I have with me a colleague, Dr. Vila Sakitipakorn. She is a fellow at Cincinnati and soon to become an attending. And she's going to go off to Thailand and set up her own department. So the way we had envisioned this is to be very interactive. When I had put in this suggestion for a proposal, I had hoped a lot more people than just two of us will be there. But several people emailed and said that they had conflicts and too many meetings to go to WMS, AA, and EM. But please keep us in mind. We are hoping to start a very dedicated pediatric series. And Dr. Katz just mentioned that she's very interested in imaging. So perhaps next year, we will have a lot more speakers. So if anybody's interested, I'm also on the science committee. So I'm happy to help. So my name is Matsula Thangaraj. I'm at Virginia Commonwealth University. I'm a child neuromuscle person. All right. So my title is called Unicorns and Zebras, Some Pediatric Neuromuscle Patients. These are all patients that came to me and that we followed. I found it extremely humbling learning to take care of these patients because we think, oh, we know something. But it turned out that there were a lot of surprises. So these are my disclosures. I'm supported by KL2 and NCATS, and I've been supported by MDA. My only conflict of interest is I'm a speaker for NS Pharma, but I'm not going to be discussing their product or anything off-label today. So this is the outline of my presentation. I'm going to go over three patients that I've taken care of in the past year. Some of it seemed straightforward, and I felt like I had a good bearing. But in terms of, as you would see, in terms of taking care of them, it was very challenging. And then I will go over a little bit of unifiers and distinguishers between these three patients, and then talk about my experience as to how I think we can create some opportunities for standardization in terms of how we approach these very complex care patients, and also set up some guidelines and research scholarships. This is my first patient, ZW. We were consulted on this 15-year-old boy because he had been complaining of fatigue and muscle weakness, relatively short, four months. And it really began with heel pain. And he had presented to the PMD and then the other colleagues. I'm not going to give away my diagnosis so quickly. He got a diagnosis of plantar fasciitis. But what was very remarkable about him was within four months, he had really had a very rapid decline to the extent that he needed support in terms of activities of daily living. He couldn't walk. And then both him and his parents reported that there was a lot of muscle wasting. He didn't have any truncal weakness, no arm weakness, no bulbous symptoms. Anyway, so in terms of review of systems, there was nothing rheumatological, no joint pain, no sicker symptoms, no systemic symptoms of weight loss or fever. And he denied any recreational drug use. This was his exam. What was very remarkable was that he had pallor and pedal edema. And his neuromuscle exam was not really localizing, just proximal muscle weakness, which was more severe in the lower extremities. His strength in the upper extremities were normal. And his deep tendon reflexes, both in the upper and lower extremities, were sluggish. So this was his medical history, very complicated. He had a diagnosis at age 10 of segmental glomerulonecrosis, for which he had been on multiple rounds of oral corticosteroids. He had a cadaveric kidney transplant, which he rejected. So he had multiple biopsies during all of this time. He was covered with corticosteroids. And he had end-stage renal disease. He also had secondary hyperparathyroidism and anemia of chronic renal failure. And he was on dialysis three times a week in the unit. And then he was awaiting a new donor. So who's going to be the bravest person in the audience who can give me? I really meant it when I said these are unicorns and zebras, right? So my first differential when we called was really, well, could it be myosin losing myopathy? He had several risk factors. He was not moving. He had chronic renal disease. And it's really an acute to subacute progression, 40 times more common in the setting of transplant patients. The one thing he did not have, but usually these patients would have, is respiratory involvement, diaphragmatic weakness, which you would see because you get called from ICU. But that was a little bit of a surprise for us. But I was happy that at least he didn't have respiratory involvement. The second one is, of course, endocrine myopathies. Hyperparathyroidism, very well known to cause atrophy and myalgia. Usually, they will have calcinosis. But the only thing that didn't fit into his picture was sluggish deep tendon reflexes. In hyperparathyroidism, they tend to be brisk. Somebody also brought in, maybe he had a very atypical LGMD. We see these double diagnosis, or maybe a Becker phenotype who had an in-frame mutation. But that didn't, sort of like, he had no prior history of rhabdo or fatigability. There was no family history. And then, of course, corticosteroid myopathy. I know Dr. Griggs usually like to say that is truly a unicorn. I don't know whether if you believe in corticosteroid myopathy or not. But he had been on long-term suppression and a steroid. So we did entertain that. So his initial labs, nothing remarkable. His CK and aldolase were all normal. His MAG was slightly low, but he had been on dialysis. And his phosphorus, of course, because of his renal disease was high. Of course, his parathyroid PTH was extremely high. So he did have a diagnosis of secondary parathyroidism. So when I saw him, really the pain was such a very remarkable thing. But in the setting of normal aldolase and CK, we did send immunology labs. He did have high titers with ANA. And his rho 52 was extremely high. So normal, I think, cut off is like 14. His was 200. But he absolutely didn't have any rheumatological symptoms at all. So it was hard to say, well, could just be an outlier. But he had also been on immunosuppression tacrolimus. So it was hard to say, OK, this could be truly positive. He didn't have any other rheumatological markers. He did have an in vitro panel because of the concern for atypical LGMD-Becker-like, including DMD-DEL duplication, which was negative. We did get musculoskeletal MRI. Natalie, next year I will put up these images because I will learn to familiarize how to read it. Those sequences really make me very anxious. So maybe next year you can present. So he did have a lot of intermuscle and fascial edema in the posterior compartment of his lower extremity. And I think, looking back, the fact that there was so much inflammation in his quadratus plantus, I think it was really giving rise to his heel pain, which was mistakenly taught as plantar fasciitis. So the big challenge with him was he had also been struggling with depression because he had received a kidney transplant and rejections. And he was coming to the hospital several times for dialysis. So there was this chronic medicalization history on him. There was a bit of a struggle for us to have insurance actually cover for a muscle biopsy. So there was a delay in even getting that. And then what muscle, because he had so much wasting, so you really had to choose a muscle which was not extremely atrophic. And we did go with the right quad because the surgeons felt that could be more easily accessible because the posterior compartment of the leg can be very challenging to biopsy. But it turned out that there were very few inflammatory cells, no perivascular atrophy consistent with domino myositis or vasculitis. We did send it out for a secondary to wash you for additional stains because, well, what if he had missed anything? But that turned out negative as well. So the very first thing, because of his very high titers with antero, he got two rounds of ritaximab. Then we followed this IVIG, methylprednisone. And right now, he is on oral steroids. Unfortunately, really, I think he's lost so much muscle bulk and muscle function that he's also developed functional contractures. And then he's become wheelchair-bound. And then there were some social drivers, some difficulty with access coming and staying on physical therapy as well. So really, it has escalated his burden of disease. So the final diagnosis was immune-mediated myopathy due to antero antibody. But he did not have any other features to suggest connective tissue disorder or Sjogren's. There's a very nice publication from Australia where they've looked at about 150 patients with antero. And they have thought that one subset of Sjogren's, which is slightly atypical with antero, can also have a spectrum with immune-mediated myopathy but may not have to have Sjogren's. But in our patient, he didn't have any other rheumatological involvement at all. So this was his recent exam. Really, I think the contractures are the ones which are more disabling, and the muscle bulk, and he is non-ambulant. He has had, I mean, in some ways, he has had no disease progression. He doesn't have any respiratory involvement, no upper limb involvement, or bulbar features as well. So I will move on to my second patient. This is another 13-year-old girl who actually came to the EMG unit because the outside physician wanted us to rule out left brachial plexus injury. So the real history was that she had gone on vacation with her parents to Mexico over spring. And they told me that she sort of hit the wall and hurt herself, and following which, she really had difficulty with lifting her arm and her left shoulder. There was also a history around this episode of viral symptoms, and they thought, well, maybe this was post-infectious. So she had been seen by an orthopedic physician in the community. I think they also ordered an MRI, but in retrospect, I'm very happy that they ordered the EMG, because if I had seen her first, that would not have been my choice. So sometimes other people's mistakes works on your favor. So when I saw her, she had severe wasting of the supra and infraspinatus, but this was really asymmetric just on the left side. She did not have any other weakness anywhere else. No facial weakness, no vulva weakness, nothing in the lower extremities. Her exam was stone cold normal. The one thing that I was very grateful I did before I started the EMG was I dug into that MRI report, because in the conclusion, it just said edema within multiple muscles. And please consider brachial plexus injury. And sure, you can have post-Parsonage Turner Syndrome. You can have muscle edema. But when we looked inside the report, there was a lot more, because there was more widespread involvement with supraspinatus, infraspinatus, teres minor, major, and also triceps. So this was already in the EMG suite, you're like, oh, wow, like imaging and like, OK. But it was good to sweat a little bit. So then the differential was, well, it could just be in the setting of viral infection, just remote Parsonage Turner Syndrome. We did think of brachiocephalic myasthenia. There's been some occasional reports that they can present asymmetrically, but then will progress to have upper extremity involvement. And then just LGMD, although this seemed a little bit atypical, because it's just a month history, two to three months history of asymmetric weakness. The most interesting thing was this aldolase. I've never in my life seen this high, because the lab actually called me. Aldolase level was 150. CK was very, very high as well. So this got us very interested. So we did repeat a shoulder MRI, because she had had one outside. And this time, her edema was persistent on imaging, but she also began to have fat infiltration. So some inflammatory changes with some secondary fibrosis in similar muscles. But one thing that was interesting was that there was a spread, because now not only tricep supra and infraspinatus, but she was also showing this in deltoid muscle. So we did send a WashU panel, and her SRP54 came back very, very high. And then the PMs, cleral 75 antibody, was positive. So she had dual immune myositis panel. So with the SRP54, one of the things that to be very concerned about is an occult malignancy, paraneoplastic syndrome. So she got a pan MRI. All of that was negative. And then in the second imaging with the pan MRI, they did pick out inflammation with other group of muscles, so semimembranous and long head of biceps. But truly, four months earlier when we had seen her, she did not have any clinical weakness. So the only outlier was those labs, which we did. And she did have lumbosacral paraspinal muscles her looking inflamed as well. So there has been some reports that if you do EMG and you can have fibs in the paraspinal muscles, it's very indicative of Pompe. But her EMG was unremarkable, but we still didn't want to miss it. She didn't have cardiomyopathy, no enlarged tongue. But we did send genetic workup from Pompe's, and that was negative. There has been some occasional reports of like a TK2 mitochondrial myopathy that can present with the paraspinal muscle involvement, so we sent that as well. That was negative as well. So we pushed ahead for a muscle biopsy because she had this dual antibody. I was not very familiar with this phenotype at all. And then it was more to see how the extent of muscle involvement prior to starting therapy, although we knew that both the CK and aldolase was very high in her case. So she got a muscle biopsy, which just showed some occasional atrophy, but no inflammatory infiltrate at all, which I felt unfortunate. Anyway, so within a month, parents and this child reported that she was having difficulty walking up the stairs. She was becoming a little bit short of breath. She was having a little bit of fatigue with her upper extremities, not able to do all of those, but definitely no skin rash or joint pain. So because her titers were very, very high, we started her on ritaximab. She finished two rounds, but she continued to have weakness, so she went on to have IVIG. We got rheumatology on board, so they felt that this was a very atypical but still belonging to immune myositis myopathy, so began her on methotrexate, on steroids. And I've never taken care of a child whose aldolase level persistently is high. Her most recent aldolase is still 180. So despite all of this immune modulation we have given her, she still has significant myositis. So her final diagnosis is immune-mediated myositis myopathy due to SRP54 and anti-PM scale 75. She has no evidence of connective tissue disorder and malignancy. All right. This one, I promise, is relatively easy for you guys. This is also a 15-year-old African-American boy who actually presented to the ED, and neurology was consulted. He came with a four-month history of wardling gait. So his parents had separated. He had just had a recent bout of COVID, but didn't have any history of rhabdo, no upper extremities. So he had been with dad, but then came mom. He was taking care of him that weekend and really found that he was not his usual self, staying more sedentary and not wanting to walk. And then review of systems was positive for significant weight loss. There was a family history of sarcoid and rheumatoid arthritis, but he himself didn't have any rheumatological symptoms. So in the ED, they got a CK, which was very, very high. A little bit of liver enzymes elevated, which we know can happen in muscle disease. So they thought he had like inframe and becca and said, oh, please, you can follow the neuromuscle person. But any of you guys taking care of becca patients, you know it's not going to come with four-month history. Even with inframe, the parents will say they would have had some symptoms, some fatigability, although I suppose you can have an intermediate phenotype. Anyway, when I saw him, he had significant muscle wasting in his lower extremities, significant neck flexion weakness, and then paraspinal muscle loss. He was a skinny lad, very tall, and this was really shocking to see. But when I was training, Alan Pestrong had taught us, I mean, if you see a young boy who had been relatively healthy and very, very high CK, there's only one diagnosis. And I told Cliff that morning, so when parents came, I said, I know what he has, but I just want to confirm it. So I had to get on to the right side of the parents and didn't want to lose their trust. But luckily, I turned out to be right. So his aldolase as well was sky high. It was 177. His myasthenic panel, his liver function, thyroid function, everything was negative. We did pan-CT him. It was all negative, echo, PFT, normal. So because somebody had thrown in that becca, we had sent an in vitae panel. Everything was negative. But he turned out, when we sent the antibody panel to wash you, his SRP was sky high. So he did have SRP antibody. And that's exactly what Alan had taught me. He said a quick onset of muscle wasting, very high aldolase, and CK. There's only one diagnosis, SRP. So this time, I got it right. So he did have significant edema on his muscle imaging of paraspinal and psoas muscles. And we biopsied his left paraspinal, which showed a little bit of inflammatory cells, but nothing remarkable at all. He got two rounds of rituximab on prednisone, actually doing very well. Hasn't recovered that much muscle, but at least he's gaining strength. So those were the three patients who I felt really taught me, I think, to appreciate the spectrum of the immune myopathy, myositis presentations. One thing that was common was they were all African-Americans. And I know that African-Americans can have higher disease burden. This has been reported in MS and neuromyelitis optica. Our first patient had HLA typing, but the second and the third patient, I mean, there was no need to do typing. And all of them had acute to subacute presentation. But I think what was very remarkable was that despite treatment, two out of the three patients really had significant decline in neuromuscle function. There was also this asymmetric weakness in immune myositis, as presented in patient two, which I had not ever seen. And then just the poor response, despite escalating with multiple rounds of immune modulation. Some of the challenges were, I mean, we are at VCU. We are 100 miles from the NIH. GW has a very large pediatric rheumatologist myositis clinic. But really getting the patients a second opinion was very challenging, at least with our first patient, who was already extremely medicalized, dealing with chronic medical illness. Them wanting to go to another institute, set up those relationships, and then get a second opinion was very, very challenging. There was some, we had to jump through some hurdles with like muscle biopsy, like imaging, and like bringing those teams. So for me, it felt that in addition to all the challenges we're looking after, just navigating those spaces, getting all of those specialists was a bit challenging. And then really, for our first patient, insurance was a major, major issue. They wouldn't cover physical therapy. They wouldn't cover his inpatient rehab. So there was a significant amount of social drivers of health impacting our care delivery. We also don't have a joint rheumatology neurology clinic, especially in pediatrics, at least in the adult world. I know my colleague, Dr. Gwathwe, is very interested. I think they, I want to say, I think they tend to see a little bit more patients than us. But really, the rarity made it very challenging. But when we started developing, when we had these three patients, what I began to do was to go to a rheumatology clinic and see those patients with them, so that we could have at least a shared, start talking about like how we should, because there was really no protocols. There was no standardization. Imaging sequences, yes, but how should we follow a protocol? Can we set up an institutional protocol when you have these rare presentations with immune myositis? And also, with muscle biopsies, this would be a possibility to have a repository of imaging or muscle biopsies, because they all get archived tissue. And maybe even do genetic testing on them, because I was really surprised. But just the paucity of inflammation, which went really out of hand with the severity of their clinical weakness and their lab investigations. And then there are newer animal models coming out, for like scleroderma and rheumatological myositis models. So I think that would be something that we would be, that we could in the future harness. So I'm happy to take some questions. If you have burning questions, alternatively, we can give the podium to our colleague, have her present, because there will be another bit of a unifying theme, keeping the antibody theme going. And then we can collectively wait for questions afterwards, if that works for everyone. Thank you. Come. Peach. All right. Hello, everyone. Thank you for inviting me to speak today. This is actually my first time that I'm speaking in NAM, so I'm a little bit excited. You mean nervous, too. All right. So I'm currently like a fellow at Cincinnati Children's Hospital, and I have nothing to disclose. So I'm going to present two cases, but the first case will be a case that I'll present a longer one, and this is kind of a theme that kind of autoimmune, like an inflammatory process. All right. So I'm presenting a case. One is a 15-year-old female who has a previous past medical history of juvenile myoclonic epilepsy, and she has been on an appropriate birth table on her seizure, and she started to have like this back pain and weakness about like a week, and then her back pain started around like mid-back and then like migrated to like more lower back area. She felt like generally weak that she like stumbled, like having like some weakness. I mean, she called it weakness because she couldn't walk like properly, and she needs like some ADL assistant, like, you know, walking like to some place or some place because she cannot walk very steady, and she did have like some static sensation of like her feet, legs, and hands along with that, too. This is kind of progressing in like one week. So then she also like doesn't have like any fever or headache or her seizure has been like well-controlled. She also have like some systemic symptoms, including like nausea, poor PO intake, and then like some mildness, too, at that time. So she went to the ED for evaluation, and then neurology was consulted in the ED. The exam there showed that she has like normal motor strength and no cranial nerve abnormalities, but she did have like diminished vibration sense of her bilateral feet up to her knee and then like the impaired proprioception in her toes. She had a toxic get and then have the absent reflexes. So if you like see this picture, type of picture in like the ED, you would think that, oh, this is something that could be, you know, like acute, I mean, it could be like acute demyelinated neuropathy, that involving sensory, although I mean her motor right now is seemed to be preserved. So the differential diagnosis at that time will be like acute onset of sensory ataxia, absent reflex, but the motor is good. And so of this, it's probably like in everyone differential diagnosis, like Guillain-Barre syndrome, sensory variant, like Miller-Fisher, although she doesn't have like the full triad of Miller-Fisher, because she doesn't have like ophthalmology or like any cranial nerve involvement at that time. And acute sensory and neuropathy, that is the main one too. Toxic neuropathy with acute or subacute, like presentation and vitamin deficiency, like vitamin B12 or vitamin E deficiency. Those could be two infectious causes, because she did have like some symptoms of like systemic malaise, poor intake, and could be like any viral infection, or she could have like Lyme disease, or peroneoplastic syndrome, that's one of the differential diagnosis, but usually like not acutely presenting like this. So she had a further investigation, and her labs came back like pretty, I mean, like the basic lab's pretty normal, except just slightly elevated CRP. And then she got a LP lumbar puncture, CSF, showed like some vibrate cell and leukocytosis with like lymphocytic predominance. She had like slightly elevated protein, but her ME panel was negative. And the MRI spine, she had a whole MRI spine, it was normal. So at that time, I mean, of course, like, you know, presentation with acutely presenting for kind of sensory like ataxia with like, you know, only sensory part and absent reflexes. So we treated with like the IVIG for like inflammatory neuropathy, it could be like Guillain-Barre or ASAN. Yeah, and then she did have some improvement in her sensation at that time, but still like still have like some pain, some hand sensation that is, the feet is still like numbing. And her gait instability initially was kind of a little bit better at that time. But after she was in the hospital, I mean, about like two weeks of her onset, she started to have like a very severe like burning pain sensation in her hands and her feet. And that is something that actually get, I mean, affecting her walking much worse, because she cannot really walk, she refused to walk because of like a toxic gait and also like because of the painful sensation in her feet. And so she was sent to like be in the rehab, inpatient rehab afterwards. But before, because of given like this, unable to like walk and then have a very severe pain. So and at that time, it's about like two weeks after out of her like symptoms. So we did the nerve conduction test and found that she had this kind of diffuse, broadly like abnormal of her like axonal type of the, like this one is upper extremity. So very diffuse spreading. And the lower extremity is also like no response there. The motor did have like some slightly like borderline, well, like a near normal velocity would maybe decrease there. It doesn't fit with like the sensory fighting. So that's something that we will just, you know, like keep in mind and like follow up it later. The EMG, she did have like one brief of run of the positive childbirth, but otherwise is pretty normal, you know, exam. So the impression at that time would be like the diffuse axonal sensory polyneuropathy with significant evidence of like demyelination. And the interpretation for her motor that have like some velocity that are slightly off at that time is less clear significance. So we're just going to follow up on that later. But her main picture seems like to be like more sensory symptoms and like axonal sensory neuropathy. So her progression at that time, she continued to have an ongoing pain that is very severe and she received like multiple injections, including like morphine and ketamine drip and also like eventually she has to get like a lidocaine injection. And that seems to be like very helpful. And then she was started on the lacosamine for her neuropathic pain. Her hospital stay was kind of complicated because of her pain management. That's why she was in the hospital for like about six weeks. So given her pain and unable to ambulate at that time, like she had a lot of pain and there were like initial investigation was kind of showing that she probably have some, you know, like axonal polyneuropathy, maybe like some inflammatory process. But we did not actually at that time did not send out any antibodies. And the MRI initially did not actually find anything. But then we repeat the MRI again and it showed that she have like some enhancement in her 5 in the brain MRI and then also enhancement in quadricline and multiple nerve roots dorsally. So I was just showing you like this imaging. So this is like at a hand and not like a quadricline and the dorsally like enhancement of the nerve root there. Is it like the axial form? It might be difficult to see, but it's like on that side. So these are done like about a month after her presentation. And so given that like significant change of her MRI finding from like the first presentation and then that one. So we did take another lumbar puncture. And I mean, it's not that unexpected that a protein is elevated higher than the previous one. But the vibrocell is all, you know, like quite normal. And so we send out the antibodies at that time. These are negative. The Lyme disease like antibodies were negative too. And then given her severe pain, the TS, HDS was sent and it was positive. This is a WashU lab. So it's 31,000 units there. So given this, we actually, I mean, from like my experience and talking to my attending, it seems like we don't have a lot of patients who like have this, especially in Peds. So we diagnosed her with like immuno-mediated neuropathy associated with this TS, HDS antibody. And she received a second round of like IVIG with the IV metupresolone, giving her like significant pain and like the presentation is still like kind of ongoing, like inflammatory process. So after that, she seems to be a little bit better. Her pain is more controlled, but also like have a lot of like pain medication too. And she continues to receive this IVIG every month after the discharge. So we follow up her four months later outpatient and we did like repeat the nerve conduction test. The sensory exam is still no response on the selected nerve. And the motor, I mean, it's pretty normal. Just maybe that one is still on a motor that we saw before. Still slightly, the velocity is slightly decreased, but it's only at the risk of reversible at the elbow too. And then we repeat the EMG that's have like some of this kind of self-acute chronic fighting, but no active, sorry, no active ongoing like, you know, version that we see. So for the summary for this case is acute onset of sensory ataxia absent reflexes. Subsequently, I mean, progressing to like neuropathic pain, which could also like have some component of like small fiber neuropathy, small fiber neuropathy pain because her pain seems to be more like kind of burning sensation in her hands and feet. And yeah, but unfortunately we did not do like any other testing to like prove like the small fiber neuropathy part. Her nerve condition test show diffuse axonal polyneuropathy and she had this TSHDS antibody positive. Yeah. Oh, and the TSHDS antibody is the dry cell-fitted heparin disaccharide. After the treatment, she gradually improved on the symptoms with one IVIG and that one course of the IV metaprognosome. We follow up her again at one year after his symptoms. So all the sensation has resolved and she still have like some pain in her hands and feet. Occasionally, it's not all the time now. It may be like when it's getting cold or with specific like situation. And her nerve condition test is very near normal. All the sensation that was no response before is all coming back and pretty near normal. And then we repeat her antibody again. It was negative. So a little bit about this dry cell-fitted heparin disaccharide. It has been like a biomarker that reported more in immune-mediated neuropathy. The previous, you know, they showed that on the nerve bouts you have like more axonal loss than no like demyelination. Some of the deposits of this like complements and the IgM in the muscles, fiber, and also like this is a nerve one. But it's mainly like around like kind of the capillaries or like the veins. And this is another article that reviewing like this antibody and then showed like inflammatory process in the nerve fiber around like the EP neural capillaries. Clinical manifestation, it was reported initially to have like kind of mixed picture of like large axonal neuropathy and with the small fiber neuropathy. It has been like more reported in like cryptogenic small fiber neuropathy in the past like, you know, like 10 years. A lot of people like have looking into that. And then this is another group of doctors in Mayo. They did like this review of the kids in Mayo and then like found that most of the kids, I mean almost half of the kids, like have like length-dependent pulmonary neuropathy. And also other here also have like small fiber neuropathy. And well, I mean, and all this is actually in adult population, like the mean age is like 40 to 50 years old. And usually patients have like some kind of autonomic symptoms too with like kind of small fiber neuropathy. And this is what they showed that have like kind of this patterns of different patterns of like the more regulatory sweat test. So it's kind of like not a very distinct or like unique presentation for this autoantibody. It could be like any kind of presentation. It's not, you know, if you have this autoantibody, you cannot really predict like if it's going to be which type neuropathy as like other antibodies that might be able to like more be like being like more specific. So, and the treatment of this antibodies is still IVIG is the one that reported on the most for the treatment. But the study have shown that there was some like uncertain, like responsive to the therapy. Some of the patients will like kind of get better, but some maybe like not getting better. So there are kind of limitations of like the using this as a biomarker, whether this is like a real, you know, like a culprit for like this autoimmune median neuropathies or if there's any other thing that combined all together. But of course, like, I mean, this has been like very reported in pediatric cases. And we found this for her, for this patient, it's kind of fit with the picture that you have like kind of axonal loss, also axonal polyneuropathy. And then like some of the small fiber neuropathy symptoms with like a pain burning sensation. But although we did not actually prove it with like any testing of like autonomic skin biopsy. So that may be a limitation of our cases. So then we actually have another case that presented kind of almost like around the same time. He's a 12 year old boy with some ADHD. And then in the past few months, he has been having like this intermittent GI symptoms with like abdominal pain that he has been like falling with like the GI doctor. And he presented to neurology because of like the leg pain, worsening leg pain in the past few months as well. He did have like some foot numbness that he presented he complained about. But it's not like some the pain and also the numbness seem to be like occasionally is not like all the time comes and goes. But also like it has been worsening in the past like few months that limited his activities. So his exam on the first neurology visit, he had like normal pretty normal strength sensation reflexes. And his gait is normal too, but just like have some pain randomly. So we did do the nerve conduction test and it is show like some. that I put, okay, here, the sensory exam has like, oh, sorry, sensory nerve conduction tests have like this no response of the perineal sensory and then the left sural sensation too. It's asymmetric, it seems to be more involving in the left side. The right side had like somewhat of maybe slightly like a lower amplitude. His ulna is normal. This was done outside hospital. They did not do other nerves at the time. And the motor exam from the outside hospital as well, they have this, like a peroneal motor is no response with median motor has some prolonged onset of latency and then reduced amplitudes. But the tibial right and left is normal. And then the EMG evaluation, he did have a pre-normal EMG needle exam. So the impression from the outside hospital when he presented to us is asymmetrical, like sensory motor pulineuropathy seems to be more axonal than greater than like demyelination characteristic. So we saw this, I mean EMG and then his, but his exam is totally like normal at a time. And so given like kind of subacute to like chronic onset, we did send out like the panel, the labs and the panel that it came back. He has like a CSF labs at a time that normal and then MRI is normal too. And we did send this like motor and sensory puline, motor and sensory neuropathy panel. And this came back with the IgG against his fibroblast growth factor receptor, three antibodies that come back. His pain symptoms kind of somewhat responsive to like IVIG treatment, but he still have like the pain comes and goes like frequently and his pain, he doesn't, sometimes it's like burning sensation, but sometimes it's just like pain when he like kind of using a lot of muscles. His, we also like send his genetic testing is because given like some kind of a typical presentation, like he had like this EMG that are like asymmetric. We wonder like if he has like any underlying like hereditary neuropathy or things like that too. So we did send out genetic testing and it come back that he had this pathologic variant of PMP2 to deletion. And so we follow up him up. I mean, he is getting better, but also we did another EMG at four months later and all the sensation that it was reported in the previous EMG, they were normal this time. And the median model that was previously abnormal is also like abnormal now. He did still have like some abnormality in his motor, the perineal motor. And, but it was, I think initially it was like no response. So this case is not a straightforward case. It could be that he had this PMP2.2 deletion underlying, but doesn't have any symptoms. But then later, maybe he have this autoantibody that positive that could causing this acute and subacute presentation for his symptoms. And so for him, our plan is to follow up him. And later on, probably we'll repeat the antibodies again and then see if those are resolved with this treatment or not. We still question about if this antibody actually the real culprit for him, too. So the FGFR autoantibody also has been reported in autoimmune neuropathy. And sometimes, they can be accompanied by the TSHDS autoantibodies. The literature recently usually reported all these two antibodies together for the immune-mediated neuropathy. This is antibody against the receptor intercellular domain. In the previous research, it has a high positive predictive value in non-linked dependent immune-mediated sensory neuropathy. But later on, researchers reviewing the cases, seems like the clinical correlation of this antibody to the clinical presentation is still unclear. Some of the patients who have this positive antibody, but they have maybe the autonomic function test or the skin biopsy for the small fiber neuropathy, it doesn't really correlate that well. So this antibody still kind of uncertain of significance sometimes if the picture doesn't really fit with the presentation. Those are the two cases that I found that rarely, we did not find a lot of inflammatory, like this small fiber neuropathy-specific antibodies in the kids. So that's why I brought this up. So the take-home message just from me, and wanted to just give it to you guys, is that these antibodies have been more reported. We can just keep that in mind if we have suspicions for some small fiber neuropathy or a typical presentation that we can send it off. This actually included in the WashU, the immune-mediated neuropathy, but it depends on which panel. So you might have to look into that if it's included or not. And it is important to follow. I mean, of course, we are neurologists. We follow clinical patients. And sometimes you might not get initial investigation that you're telling you what it is. But later on, the investigation can change. And it's something that we follow our patients and then diagnose patient later. So the testing of the antibodies can help with guiding of the treatment. But we have to keep in mind also that sometimes these antibodies So, this is what I also like keep in my mind that in pediatric cases, we do send a lot of genetic testing, even though sometimes it's like kind of inflammatory, though. But hereditary neuropathy or like other hereditary genetic disease can also be underlying and then like something, you know, like get on top of that, too. So that is something that we also need to think about to impede kids. All right, so thank you, and this is my team at Cincinnati Students. So if you have any questions, like Dr. Matula said, that we can ask right now. Thank you. I'm not sure it'll cover Fabry, but that's a good thought that We send out the comprehensive neuromuscular panel, which usually included like most of the neuromuscular diseases for both of the patients. I think that's. Symptoms, but we try to get mother's sample to see if it's running in the family. It's also not typical in a 15-year-old to do skin biopsies. You'll have to do skin biopsies and know normative values. She's a near adult, but in kids, the second one was 12, that would be hard. And and what do you guys do the skin biopsies for to establish a diagnosis of what? small small fiber neuro I've had good luck, three to four weeks, sometimes five. I think I don't tend to send over the holidays, which I think is always the song, but yeah. Never, never say never die, but never so far. So Mayo also has, but they have such a long list and by the time I figured out the CPT code, I'm like, okay, but I think because I trained at Wash U, you can say, okay, I can trust these results. But sometimes what they do, like I think in what she had presented, they'll only give you Western blot plus minus. It doesn't give you the titer and I think that can be a little bit challenging, especially with this THST. I had a patient with also suggestive of pain neuropathy, but also like, you know, erythromyalgia and you don't know the clear significance of its first minus, so you can repeat it or use another lab. For me, I run into that challenge. They got bought out, right, by LabCorp? Make friends with a Neurogenetic Counselor? Oh, no rheumatologist, and they are not going to have an MDA. There is no space for one more paper. No. So we don't have a joint rheumatology neurology clinic like some of the adult people, they do have. But I think taking borrowing parts of a PMR person and a pulmonary, I think, would be very helpful, especially if they have some interstitial lung disease. But the rheumatology and nephrology, they are friends. I think they also share the same pod, so they are talking all the time. But for my patients, I have no difficulty sticking my head and saying, I want to be there. I think they also tend to be a little bit more aggressive with immune modulation compared to us. All right, if there are no more questions, I give you back half an hour of your time. Please submit some candid feedback so that we can continue these pediatric sessions in the future as well.

pediatric neuromuscular disorders

immune-mediated myopathies

neuropathies

diagnostic challenges

antibody testing

treatment response

muscle wasting

sensory neuropathies

interdisciplinary collaboration

standardized care protocols