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Um, and um, I'm currently working with the hospital plumbers. And uh the topic of my today's presentation is neuromuscular disorders. Um, might I might uh be explaining too much in detail about some of the neuromuscular disorder because I've seen some good cases, um, especially one of the case which we are going to discuss today um, in this presentation. So I'll be touching on different um, um pathologies related to a neuromuscular disorder, especially to the disorders of the muscle itself. However, since it's a very big topic, um I will, uh, then, uh the first part of the discussion will be basically to touch base with uh the common disorders that on the level of 12 and level should know. And on the other hand, um I'll be explaining to you some, uh, one of the interesting case. Um and there will be uh very fine iss that you might be able to, uh, you, you, uh, you guys might be able to uh get into practice and uh have some vision about um these pathologies so that one case report will cover so many things as well. So let's, uh, move towards, as I said, my one of the much topic is basically neuromuscular disorders. So, what are neuromuscular disorders? The other disorders of the nervous system and the muscle itself. And these disorders can result from problems with the nerves that control the muscle movement, which is motor neurons, the muscle or the neosar junction neosar disorders can be occur. It can be genetic and the severity also varies and the symptoms also varies as well. And some of the common categories and examples of the neus disorders are as first, the most famous one, the most common one is motor neuron disease. Whenever we think about neuromuscular disorders, the first thing that comes in our mind is a motor neuron disease. And of course, it is not very rare. It's very, it's very common actually uh that we see a lot during um especially at 10 weeks and in the hospital as well. So, motor neuron disease, um it is a brought and it has got two sub very uh uh the the sub divisions of the motor motor neuron disease. One is the als which actually includes upper and lower motor neuron signs. Usually the patients have muscle weakness and atrophy. And the other one is basically the spinal muscular atrophy, which is a genetic disorder and is characterized by low motor neurons in the spinal cord resulting in a muscle weakness and atrophy. We have got some peripheral nerve disorders which my colleagues have covered in the past, which can also lead to muscular disorders. So for example, peripheral neuropathy that nerves that are damaged due to infections, diabetes or autoimmune conditions. And the other one is GBS, which is also famously one of the autoimmune disorder that affects the peripheral nerves that leads to ultimately muscle weakness and leads to paralysis. And we all know GBS has got a very strong correlation with um uh diarrhea and infections. Um The third one of the neuromuscular disorder is a muscle disorder, which I will be focusing on which are called myopathies. And it's a very broad topic. So I'll try to cover as much as I can. Now, what are the muscle disorders? What are the myopathies? So, muscular dystrophy is one of them. It's a genetic disorder and it is characterized by progressive muscle degeneration and weakness. And the example includes Du and Becker's muscular dystrophy and the other um division of the myopathies or muscle disorder is the inflammatory myopathy, for example, polymyositis and dermatomyositis, which we are going to discuss in our next slides as well. Some neuromuscular junction disorders, for example, myasthenia gravis, which we also commonly see in our clinical practice. Um These are autoimmune disorder in which the immune system targets the muscular junction and that leads to muscle weakness, particularly in the face and in the neck and leads to some bulbar type of symptoms. Um some metabolic disorders, um sometimes leads to um neuromuscular disorders as well and some are mitochondrial myopathies that affects and causes the muscle weakness. Some are channelopathies, for example, periodic paralysis, for example, potassium channel induced or hyper hypokalemic periodic paralysis leads to muscle weakness and paralysis and lastly movement disorders such as Huntington's disease. It's a neuro degenerative condition, but of course, it affects the nerves and muscles and leads to muscle control disorder. Now, as I mentioned that I will be more inclined towards the muscle disorder itself, which is a myopathy. So I'll be discussing different type of muscle disorders that we usually see in our clinical practice in our emergency departments and clinics mostly. So, number one, which is very common and we all should know about and uh usually comes in the exam as well. It's polymyositis, dermatomyositis. And now what is this? Basically, it's basically an inflammation and it's usually symmetric. That's very important. Um It's, it can be subacute, it can be usually it's proximal as compared to distal and shoulder and hip Gle. They are the ones that are mostly affected. Dermatomyositis usually is seen sometimes in adulthood, sometimes in childhood. But polymyositis is very rare before the age of 18 years. There are some skin changes as well. And of course how RSH which is on the eyelid edema and purplish, discoloration on the eyes is very common in this condition. Gottron papules, which is basically the bapi rashes or the knuckles is very commonly seen. And um of course, it is associated with malignancy, lung malignancy and sometimes associated with interstitial lung diseases. Now, whatever I have mentioned will also be, we will be discussing in the case presentation, which I'll be explaining in the future in my next life. Now in poly and how we investigate, if you suspect someone, what other tests that we should do. Now, creatin kinase, of course, is a muscular disorder. So, creatin kinase is moderately or severely elevated um E MG was so my perfect veteran and anti mi anti jo and anti srp antibodies can come back positive. All of these antibodies are not 100% but 50% of Joo antibodies are seen in interstitial diseases come back positive. We also, of course, as mentioned that poly and dermatomyositis, they usually seen in the patients who have got either malignancy or interstitial lung disease. Pulmonary function test should be done in these patients. So this is how we should initially approach the patients with uh this condition. Now, what's the pathophysiology? What's what's the histopathology? So, as I mentioned that mostly is associated with malignancy, 62 6 to 45% associated with dermatomyositis, malignancy associated with dermatomyositis. Although some connective tissue disorder, for example, rheumatoid arthritis, Sjogren's syndrome. S they are also associated with uh these connective disorders. Now, in histopathology, we can find in dermatomyositis, we find per fascicular atrophy and you also find inflammation which is a perimuscle and perivascular inflammation. And we sometimes find membrane, a complex deposition on the blood vessels and polymyositis. Um we may find some endometrial inflammation, invading non necrotic muscle fibers and Endomysial CD eight T cells. And these are basically found on the muscle biopsies. Basically, these are the findings that we find in the muscle biopsy. How do you treat uh the patients like this um steroids, methotrexate. And sometimes we need IV and plasma exchange and very rarely, we sometimes use um very rarely we use riTUXimab. Usually the initial mode of management is steroids I or IBA G. Second one is inclusion body myositis. It is not as common as poly in dermatomyositis. It's usually onset is basically um greater than 30 years old. It's male pre uh predominance and it's asymmetric if you compare it with the poly Inderal myositis and the most important thing which we usually ask in the exams as well that it, where does it affect or what is the pathognomic signs of suspicion of inclusion? Body myositis is basically finger flexors, wrist flexors and quad recept. This is one of the common common tested things that are asked in exam tested questions, dysphagia is not very common in inclusion body myositis. Now, now you can see here that CK is not a very specific, it's one of the, it it could be a sensitive but it's not a very specific in the muscle disorders because in most of them, it's mild to moderately raised. So CK is mildly to moderately elevated and the emg will show myopathic and it says the infection potential is often reduced amplitude, um can have antibodies against cytosolic five nucleotidase. The pathophysiology basically is it has got some association with autoimmune diseases and the histopathology is very important. You'll find Renova and mononuclear invasion of nonnucleic fibers. There is no effective treatment for inclusion body myositis and usually we start with the steroids but immunotherapies like riTUXimab is a, they are not very responsive to inclusion body myasis as compared to poly and dermatomyositis. The third one is a very busy slide, but this is the most important slide for muscle disorders, acquired myopathies. There are many conditions that can affect the muscles and I'm trying to make the base of this before I jump to the case presentation is because we should know about in our clinical practice when the patient comes to the hospital, what things should be observed, what things should be connected when the patients are coming to the hospital with weight loss, with muscle loss, with muscle weakness. We receive so many calls in our um uh day to day setting um from junior doctors as well and of course, from um uh different staff members as well when the patient comes to the hospital and there's a weakness. The first thing comes in the mind is a stroke. Stroke can be a cause of muscle weakness, but there are other causes as well that can lead to muscle weakness and subsequently lead to muscle loss. So apart from motor neuron disease, which is very common. Apart from other disorders of muscle metabolic causes are very, very important and they are missed a lot. So, starting with acquired myopathies, we have done, we have, we have reviewed poly in my and inclusion body myositis. The the the most important one among all of them is acquired myopathies. For example, the condition like amyloidosis, the accumulation of amyloid causes neuropathy and it can cause symmetric proximal muscle weakness. So it can lead to myopathy. The other one, the most important 11 of the most important one is a critical illness myopathy. So, patients who are on severeness, patients who are in it, patients who have been in the hospital falling excellent for a long time commonly. Uh these are the patients who can develop this critical illness, myopathy. So what are risk factors for critical illness, prolonged, severe illness, corticosteroid use of corticosteroids association with neuromuscular blocking agents is unclear. Common causes of failure to wean improvement. What we'll find in biopsy in biopsy, you can find myofiber necrosis and absence of myosin thick filaments. The other causes are toxins, infections and infections such as bacteria, virus, parasites, fungal infections, alcohol very commonly can cause myopathy. There are medications, very commonly known statins as we all know it can affect the TMG coa deducta and it can lead to myopathy. There are some other medications, cycloSPORINE, amiodarone, antiretrovial medications, of course steroids and antimalarial medications and chemotherapy medications which can also cause myopathy. And as I mentioned, some virus and bacteria and fungal and parasitic infections can affect the myopathy as well. There are some nutritional endocrine myopathies, for example, thyroid disorders, hypothyroidism, hypothyroidism that can affect the muscles. And of course, diabetes can cause acute muscle infarction and cortisol disorders, parathyroidism, hypoparathyroidism. So, these are some of the metabolic causes. These are the acquired myopathies that sometimes are missed. And as a fi one fi two, these are the common things that should be assessed when the patients are coming with a muscle weakness. And um if it's a subacute muscle weakness, of course, if the patient is coming to the hospital with acute muscle weakness, then um the scenario changes. But if it's a subacute, if it's like going on for weeks or I would say months, then of course, metabolic causes should come first as compared to the acute causes such as a stroke or other things or toxins. Ok. So yes, have got one of the important condition called Duchenne muscular dystrophy. And uh they are called muscular dystrophies, basically Duchenne and Becker, muscular dystrophy. Now, Duchenne muscular dystrophy, usually they are seen in Children and Beckers are seen in the adult. The age of onset is 2 to 6. The one of the pathognomic signs is a goer sign in which the patients try to sit up from the uh uh stand up from the sitting position by walking the hands up the thigh. It's called goer sign that predominantly shows us a proximal weakness and frequent cardiomyopathy and conduction abnormalities are seen that usually uh takes place by a second or third decade from respiratory and colic failure. Um Laboratory investigation will show 550 to 100 times normal emg may show my myopathy. Um and the pa and of course, the histopathology will show necrotic and regenerating muscle fibers and increased connective tissue and inflammation As usually mild treatment is supportive and these patients usually develop these tendon contractures. So um need more for support. In that perspective, they sometimes cardic diseases, respiratory weaknesses. There is no any specific treatment. I mean we can treat it with the steroids temporarily, but it has got significant side effects and patients usually have got not a very good prognosis, especially with the um um aspiration and with the the respiratory and card failures. Um that is common reason, 2nd and 3rd degree of life beers coming towards adult. It is a partial loss of dystrophin gene. It's an excellent recessive disorder and it is the patient keeps on walking at the age of 15 by definition. But as the age progresses, the weakness starts and histopathology will show similar to Duchenne muscular dystrophy. But dystrophin stenting can relatively be normal, but the CK will be very, very high. And I think it's basically, it's the giveaway is the back is usually seen in elder people and was seen in the younger group of Children. One of the fancy one is Emery Rius muscular dystrophy is due to the gene that is affected. It's called amyrin. Amyrin is a nuclear membrane protein. Um I think in this kind of patients, usually they have got these tendon contractures in the aqueous tendon and the elbows and there's a humor of peroneal weakness and of course, cardiomyopathy and connection abnormalities are found. But I think the common thing, the common findings are the contractures which are seen in Emery, Drf muscular dystrophy. And it is one of the tested questions as well in the exams. Then there are some limb girdle, muscular dystrophies. Um The, uh this looks very complicated. However, I think, um it's a, there's a, um very interesting, um not a patient. I saw a reality show in which there was a patient who had this rippling muscle disorder and it was, the show was basically to, I think it was a kind of a talent show or something. And um if you guys find time, uh if you guys have seen that show that's fine. Otherwise just find on the youtube rippling muscle disease and you will never forget. And three limb muscular dystrophy. So basically what happens is um the muscles keep on rippling in this patient. So, limb muscular dystrophy, they are of different types, but, but most of them have got cardic conduction defects. So they are divided into two types LGMD type one, which is a one do. And LGM type two, which is also one for the understanding. I think um what we need to remember is that um LGMD one B has got cardic condition defects and it's got some contractures and C is a rippling disease. Well, that are also important. But I think for the, the stage of FA one FFA two and level, I think the commonly tested one are CIN three gene that is affected in limb g muscular dystrophy causing a rippling muscle disease. And of course, the lemon gene mutation that cause cardio connection effects. No, the reason for um touching base with all, all these uh muscular disorder was to discuss um one of the case with you that I reviewed uh during my timing week. Um and I hope you guys find this interesting as well. So this is a 56 year old gentleman who has got a previous history of alcoholic liver disease has got ischemic heart disease. Um And COPD, he's got a history of medications that you take include statins and aspirin and bisoprolol and Carbocysteine. Social history wise, he has got limited mobilization because of COPD and he's a chronic smoker. Uh from past 40 years, he has got some exposure as well as a part of occupation and he's chronic alcoholic. He has got no, any family history for neurological disease. So basically this guy who has got coronary al he's a guy who's an, he's a guy who's got COPD no family terminological disorder came into the hospital, came in directly to the emergency department. Basically, the reason for the initial presentation was, uh general decline. Uh, symptoms was basically weakness in arms and legs. As we all see in our emergency department. The reason for coming to the hospital, uh, hospital, most of the time is the generalized weakness. There's not a specific weakness. It is a generalized weakness. It's not unilateral weakness, it's not one sided weakness. It's not acute. It's a gradual one week history of weakness in arms and legs associated with problems with swallowing and uh some speed changes as well. He also had decreased oral intake and uh he had some weight loss from past six months. He's lost around 2 to 3 stones. So he was initially assessed by the team on examination. He was alert and oriented. He was maintaining sets, but he was requiring 2 L of oxygen. He was afib and difficulty in swallowing of both solids and liquids and there was generalized muscle weakness. So, till now, as you can see, there's nothing neurological that should be coming in. The initial investigations were done. Um And we found that is quite high creatin kinase was 18,000. But at the same time, you can see the liver functions are quite deranged. Now, ast gamma GT and A they were high. But we always, it could be due to cirrhosis of the liver because uh he did not diagnosed cirrhosis but he has got alcoholic liver disease and he's a chronic alcoholic. So we were suspecting it could be due to that. Magnesium was not very bad. It was 0.64. He had a chest X ray which showed some predominant emphysema. He is known to have COPD and there was some more opacification of right angle. So we thought it would be an infection c was not very high at that time though he was treated as well as infection. Given the hypoxia, he was having, he was maintaining sex on 2 L oxy. His statins were suspended because of that was very high. That's what we all should do that if the patient is coming to the hospital with a high CK, try to suspend those medications that can affect the muscles and also that can affect the kidneys. We get some IV fluids. Um, and the patient was known to him already because this guy was having um, um, alcoholic liver disease. He was admitted to surgical board. Um, he, since he was known to have a LD and he was having worsening liver functions during this time. As always, he had a CT had a scan. So when our patient comes to the hospital emergency team, emergency department team, most of the times, if they're, if they're suspicious for anything, um, they sometimes do CT head scan and uh most of the times, uh they, they do find abnormality on the scan, but the CT head scan was normal. In this case, it's very nonspecific to have generalized weakness in arms and legs. So the localization doesn't match. MRI scan was performed as well. MRI whole spine was performed by the Hepatobiliary team when he was admitted in the Hepatobiliary Ward and there was some disc degenerative disease was found, but there were old changes, there was nothing new. So once they were done with all these investigations and patient was still having dysphagia, swallowing difficulty, um that was raised muscle pain. They sent a referral to one of our team for ongoing dysphagia. Speech changes and generalized muscle weakness since admission. So when I assessed him, he was alert and oriented. His GCS was 15 by 15. His current of examination showed no ophthalmoplegia. There was no defect in central or peripheral field of vision. There was muscle weakness, he was drilling flour, there was dysphagia. He had mild difficulty in formation and articulating the words, but he was not having any name. Um worth finding difficulty. He had difficulty in articulating the words and his phonation was basically affected. His cognation was not affected motor examination wise, he had generalized muscle wasting. Significant proximal muscles were affected in the upper and lower limbs and there was tenderness to palpation in all the limbs and the upper limbs. The proximal muscle was three by five and distal, it was four by five. Distal muscle weakness in the upper and lower limbs were reduced but proximal were more reduced in terms of the power. Um I checked this fatigue ability test. There was, it was negative. Um, sensation reflexes, tone coordination was normal. His gait was normal and uh sorry, his gait was not performed because I was, I was afraid he should not fall. So he was at risk of falls. So his gait was not performed and his splinters were down going. I don't know. Um, if anyone wants to say anything till now about what is going on with this patient, any thoughts, I don't know how many people are joined here. There's, uh, there's 24 other than us. Ok. All right. There'll be lots more on the live stream after who can or the recording after. So guys tight. What do you think in the chat about what might be going on? Yeah, they can write in the chat. I cannot see the yet. So. Oh, that's ok. Yeah, I can. So it say someone said polymyositis. Hm. Yeah, which was also what I thought but I am ST ok. Yeah. So I also thought the same, it could be polymyositis. It's not a bad start. So, on my assessment, my clinical impression was it could be polymyositis. And the reason was because I was suspecting it could be underlying malignancy and because he has got this history of asbestos exposure, he's smoking, he's taking alcohol. I was thinking it could be underlying malignancy and ultimately, he's leading to polymyositis and muscle weakness. And he raised and my other impression was it could be drug induced because he was on a statin. So it could be ST induced myopathy. But he has been taking students for quite a while. It's not something which is new. He's been taking for a long, long time. Um, his CK levels were high, his muscle weakness was symmetric and there was a weight loss and there is a suspected underlying malignancy of and of course, history of smoking and statin use. That's why it was my clinical impression. The other officials that were coming in my mind uh was uh myopathies secondary to metabolic disorder. For example, alcohol, alcohol can directly affect the muscles, endocrinopathies such as thyroid functions. And um I was thinking about it if it could be A and D, if it could be lower motor neuron disease leading to muscle muscle weakness, or it could be poly poliomyelitis, which is not very common in this part of the world. Um lead poisoning or spinal muscular atrophy, less likely I was thinking it could be peripheral nerve disorder, but it was very low in myofascial. But more so it was more of polys and its acid induced myopathy. And of course, uh lesion in the upper motoneuron, for example, the space a lesion, acute stroke syndrome, demon disease infection, vascular anomalies were very lost in my differentials because I was keeping these differentials as well because the patient was having bulb weakness apart from the limb weakness. So my plan of management at that time was to start on uh methylprednisolone, 1 g intravenous for three days and send HGC antibody that we usually find in patients who have got a statin induced myopathy. As we have discussed. Initially, I sent the MYO is a screen for the patient for all the tests that we have discussed. Um in the start of this presentation, I requested the nerve collection studies and EMG and depending on the NCS and EMG I thought we'll see whether we need to do a muscle biopsy in this patient. So nerve connection studies showed signs of severe polymyositis, but there was no signs of possible neuromuscular junction disorder and we were quite convinced that it could be severe polymyositis and we should be treating this patient accordingly. Um On day three of intravenous steroids, the started improving from 18,000 to it become 10,000 gamma GD also improved um to 116 from 233. So, since the symptoms were improving, we switched from intravenous steroids to the oral steroids and we thought that we are going in the right direction in terms of diagnosis. So on day five, we discussed with histopathologist and of course he was scheduled to have a muscle biopsy. So this is a muscle biopsy result or slides of the patient that are reviewed in the ward and the biopsy has been taken from deltoid muscle. And you can see there's a pale necrotic um area in the center of the muscle biopsy. And if you see here, this is also a necrotic fiber staining and there's uh no deposition of membrane complex. So I discussed with the neuropathology, uh histopathologist about what it could be. And he gave us the final um summary of the muscle biopsy for this patient. You mentioned that uh there's no inflammation to support the diagnosis of myositis and the features suggest acute necrotizing myopathy and we should exclude toxic drug induced metabolic paraneoplastic and immune mediated causes of this patient. So initially, we thought it could be polymyositis. Now, the biopsy has come out to be something totally different. There's acute necrotizing myopathy and there's no signs of inflammation found. So it means that what we found on the nerve connection studies was different and what we found on the biopsy report was different. So who um I mentioned about the new muscular disorder? I think it's a are good. Um ok, I think we should go for from here. Yeah. Now what is necrotizing myopathy? So this is basically what the report found acute necrotizing myopathy on the deltoid muscle biopsy result and what is necrotizing myopathy and why it is important in neuromuscular disorders? And um what we should, what what what are the uh objectives that uh we should learn from from this, from this case. So what is necrotizing myopathy? It's a newly defined form of idiopathic inflammatory myopathy or myositis. It can also be referred to as necrotizing autoimmune myopathy. What happens in these is uh, muscle biopsy shows much less inflammation in the muscle tissue than polymyositis patients. But there are increased evidence of muscle cell death or necrosis. Now, what are the causes of necrotizing racy? Let's talk about the symptoms. Symptoms are more or less the same and the weakness in the muscles closest to the center of the body. Difficulty in climbing the stairs or standing from the chair, difficulty in lifting the arm over the head and falling repeatedly and difficulty getting up from the fall and feeling of tiredness and then in neck and auto myopathy, there are some tests or there are some associations that needs to be done. For example, these patients are very prone to have HGC and antibody positive. If they are statin exposed, these patients are known to have anti srp antibody positive. Some of these patients also have malignancy that is associated with them or they are associated with connective tissue diseases. So these were then are four main objectives to rule out in this case, following the biopsy result showing nes autoimmune myopathy. So as I mentioned, the biopsy mentioned, necrotizing autoimmune myopathy. We sent HGC antibodies. Now, what are the HGC antibodies? It's a key enzyme. It's a HGC, it is a key enzyme that is uh used in the protection of cholesterol and patients who have anti HGC antibodies and use the statin medications to control high cholesterol may unknowingly develop this type of a statin induced necrotizing myopathy. So we have to check this type of the antibodies against these receptors. Now, how does it work? So, it's stiff and expose, exposure leads to muscle injury that leads to increased regenerating muscle fiber that causes increased MGC expression. And in the genetically predisposes people of HLD 11 that leads to immune mediated necrosis. It's one of the proposed pathogenesis of statin induced necrotizing autoimmune. Now, the second antibody which is also very closely correlated with necrotizing autoimmune myopathy. SRP. So SRP antibodies appear in the blood test in many ex experience in the patients experiencing necrosing myopathy. And uh these patients al also have cardiac involvement. Now, coming back to our case, we had to rule out these four causes following the biopsy result, whether it's immune mediated, whether it's toxic or drug induced, whether it's metabolic as we discussed before in our presentation or whether it's paraneoplastic, we have to rule out these four causes causing necrodes myopathy in this case. So we send these antibodies, we sent cr antibody, it came back negative, we sent SRP antibody, it came back negative and we send myocytic a screen. As you can see here, we sent all the ETS a screen panel including anti is one that came back as a negative in this patient. Now, the second thing was to rule out if there's a toxic or drug induced cause causing necrotizing myopathy. So in this scenario, what are the toxins that could be causing this? So for example, alcohol, he was taking alcohol, he's a chronic alcoholic, cocaine, there was no cocaine history for them. He was on lipid lowering medications, antimalarials, he was not on and colchicine he was not on. So patient was on the statins. However, HGC antibody came out to be negative. In this case, there was no recent history of binge alcohol intake. When I took the history from him, he had a history of chronic alcoholism, but there was no any recent history of um binge alcohol intake causing this significant uh clinical symptoms to be affecting especially muscle loss and everything. And when he came into the hospital, there was no signs of rhabdomyolysis or AKI he had a that was high, but his phosphate levels were normal on arrival. So, and we also sent some more tests to rule out if there is a metabolic cause of this necrotizing autoimmune myopathy such as we checked his diabetic profile. His once he was 32 that was normal. His glucose, potassium calcium were normal thyroid functions and parathyroid functions were normal and there were no systemic signs of Cushing's Syndrome. So there, so we are now uh having limited answers about what it could be and what is the cause of this patient's necrotizing autoimmune myopathy. We will send connective tissue diseases. Um Antibodies such as is sent for M and Joe. They are basically for um poly Inderal myositis. We sent anti SCL 70 antinuclear antibody DD, uh mitochondrial antibody, smooth muscle anti antibody and L1 LG antibody um and gastropar antibody, they all came back negative and we also sent some antibodies, they also came back negative as well. So the three most important conditions that can be affecting and causing myopathy, Sjogren syndrome, scleroderma and s and seems to be they all were negative as well. We sent some paraneoplastic antibodies as well because cancer was also in one of our differential causing poly inomyositis, but the antibodies were negative. And at the same time, we also sent some tumor markers, for example, c 99 psa and alpha fetoprotein. And they all were normal. We sent some paraneoplastic antibodies and they all were negative as well and he wrote R two and, and they all were negative. Apart from the blood tests, we also do the ra we also did radiological investigations in this case to rule out if there's underlying malignancy causing uh myopathy. And we performed CT for when he came into the hospital, there were no signs of pe and there was some emphysema but it was uh a small nodularity on the lower dose. Um That was in fact, in etiology, nothing like a cancer CT was done one month before admission due to weight loss. And uh a chronic liver disease, it was performed by GP but there was no features of malignancy at that time and he had a pet scan as well. Um And that was normal as well, but it was done by scan, was done in 2021 and he had a pet scan after that as well when he was discharged from the hospital. So since all the antibodies were negative sero negative immune mediated necrotizing myopathy was considered as a likely differential for this patient. So it's now what is sero negative immune mediated necrotizing myopathy. So we've got some articles about immune mediated necrotizing myopathy and the patients who have got HGC are antibody negative and SRP antibody negative. They are called immune negative necrotizing myopathy. And this was one of the case of immune negative necrotizing myopathy. We have got I gone through some of the literature search and there has been some cases, especially one of this case, a toy case of antibody negative immune mediated necro myopathy with severe cardic involvement. It's uh one of the case in Japan Society of Medicine and there is one more case of a child who had this all these antibodies done nerve connection studies, antibodies, blood tests and radiologic investigations done. And at the end, the diagnosis was made as immune negative necrotizing myopathy. Now what we did after that, we did all these investigations, we realized that there is no antibody that is positive, but this gentleman is still declining and he has got this muscle loss. He has got bulbar symptoms and they have started steroids, but the CK started improving. So, what we did was we managed to oral steroids. After completion of three days of IV steroids, we gave oral steroids for two weeks. Um His was significantly improved from 18,000 to 69 over the treatment course of three weeks, his dysarthria and swallowing difficulty was completely resolved and he was referred to one of our, our hospital for rehabilitation. Um And then I had a discussion with one of our neuromuscular specialist in my hospital and she preferred to review the patient in the in her outpatient setting. And um she basically switched the patient to mycophenolate moet, one of the immunosuppressant. It was a by the scan until the time he was going to rehabilitation, but his pet scan was delayed because he ultimately developed COVID infection in the rehabilitation unit. So his pet scan, all the, you know, it takes months and months for the pet scan to be performed. And when the date arrives, he developed a COVID infection. So pet scan could not be performed ultimately. But of course, we had a pet scan of 2021 and there was no malignancy found at that time, although he was having weight loss since then, but there was no dysphagia or clinical symptoms of dysphagia at that time. Ok. Now, currently, there are no randomized trials for treatment of necrotizing myopathy and the treatment recommendations are therefore largely based on expert opinion. Some people say that treat with oral prednisoLONE 1 mg per kg uh for 4 to 6 weeks or IV methylprednisolone 1 g for 3 to 5 days is the first line of NM immunosuppressants such as methotrexate, mycoid azaTHIOprine can be added during the course of the treatment and for refractory diseases, I DLG can be trialed, but there's not any clinical guidelines made for sero negative immune mediated necrotizing myopathy. And uh that's one of the case report that uh uh also mentioned about uh um C negative necrotizing automath with response to IV IG. Um And of course, there are multiple other case reports who I mentioned that I vi do use as a mono has got a promising outcome. Um So the take home message is that this case was unique because uh our patient has a history of stent exposure and uh muscle biopsy found immune mediated necrotizing myopathy. And uh we initially thought the diagnosis of statin induced immune mediated necrotizing myopathy, our patients has negative HDC antibody. And um although the patient was uh not had a history of prior or current history and exposure, he has, he still had a act myopathy. In addition, his suspected underlying malignancy, given history of ALD and liver lesions may have been a contributing factor was a diagnosis of co negative im And m if there is a suspected immune mediated necrosing myopathy, early muscle biopsy must be performed. So that's very important and aggressive management with steroids. Uh um And Ivig has shown better results. So it is bit quite in detail that I went through the muscle disorder because I wanted to discuss this case with our junior audience. Um But at the same time, um I want you to touch base with these uh common causes of myopathies that I discussed in the start. So I hope that this discussion has helped you in opening the horizons of uh differential diagnosis in a complex patient when they come to the hospital. And the first thing first is to rule out the basic things um and uh the common things and then look out for the uh the uncommon ones. So in this, in this scenario as well, we ruled out the common things first in a patient with myopathy and then slowly and gradually when everything comes back negative, we found out something extraordinary. So that's my advice to all the juniors as well to stick to basics. And uh um just uh um rule out the common things first. Thank you. Thanks very much thea that was um really well uh as someone who wants to be a neurologist, that was uh that was absolutely fantastic. Um Has anybody got any questions um type them in that if you do, um I've just put in the feedback in there as well. If you fill in the feedback, you should be able to get a certificate and it's really helpful for us as well. Um It's definitely informed the way that we provide teaching in the past. Um So, yeah, feedback. We do listen to it and we do make modifications. Um I'll just give it a few seconds to see if anybody responds. If not, just to, just to advertise that we have got two more sessions coming up over the next couple of weeks. Um, before we sort of try and have a think about where to take neurology, the Neurology series in general because we've covered quite a lot of the topics um that are the more common and now we're moving towards more uncommon things such as what Zans presented tonight. Um So it'll be interesting to see how the feedback develops. We've got another session on Parkinson's, which I think probably is one of our last sort of common condition sessions. And then we've got a registrar doing a session on neuroinflammatory disorders as well. So things like MS and the sort of other comedians in the mix that um come up. Um OK, I can't see that there is any questions being provided, like I said, um please fill in the feedback. Um But if we don't get anything in the next 20 seconds, I will um take us off broadcast, you'll be able to watch this on youtube. Um And yeah, like I said, thank you for coming. Um If you provide, can provide feedback, it's really helpful for Xu Xiang and myself. Anything else you wanna say? No, thank you so much for giving me the opportunity. And I thought that uh um I should contribute um um at least a bit to our colleagues, especially the junior doctors. And uh of course, um it started very, very easy and something that we have already read and understood for a long, long time since medical school. But in the end it come out, came out to be something totally different. Yeah, I think, I think in general uh particularly the muscle disorders. I think medical school is very good at teaching you about myasthenia and lumber eating syndrome. As soon as you get beyond the neuromuscular junction, even in the M RCP, it's essentially neglected beyond dermatomyositis, like you said at the beginning. So it's really helpful to have that comprehensive oversight anyway. Right. I'm gonna take us off broadcasting and then um yeah, feel free to drop any messages in. Um And uh thanks very much Natalie that's um that's really helpful. Um And yes, I um yeah, like I say, it's good having a multidisciplinary audience as well. But, right, we're going to shoot off and we will see.