Hello, my name is Alex. I'm one of the neurologists at, at Davies, and, and so this webinar is essentially looking for, or sort of describing, tetanus. And, and the idea behind the presentation is to try to get a bit more familiar with this as a, as a disease, .

How we might expect to see it from a sort of clinical presentation point of view, what diagnostic tests there are, how we treat it, and, and what we might expect, prognostically from, from these patients. It's one of those conditions that I think we don't too commonly see in, in sort of first opinion practise, much in the UK. And, and I think that's just reflective of the fact that it's just not that common a condition.

In a referral setting, I see quite a few cases that come to me from, from different places, and, it's one of those diseases that I think a lot of people have at the back of their minds, but, That actually haven't seen many or if any, clinical cases of it. And so to recognise the sort of quite pneumonic clinical signs associated with it, I think can be trickier than most people anticipate. So the idea, hopefully by the end of this webinar is that people will be a bit More comfortable in terms of, of recognising it as a, as a disease, and then also sort of knowing what you might be able to do in the first opinion practise setting, but also, you know, if they end up being referred, what we tend to do, more in the, in the hospital setting.

So I guess to start with, one of the things that we, often think about with tetanus is the different susceptibility depending on, on the species. So I guess maybe from a veterinary point of view, most people would be quite, happy that probably maybe the most common species that we see it in, would probably be, be the horse and, and as most of you are aware, That's probably why we, vaccinate this particular species against it, primarily because, they are more susceptible and, and maybe are in an environment where they're more likely to get the sort of injuries or wounds where, they might, you know, might get that particular infection. So, horses are, are pretty susceptible species.

You'll see, sort of throughout this presentation, we've got a couple of case examples of, of dogs, and I guess that's the species that I would more commonly see based on the sort of practise that, that I do. They are less susceptible than, than horses, so we think about maybe 600 times less susceptible than a, than a horse, but can obviously still, still get it. Even less susceptible to it than, than dogs would be, would be cats.

. And I don't think I've ever seen a cat with, with tetanus, but it certainly has been, has been reported. Interestingly, like out of all the, the species that we've looked at and examined, probably the most susceptible species, actually the, the guinea pig, which is maybe not something that most people know or, or would expect again. Never seen a, a guinea pig with tetanus, but, but apparently the most susceptible, or one of the most susceptible species.

And somewhere in the middle would be, our sheep. Generally, it tends to be, that, you know, the more, omnivorous, species are, are less vulnerable compared to, you know, the, the herbivores. But generally, sort of in the middle, would be our sort of sheep, goats, and cattle, they're all reasonably resistant, whereas sort of horses and other random species seem to be a bit more susceptible.

. Like I was saying, the, the, like I said, the main thing that we tend to see is, is the horse in our clinical practise, and then occasionally the, the odd dog. . People tend to sit roughly in the middle, so maybe slightly more susceptible than, than dogs, but obviously less than, than most of the, the herbivores.

And we tend to see more generalised tetanus in people, rather than the localised tetanus, primarily because of, again, the resistance. But as you get sort of lower down the susceptibility chain, you might see these species getting more localised tetanus because of their more innate resistance to, to tetanus. I guess, interestingly, birds are resistant to tetanus and and other species.

These what they call sort of uyothermic animals such as sort of frogs are resistant to tetanus intoxication if they are maintained at a lower temperature. So frogs are less than 18 degrees, you shouldn't see any signs of tetanus, whereas, even if they've got sort of circulating tetanus and toxin. But they become more susceptible at higher temperatures.

So frogs that are kept in sort of greater than 2728 °C, are more prone or can potentially be susceptible to, to tetanus intoxication. But like I say, most of this webinar will be primarily looking at, at small animals, and primarily sort of dogs, in terms of sort of the cases that we've, we've got as, as examples. In terms of the slightly sort of dull side of things, in terms of the bacterium that causes tetanus, it's a Clostridium tetini, It's a gram-positive rod, and it's an obligate anaerob, and the spores, are pretty ubiquitous in the environment.

So you often find them in soil or, or faeces or, or dust. Any sort of environment where there's a quite a high moisture content or organic content, it's quite likely you'll have potentially some spores from Clostridium tetini. And in terms of the spores, they are, sort of round and, and terminal, and, and often you, see that they have this sort of characteristic, sort of shape at the end of them, which often people call it like almost like a drumstick, shape in terms of how they look under, under a microscope.

And the important thing about these spores is that they are highly resistant. So even to heat or, or disinfectants, they can really survive for quite prolonged periods of time without being, being eradicated. So even in the cleanest of environments, it's still possible to have these spores from, from Clostridium tetite.

And in terms of how it causes the disease. So, The important thing, well, the most important thing that these patients need to have is some sort of wound, normally a contaminated wound with obviously clostridium potinide that then causes the signs. So deep wounds with sort of little exposure, to air, and normally in the presence of some sort of necrotic tissue, will ensure sort of the perfect environment, for spore germination, and that would give us more of this sort of anaerobic conditions.

You then get this clostridiumestinide. Growth and then you get the subsequent production of the neurotoxin tea spasmin. And it's this, you know, this invasive bacteria, it can't really enter the body unless there's a wound.

So if there's healthy cells or non-necrotic tissue, then you can't get tetanus. It needs to enter via either a wound or some sort of necrotic tissue, and then it needs to then produce the, tetanus toxin to cause the, the signs that we're seeing. If you've got any damaged or, or live cells, then you're potentially at risk of, of getting it.

And with the Clostridium tetini, it then germinates into what they call the vegetative form, and then once it's in the vegetative form, it can then cause a local production of this tetanus neurotoxin, that can then spread around the body. And in terms of the sorts of wounds that we might find, so you can get these wounds in, in limbs, and so either distal or proximal limbs that might just be, traumatic from, you know, cuts, whilst out in the environment. You might get some wounds that we, do ourselves.

So if you are, you know, castrating sheep or, or cattle or, tail docking or, Any umbilical, umbilical infections, or even ear surgery in particular patients, that can cause the right sort of environment for, for Clostridium tetini, or obviously, horses that have penetrating injuries to, to their hooves or their feet, particularly when they're outside in, in, in the fields or in mud, again, it can cause quite a good environment for, this particular bacteria to, to enter and then to produce the, the neurotoxin. In terms of that neurotoxin itself. Later on, we'll talk a little bit about how we treat these patients, and one of the things we do is to provide them with an antitoxin.

And even though there are different strains of Clostridium intestinide, it's important to remember that the antitoxin is effective against all the different strains. You don't have to worry about being specific to that particular strain. It should work with, with all of them.

And in terms of the, I guess the pathogenesis of, of the, the disease, what tends to happen is once the Clostridium teanite enters that contaminated wound, it sort of gets transferred or, you know, changes into the, the vegetative form, and then it produces this neurotoxin. And this neurotoxin enters the, the bloodstream and attaches to your pre-synaptic membrane. So this is where we're looking at number 6 on our, our diagram.

And when it attaches to that pre-synaptic membrane, it's transported up through the axon into our central nervous system, and it goes through and binds to our inhibitory interneuron. And that's really important because as it binds to our inhibitory interneuron, the light, what we call the light chain is freed. And this then targets this vesicle associated membrane protein which is called synaptic rein.

And the reason that synaptic ren is really important is that this then inhibits the neurotransmitters GABA and glycine being released from this inhibitory neuron. And so with these inhibit neurons, they basically release these two neurotransmitters, like we say gaba and glycine. Both of those neurotransmitters inhibit your main neuron.

And because of this tetanus anoxin stopping those two things being released, it means that this neuron here is no longer being inhibited. And because of that, you get all the acetylcholine accumulating, and because there's no inhibition, the acetylcholine gets released into your synaptic cleft. And that's really important because this then causes this, you know, controlled release of acetylcholine.

And because of that, you get all the signs that we associate with tetanus in terms of the muscle rigidity and the excitement and the, extra sort of extensive, changes we see throughout the body because of this excessive acetylcholine, release. And that's all because of the lack of inhibition, because of the lack of GABA and glycine being, being produced. And so you get this dramatically increase in muscle tone and, and rigidity, and often that can affect the facial muscles to begin with, but then as it becomes more generalised, it then affects the, the limbs of the body and, and, and other areas of the body as well.

And so with technis, we sort of briefly mentioned earlier that you can get local forms or focal, some people call it, or more generalised techniques. Again, in a second, we'll sort of look at those two in, in a bit more detail and see the difference. In terms of the clinical signs, we normally see the clinical signs occur about 5 to 10 days after a wound in which the bacteria has, infected, but it can vary.

So in some patients, it can be as little as 3 days, but, up to 18 days has, has also been reported. . In cats because they are more resistant to tetanus, it can take longer for us to see clinical signs develop.

So in cats, it might even be as much as, as 3 weeks before we sign, see signs of tetanus, occurring in, in those particular patients. And in general, the thing to remember with tetanus is that you get some quite, you know, papinemonic clinical signs. You see this increase in muscle tone, and this increased rigidity, and this really sort of stiff, stilted gait.

Often when you see these patients moving or walking, either horses or dogs, you see that their sort of base of the tail is elevated slightly up and out, as if they look like they're about to, to go to the toilet, but it's constantly elevated. You get this trismus, so they're often unable to open their, their mouths, and often the most common thing that people associate with tetanus is this phrase, risus sardonicus, and, and that is Latin for, for scornful laughter. And so these patients have really quite a, a change in their facial expression, and that often their, you know, their ears are pinned back, their sort of brow is quite thorough, their face appears quite stretched, and it almost appears like they've got this really sinister grin going on.

Another thing that we often see, and I've got an example of this, in a Labrador later on is that they often get an ophthalmist and a secondary sort of protrusion of both, third eyelids that looks like they've got a bilateral, third eyelid protrusion going on as well. But the main thing to remember is that you get this sort of rigidity in these patients. They've got quite tonic and prolonged muscle contractions, and then they also have these sort of shorter more titanic spasms where they have little contractions of their muscles that can often be triggered by, you know, sound or touch or even lights, and they get quite quite excitatory when they have certain stimuli.

If we look at these patients that have a more localised or, or focal tetanus, like we were saying earlier, it tends to be seen more commonly in those patients that are thought to be less susceptible. So we, can see it in, in dogs and occasionally maybe more commonly in, in cats if we see it at all. And what tends to happen is it's, it's basically they develop rigidity in muscles which are closest to the wound in which that bacteria entered.

And you can then often see these sort of secondary tremors as well. So you can see a localised or focal tetanus affecting just the face, but you might You get a, a rhiza sardonicus, you might get, muscle changes in the ears going back, just around the eyes and the face, or you can get it in one, particular limb, where that limb itself, might appear quite, quite rigid and quite extended and, and difficult to, to flex. You can get patients that start off with a, a more localised or, or focal tetanus, and then with time as the bacteria starts to replicate and the neurotoxin becomes released and starts to spread around the body, it then becomes a more, more generalised form of the, the disease.

In terms of the generalised tetanus, this is probably more the most typical, cases that we tend to see. It initially, we think affects the, the muscles of, of mastication initially. So they get this trismus and those facial muscle changes, and then it affects the trunk and the upper and lower limbs.

These dogs often walk quite stiffly with a sort of rigid extension of all limbs, and like I said, often they have this sardonic grin and maybe some, some muscle tremors. One thing that everyone always describes these patients as being as being really tight and contracted in their, their muscles. And there has been, you know, some people report that the muscle contraction and tightness has been so strong and so fierce that it can cause ruptured tendons or even patients have been known to, to break their bones because of it.

But often because of the signs that we're seeing, particularly the rigidity of the, the master and the temporal muscles causing this trismus, often these patients aren't able to eat, and, and sometimes even that degree of, of muscle rigidity and sort of spastic paralysis that we sometimes see in these patients, it causes them to be not just recumbent, but epistotonic, so they are on their side. Often their head is going up and, and back, and they're almost sort of arching with their back over, and often all four limbs are extended. So occasionally from other neurological conditions, we see patients that might be in like a the cerebric with the cerebellic rigidity where they're in later recumbency and epistotonic with either 2 or 4 limbs being extended.

Some severe cases of a generalised tetanus can, can appear like that, in these patients, particularly. And we often all can see these patients then get some autonomic signs associated with them. With tetanus as well.

In terms of the autonomic instability, it's normally in the more severe cases and, and can sort of result in either a tachy, or bradycardia, and they often get some form of respiratory compromise. They get dysphagia, and often they can get sort of urine retention or an inability to, to avoid the urine as they might do normally. And that can be because the urethral sphincter can become quite hypertonic, and then they can't urinate as they might do or might be able to do, to do normally.

The autonomic signs normally occur about 1 or 2 weeks, later than potentially the, the, the other signs that we might see that we just described. And it can be a bit episodic. So initially, the, these patients can be quite tachycardic, quite hypertensive.

If they're able to, you often see that they're sweating, with a high temperature, and then they can quickly change and become bradycardic with them with low blood pressure, and the hypertensive. And The autonomic signs or these changes can in itself cause these patients to, to pass away. They might end up having a respiratory failure either because of paralysis of, of the diaphragm or, or some of the respiratory muscles.

Sometimes they get like a laryngospasm, or sometimes they have a, you know, a suppression of the respiratory centre, in the brain. They can have cardiac failure as well, these patients, for, for, because of what's going on from an autonomic dysfunction point of view. Often that constant muscle contraction and sort of extensive rigidity can cause these patients to become really quite hypothermic.

So it's really important to keep an eye on their temperature and to try and control that as, as effective as possible. And, and as we mentioned, you know, often we always concentrate on the external signs with these patients in terms of the, the muscle contraction and the rigidity and everything else, but often we forget sometimes that there's some gastrointestinal and urinary dysfunction. And so an important part of the care for these patients, which we'll, we'll come on to is to, to make sure that they have adequate nutrition.

But also to make sure if needed, that they have a urinary catheter in place so that they can, you know, we can empty their bladder without them having to, to do that themselves, mainly because of the change in the urethral tone, or just because of the generalised or dysfunction that these patients, can potentially, can potentially have. In terms of other species, so like I say, I guess in my line of work, in terms of what I do at the moment, the most common species that I tend to see tetanus in now would be, would be dogs. But certainly if you are a, a large animal vet, then you probably might have seen a few cases in, in horses.

You tend to split horses into two forms. You have the acute or, or subacute form. In the acute form, you get this sort of spastic paralysis that rapidly spreads from the head to the respiratory muscles and then to the, to the limbs.

These horses often have quite generalised convulsions. Often they're sweating quite, quite badly. And, and because it's quite an acute, quite progressive, quite severe form, the majority of these horses die within a day or two, primarily from the, the respiratory failure that, you know, correlates or, you know, comes with the, the signs that we're seeing.

Or you get a more subacute form, which is a little bit slower to develop. So it can sort of be more like weeks rather than days. So, you know, 1 to 3 weeks in terms of the development of the, the signs.

And this is the form that you might get some horses recovering from. The prognosis is still quite poor, but you know, there are some horses that can, can get through it. They are much more hyper aesthetic.

They have this sort of bilateral, prolapse of the, the third eyelids. They have difficulty eating, difficulty swallowing, often have, This sort of tris or difficulty with their masticatory muscles. The nostrils often appear quite, quite flared.

They have a similar, you know, rhizoidonachus, you know with the stiff, sort of vertically held ears, and the faces are quite stretched. And then often, obviously the, the muscles of the neck and back and, and tail are similarly, tense and extended as you might see in, in other, in other species. In terms of tetanus and, and horses, it's important to, to probably realise, which most of you might do already, that the mortality rate is, is quite high.

So close to 70% of horses that are, are diagnosed with tetanus won't, won't make it. . They have found a few indicators that might suggest a slightly better prognosis.

So if, if the horse remains ambulatory, or if they're still able to eat and drink throughout the disease course, then maybe the prognosis is slightly better. But, you know, as soon as they stop eating or drinking or become. Non-ambulatory or show quite generalised forms, and the prognosis really does work for these patients.

I just put this paper in, it's quite a nice, paper looking at quite a lot of, of horses. It's two parts, and it gives quite a nice summary of, of tetanus in, in horses, from both a sort of a diagnostic point of view, but also what you might expect from, from treatments and, and prognostically for, for these patients. So I thought we could maybe sort of start with one of our, our cases that we've, we've seen in the, the hospital setting.

He said, this is Henry. He, he's a 5 year, 5 month old male neutered lurcher, and he went missing from his owners about 2 weeks. Prior to the presentation with us.

And when he returned, they found that he had several wounds, on his, on his limbs. So whether he got caught by barbed wire or something going along those sorts of lines. He was taken to their vets and they had a look and cleaned and washed the wounds and placed them on some anti-inflammatories.

And he was doing fine. Everything seemed fine, but then after about 10 days, he only started to notice, he started to show some, some other signs. And they described the space as being quite stretched, and just in general, he started to appear quite stiff and had difficulty getting up and down from, from recumbency.

And so this is Henry when he first arrived at the clinic. So, so straight away you can see his gait is, is a little abnormal. He's got quite a stiff and, and stilted gait.

You can see his tail base is maybe slightly elevated, and the sort of where he holds his tail is, is a bit abnormal. But most obvious is this facial expression. So again, you can see, He, his ears are sort of drawn back and drawn together.

His lips are drawn back. He's got a slight wrinkling of his, his forehead where the muscles contracted. He's got some mild bilateral protrusion of his his third eyelids, and he has this quite typical sort of rises sardonicus sort of grimace on his, his face.

He's got a general sort of extent of rigidity, but you can see the rest of his neuro exam is, is quite normal, as you'd expect most of these patients. You see the little little snarl at me when I'm doing his postural reactions, but, but generally, you wouldn't really expect to find any other neurological deficits. And you can see these little wounds going down his front right limb, that they found after he went, he went missing.

And so the way he presented is really quite typical for a dog with tetanus in terms of that stiff, stilted gait, the extensive rigidity, but also the change in, in facial expression with that rise of sardonicus. And that coupled with the, the wounds that we identified, make it, you know, very likely to be presented with, with tetanus. In terms of trying to have a little think about what other differential diagnoses we might have on our list, like I say, typically with tetanus, the signs themselves are quite badly you want it for that disease.

And once you see those signs, and particularly if you see that they have a, a, a wound that would correlate with them having a, a proteinal infection, then that becomes certainly the most likely diagnosis. If you were to try to come up with other differentials, these would be the sorts of things to, to have a think about. So I've never actually seen a case that potentially, striing intoxication can show a similar clinical picture and is sort of the really the only other condition that might mimic the signs that we see in, in tetanus.

But like I say, you wouldn't normally expect, those patients with stri need to also have a, a wound that one need to always, always look out for. The differential diagnoses that you might have on the list would be like a hypocalcemic tetany, but again, it wouldn't typically look like the patients that we saw or see with, with tetanus, but always worth just doing some blood work to make sure we're not seeing some electrolyte disorders. Some sort of myopathy or, or myositis, either generalised or, or focal, you know, you might find that these patients have a slight increase in extensive tone or, or rigidity which might mimic some of the signs of, of sickness.

Occasionally I have a few patients that have been referred to me. Thinking that they have tetanus, and actually they've had a masturatory myositis which causes them to have a trimus and causes them to have slight swelling of the muscles of mastication, which can cause them to have a slight change in in facial expression. So that's one thing to have a look out for.

Normally those dogs tend to just not. They are not able to open their mouth. They don't often have a wound and that their faces aren't as stretched or as tor as those with tetanus are, and often the ears are in a normal position, but it's always worth thinking about that as a potential differential if it's just affecting their, around their head area.

Normally those dogs with the mastic KG mas I just have a very normal gait, whereas obviously those dogs with tetanus, particularly if it's the generalised form, you'd expect to have a much more stiff and stilted gait. That's another thing to look out for which might make it a bit more a bit more sort of suggestive of what we're, what we're dealing with. And in terms of the diagnosis, like I say, the majority of patients with tetanus, you get a pretty good clue that it's it's primarily based on the signs that they're showing, so the change in their facial expression, but also the way that they're walking.

. Earth might do sort of a haematology and biochemistry just to check, you know, that they're systemically well otherwise. And with that, you'd probably expect it would be relatively normal in patients with tetanus, other than maybe an elevation in their, in their CK. In terms of other things you could potentially consider.

So if you have a patient with vocal tetanus, one thing you could consider doing, would be electromyography, and you might expect to find that those patients have a sustained muscle depolarization, often for the EMG. You might need to do this under general anaesthesia. And so then that could be an opportunity to do other things that we will talk about a bit later on, like thoracic radiographs, if you want to check for any signs of aspiration pneumonia, but also if you want to place some feeding tubes, it might be good to do it under the GA at that sort of time as well.

Some people ask about, you know, whether you can identify, circulating, neurotoxin. You can do serological testing, to demonstrate a tighter against technospasmin toxin, but it's not generally thought of as being that useful, particularly in a clinical setting, as it's, So it might only be really useful if you have a case of vocal tetanus, which you're not too sure about. The difficulty with it is that you have to, supply sort of control animal samples to be then to make with the suspected tetanus case so they can make a direct comparison.

So theoretically, it's something that is done or can be done. But in all reality, I don't, we've never done that, and I, I doubt we would need to do it based on how these cases normally present. Another question that people often ask is whether you can isolate, the Clostridium intestinal bacterium from, you know, contaminated wounds.

The problem with that is that, you know, there have been papers looking at how successful it is at trying to isolate, the bacteria from, you know, confirmed cases of, of. And there's this paper recently that they took swabs from 12 wounds of dogs that had tetanus, only 4 of them came back culture positive. So if you get a culture positive, I guess it's quite nice because it might, you know, confirm that you're on the right track, but if it's negative, then it doesn't obviously rule it out.

. With the culture itself, it has to be performed under quite strict anaerobic conditions because of the fact that it's an obligate anaerobic, so that's the thing to, to bear in mind. And the other thing, I guess people often wonder about whether you can, detect antibodies against either of the tetanus neurotoxin, or the bacteria itself, but often they aren't detectable in, in non-vaccinated people animals, even those that have recovered from naturally acquired tetanus. So again, not something that we often do or we tend to do.

That would be in any way helpful . For these for these patients. And so then I guess we come more on to how we, we treat them.

And so there's a few things that you should consider when you're treating a patient with, with tetanus. And we'll sort of go through each of these in, in a bit more detail over the, the next few slides. So the first thing to, you know, always remember is that there There's a, an antitoxin that we use in these patients, which should be, should be given.

Often it's important to find a wound and to to ride it. Often they'll be placed on antibiotics. It's important to have some sedation and muscle relaxants on board if these patients are going to stay in the hospital.

The most important, and one of the most important things is the supportive care that we provide, in the hospital setting to make sure it's as, a good an environment as possible for these patients to recover. Often the muscle contraction and the, the rigidity that the patients have can be quite painful, so it's really important to provide analgesia. And and then also they are might be used for magnesium and sulphate, which again, we'll come on to, too shortly.

So to take the first flow in, in a bit more detail. So there is an antitoxin that we often use for patients we suspect to have tetanus. And the idea is that the free circulating, tetanus neurotoxin can be neutralised with this.

The one that we typically use is the anti-tetanus, equine serum. And it's really important to remember that I don't know if you can think back to that diagram we had towards the beginning where we had our synapse and you could see the neurotoxin entering a synapse. As soon as it enters the pre-synaptic neuron, the antitoxin will no longer be effective against those that are within the neuron itself.

But all the free circulating neurotoxin, can be neutralised by the, the, the anti-tetanus neurotoxin. And so it's worth administering for those, You know, the, the non-bound tetanus toxin if that makes sense. And for that reason, it's really important that if you're gonna do any form of wound debridement or cleaning, that you should give the neurotoxin or anti neurotoxin prior to, to doing that, because as soon as you start to clean the wound or debride it, and there's a good chance that you might get more neurotoxin being produced.

And so it's really important to, to give these patients the antitoxin prior to, to doing that. The way you give it can really affect its availability. So if you were to give it subcutaneously, it can take 2 or 3 days to reach therapeutic levels.

Whereas if you give it intravenously, it's much, much quicker. And so we tend to give it intravenously over about a 30 minute time period, to get it into the system as, as quickly as possible. And once you do administer it, the levels of, Antitoxin will be maintained for about 2 weeks.

And so there's no need to give it more than, than once because 2 weeks will be more than enough to, to stop any more, tetanus, toxin binding to your, to your synapses. And if you were to give it more than once, there is an increase or greater risk of anaphylactic reaction. So it's certainly not worth doing more than 11 dose.

Often with these patients, I would do a test dose, so I'd inject either 0.1 to 0.2 mLs just under the skin.

So I keep a patch of hair, and then sort of mark it where I inject and monitor that site for about 30 minutes. If you see a local reaction or some sort of wheel forming, then it might suggest you are more likely to get an anaphylactic reaction if you were to give it intravenously, the, the total dose. But if the skin otherwise appears normal, then it's, then it's fine to, to, to give the dose hopefully.

In terms of the dose that we, we give, there's little sort of consensus on the, the correct dose of, of tetanus antitoxin. That's quite a varied dose range. In the literature, they tend to suggest anywhere between sort of 100 and 1000 units per per kilogramme.

But I wouldn't give more than a, a total of 20,000 units per animal. So, I would do it based on, on the size of the animal and, maybe go in the middle of, of those two ranges. There is some suggestion that, you know, focal tetanus, if you gave up a local injection, maybe about 1000 units in the limb that's affected, so just an approximal part of that limb, and then that might be effective in, in trying to, to help with the more localised time that we see in those patients that can be useful in, in a focal or, or localised tetanus as, as well.

But the main thing to remember about the, the tetanus antitoxin is to do it prior to any wound environment or, or cleaning, and to always do a, a test dose and just do it the once, you don't need to, don't need to repeat it. The second thing to, to consider is, antibiotics. So the antibiotic of, of choice for patients with tetanus is metronidazole, at a dose of normally about 10 to 15 Migs per pig, initially intravenously every 8 hours in dogs and every 12 hours in cats.

. I tend to do this for at least 10 days, as a total course. You can switch to, oral metronidazole if either the patient starts to eat or you have, some sort of feeding tube, in which case, you can, put the tablet directly into their, into their stomach. If you don't have metronidazole, then you can consider other antibiotics, but certainly, it's worth having some metronnizole in, in stock because that's certainly the, the go to for, for this, this disease.

And then one of the most important parts of, of the treatment is, is wound department. So, again, once you've given the antitoxin, then any wound that you find should be really thoroughly cleaned. Any foreign material or any nerotic tissue that you find should be, should be removed.

Always have a little look for any nail bed infections or any focus of, Sepsis. Some patients with mastitis or, or sort of reproductive tract infections can cause tetanus. Even too through abscesses, ear infections, umbilical infections, in or grand abscesses all have the potential to cause, tetanus.

It's worth having a really good sort of general clinical exam and and search for any particular wounds that you might be able to either debride or, or clean. Once you identify or if you're able to identify it and divide it, it is thought that it gives you a, a better or improved prognosis, because hopefully then you can stop the, any more neurotoxin being, being produced, and the bacteria from, from replicating. If you are to debride these wounds or in some cases, you know, amputate toes or, or do anything with surgery, obviously, then, often these patients, because they're so hypoesthetic and so reactive, will need a full general anaesthesia.

And often it's recommended if you're going to be flushing a wound or cleaning it, that you should use hydrogen peroxide, mainly because of the, fact that the Clostridium techni is an obligate anaerobent, so that would be much more effective to try to, to neutralise it as, as much as possible. One of the main sorts of things that we use in these patients whilst they're hospitalised is, is muscle relaxants, and they get such muscle rigidity or techne, that it can really cause a lot of their clinical signs, you know, they can often be quite uncomfortable with it. It can be quite hypothermic with it.

It often makes them unable to, to ambulate, often makes them unable to eat. And so if we're able to cause or, you know, induce some degree of muscle relaxation, often that really can help these patients. My go to is a benzodiazepine, so I normally do either diazepam or or midazolam CRI initially and see how they respond.

If they need more, then I often combine it with a phenothiazine. So normally, ACP as a CRI or as a, as a one off potentially to, to help with the, the benzodiazepine. And we'll start using megapo more a bit more often, particularly if you have a PEG tube or something that you can pop the tablets down in, in easily.

I normally do a dose of sort of 20 to 45 milligrammes per kilo. . You can also potentially do it, directly as well if you haven't got access to the patient's not eating is another way to, to consider using it.

But remember, it is a CNS depressant. So, if you're using other medications that might be, sort of depressing, there's such a nervous system that can exacerbate that. So these patients might end up appearing a bit obtunded.

I try to avoid things like opiates in these dogs, but certainly, you know, they can be quite uncomfortable, particularly with the muscle. Rigidity. So I always have these patients on, some paracetamol and maybe even a non-steroidal, if it's possible, to try to help with any potential discomfort that they might be, they might be experiencing.

And then in terms of something else that we have started to use a bit more, more frequently is the magnesium sulphate. So it is thought that, you know, by using this, you might be able to reduce the muscle spasms, as well as potentially combating some of the autonomic dysfunction that we see in these patients. .

We tend to administer it so that we get to a serum magnesium concentration between 2 and 4 mmols per litre, and that range is based on, on human papers. We're lucky here that we can monitor the levels so every few hours with the lab and see if we're getting close or over that particular serum concentration, but I know that a lot of patients don't have that, that access. One thing you can do though is to check your patient's, patella reflex, because if that starts to reduce or be diminished, it might suggest you're going slightly higher or too high with your magnesium and sulphates and so then you can taper it back down if your patella reflex is starting to, to be diminished.

In terms of, of how it works, it's thought that at the sort of new muscular junction, magnesium decreases calcium's entry into the presynaptic terminal, which causes a, a decrease in the amount of acetylcodeine release, and then you get this less sort of muscle contraction because of the lack of acetyl codeine release. . So they thought that the magnesium itself might synapse or, or interact with your post-synaptic motor end plate, and so then it might stop, as lowly, clinging to the post synaptic membrane as well.

So it sort of works both in the pre-synaptic and post-synaptic, if you like. With it, I often have these patients on an ECG and often check their systemic blood pressure, because you can get bradycardia and hypertension with, with magnesium, and obviously it's important to, to monitor these patients for any sign of, of respiratory depression. And then in terms of the other thing to really consider with these patients is primarily your, your supportive care.

So the first thing is nutrition, like we're saying before, because of the autonomic dysfunction and maybe the gastrointestinal, you know, reduced motility, but also combined with the fact that these patients often have a much higher metabolic rate due to the muscle spasms and contractions. It's really important that they have their nutritional requirements met, and, and normally increased to what they might normally have. The problem with these dogs, is that they are normally unable to eat or unable to swallow for themselves.

And so often we have to place, feeding tubes to, to help them. And you can see this patient is a tetnis dog that will come on to a little bit later on, that we placed a, a PEG tube in so that we could get proper, nutrition into, to him because he was unable to, to eat. So that's one really important part of the supportive care that, you know, these patients need.

The other is to try and keep them in an environment where they are going to be happy for because often these patients have been with us for days if not weeks, and they're so hyper aesthetic and hyper excitable that can often exacerbate some of the signs that they're showing. So for us it's really important to have them in a part of your clinic or ward that's really quiet. That you can sort of dimly light, often at the earplugs or cotton wool in these patients' ears, often need a lot of nursing care that they need to be changed or, or moved every 4 hours onto to a different side.

I always place a urinary cat with these patients because often, they, they're unable to urinate, because the urethra is so hypertonic or They aren't able to posture or to, to ambulate as they should. So it's always worth facing a, a urinary catheter. Obviously, as you just covered, the, the feeding tube.

And so often the amount of nursing care these patients need over the days and weeks can be underestimated, but it's probably one of the most important parts to, to looking after them. And when you're moving them or trying to get them into a different position, that's when you often find these patients become really rigid and really extended and really hyper-excitable because of the, the stimulus from the movement or the sound or, or even just touching them. So, I mean, it's something that needs a lot of care and attention and, and time to do, to do properly.

And that's probably one of the most important things with, with these patients is, is time, because this isn't a quick disease that's going to be fixed within a few days. Normally, this takes weeks. And, and the reason for that is because as soon as you get binding of this neurotoxin to, to the neurons, it is irreversible.

And so what we need to wait for is the generation of new sort of pre-synaptic, Nerve terminals and complexes to then see an improvement in in clinical signs. So you might have these patients come to us that have a generalised tetanus where they're, you know, stiff and have the rhiz sardonicus and become non-ambulatory, and they might be like that for a couple of weeks before we start to see them. And so it's really important when we have these patients that we communicate to the owners that the, that these dogs aren't going to get better quickly.

Often they're going to look quite terrible for, for quite a, you know, pronounced period of time. And for that reason, it can get really quite expensive to, to treat these patients. In terms of prognosis, it can be really variable.

So it depends a lot on how they present, how severe they are, but if they've got focal or, or generalised tetanus, these patients often are with us in hospital for, for a long, long time, and, and often they are really sort of quite intense patients to, to care for. And so often they need a nurse with them the, the whole time in terms of the care that they need to, to make sure that they are kept, happy and, and also quite, kept quite quiet. Because of the constant muscle contractions, they are at risk of, of hypothermia, because they're often recumbent and unable to open their mouths and unable to swallow.

They, they've got quite a high risk for developing aspiration pneumonia, and one of the main causes of death in these patients is either cardiac or or respiratory failure. In one sort of paper we looked at about a 28 day survival was found to be around 77%. But like I say, it really can vary, and you'll see in the next slide actually, other the sort of mortality or spiral rates are.

Between 50% and 90%. So it depends a lot on how they present. I often say to owners that, you know, about 50% of these dogs also come to either aspiration pneumonia or, or cardiac or, or respiratory failure.

It just depends on, on, on how severe they are when they, when they come. It is thought to be a quite a significant association between, younger patients and the development of more clinical science. If you have a young adult developing tetanus, maybe a slightly worse prognosis.

And there's some sort of good, prognostic indicators in the sense that if the heart rate or blood pressure values, are going to be normal for, for the majority of the time, that might be a good prognostic indicator, according to, to one particular study. Sort of more focal or localised tetanus is thought to be associated with like a lower mortality and a, and a faster recovery. Another paper found that there's sort of three core prognostic indicators, and they're pretty much ones that you might expect.

So if the patient becomes non-ambulatory, if it becomes a pitonic, like the, the dog on the, on the right-hand side, or if they develop seizure activity, any one of those three things are thought to be a, a negative prognostic indicator for, for survival. The average time that these patients are in the hospital with us tends to be between sort of 13 and 17 days. So I would say to owners it'll be at least 2 weeks before, before they get home, but certainly I've had patients that have been with me for, for longer.

Majority of dogs, we think recover completely within about a month. Cats, we think, take, a lot longer, normally, normally several months. But again, this can be highly variable between, between patients.

And, and like I say, that's the fibre rate itself, can really vary with some people saying 50% and some people say 90%, but I think it depends a lot on how these patients present, what sort of hospital they're in, and what sort of care they receive. So, so it's quite a varied prognosis at the moment. And the only other thing to be aware of is, again, a relatively recent paper looking at this association between REM sleep behaviour disorders, and tetanus and dogs.

So it looked at a bunch of dogs that had, tetanus, . And they found that almost 50% of them developed this abnormal dream enact enactment, which they call this REM sleep behaviour disorder. And normally, these owners are reporting that these patients are twitching or running or, or vocalising in their sleep.

And often they described it as violent nightmares, or almost seizure-like in, in 40% of dogs. And They trialled different medications in these patients, so a lot of these patients were put on antihyletic medications, but that didn't really prove to be effective. I'll just skip back so you can see the video again.

So this dog was fast asleep, and then it started doing these sort of convulsions and, and movements, and you can really see why owners would think that the, their dogs are having some form of seizure or, or nightmare based on how violent the Their essential dreams are. And, and it's crazy to think that, you know, 50% of dogs that have had tetanus will have this change in their, in their sleep behaviour. The thing to know about this is that we think that in about half of these cases, this will resolve by itself, within about 6 months.

So there is a thought that, you know, with time, it, it will improve. And this is something that we often see in humans with tetanus as well. They often get these, sleep disorders or behaviour disorders after they've recovered from, recovered from tetanus.

Great. And so I, I thought we could maybe finish with another case just to get you as familiar with this disease as, as possible. So, this is Archie.

He's a 6 year old, male neuter Labrador. So he had a nail bed infection that the owner saw maybe about 10 days ago, that looked like it was just healing by itself, so they didn't, take it to. So a vet and just left it heal by itself, which is going fine up until about 2 days prior to when he came to, to us, where he started to become a little bit stiff in, in his limbs, and again, they sort of commented that his facial expression started to change.

And you can see that already in this picture here. He's got obviously some slight salivation. His, his face appears quite stretched, his, sort of forehead's quite, priest, the ears are back, and he looks like a dog that's got, almost rises up like it's like we discussed before.

And this is when he first came to us, so you can see he's got this really quite stiff, stilted gait again. You can see the base of his tail is, is elevated and sort of protruding outwards abnormally. You can see he doesn't really flex any of his limbs.

His ears are back, his face is stretched, his eyebrows are sort of crumpled close together. He's got some slight hyper salivation. He's got, again, this typical rises sardonicus facial expression that, you know, we, we know is really sort of patternmnemonic for, for tetanus.

And just that basic, like, when you see that, their forehead sort of, creased and their ears back like that and their face just appearing stretched, always have tetanus on sort of top of the list as, as differentials. So this was when he first came in and, and we put him in that wards, because that's one that we can keep nice and dark and quiet, and settled, and, and he, was in there for, for two weeks. .

In terms of diagnosis, obviously based on what we now know, I hope you'll recognise him as having quite a, a typical and classical gait and, and face electpression for, for tetanus. In terms of diagnostics, so occasionally what I might do in these patients is to do some thoracic radiographs, it's primarily just to, to check that we haven't already got any. Evidence of, an aspiration pneumonia, makes sure we're not missing anything like a, a negroesophagus.

Or often just do a routine haematology and biochemistry. In his case, it was pretty normal. I think he had a slight elevation in his CK, which isn't surprising given the, the muscle, contraction, but otherwise, the rest of his blood work was, was quite normal.

In terms of diagnostics, that's all we needed to do with him, primarily based on the fact that the signs were so, obviously associated with it, with, with tetanus. In terms of what we did treatment-wise for him, so he was given, sort of 500 units per kilo of antitoxin. We initially did a test, sample into his skin, but he didn't have any, reactions, so we gave it intravenously over, over 30 minutes.

. We started him on fluids, and we gave him some sedation. The nail bone infection looked pretty much cleared up where the only reported it was. There was no obvious sign, of any infection there at the moment, so we didn't do too much in the way of debridement or, or cleaning.

Occasionally, I've had patients in the past where people have had active infections in The digits or the nail beds. And I know some people, opt to, amputate those digits, to try to get a good, you know, resolution of the infection as possible prior to, to treatment for the tetanus. So it can be something that is, you know, quite drastic in terms of of the surgery that these patients have.

It really depends on where the wound is and, and what sort of wound does to what treatment they have. He was started on a, a CRI of midazolam, and we also gave him some, some ATP, yeah, he was on some paracetamol as well, just to make sure that he was comfortable, and we started him on, on intravenous metronidazole. One thing I often put patients on just because I worry with all the medications, plus, you know, obviously how they are in general is the last thing we want them to do is to feel nauseous or to, to vomit or regurgitate as well and I put them on some anti-nausea medication, either more oftenant or about trying to try and keep them as acceptable as possible.

Archie did deteriorate in the first sort of 24 hours whilst he was, he was with us to the point of becoming non-ambulatory and really quite marked resmus, and so certainly not in any way able to, to eat. And so, so we, placed a peg tube in him and an indwelling uric catheter so that we could provide all the care that he needed from a nutrition point of view, but also so that we could make sure that we could empty his bladder, as much as we, we needed to. And in terms of the outcomes, like I say, first rate for 48 hours is quite tough for him.

He did, he did get a lot worse and, and that's generally what we, we often see. He was stayed with us for 14 days, and at, at discharge, he was unable to, to walk for himself again. He was still a bit stiff and still completely unable to open his mouth fully, but he was able to eat at that point and unable to, to move around and was certainly on the way up and, and improving.

. And the only reported about, you know, a week or two after discharge, they went back to how he would normally walk and, and eat. So he had a, like almost a complete resolution of his signs, by about week, week 4. But similar to what we were discussing earlier, this owner did report that Archer started to have, have nightmares.

So again, it's this REM sleep disorder that we've seen, and this is a video they, they sent me of him, you know, being asleep on his bed and having these really quite sort of violent, nightmares that they described. And, and like I said, unfortunately, there's no real medication that we tend to give these dogs that we know is effective. We often just say to, to give them time and, and hopefully over the coming months, they'll become less frequent and, and less severe.

But it can be pretty distressing for, for owners to see those. So it's always worth warning them that if you do have a patient with tetanus, And they do manage to, to get through it. Just warning is that this is a possibility so they don't get too panicked at home and they they start to have these, have these episodes.

But I think that's it. Hope that's been, been useful and just to go through a few, a few cases and to just get a bit of a, a grip as to this as a condition and, you know, what you can do about it and, and how to treat it. Like I say, it's not the most common, but when you see it, it's one of those ones that you don't tend to, to forget, and it can be a real challenge to, to treat sometimes.

But, but it also can be quite, quite rewarding. So hopefully, that was, that was useful. Thanks very much.