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Good afternoon, everybody. Welcome to the second session of the B s s. Our grand rounds. Uh, firstly, I mean, regarding the last grand rounds I had a few queries about the MRI is a limit on the home page. So I think many of you would have worked it out as a case of, uh, MRI findings in serious atrophy of bone marrow. But I have posted the link to the case report as well. If anybody's interested So now moving on to today's grand rounds, which is on muscle pain, I have a pleasure to introduce our speaker's. For today's session. We have a doctor, Dmitri Amira's who's a consultant radiologist at the Imperial College Trust and the senior ordinary clinical lecturer at the Imperial College London. Uh, he has started the globe. He's obtained a fellowship in Musculoskeletal Radiology in Fremantle Hospital, Australia. He's consolidated his training with observer ships in uh, the AMC in Amsterdam and Auckland Hospital in New Zealand. He is also a keynote speech, a speaker for the Microsoft and Cannon and, uh, also a co author on position paper on use of augmented reality in healthcare. And the main thing is like you know, with this, uh, muscle paying topic today, he's developed a dedicated ultrasound guided muscle biopsy technique for investigation of the muscle pathology and, uh, and is a leader in, you know, myopathy. So that's why he will be talking to you about muscle pain today. And, uh, I had the pleasure of introducing other speakers who are rheumatologists and pathologist So Doctor and Kindler, rheumatology consultant at Imperial College London. And she is, um, an accurate physician, associate medical director. She's also the clinical coach for Imperial Trust Sepsis, big room, digital project. And we have Doctor Clara Limbach, who is a consultant neuropathologist at Oxford University Hospitals. She was the head of neuropathology and neurovascular unit, Imperial College Healthcare NHS Trust. So welcome to oil our speaker's. So this is truly a grand rounds with multi specialty approach and I will invite now, Doctor, um, it has to take over the floor. Thank you. Prolia Prolia asked me to do this talk when we were working at the Commonwealth Games, and I think I must have been very optimistic at the time, thinking I had lots of time to prepare everything, but it's actually been a really great opportunity to work with my colleagues and and Clara personally. Thank you both for helping me with this grand round. Um, it's going to be a big emphasis on MBT working, which hopefully you'll see through the stream stream of this talk. So I'm just going to talk to you about investigation and diagnosis of muscle disorders to start with. And then we'll go into a bit more detail from an Aunt Clara about both the clinical side of things and the pathological side. Um, I've put a poster up there of myself when I was a radiology trainee. Actually, no, that's on response. Mega. But if you ever wanted to learn anatomy, your muscle anatomy, there's there's a great specimen there to look at. So anatomy is actually very key to some of these diagnoses. Um, but first of all, I just No, no disclosures from any of the speakers know relevant financial relationship to exist when we go to classifying these muscle disorders actually can be quite complex, because I've put them into into discrete categories here. But there's often some interplay. Um, so hereditary diseases are the ones you would be familiar with in terms of lingered. A muscle dystrophies do sends muscular dystrophy famously. And then there's a big set of acquired disorders, and I've broken these into kind of those that inflammatory and those that aren't inflammatory. And obviously there is a big kind of big cross over in that field as well. Then you've got your infectious one's, your immune mediated, and those can be broken down into into several subsections. And we'll go into more detail in some case examples as we go through that. And then there are some clearly sort of neurogenic cases, and there are some specific types, like spinal muscular atrophy, which you, which you may have heard of. So, um, in terms of clinical features, um, there are quite a few key factors here, and, uh, in essence of true MBT and do you do cut in? If I say anything, that's wrong. But you you do want to understand, uh, their muscle pain there. Weakness. Is there a sensory component to this is an autonomic component to it, Um, and then also their distribution. So most neuromuscular disorders are prominent. The legs very early on, you can make some differentiation about a proximal versus distal and where there's symmetry as well. So most of most of these disorders are symmetric asymmetric. You may be thinking about specific neurological things or or perhaps inflammatory neurological causes. Um, And then obviously the temporal effect is that when did this start? How long has it been going on for, um, and then familial? Is there a family history of these things? Is there a history of continuity in the family Things all relevant, And then we'll go into more detail about laboratory tests. But, um, CK is obviously very important. And that level of CK can help, uh, further subdivided. Which ones are more are more likely, uh, the MG and conduction studies are very important, although it can be as some of you may have. Some experience can be sometimes a bit ambiguous. Uh, now with finding actually antibodies and anti panels much more useful as more and more being developed and can be very specific. But there are some specific myself center bodies and there are some non specific vitamin disorders can also cause, uh, muscle disorders. So it's important to to look at those and and have a wide spectrum and then obviously imaging and muscle biopsies, as we mentioned already. Um, in terms of imaging techniques, When I first broke this talk, it was to look for that fat content. It was just the one. But there's been a lot more work done now on using Chemical Shift artifact and Dixon sequences and also some work done on spectroscopy. Um, when you're doing this, you're predominant looking for a pattern of disease, uh, in terms of which muscles are involved, but also what's happening at the muscle level. So I find that most easier just to perform this on the actual level because they're comparatives. Most of the imaging studies that you were to look at have got actual images. So actually, at Imperial, we just do actual imaging. And we spend more time in those scans that we get better quality imaging, um, looking for acute abdomen and I'll say edema. And that's very important. What we're looking for is high fluid signal. Um, uh, Stir is the mainstay for this, um, some places do you use to to fat sat, and there are some issues with that again. Now we can start using Dixon, and there's also spare techniques. Um, and sometimes it's important to look at, um, the whole body when we're looking at this. Most of the time, most of the studies look at thighs and caths, but you may want to look at the upper limb as well, and also actual disease. Um, especially important for monitoring disease, which I mentioned there, um, in dermatomyositis is important to exclude malignancy, and we usually do a pet CT. Uh, if there isn't a specific antibody with their data mastitis, and then again, you can look at the spinal cord. If you think this may be neurological, I put a link to the paper published recently include Rapid, which is talking about quantitative assessment over visual assessment. Just an interesting one to look at just in terms of artefacts. Um, with fat suppression techniques, you can get poor fat suppression, which, unfortunately, a lot of us are familiar with, which makes it very difficult to interpret the peripheries top of the bottom of the of the image that's been acquired. We tend not to use TT facts that we mainly used, uh, maybe because some of our machines are aging and the quality is not good enough, so I would urge you to be very critical about the quality of your imaging and make sure you're using the best technique. Um, this is an image of stir with, unfortunately and chemical shift artifact, so it's simulating, um, kind of a fascial inflammation here, but you can see it's both on the same side. Um, there's nothing on the contralateral side here. This is a chemical shift artifact and the way to fix this. Increase your bandwidth on your stir sequences, and so it's really important to have a good relationship with your radiographers and give them some good feedback about the imaging that they're doing. Um, you could also start using other techniques such as Dixon and Spare. But do do you work together with your medications on that? Um, in terms of biopsy, I put some links there towards doing image guided biopsy. Some of you may be interested in that. This is the biopsy needle that can be used, which is actually a modified you ch biopsy needle biopsy. Disposable went out of stock. It's actually fantastic biopsy needle. And if any of you considering doing image guided biopsies, I'm happy to give some support on that, and I can say. Actually, all our patients have done tolerated really, really well and very few complications. Um, sometimes you do need to get surgical biopsy, and we are going to discuss the case. The case that they did have a surgical biopsy there are there's more potential for complications. So far, all the image guided biopsies are have only had minimal complications. But the bonuses that you get lots of tissue, which you may need for genetic analysis, which we'll talk about. Um So yes, there's some links down some codes. If you wanted to look into more detail and then just to kind of emphasize this multidisciplinary approach, um, you know, a neurologist, rheumatologist, pathologist and more and more geneticists helpful to look to look at these muscle disorders. So I'm going to pass on now to Clara, who's going to talk about the pathology. And I think the reason why that's important is because, um, the pathology does actually predict some of the imaging features that we find. So it's really important to understand that part of it of the disease process. And it's not something that we are actively talk. So I thought it was really interesting for the better start to have a look and understand some of the pathology. I found it incredibly interesting when we do our mg ts and Clara is excellent and explaining it to pure nervous like myself. So I'm going to hand over to Clara, and hopefully she'll be able to share her screen. Thank you, Dmitri. It's great to work with you again. Uh, I agree. The imaging clinical and pathological correlation muscle bulbs is is, uh is really interesting. Let me, uh, share my screen. Can Can we see it? Can you'll see it? Not yet. Now. Yes. All right. So, um what? Dimitry asked me to prepare a short, um, a brief overview of the assessment of muscle boxes for nonneoplastic disease. Um, and, um, for this type of bug, the pathologist, um, typically use a systematic approach. And if I try to keep it very simple. So the basics the, uh, features that we, uh the main features that we look, um, that we examine our the fiber size, the fiber shape, the fiber type of the distribution. In some cases, there are changes in the internal architecture of the muscle fibers such as vacuum hose or course or targets and then the inflammation and inflammation. Of course, the key, the key element is the inflammatory the cell infiltrate. Um, the cell types as well as their distribution, is important. There are also some other features, such as necrosis and some immunohistochemical market that we use. But the most important one is, of course, the type of inflammatory, uh, cells. And if we start with, this is an ideal muscle biopsy. Why, for, uh, two main reasons or actually, three. Maybe the first one is the orientation. So the muscle fibers are all in cross sections, and that's what we want to see. If the longitudinal will lose a lot of information, what is the fiber fiber size that the fiber shape this is all, uh, lost? Sometimes it's difficult, but once the body has been taken, it can be quite difficult to orientated, particularly small bowels. It's like the needle about is a bit easier with the surgical ones. Here is really good. Um, the second reason because there are no artifact and, uh, a number of artifact that can be introduced in muscle boxes. Remember, muscle bulk of the tissue is frozen, which is different from most other types of bosses. Um, and working with frozen tissues a lot harder. Uh, the tissue is more, uh, delicate. Uh, some artifact that are, uh, your fault. Let's call it that way. That introduced even when the buzz is taken. If there's too much pulling or maybe during transport, if it takes too long about it, stays to longer term temperature is also not good. And then the worst one, which is actually our fault, which is the freezing artifact, which is a complete nightmare for the pathologist. Uh, there's It's crucial because there's no way we can fix it. So if the muscle biopsy has been bad badly frozen, there's nothing we can do about it. Often, a lot of information is, uh is lost. The morphology is really compromised, and sometimes there's nothing else to do and repeat the boxes. Um, well, the third reason why this one is a perfect muscle muscle biopsies because the muscle is perfect here, there are no changes. Uh, it doesn't mean that there is no disease. Sometimes we get normal normal histology, either because of a sampling error. Maybe the changes are not in our specimen because after all. It's just a tiny bit of a muscle that we see. It can be more focal some other times because the disease that actually does not cause changes that are visible histologically. Um, for example, this happens quite commonly with mitochondrial disease, where maybe the muscle can look entirely normal histologically. But there are changes. And in order to find them, we actually have to do a molecular enzymatic, uh, test. And that's when sometimes we need more, uh, more tissue for this type of test. But if we look at this is we take it as an example of a normal muscle, and we'll compare later with the disease part common disease, patterns of disease that we see. So here, um, we see the muscle fibers are all about the same size, the preliminary shape, um, the nuclear or the peripheral, the muscle fibers, the cytoplasm is uniform, and there is no endomysial connective tissue. Better said it's minimal permission. There's a bit more, and that is normal. It depends also when the buzz is taken from, but there shouldn't be much Indonesia connective tissue. Now, if we compare, we can start with. We'll start with the Dystrophic uh, pattern. Um, if we look here, there is a significant increase in variability of, uh, muscle fiber size. We see there are some large hypertrophic fibers, and we see the small, very small, a trophic fibers in some, there's almost no cytoplasm left. It's only the nuclear we can see. We often refer to this as nuclear clumps or nuclear bags or pin pricks like this one here, um, so really marked variability in fiber size, um, together, where based in this case, we see many central nuclear. And the reason is because this is a case of myotonic dystrophy, and this is a very typical feature of, uh, diatonic dystrophy, the central nuclear. It's not specific. We can find it in a number of other disease, but in the right clinical context and with the variability of fiber size, Uh, it is quite, uh, typical of myotonic dystrophy. There is a minimal increase of, uh, Indonesia. Connective tissue here is really subtle. But now, if we look at another, uh, dystrophy, this one, uh, actually dystrophy neuropathy here we can see how there is a market increase in connective tissue. There's also already some fat replacement. The white blebs that's fat. And again, many small fibers and some very large hypertrophic fibers. And we look at the fiber sizes they are around that they're not polygonal anymore. This is also a common characteristic, actually quite characteristic of, uh, the, uh, muscle dystrophies. And one more example. Um, this one here is a congenital muscular dystrophy visit about seeing a three month old baby, and we can see and even more market increasing connective tissue. And the fiber's not only are many traffic fibers, but they are all very rounded, which is a typical pattern of the congenital muscle dystrophy. And we can see here what I was saying before the longitudinal fibers. All these areas here cannot be assessed, and there's a lot of this in the muscle, but you can see how good part of it sometimes half of it or even more, is essentially used it from the, uh, for the psychological assessment because of the wrong orientation. Okay, so, um, let's move now to, uh, this example here. Here. We can also see there's increased variability in fiber size, but the fibers are mainly small. There's no there are not many hypertrophic fiber's. Just maybe a few, and the small fibers tend to group together. So in a way, this looks looks less chaotic than in the dystrophy pattern. So there's not this, uh, mix of small and big fibers next to each other. Really? The main change is the atrophy. Uh, there is also some increasing connective tissue, which is more paramnesia than Indonesia. And if we look at higher magnification here, we can see that the small fibers not only the group together, but also the shape So we don't have around fibers here. They're mainly the polygonal and the smaller ones. The traffic ones are, uh, triangular. We call them angulated fibers, which is highly typical of, uh, neurogenic myopathy. Um, it's caused by, uh, renovation from the master Bossy. We cannot in for the cause anything that it's upstream of the muscle. Essentially, axonal loss can cause with pattern. Um, and another important element in, uh, neurogenic pattern in is, uh, the change in, uh, fiber types, which is a sense with immunohistochemical tree. There are also some other, uh, standing that we can use, but the one that we typically use now is immunohistochemical for slow and fast miles in Uh, and if we look here at the small fibers, they're both in this case here. They're both, um uh, expressing fast miles in. So type two and fibers expressed in slow miles and type one fiber, which is really important in, uh, renovation that we have to find a trophic fibers of both types. If you think about the mechanism, how this happens when we see a trophic fibers of only one type, Usually it's something else. It's not neuro cardiogenic. Um, and another common finding in, uh, neurogenic uh, myopathies, um is fiber type grouping This is not caused by the innovation is called by renovation, so you will not always see it. It depends on what was going on at the time. The box it was was taken. But if there is renovation, we'll see it instead of having the u the normal checkerboard pattern of slow and fast miles in a bit, like you see in this area here what we see our groups of fibers of the same type. So this is, uh, fast miles in here. There's a large group of positive fibers, and here there is another group of fibers. They're all negative and here again, fibers are all positive and the same in this upper case here. So, fiber type, uh, grouping. Sometimes the atrophy is, uh, the traffic fibers, um, located the periphery of the, uh, muscle fascicle what we call a peripheral testicular atrophy. And it's quite characteristic of some inflammatory myopathies in particular dermatomal diabetes and, uh, the, uh, anti center type syndromes. Of course, to call it, uh, my anxiety is we have to see some inflammation. So if we look here at the left, we have the peri testicular atrophy, which we we usually see quite well on just the routine age and is staining, but it can be highlighted by immunohistochemical tree. Here is neonatal mitosis and atrophic fibers re express, uh, the neonatal isoform of my cousin. Uh, And so when it started when it's focal, it can be quite helpful. This pattern and here on the right, we see it. Inflammatory infiltrate, which also in dermatomyositis is typically pay for secular. And the cell type is important too. In the hematoma societies, it's, um it's usually quite mixed, So we have both B and T cells, and the T cells are typically more CD four positive than CD eight positive. And here to compare another type of inflammatory, uh, pattern, Uh, myopathy. In this case here, it's including body, my anxiety's and we can see that inflammation here again. It's lymphocytic, but it's scattered in the testicles. It's not very follicular. And this is the pattern that we see in IBM as well as in the clinical, uh, polymer societies in IBM. We also look for, uh, you probably know the Raymond vacuums. There are many in this case here. Sometimes there are very few. Sometimes we don't find it all depends. We were lucky. So association or vacuums with Indonesia? Uh, lymphocytic, uh, inflammation is highly typical, uh, IBM and in IBM differently in dermatology societies, the usually significant component of CD eight positive lymphocytes just like here. And then I wanted to show one last case of something that we've been seeing more frequently in, uh uh in recent times, which is, uh, another inflammatory. My opposite the checkpoint inhibitor associated myopathy in which, again, the inflammation is Indonesia. The numerous fossil inflammation associated with necrotic fibers no necrotic fibers can be found are not specific at all that can be found in any kind of inflammatory myopathy, uh, as well as in many, uh, dystrophies. But the interesting feature of this type of myopathy of necrotic fiber clustered together just like they're not scattered as we see in other, uh, inflammatory myopathy is, but they clustered together. Um, and I think that, uh, this was the last case that I wanted to, uh, show here. Thank you very much, Clara. That was really, um, really useful even, You know, I find it very useful to understand, um, understand the pathological side of things. And I think the thing to take away from that for us radiologists, is to think about that kind of macro anatomy. You mentioned the pain, my seal and particular, uh, infiltration. Um, and then now, now what we're going to do is talk about some cases where we've got imaging. We've got clinical details that we've got some pathology, Uh, and we're going to basically enact an M. D T. And we're going to go after those cases. We're going to talk about this particular case. We kind of flipped the ground round on its head a little bit. So this is the first case. Um, so It's an adult male with thigh pain. Nodules on the elbows possible Got trans patch is on hands and a facial rash. Um, they've got a raise C k a positive and a and a normal e mg. So I'm going to show you the MRI trying to do the MRI findings. So because we haven't got, uh you haven't got you here, I'm just going to explain what we can see. Um, so there is some inflammation around the kind of peritesticular distribution. I want you to think about some of the cases that that Clara shown you. Um, and try and think about what? Just on the imaging side. What you think the pathology might look like? So if you look here, it's quite symmetrical, and it's in the muscle, and it's involving up to the fascial margin. I can see that here. So, um, that's this area identified, and there's the images of the Well, this is the vastus lateralis. We've got some pathology slides here, and I don't know if you wanted to talk about some of the car. I know that these are not the best images, but these are these these patients images. Um Yes. So when you show them before, uh, I was saying here I can show what, uh, suboptimal above. See how it looks like. So if we look here on the left, the HPV, we can see a lot of, uh, longitudinal fibers, the ones that we said, uh, useless. So we can't really, uh, analyzed, Uh, there is a central area here in which, um um, uh, a cross section fibers. Um And, um and there seems to be a peripheral vascular pattern. It's not perfect because, like the beautiful picture that I found that I showed you before that I would try to do, we'll try to find the best pictures available, Uh, in this one here just because of the orientation, we can see a few fibers that are, uh, the periphery there are smaller than the the other ones, but it's not so clear. So easy to say is in a, you know, well oriented boxing. Uh, and I believe there is also some not freezing, but some folding some artifact in the connective tissue between the artists. Uh, so yes. And in here in the h, Any at least modification? I don't I'm not sure if there is any inflammation I see there on the left, maybe a few small blue cells could be lymphocytes. But I'm not actually sure that there's not not marked inflammation. Let's put it that way in terms of cells. But what we see here in the center, which is great and you're showing this one because I didn't show the MHC one which is a very useful, uh, immunohistochemical market for inflammatory myopathy, is because when there is not much inflammation is in this case here, we can see the MHC one can be is telling because usually it's not upregulated in other diseases, it's only in inflammatory. Myopathy is with a few exceptions. Um, and, uh and here we have some, uh, fibers that are positive in dermatomyositis. That should be again more powerful particular. But here it's a bit difficult to say because again of the poor uh, orientation, Um, and what is almost unique, I would say to, uh, dermatomyositis is the compliment. The position in capillaries? Uh, here are those fin stripes in between muscle fibers on top. If you even higher up, there's a like a strange votes. They're not the easiest to assess So it's yes, the very important to find, but they're not. So it's quite subtle, faint immunohistochemical staining. But when you see them, it's quite characteristic of, uh, hematoma anxieties. And it's one of the features that differentiates this from example and and, um, uh, anti sensitive syndrome in which the pattern paraphasic your pattern is quite similar, but there shouldn't be compliment the position in the capillary. So, um, this patient was diagnosed with tomato sinusitis, and they were actually Joe one positive. And I've managed to get some follow up on this patient, uh, and they've got some features of NS i p, which is associated with Jay one antigen antibody. Um, and I don't know if you wanted to come in at all. So when we think about as rheumatologists matter most scientists were fondest of the anti synthetase antibodies, of which no one is the best characterized because that that's the disease that feels most rheumatological and that these are the patients that get prominent muscle and lung disease, but also an erosive joint disease. They sometimes get terrible lung disease with, um, diffuse alveolar damage, which can be very severe. Um, but you can get many of the different types of muscle antibodies can give you the same phenotype. You can see dermatomyositis with most of them. Um, but the combination of lung and muscle suggest it's one of the anti sympathies antibodies. Okay, so that was our first MDT. Hopefully, all in the audience. You managed to work out. We were talking about the maximum cystitis. Okay, so we got our next case. So adult female, generalized weakness, fatigue, dysphagia, breathlessness and objective proximal thigh weakness on examination. So we had a raise. Seek a positive ana and a row 52 positive. Another antibody. This is the imaging. So this was I was trying to show you some good images, but these are the kind of images they're not. They're not the best, but we can see some demon posteriorly. And then we can see some asymmetric involvement of the anterior compartments. Um, so we did a muscle biopsy. I think this one we did on the image guidance, actually. And we did some biopsies. I don't think it's a semi membrane OSIs. So I don't know if you want to talk about them, but I think this one showed some necrosis. Um and, uh, some inflammatory Infiltrate. Um, so, uh, across I'm looking at the your images on across. It's usually it's quite easy to see already on a church you need The fibers look pale, but this modification I'm not sure if I can see them. Uh, from here, Um, I don't know if you can see them. Uh, I wonder if some of these ones down here, but it could be that they look like that, But I can't. I don't want to. It's possible. It's, uh, sometimes. So there are two ways to identify on. Hmm Microfibers. Even because they're paid, there's a lot of structure or because they're invaded by macrophages. There's psycho psychosis, um, and, uh, on the on the right. So there are two good markers that we can use when we are not sure if we see on the crisis or not. One is the one that you have here, which is the acid phosphatase, which is positive in macrophages and necrotic fibers. So maybe that up there, if you go a bit higher up there's a big red area that could be a necrosis or a cluster of macrophages there as well. Yes. Thank you. Um, the other good market is compliment. Necrotic fibers are positive for compliment, but a PPI has been used for much longer. Of course. It's a great, uh, much cheaper staining. Um, and in the middle here, uh, there is a regulation of MHC one, uh, and we compare with when we look at the the dermatomyositis here. It doesn't look very fast. Irregular. This was a better boxy than the one we had before that scattered in the physical. And that's what you see, Everything essentially in anything in any inflammatory myopathy. It is not a dermatomyositis, and he's into the syndrome. We see this type of pattern. Okay, So I don't know if any of you want to take a guess. You can put some messages in the middle program and just put in a chat what you think you might be, but I'm prayer. Do you do you got in? If anyone to put any suggestions in, I'm trying to encourage the masking. Please type in your responses and have a goal at the diagnosis. But, uh, it is quite difficult. Yeah, this is a tricky one. So from from the imaging side, because it's a posterior compartment. Um, and there's some evidence of necrosis. Now, I, um if you were to give contrast, you may see some patchy enhancement of the muscles, which you can see in the process. I feel like the enhanced the edema here is slightly patch. You can maybe see it better in the rectus, but it definitely looks a lot more central. Just like I was saying on the MHC one, it looks like they're not carry fasciculus. It's very central. So for me, because it's posterior, um and and it looks a bit necrotic. This can be one of two things HMG coa A or SRP. So this was SRP, uh, and there was a positive SRP antibody. Um, so the imaging pattern is really helpful because it's if it's in the hamstrings more than it's anterior. Then you start thinking about these immune mediated necrotizing myopathy. So, uh, the ro antibody, probably which is typical of Sjogren's syndrome, goes with many autoimmune diseases and might have been a bit misleading here if it's srp um, it cannot its own be associated with a sort of low grade connective tissue. Myositis. Um, the anti SRP myositis is the most severe of the autoimmune. You see, prominent necrosis and clinically, you very often have this very severe, uh, pattern where you've got the breathlessness as well as my weaknesses. And and these patients often require very significant immune suppression. And you don't always get complete improvement. So can I just add something? Yeah. Um, So, yeah, I agree, because on balance there is necrosis, but there's no inflammatory infiltration in terms of lymphocytes. It looks like this group, the immune mediated necrotizing myopathy. So there's MHC one of regulations and immune mediated mechanism, but not no lymphocytic infiltrate. I agree that what is a bit strange, but it could be again just a sampling that for an S R p one, I would expect more necrotic fibers that what I see here. But that's something that, actually, you guys, maybe you can tell better than me because I'm limited to, you know, the little sample that I have maybe every elsewhere. There's loads of necrotic fibers. Thank you. I think it's really useful, and it's and it's It's a good thing you picked up there about the inflammatory versus necrotic numbers. How you can look at that. What the ratio is. And it probably fits well with the fact that we generally use rituximab, which is an anti B cell. But it's predominantly anti antibody, the plasma cell memory cell. Um, so that it improves, Um, that we see quite good results in SLP when we can use rituximab. Brilliant. So case three. It was an adult male with generalized weakness following initiation of statin therapy. Um, no bubble weakness, but proximal weakness in the upper limbs and lower limbs. Race E k negative and A and E N A. And the head of my pathetic MG pattern. So I'm showing you another poor quality image, But you can see there is some bandwidth problems here. But there is definitely edema in the rectus femoris, some sartorius and again in the posterior compartment. Definitely So many tendinosis is involved, as well as the doctor Magnus. So, um, let's go and talk about the histology against heart and if you can see that Well, all right. This one is a nice box again. Good orientation. Good preservation. So now I can't hide behind There's artifact. I don't know what it is. Um, So, um, again, I see some pain fibers, which May. There may be some necrosis I don't see much, Uh, many lymphocytes. So maybe again More more necrosis and inflammation. So it would be more of a in keeping, uh um, maybe when the immune mediated necrotizing, uh, there is MHC one up regulation, which is again podiatry and not very fascicular. Um, and there is no complement position, which makes me think that in this, uh, the the image here, they're not necrotic fibers, because, well, should be actually positive for, uh, complement. But maybe it's just in this capture. Maybe they're just not here on the left. Maybe there is one that is positive in the middle. Some a bit higher up. More to the left. More, more, more. They want a big one. That could be a necrotic fiber. Um, so yeah. Immune mediated, possibly necrotizing. Yeah. Yeah. So I don't know if anyone's guess this one, but this is related to the statin therapy. So this is an HMG coa a reductase antibody. Myopathy. So it's a reaction to the statin. Not exactly a drug myopathy, but it's an inflammatory immune. Mediated. Inflammatory. Uh, necrotizing myopathy related to the statin therapy. We see this quite a lot of extreme and and again it's got that mostly posterior compartment use. And then there's that history of of statin use and again, perhaps some patchy edema in the muscles. And again, nothing paying particular. Um, okay, so I think we'll do one more case, and then we're going to move on to the to the main case. So this one is an adult male, long history of impaired grip, difficulty getting up, facial weakness and thinning of forearms and right leg race E K negative and a negative myositis, uh, antibodies and then my pathic mg. And then he's got this imaging appearance. So it's again. Now we're looking at the anterior compartment. There is fatty infiltration of the T. One image is asymmetric. There is some involvement vastus lateralis and then on the stir sequences, you can see that, actually, there is some edema going on, and this is now central. It's not paraventricular. It's very central. Um, and then now we've got some pathology slides as well. I don't know if you get this one quickly. You did show an example of this area as well. All right. This one should be should be easier Even without the histology, I think I can sort of tell what this one could possibly be. We have the features of IBM here on the already on the go. More on the left. Uh, the, uh We see a few evacuated fibers, and there's also one ragged red below one. Mitochondrion deficit is common in in IBM. Um oh, that's an H. And it looks almost like a tumor. It's very green. Uh, I'm not sure if that's an h any actually. If you know, if I see the red, red, red, red, that's also a Gomer, Uh, the one in the center again and Gomorrah with all the vacuums. And then on the right there is once again MHC one up regulation, which in IBM is patchy, just like in all the myositis excluded dermatomyositis type. So thank you so much, Clara. So this this is a clear inclusion body myositis the clues of the age and then the distribution use the anterior compartment. Um, sometimes there can be sparing of the rectus femoris and involved in the middle gastrocnemius. And then you've clearly outlined the pathological findings there. Um, and often these patients have got fatty infiltration by the time we see them. So I think what we'll do is go straight to the case now, just in the interest of time. So I'm going to flick through, have one other interesting case, but I'll go, so we're going to handle it. And but I think the idea is now we've done an M d T. Now it's your turn to to MDT and have this case, which we all found difficult. So let's go through the presentation. So you've got it now, right? Myositis. It's easy, right? Clear cut imaging clinical, uh, serological and pathological features that it's always easy next slide to me. Thanks. So this is a 17 year old boy who presented to a Andy in a bank march with fevers. Essentially, he was a semi professional football, but I hadn't been able to play for a bit at college. And on presentation to this trust, he described a two day history of fevers, a sore throat for 2 to 3 weeks, a husky voice for 3 to 4 weeks, very few other systemic symptoms that he was telling about this point, um, some lower back pain, and that's actually what had stopped him playing football? Um, no neck stiffness, no rashes, no foreign travel. But he had really puffy eyes, Um, and an increase in peri orbital swelling over the last two weeks and that now he almost couldn't see. And the one day history of hand swelling bilaterally he'd had a very recent prolonged admission. Are neighbouring Trust where he had an MRI which will show you shortly, which showed some, uh, edema in the muscles he had did have a race e k and a ferritin. And he had a positive test for, uh, streptococcus. He had an A S o t. That was positive. And he had race, er race e k, but relatively low, uh, level so in the thousands and a high ferret in and he'd had cytopenia. So he had a neutrophil count, which had gotten his lowest 2.2 with some evidence of inflammation. So, in view of the pronounced, uh, blood changes, he had a bone marrow to fine, which really didn't show anything very much and in particular didn't suggest HLH next slide. Uh, this is the S H. O s examination from when they came in. This is the kind of examination documentation you get when you switch to electronic patient record, it has the advantage that you don't have a diagram for chest with an arrow through it. Um, but there there are other typical features of a clerking examination. So essentially he was. Well, you will notice that the neurological and musculoskeletal examination in somebody who has a history suggestive of myositis is no gross neurology. Um, we're working on it. Um, but essentially, he had marked peri orbital swelling. He did have non pitting Swelling of his hands and feet had quite a lot of pain. Um, I didn't see him until two days after this, but he was He was, uh He was a frightened teenager, and he he wasn't. He didn't He didn't talk much. Um, he didn't engage much. Um, and he was quite difficult to examine. Next slide. His bloods were relatively frightening. So he had lowish at this point. He had lowish neutrals. He had normal platelets. They fell later. He had a raise lactate. He didn't have much inflammation, but he did have a ferret out of 10,000 by this stage and a c k of 12,000 with signs of macrophage activation which do suggest HLH um, high triglycerides, low fibrinogen under arranged LFTs. And when I examined his muscles, he was, uh, globally week worse approximately, uh, than, uh, distantly and mostly a grade of three out of five. Our first test results back suggested that he was a in a positive. He had this periodically edema with some increased swelling, which we thought was a heat rash. Although oddly, if you see the dermatomyositis, you would expect, especially juvenile dermatomyositis. You'd expect to see nail fold capillary dilatation, which he did not have. But given how sick he was and his blood test results, we assumed that he had juvenile rheumatoid arthritis or Lupus. Uh, he had an associated him a fag, acidic syndrome, at least on the blood test. Or you could call it a macrophage activation syndrome if you're going to take the fact that he didn't have it on his bone marrow. Um and we agreed, uh, following the skin, Martha for treating this in rheumatological conditions to treat him with IV methylprednisolone to try and switch off inflammation. I'm an incline ra, which is an anti I L1 agent, which can be very useful in this, especially if you don't want to use steroids because it's quite good at controlling macrophage activation syndrome. But it doesn't. If you have lymphoma, it doesn't prevent you diagnosing it or be, uh, increase the difficulty of treating it next slide. So I just showed some of the imaging. So this is actually, um it was a stir that we did. And you can see a lot of peripheral, increasing intensity, Kind of patchy looking, Um, and you can you can see that. Oops. Get back. You can see it's involving most of the anterior compartment and some patchy areas in the posterior compartment. Um, he had some other previous imaging done. So you had a CT chest of the pelvis, and all that showed was some axillary lymphadenopathy and some some. There was a comment about loss, of course, and, uh, differentiation bone. But we've had a normal bone bone aspiration, and there's a slightly large spleen, which I have not shown you on these images. And then he had a muscle biopsy, and this was the images. After the muscle biopsy, you can see some of this increased signal intensity in the muscle here and then he actually had, Unfortunately, a bit of a bleed after the muscle biopsy had a surgical biopsy and he's had a drain put in place. Yeah, yes, Yeah, I'll do this, but and then I think it's the next slide, of course to Clara. So, uh, this was on the fifth of June. Um, and this is the report that's in the note. So it says this is a very unusual presentation, which by that stage, I think we've been treating about a month. We were aware of, um, deal one positive C d a positive cytotoxic t cells. So they were all one type of C T cells basically destroying the skeletal muscle. And the sample at that stage was sent for colonel analysis, although the comment on the report was that this seemed unlikely and that the skeletal muscle looked destroyed And the next one? Yes. So that one was I I think the report from, uh, Hematopathology. Because I waited for them before doing my part in terms of, uh, inflammatory myopathy. That's why the biopsy was referred to to to me, too, as to neuropathology. So if we do go one step back, I'm not at the MG T. But I am in my office and I see this side. Uh, for the first time under the microscope, my reaction was Okay, this is not your usual. My anxiety's If we look at about here, they're actually very little muscle left. The muscle fibers are the big pink ones in the lower part and all the rest that looks blue. It's so small cell infiltrate that looks lymphoid. And if we move to the next, uh, slide, please. So at higher power again, a few muscle fibers on the left, heavily damaged, invaded by, uh, lymphoid cells and the cells they look they are mainly of intermediate size. Um, uh, they're not mature lymphocytes. Uh, the nuclear, uh, quite irregular. They're not well rounded. Some, uh, elongated. There's some atypia I can see you clearly right? Um and in between, um, I don't know if if I don't know if you can see them. Um, there are some larger cells that contain, uh, that one is probably an atypical lymphoma itself. But, uh, if you go on, if not, I'll have another slide later where I actually added the, uh, we can see them better There are some larger cells that contain some nuclear debris. And those are macrophages. Showing phagocytose is, um, and the next slide here, here at higher power we see again something that's quite worrisome. The arrows show my topic figures, which are, um, not so commonly seen in In, in, In, in the cemetery and traits. And, uh, to see so many, uh, my toes is and, uh, the next slide. Uh, here's for comparison in the system and my ascites, uh, and in this one is actually quite florid inflammation Most my insides will have less lymphocytes and this one if you want, but it's to show you not only the degree of, uh, um, muscle damage is seeing usually in, in, in, in, in, in a inflammatory myopathy which, of course, is much less than what we see in this case here. But also how the cells here they're they're smaller. There are a lot more regular. So this is the the usual, uh, inflammatory myopathy is with a lot of lymphocytes. And if we go to the next slide, So the immunohistochemical here was telling, because if you look on the left, all the lymph node itself your CD eight positive, which is very unusual. I mean, in, in, in, in in any kind of inflammatory process. It should be a mixed even in IBM. Or we said before we see, see the positive cells, they will not be all CD eight positive if we look on the right. The CD four. What is actually picking is macrophages. Mainly they're larger cells. And if you compare with immuno under, which is C. D 68 that's a macrophages market CD four labels both CD four positive lymphocytes macrophages. Most of the C D 68 most of the city for positive cells are actually also see the 68 positive there, macrophages and lymphocytes. And on the left down, we can see they're not essentially not a single B cells. See, the 20 is, uh, negative. And then on the next slide, I think I have the proliferating fraction, which is is very high. Of course, many inflammatory cells. It's It's quite high, too. But this one is really, uh, I would say 50% of the cells are positive, and then the last year, which is what I was trying to show before. But you can see it here if you look at the arrows. So those cells in between our macrophages and they contain nuclear and then a couple of them the upper the upper arrow There is a red cells in the middle. It contains a retro site. It's the little red circle in the middle. Sorry, Demetria, I'm trying to Yeah, you see, Yeah, those are retro sites. And there's one inside the macrophage a little bit below, so it would fit with. There's not only phagocytosis, but there is also, um, I phagocytosis here. Of course. This is not something that's diagnosed on a muscle about this histologically. We will need either to find it even the bone marrow or in the spleen and the liver, but it would fit. And then this macrophages like, infiltrate infiltrate of fibrocystic cells is a minority. The majority of the cells here with atypical CD eight positive cells. So at this point, for me, this was not a primary muscle disease problem. It was a hematological problem. And actually, I just packed everything and sent to dermatopathology, which was really helpful. Um, yes, I'm very happy because this is now We were quite stuck And he had quite a different course, as you say, Uh, maybe he had a bleed into his muscles like we did a surgical biopsy rather than because we needed to give him a general anesthetic. Like I said, he was scared. Adolescent, Um, we were still would have this soft a n a result. And we still because he had him a phagocytosis which again, could be inflammation or neoplasm. Um, we were I was very convinced that this was the pathology. Our pediatric dermatologists. We're not, um, despite the fact that he dropped his platelet count two at its lowest 23. But, uh, and next slide, um, his creatinine kinase did actually fall with methylprednisolone anakinra cyclosporin and eventually etoposide, um, and his ferritin came down. So we probably started to get on top of his, uh, haemophilus citosis. Um, but we wanted to try and, uh, do a sperm salvage for him because he was 17 and we were treating him with etoposide. Um, we got no usable sperm from his testicle. He got a subsequent infection and in fact, lost that testicle with quite a difficult course next side. So this is just the point at which we went. His HLH is not improving. We need to change his treatment and involved hematology, at least to discuss. Although they continued to not believe that this was a primary hematological problem, Uh, I discussed it with colleagues Gosh, at the vasculitis meeting and one of my colleagues from gosh came over to see him and agreed with me that this probably wasn't the matter. My sight is both because of the lack of response to treatment and because he didn't have typical nail fold changes next slide. This really summarizes where I was at this point. But then, fortunately, as Clara said, she sent his biopsy to the, uh, hematology oncologist next side. And those T cells were all clonal and they were all in the muscle and all of that him a phagocytosis was actually taking place in the muscle. There was no evidence of it into bone marrow Biopsy's. It was not in the CSF. It was not in his multiple. It was not in the testes. We we thought that maybe that his testes were involved because he had no sperm. Um, and he was transferred to the adolescent service at U. C. H where he had a bone marrow transplant for his lymphoma and did quite well. But like I say, he was a scared adolescent. He had a really very difficult time. He had psychosis to steroids. He he lost a testicle. He had a bleed into the muscle. He had a very prolonged admission by the time it was all over and has since I discovered from the notes writing this presentation defaulted all followup at U. C H came in last year with intercourse or sepsis and did really well. But again is still not under follow up, I think next slide. So the conclusion from my part of this was this young man involved in his care across three trusts, uh, and three of our sights by the time uh, neuro neuro adult neurologist who was a specialist in muscles. Is that Karen Cross? Um, the sperm salvage and hematology hematology at Hammersmith And he he was here with us at Saint Mary's. So he was looked after by me as an adult rheumatologist and with my pediatric rheumatology, hat and colleagues. Um, he was looked after by we had reviews from both adult and pediatric neurology. He came in under adult general medicine. We transferred him to the pediatric i. D team so he could be on the Children's ward. Uh, we discussed him at great length and multiple times with pediatric rheumatology, adolescent hematology, uch and adult hematology, both about his clotting and the HLH. On presentation. He had multiple involvement with the pediatric surgeons, both for biopsy, uh, testicular surgery and the bleed which required drainage, obviously radiology pathology. And that really is why MDT working is so fundamental to how we deliver care to patients. Thank you so much. And thank you for going through that case, which was, you know, one of our most challenging ones. I think that we've ever covered I think we're coming towards the end of the talk there. But I mean, I guess from the imaging side, what I learned was that all that all that's bright on t two is not a Dema, which I think is a classic one. This was infiltrated disease. You could easily mistake that for dermatomyositis, but actually, um, that was actually inflammatory. So I mean, infiltrative cells rather than just inflammatory cells. I think that's the important take home. Um, do you look carefully and think about other causes for t two, uh, brightness. I don't know if you've got any questions or clarify. Don't know if you wanted to say anything else. Yeah, I mean, I don't I think everybody is stunned by, you know, the complexity of the case. And, uh, it's amazing. You know, uh, the experience of having three of you discussed that very complex case has truly reflected what happens and why you need an m d t good mdt to solve these cases. So I think it's good that, you know, we have the recording for people to go back to, because it is, but, you know, difficult, uh, topic, You know, my bursitis. And, uh, it is, uh it has always been a conundrum for the clinical world and for the radiologist. So I think it's amazing, you know that. I mean, I was I was baffled by the case. I mean, it was so difficult and clinically also trying to manage, uh, in that age group was a challenge in itself. So I don't have Yes, I have some thank you coming through on the messages, but I don't think I have any particular questions. One thing I just wanted to ask, uh, Dimitri was like So what is the pathway like? Uh, do the biopsies Are the biopsies performed by histopathologist Or, you know, from can I invite all the other speakers as well? Uh, yeah. So at the moment, Imperial, We, um the surgeons do the majority of the biopsies, and we've started to start running a radiology imaging based ultrasound biopsy service, which is which is what you're looking at. But we're starting to build up to get a bit more resilience and trying to offer that as a as a service. But it's generally done surgical biopsies. I don't think we've got some clinicians doing any needle biopsies at the moment. And, uh, so as a as a very junior rheumatology registrar, we used to do blind needle biopsies with something that looks very much like your needle. But it was never that much fun, because you never quite know where it's going. Um, so I'm I'm much more keen on your, um your ultrasound guided that you do, and I don't, um, the huge advantage of your ultrasound guided services. You're part of the muscular, the myositis mg t And when we try, and particularly on this site when we tried, we've had a recent case. When you try and do a surgical biopsy, no matter how careful you are about it, no matter how much I send my register R S H o to pick the biopsy are tell nobody to freeze it and to take it themselves in a taxi to tear across. There appears to be literally no way to make sure that the biopsy gets in the right state to the laboratory and is handled properly. Whereas if we do it in a planned where a planned list the lab knows about on the correct site, we get much better quality biopsies. Um, and I would much rather am to do that. But he was quite sick, difficult to transfer and really very frightened and quite needle phobic by that stage. So it wasn't an option. Uh, you know, your experiences at Oxford now you know you're there. Um, here they are, all surgical. Um, a biopsy is, um, the one of the my colleagues used to She used to do them herself, but I think now the trend is a pathologist. Don't perform the biopsies on their own anymore. Uh, and she used to do surgical ones not near the ones, because she was trained in surgery. But you see less and less pathologist doing, and just to pick up on the point that you may be right at the beginning. Actually, when you're talking about normal looking biopsies is that it could be a sample error. So one of the things that's important as usual imaging to guide the biopsy, just as you would in a cancer case. You want to go for the for the bit. That's a typical and often you know, the CT will say this muscle is fine, the whole muscles involved If we get, we make. If it's a surgical one, this image guiding one, it's a lot easier to correlate. And absolutely that's great because you want to avoid the normal muscle and you want to avoid the muscle that is too affected because then you get end stage changes that they are very specific. There's a lot of atrophy and fat sometimes, so you can't really do much with those. So I think it's great. I really I really enjoy doing working with you with this box is absolutely, uh can I ask you to this two unshared the Yeah, I can see all the speakers together, and, uh, yeah, Thank you. Thank you for that. So I think I mean, I would like to thank the speakers because it's a very busy that you that, you know, everybody has, and you spend one hour and, uh, I'm glad that, you know, uh, those who are not being able to attend live will be able to access the, uh, recording. Because, like I said, it's quite a complex and quite difficult topic. And it's nice to go back and, you know, look at what has been taught. So thank you once again and, uh, the next, um, you know, BS. Our session would be on meeting, and it's the date will be out soon. So, um, once again, thanks to Dimitri, thanks to Clara. And thanks to an for, uh, making it possible to have a real you know, MGD discussion about a very difficult topic. So thank you. And I think we have filled on the line from medal, and he wanted to say a few words about his platform. Can I invite Fill please. Thank you so much for for having us. And what a great Um uh, kind of case, uh, description of watery. My name is Phil. I'm a medic by by training. And I just want to say thank you for partnering with us on on this journey. Our mission is to make healthcare training accessible to healthcare professionals everywhere. Why? We need to train 18 million more healthcare professionals by 2030. And the Lancet describe what they what. They term severe institutional shortages in our healthcare training capacity. What's even worse is that where that problem is at its greatest, the resources are at their least. And there are 11 countries on the continent of Africa which do not have a single medical school. There are more than 20 with just a single medical school. But it's not a problem that's a far off problem. It's a problem that affects so many countries around the world. In Time magazine, they talked about the U. S. Position shortage only going to get worse. And in BBC news in the summer, the headline was, The NHS in England is facing its worst staffing crisis in history. And when we look at the numbers. Actually, we can see that, uh, clinicians are having to spend a lot of a lot of their own money actually pursuing teaching and training. For instance, study from the Association for Surgeons and Training talked about the out of pocket cost to surgical trainees over the course of their training, being up to 71,000 lbs 1300 lbs of which every year is spent on courses and conferences. And our mission is to try to make that healthcare training accessible for everyone. It shouldn't be those with the greatest ability to, and it shouldn't be something that's locked into being a tick box exercise for the wealthy. And and so we're really passionate about working alongside. Amazing organizations like BSS are to make your teaching and training accessible to people accessible to people in the low, middle and high income settings live and on demand. And and that's that that really is what we're all about. And we only believe that the best way to actually do that is to work alongside organizations to collaborate in this space in healthcare with other healthcare organizations, and when we looked at high organizations were doing that teaching and training. We saw that so many of them were setting up a place for registration, delivering a live video call in another place, pinching into Google Forum to collect feedback manually, making certificates, downloading a video and adding it to me or YouTube, adding in another link to allow people to give feedback for on demand, which has now become a thing. We're busy and on call and all night and have families and and and actually as busy clinicians, that's probably not the best use of all of our time. And so we've tried to solve some real problems for healthcare organizations on the ground to streamline that. Oughta me at that end to end and, um, doing so, we are working alongside amazing organizations to try to make that healthcare training more accessible. If we can help save clinicians some time, hopefully that's some more time that we can invest into more teaching and training. Over the last 18 months, we've helped 1500 healthcare organizations collectively deliver about 5.5 1000 courses, two colleagues, 171 countries, and the impact of that is sometimes, uh, sort of impact that puts goose bumps on on your skin. I'm just going to tell one story, and then I'm gonna leave you to enjoy the rest of your days, but that that impact is seen on a kind of humanitarian basis as well. So in April of this year, we had some people reach out on our support channel on metal. You'll see on the right hand side that, you know, we ask you to verify when you're joining. I met all events as a health care professional. It means that organization can truly make their events as accessible as open as possible with the safety and security that knowing that it's actually healthcare professionals who are joining and you're not going to get some bombing. And you're not going to get those nasty things that happened in other open access settings. But in a single week, we had high tens. If not hundreds of people reach out just to say they couldn't verify their accounts. And when we reached out to ask why the same answers were coming back, people were saying, I don't have access to my institutional email address, or I don't have a letter from my dean to say that I can access medal and I didn't think it was that important, actually, before I fled the country and what what happened was that there were a group of Ukrainian medical students who we're learning every single day, seven times a day for two months on metal. And what happened was that an organization, a wonderful organization in London called the Crisis Rescue Foundation had recruited 250 doctors from around the UK to deliver teaching and training to these students during the Ukrainian war. And in doing so, they weren't doing some sort of imperialistic UK teach the Ukraine thing. They were actually trying to free up medical professionals on the ground who were all trained medics to instead of providing face to face patient care to, uh instead of providing face to face medical education to provide face to face patient care to bolster their resources. And that's the sort of thing that we can only see when we all work together and and club together in this space. So just to say, a massive thank you to the BSS, our team, for kind of working alongside us on that mission and we're we're really passionate about about this space. So thank you. I hope you had a really great session and keep up with all of the amazing work. Thank you. Thank you. For, um, and and Clara, if you want access to the recording, I will see how we can get it to your training as well, if they are interested. So I will see how you know we can make it available for them as well. So thank you once more and, uh, have a good weekend. Thank you. Thank you very much. And, Clara, thank you very much.