Dr. Colin Franz discusses the major neuromuscular complications associated with severe COVID-19.
welcome back everybody. It was it's been a good morning so far. And the uh some some good talks in the morning and looking forward to the talks we have coming up here in the uh in the second part of the morning. Our our next talk by dr Colin Frances because about neuromuscular complications of covid, a very kind of uh topical issue, you know that if been seeing uh more patients in acute rehab unit and uh so want to have be able to learn more about some of the things that are that we're seeing with the the post covid patients. Um so very pleased to have uh dr Colin France. He's the director of the regenerative neuro rehabilitation laboratory as well as a physician with board certifications and neuro muscular medicine and fizzy Tree. Doctor France has overlapping research and clinical interests and neuromuscular disease rehabilitation, gene therapy, nerve repair and disease modeling with uh with induced pluripotent stem cells. His ultimate goal is to develop more personalized rehabilitation medicine to help his patients with neuromuscular disease. His research is supported by the NIH NSF Craig H. Nielsen Foundation and Foundation for Physical Medicine and rehabilitation. Recently he has identified and published several studies looking at the neuromuscular complications of severe covid 19 from a rehabilitation medicine perspective. Thank you very much. Doctor conference. Thank you. It's a pleasure to be here. Um I uh have no disclosures, I will say that coming to a conference on brain injury that is, and although my clinical work is heavily on neuromuscular medicine, uh my research really focuses on neuro trauma. So we do research on individual genetic factors that can influence your trauma outcomes from brain injury, spinal cord injury and peripheral nerves. So this is a conference of great interest to me um as someone who uses the clinical observations sort of reverse translate into my research from all within the different areas in our rehabilitation hospital. But today I'm excited to share information that we have sort of through some serendipity and um you know, in terms of where Chicago was in the first wave of the pandemic and describing some of the initial prototypes are the characteristics of patients who are admitted to inpatient rehabilitation after covid. And so this this data set was not something I was planning to kind of collect information on, but sort of it sort of found me. And what I hope at the end of this pocket that you can do is understand the major neurological complications of severe covid. These apply to patients throughout an inpatient rehabilitation hospital setting. And so these clinical side we should be familiar with whether it's a traumatic brain or brain injury medicine or are there uh this sub disciplines of rehabilitation medicine. And also I'll explain to you in terms of how an approach and how it's been used for these electro diagnostics, advanced imaging that are available to patients and inpatient rehabilitation facility To both understand, you know, the diagnosis localize the injuries and establish some causality of what happened that caused these injuries in these covid survivors. So Just quickly, I mean this is the first submitted. So I gave the most up to date information at the time. But in terms of the number of COVID cases in the worldwide over 163 million, this is probably under representation of the true numbers of course. And in the United States at the time that I submitted the slides was 33 million Case is over 500,000 people have died. And you can so you can imagine the scope of the problem of course. How could we not, we've all been living through it and where you kind of look at our trends in terms of case numbers, case the rate of covid infections, the United States. So you can see, well we're not as high as we have been. You know, the late 2020, early 2021. Our numbers are still kind of higher than our or approaching or similar to like the first wave of covid pandemic. So we're by no means through this and therefore understanding and you know, we're gonna be dealing with these complications. We're gonna be dealing with this disease uh in the rehabilitation setting in terms of survivorship and for for quite some time. So it's important to understand what this disease can do. And I thought I'd start off with a clinical case of someone who was actually admitted to our facility and has been described as having to write him, he plead your pattern And I put a question mark there because there was a bit of a mystery of what was going on. He was a 16 year old man with a history of hypertension, coronary artery disease. And HIV presented to our facility with right, much right sided, worse than left sided weakness and sensory loss after a prolonged hospitalization for severe covid. He was actually in the hospital, as you can see with the acute admission lasting over two months before he's admitted to us. And when we examined him, because they asked me to take a look at this fellow, uh you can see that describing his weakness and sensory deficits that he had weakness on both sides of the body. But I want you to appreciate that there was a symmetry worse on the right side, um including approximately distal muscles on the right side, distinguishing it from the left side, as well as the key that there was another key feature for him was that there was loss of sensation, not just weakness. And that sensation loss was also much worse on the right side of the body. So before the question was, why was this the case? And before he came to our hospital, there was concerned naturally for something like a stroke or other lesion in the central nervous system. But imaging had excluded any significant uh uh any structural explanation for this, although there were some small uh enhancements in the basal ganglia and nothing too significant even in the cervical spine. Um They thought about peripheral nerve and the image the bright break, a plexus, but there was no demand, no thinking, none of the changes we see on mris of nerves that suggested that there was an injury at that particular location. So um uh the clinical conclusion that was given before he was transferred to rehab was that this was stemming from critical illness. No myopathy. And I will point out, you know just as someone who sees a lot of patients and there's a lot of consults for norma presentations in our hospital and as well as in the acute care facility that's across the street that that the critical illness myopathy pattern, you know, which I highlighted here with these on the left should be affecting shoulder girdle and and and and uh huh colonel muscles but typically not these muscles down the lower arm, over the lower like. So that didn't quite explain everything and had some features. Yes, but it didn't explain the entire presentation. Also if you have a critical illness neuropathy, it's usually very symmetric. And this was if you look at it centralized deficits was not symmetric at all and much worse on one side of the body than the other. So this was a really great explanation. There have been limited ability to do electro diagnostic especially early in the pandemic due to infectious disease considerations. And and so we're eliminating some of the studies but rehab were often clearing some of these patients for for these precautions that were able to do some of these studies and this patient's exam. I'll never forget it because you can see there's a lot of text here which I hate to show. But the point is look at all the different sites of nerve damage here. This is a very uh what we would call a monitor right is multiplex pattern but multiple modern rapa, these radial nerve right on a nerve left owner, right, median, left, median, a psychotic nerve on the right. And uh and then this was all superimposed on the background of the myopathy which explains the proximal submit relatively symmetrical proximal patterns. Um And then all the asymmetries there's also a clinical suspicion for right lateral from subcutaneous modern apathy, although that was improving electro diagnostically. So the question is why why does this happen? And for a lot of these presentations we don't really you know, that's we'll talk a bit about what the what this virus can do and but we don't really know always know the answer to that question and certainly were of great interest to us. But um in this particular case there was at least the psoriatic injury. This is the thigh, the right leg where you can see that hypo density here with the arrow sign they're pointing towards it and I sort of uncirculated there. And this was actually one example where these patients are often on any coagulation uh because of the waggle apathy with this uh associate with this infection. And this patient had developed a spontaneous, like an intramuscular hematoma and that was identified as at least explaining one of the modern repetitions or the right sadiq. But the point isn't, the point isn't totally to take away the some of the stuff I wanna talk about later, but it's just this is going to come up time and time again. Um when you see these patients and it was going to come up a few times when I talk is that you need to be very weary of a typical deficits, a symmetrical weakness and things that just don't make sense in post covid patients because often it's very difficult to come up with a clean localization often because they have multi folk hole disease, mostly focal lesions with respect to the peripheral nervous system in the neuromuscular system. So let me step back there. So hopefully I got your attention a little bit. Um And I'll say that well I'm not uh immunologist by training. I can tell you some of the basics here about how this virus um the SARS-cov-2 virus combined to ace two receptors. It internalized into cells often epithelial cells in the upper airway um and lower airway it can then, once it's uh internalized into a cell hijack some of the translational machinery it can it can activate the toilet Uh colic receptor three which can lead to really. I think we're well established out there that there's a pro inflammatory component, this uh inflammatory cascade, that uh a lot of these interleukin are then up regulated and secreted. And the stealthy thing about the covid infection, from what I'm told by reviewing the literature and talking to my colleagues in infectious diseases that ordinarily when you have a viral infection, there's an inflammatory response that starts shortly thereafter and they kind of mirror each other and until the viral load is um reduced. But as part of our immune response. But the initial part of the uh sarah's Kobe to infection, the covid Christine covid disease is is often lead to like a lot of viral load developing met hidden from our immune system and then a very delayed immune response to that leading to a very heavy but overreaction. In terms of the amount of inflammation that occurs and who's most at risk for having a severe infection. Well, I'm sure you've heard some of the risk factors, but I think the 22 of the main ones that come up over and over and reflected in this population is patients who, particularly of older age who are much more likely to have severe infection and inflammation and obesity. And both of these conditions are associated with higher levels of inflammatory markers at baseline and also much more severe response to this infection. Um, and then looking at the way that this disease has been associated with so many different complications affecting so many organ systems. So because the systemic, the inflammatory response referred to often as a cytokine storm, um, you can see that it can impact a lot of different parts of the body with respect to the central nervous system, which is so important to relevant to this conference. Uh some of the most common manifestations in severe covid patients, confusion, delirium, uh even aphasia and and seizures in some cases. Uh interestingly in this review as the new England Journal, that they want to go um you know, I kind of put this emoji here, rolling my eyes because they actually didn't really focus on anything neuromuscular complications which we've seen so much an inpatient rehabilitation. And also I'll point out that, well, we do note that there are central nervous system complications. There's not, they're very limited data for a widespread uh central nervous system kind of indirect involvement, infection from the virus. And so these tend to be more indirect effects. Speaking about the neuromuscular phoenix types, so which are I think are really under emphasised in many cases, when you go back to the start of the pandemic in Wuhan china, you can see that Some of the earliest reports, so describing the 1st 200 214 hospitalized patients out of the this hospital that was at the initial uh phase of the pandemic in china, you can see that the first complication that came out in this that was in the neuromuscular system was a muscle injury type when they defined by elevated in this C. K. Or the creek and kindness and uh kinase enzyme. It's called hyper sick anemia. And you see the for people who are used to looking at these numbers of elevation to a level of 400. Isn't that impressive? Which was the median amount. And often that would probably not raised much of an eyebrow for someone to have that level who walked in a neuromuscular outpatient clinic without symptoms. But the range was quite broad and it was the first clue that maybe the muscles were involved. And later on what I think caught a lot of headlines was this potential association with DeAndre syndrome, sending paralysis neuropathy that that could be triggered at least was Associate with five patients in a case series in the New England Journal out of a group in Italy. And fortunately as time has gone on, I think we've realized that it doesn't seem that there's clearly an increased rate of Guillain barre syndrome since the pandemic started. Although it can be triggered in patients with the infection, it doesn't seem to be occurring at a higher rate than it has and by, you know, by historical standards and the patterns of G. B. S. The variants that we see are about the same ones that we've seen in prior years. Nevertheless, the very was very early on for for you know, in the pandemic. And we're getting this information that was obviously a very you know, still a lot of fear out there. But that was one of the scariest things that that could be triggered. And then we had a report on impatient, we had patients post covid who Had this uh modern writers multiplex pattern, which I guess was telling you about there. And that one fellow where almost 15% of the patients who came into our unit and this was reported at initially in July and was that came out of print in September had at least one or more peripheral nerve injuries. Out of 80 83 patients. The 1st 8 3 that we had admitted. And we found a strong association with being managed in quote unquote the prone position and we'll talk a little bit about what that is um for patients who are at severe covid and were in the ICU. And then another study looking at muscle involvement with myopathy reported. Now in 3% of the patients out of a larger study in Spain um sort of laying the groundwork for some of the early complications that were being reported. And we'll talk to expand a little bit more about those. So that gives you a bit of a timeline. So I will tell you that what we've seen, although we're still understanding more and more about covid long haulers. Um and trying to put that data together the vast majority of these severe neuromuscular issues are in patients with severe disease and are survivors of severe covid. And these are the patients who come to inpatient rehab at a higher the highest rate in terms of covid post covid patients. Uh And I'll point out that we look at the timeline from the pre symptomatic phase to the onset of symptoms for covid infection, and then we follow them in terms of the days until they get hospitalized. What we're seeing is His patients often presenting to us after a month or more in acute care coming. Um not everyone who gets of course the star is Kobe to infection will get the hospitalist or certainly not critically ill. And that's maybe 5% of the patients. But a very high percentage of symptomatic patients develop shortness of breath and respiratory symptoms. And and I think um the the respiratory disease, the covid acute respiratory distress syndrome. Air DS has led me to learn a lot about what pruning is and I'll explain to what that is in a second. And this is just from a review paper we did on some of the uh neuroimaging findings and Covid patients showing someone uh in a prone position here laying on their belly and some of the nerve sites that we were interested in highlighted there. I'll come back to that and but briefly what is prone e and why should it matter to you? Well it turns out that there's guidelines that I became more familiar with once we started hearing a lot about this but they they actually existed for management acute respiratory distress in the before covid. But it was the covid where this I think became very where at least on my radar as an intervention that's done in acute care where patients who received an intubation are being screened and often in a very regimented fashion that they meet Children parameters actually being offered management and flipped and being basically flipped on their belly to treat refractory hypoglycemia and acute care. And so that comes back to this uh to this position. So patients are spending a lot of time in this position and this certainly puts forces in places that ordinarily don't bear a lot of weight. Um and if anyone wants to try laying on their stomach for An hour or two. And typically these patients lay for 16 hours at a time for recording session. Um You can see how that would feel but laying on being flipped and laying on your stomach in the intensive care. Um This was being done because there's a number of trials including the landmark civil trial that showed that this actually creates survival and reduce mortality for an Air B. S. And so we learned though this year, more than before, that there's certain complications that come from lying on your stomach for these sessions, pressure wounds to the face and knows that some of you may have seen if you've seen these patients, but also these neuromuscular complications that we think are very strongly associated with it. And so that's where I'm telling you back. So I started To hear about this now in my hospital on May 2020 that there was some of these patients with asymmetrical critical illness neuropathy that like the fellow I told you about and this seemed to be occurring although in a half shell, a few, a handful of patients who have been prone. And so this is just taking us back to where we were in terms of that point of the pandemic there. And Chicago was definitely one of the hot spots that early in the pandemic just after new york city. And so what we did is we actually reported on uh that cohort that I had indicated and I'll tell you what about that. But this is a patient here, uh depiction of a patient here in a typical swimmer's position, which is one of the positions you'll see patients in when they're being thrown. And uh in some of the sites that we think are vulnerable either through compression attraction mechanisms, particularly in the upper extremities. And our team actually produced a little heat map of some of the sights, including some areas in the break up plexus, nerve injuries, often around the shoulder and to the upper arm, and one of the hottest spots of all was inside the elbow, where the owner nerve was often trapped. And we mapped it out showing it on the upper stream because the vast majority uh Over 80% of our initial description was was upper extremity injuries, which was pretty impressive, although we did see a few injuries in the lower extremity. And and this was representing, like I said, Almost 15% of the patients in our hospital at that time. And again, that association with being managed in the prone position was something we couldn't ignore. About two thirds of the patients who were admitted at that time were based on the cohort analysis were probably prone and about a third weren't yet. Almost all the nerve monitor, right? This multiplex cases we saw were in the prone patients. Um And these injuries tended to be on the severe side when we call it. The ex army says it means that the more severe injury where axons instead of just demoralization and loss of insulation around nerves which tend to heal better. These tend to be slower recovering injuries that were that we were seeing so more severe injuries. And we used a lot of advanced imaging to help figure out what was going on for example to determine that these were occurring because of that. Like you saw earlier that hematoma but in this case. And forgive me that this is this is the MRI of the elbow here showing an owner nerve entrapment. So this is the medial and lateral pecan dials. And uh and then the owner bone. And so you can actually see this bright spot here is the owner nerve, which usually isn't this bright. Um but because it's inflamed with overlying edema of soft tissue, so applying compression mechanism damaging that nerve and that swimmer's position that you see people prone. And we sort of referred to it internally, it's like maybe a swimmer's elbow because these patients were spending a lot of time at that elbow down, putting pressure on that nerve. And then this is unpublished data. Now another 22 patients. uh well 10 more in addition to that 12 and uh that that I had summarized here by uh ross Malik, our chief resident in PM and are at Northwestern. And you can see that the owner nerve at the inside of the elbow, the radial nerve on the outside of the elbow or two very hot spots. They're accounting for almost 40% of the injuries. Just between those two sites. We see a lot of other uh injury sites occurring less frequently. But this is uh Where we get that sort of description of being a modern writers multiplex. And and almost you know when you look at it, this is representing 22 patients but 37 different nerve injury sites that we saw. So a lot of damage. Like you saw the extreme example that one person who had, I believe eight different injuries, all in 11 individual. And what we've done. And we've worked really heard is not just the rehabilitation of these nerve injuries but the prevention of them. And working with our intensive care unit um on improving the position because it's pruning at this with this many patients um Meeting the requirements for protein for their A. R. D. S. Was something we weren't that familiar with apparently in our ICU. And I've worked with them Taking information What's known about 20 patients for long periods of time from the surgical literature that surgeons of the spine anesthesia, anesthesiologists are quite familiar with positioning patients to prevent injuries. And we learned a lot from them and and trying to find better positions to protect our patients. Um And that was something that's sort of a pre debilitation thing because we're doing a rehab information on patients even to prevent complications before they come to the impatient rehab unit. We've also been very interested in using technology to protect and monitor some of these vulnerable sites. So we, for example I told you the owner nerve at the elbow is the most common single site. So we have these wearable patches that are Engineering group at Northwestern has developed which is basically this very small little Um all you know the entire devices and encapsulated here and has a battery for power. So it can last for about 20 hours a pressure sensor and can basically provide real time monitoring and transmit to a wireless device like a cellphone. And here is attached just to the media lab above the media lexicon of Oh in a patient who uh was self groaning. So this patient was laying there with his up and down and you can see that the pressure tracing, which to be honest, we still don't know in terms of the the exact amount of pressure before these injuries can occur. Although you can see how sensitive these monitors are to perturbations in terms of when the patient's repositioning themselves and able to maintaining very long recordings we can record. Often we would record for two hours at the time and just did some pilot studies on both elbows to monitor these vulnerable areas. And although we don't have uh you know uh figured out in terms of how to use these. But we convention as the future now that we show the feasibility that we can put these on patients to monitor vulnerable sites and have an alarm or some sort of warning presenting to the medical staff so that they can then reposition the patient, there's too much pressure. And so we're actively working on that. Which is also something that came out of this uh this past year sort of out of out of nowhere wasn't really on our radar or something that we were interested in researching. Um and then in terms of other complications of covid affecting the neuro muscular system and affecting our impatience in rehab, I sort of show that although there's myopathy and poly neuropathy, G. B. S. That I mentioned, but I would say that you had to really focus on one other kind of complication other than this. Modern writers multiplex, it's really the muscle involvement, the muscle damage, pauline, Europa. These can occur and G. B. S. Does occur not the most common thing out there before the pandemic and it's still not that common but we do see it and impatient we have, of course. But let me tell you a bit more about what we've learned about the muscle injury because covid patients um like I said, there's that elevated ends into the Matic evidence of muscle damage in the original cohort of Wuhan. But they're in that false study in Spain that was showing about three Of the MG confirmed myopathy is compared to about 9% of just people with elevated enzyme. So, so indicating that this is generally clinically what we would consider a more substantial muscle injury or myopathy with the electro physiological confirmation. And then other groups have since shown either out of italy with a larger study and of Sweden and nice. Well then I see you study that That this critical illness myopathy is occurring maybe even up to uh 6-10% of the patients that are being managed in critical care. And we don't have a great idea of this, of this rate in non covid patients. And we're trying to work through that. But it is a substantial burden when you think about the, For example, the 33 million that have been infected with this virus in the United States and percentage of them uh, that have had critical illness, the severe illness that may be affected by something like this. And, you know, one thing that was also striking when I go back and I look at our table of those patients Is when we really looked into how long we were being managed on a mechanical ventilator, they averaged over 33 days of mechanical ventilation. So this really speaks to another issue with these patients is I mean, this is a very long times on mechanical ventilation. Why? Uh they require such a long time is not clear. But a lot of the thought had been from the covid pneumonia and the direct involvement of the lung tissue. But more recently, as you can see, a group out of the three sent major centers in the Netherlands had reported some interesting results on the diaphragm muscles. So another neuromuscular complication. The breathing muscle where one um There were some people who died in critical care in the Netherlands in this cohort That about 15% of their patients had direct viral load or direct infection of the diaphragm muscle themselves with car SARS-COV-2 RNA, indicating that it is possible in addition to having respiratory infection. Yeah, that you can have direct muscle infection with this virus, although it's important to point out that the majority of patients did not have evidence of muscle infection. These are patients who succumb to the disease and the managing the ceo. But then the patients compared to other patients with other who are in the issue and succumb for other reasons. When you compare the standing of the muscle tissue looking for fiber optic changes, you can see with these representative images that we're highlighting with and read the amount of fiber optic tissue change. That the amount of muscle fibrosis of the diaphragm was much higher in these covid ice you patients indicating, again, something a bit unique about the covid infection beyond just other forms of critical illness. So that is what happens when people succumb to covid. But what about the function of the muscle? What about the function of the muscles and people survive? Well, the gold standard of looking at muscle function or or or pulmonary function would be a pulmonary function. Testing forced vital capacity and and these sorts of metrics. However, these are also aerosol generating procedures so they're not widely available. Certainly not in people who are actively shedding virus with the with covid because of the risk for infection of the health care workers. So one thing that has been a very useful work around for us to get a sense of diaphragm function has been neuromuscular ultrasound or uh and and a lot of rehab facilities have access to the point of care units. And you can actually look directly at the diaphragm through the ribs, at the lower intercostal spaces. You should be eight or 9th intercostal space along the anterior axillary line, where you compete between the ribs where the diaphragm sort of domes up here. But you can actually see it right against the chest wall there and measure things like it's thickening and it's a thickness. So for measurements of contract ill Itty and atrophy. And let me show you, you know some work by a fellow Alexis Wolf and a very one of the senior resident selling for who worked really hard on this, scanning a lot of patients and looking through their critical care uh events so that we could understand a bit more of what was going on in these covid survivors. We looked at it 25 patients consecutively came into a rehab unit and performed these ultrasounds on them. And what you can do is, so this is showing you the ultrasound scan. You see this is at the eighth intercostal space between the 9th and 8th rib here intercostal muscle and then between these two bright lions. You see this is actually diaphragm muscle. And so this is sitting against the chest wall here and this vantage point this intercostal window. And you can actually easily visualize the diaphragm and many of these patients and when they take a breath in, as you can see in this person, you can see the thickening of the muscles. You can actually watch the muscle contract and look at the quality of the correction. And so this is a very um useful technique and dynamic technique to look at the function of the muscle and other people. This is another patient where there's a lot of atrophy of the muscle. I kind of highlighted there with those deadlines. What I show is that sometimes you can actually also use the anatomy. Like this is the piece of the loan, descending down and pushing that off the chest wall to confirm your anatomy and watch what it paralyzed or atrophied muscle is doing. And so we were really curious about how covid patients particular compared to other survivors of the critical illness or ice you survivors in terms of their persistent shortness of breath, which I mentioned, it was one of the most common symptoms, whether or not there was any neuromuscular underpinning to that. And so we we have this cohort of, like I said, uh, These consecutive patients, 25 patients admit it and I will point out that compared to other studies, that these patients actually are. The median was 43 days. Uh sorry, the average was 43 days on the on a mechanical ventilator. And with the covid survivors and that, and we were able to actually match that with another cohort of of non covid iCU survivors, 11 patients uh and compare their function. And so what we looked at were two main parameters that people who do a lot of the work with no mask ultrasound of the diaphragm. Look at it's the thickness of the diaphragm muscle at rest. And then how much it thickens when you take a breath in. And you can see that, although there's not, although there is some probably some atrophy compared to healthy control individuals which we didn't have in this study. If you look at the thickness of the muscle, the muscle bulk between non covid and covid survivors post, I see you are committed to rehab is not a significant difference. Um, and this dotted line here is indicating the lower cut off of her normal. So so some patients do fall below that lower cut off, but the average is about it. But what was striking and here's it was the thickening ratio or the contract ability, the diaphragm and particularly in covid patients who survived critical illness compared to non covid critical illness survivors, we see a very substantial and significant decrease in the contract ability. So instead of you need to contract and dick in the muscle by more than 20% to be considered normal. And uh, we we see often see very weak contract ability in covid survivors, which is probably contributing in addition to the the interferon camel lung disease, the covid pneumonia fibrosis, that can happen in the lung tissue. I think this implies that there's also a neuro muscular component to why these patients remain short of breath for so long. And we're only starting to look at this in some of the long hauler populations as well to make some more sense of it in terms of the non hospitalized patients. So I have a few more clinical cases here. I wanted to go through uh that that would maybe be a little bit more interesting, especially of course we get towards the end of the morning here. Um So, and I think they'll also highlight a few the key points. So in other cases, This patient here, Mr. Ari is a 66 year old male post Covid survivor. Uh He had a history of prediabetes in a prior cardiac arrest but he also developed a complication which we've seen in a number of patients who we're in the ICU. With Covid which was a spontaneous pneumothorax. And he actually required emergent placement of a chest tube. Uh And it's critical and is acute care phase before it can be inpatient rehab. He also required a traitor gastric tube. He had this severe pneumonia pulmonary embolism and he was prone three times. But and this ultimately is a protracted 48 course 48 day course of mechanical ventilation. We saw 219 days after he was disturbed from the I. C. U. And so that pneumothorax, what did that look like? Well this is the day before he had it and that was on the left the chest X ray that he had. And then you can see this massive lungs filled here where the air because the new authorities the air filling that side and deviation of some of the midline structures over to the left side. So they found this. And of course, uh immediately place your chest tube to decompress that air. And you can see it. You know. Actually a few days later they did another chest X ray. Yeah, this is actually a part of the Scout sequencing for a cT scan. But you can see the right hemi diaphragm was elevated compared to the left. And so this this finding, although not that sensitive, is usually very telling or very specific when you see this extreme asymmetry between the diaphragms for frantic nerve injury And the correlation to that, like I said, this is over 200 days later. Is that right side of the diaphragm uh is extremely thin and does not change in thickness with inspiration. Expert in exhalation compared to the left side, which in this patient we'll probably was weak initially. At the point that we saw him, the left side was contracting lovely great thickness, great appearance and great change in thickness to respiratory cycle in this patient. And so the diagnosis here was a right frantic monaural apathy and that was probably an i a transgenic um um reason for that injury due to the test tube placement, Which is just something to be weary about because we don't always have chest X rays or and these things are not always emphasised to us when patients come to rehab. But that really uh affected this patient who now over 200 days after his uh his acute care course was was going to attack and nursing home before coming back to the inpatient rehab. So he had an extremely long course and I think that some of the persistent dystonia, there was clearly related to the diaphragm paralysis from the frantic nerve injury And those can recover. But the recovery time for frantic nerve injuries are often in the order of, you know, one two years, sometimes as late as three years post injury before we seek a contract ability but return some patients don't recover all the function after nerve injury like that. Another case here, Mr. C. He's a 50 year old male with diabetes who also needed a chest too, but not for a pneumothorax and he um was in the ICU for 40 days on mechanical, been later and had an L. Tax day. We saw him 65 days after his discharge with persistent shortness of breath. And I think that one of the things in this patient on that side where he had the worst function was on the right side of the chest tube. So he may have also had some of a frank nerve injury. This is just showing the impaired contract ability over time. And it's but he also clearly from our clinical impression of the clinical exam with weak Shoulder and approximate leg muscles had some myopathy. But we saw that he, unlike that other patient who after 200 days was still having paralysis, he gradually improved. And by the time we uh um uh did his last scan which he came back for an outpatient scan, we actually saw that he had recovered very nicely his contract ability of that muscle, which gives us a little bit of optimism that even though there may be um direct muscles infection or even or indirect effects on the muscle that these things are recoverable. Um sources of impairment and that rehabilitation can work for these patients. And so I thought you know the time frame those is looking at this muscle weakness can improve. But for this patient it took before we come from an improvement of about six months. So at this point I thought I pause kind of recap what we just went through and take some questions. But I want you to know that you know of course that we did focus a lot of the neuromuscular complications. There's going to be talk tomorrow on more tailored to brain injury considerations for the Covid infections. But I want you to know that we've seen particularly in patient rehab world, major what the major neurological complications are with this infection. They're actually pretty frequent affecting both when you put together the peripheral nerve injuries and the myopathy. And I failed to mention on the on the diaphragm. Um in terms of diaphragm dysfunction, that was almost just 76% of those patients. Of the 25 with Covid had diaphragm dysfunction as opposed to I think about the third of the non covert control. So it's also very can be very prevalent. This this post I see weakness in these patients. The myopathy the DMG confirmed is less, is less common but still representing, You know, somewhere between 5-10% of the patients and the peripheral nerve injuries. In our in our rehab populations are Between 10 to 15%, most likely. Mhm. The clinical signs of these things, the clues that you need to have as a as someone who might be taken care of one of these patients, these asymmetries in their exam, asymmetrical weakness or in the case of the diaphragm, just persistent and proportion. Shortness of breath. The chest X ray or cT scan doesn't look that bad, but the patient is subjectively very dis nick or objectively that maybe include that the diaphragm is contributing not just the lung tissue itself is not the only reason these patients the shortness of breath. And then we use electro diagnostics and advanced imaging to localize diagnosed and established the the causes of these complications. And I think the inpatient rehab setting is an ideal place to do MG on these patients because they are often not available during acute care and also in the outpatient setting. It's still worthwhile and can be prognostic in terms of the severity and the often times were considering whether or not we need to refer these patients for surgical opinion as well if the injuries are too severe and then depending on what the causes, we sometimes have no idea that there is something like a hematoma which which is all the more reason to pursue advanced imaging to see if we can understand anything about what causes them in certain cases. We're learning as we go along with the pandemic, but the more we learn, the more we understand that these are this is over the complex issue. And there's not one, just one reason for these things. So stop there. Thank you dr franz. Uh I really appreciated your insight into this, I think, you know, as we as time goes on and you know, we're taking care of these patients on a longer term basis with a lot of these uh long collars that we might be seeing other things popping up things that we didn't necessarily attribute to the disease that we might be finding out later. Um and the interest of time to stay on on schedule. I still want to encourage questions. Um but uh we can pass the questions if we can pass the questions on to you uh as a roll in and then um if we can get your response to those, but uh we're staying on on time. I'd like to go on uh just to the next talk, but thank you very much, doctor friends, I really appreciate it.