Episode 76 - Neuromuscular Emergencies

Hi everyone, and welcome to the Neurology exam prep podcast. I'm Wayne Zong, I'm rising PGY3, joined by Dr. Billy Signarelli and Dr. Jeff Dewey, our System Program Director and Neuromuscular Specialist. Hey everybody, here you guys. Today's episode will focus on Neuromuscular Emergencies, but through the lens of arising trainees, it will soon be seen in these types of consults in the emergency room. So Dr. Signarelli, why are some common consults we see in the ED, and how would you approach these Neuromuscular Emergencies? Yeah, so I think that when you're worried about a possible Neuromuscular emergency, it's important to first kind of consider what are the key kind of consult questions that arise and in knowing that question, thinking about what is the worst possible thing it could be, though for the purpose of what we're doing today, you can kind of assume that it's going to be an emergency or on the scale of the worst possible thing that you might encounter in the emergency department. So the common questions that I've at least encountered, and I think many other residents have encountered themselves, things like numbness, other things such as weakness, and you may also get issues with breathing. Yeah, Bingo, I think the two groups of things you're going to get as the emergency Neuromuscular situation is dysmere and caracquinas syndrome, and if you're prepared to recognize either of those quickly when you walk in the room, everything else you have time to think about. And even though you have a little bit of time, but you don't have much and you don't want to spend the time trying to figure out what you're looking at. So I think we could address some of that today. Excellent. First off, we're trying to tackle numbness. So when I hear about numbness, the thing that kind of rings a bell, the thing that comes to mind most and likely comes to most residents is Guillain-Bray syndrome. So what is Guillain-Bray syndrome? It's actually a spectrum of disorders. And most commonly when you say, "Yan-Bray," you're referring to one in particular, known as acute inflammatory, demyelinating, polyridicular neuropathy, otherwise abbreviated as AIDP, but it can also include other types of Guillain-Bray syndrome of disease, such as acute motor-sense reactional neuropathy, known as M-SAN, and things like acute motor-axonal neuropathy, known as A-Man, and other variants, which some may be familiar with, such as Miller Fisher syndrome. These diseases are fairly common in terms of neuromuscular emergencies, and there's about one in a hundred thousand that are encountered in emergency departments in a given year. Most commonly, people that have a Guillain-Bray-like syndrome, or related disorder, present with distal of proximal symmetric weakness, which usually is following an acute infection, some sort of upper respiratory or lower GI-like syndrome, can also happen after things such as vaccinations, mainly with live vaccines. And it can also happen after things such as drug exposures and other severe medical conditions. The common presentation of these people outside of distal and proximal symmetric weakness is that the weakness itself is quite progressive and can be quite severe. When we're following these people kind of longitudinally, the native that we would expect is roughly around two weeks, but it can stay quite severe and even worse in a four-weeks. In that same cohort, about 70% of people can develop substantial, cranial nerve involvement with up to a third progressing to full-on quadriplegia and up to a fourth requiring some form of mechanical ventilation. Now when we're talking about the progression of the disease, it's important to keep in mind that while it can worsen for up to four weeks, if the disease continues to progress past four weeks or becomes even more severe despite treatment, it's important to consider other mimics of Guillain-Barre syndrome, things such as infectious, inflammatory, perineoplastic, or along the lines of CIDP. In line with the distal and proximal symmetric weakness that we see, other symptoms that are associated with the weakness include things such as early loss of deep tendon reflexes and commonly patients will complain of varying degrees of sensory loss and peristages. I know in my experience, the peristages in the weakness can sometimes be temporarily related where people come and first with peristages and afterwards develop severe weakness or vice versa, but I believe that is a product of the underlying condition and which type of acute pulmonary ridicule neuropathy, the patient is experiencing. In your experience, Jeff, have you seen patients present with weakness first, peristages first, a kind of a combination? Yeah, it really does vary. I think that the textbook presentation is a little bit of tingling that then rises and as it rises, the weakness follows, but as you said, they can one can be more predominant. And I think it's important to just clarify that it's not a length dependent neuropathy. It's often a distal predominant weakness or sensory loss, but the nerves are being attacked all over. It's just the longest nerves accrue the most damage first, but I think it's helpful to remember that little path of physiologic correlate. Yeah, good clinical tidbit there. Next up, we can talk more about the work up for this disease process. So for Guillain-Barré syndrome, things that are incredibly important as with all neurologic conditions is the neurologic exam and in the instance of this weakness and numbness that we see, it's important to do things such as serial strength of reflex examinations in these patients. Outside of examination and on the scale of further diagnostic interventions, one of the most commonly done procedures for patients with question of Guillain-Barré syndrome is a lumbar puncture and they commonly look for a high yield word that medical students and early residents will commonly try out known as albinocytological dissociation. Itself is simply elevated protein without associated pleocytosis, but it's important to know that this does vary with each type of Guillain-Barré syndrome disease in that elevated CSF protein can be absent early on in the course if someone got an LP very early and that can even be delayed to later on. When you do a lumbar puncture and you assess the CSF profile, it's important to note that if there is a highly inflammatory picture, such as greater than 10 wide blood cells, that should raise a red flag for alternative etiologies, including things such as lumb, sarcoidosis, HIV or other meoplasms, which can affect the CNS axis. In terms of EMG, electromiography and nerve conduction study, not particularly helpful in the early period, as commonly the studies can be normal or may have just minimal changes things such as prolonged or absent f-waves, so the studies don't accurately show the evidence of demyelination in the early period, but as things progress in the symptoms become more severe, those findings will likely become more evident on an EMG and nerve conduction study. The last thing about diagnostics that is important is when to get an MRI. So in my experience, an MRI for the purpose of a patient with a clinical syndrome that seems most consistent with Guillabre is not commonly routine. It does get ordered in the instances of atypical history or unexpected exam findings. For instance, patient may have mixed hypo and hypereflexic features or they may have hypereflexia with numbness, but then also pyramidal track signs. In instances such as this, MRI of the spinal cord and lebosacral nerve roots is usually ordered to exclude things which can be memakers such as two religions on the spinal cord or severe generative changes and even spinal cord compression. Jeff, you commonly get an MRI of the lung bar spine for patients with Guillabre is that sort of just academic. I think it's an interesting academic exercise because you'll often see this enhancement of the Caudi Aquina, which is really the ridiculous part of the ridiculous neuropathy or neuritis, but I've never seen an MRI of the lumbar spine confirm a GBS diagnosis. It's really more important when the history or the illness script doesn't quite match with a subacutely or rapidly progressive process. If there's a sudden onset, if there's any back pain and you can actually see pre-significant back pain in GBS, but of course, if it's a legs-only syndrome and there's back pain in autonomic dysfunction, you're also going to worry about conus versus Caudi Aquina syndromes. I have a low threshold to get it, but if I'm seeing everything else you're mentioning, I think it's pretty low yield unless you're really worried about a memaker. I would also just add to this diagnostic list that I think hopefully goes without saying, but you would get the basic labs. The other thing you always want to get on these patients early on is an ABG. The peripheral oxygen set, and we'll talk about complications, is the last thing to go. That's first on my list when I walk in the room and I have any concern for respiratory dysfunction. Jeff, as a rising FGY2 of the incoming class who are commonly seeing these ED consults, when you first assess a patient, what are you looking for with associated complications? This is the radar you want to tune as a trainee, as the sick versus not sick or the o-goodness factor. I have different words for it than I'm going to put in a podcast, but you want to be able to walk in the room and know how urgent the next steps are, which is really the ABCs. Those are the things that are going to get you. If it takes you an extra hour to figure out its GBS and start IVIG, that's not a big deal. But if you miss a chance to intubate electively versus urgently, that could make a big difference. I think I'm looking at the patient, are they in distress? Are they using their accessory muscles to breathe, trapezius, SCMs, intercostals? Are they speaking in full sentences to me or do they have to stop and take breaths? Are they having problems keeping their head up, suggesting mid-servical weakness at the level of the diaphragm? Then, of course, level of arousal and consciousness and vital signs in the monitor will tell you a lot. But, again, don't feel good about a decent SPO2 in a patient who, to your eye, looks like they may be teetering on respiratory distress or respiratory failure. Always get that ABG first and let the clinical picture sway you more than any of these values other than perhaps PACO2. The other thing I guess I would add on the initial assessment is the hallmark finding of these autoimmune polyradicular neuropathies is hyporeflexia, sometimes even before there's weakness in the limbs. That has to do with that early attack on the nerve roots. As soon as that sensory motor, AFR, and refructs loop is sufficiently interrupted by inflammation, you're going to drop your reflexes. When a patient has normal or particularly if they have brisk reflexes, you should be thinking about something else. Unless, it's one of the very strange variants like fringo cervical brachial disease, in which case they may have preserved DTRs, especially distally. But those are the exception, not the rule. Thank you. We can summarize all of the respiratory support and triaging towards the end. After we have clumped all the disease process together, how would you approach the acute treatment of GBS? So in a cute setting, two modalities that are commonly used for treatment of GBS are IVIG and Plex or Plasma Freces. Now, these two treatments have actually been studied in the past and studies have shown that no significant difference in reducing the amount of disability in patients with Gambray than a treated with either at four weeks after onset. Knowing that, the choice of which one to choose sometimes is institutionally dependent. And for example, at our institution, Yale, it's much faster many times to get IVIG ordered and sent to the bedside for these patients than it is to get Plasma Freces or Plex. These Plex also require specific lines and it also requires working with the microbiology lab to get everything set up. So going along the lines of IVIG, the standard treatment, everyone should know, is 2 grams per kilogram of ideal body weight, which is done over about three to five days. Whereas Plex or Plasma Freces is about one to one and a half exchanges that is done roughly every other day for a total of five exchanges. With both of those, it's important to note that another treatment modality for other disease processes, steroids, is what I'm referring to, is not commonly used or even recommended in the setting of Gambray syndrome. Thank you, Billy. In terms of weakness, there is a very broad differential. The acuity of the presentation can guide how we treat our things in the emergency room. To target this more in the lines of neuromuscular, how would you approach an indolent process of weakness through the lens of a neuromuscular doctor? So from my standpoint, as with all neurologic and neuromuscular emergencies, it's very important to get and accurate history from the patient. If we're considering neuromuscular junction pathology, one of the tell tale signs will be some form of fatigable weakness. What I'm commonly referring to is the most known neuromuscular junction disease, myesthenia grobis. People that present with an exacerbation or new onset symptoms of myesthenia grobis kind of fall into two general demographics. The disease process itself is bimodal, being that it can present earlier in someone's life, saying they're 30s, which is more common in women, and then later on in someone's life in their 50s and 60s, which is more commonly seen in men. You may ask, what is myesthenia grobis, as we learn in medical school and then we experience in residency, myesthenia grobis is the presence of auto antibodies, which target antigens on the post synaptic nicotinic acetylcholine receptor complex. But all of this is occurring within the neuromuscular junction itself and on the post synaptic neuron. What happens is that these antibodies bind to this nicotinic acetylcholine receptor. They prevent its activation cross-linking, and over time the receptor is destroyed via complement mediated destruction and can then be enveloped to the point that there is a significant drop in the end plate potential, and there's a lack of activation of the muscle despite the acetylcholine that's lingering in the neuromuscular junction. That then clinically manifests as fatigable weakness, and we can even see the decrement in the end plate potential on EMG studies in patients that have myesthenia. As I mentioned before, with initial evaluation history is paramount, and these patients with myesthenia or myesthenic exacerbation will have fatigable weakness, which you can elicit with sustained upgaze or repetitive flexion extension, abduction, abduction of the extremities. You can also witness ocular bulbor muscle weakness, so patients may have notably visible facial droop, or they may endorse a history of double vision near the end of the day. Perhaps they're watching a long movie, and then the beginning they can see the movie clearly, and at the end they just know everything is just blurry. But it's important to know that the disease presents in a polymorphic manner, and that some patients may have ocular symptoms, and then others may have more symptoms associated with extremity weakness. In addition to fatigable weakness and weakness of ocular bulbor muscles, as we discussed previously with the importance on ABCs, it's very important to note that myesthenia can lead to respiratory failure or severe dysphagia, which can lead to aspiration and respiratory compromise, and those numbers are along the range of 10-20% of patients that have myesthenia. When we examine these people in the ED, and we have a suspicion that there's a neuromospular junction pathology, we want to really elicit that fatigability and assess for other corresponding findings. So, like I mentioned before, we'll have sustained upgaze and we'll be looking particularly for tosis, or the development of dypopia. You may have a patient repetitively do-adduction and abduction to see proximal weakness and fatigability. You can utilize neck, flexion, and extension to get another more tranquil form of proximal weakness, and then you could even have a patient count to assess for respiratory weakness. This is the count test where we have patients take a full deep breath and then proceed counting from one to the highest number that they can reach. All of these are metrics to try and identify pathology in the emergency department that is concerning for a neuromospular junction process, which is most commonly myesthenia progress. But outside of physical exam and history taking, there are some lab studies that we routinely collect, or less routinely collect, and they each have sort of their different utility in that many of them take some time to come back, but we can talk about a few of those. Three common ones that we see drawn on psorologies are fetalcholine receptor antibodies, muscle-specific kinase receptor antibodies are musk, and LRP4, which stands for LDL receptor-related protein 4. Jeff, do you send labs on every single patient that presents with a likely myesthenic like syndrome in the emergency department? I do, and there's a couple of reasons. First of all, they're pretty high yield, as you said, percentage-wise. We have a good chance of finding an antibody, and LRP4 is now, I think, being used more clinically than it was even a year or two ago, and there are other antibody tests that are being developed when you might see as anti-titan. With LRP4 and Titan, it's not entirely clear if they're pathologic or just secondary markers of pathology, so we interpret them with a grain of salt. But the point being, I do send them as early as possible, because once you give a patient IVIG, if you're going to do that empirically for an exacerbation, you make it a false positive going forward. So your best chance at a true positive is before you've done any immune therapy, either immunosuppressive or sort of immunoeadjunctive with IVIG. And Jeff, a common tool that neuromuscular doctors use is an EMG, but how commonly do you use it as an inpatient addition diagnostic tool? It certainly has a role inpatient, but I think most cases are fairly clear clinically, and you can use some other tips and tricks at the bedside to come up with what's going on, and really what you're trying to prove is fatigability. You've probably seen videos of the ice pack test where a patient with TOSIS will have an ice pack put over their eye, and very briefly, after a minute of ice, the TOSIS is much improved and then it gets worse. That in itself is very suggestive, and it's really the same as doing a repetitive nerve stem on an EMG of the orbicularis muscles, which are easier to access than the levators. But anything that convinces you that the weakness is fatigable and narrows your differential quite a bit. So if you feel confident in myosthenia based on a history and an exam showing fatigability, our repetitive nerve system is probably not going to change your immediate management. And we'll talk about ways you could get fooled by limbs in a little bit. That might be a reason to do this on the earlier side. But the quality of studies in the emergency room is terrible. It's better inpatient, but you really want to try to do this in a controlled lab with electronic suppression. It's to give you a high quality study because the margin of error, you're looking for a 10% document in amplitude. So a little bit of background noise can screw that up quite a bit. So we would like to have a high quality study if we can. Yeah, Jeff, you mentioned limbs. So to touch upon that, the abbreviation LEMS Lambert eaten myostenic syndrome related, quite somewhat different from myosthenia gravis in that in both diseases, there are auto antibodies, which are in the neuromuscular junction. But in this case, now we're focusing on the pre-snaptic neuron and we're targeting calcium channel. So the disease pathology, while it does have fatigability, it sort of works in the opposite direction where people and patients have proximal muscle weakness and may have ocular symptoms as well, such as tosis, but with repeated use of these muscles, we find that they actually become stronger and that weakness kind of improves. This is a disease that is parented plastic and most commonly seen in patients with some form of lung cancer, likely small cell lung cancer. So many times it's not at least in my experience, the presenting symptom of someone with lung cancer, but it can be a finding when that disease has progressed later on in their life. Yeah, I think that's a huge distinction because you don't want to miss a perineoplastics syndrome in there by an associated pregnancy diagnosis as early as possible. And I just want to specify that the kind of activation that makes the muscle stronger in limbs is tetanic activation. So when you know one of the classic pearls we learn in neurology residency is a slow hurts, repetitive nerve stimulation can look the same in limbs and mg, but at 20 hurts a very fast hem creates a large amplitude increase in limbs and that's what distinguishes it. Tetanic contraction is essentially the same thing, you're firing the maximum frequency of impulses through the neuromuscular junction and thereby overwhelming calcium clearance and actually strengthening or improving the release of acetylcholine in there by muscle strength. So we don't really do these 20 hurt stems, even though they're a fun academic point because the patient can 20 hurt stem themselves without the pain by just contracting their muscle fully and holding it for 10 seconds. And one of the telltale signs of limbs, even without an EMG just at the bedside is depressed reflexes that improve after 10 seconds of tetanic contraction. So if you see that, it's not myesthenia. You can almost be confident that it's lens and then go about proving it and looking for malignancy and such, but it's a great tool to have in your back. Yeah, once again going back to the importance of that neurologic exam. So that we discuss two most common neuromuscular junction disease pathologies. We can talk a little bit about treatment. So in both instances, and just like we can on brace and drum, the need for respiratory support is very important, perhaps even more so in patients with myesthenic crisis because of the severe diaphragmatic and respiratory weakness that can result. So when these patients is really important, as we will later on to discuss to evaluate your ABCs, and then once you have made the clinical determination on the best respiratory treatment moving forward, whether that be non-invasive positive pressure of inhalation such as bipat or intubation, then we can move on towards working on treating the patient's exacerbation. So to briefly touch base, those two things that we would be looking at are very similar to Guillain-Barré. That would be once again IBIG and Plex, which have been studied for the treatment of myesthenic crisis, ultimately some studies have shown that Plex may be slightly more effective and quicker, and that's especially in musk antibody positive myesthenic syndromes. But I believe both are still commonly used together and have overall equal efficacy for acetylcholine receptor positive antibody related myesthenia, is that, right? Yes, that is correct, and it a little bit has to do with comorbidities, too. We think about the issues with that IBIG being hyper-quagulability, and then with Plex being fluid shifts, a central line, a longer treatments. So there are risks and benefits to either, but yes, if all things being equal, I think I would probably prefer Plex when the antibody is unknown. And another common medication that is given in myesthenia is predestineine, or myesthenine. When would you give and hold it, especially in the impatience that? So my big concern about predestineine or myesthenine is some of its side effects. So if you think about the syndrome of colonesterase inhibitor poisoning, or organophosphate poisoning, it's basically leaking from everywhere, lacrimation, salivation, diarrhea, vomiting, urination. And so that's fine, except when you're trying to protect somebody's airway who's teetering on respiratory weakness, and they start having hyper-salivation, and they already have a bulbara weakness, and they may not control their secretions. So I'm really cautious about mestonon, partly because it's not a disease-modifying drug. I have never seen a scenario in which mestonon saved somebody in myesthenic crisis from intubation. And that would be the one time you would use it on day one, is if you're trying to prevent intubation. So there's really no benefit in starting it right away. I think you're better off waiting, going slow. Now if they already have the tube in, that's a different story. But when there's a little bit of unknown, I don't think mestonon is worth the risk personally. And Billy, another part of treatment are steroids. And we can briefly talk about this, and it's related to ICI, induce myesthenia, worry your thoughts on steroids. And steroids are important for treatment. Oftentimes, patients are on them in the outpatient setting at higher doses, and when they come in with an exacerbation, that dose is decreased because steroids can paradoxically worsen symptoms mainly in terms of worsening secretions or worsening muscle fatigue while they're already undergoing a crisis while inpatient. So I've seen, for the most part, steroids either entirely discontinued or just significantly decreased dosage wise, but things such as high dose steroids are not recommended for patients with a myosthenic crisis. And the setting of the immune checkpoint inhibitor related myosthenic crisis, it's actually the opposite because this is sort of how I think of it as more of a severe robust immune response. So you want to quell the immune system with high dose immunotherapy, that being steroids. So ICI checked related myesthenia, steroids is commonly used, but in true myosthenic crisis where there's acetylcholine receptor antibodies, it's avoided. And you brought a couple of thoughts to my mind with those comments. So yeah, I think actually, if someone comes in on mestinosis steroids, I hold them both in the setting of crisis. For the reasons you mentioned the steroids, the other thing is when patients are cruising toward a crisis, they're getting more symptomatic. It's not uncommon to start taking more mestinone because that transiently relieves the symptoms. And I've seen it and definitely heard about patients showing up taking two or three times their prescribed dose of mestinone for the last week and giving themselves colon esterases inhibitor toxicity, which looks almost identical to myosthenia, except with the excess secretions and everything. And the only way you really know is to hold the colon esterase inhibitors while you manage the airway and do all these other things. So I think it's really important to remember both of those in the acute setting. And then yeah, I think in neurology, we often think of IV corticosteroids as one gram a day for three to five days. But that's really the CNS dosing and for peripheral diseases like myosthenia, you can often get away with 125 milligrams of solumedral daily for five days and get equal efficacy with much less aggressive side effects in terms of glycemic issues, insomnia, agitation, psychosis, etc. Excellent. The next part of weakness as we move more approximately in our neuromuscular emergencies would be closer to the spine, especially the anterior horn cell. How would you approach these emergencies, Billy? Yeah, so when I'm worried about pathology that involves the anterior horn cell in the acute setting, two things that I commonly would be concerned about are a first present patient of undiagnosed ALS or more severe acute flaccid myelitis, the one being the generation of the spinal cord and then other being inflammation of the spinal cord. Now just to briefly touch on ALS, we've mentioned it before, but it's one of the most common forms of motor neuron disease and adults. And in the emergency department, you will see upper and lower motor neuron findings, things like atropyphysiculations, hyper-reflexion and hyper-reflexion spasticity, generally these people only present to the emergency department with severe symptoms requiring intubation and it's not common for them to present with severe symptoms from the beginning of their diagnosis. What's more likely to be found in the emergency department is acute flaccid myelitis. So this is pathology of the lower motor neurons within the brainstem and the spinal cord. These anterior horn cells and it's commonly in the sending of a viral infection. Now many years ago, worldwide, the most common disease organism was polio, but that has since been eclipsed by West Ninovirus and more recently eclipsed by Interovirus D68. Now these people will come in with a common pro-drome of respiratory upper respiratory infectious like symptoms, cough, runny nose, fever. You may even have patients with GI pro-drome, so diarrhea, abdominal pain. And once infected and involving the nervous system, this disease process can progress quite rapidly over a scale of a few hours. Patients can have wide range of symptoms, which range from an isolated aseptic meningitis with things such as headache, neck pain, nukal rigidity, can even involve later on the entire neural axis leading to severe weakness and possibly even encephalitis if involving the brain. Now the symptoms that we'll find on exam of these patients in the emergency department, similar to the previous ones, are muscle weakness, generally with propensity to have proximal upper extremities involved more, usually in an asymmetric manner. You will also have loss of decreased tone, hyperreflexia, and in severe instances, you will have possibly respiratory failure or bulbor muscle weakness leading to dysphasia and aspiration. Yeah, so I think with acute flaccid myelitis epidemiology makes a difference and a really careful social history and travel history and just general history are always important. I was still the students, more history, less mystery, and it's important to remember that we think of polio as an eradicated disease. But as of recent data, it's still endemic in Afghanistan and Pakistan. And it's rising around the world, and also as we've seen it may, there's certainly a risk, it could re-emerge in the United States with vaccine hesitancy and the anti-vax movement. So it's important to always keep polio in the back of your mind. Every year, there's a case report about a polio case in the United States. And unfortunately, as vaccination levels start to drop, that may erupt very quickly. But certainly in, for instance, New England, where we are, probably West Nile is something we see much more commonly. I see that once a year on service. And then obviously, as you mentioned, the center of iris strain that's kind of making an emergence is a little bit scary too. But all of these typically have some form of febrile illness pro-drone. It seems a little counterintuitive to think of ALS as a neuromuscular emergency. But not uncommonly, patients can sometimes actually ignore bull bar onset ALS for much longer than you would believe. And so they show up in impending respiratory distress or having aspirated. And then a lot of times what happens is it's a patient with a known diagnosis who has chosen to forego or at least postpone tracheostomy or a pegged tube and then aspirates and has a sudden decline or gets another illness in the stips them over the edge. So it is not uncommon to see ALS as a denovodinagnosis in the emergency department or ICU once or twice a year at a large center, at least. In terms of workup for this pathology, we commonly work on MRI. And when we're assessing acute fibrolysis or anterior horn cell pathology, things that we will see are increased T2 signal or enhancement of the ventral horns of the spinal cord and nerve roots of the spinal cord. If we see that or if the study is unremarkable in both instances based on the asymmetric weakness and concerning clinical features, we will also likely order a lumbar puncture to assess CSF and evaluate the CSF profile. In the instance of acute flaccid myelitis from a viral etiology, CSF studies will show in the early phase a neutrophilic pleocytosis that shifts to a lymphocytic pleocytosis usually within the scale of a few days. This is also associated with elevated protein in the scale of 100 to 300 mg/dL, but can go up to 1g/dL by the second week. So you may see some very high levels of protein, two or second week after the disease process has been initiated. And then lastly, treatment for this disease is actually quite challenging. While Guillain-Barré and myesthenia gravis can be treated by things like IVIG, Plex and in some instances steroids as we discussed, those modalities have unfortunately not been shown to be affected in acute flaccid myelitis. So the mainstay of treatment is supportive care, but whenever I hear the term supportive care, I always sort of wonder, well, what is that, you know, entail, what is supportive care? Jeff, do you know what they refer to in terms of supportive care for these patients with acute flaccid myelitis? A lot of it probably has to do with contracture management and bowel bladder issues. Certainly, these patients are at risk for nearby structures being affected and having issues like that. There's also sometimes an element of pain, although often not. And then respiratory and nutrition support, as you mentioned. Thank you, Jeff. And thank you, Billy. We move on to our last anatomical region, which is the muscle itself, a much rare presentation in the emergency room, but still possible. How would you approach myopathies in acute cell? When evaluating myopathies in the acute setting, a lot of times patients will come in and they will complain about some form of generalized weakness that you later through your history and exam elicit that they have severe proximal greater than distal weakness. These kind of patients should ring a bell that there's likely either a neuromuscular or myopathic etiology, either neuromuscular or myopathic disease process that's occurring. The difference between the two is that while myastenic neuromuscular junction disorder diseased patients will have decreased reflexes over time, patients with pure myopathies should have relatively preserved reflexes unless the muscle weakness is severe or it's in the later stage of the disease that is maybe a disease that's progressing. In those instances, you might get some diminished reflexes, but for the majority of times, there should be some preserved reflexes that can kind of separate the two. The presentation in general is this proximal greater than distal weakness, which does worsen over longer periods, and it's not likely to present with immediate respiratory copper mines. I feel like that is a much later manifestation of the disease. Most of the muscle groups that are affected aren't entirely the diaphragm. It's likely something more proximal, the biceps and the quadriceps. Jeff, have you ever seen a myopathy or myocytis where the diaphragm is affected first? They initially present with respiratory copper mines? Not in the inflammatory setting. I mean, there are patients with congenital muscular dystrophy who can have early diaphragmatic weakness, but no. In the acute ED emergency setting, nothing I've seen. I'm sure it's been case reported, but I'd expect this as sort of as much. We're evaluating myopathies. It's important to order some diagnostic tests, which can really kind of ring the bell that there's a muscle pathology occurring. The most common one you'll see ordered, usually by the emergency department itself is creatinine kinase or CK. That's important because CK can also be elevated in rabdomylicis, which would be muscle breakdown or muscle injury due to some other pathology, likely some other form of medical illness. But it can also be elevated in patients with primary myopathies or myocytis disease processes. Another lab that is ordered, but maybe not commonly utilized is myoglobin. When muscles are inflamed or irritated, broken down, outside of CK, myoglobin can be elevated in the serum, but can also then be excreted in the urine, so you can test for both my elevated levels of myoglobin in the serum and myoglobin urea in a urine study. In addition to serologies and urine studies, we utilize EMG and muscle biopsies in patients that have concerning features of myocytis that has progressed. I know most recently I had a fairly interest in case of vasculitic myopathy where initial muscle biopsy was normal, but symptoms had progressed to the point where repeated biopsy was warranted that did show inflammatory findings. That was actually based on repeated MRI of the muscle, which is another diagnostic tool. If you're worried about myopathy or myocytis, usually clinical diagnosis should be sufficient, but an MRI can show inflamed muscle where it would be T2 hyperintensities or evidence of a DMA within the muscle group in question. One of the some types I had already mentioned just now, the necrotizing or vasculitic kind of myopathy is part of a group of many different immune mediated myopathies, which exist, and these are the things that were worried about when people have a myopathy because they could present so severely. So to go over those again, we have necrotizing myopathies and inflammatory myopathies, and these include things like polymyocytis, dermatomyocytis, and inclusion-bodymyocytis. The clinical presentation is a rapidly progressive disease that's associated with very high levels of creatinine kindness, and you can find inflamed muscles on biopsy in review of histopathology. If we're considering non-immunmediated myopathies, this is when you should consider things such as drug toxicities, infections, endocrinopathy, or even some hereditable myopathies. In other instances, patients with transplants can develop graft versus host disease, and they can develop severe myopathies in the setting of autoimmune inflammatory states. Lastly, treatment of myopathies is fairly similar to some of the other neuromuscular emergencies we've encountered, but in this instance, steroids are the mainstay. We like to start out with, if possible, hydeosteroids such as methylcredinisolone, 0.5 grams a day to 1 gram a day, roughly for three to five days, and this is followed up by methyl trexate at 0.3 milligrams per kilogram, weekly-based. Later on, if symptoms are still severe, despite initial immunotherapy, second line would be retoxamab, which we can do at 750 milligrams per kilogram, given twice, with doses roughly two weeks apart, and then as with myesthenic crisis, and with Guillain-Barré, IVIG has also been shown to be an important therapeutic modality, and we give it a dose of just like previously, two grams per kilogram over three to five days. Thank you, Billion Jeff, for a neuronatomy-based approach to neuromuscular emergencies. As we evaluate the impatience in the ED disposition, it's commonly dictated by the respiratory needs. Jeff, how would you assess someone's respiratory status? So again, I think the first assessment is actually qualitative. You will be able to tell, and especially as you do more and more of this, who looks scary from a respiratory perspective, and who doesn't, are they able to lie flat, or are they sitting up, hunched over, excessive breathing, drooling, speaking in one to two, or all the things we talked about earlier. But if you want to put some numbers on it, I think that main things you should be doing are one, again, trust your ABG over your peripheral oxygen saturation. So I have a low threshold to get an ABG early. You can trend CO2 on VBGs, whatever you're doing, that's minimally painful for the patient, watching it's really their ventilatory status that's going to be the issue, not their oxygenation. The other thing that you can do early and often are measures of respiratory strength, such as negative respiratory force and forced vital capacity, or what we call NIFS and FECs. And I think of sort of basic levels for the average sized adult. You want your NIF to be minus 20 or more negative, that's kind of the bare minimum. And your FEC to be around 1.5 to 2 liters, again, for the average sized adult. Take that with a grain of salt or adapt it to the body habitus. And one way you can kind of get at this without any specialized equipment is what we call the single breath counting test. So you have the patient inhale as fully as they can. And then as they're exhaling, you want to have them count until they run out of air. And you can't have them count as fast as they can. That'll be an accurate. They should count about this fast. 1, 2, 3, 4, and then wherever they end up, you multiply that by 100. And that is their approximate FVC in CCs, or sorry, excuse me, a milliliters. So if someone counts to 20, they have a two liter forced vital capacity. Anything less than 20, I get concerned, especially if they're a normal or a bigger person. And then I map that all together with the other things we've talked about. And I have a fairly low threshold to intubate, as we'll talk about. Yeah, to echo a lot of what Jeff said, I think that a quantitative kind of way to assess these patients and then to determine their level of care really does start off with looking at the whole patient and really focusing on those ABCs. So to kind of go off from that a being airway is probably the most pertinent thing to assess in these patients if you're worried about a neuromuscular emergency. Because breathing requires strength and functioning of bulbar and upper airway muscles to clear secretions and prevent aspiration, which can then be a vicious kind of cycle where they have respiratory weakness, they aspirate, they have worsened respiratory weakness, and then you have a patient that is in dire need of intubation. So it's really important to kind of see those imminent respiratory failure signs, which on exam commonly can be accessory muscle use, which is used of the external intercostals, the scalenes, the strachylamastoid, abdominal muscle use such as when coughing or breathing, you see those things that's usually someone that's about to get infinitely intubated anyway in the emergency department, but it's good, it's important to pick up on those things, especially if they just start appearing in front of you. When you're examining the patient, so some key exam features that can be used as both metrics of a patient's respiratory function and helpful tools to know about a patient's level of care once they are admitted from the emergency department are things like diaphragmatic strength, level of bulbar dysfunction, presence of paradoxical breathing, and as Jeff mentioned, the single breath counting test. So for diaphragmatic strength, you can actually approximate this by looking at a patient's neck, flexion strength, if that's fairly weak, you can make an assumption that there is some weakness of the diaphragm at the very least, and this is someone that may need more frequent respiratory monitoring, in terms of bulbar dysfunction, it may be immediately evident through the patient's speech. Quite nasally, that could be indicating a flaccid dysarthria, they may even give you a history of difficulty swallowing their last meal or coughing up increased secretions, they may even be having a turkey sandwich in the emergency department start coughing hot in front of you, so these are things to really kind of pick up on and consider warning signs from pending respiratory failure. The paradoxical breathing is something that occurs when you see the abdomen sort of in desynchrony with what a patient takes their breath, so when we normally breathe, diaphragm goes down, and then you kind of get this hole in your stomach, and then when we breathe out, the abdomen comes back out, that can be reversed, and when that is reversed, you have a paradoxical breathing, and that is a strong sign of impending respiratory failure, that means the muscle is too weak to kind of to compensate. Lastly, the single breath counting test, as we touched upon, is a fairly good metric to approach forced vial capacity and very useful in finding a patient that may be a high risk for respiratory failure. Jeff, as you mentioned earlier about the common test that we do in the in conjunction with our respiratory therapists is the force of vial capacity and the negative inspiratory force, how common do you see we do the maximum expatory pressure? My experience with those is typically more in the outpatient setting. There is some evidence mainly in degenerative neuromuscular diseases, muscular dystrophies in particular, but also ALS, that the earliest signs of respiratory failure are reduced, maximum inspiratory and expatory pressures, but if you ask any pulmonologist, they will tell you that these are the hardest for the patient to perform well, and are the least reliable, commonly used aspects of a PFT. So I always take it with a grain of salt, if a patient's FVC and FVV1 are 100% predicted, and they have 40% MIP and MAP, that may or may not be relevant. So I don't typically use them in the emergency room for all of those reasons, especially if there's any oral weakness, there's going to be an issue with oral seals around the device, and their MIP and MAP will not be very reliable. So I tend to use them more as predictors of long-term respiratory failure and more slowly degenerative conditions. Thank you. And now that we have a good triage of our patient assessment of their respiratory needs, how would you make the decision between BIPAP and like non-invasive ventilation and intubation? What is your threshold to go for BIPAP versus straight to intubation? I much prefer to just go for endotracheculine intubation. Again, these are more than likely going to get worse before they get better, and BIPAP does not protect the patient against aspiration, other mechanical pressure issues externally on the airway, and it just is much safer to intubate. It's often pretty quickly reversed if they're sort of teetering on the edge, but in also in a lot of cases, they may spend a week or two needing respiratory support, and they're just not going to tolerate a BIPAP mask for two weeks straight, not to mention the other issues. I just covered. So I could probably count on one hand to the number of patients where we've ridden the edge of needing an ET2, but stuck with BIPAP and got away with it. So I have a very low threshold, just to electively intubate or originally intubate. It's almost always reversed within a matter of days in some of these shorter or more acutely progressive diseases that are easily reversed, where there's no nerve or myelin damage. And so I think unless the patient has a DNI and non-advasive ventilation is your only option, ET2 is much better. Yeah, I would say for the majority of cases, it's best to do the most effective thing to prevent respiratory failure, that being intubation most commonly, and how I kind of look at it when I see these patients with neuromuscular junction, weakness, neuromuscular disease pathology. I try to look at the whole clinical picture and kind of see where this trajectory of this patient is going in the moment, which is tough, but like Jeff said, a lot of the times it's just there already seeing you during an exacerbation and things are going to get worse. So you really should have a low threshold for intubation, but some useful metrics that people in neuromuscular medicine and some residents in the emergency department commonly echo that can be used to help sort of point towards the necessity of intubation are abnormalities in the respiratory function tests. So a good rule of thumb that we commonly talk about is the 20, 30, 40 rule. And so that's just a way of knowing the lower limits of these respiratory function tests and when to kind of really pull up the red flag like it's time for intubation. So to kind of break that down, the 20 part is referring to forced vital capacity. So if you have a forced vital capacity that's left then 20 milliliters per kilogram, that is highly concerning and is a strong indication that if the patient isn't nearing intubation, it's something you should be considering. The 30 is referring to either maximum in spritory pressure or negative in spritory force. And that is dependent on your institution, what metric is recorded by the respiratory therapist, but here at EL we do negative in spritory force. So less than negative 30 centimeters of water is highly concerning. And lastly is maximum expatory pressure, that's lower than 40 centimeters of water in recorded on respiratory therapist reading that's something you should be highly concerned about. Other things clinically that would kind of lead me personally towards wanting to intubate a patient are severe ball bar weakness, severe dysarthria to the point they're having difficulty forming words or any evidence of. Immediate aspiration or recent aspiration, I can say I'm talking to someone and I know to sit there aspirating, I think it's probably time to start with the intubation because treatment as we know can be effective, but usually the improvement is not as readily apparent and can take the scale of days for some pathologies and weeks in the setting of other pathologies. It's probably good just to think about sort of a big picture for how these patients are managed once you've triaged them from the emergency department in terms of dispo, I think I always. If I'm anywhere near the fence, I aim for a level higher than maybe I think they need better for them to spend a day and step down when they didn't need it or a day in the ICU when they maybe they didn't need it, then the other way around because. Things can happen on the floor with more nursing to patient ratios and things that just don't get noticed when they should and these patients often can get into a fairly vicious spiral of respiratory weakness leading to hypercarbia making them sleepier making their weakness worse and they can snowball very quickly. So I tend to be very cautious about disposition once the patients stable you've initiated your immune therapy, you're not necessarily out of the woods. Some of these diseases will take one or multiple rounds of immune therapy or may not respond immediately. And even when they do plateau, there are other things going on and so I just wanted to drive everyone's attention to the things that will sneak up on you if you're just focused on their sensory motor exam and that is things like pain. So GBS in particular can be quite painful, a lot of the inflammatory myopathies can have pain in the neural, the neuropathies patients tend to respond well together, pentanoids. But I have seen cases where we need a short course of opiates or even a PRN opiate on hand for sleep or severe exacerbation. Nutrition is a huge issue, these patients need caloric intake, they need to maintain their muscles, they need protein. They have a very low threshold to place an NG tube with any bull bar weakness, if there's a concern for aspiration, especially if it's a weekend and you can't get a swallow study for three days and they failed their bedside swallow. And then you can, you know, complete electrolytes and do all the other things you need to do. And electrolytes are particularly important or relevant because a lot of these patients can have significant dysautonomia. So anyone with an acute inflammatory neuropathy or a limb's exacerbation needs to be on telemetry need to watch very carefully for even proxysmal arrhythmias, blood pressure swings, as well as bowel and bladder function, urinary retention is quite common and can lead to some issues. So you should be bladder scanning. I've seen patients need in willing catheters need to be very aggressive about bowel management regimens. And then of course, this is just seriously challenging and scary. By definition, unless they have an encephalitis with West Nile virus or an acute flash of myelitis, cognition is not affected. And so these patients are often very anxious, scared, depressed. I've seen patients spend a month or two on a ventilator over the holidays. We've had patients who are pregnant and we're trying to manage that along side their autoimmune disease. And so it can just be insanely challenging for everybody involved. So take care of the patients, take care of their families, take care of yourselves, bring in all the social support that you need. And then again, I think, you know, just constant vigilance with these patients because they can turn on you on a dime in the first few days. I think the best predictor of the next few days is the first few days. So just be really careful early on. Thank you, Jeff and thank you, Billy. We hope that you found this podcast helpful, especially for the incoming BGY2's as they tackle on the arduous year of emergency room consults. We also want to congratulate Billy on his fellowship as he moves on to his next endeavor. We hope to have you on a podcast again as the next new muskere expert. Thank you. I love to be back. [MUSIC]