It is 10 on my clock, so I think we'll go ahead and get started. Although my co-presenter, Dr. Zaidman, just left, and so hopefully he comes back at some point. Oh, there you are! Oh my gosh, I thought you had left. And I'm calling you out like that, too. What a great start to the session. I'm Mike Cartwright, I'm a neurologist, a adult trained neurologist, and about 10 years ago, our pediatric neuromuscular person left us at Wake Forest and went to the beach and started a practice there. And so I started seeing all the kids at our practice, and it was right around the time that a lot of the gene therapies and antisense oligonucleotides were coming around, and so it was just really exciting, and I kind of fell in love with the child neurology aspect. I still see a lot of adults. I do an ALS clinic, I do an adult MDA clinic, but I also direct our pediatric MDA clinic and see kids there, and then I see kids in the EMG lab. And so last year was the first year that we did this talk, Dr. Zaidman and I, who is here, and it went pretty well, I guess, I don't know. They asked us to do it again, and so we're bringing it back. Dr. Zaidman's gonna speak first, and then I'll talk after him. I wanted to start by just asking who all in here sees kids? I figured probably everybody. Yeah, almost everybody. And then who is doing ultrasound? Oh, yeah, I like this. I think that was like 100%. And then who does ultrasound in combination with EMG in their lab? Yeah, pretty much everybody. Okay, do we need to do this talk, or should we just all pow wow and discuss how we do things? Awesome. Last year, that wasn't the case. It was like a 50-50. Five years ago, it would have been, I mean, y'all would have been seeing pediatrics, but nobody would have been doing ultrasound, or not many, and so that is fantastic. Okay, they tell us we should do disclosures, so I have royalties from three textbooks. This one's a new one. Dr. Mamarabadi just had this published like three weeks ago or four weeks ago, and it's a good one. It has a lot of images in there. It's a curriculum, and so if you have residents, medical students, fellows, that wanna get started on neuromuscular ultrasound, I think it's a good starting point. Okay, so I'm gonna do a brief introduction. You all know this, because you do a lot of ultrasound, but ultrasound was designed in the 1950s. It is using sound waves that we cannot hear, right, so it's in this ultra range up here, so when we are doing ultrasound, especially in kids, we're using transducers that are 12 megahertz and higher, and so way up here, this is 20 megahertz right there. The highest frequency that I use is a 70 megahertz transducer. As you all know, the higher the frequency, the less the penetration, but the better the resolution. The 70 megahertz goes one centimeter deep, and so that's actually not bad for infants and for young kids. You can see quite a bit. That same device has a 48 megahertz, which will go three and a half centimeters deep, and so in kids, it's fantastic. You can get these incredible images, and you can see that they have a lot of tissue in their body, and because their limbs are small, they don't have much subcutaneous tissue, and so it works quite well. I show this a lot, but this is an old oscilloscope, and oscilloscope technology was used to make nerve conduction technology and EMG technology. It was also used to make ultrasound technology, and so electrodiagnostics and ultrasound and I've shown this already this week. I probably should change this, but basically as computer processing has gotten better and better and better, and it gets every six months, the number of transistors that can go on a capacitor is just increasing, increasing, increasing, and so as the technology gets better, imaging gets better, costs go down, and we have this situation. So in the 1950s, if you did an EMG, and you got a voluntary motor unit, it would look like this. In 2024, if you did EMG, got a voluntary motor unit, it would look like this. They are the same, and so it's not exactly true. It was analog, and now it's digital, and there's a lot of software that's changed on the EMG devices that makes our lives easier, but the real, the technology has not changed that much, and so you know where this is going, but in 1950, this was a fetal, this is an ultrasound of a pregnant woman looking at the fetal head, and they would measure a blip here and a blip there, and they would get a biparietal width, and then they would do an X-ray of the woman's pelvis to see if the head was gonna fit out of the pelvis, which is a terrible idea. They quickly realized you shouldn't X-ray pregnant women, but that's what they would do, and they would say, you need a C-section, or you can have a standard vaginal delivery, and they would make that determination, and this is what the ultrasound would look like, and so what do you think a fetal ultrasound looks like now? These are twins, obviously, but this is what it looks like now, so it's incredible. It looks like a drawing or a painting or something like that, so you get the idea that the image resolution has greatly improved over seven decades, and it's going to keep exponentially improving, and as the imaging gets better, the devices will become, oh, here's even more incredible ultrasound imaging, so that's not a in vivo picture. That is an ultrasound, three-dimensional ultrasound of a developing fetus. The devices will become smaller. They'll become more portable. They will become wireless. It's, the technology is just gonna keep getting better and better. They're gonna, it's already been incorporated into some of our major manufacturers have incorporated ultrasound into their EMG machines, and that's really cool. It makes it a whole lot easier to go from one, from nerve conduction back to ultrasound, back to EMG, which is awesome. That's gonna keep getting better, and then there's been several talks about AI in this conference, and so this is, these are several different AI programs that were used. Each one is a different, this is the source imaging, but then these are different AI programs to identify and measure the median nerve, and I was talking with Dr. Wooten, and we were talking about how AI is gonna change all of this that we do, and so the companies like Natus and Cadwell are already thinking about, as we scan nerve and as we scan muscle, can we get real-time echogenicity? Can we get real-time histograms made? Can we automatically measure the nerve as we're scanning? Can we get sort of like a mean nerve and then a standard deviation so we know how much the nerve is changing in caliber, and just quickly, immediately get that on the machine, not having to take this off the machine and put it on a separate computer, and so it is all coming together rapidly. I would guess this kind of technology will be on the ultrasound devices in, I don't know, five years maybe, something like that. It'll be there soon. It probably is on some devices already. I mean, it really, like every six months when I look into a new ultrasound device, there's something new and crazy and incredible, so. It, as you all know, is an ideal, ultrasound is an ideal modality for kids for many reasons. It's very high-resolution. It's higher-resolution than MRI. We can see more detail than we can with an MRI. It allows for multiple views, so you can get multiple orthogonal views as you're scanning a child. There's no radiation, so if you wanna scan and then bring them back a few weeks later and scan again and then scan six months later, that is not an issue at all, and then obviously, compared to nerve conduction studies and EMG, it's relatively painless. There's a little pain if the child is scared and mom's having to hold the child, but for the most part, it's a painless study. So, without further ado, I will introduce Dr. Zaidman. So, you all probably know Dr. Zaidman. He's a professor of neurology and pediatrics at Washington University in St. Louis. I met Dr. Zaidman a long, long time ago when he was first interested in ultrasound, and we started talking about it, and he's been interested in muscle ultrasound for 15 to 20 years, and is gonna give our talk about imaging muscle in kids. He is an absolute expert in this topic, and so we are very fortunate to have him. I'm gonna do a talk on nerve, and then we'll do question and answer at the end, but let's give a round of applause for Dr. Zaidman. Thanks, Mike. Yeah, you're welcome. Look, he doesn't even need the stairs. He just jumped up like three feet. That's impressive. Oh, man. All right, go get him. Thanks, Mike. Oh, Lord, getting called an expert over and over again is not, it doesn't feel right anymore. There's room at the table. Let's just put it that way. I've been doing this for 15 years. Somebody else come up here and give this talk. It would make my day, it really would, and you can tell I've been doing this 15 years because I have this awful blue-yellow font situation going on, and I have to apologize for that because I need to change it, but everything screws up when you put it in there, and I just, anyway, you have to suffer it. I don't have any real relevant disclosures except that I gave some of this talk last year, and also I should disclose that when it comes to measuring things with muscle ultrasound and doing quantitative muscle ultrasound, I kind of geek out. So I kind of, in updating this talk, I tried to diminish that a little bit. Is anybody here interested in that, quantitative muscle ultrasound? Sometimes there's a few people. Okay, well, I have about that much in on it. So I'm gonna real quickly go through the basics here, which is this is what a normal muscle looks like, and probably everyone here knows what normal muscle looks like. Can I see a hand if you know what normal is, you feel good about what normal is? All right, okay, then let me go through it. I think it's well, we'll see what happens. I oh, yeah. Oh, yeah. That's good Yeah, that's good Is that better for everybody else? Oh, yeah. Okay, so you can see the bone. It looks nice and crisp You can see the subcutaneous fat, which is right there at the beginning and I'm just say The subcutaneous tissue is very very easy to compress. So if you're in the business of Measuring subcutaneous fat what you can see there is you can see the fascia of the muscle and the short axis has a rounded appearance Everyone appreciate that that's because I didn't push very hard on it Do you see though how even the subcutaneous fat has kind of a rounded appearance even but you see it's flattened just a little bit Right here that would alter the measurement And so it's you if you really want to measure this you have to put a ton of gel and barely hold the probe in The gel, okay, so you're not compressing. So even this image technically is not sat not satisfactory for measuring fat By the way, these are the layers of the skin these two lines right here in case you're wondering that dermis and epidermis pretty cool And then within the muscle you can see of course this fibro adipose Septa or these vibrations which which come together to form the myotendinous junction and eventually coelic Kind of kind of come together to form the tendon So that's normal muscle And when you have myopathy the muscle gets too bright and so it gets white and In generally speaking. I think it's a diffuse whiteness or actually to me It looks like that ground glass appearance to talk about when you're looking at chest CT to me. It kind of looks just like that And you can see these different examples and you can't really make a diagnosis of which muscular dystrophy you have just by saying the muscles white, but you can see that it is abnormal and If you're interested in doing clinical muscle ultrasound in order to diagnose muscular dystrophies You can go to another talk because this is what you see and a slide number four and you're pretty much all set ready to roll So if you're want to dive into it, we can but if you walk out of here You've you can check the box. You know how to do it There's a rating scale, of course on this Old old rating scale very simple grade one is normal You see I have the subcutaneous tissue the muscle and the bone there for grade one Grade two is that the muscle looks a little bit white But the bone still looks normal or close to normal which you can see there grade three is that the muscles obviously abnormal But you can still see bony reflection in grade four you lose the bony reflection and that's because the signal is attenuating as it passes through the different echo density of the Mostly, it's from fat and fibrosis to talk about that in the bone signals essentially gone and that's grade four So, why does the muscle get bright? It's it's It's a result of increased fat and fibrotic tissue Generally speaking that causes the muscle to get bright and so it is particularly good at picking up muscular dystrophies Which are characterized by increased amounts of fat in the muscle and increased amounts of fibrosis in the muscle and this is an example from Sigrid Pillan and Sigrid Pillan really brought quantitative ultrasound into the modern era and Did a tremendous amount of work before she decided to do pivot and become a sleep medicine doctor actually But she did all her PhD work in this. She's a physician in the Netherlands child neurologist. She's a pediatric sleep now just Surprising but this is studies in dogs so she could correlate the echo intensity with this sort of fibrotic The amount of fibrous tissue in the muscle from the dog muscular dystrophy models here Which means that if you have something like a myopathy that is not characterized by having lots of fat and fibrosis in the muscle your sensitivity to pick up abnormalities will go down and To be fair that's a that's challenging because it's not hard to check a CK, right? So if you're wondering like do you have a disease and you're not dealing with a destructive pathology in the muscle? That's like a dystrophy Ultrasound suffers too It's a hard diagnosis to harder diagnosis to make you can see here also from Sigrid Pillan a study of 28 kids with pretty well defined mitochondrial myopathies and The and there you can see the examples and you would argue that's a normal on the left Which is would be a grade one and that is a pretty weak Grade two on the right Right fair enough. And and and so quantitating the signal she was able to detect Oh, you know only a small fraction of these children with abnormal Muscle echogenicity and they were all over age 5 because presumably the pathology had had time to sort of progress a little bit You know or maybe in its severity in each individual patient Okay, that's muscle disease But of course you can see nerve diseases as well and in nerve diseases the muscle also gets bright but it's typically in a more advanced state and also gets atrophic and You can measure What's called the fat to muscle ratio? and And so here's the fat and here's the muscle and here in muscular dystrophy that ratio is preserved Whereas in a neurogenic condition better described better shown over here You can see there's a there's much more fat than there is muscle. So As the fat thickness increases in relation to the shrinking muscle you get a kind of a flip of the ratio It's two parts fat one part muscle or something like that. Whereas here it's it's almost four parts muscle one part fat You Can get this moth-eaten appearance by the way see this little rim of spared tissue that's also been described in SMA Okay, so Let's talk about muscle thickness How do you measure normal muscle thickness? I already told you some of the technical issues involved You need to make sure that the muscles not being compressed It's it's it's easier than it is to not compress the subcutaneous tissue So measuring muscles a lot easier technically than measuring subcutaneous fat and here's some examples you and it and it is important to sort of know exactly these techniques and Because if you don't have the muscle oriented correctly, so for instance if you're imaging Diagonally this way and you're referencing a value that was made this way. It'll throw it all off here You can see the bony reflection is oriented in a way So this little part here is flat and so you get this Sorry you get this straight up and down here and the both Cross-sectional area of small muscle and thickness of large muscles have very good test retest correlation with MRI So it's it is an easier way to do it And I don't think it suffers as long as it's done technically accurately same with any test, right? You got to know the technique So that's for measuring muscle size What about what we all care about is, you know, do you need to biopsy this kid to figure it out? and these days it's genetics first and then Imagine and then the biopsy and here are two children both toe walkers both with normal CK ages 8 and 7 with with one with a slow run the one with the worst looking muscle there and the other with a normal run and Man, these slides are 12 years old And I looked both of them up last week to see if I could tell you what was wrong with these two children and They were both lost to follow-up and I hunted them down every which way I could electronically so I don't know Neither had a biopsy at the time when I was doing this. Nobody would have trusted me to say this image is abnormal So, I don't know what happened to him, but the question remains What do you does this enough to flip somebody into like a bigger workup this grade to? Techmat score on the left there So here's grade 1 2 3 & 4 and here is the diagnostic Sensitivity as to whether a child with each grade Ultimately was determined to have a neuromuscular disease or not and you can see grade 1 over here was normal You can see grade 4 over here was all abnormal a grade 3 all of the children had neuromuscular disease that leads grade 2 And so grade 2 you got it like a 50-50 shot of having a neuromuscular disease So that seems awesome, right? I mean look at the hundred percent Specificity of the abnormal grade 3 & 4 ultrasound everybody gonna go home and start doing it, right? Except what I'll tell you is this person runs into your exam room This person walks into your exam room this person limps into your exam room and this person wheels into the exam room So you do not need an ultrasound to diagnose the neuromuscular disease in these two children And you don't need it in this child typically to exclude one So you're left right here, which is pretty much where you started anyway at the bedside So I'm not saying no, I'm just wanting you to understand how to how this stuff plays out, you know in the clinic So can we do better than that by measuring all of these things and that's called quantitative muscle ultrasound And when I started giving this talk, this was like brand new and now everybody's knows what it is we're talking about you basically circle the thing you dump it in some program and it spits out the grayscale image of this and and here's an example of the normal histogram of the Varieties of white and dark in here and here's the boy with Duchenne at only three and a half years old with a grade Two HECMAT score and this in this in here's again the thickness and cross-sectional area data. We're liable to MRI Here's the echo intensity Reliability having two Raiders So the reliability goes up in terms of scoring this between two Raiders compared to doing a HECMAT scale between two Raiders Which is much less reliable. So the inter radar reliability is better and you can get Really nice positive and negative predictive values in children over age three where the disease has had some time to sort of show up in the muscle And this includes children with easily diagnosed conditions like Duchenne muscular dystrophy in this database, okay Andrea Boone who's here wandering around if you haven't met her you should say hi She does all the diaphragm stuff and she's way invested in using this and I can tell you that Nens van Alphen also in the Netherlands. She's a neurophysiologist I have heard recently that about half of the people that go to refer to their EMG lab They put through a standardized ultrasound quantitative protocol and they don't do EMG Looking for neuromuscular disease And so how do you get to sort of that level of confidence in your protocol for a quantitative decision-making about yes no decisions for people and it is It is in depth It involves a you know a standardized protocol of multiple muscles and it involves multiple decision trees meaning if you have one muscle that is a Z score of More than 3.5, which means it is really easily obviously abnormal Something's wrong in that muscle, you know, that's of a that's a nerve or muscle problem Or you can have two muscles that are just over Abnormal meaning a Z score two and a half many members Z score is a standard deviation, right based on normal values So anything a Z score greater than two is two standard deviations above the mean of the normal But you can have three muscles that are only one and a half standard deviations above the mean So they are all technically normal, but all three muscles are at the higher end of normal That would also be your decision tree so you can see how these quantitative protocols get into Thresholding decision-making that would be a little less Obvious just scanning and doing it qualitatively that makes sense Yeah So pretty complex and here's an extended protocol for less than in more than six muscles With all these multiple decision trees about how to threshold in order to decide where you're at and look even with all of that You end up in these but with these borderline categories at the end So, how does this sort of protocol perform? I mean not not terribly I know the sensitivity of this sort of things 84% for picking up any neuromuscular disorder not just muscle disease Okay, nerve diseases to the specificity meaning if it that if it's abnormal you have a problem is is close to 80% Of course the PPV and NPV depends on your population and And so this is work Andrea Boone did which is really very very High high quality in my opinion and even with all of that of their cohort of 138 people 69 of them ultimately did not have a neuromuscular disorder and How did it perform in those people right because you don't want to send people for the workup that don't have it and And why and of these 69 without about a fifth of them even with this complex protocol had an abnormal Ultrasound result. So who are those people whose muscles don't look right, but don't have a neuromuscular disease Maybe like the toe-walking boy. I showed you for instance with the grade 2. Well, they were heavy Or they had a CNS disorder in which their muscle had not been used appropriately like cerebral palsy Okay, or some severe encephalopathy and in addition to that 20% of abnormal ultrasounds 20% of patients in out of the 138 ended up in the borderline category where you still didn't know. Okay So why why can't we do even better than that I mean those protocols are pretty in-depth and one reason is probably this do these two people have the same Size muscles do these two people have the same muscle echo intensity and how can we answer this question? And is it straightforward and the answer is not really straightforward Why or why not? We don't really know a hundred percent. I'm gonna try to get into it. It's interesting to me This is where I kind of geek out on the quantitative stuff But let me first tell you here's just measuring muscle size of the thigh and some other muscles you can see over here, but this one is the thigh the quadriceps and over the lifespan and I'm looking around the room and and most of you are probably still over here But some of us are getting over here And if that's not depressing enough, you can see at the end of days Your muscle thigh thickness is pretty much where it started So that's sarcopenia for instance but it also demonstrates the issues of measuring and developing normal values across populations of people and That's just like I said the thigh but each muscle has its own sort of course So you can see the sternocleidomastoid doesn't really change a tremendous amount This is left and right and this is males and females. So the different colors here are left and right Whereas the biceps when you know young men go through puberty and are out there, you know at the clubs and the tight tight shirts You know who's seen that? You could the bicep gets real big and it's not but it doesn't last You know, so buyer beware So That's what happens with the with the muscle thickness Muscle brightness, you can see doesn't quite have that peri puberty Bump, you know, it tends to stay mostly a lot more flat In terms of the echo intensity, so let's now focus just on children Well in children you can imagine that the muscle thickness is definitely going to increase as they get older, right? Because they are growing and everything gets bigger and you know that without me showing you this graph But the echo intensity not so clear here the TA in a four-year-old compared to the TA in a 12 year old and I think You can all see it's a little brighter right in the 12 year old and you can in fact If you didn't think so look at the histogram much brighter that way and the quad same thing But the other muscles they studied didn't really show any relationship in the echo intensity with age So basically flat which is easy for quantitation because you've got one normal value per muscle doesn't matter how old you are So that's sort of encouraging Here's another study which came to the same conclusion here muscle thickness goes up with weight Sorry, the mouse is going haywire on me Muscle thickness goes up with weight but Echo intensity was independent of any of the investigated variables age weight height and gender so they did not have to Modify their echo intensity normal values for those parameters. You might guess would need to be modified Yeah, everybody with me sounds great, right? Let's go Here is an awesome Relatively recent study that I did not show last year an amazing effort in almost 300 normal children age 5 through 9 They have their rectus femoris muscle thickness measured their subcutaneous fat measured their muscle area measured and their echo intensity measured and then they Had a what they call a corrected echo intensity measurement for depth Because you know if you have thicker muscle fat the muscle moves further down the image and you need to correct for that attenuation in the signal So they looked at this very carefully and then they also made these children go through a battery of physical fitness tests they looked at their Cardiorespiratory fitness their upper and lower muscle strength how agile they were and their overall fitness levels And then I love this they characterized them as being either fit or not fit so And then they looked at all these outcomes and what do you think they found with the echo intensity This is what I have named the couch potato effect So you can see here the black bars are the children they decided were fit and the Gray, they decided were not fit based on each of these tests cardiorespiratory fitness hand grip strength Standing long jump and speed agility. Remember they're just looking at the quadriceps. Okay, and so the less fit children have higher muscle echo intensity even accounting for the Subcutaneous fat thickness even in the corrected EI that they did and it's actually How unfit you are has this very sort of linear? Correlation with your echo intensity and here's an example of a fit looking muscle and an unfit looking muscle And I love this paper because I can tell you this is true because I've seen it for 15 years I see it in adults and I see it in kids. So when I sort of I Do this qualitatively just so you know but I kind of judge my Thresholding when the person comes in the room based on their physical fitness level and also their obesity and it's well known that obesity makes Your echo intensity go up well described. Okay, but this controlled for fat thickness So this is just fitness of the muscle itself. So Leave the meeting and hit the gym as the suggested device now We talked about age and its effect on echo intensity, but that's also not entirely true. These are infants both pre What's the word? not pre term and And term infants and muscle thickness and these you can see this these 24 week 30 week and birth Six months and 12 months and the fat the amount of water Content in the tissue really does change over time and this is the echo intensity of three different muscle groups Which you can see does go up. So infants have dark dark muscles. Basically is the answer here and and and That impacts Its utility of this quantitative muscle ultrasound in these populations So here's a seven day old with bifacial weakness club feet respiratory weakness poor suck-and-swallow obviously abnormal child High suspicion of a neuromuscular disease. Here's the teeny Very dark tibialis interior. That's normal thickness for a baby. Here's a quadricep. It also looks pretty normal Thickness which looks perfectly normal in its echo intensity and this child has myotonic dystrophy So not every disease makes the ultrasound go abnormal Even if it's very severe and the child severely affected including bilateral club feet now Maybe the thickness would be technically lower on the lower end But you can't eyeball that and say there's a neuromuscular disease in there and there clearly is so Not all is lost because you can see obvious abnormalities within the muscle just by doing comparisons, you can see there, that's the semitendinosus, there's the membranosus, which is normal, and there's the gracilis and the adductor, which is less normal. And I'm gonna speed up a little bit here, because I'm taking too long. This is an example of Pompe disease. When I see intermittent muscle involvement or selective muscle involvement, I think Pompe. And this is also something sort of unique about inflammatory myopathies, including Pompe or irritable myopathies, which is the muscle signal can get very bright, as you can see here, but the bone signal is preserved, which you can see here. So this is not a dystrophic process. The increased echo intensity is being caused by something else, not increased fat or increased fibrosis. And that affects the attenuation of the signal differently. You can see that here. So there's a lot of newborn screening for Pompe. Does your state newborn screen for Pompe? So you might think I'm gonna ultrasound all those children to decide whether I need to put them on their ERT or not. And we do do that. I have not found it to be particularly helpful, by the way. And here's a study looking at infantile patients, which are severely affected and clearly need to be on ERT. And this is the infantile-onset Pompe patient over here. And these are the late-onset Pompe patient. This is normal. This is the late-onset patients over here, showing a couple different things. Here's the selective muscle involvement of the intermedius, which I thought was a specific pattern for Pompe. Published that, but turns out it's not, because here's the reverse. And here's a variation of the reverse. And here's both muscles being severely abnormal here with the preserved bony reflection. Same here, preserved bony reflection. Same here, preserved bony reflection. So I threw in some cases to make this a little more interesting. So this is a newborn with arthrogryposis multiplex congenita. So you can see there's no muscle here in the deltoid. There's no muscle here in the bicep. There's patchy involvement. Look at the spared rectus femoris, but the abnormal lateralis and the abnormal intermedius in the quad. There's nothing in the triceps. Here's the vastus lateralis over here, very abnormal. Here's the intermedius. And here's the rectus, and here's the absent muscles in the adductor compartment over here. So this is what amyoplasia looks like. This infant here is another example. This is a four-month-old here. Very thin muscles, looks a lot like SMA. And this was probably a motor neuron disease. The EMG looked neurogenic. We never figure out what these things are genetically. And interestingly, here's the normal legs, TA, quad. Here's the wrist extensors. That was at four months old. And four years later, all those leg muscles are essentially normal, but persistent weakness in those muscles with the amyoplastic muscles. So I do use this for arthrogryposis, and I get a better sense of which muscles are likely to work and which won't. And I can kind of give the family a little bit of practical information about where I think the deficits will be. And it's a lot easier than the exam itself. And I think it works pretty well, just practical. Everybody wants to use this quantitative muscle ultrasound as a biomarker, and I'll let you read these criteria. I've become very pessimistic in my old age. I'm really exacting. So when an enthusiastic person comes up to me and says, ultrasound and biomarker, and it all comes out in the same sentence, my toes start to curl just a little bit because I think you need to be really thoughtful about the purpose of a biomarker, right? It has to do better than the things we already have. It has to be better than the physical exam right off the bat, because otherwise you're just gonna publish a paper about it, but no one will ever find it of great utility. So this is like the world's greatest biomarker right here. All these criteria, which I think are useful to think about before one launches on a career exploring it, which I did. So here's three brothers, all with Becker muscular dystrophy This is an old, old slide, but I can tell you this boy here was playing on his high school volleyball team, and this boy would ride his bike around college campus. So they were very minimally affected boys with Becker. Not normal exams, but minimally affected, and you would not say they should be minimally affected based on how this muscle looks. You'd think they were severe. So you can get the sense of how this could be a biomarker, because you know what's gonna happen to them over the arc of their life. They will decline, they will lose that function, but they hadn't yet, but the muscle looks terrible. So that would be a early sign of disease that would theoretically predict their decline. So I got excited about it, and I did all these measures in Duchenne, and you can see here cross-sectional examples of how muscle in Duchenne gets more bright over time. And Dr. Janssen and other folks in the Netherlands did a longitudinal study and showed that, as you might guess, that signal gets brighter over time. In older children, I put out a little small study of younger children with Duchenne to show that that muscle also was likely slowly increasing in its signal intensity over time, even at young ages. And finally, collaborated with Seward Rutcove at Beth Israel and did a very large NIH-funded study where we really tried to show prospectively whether this was a reasonable thing to follow or trend over time in boys with Duchenne and whether it could impact clinical trials. And you can, first off the bat, these are controls. You can see the variance in the measurement for the controls, and you can see the boys with Duchenne are obviously abnormal right from the start. There is a small increase over time here. This is two years over time, but it's not equivalent across the populations, which would have made it very nice. The younger boys over age seven are mostly flat, and the boys under age seven, boys over age seven is where the increase starts to happen. And that's very similar to the other functional outcomes that we use, and now the issue is sensitivities and variance and which one has greater sensitivity, less variance. And if you're looking at boys older than age seven and you had a drug that would make this line go flat, you'd only need 25 boys in order to detect that in this, using this as your primary outcome. So it has some, there's some room there for it, and MRI can perform similarly, if not better, and that's starting to be incorporated into some trials. But ultimately, we need to know their function at the end of the day. We don't know how well this correlates with their function. Okay, here's a four-year-old with progressive leg weakness, and you can see this is what the muscle is doing. It is just twitching away, but actually the forearm muscle also twitching away. Mike, I'm sorry, I'm gonna go a couple minutes over. Did anyone know what this is? You do, this is spinal muscular atrophy. You could have guessed ALS, but you know it was a motor neuron disease, it's not a muscle disease. So that's what SMA looks like. Hopefully you'll never see it because we're treating it, but actually you might see it. Why is that? Here again, new paper. This was a study from CHOP where, what they were actually interested in is whether if you put a newborn screen-identified SMA on dual therapy, they did better than if you put them on monotherapy at a very early age, so before day of life 60. They followed their clinical outcomes, but I'm gonna focus just on the ultrasound outcome, which is that the two copy children had progression of their disease. You can see this is baseline and this is follow-up, and this is baseline and this is follow-up. So the treated newborn screen-identified two copy kids continued to show progression of their normal at day five to abnormal at day 82, despite treatment, either monotherapy or dual therapy. Dual therapy meaning Spinaraza and Zolgensma or Rizdoplam and Zolgensma, okay? So not only that, but they all developed fasciculations like I just showed you, and the three copy kids did not. So here's the three copy kids at baseline, two copy kids at baseline, 100% normal, nearly 100% normal at baseline in terms of echo intensity. No fasciculations here, almost no fasciculations in the two copy kid. And then you look at them over time and you can see the age here. So they followed them for quite a long time here, a couple of years. These are the three copy kids. They continued to have 100% normal looking muscle and no fasciculations, and you can see here all of the abnormal echo intensity here in the monotherapy, dual therapy, or mono, and then added later. So this was preemptively dual therapy. And then all of the fasciculations that developed. So I think this is neat. I mean, it's not encouraging, but it's neat in a different way to assess and think about what's happening with the disease, right? And the question is, is this because they'd already taken a hit and you stopped it, but you can still see the result of that acquired over time? But what I find encouraging about this is that these kids were normal at birth. So that, I think, is what the good news here is. They weren't born with tons of fasciculations everywhere. So I still think there's a window there to try to make the two copy kids turn out like the three copy kids. It suggests to me that the SMA disease in these two copy kids was not longstanding for months in utero. Because here, you can see it evolve over months once they're out. And then lastly, I'll just mention another neat and relatively rapid change you can see in muscle, which is if you are intubated in the intensive care unit, your diaphragm thickness drops very, very quickly. And this is a very interesting phenomena that we studied. And in fact, it happens, the diaphragm between infants and children tends to sort of have the same small amount of atrophy in the intensive care unit. But infants tend to preserve their other skeletal muscle thickness, whereas children a year and older tend to decline it. So something's, I like this, this makes sense to me, because infants lay around all day and children walk around all day. So you know if you're gonna lay around or be paralyzed, whatever, your muscle atrophies, everybody knows that. I think something's different about the metabolism in the infant muscle that sort of protects against that, at least a little bit. I might be wrong, but there's some difference here. There's also a central component too. This is without TBI and with TBI. You can see the kids with brain injury atrophy more. So that's probably just tone, if I had to guess, affecting the thickness of the muscle. But this stuff interests me. I don't know what else to say about it. I think it's neat. So all that being said, there's just an immensely practical component here that you don't need to have listened to this lecture for, because here's a teenager with left shoulder weakness after a lymph node biopsy. And I can tell you without doing any EMG here that the trapezius on the normal side is a lot thicker than the trapezius on the other side over here. And here you can see again at the mid-level and here you can see at the lower level here, the inferior trapezius, that little thin rim right there. So, you know, this is totally worth it, you know, to get good at this. You don't have to dive in on the quantitation of it to use it. It's very practical and I will leave it at that. Thanks for coming. I appreciate your time. Thank you. Let me introduce Dr. Cartwright. Dr. Cartwright is a consummate educator and just a phenomenal friend and an easy speaker. He's at Wake Forest, he's been there a long time, he's very helpful at the beginning of my career. If you are interested in hearing some enthusiasm about your career, I would encourage you to talk to him and then you can come talk to me after that. Thank you. Thanks. All right, thanks Dr. Zaidman. Let's see if I can figure this out. And we'll do questions at the end, is that okay? We'll save, my talk's not very long, we'll save 10 to 15 minutes for questions. Let's see, let's go through this. Okay, so Dr. Zaidman talked about muscle, I'm gonna talk about nerve. I have got those disclosures. I've got two objectives. And then I'm gonna talk about reference values of nerve cross-sectional area, not super exciting, but it's important. I'm gonna talk about how, sort of practical stuff, like how we set up our lab, how we scan the kids. I'm gonna talk a little bit about common scenarios that we see in the lab. And then I have four cases, depending on time, I may add a fifth that I just got some information on this morning that I thought was super interesting. I'd like to hear your thoughts on this. And then some conclusions. So I did those already. So at the end of this talk, hopefully you can describe how ultrasound is used and the diagnostic approach of suspected nerve conditions in children. And then describe the ultrasonographic changes that occur in the nerves of children with certain conditions. I already did this, but why we do it, no radiation, it can be repeated, no sedation. That's a challenge with MRI. So Dr. Zaidman mentioned MRI as a good option for, potentially as a biomarker for muscular dystrophy. The sedation part is a challenge with MRI for sure. Very high resolution, tailored approach, and painless. Okay, so when I first started doing nerve and muscle ultrasound in the lab and as a research possibility, this was in like 2006, there wasn't a whole lot published. And so we decided that the first thing we should do is make reference values. Because we didn't know what normal cross-sectional area of the median nerve was in the wrist or the forearm or the brachial plexus or the sciatic nerve. And so we really didn't know. We didn't know what changes occurred in ALS or CIDP or Charcot-Marie-Tooth and different types of CMT. So we started really basic. And we were like, let's make reference values. And so we did. We started with adults. We made reference values. We would collect, we would recruit between 30 and 50 adults and we would scan their median nerve from the wrist to the axilla. The ulnar nerve from the wrist to the axilla. Then we did like a whole bunch. We did one study where we did the vagus and the musculocutaneous and the sciatic and the tibial and the serral and the fibular. And we did a whole bunch. And so we gathered all that data. And then we started to realize that there were differences based on age and body habitus. And so if you read a bunch of these studies, some studies will suggest that nerve area correlates best with height. Some say with age, some say with BMI. The majority of studies, the best correlation is with weight. And so I think that that's probably, in my mind, the most important factor is as somebody gains weight, if it's a child growing or if it's just an adult gaining weight, that's where the nerve size increases the most. And so then we started thinking about extremes of age. So kids and people over the age of 67, which doesn't seem very extreme, but that's what we called it. And so we did a study and it's not huge. It's actually, it's pretty small. But we initially just gathered, we had like our kids come into the EMG lab and did ultrasound of their nerves. And so there's a lot going on up here, but this is kids that were age zero to three, age four to six, age seven to 11, age 12 to 16. This was our data from the adults. And then this was our older cohort here. And so you can see, we only had like a few kids in each one of these ranges, but it was just to give us an idea of how big nerves are in little kids and infants and one-year-olds. And they're small. So the median nerve at the wrist is like four millimeters squared. In most adults, it's about 10 millimeters squared. And then what we did is we added up all the numbers. And so we got a total and you can probably see that better here. So this is just, this is kind of what your nerves do over time. If you add multiple sites together, your nerves get bigger as you age. And they go up quite a bit initially and they do continue to go up. I think some of this up here and maybe even here are some asymptomatic entrapment neuropathies that made their way into our study. And so I would say that when I think about this, when I conceptualize it, I think about the nerves increasing cross-sectional area until age 15 or so, and then probably flattening out a little bit more here. But just an idea that the nerves are gonna be very small in little kids and they're gonna increase pretty rapidly as kids grow. And so then our data was combined with 12, 14 other studies in a systematic review and meta-analysis. And so this is looking at over 800 children and 5,000 nerve measurements. And this publication has reference values and they're not that far off from these values. And so we use these in our lab and they work pretty well on a day-to-day basis. So that was where we started. And then we started scanning more and more kids. The way that we set up our lab is that we have, we have six rooms with an EMG machine in each room. And then we have three to four ultrasound devices. One of them is on the EMG machine, the others were wheeling the device into the room. How many people in here use sedation for their kids in all their electrodiagnostic testing? Oh, nobody, maybe, yeah. And who uses it on, yeah, maybe, do you? Who uses it on like, say, 50% of their kids? No, 75, I mean, 25? Yeah, 25%, 25%, 25%, okay. Yeah, I think we use it on maybe 5% of our kids. We'll use sedation, like if they're going to get an MRI and they need to get sedation, then we'll bring the machine down there and do it at the same time. If we need to do a RepStim, we use sedation. But otherwise, because we use ultrasound, I think, we are able to do 95% of our studies without sedation. And I'm trying to think of the last kid that we did with sedation. It was probably nine to 12 months ago that we did that. Dr. Meiling, do you remember us doing a sedation case? Yeah, so Dr. Meiling was our fellow last year and it sounds like we did one case, which sounds about right to me. So we don't use much sedation at all. And at some point, I decided it made a lot of sense to do ultrasound first. Instead of doing the nerve conduction studies and the EMG in kids, it made a lot of sense to do ultrasound first. And Dr. Rairdon, who is currently one of our fellows, he's not here, but he helped out with this study. And so what we did is about five or six years ago, I thought we should just do ultrasound first in all of these kids. And so we did that. We had not been doing that. We did it. And then that's sort of a quality control initiative. And we did that. And then I decided we should look at that. And so Dr. Rairdon pulled like the first 21 kids that we did with ultrasound first. And then he did aged match controls to those 21 kids of four to one matching to look at the kids before that when we did electrodiagnosis first, just to get an idea of how much this helped us to cut down on our electrodiagnostic testing, our painful part of the test. And so here's what he found. And let's start at the bottom, I guess. And so this is our control group. Again, these people got ultrasound. These kids got ultrasound first. These kids are matched by age and somewhat by indication as best we could. And so the muscles sampled in the ultrasound first group, on average, we sampled one muscle. And in the control group, it was 2.66. This was statistically significant. The nerves stimulated was lower in the ultrasound first group than the control group, but didn't quite reach statistical significance. And then if you combined the two, the nerves plus the EMG, on average, there were 3.75 tests that were done compared to like 6.5 without doing ultrasound first. So this is kind of like a, sometimes I joke and say we should publish these things in the journal of duh. It's just kind of like, duh, of course that makes sense that we were gonna do fewer. It's like some of the stuff that Craig said, of course that muscle's gonna look different as you age or you're heavier, whatever it might be. But it was good to actually do this and to show that we could really dramatically cut down on the electrodiagnostic tests that we did. I added this slide, and I've been just sort of thinking back on the last several years and the scenarios that we most often see in our lab when kids are referred for some form of diagnostic testing. And I see a lot of developmental motor delay. And there's always this question of, is there a peripheral component? Is there a neuropathy? Is there a myopathy to help narrow down the differential diagnosis? I see a decent number of questioned polyneuropathy cases. So it might be a kid that clearly has a neuropathy, they're areflexic, they've got distal weakness or sensory loss, or maybe they just have high arches and difficulty ambulating. So I see that a lot. And then trauma, we see a fair amount. So we see a decent number of supracondylar humeral fractures that either get surgically fixed or sometimes get put into a sling. And then we sometimes will see a radial nerve injury and sometimes even median and ulnar nerve injuries in that situation. And then the last traumatic case is the brachial plexus injury. So we see birth injuries. And then we see kids that are riding on bikes or ATVs or cars and get brachial plexus injuries. I don't know. So you all, I'd like some feedback. You all do ultrasound and nerve conduction studies in kids. Any other scenarios that you see a lot in your practice? Or does this match up with what you all see? Yeah, there was a hand in the back. Yeah, that probably goes up. So the answer was about 30% functional neurologic disorder. And so that sometimes to me goes into the same category. Like a kid is not doing something that the parents or the physician or everybody expects them to be doing. And so some of these up here probably do, a lot of those end up being normal studies. Some they truly do have a motor delay that's caused by some genetic cause or autoimmune cause. And then some of them may be functional neurologic disease. Yeah. I can see that. Toe walking, that probably goes with either the polyneuropathy or this motor delay type thing. Yep. Toe walking. Anything else? Okay. So probably a similar matchup. Okay. So I've got, I'm going to do cases and I've got four cases and then maybe we'll have time to do the fifth case. We'll keep an eye on the time. These are like the last lectures of the whole conference, aren't they? I don't want to keep you too long. You'll need to drive home or fly home. Yeah, exactly. I'm going to get kicked out of my room. Okay. So the first case. So these are just, I think, kind of classic cases. So a 15 year old boy came to our EMG lab, had high arches and had decreased reflexes. Exam showed normal strength and sensation, slightly high arches and areflexia. And we did ultrasound first to limit the number of electrodiagnostic tests. And we scanned. So this is, let me back up a second. So when I see what could be a polyneuropathy in the EMG lab and I'm thinking about doing ultrasound, this is kids or adults, I often scan the upper extremity. It sounds strange, right? Usually the symptoms are much more pronounced in the lower extremity, but we are more skilled at scanning the upper extremity. We have, I think, tighter reference values in the upper extremity. And a lot of these conditions will manifest, they're polyneuropathies that will manifest throughout the whole body. So this kid, we decided to scan the median nerve. And the median nerve in the forearm is 25 millimeters squared. He's 15 years old. He was pretty thin. So I would say that a normal median nerve in the forearm in a 15 year old that's pretty thin is probably about seven or eight millimeters squared. Would you all agree with that? That do this? Yeah. So seven millimeters squared, clearly abnormal. If you go up the arm, this is in the antecubital fossa, it's 37 millimeters squared. And this is the ulnar at the upper arm and it's 30 millimeters squared. So it was pretty consistent as we scanned from the wrist to the axilla and the median and ulnar nerves. And so I'll ask you to think about this. What would you do in this scenario? So these are all real cases. This kid came probably two years ago to the EMG lab and this was the scenario. You can just think about what you might do. So we did a little bit of nerve conduction study. Not much. We shocked the ulnar nerve. The latency was 10 milliseconds. The velocity was somewhere in the 10 to 15 meters per second. And then of course, they're like, well, yeah, my dad does have high arches and my aunt has this condition called CMT and she's got a PMP 22 duplication that they didn't quite say that. But, you know, it quickly became clear that this kid had a very consistent nerve enlargement probably everywhere we were going to look. We probably didn't need to do the nerve conduction study part. Probably didn't need to do the ultrasound part. I mean, we could have probably diagnosed this if they had come to clinic by just saying, yep, that looks like CMT. Let's do a cheek swab and be done with it. But they were in the lab. When they come to the lab, you've got to do something, right? And so we did the ultrasound and that was the case. Okay, case two. I like this. This is a patient I've seen for a while and he's a very memorable little guy. So 11-year-old boy. It was in the fall and he was playing baseball and he was not doing quite as well as the other kids and then he started having trouble writing, you know, just holding a pen or pencil in school. And so he had, it was a little hard to say how long he had had weakness, but it seemed like about three months of difficulty. An exam, again, he just came to the EMG lab. He had weakness in all limbs. He had decreased and somewhat inconsistent reflexes in all limbs and then mild distal sensory loss. And so how would you proceed with testing here? You don't have to answer, but just think about what you would do in your clinic, in your lab. So we did ultrasound first. And so, again, he's 11 and we started with the median nerve in the forearm. Again, I would think an 11-year-old median nerve in the forearm should be seven millimeters squared somewhere around there, and his was 13 millimeters squared. And then as you scanned up the arm, the fascicles all coalesced, it became very sort of hyper. And then if you change the angle of incination, it would quickly become hypoechoic. So it was very anisotropic. If you look here, this is at a perfect 90 degrees with the transducer. If you just change the angle a little bit of incination, it completely, the nerve itself, which is this right here, became very hypoechoic. So it was extremely anisotropic. And this is the brachial plexus. Each root level of the brachial plexus should be about seven millimeters squared, and it was much bigger, about double that, 15 millimeters squared or so. And so think about what you would do with this little kid, 11-year-old boy in the lab. He was pretty tough. You know, sometimes you can just tell, like, who's going to tolerate the testing well and who's not going to tolerate it well, and it was pretty clear he probably would do okay. So we did do some nerve conduction studies on this kid because this could be a hereditary polyneuropathy. This could be an acquired polyneuropathy. And I guess from an ultrasound standpoint, I thought it was probably acquired. I didn't show you all the images, but the median nerve, like, at the wrist was about seven millimeters squared, and then the forearm was 13, the upper arm was 20, very anisotropic. So I was thinking, and then the history, right? Three months of symptoms, clearly no symptoms before that, no clear family history. I was thinking probably an acquired polyneuropathy. So we do our nerve conduction studies. Here's the median. The latency is 16 milliseconds, so quite long. The amplitude is quite low, and maybe there's a conduction block when you stimulate at the axilla. The velocity is super slow, eight meters per second. The ulnar is similar, and then maybe a conduction block, pretty slow. The tibial is super low. Those are hard to know what to do with those, but very, very slow and low. And then the F-wave, 120, median F-wave. So incredibly long. So what would you do in this scenario now? Again, these are all real cases. You don't have to answer, but just think about what you would do. So I'm going to hold off a second there. So what I thought I would do is, I thought that this was probably consistent with an acquired demyelinating, well, to back up, a severe sensory motor demyelinating polyneuropathy with likely acquired features. The ultrasound was pretty multifocal in the enlargement. And so I thought this was most consistent with, likely most consistent with CIDP. And I debated doing a lumbar puncture to look for elevated CSF protein. Would you all do a lumbar puncture in this scenario? I see some heads up and down. I didn't. And then I debated just treating. Would any of you just treat in this scenario? I see. You can't nod both, Craig. You can't do both. I mean, yes, you can do, yeah, okay, fine. Craig does both. Yeah. So I considered the lumbar puncture. I didn't do that part. And I decided we would just try and treat and see how this kid would do. So let's see. Yeah. Diagnosed with a severe sensory motor demyelinating polyneuropathy with features consistent with an acquired process on nerve conduction and ultrasound. Most likely CIDP based on our history and our testing. We did five days of IVIG and he greatly improved and went back to playing baseball almost normally. And then the history, I guess Guillain-Barre was also in the differential. The timing was a little unclear with this kiddo, but it wasn't, it was in that subacute range. It was probably more than four weeks, probably more like three months, but it was a thought. So we did a one-time treatment with IVIG. He got a whole lot better. Eight weeks later, he worsened. We gave him IVIG again, sort of a maintenance dose of a gram per kilogram over one day. He got bad headaches every time he got the IVIG. So we would add a little steroid and some Benadryl and some Tylenol and stuff. And then it was clear that he would relapse and he would get better and he would relapse and get better. So we put him on maintenance IVIG. He'd get it about every 10 weeks or so. And he's been off of therapy for probably three or four years now and is complete full function. I would guess he's 16 years old. He was 11 when he came in, so maybe five years. I saw him maybe three or four months ago and it was kind of sad because he was, it was going to be, you know, it was, it wasn't really sad, it was a happy, but he was doing incredible. He's in high school, he's driving, he's got no issues whatsoever. He was, he's super fun to talk to, but it was, I was like, I don't think I need to see you anymore. And he probably, it had been like two years since we'd last given him IVIG. I was like, you know, if something happens, call me, but I think you can go. And so it was a little sad to see him go, but he did incredibly well. And he was one of those early on, I think he was one before we had switched to the ultrasound first protocol, but we decided to do ultrasound first in him. So he was like one of those that, that really put this in my mind that we should do it this way. We also had a kid, it goes back to the muscle disease one, who came in, the one that I really decided to switch on was he came in, he had a high CK of like 2000 or so, and was waddling, was also playing baseball and was kind of waddling, couldn't throw it as fast and thought for sure it was going to be muscle disease. So we stuck a muscle. We decided no nerve conduction studies, stuck a muscle, it was normal, stuck a second muscle, it was normal. I think we did deltoid first and then iliopsoas, they were both normal. We had to step back a second, decided to go in there and scan him, found a clearly abnormal, I think it was either triceps or biceps, I think it was biceps, clearly abnormal biceps, super bright, homogeneous ecogenicity, stuck the biceps on probably that same side, tons of fibs, myopathic units, and eventually biopsy the left side, glycogen all over the place, did genetic testing, he had Pompe disease. And so that was the one, and when we did that, and I was like, we should have done ultrasound. I mean, he was, he was tough, he tolerated the EMG, but had we done ultrasound first and that kid, we would have stuck just one muscle, we would have known immediately and could have gone from there. And so that's when we flipped the switch and started doing ultrasound first on everybody. Okay, I got two more quick cases. This is kind of, this was an interesting one. So this was an 11-year-old boy that's came in for limb asymmetry, and I found it kind of hard. You look at this little guy and you're like, is the, is the left leg large or is the right leg atrophic? You ever had that scenario? And you're looking at them and you can't quite tell which one's which. And so, you know, they show up in the lab, you don't know what's going to come in, this comes in, and we decided to ultrasound first. And so we looked at the larger leg, and clearly the fibularis longus was much bigger on the larger side and very abnormal appearing, hypoechoic, almost looked like there was a structure within the fibularis longus muscle. And so I decided not to EMG that because it could be a tumor and you don't want to spread malignancy. And we sent this kid for an MRI and they said, yep, looks like a lipoma. And then he went and had it resected and it was a lipoma in his fibularis longus muscle. And so we did no electrodiagnostic testing in this kiddo. It was 1.5 times larger on the left than the right. Normal echo, normal Doppler, EMG deferred, MRI consisted of lipoma, confirmed by biopsy. Fourth case, how are we doing on time here? So a three-year-old girl who had trouble moving her fingers and came to the EMG lab. And on exam, it was not clear to me that she had any abnormalities, no clear atrophy in her hands or her forearms, no clear sensory loss. It was on exam, I would say, it was quite challenging to know what to make of this difficulty moving her fingers complaint. And so in her, we did ultrasound first and found that there was enlargement of the median nerve at both wrists. So in the forearm, her median nerve was five millimeters squared at the wrist on both sides, it was 11 millimeters squared. This was another one of those cases where they probably didn't need to come to the lab because when you start asking more questions, and we didn't do any further testing, you start asking more questions. Her brother had seen me like three years earlier and had been diagnosed genetically with HNPP. And so it was clear that this little girl had HNPP. She did not need to come and get, I mean, maybe the ultrasound was helpful to say, yes, this is truly a focal mononeuropathy, but we did testing and there was a PMP 22 deletion in this patient. What do we do for the HNPP? We did not do surgical intervention or splinting or we just sort of did education that you have this condition that you're much more likely to develop entrapments. She was three and so I thought that maybe in the future she might need a release or an injection or both, but it was much more about education. And I was having an interesting conversation before we started the talk today with Dr. Bland, who's in the front row over here, who told me that he thinks, and I think he's probably right, that he has diagnosed the earliest case ever of carpal tunnel syndrome. How old do you think the individual was that Dr. Bland diagnosed? Anyone? Two years old, did I hear? Earlier. Three months old. Dr. Bland can explain this to you, but this person has a family history that sounds like HNPP, although their genetic testing was normal. So lots of family members with mononeuropathies at entrapment sites. The mom had carpal tunnel diagnosed at age six years old and then her baby came in. The mom said the baby's not using her hands right and they did ultrasound and electrodiagnosis on a three-month-old and made that diagnosis, which I thought was kind of crazy. Not crazy for you, crazy that there's a three-month-old that has this. I would never call Dr. Bland crazy. He knows everything about everything. Okay. Can I tell you about a fifth case really quick? I think we've got time, right? So let me tell you what you think about this one. So this is a woman that we saw last Wednesday. It was in lab last Wednesday. There was an inpatient that was going to be discharged that day, and of course they needed their EMG. In retrospect, again, like some of these, it made no sense to do an EMG that day, but whatever, we did it. So this was a 30-year-old woman, and when she got down to the lab, she was Spanish-speaking, so we had the interpreter. She told us that when she was seven years old, she was diagnosed with leukemia. And she got chemotherapy and got really numb and really weak in her lower extremities and her upper extremities, and was diagnosed with Guillain-Barre, got IVIG, got better, didn't completely improve, and has had some sort of nerve symptoms her whole life. She's now 30 years old, and so she was in the hospital because she had just delivered her first child. And she said that when she was about six months into this current pregnancy, that these symptoms came back, and so she had a lot more numbness and tingling in her hands and her feet. And she was going to be discharged that day. The baby was fine. Except for this, she had an increase in symptoms, but over the last three days, her symptoms had gotten better. Not resolved, but gotten a bit better. So they were really bad at like six months into the pregnancy. She had delivered at full term, and the last few days, the symptoms had gotten a lot better. So she came to the lab, and I was talking to our fellow, and I was like, the differential is broad. She could have had Guillain-Barre back then and still has persistent symptoms and had recurrent Guillain-Barre. It could have been CIDP back then and just has had symptoms and has not been treated. It could be that she has either one of those two and then got entrapment neuropathies from being pregnant and has carpal tunnel, because her symptoms are worsening in her hands. It could be that she has, you know, a hereditary neuropathy and that this is all just hereditary neuropathy. And so it was really broad. And so we brought her down to the lab. We did ultrasound on her, and her nerve cross-sectional, I don't have the pictures, but the nerve cross-sectional area, median nerve in the forearm was about 25. It was about 30 in the mid-arm, in the antecubital fossa. It was about 40 as we got up the, like to the mid-arm to the axilla. The ulnar did the same thing, was very big distally, but got even bigger as we scanned up the arm. It seemed to consistently get bigger in my opinion, not like it was multifocal enlargement. We did nerve conduction studies, and there were some amplitude drops with proximal stimulation of not 50%, but maybe like 25% drops. And so that was that. And we did that study. She was going to be discharged later that day. I was kind of left with, yes, there is a severe demyelinating sensory motor polyneuropathy. We need to see her in clinic because we need to do some further workup. And where would you all start with further workup in this patient? Yeah. I hear genetic testing from Dr. Zaidman. Yeah. So we recommended genetic testing, and she got it like as she was going out the door, like we discharged her. She went to the outpatient lab, got the genetic testing, and it came back this morning, and she's got a PMP22 duplication. So this whole time, I assume, this has all just been CMT. And you look at her, her feet were very CMT-looking feet. And her family history, it was not clear that there was a family history. So she has a PMP22 duplication. I would guess that she probably, there's this theoretical you can have on top of a hereditary, you can have an acquired demyelinating process, so CIDP on top of CMT or Guillain-Barre on top of CMT. I would guess she just had CMT the whole time. That chemotherapy worsened, had a physiologic stress with the pregnancy, worsened, and it was probably just CMT this entire time. But literally, like at 8 a.m., I got that genetic test result back, which was quite interesting. Okay. So those are the cases. My conclusion, ultrasound's a natural complement to electrodiagnosis. It is fantastic for children for all of these reasons we've discussed. It's going to keep getting better in terms of resolution, cost, portability, different types of imaging technology, and share your feedback, claim your credits, and that is that. Thank you. So Dr. Zaidman will come up, and we are happy to answer any questions you all may have. Yes. It's a fantastic question. I heard Dr. Zabin whisper. He's like, oh, yeah, I have that same question. Sometimes it's very clear. Sometimes the nerve is truly normal in multiple segments and truly huge in other segments. It might be 7 millimeters, 7 millimeters, 8 millimeters, 34 millimeters, 7 millimeters squared, and 56 millimeters squared, 100 millimeters squared. And so sometimes it is very clear. I think that sometimes it can be challenging. I thought that woman, the last case, hers clearly slowly got bigger as it went up the arm. So we think about a genetic condition as being affecting everything equally. Everything's gonna be symmetric. Distal proximal is gonna be the same. It's not exactly the case, but that's the thought process, whereas CIDP, Guillain-Barre, is gonna be much more multifocal. The degree of change, like the percent change, I can't give you an exact number. It is sometimes striking and sometimes not so much. And the thing that really complicates this is that there are some CMT forms where you do get multifocal enlargement. So like a FIG4 mutation and a PRX mutation that both cause CMT, you can see multifocal enlargement. And what really complicates it is that there have been reports of people with those kind of mutations, and they also have conduction blocks, people with those kind of mutations, and they sometimes get better with IVIG. Whether it's placebo effect or true improvement, the case reports would suggest there's true improvement. And so that's super complicated. And in that scenario, I think there may be people that are predisposed to actually developing some immune attack on their nerves. To go back to your question, I don't know. It's like you know it when you see it sort of thing, but it can be, there's lots of gray area in there. So there is, sometimes it's striking, but sometimes the change is maybe only 10, 20%, something like that. You have a better answer for that? No, you're always right on the money. But I have a different way of saying the same thing. Yeah, go for it. A couple important observations. In CMT, the nerve in the arm, median and ulnar, is what I call uniformly enlarged, meaning it will be big in the forearm segment and the arm segment. If you look at the antecubital fossa, the ulnar groove at the elbow, or the wrist, in CMT, it will be smaller, because there's a pressure on the nerve that prevents it from looking, quote, uniform. So I use the word diffuse rather than uniform when I describe the enlargement pattern you see in CMT, and I'm just talking about median and ulnar nerve, and I'm talking about non-entrapment sites. Diffusely enlarged, meaning it's enlarged at all four places. I didn't think the degree of enlargement was a useful differentiator between an acquired and an inherited in that way, but other work, the UPSS sum score, and these, what are called heterogeneous index, I think is what they call it, or the inter-nerve variabilities, which is what you're asking, the size of the nerve in the forearm compared to the size of the nerve in the arm. That's higher in acquired, but it also can be high in CMT. So I don't use that. So the important point here is that in CMT, the nerve at the wrist or the nerve at the elbow will be smaller than it is at the forearm and the arm. So that doesn't mean it's acquired, that variability, because the entrapment site kind of squeezes it. The other, the counterpoint is also, you can have CIDP and the nerve can be enlarged at the median nerve and the ulnar nerve in the forearm and in the arm. So if you have a diffuse pattern of enlargement, which is the word I use for that, it does not differentiate. If you have what I call regional enlargement, meaning the median nerve is enlarged in the forearm, obviously enlarged, not a little big, twice normal, and the ulnar nerve right next to it is normal, that's very unusual for CMT. I call that regional enlargement, and that would favor CIDP. So if you see a regional enlargement pattern, I think CIDP, Mike's correct, doesn't mean it's CIDP, but I think CIDP. If you see diffuse enlargement, it could be either CMT or CIDP. And that I feel still pretty comfortable with after all these times. Now, it's only useful, of course, if you see the regional pattern. You don't always see that. But when you do see it, you really should go whole hog, I think, on being aggressive about the workup and the treatment. And fascicles, too. So acquired, you can have fascicular enlargement. In CMT, you might have fascicles that are slightly large and prominent, but they're all gonna look like that. In CMT, you will sometimes get individual fascicles that will become incredibly large and sometimes very hypoechoic and sometimes hyperechoic. And so we don't exactly know what that means. And I think it's potentially important for prognosis in some of those cases. But yes, the fascicles changing as well can indicate that this is an acquired process. Let me say one other thing about this, too. The NCIDP in acquired, the most pronounced nerve enlargement or the most sensitive place to see the nerve enlargement, if the nerve's gonna be enlarged, it's not always big, is gonna be up here, the median nerve in the arm and in the brachial plexus. So it is a proximal predominant pathology, particularly in patients who haven't had it forever. So that sort of bigger here than it is down here is tricky, like Mike said. Any other questions? Yes. Yes, sometimes in CIDP the fascicles themselves are, so it's been described that CIDP can have everything. It can have a normal nerve caliber with bright fascicles, it can be enlarged with dark fascicles, it can be enlarged with bright fascicles. The enlarged multifocal fascicular enlargement where they're really bright I think is pretty specific to CIDP. And so those cases that you have seen, but not all CIDP has that. It's probably a specific but not sensitive finding for CIDP. Yeah, using a longitudinal view instead of a cross-sectional view. The cross-sectional view, what you kind of have to do is scan rapidly, and then you will see this enlargement, and it becomes more clear, because if you're scanning slowly, it can become harder to see. And so I do usually use, I rely more on the cross-sectional view, but if I get to an area where there's enlargement, I might turn to a longitudinal view at that site. Yeah, I use the longitudinal view only to confirm it if I can't quite tell on the cross-section, because sometimes the fascicular enlargement, which should look like a P, you know, it goes poof like that, when you're scanning, sometimes the perineurium becomes indistinct in certain areas, and so a fascicle that's well seen sort of will blend into fascicles around it and then become well seen again. That's not an enlarged fascicle, that's just that the perineurium in that particular view isn't distinct, and so it looks like that fascicle enlarges, but it doesn't really go like that. When you turn on long view like that, you won't see the perineurium go like that, you know, so if you can capture in long view a thin perineurium that maintains its integrity and goes like that, then you have fascicular, focal fascicular enlargement. If you can't see it in long view like that, it's possible. Also in long view, usually the perineurium is easier to see, it doesn't fade in and out, so that area you're worried about, you swing into long view on it, if you can capture what you want to look at, it's not easy, then it's a credit card thin slice, you've got to be right on top of it, you should see the perineurium, and it will not, you know, enlarge like that, and then you don't call it. So I don't scan in long view, I scan in short view, and I use long view to confirm my impression, because long view... No, I'm not one to repeat nerve conduction studies, as you can tell, some people think nerve conduction studies in EMG doesn't hurt, I hear people saying this, and I don't know, my experience, I can do it on myself and it doesn't bother me that much, but patients don't like it, and so I did not repeat his nerve conduction studies. It's a great question. I've probably been having a discussion with him, probably the slowest move I've ever seen. Yeah, yeah, yeah. He was a little scared by the whole situation, too, and so, but yes, it would have been cool to see what his ultrasound did, too, I mean, in retrospect, he actually, he's the kind of kid that would come back and would say, yep, you can go ahead and shock a few nerves and you can do some ultrasound, so out of academic interest, maybe I could, but I guess I didn't see a whole lot of clinical importance to it. He got better. Yeah, so Dr. Bland thinks that they will remain permanently slow, you think they'll improve quite a bit, but will stay slightly abnormal, and how about the, what do you think about the ultrasound? I think so, too, yeah, I think that is correct, which is what makes my fifth case, the woman, just so hard, like you don't know how much they're going to improve, right, she had this when she was seven years old, and should her nerves at age 30 look normal or still slightly abnormal, and both by ultrasound and electrodiagnosis, so no, I don't have those answers for you. Maybe I'll ask him to come back. Any other questions? Yeah. It's a great question. So the question is looking at the vagus nerve and acquired versus hereditary Polyneuropathies, I'm not aware of it in kids in adults. It's been done so the vagus nerve has been scanned in Guillain-Barré and to see if that correlates with the degree of Dysautonomia and the people at Guillain-Barré And it does sorry I should have concluded my thought but um I I'm not aware of that type of study in kids With CIDP or CMT. It's a great thought. It's an interesting question I guess there's less a lot less Dysautonomia and CIDP than there is in Guillain-Barré. So you may not expect that to be abnormal It could be the reverse yeah, yeah sounds like a project for the future just don't say biomarker Any other questions, thank you. All right. Thanks everybody

pediatric neuromuscular disorders

ultrasound diagnostics

Dr. Mike Cartwright

Dr. Zaidman

pediatric neurology

muscle and nerve diagnostics

muscular dystrophies

congenital neuropathies

hereditary neuropathies

quantitative muscle ultrasound

demyelinating polyneuropathies

diagnostic advancements