what else we see with these dogs, this this disease in these dogs. We often see it in, in Jack Russells and and restsies more than other breeds.

We might see it in the autumn and winter months, more than in the summer and spring. There is an association with, Campylobacter. And so in those cases, in which faecal samples were collected within 7 days from the onset of their clinical signs, those dogs with a polyrejective neuritis were 9 times more likely to be positive for Campylobacter compared to control dogs.

And there's a 6. Significant association in these dogs that were fed raw chicken and having Campylobacter. And so it's just worth bearing that in mind and asking these owners, you know, are they on a raw food diet and, and how likely is they might have Campylobacter in their faeces that might be a trigger for this as a, as a disease.

We often also see that these dogs have a significantly lower vitamin D concentration, but again, how clinically relevant that is is is tricky to know. And there's also a fair bit of research looking at these anti-GM2 gangliloy antibodies in these dogs with poly polyradicular neuritis. So similar to the Guilian-Barr syndrome that we see in in people.

You'll see at the beginning, when we're talking about diagnostics in these patients that you can do electrodiagnostics. So we can do EMG and motor nerve conduction velocities, and you might expect some changes after about 5 to 7 days of the onset of this disease. You might get some fibrillation potentials and some positive sharp waves, and you might see an increase in the F wave latency or.

Ratio in the nerve conduction velocities. It's quite rare that we do the electrodiagnostics in these dogs because clinically they're quite, I quite suggestive of this disease, but just something to bear in mind. And occasionally also if some do a spinal fluid analysis, often you might see an elevated protein in the spinal fluid, which is a non-specific finding, but again, just might add a bit more weight behind this as a, as a diagnosis.

And then in terms of how we treat it, so there's not any real effective treatment. We have tried human IV immunoglobulins in the past, and, and that can you know improve their response to, to treatment, but actually, you know, a lot of these dogs will improve, if given the time and the support and, and physiotherapy and bladder management that they need. So you'll see in this sort of graph, often we expect these dogs to initially deteriorate over the first.

Few days or few weeks to become non-ambulatory, maybe tetraporetic, maybe even tetraplegic, they then sort of plateau and stay at that level for quite a few days. And then with time over the subsequent weeks, we saw a slow and steady improvement in their ability to ambulate. The danger with these dogs is if they continue to deteriorate initially to the point of becoming tetraplegic, occasionally they can have respiratory problems, so they stop being able to breathe for themselves and unless you can mechanically ventilate them, often they're put to sleep at this point.

But if they plateau and stabilise, you know, without having any breathing difficulties, it's worth giving them time and lots of physio, and just managing their bladder, lots of supportive care, because the vast majority will then slowly improve over the coming, coming days and weeks. And those dogs that were treated with IV immunoglobulin normally took about 28 days, to improve, get back to walking from the onset of their signs. And those dogs that, that we don't give that to you, they take a little bit longer, normally about maybe 10-ish weeks depending on, on, on their, the speed of recovery.

But I've had dogs that can do much better within 2 or 3 weeks, and some that take a lot longer. So it can be quite a variable course. In terms of how quickly they they improve.

And so overall, the prognosis is, is good for these dogs as long as they don't get any breathing difficulties in the first few days. It's worth giving them time and and the rehab and the support. The only thing just to bear in mind and to, to warn these owners is that there's a chance that we might see a recurrence of the disease a few months down the line, and where we might see them become non-ambulatia again or tetraporetic.

In which case we treat them the same way, give them time, give them support, but it can just be a bit heartbreaking to go through the whole process again, if it's been a few weeks or a few months before we got them back to back to walking. And so the main thing with this disease is that like I say, a lot of the diagnostics we would expect to come back as normal. We're just trying to rule out other underlying reasons for them to have developed this or any other neuromuscular disease.

And if we have, and we're pretty convinced with our our diagnosis and giving them time and support, a lot of these dogs will, will get back to walking. Perfect. Right.

So our next case is Horatio. He's a 9 year old male neutered Tibetan terrier. And he came to me with about a, a two-day history of progressive weakness, sort of wretching and vomiting.

He'd be bringing up lots of fluid and saliva, and he had quite a, an abnormal gait. So this was him when he, he first came. So he's really reluctant to walk.

He can stand up, he can ambulate, but as soon as you start to get him to do a few steps, he, he really struggles to, to walk very far at all. He becomes quite arched, his, his pelvic limb, gait becomes quite short strided. It becomes sort of lower to the ground, and he just can't walk more than a few steps.

You can see he's quite alert, he's quite, he's quite responsive. He, there's no, sort of concerns with his, his mentation. And when we support him and, and check his, his poor placement, you could see he's got good, paw placement in his, his right thoracic limb there and his, and his right pelvic climb.

And again, with these cases, these neuromuscular cases, the main word that I always think is the, the thing to remember is just how, how weak they look, how, how poetic they look. They're not really ataxic. They're not really wobbly.

They don't sort of lose their balance or stumble over. They're just generally quite, quite weak. But you can see when you support him and you check his ball placement, actually it's, it's surprisingly good given how severe his, his gait is.

And the rest of his examination was pretty normal. The only other abnormality was his palpebral reflex. You can see it's quite, quite reduced.

It sort of gets worse the more you, you test it. So it's what we call a, a fatiguing palpebral reflex. But otherwise, the rest of his cranial nerve exam was within normal limits, so no other cranial nerve deficits other than that.

Let me check his reflexes, you can see his thoracic limb has quite a a good withdrawal reflex. And same for his, his pelvic in there as well. So, so pretty good, pretty brisk, withdrawal reflexes.

And when we check his patella reflex, again, pretty, pretty good. And we looked for any neck or, or back pain just to see if there's any, you know, neck or spinal pain and, and nothing obvious on on palpation. He seemed quite comfy when we were checking those different, different areas.

And so again, I guess the first question we try to answer with these patients is, is where we would neuroanatomically localise. And similar discussion to you before, you know, he's not an ataxic dog. He's not got postural deficits.

It's just this generalised weakness that worsens with, with exercise. He's a little bit different from our, you know, previous case, you know, the previous polyrediction neuritis, and the fact that he's got intact reflexes, and that's what I think sometimes confuses people with these particular cases is that, you know, even if they're weak and they're poetic or tetrapoetic and exercise intolerant, actually their neurological exam is pretty normal. There's no change in his reflex, there's no change in his partial reaction.

It's just that he's so weak, he can't walk for more than a few steps. I guess the other big giveaway with Horatio is his reduced or fatiguing palpebral reflex, which is er potentially clinically significant. And so I would localise him to the neuromuscular system based on his, you know, worsening tetraoresis with with exercise and this sort of fatiguing how people reflex as well.

And so he's a Tibetan terrier with an acute, progressive, sort of non-painful again, quite symmetrical neuromuscular disease. And again, we have the same five differential diagnoses that we would consider with him. But obviously presenting quite different to, to Toby, our first case in that he gets worse with exercise.

He's sort of vomiting, hyper salivating, regurgitating. He has this fatiguing palbr reflex and, and his reflexes are otherwise quite, quite normal. And so he would be quite suspicious for a dog with myasthenia gravis.

And so based on that, often what we do is then do a tenon test, so arohonium chloride. We inject intravenously and we'll come on to this in a bit more detail later on. But you can see how much better he is and how much happier he is to walk once we give him that.

Particular drug. And so it doesn't want to come back towards the camera, but as you go off towards the grass, you can see he's much more willing and able to to ambulate, particularly those back legs, his stride length better. He's no longer short strided.

He doesn't sort of drop down on that that back half. So a really good positive response to herohonium chloride. Which is important because that helps us to push us to a particular diagnosis for him based on based on that response.

And so for him, we would do similar to what we did for these cases in the past, so a full haematology and biochemistry, which was within normal limits. We then did some, thoracic radiographs and and abdominal ultrasound scan. His ultrasound scan was quite normal, but you can see in his thoracic radiographs, he has this sort of radio opacity in his cradial mediastinum, which when we sampled, was consistent with a thymoma.

And we also sent off, some blood for antiastocholine receptor antibodies, and you can see this time he is positive. So 4.15 nanoms per litre, when it should be less than than 0.6.

So Horatio ticks all the boxes for a dog with myasthenia gravis. So the fact that he fatigues with exercise, the fact that he had such a positive response to the tense salon, the aiohonium chloride, the fact that he has, sort of hyper salivation and, and, and sort of regurgitation, and then obviously with the antiastycho receptor antibodies being positive, that gives us a pretty good definitive diagnosis. Now he's a bit unusual in that obviously he had a thymoma.

And so often we do see that in dogs with myasthenia gravis and as the cause of the myasthenia gravis, and that's one of the benefits of doing thoracic radiographs in these cases, because that will help us again narrow down the differential diagnoses. There's a paper here that I just popped in and it's about 116 dogs with thymomas, and of those, about almost 20% have signs of, of myasthenia gravvis. And when that tumour was removed in about 84 dogs, about almost 20% had a tumour recurrence, and the median survival time, with and without surgical treatment was 6, 635 days and 76 days.

So quite a big difference between surgery versus more medical management. And so the presence of, of myasthenia gravis or megaesophagus at the time of thymoma diagnosis wasn't associated with survival time. But often when you remove the thymoma, the ability to control the neuromuscular signs, you know, the signs of myasthenia gravis can be, can be a bit better.

But in those dogs where you don't have a thymoma, you don't have a cranial medial sinal mass, and we think of it as more of an acquired or immune mediated, myasthenia gravis, and the antibodies are targeted against those sort of nicotinic astycholine receptors. So it is a junctionopathy, so it's not the nerve, it's not the muscle, but it's the junction between the two, and that's been targeted in dogs with with myasthenia gravis. You can get focal, generalised or or quite acute sort of fulminating forms.

And typically with these patients, we see them have a bimodal age of onset. So often we see them, either quite young dogs or quite old dogs, so normally sort of 3 or 10 years old, and they typically present with muscle weakness, that's worse in the the back legs but can affect all four limbs, and typically it's worsened, with exercise. And also really interestingly, in these dogs, megro oesophagus is, is quite a common finding.

So in more than, almost more than 80% of dogs with myasthenia gravis, we'd expect to see a megaesophagus. It's less in cats, about 40%, but certainly a lot more in dogs. And that's another reason why the thoracic radiographs are quite beneficial because If we see a patient such as him with a megaesophagus, it helps us push us towards myasthenia gravis, rather than, for example, a, a polyradicular neuritis.

And it's also quite useful to obviously rule out a cranial mediastinal mass, such as a thymoma, but also good to help us rule out any signs of early aspiration pneumonia. Cause that's the problem with these dogs, is that they're very susceptible to getting aspiration pneumonia. In terms of the, the sort of tests that we can do, so you saw Horatio's response to the edgeophonium challenge test, and it normally gets quite a, you know, a marked improvement.

You can do electrodiagnostics, and again, you might expect, when you do a repetitive nerve stimulation that you see a decrement over, over 1010 rays, that's something you can certainly do. But certainly the gold standard is to send blood for anti-asylcodium receptor antibodies, because if that's positive, then, then you've got your answer straight away. And in terms of how you treat it, we often start them on pyridostigmine.

You'll see in the formulary, it's normally 1 to 3 milligrammes per kilo, every 8 to 12 hours, and slightly less in, in cats. I typically start at a lower dose than this. I normally go sort of 0.5 a 1 milligramme per kilo and then sort of titrate up slowly.

. The problem with this as a treatment is that if you go too high too soon. Sometimes the side effects of it can present into sort of worsening clinical signs, so they might appear more tetrapporetic, more excise intolerant, they might, might regurgitate more and often people get confused whether it's progression of the disease or whether it's the medications themselves. So if you start at a really low dose and slowly, slowly titrate up, and hopefully you'll be able to distinguish whether this is, you know, a response to medication or, or whether it's actually the, the disease itself.

People sometimes often add in other medications, so sometimes people use steroids if they're wanting to to immunosuppress or if not getting a good enough response to just the period of stigmine. But the problem with the steroids is that often these dogs are quite prone to aspiration pneumonia, and that's probably the biggest cause of of death in these cases, and in the sense that the majority Dogs with myasthenia gravis will enter spontaneous remission, normally within about a year after diagnosis. The problem with these patients is that only about 50% of them will make it to that point because the other 50% often die or put to sleep because of the development of of aspiration pneumonia.

It's because they have a megaesophagus because they're constantly regurgitating. And potentially because they have are immunocompromised, these patients are really at risk of, of a pneumonia and that's often what what gets them before they, they enter remission. And you mentioned before about this edgehonium chloride test, so this is basically a short acting anti cholinesterase agent.

So it removes or acts against the anti cholinesterase, and so it allows more asyl codeine to be available in your synapse to to then be released and bind to your muscle. So we normally give 0.1 to 0.2 milligrammes per kilo intravenously.

The slight concern with this when we do it is that you might overstimulate the astralcoine receptors. And that might then result in a. And if you see that, these dogs normally have either some respiratory paralysis, some salivation, often they can really vomit and, and defecate and urinate.

They can become quite bradycardic and and have some bronchoconstriction. So to try and make it as safe as possible, I often pre-treat them with atropine. So I normally give them a 0.02 milligrammes per kilo dose of atropine into their muscle.

And then I have a second dose, again of a 0.02 mix per kg, ready, so that I can give it intravenously if we see them develop, this clonergic crisis. It rarely happens, but I always have it there just in case, in case it does.

And so just to give you another example of this herohonium chloride test, you can see this doggy again has signs typical of of generalised myasthenia gravis. You can see she can't walk very well at all, or more than a few steps, particularly worse on those those back legs. We then injected her with herophhonia.

Chloride, after giving her some atropine into her muscle, and you give it a few seconds and then after a few seconds, see what she can do in terms of her gait, and see if it improves. And you can see pretty much instantly, as you start to walk her away, she, she's much, much better. And so it can be a really rewarding test, because these dogs who can't walk from you, you know, away from you for 2 or 3 steps can now suddenly walk and appear quite, quite normal.

And it's really good because it makes, you know, you're on the right track in terms of this being masked in your gravis once you see this, this response. It's only gonna last for a minute or two. After that, we'll start to see the signs recur and the weakness come back.

So that's the, the sad part about it. But. We know that they're, they are responsive, and then we know that we're likely be dealing with the dog with, with myasthenia.

The problem of having a little bit at the moment is that, you know, to get adrenium chloride or tensone is pretty tricky at the moment and so often we aren't doing it or using the stigmin, but if you do have some or you can get it, it's definitely worth trying that in those cases you suspect to have have myasthenia gravis. And so, if you move on to, to Ebony, she's a 4 year fema neutered, domestic short hair. She, again, initially became quite weak on her, her back legs, but it progressed to affecting all four of her limbs.

Otherwise, no other major concerns for. For the owner, she was quite well with herself, quite bright, quite alert. No obvious, discomforts and no, no pain anywhere that they could see, but just not able to, to take more than a few steps without collapsing down and, and not being able to stand or, or, or move on all four of her limbs.

But when we do her neurological assessment, you can see her hopping responses are, are pretty good. And you can see when we do her postural thrush, she's got good movements in in both her back legs. When we check her reflexes, you can see she's quite reduced in that thoracic limb, you know, quite reduced withdrawal reflex.

And again when we check it in her back left leg as well, where we sort of try and pull it away, normally she should pull it up into her, her abdomen and you know, withdraw it away from us, but she's just not able to do it. She hasn't got the strength to to pull her her leg back in. But the rest of her examination was, was pretty normal.

She had normal coronial nerves. Hermentation was appropriate. Her posh reactions were fine, her hopping was fine.

It's just this, slightly reduced reflexes affecting all four limbs. You can see she has patellar reflexes, maybe slightly reduced, but, but certainly, they're a little bit, in both her, her back legs. You can see Jimenez responses is there on the right side and on the left.

And the rest of her cranial nerves were, were within normal limits. So again, I gave you a few options, but I think by now, you know, that we're dealing with a problem affecting her, her neuromuscular system. And so again, we would do similar investigations to our, our previous patients.

They start off with the haematology and biochemistry in her case, again, pretty normal, no significant abnormalities. We checked for toxopassma again, negative and FERV negative. And then we did her thoracic radiographs, and again, you can see this cranial medial sinal mass, which when we sampled, came back consistent with a ymoma.

We also sent blood work to check for, astalconium receptor antibodies, and you can see she had quite a, a high titer, 16.02 nanoms per litre, so much higher than it than it should be. .

The thing with myasthenia gravis and and cats is that you don't often see megaro oesophagus as commonly as you might see in in dogs, and that's primarily because of the increased proportion of smooth muscle, in their esophabus compared to dogs, which is mainly skele. Muscles, we see it maybe in about 30 to 40% of cats compared to more than 80% of of dogs. So don't get confused if when you do your thoracic radiographs in, in cats that you think might have myasthenia gravis, that if they've got a normal looking oesophagus because often we see that as well.

Treatment is very similar, so again, here at the stigmine, we might see a response, some people use steroids as well and or a combination of, of both. And in terms of cats and and myasthenia gravis, those that get acquired myasthenia gravis, again, has quite a high euthanasia rates, quite a poor prognosis, about, you know, 60% of those might be, might be put to sleep. We see it more commonly in Abyssinian or and Somali cats, with an increased incidence and really interestingly, about 50 or more than.

50% of cats with myasthenia gravis have a thymoma, which when you compare it to dogs in this paper where they had almost 1200 dogs with myasthenia gravis, only about 3.4% of dogs had a thymoma. So we see a thymoma in cats causing myasthenia gravis much, much more commonly than dogs.

So always worth checking on doing some thoracic radiographs to check for the presence of, of that mass. And in almost all cases of cats with myasthenia gravis associated with thymomas, they needed, medication following its surgical removement to still control and manage the myasthenia gravis. So occasionally in dogs, when you remove the thymoma, the signs of myasthenia gravis dramatically improve, and we don't actually need to medicate them at all, whereas in cats, it's quite likely they'll still need period of stigmine or steroids or, or a combination of both.

About 9.2% of myasthenic cats go into spontaneous remission, but they're normally those ones that aren't associated with a thymoma. Whereas in dogs, we reckon a spontaneous, remission in about 90%, in those dogs that are, you know, acquired non-thymoma myasthenic cases, and in people, it's really variable again, depending on the, on the cause.

And so we started this lookout on on period of stigmine and and you can see much, much better, able to now ambulate and to move around. Still a bit tetraporetic, maybe slightly worse on those pelvic limbs, but, but not much improved compared to, to how she was before. And there's another paper looking at sort of the long term outcome of cats with acquired mass in the gras, and this is slightly different in that these cats, none of these cats had a cranial mesinal mass.

It's looking at these cats that just had the acquired form without a thymoma. And if they don't have a cranial mesinal mass, they don't have a thymoma, they actually have quite a good, excellent long term outcome. And the majority achieved remission within about 6 months following diagnosis.

. And and so if you have a cat with a thymoma or you have a cat that's showing signs of myasthenia gravis, it's always worth doing thoracic radiographs because it really then allows you to give an idea as to what you'd expect prognostically. And you know, if they've got a thymoma pretty poor, if they haven't actually quite a good prognosis, and it's also worth always checking astalconium receptor antibodies in those cases that you find or have a mass in the cradial mediastinal area. And just remember also that you can get an acquired myasthenia gravis in cats er if they're being treated for hyperthyroidism with methimazole, so that's something just to bear in mind if you've got a cat that's showing your muscular signs and it's also on methimazole treatment.

And then the only other thing just to bear in mind is this paper, we found that if you do this wheelbarrow exercise stress test in cats, it might be quite good diagnostically again to, to help us realise that there's some skeletal muscle weakness. So you basically hold up their back legs and, and then we'll wear them on their front legs and often after the 2nd or 3rd step, they'll, they'll buckle and not be able to, to ambulate. And that's quite suggestive of a cat, certainly with neuromuscular disease, often being a myasthenic patient.

And that's the thing with cats, and that's why I wanted to, to put them in this presentation, because with sort of neuromuscular diseases in cats, you can get the weakness being caused either by a primary neuromuscular disease or a disease affecting another body system, that's then giving us a secondary outcome. And so cats are slightly different to dogs and they often, because they haven't got a nucle ligament, and we see that they can have quite a low head carriage, with neuromuscular disease. So they hold their head much lower than we might expect, and they often get this dorsal displacement of the, the scapula.

So the scapula appear almost quite. Prominently high. And so the way they move with the low head carriage and the way they have this sort of slightly elevated scapula can be quite consistent with the patient with with neuromuscular disease.

As you can see in this cat here, obviously his gait is quite poetic, quite weak, but the scapula are quite dorsal and with quite a low head carriage. And you often you see this sort of pomegrade or plant grade stance, you can see in his pelvic limbs, these sort of hocks are touching the ground the majority of time, with this sort of quite stilt, stiff, stilted, choppy, choppy gait. And so the way that he's walking is very consistent with a, as a cat with neuromuscular disease.

And so if you have a cat that comes to you that has a low head carriage, there's a long, long list of differentials that we might have that could be causing a neuromuscular disease as part of the the low head carriage. And so some might have an ammonium chloride toxicity. So we sometimes see this if ammonium chlorides used to acidify the, the urine, if you've got like a urolithiasis, and that can increase the potassium loss through the kidneys and then cause a hypokalemia and then cause you know, this sort of weak muscles in the neck, giving us a low, low head carriage.

Sometimes we see it hereditary, so like a low head carriage in in Burmese cats and, and Devon Rex cats, . Hypernatremia. And so this is seen in cats that are hypogipsy, and the signs are quite transient and thought again, probably due to the low intracellular potassium.

And you might see that the creatinine phosphoarnase is is increased, so was worth worth checking that. Hyperthyroidism again can give a lowhead carriage in in cats, it's quite uncommon, we reckon. About less than 20% of hyperthyroid cats will have muscle weakness and only about 1 to 3% might have ventro flexion, but again just worth bearing in mind.

Hypocalcemia, again, it's quite rare and can cause low head carriage. You might also Expect to get some muscle physicsulation, some spasms, some tetany, and occasionally we might see some seizure activity as well, which is worth bearing in mind. Hypokalemia, that's probably the most common cause of neck ventroflexion and muscle weakness in in cats.

So about 30% of cats with chronic renal disease are hypokalemic, and so some of those might show a low head carriage. Idiopathic polymyositis, you might see as well, giving us a, a low head carriage, it's quite uncommon. You often get like a stiff gait, you get some muscle pain, but you also might get a low head carriage.

Martin your gravis, as we can see, again, not the most common, but can certainly cause neck vent reflection in about 50% of these cases. Organophosphate poisoning is a possibility. They're particularly cats are particularly susceptible to it, particularly if they're in and around insecticides.

And so if they get repeat exposure, you can get this low head carriage. Polyneuropathy will come on to a little bit, but there's a possibility. Cats with shunts again, occasionally can present with a low, low head carriage, .

Again, it's not the most common. You often see other signs with it, but it's a possibility. And again, those cats that are thiamine deficient can also give you a low head carriage.

So if you have a cat that comes to your clinic and you're suspecting your muscular disease and they have quite a low head carriage, just bear in mind these as potential differentials, and you'll see a lot of them are related to electrolytes and a lot of them are indirectly related to a hypokalemia. So it's worth checking sodium, potassium and calcium in these patients because that might in itself give you an answer quite, quite quickly. And so with cats, similar to dogs, we often do a similar sort of workup, so the blood work, maybe the as receptor antibodies, some thoracic and abdominal imaging, to see if we can get a bit more, a bit more information.

And I just put this case in little Bella. So she's a 9 year old female neutered domestic short hair. And she had chronic renal failure and a recent onset of, of quite bad diarrhoea.

And when we checked, she had quite a, a low potassium, and she's quite a good example of a cats when they present to us with a really low head carriage and these sort of dorsally positioned scapula. So you can see, she really struggles to lift her head up, even when she's walking about. She's quite a.

An obvious posture. And again, this sort of really dorsal elevator scapula, pretty suggestive of a cat with a a neuromuscular problem. So as soon as you see one of those, it's worth checking the electrolytes, because if you see that she's got a low potassium and you correct that, you'll probably see an improvement in her neck carriage and her mobility, within a, within a couple of days.

And the rest of their neurological exam can can be pretty normal other than this reduction of, of reflexes. So you're still checking these withdrawal reflexes to see if they're, they're present or absent, and you can see that she has reduced withdrawal reflexes in both those, those front legs. And again, in the back legs, just too weak to pull them back into her abdomen.

So when you have this patient that is ambulatory, but tetraporetic with reduced reflexes in all four limbs, but most significantly, there's really low head carriage and they sort of dorsi elevated scapula when when she walks, and certainly you'd be suggestive or. Suspicious of a neuromuscular disease, and the first thing I would always check in the cat would be their potassium and just checking the other electrolytes, because that might be enough to give you an answer, particularly if we know that they are, you know, systemically unwell with other conditions. If they've got renal disease and if they've got other GI signs, and they're quite prone to getting these electrolyte disturbances.

And then also, little Louie, he's a 7 month old male neutered, Russian blue cross Bengal. And he came to me with an acute progressive history of difficulty walking on his, his back legs and a difficulty jumping up. So you can see him here.

He's got quite an abnormal pelvic limb gait. You can see he's quite planter grade, on those back legs, and the front legs look not too bad at all, but just not able to walk for more than a few steps without really struggling on those, those back legs. And you can see otherwise he seems quite, quite well in himself, he's quite bright, he's alert, it doesn't seem overtly painful, just really short, strided, stilted, and low posture to that back end, and really, again, really quite weak when he tries to move, not able to stand up on those, on those back legs.

And so from his examination, he was ambulatory but tetraporetic. His thoracic limbs were mildly affected, but he was certainly worse in his, his pelvic climbs. And we checked his ball placement, it was pretty normal, as, as was his hopping in all four of his legs.

But again, significantly, his withdrawal reflexes. But absent in both his back legs and, and quite reduced in his front legs. So that's the main giveaway with these cats is that they have reduced or absent reflexes in all, all four limbs.

Otherwise, his cranial nerves were normal. There's no pain on spinal palpations, so again, neuro localised to the neuromuscular system. We did haematology, biochemistry, normal.

FELV FIV was negative, toxoplasma negative, thoracic radiographs and scan all normal. We checked for masasthenia gravis, but he was negative for his astocholine receptor antibodies. And we did an EMG with him, and he had abnormal spontaneous electrical activity.

With these sort of fibrillation potentials and positive sharp graves, in all the muscles when we checked it both left thoracic and left pelvic limbs. But we didn't go ahead and do nerve or muscle biopsies because with this, we were pretty suspicious that he had a demyelating and remalelating polyneuropathy. And this is a disease that has been reported in the young Bengal cats, and he was half Bengal, which would sort of make sense with that.

But I have seen it, or we do see it in other breeds of cats as well. And, you know, quite typically they present and they're quite young, normally sort of 6 or 7 months old, sometimes a bit older, and they have this sort of progressive weakness, worse in their back legs, that can then affect their, their front legs. So this is quite a nice paper.

It looked at 37 Bengal cats with this condition. And the mean age of onset was around about 10 months, give or take 8, and you normally have about, a mean duration of clinical signs of, you know, it can be a few weeks, a few months before they then start to, to get better. And they often find this, you know, initially with pelvic and thoracic limb weakness, they become quite intolerant to, to exercise.

They're quite a stiff, sort of stilted gait, often there's plan to grade stances and just have a, a real decreased, ability to, to jump up on, on sofas and, and beds. And so the thing with these cats is that always the pelvic climbs are affected, but they can also progress to involve the thoracic limbs as well. And from this paper, we can see the most common sort of neurological signs, often there's plant grade stances, often tetraporetic, sometimes just paraporetic.

They're weak and stiff and stilted and unable to, to exercise. Spinal reflexes sometimes reduced in all four limbs, sometimes just the pelvic limbs, but there were 5 cats in this paper that had normal reflexes, so it's just the tetraparesis rather than the actual absent reflexes. And they describe maybe some slight discomfort in about 14 of these cats.

They wonder whether it's more muscle pain, when you sort of palpate along the area, not overtly painful, but just some slight discomfort. And some of these patients also have some pelvic limb muscle atrophy. And often you'd expect blood work and imaging to be quite normal.

On the EMG, just like in our case, you have these positive sharp waves and fibrillation potentials. And you do get a reduced motor nerve conduction velocity in most of these cats. And if you were to progress and do musclear nerve biopsies, you'd expect to see these quite thin myelin sheaths and thin myelated fibres, surrounded by these unusual schwann cell processes.

So you can get histopathology diagnosis if you need to go that far. But often actually with these cats as they present, they're so typical in terms of being quite young. Cats, often quite pure bred cats, and normally Bengal cats, and normally they present so typically once you rule out any other underlying condition like myasthenia gravis, or like any other neuromuscular disease, by giving them time, we'll see a good majority of them improve.

So in this paper, they found a complete recovery in about 50% of cats. It can take time, you know, there's about 3 months, 4 months before we start to see them get back to normal, but it's definitely worth giving them time and and physiotherapy and supportive care. We've got a partial recovery in in 36% of cats, maybe not complete, but but certainly good enough to have a good quality of life.

But again, just warn these owners if you see one of these cases, that there's always a chance that we might see a relapse of the the disease. There's a bit of a. Question mark whether we need to give these patients steroids.

I know some people do and some people don't think it makes any difference. But if I have a patient that we're not getting a good enough improvement over the coming weeks and months, occasionally I might try them on a, on a steroid to see if we can get that even better than than before. And again, you can see this is another cat.

We had, again, a Bengal cross, and again, sort of tetraporetic but much worse than those pelvic limbs. He's got this planter grade stance again. He has his weakness, when he moves around, struggles to, to get up and around, compared to a normal cat of his age.

And again, he was quite young. I think he was 9 months old when he presented. And, and this one didn't, couldn't, go for any further diagnostics, but was back to normal within about 2 months, just with time and, and physiotherapy.

And that's pretty much it. So I know that's a bit of a whistle stop tour of, I guess, the more commonly seen dogs and cats with neuromuscular disease. Like I was saying at the beginning, that the main thing to look for in these patients is a weakness and a reduced or absent reflexes, and it's very different to those cats or dogs that present to us with a spinal cord disease where they might be attaxic or might have spinal pain, or might have posture deficits.

And when you see a few and you sort of accurately localise them to the new muscular system, it then allows you to potentially do more diagnostics for yourselves in the sense that they don't need an MRI scan. What they need is primarily just sort of blood work and some thoracic and abdominal imaging, and a lot of these cases can do quite well with the right medications. Or just giving them time and, and supportive care, but they can be tricky to, to diagnose from, from the offset.

But hopefully that helps, just gives you a flavour of some of the cases that we see with, new muscular problems and, and how, how we work them up. But if you've got any questions, feel free to, to email them through, otherwise, see, see how you get on.