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The Neurotransmitters: Clinical Neurology Education
IM Board Review #9 - Neuromuscular Disorders
We continue our series targeted at people preparing for the internal medicine (IM) board and in-service exams.
Today's topic: neuromuscular disorders!
A challenging topic, but getting some basic frameworks down can make a huge difference!
Topics covered include:
- Exam signs to help you localize in the peripheral nervous system
- ALS
- Peripheral neuropathy
- Neuromuscular junction disorders
- Myopathy
- and more!
A bi-monthly podcast where we share the stories of our Caregivers, patients and...
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The views expressed do not necessarily represent those of any associated organizations. The information in this podcast is for educational and informational purposes only and does not represent specific medical/health advice. Please consult with an appropriate health care professional for any medical/health advice.
Hello and welcome back to a new episode of the Neurotransmitters as we continue our board review series for internal medicine boards on the subject of neurology. So today we are covering what I consider to be one of the biggest monsters in subtopics, which is neuromuscular disease. I always find neuromuscular disease is one of the hardest subtopics of neurology to teach because a lot of times you get one chapter and it's the entire peripheral nervous system that you have to cram into one chapter, and I know in a lot of my neurology textbooks it's often the biggest chapter. So we're going to cover a little anatomy and then a fair amount of pathology on things that are most likely to show up on the IM in in-service exams and boards. This will of necessity be a rather broad overview and I'm sure that down the line we will be coming to some of these topics more in depth. So what does the peripheral nervous system contain? So, broadly speaking, we tend to start proximally and go distally. So proximally we have the anterior horn cells, the dorsal root ganglia, the nerve roots, the plexus, both in the brachial plexus and the lumbosacral plexus, peripheral nerves, the neuromuscular junctions and then the muscles themselves. So one of the best things to do for yourself is to kind of build a framework to help us say is this more likely a peripheral pathology or a central pathology? That I'm seeing.
Speaker 1:So for most peripheral key emphasis on most these diseases tend to be less acute, definitely not hyper acute like we see with stroke or a seizure, but more in the acute to subacute to more chronic in onset. As always, we want to localize if we can. So what are some patterns that will make us think of more peripheral things? So we want to look at specifically the patterns of weakness and numbness. With diseases involving the peripheral nervous system primarily, we tend to see things that are a lot more localized, things that are involving a specific dermatome, myotome, root level, involving just one limb, as opposed to things in the central nervous system like, say, a stroke that's causing weakness in the face and the hand right. There's a little bit distance between those two things. Sometimes you'll get the entire half of a body involved for some kinds of strokes or other kinds of central pathology. So those sorts of patterns should clue you in a little bit and unfortunately there's no way around it. You do have to know some peripheral nerve anatomy to say like, oh, this pattern of numbness, this pattern of weakness suggests this localization, and we'll touch on that a little bit as we go through some of these different disorders.
Speaker 1:But it's one of the things that makes neuromuscular medicine a little more challenging. Everyone tends to learn more of the central nervous system anatomy and the peripheral nervous system anatomy does take a bit of work to get into the memory. That being said, if you learn just a few nerves and a few root levels, you can cover a lot of your bases for the most common things. So if we think of our arms as having root level innervations, primarily from C5 through T1, and then we kind of know our three main peripheral nerves in the arm going to be our median radial and ulnar, and similarly in the legs, we've got our peroneal and our tibial distally in the leg. That will cover a lot of the questions that you'll probably see on your exams. So we got to talk about exam findings as well. Right, there's always the classic ones. So for upper motor neuron versus lower motor neuron findings right, everyone remembers these. For upper motor neuron versus lower motor neuron findings right, everyone remembers these. So for upper motor neuron kinds of findings, we expect increased tone, increased reflexes. For lower motor neuron involvement, we expect decreased tone, a little more placidity and decreased reflexes.
Speaker 1:Obviously, a big giveaway for something being more likely to be central nervous system pathology is if you have cortical symptoms, and some of the classic ones of these would be things like aphasia or neglect. Similarly, having something like a homonymous hemianopia should obviously clue you into a central pathology. So let's move into our pathology and again we're going to start proximal and go distal. So first up we have the anterior horn cells and the family of disorders that obviously is going to be affecting these the most is motor neuron disease, classically ALS, amyotrophic lateral sclerosis. So the classic findings we have here are a mixture of upper and lower motor findings on our exam right, some hyperreflexia, atrophy, fasciculations, and these can involve different areas of the body.
Speaker 1:So typically our diagnosis of this is going to require both clinical and electrodiagnostic, such as on EMG evidence of these findings in at least two or more areas. You know there's different levels of probability. You know possible, probable, definite. So the more areas that are showing the typical findings, the more likely the diagnosis is correct. And the different areas we have are there's four. So we have the bulbar, the facial muscles, the arms, the legs and the thoracic typically the thoracic paraspinals on EMG.
Speaker 1:So in addition to EMGs and nerve conduction studies, we're often doing MRIs, as sometimes a high cervical compressive myelopathy or a multifocal myelopathic process could mimic a similar disease presentation. So you do have to rule out structural or other causes of spinal disorders. You may also need to get some blood work. Some common things that may show up are things like B12 levels, copper, maybe Lyme parathyroid hormone, tsh and, in addition, basic labs like CBC, cmp, so some of the other things that can mimic it. So you can at least we already mentioned one mimic with spinal cord pathology. But you can get other kinds of neuropathies like multifocal motor neuropathy.
Speaker 1:And it's also important to remember that not all fasciculations are ALS. There is benign fasciculation syndrome. Particularly if you have a younger person without weakness who's maybe stressed or overusing caffeine and they're just getting some twitching around the face or the hands, that more often is going to be something like benign fasciculation syndrome. So a lot of times you're doing some of this workup, making sure there's no red flags and kind of providing reassurance. In those situations.
Speaker 1:Treatment is mostly supportive. We don't have any definitive disease modifying treatments, unfortunately, so a lot of the best practices involve multidisciplinary care. So we're bringing in pulmonologists, we're bringing in different therapists physical occupational speech, sometimes gi and that's because we may be talking about peg tube placement for someone who may be having progressive dysarthria and dysphagia, getting non-invasive positive pressure ventilation, or even talking about tracheostomy cough assist devices, various other assistive devices that can be helpful as the disease progresses. There is also an association with ALS and frontotemporal dementia and subsequently a pseudobulbar affect. So you do have to watch out for cognitive issues, right? It's perhaps not as pure of a motor neuron disease as we think, so there can be other things going on under the hood. So you have to ask about those sorts of things as well, both when you're talking with the patient as well as family Medication-wise.
Speaker 1:Rilazole is kind of the old kid on the block. It's a glutamate blocker and it's modest for most people. The other medication that's out there is Adaravone, and this is a pre-radical scavenger. It's a little more burdensome to get administered because it's not oral. It has to be given as an infusion and, again, rather modest effect overall. So just to re-emphasize, supportive care is really the name of the game when managing someone with ALS.
Speaker 1:Next up we have our ganglia, so a sensory ganglionopathy. These are a little unusual but can be quite dramatic when they do show up on your doorstep. So these will show up, usually with a severe loss of vibration and proprioception sense, and so you can sometimes get what's called a sensory ataxia. So they can be very off balance, very uncoordinated, and this has a few unique causes that you look for. So one of the things that I've seen rarely is a B6 toxicity. So someone's drinking a ton of energy drinks that have excessive amounts of vitamin B6 may show up with this incoordination and some pain. Also you can also see a ganglionopathy, with different kinds of perineoplastic syndromes and some autoimmune diseases, in particular Sjogren's syndrome.
Speaker 1:Next up are the roots. So the most common pathology we're seeing here are radiculopathies, right, so some compression, typically from bulging discs, degenerative disc disease, degenerative joint disease, and classically we're going to see sensory involvement more than motor involvement. It's very unusual to have a pure motor radiculopathy. So if you're not having typically that radiating pain from the neck down into the arm or the back into the leg, then you should be questioning is this really correct? And you do want to make sure this is where the anatomy becomes important that the symptoms correspond to an appropriate root level. So if it's radiating down a classic root level territory, then you'd be like, ah yes, this all makes sense. I know what kind of imaging, or if I need to get imaging, that I need to do so.
Speaker 1:As we said earlier, the common causes are gonna be compression due to disc disease. Sometimes you can also see these things show up in people who maybe have a history of cancer, in particular with bony metastases. These things show up in people who maybe have a history of cancer, in particular with bony metastases. So those are just some of the things that might make you even more suspicious, and obviously a history of recent falls or trauma are going to make you a little more suspicious as well for a mechanical cause here. There are, of course, other causes of radiculopathy or radiculitis, but we're not going to be covering those today as we keep on moving into the distal peripheral nervous system.
Speaker 1:We have next the plexus. Generally speaking, we're going to be thinking about a lesion in the plexus when we see primarily one limb is involved, with both sensory and motor symptoms, and it's not really localizing to just one nerve or root level territory. So we're going to be keeping this very broad right. No one's going to be drawing the brachial plexus out by the end of this podcast. So let's hit on some common causes. So some of the things that may commonly cause a plexopathy either in the arm or the leg diabetes and this is something we're going to come to over and over again is that diabetes can cause nerve injuries anywhere in the peripheral nervous system. It is a real pain in the buttignancy.
Speaker 1:So if you have some sort of metastatic infiltration of the brachial plexus or the lumbosacral plexus, if you had radiation therapy to like, say, the upper lung field, that can sometimes involve the brachial plexus. Similarly, in the pelvis with the lumbosacral plexus trauma is a very common thing. Now we may think back to medical school and be like oh you know, they want me to say it's like an Erb's palsy or Klumke's palsy or something like that in the arm. Very often when we have trauma as a cause of, like, say, abrachial plexopathy, it often won't localize as well as the textbooks do. That's because you get some sort of stretch, injury of multiple nerves, multiple parts of the plexus, so it's kind of all affected to an extent greater or lesser and so it doesn't localize as well beyond just the plexus. And that does happen in real life sometimes.
Speaker 1:One unique thing that can cause a brachial plexus injury is something called Parsonage Turner Syndrome, aka idiopathic brachial plexitis, aka neuralgic amyotrophy. So this is kind of a strange thing. It often will present in a single limb, obviously usually the arm, and it tends to be most prominent around the shoulder girdle, so kind of proximal near the shoulder, and it will come with this kind of severe pain, oftentimes some weakness. The pain will usually subside over a span of days to weeks, but the weakness may remain to some extent and in severe cases you can get some prominent atrophy in the shoulder girdle muscles or any of the muscles that were involved. Sometimes it can go more distal into the limb. So that is something that can happen. Workup-wise we often get imaging of the neck and the brachial plexus itself, looking for any compressive lesions or inflammation. Very often these will be normal and then you also end up getting some blood work, usually looking for different kinds of autoimmune or inflammatory disorders. A similar process can also affect the lumbosacral plexus and it's thought to be also immune mediated. Some of these things can be post-viral, post-infectious. It can look in the leg very similar to a diabetic amyotrophy, which we'll talk about later, and an EMG can help you differentiate between the two.
Speaker 1:We are finally here. We are in the thick of it now. We are at the peripheral nerves. So peripheral neuropathy. There are hundreds, if not thousands, of causes of neuropathy. So what are we going to look for in terms of neuropathy? So we're looking at patterns. A lot of neuropathy evaluation is pattern recognition. So what are some of the key features we need to look at?
Speaker 1:Symmetry Is it distal versus proximal, focal versus more generalized? What are the types of fibers involved Motor, sensory, small or large, fiber, autonomic and what are the things that are going to make us more worried about different causes? And then the other thing, obviously, is the timeline. So most neuropathies, or I should say of the common quote-unquote sort, are going to be on the chronic, insidious end of the time spectrum, something in the more acute to subacute phase. You're going to be obviously perking up those red flags. So those red flags are if we have market asymmetry in our symptoms, if it is proximal more than distal involvement, if it is a named nerve or a focal involvement as opposed to a polyneuropathy, and if the motor symptoms are greater or out of proportion to the sensory symptoms, any of these should prompt an EMG nerve conduction study evaluation. I'm just going to call it EMG, so any of you pedantic people out there just get used to it. So you should be doing neurodiagnostic evaluations on those at that point in time and that should also guide your lab workup.
Speaker 1:So our most common neuropathies, say from something like diabetes, is going to be a length-dependent, that is, stocking-in-glove type distribution right, worse, distally, less bad, proximally. By the time those tend to get to the knees they start to affect the fingertips and hands. So it's going to be length-dependent, sensory-predominant polyneuropathy, typically axonal on your nerve conduction studies. So what kind of labs are we getting for a length dependent, sensory predominant polyneuropathy? And I just want to pause for a moment and say very often you will find more utility with a safety pin and a tuning fork doing an assessment at the bedside than you will for a nerve conduction study, unless you have any of these aforementioned red flags in your history or exam. Because if you have this most common flavor of neuropathy, a chronic onset, length-dependent, sensory-predominant polyneuropathy, then you're going to get more utility from doing blood work looking for the cause of neuropathy than you are from a nerve conduction study or EMG.
Speaker 1:So basic labs you always want to be checking in these people. Usually you want a CBC, at least a BMP, maybe a CMP, depending on what their other medical history may look like if they have other liver issues. An ESR plus or minus the ESR is plus or minus. That's usually going to be more beneficial for someone younger. Serum protein electrophoresis with immunofixation. Looking for any paraproteinemias, tsh is a little debatable. Very often it is going to be unremarkable. Rarely you may find something Hemoglobin A1c or a glucose tolerance test. Those are going to be, in the United States at least very high yield and then a vitamin B12 level.
Speaker 1:Now let's say we have someone with one of those red flags. Well, what are the extra tests that we're going to want to do? Well, that really depends on what the clinical presentation is. So there are, as I said earlier, hundreds of causes of neuropathy, and so the clinical history is going to have to guide you a little bit on that, and that may prompt other things. It's obviously going to prompt another EMG and that's going to make you look for things like demyelinating disease EMG and that's going to make you look for things like demyelinating disease. So we have acquired, versus inherited, demyelinating disorders. So our classic acquired disorders are something like Guillain-Barre syndrome or, on the more chronic side, cidp, chronic inflammatory demyelinating polyradicular neuropathy. The classic inherited demyelinating neuropathy is Charcot-Marie-Tooth type 1, which in reality is diagnosed probably more on genetic tests than it is in the EMG lab anymore these days, although I'm not a child neurologist so your mileage may vary on that.
Speaker 1:Other testing that you may see done CSF testing. Again, in things like Guillain-Barre syndrome you may get a lumbar puncture, looking for that albuminocytologic dissociation. You may also be checking for other kinds of inflammatory markers. Cytologic dissociation you may also be checking for other kinds of inflammatory markers. You may also get a nerve biopsy. In particular when you're thinking of things like vasculitis, that's going to be someone who presents with something called mononeuritis multiplex which is where you get these random different nerves. Your named nerves get picked off kind of in a non-length-dependent, non-confluent fashion, although over time it may become relatively confluent. You're also looking for signs of infection or infiltration with things such as cancer. So nerve biopsy you definitely want to make sure that the nerve is already damaged because you're going to be cutting the nerve to do the biopsy.
Speaker 1:Autonomic testing can also be done, although it can be a little challenging logistically, depending on your practice setting. There's a test called the QSART Quantitative Pseudomotor Axon Reflex Test. This is essentially a sweat test and it can be helpful in people who have primarily small fiber neuropathies, where your nerve conduction studies may be otherwise unremarkable and you still think like something looks a little fishy. So it can be helpful in certain disorders. A tilt table test could also be considered in someone who's having a lot of autonomic symptoms that you're wanting to evaluate further.
Speaker 1:So two broad camps as we move forward we have mononeuropathies and polyneuropathies. So mono one, poly many. So some of the mononeuropathies. Obviously a mononeuropathy can affect any nerve in the body, but we're just going to touch on a couple that are likely to show up. So obviously carpal tunnel syndrome, the most common entrapment neuropathy in the body, right Median neuropathy due to compression at the wrist.
Speaker 1:So very often on exam you'll get a history of someone who's got paresthesias or tingling in their hand. Classically they'll want to shake their hand out when they first get up in the morning, or maybe exacerbated by certain activities such as running a bicycle or driving a car, other kinds of manual related activities, and when it progresses you may get some numbness over the thenar aspect of the hand. You may also get some atrophy of the thenar aspect of the hand weakness, with thumb abduction, and so you're going to try conservative therapy first with things like wrist splints, and if that's unsuccessful, or they're already showing signs of weakness in the hand, you're going to be getting an EMG looking for signs of active denervation, make sure to confirm that the localization is correct, and then you're going to be sending them to a hand surgeon for surgical decompression. The other mononeuropathy that we're going to be talking about is Bell's palsy. So Bell's palsy, by definition, is idiopathic, so it is a facial nerve palsy or seventh nerve palsy causing upper and lower facial weakness, although this can be variable and may progress over time. So you may get people who are more lower than upper, but there is usually some degree of asymmetry. Also, if they have weakness with forced eye closure on the affected side, that is very helpful, because that is going to be more of that seventh nerve weakness. You may also see and these are some things that I think are very helpful if there is hyperacusis, that is to say the nerve distipedius isn't able to tamp down on that loud reflex, or if they have altered taste.
Speaker 1:A lot of times I'll take something either salty or sweet like a sugar. If I'm in the ED, I'll take a long tip applicator and just put some saline water on one side and see if there's impaired taste on one side of the tongue or the other. If there is, then that tells me yes, it's definitely Bell's palsy. Right, it's the seventh nerve. It's doing taste of the tongue.
Speaker 1:So, as I mentioned, bell's palsy quote unquote is idiopathic, that is to say we don't know why it happened. So that doesn't mean we don't check for things. You still have to check for things. Otherwise it is a facial nerve palsy due to X. So, for instance, we're in Ohio, where I am, so we have to check for Lyme disease, right? I check for it on every person who comes in with a seventh nerve palsy and we get a handful of people who test positive for Lyme disease every year. So this is something to keep in mind if you are in an endemic area.
Speaker 1:Other causes that you do have to keep in mind things like HIV, sarcoidosis, diabetes, as we mentioned can affect any part and then sometimes malignancy, right, if there's infiltration of that seventh nerve, that could also cause a similar presentation. The classic treatment is, of course, of steroids. There is some debate as to whether antivirals may be helpful, and you do need to provide some supportive care as well. So that typically involves eye drops, ointment and making sure the eye is patched appropriately during sleep so people don't develop a corneal ulceration. Moving on to polyneuropathies there are so many causes of polyneuropathy so we're just going to focus on a handful.
Speaker 1:So first off, diabetes-related it can affect any part of the nerve. As I have said several times, we can even start seeing some neuropathy start to develop with the quote-unquote pre-diabetes or just impaired glucose tolerance. This tends to be sensory more than motor. You will also tend to get autonomic involvement. That's why you can see that redness distally in people who have had diabetes for a long time in their legs. You can also get this diabetic amyotrophy. What is diabetic amyotrophy? So it is an acute painful disorder typically affecting the thigh compartment in someone with diabetes. And you can actually get MRIs of the muscles. You can see some swelling and edema in there. So it may seem like more of a muscle disorder on presentation, but it does have nerve involvement.
Speaker 1:We mentioned hereditary neuropathies in passing earlier. Right CMT, type 1, autosomal dominance, demyelinating neuropathy. On exam you'll typically see high arches in the feet, hammer toes, they may have distal leg atrophy. On nerve conduction studies you'll see slowed nerve conduction velocities without conduction block. So conduction block is something you typically see with acquired neuropathies, these immune-mediated neuropathies.
Speaker 1:Speaking of Guillain-Barre syndrome, so it is a polyradiculoneuropathy and it tends to have an acute to subacute progressive pattern of numbness and weakness and reduced or absent reflexes. In reality those are the only criteria. Is this progression of numbness and weakness and reduced reflexes? Often in the vignettes on tests you'll see a preceding illness, whether that's GI or an upper respiratory illness of some sort. More severe cases may have some autonomic instability associated with them. So you can see these big swings in blood pressure and heart rate and such, and that can prompt them to need to be in the ICU even before they start having any bulbar weakness or respiratory issues which can also develop. The differential diagnosis for this includes some very strange things like botulism toxicity, west Nile virus, polio which we don't see, thankfully, too often tick paralysis if you're in an endemic area and some other disorders also. So there are multiple subtypes of Guillain-Barre syndrome. The one that we tend to see in the United States most often is AIDP acute inflammatory, demyelinating, polyradicular neuropathy. But there are axonal variants AMAN and AMSAN and, of particular note, there is something called the Miller-Fisher variant which is associated with a ganglioside antibody, gq1b, and that has the triad of ataxia, ophthalmoparesis and areflexia.
Speaker 1:When we're working up someone for GBS, typically, as we mentioned, we have nerve conduction studies cooking. We also are going to usually be doing a lumbar puncture and looking for changes in the CSF, typically an elevated protein with a relatively normal white blood cell count, which is referred to as an albuminocytologic dissociation. First-line treatments include IVIG and plasmapheresis. These have been found to be relatively equivalent. Ivig may not be as quick in its action as plasma exchange but it does tend to be a little more accessible, depending on your resources available. So you kind of have to look at the treatment setting.
Speaker 1:But A second course that's something you'll see sometimes if someone's not improving as expected. It's been studied. It hasn't been found to necessarily be particularly helpful. So you do need to watch, as we mentioned earlier, the negative inspiratory force, the vital capacity, and make sure that people's respiratory vitals stay stable, especially if they are having progressive weakness to the point where they are unable to ambulate and they may be having some dysarthria or dysphagia to the point where they are unable to ambulate and they may be having some dysarthria, dysphagia, cidp or chronic inflammatory demyelinating polyradicular neuropathy typically has a relatively subacute presentation. It tends to be length dependent. A lot of times they'll have some sensory changes in the feet, maybe developing some foot drop, ankle weakness and you kind of have this progressive or relapsing weakness and numbness presentation.
Speaker 1:So nerve conduction studies are going to be the key for coming to this diagnosis, with some demyelinating changes and conduction block, and you very often will get a lumbar puncture on these people as well, looking for again this same albuminocytologic dissociation. So first line for treatment is typically steroids, usually prednisone, although you can use other therapies as well, like IVIG and plasma exchange. If the steroids are too high of a dose for too long, you will be looking at adding on steroid-sparing therapy. The most common ones historically have been things like azathioprine and mycophenolate and then you would sometimes see, in more extreme cases, cyclosporine, cyclophosphamide, and there are other immunotherapies that are now also becoming available.
Speaker 1:Something that you will see if you work in the ICU is a critical illness neuropathy, and what this is is essentially someone who spends a prolonged period of time in the ICU and they develop weakness. They've come off the ventilator, but they're awake and they just can't move. They're weak, they have numbness, and so you can also have a concurrent critical illness myopathy. Your EMG will help you differentiate between these two, but very often a critical illness, neuropathy and myopathy travel together and there isn't any definitive treatment for this entity. It's just more to help you with prognosis and to give you some guidance in terms of like. Why is this person still so weak, even though you know maybe their illness is better? They should be getting out of bed, they should be participating in rehab, and they're just not able to Next up paraprotonemic neuropathies.
Speaker 1:So this is a bit of an unusual family of disorders. So these are often sensory predominant, but they can be sensory motor, multifocal or even involve cranial nerves. So there's a few classic entities here. One of these is MGUS, or monoclonal gammopathy, of undetermined significance. Mgus is associated with neuropathy, but very often we need to do some further workup and you may, depending on your comfort level, need to rope in a hematologist oncologist. There may be things like biopsies that need to be done, bone biopsies or kappaappa lambda, light chains, etc. Etc. So you do have to maybe rope in the hematology oncology department for a little further testing, depending on the clinical milieu. So other things that can be associated with neuropathy in this family multiple myeloma, waldenstrom's, macroglobulinemia, amyloidosis or other hematologic malignancies.
Speaker 1:Another entity that they love to ask about I think it's probably more prevalent on board questions than it is in real life is POEMS syndrome, which stands for polyneuropathy, organomegaly endocrinopathy and monoclonal plasma cell disorder and skin changes. So it is a lambda paraprodinemia, and it may look very similar to CIDP in terms of its presentation, but you'll have these other things right, typically the organomegaly, the endocrine disorders and the skin changes. Those are things that you don't see with CIDP, so that can sometimes prompt further evaluation. Something that also shows up in the questions from time to time is something called DADS, which is distal acquired demyelinating symmetric polyneuropathy, which is an anti-MAG, m-a-g myelin-associated glycoprotein antibody associated disorder. Autonomic neuropathies can also manifest. They may occur with other forms of neuropathy or they may occur by themselves, so they can, as always, occur with diabetes. The classic one to think of, though, is amyloidosis, and this can either be monoclonal or it can be genetic trans-thyretin mutation related. Autonomic neuropathies can also be seen with HIV, and there is a perineoplastic syndrome associated with anti-ganglionic, nicotinic acetylcholine receptor antibodies.
Speaker 1:We made it. We made it through the neuropathies, we're past the nerves, we are now to the neuromuscular junction. So we've got two prime disorders that it's always good to know about for neuromuscular junction disorders. So first up we have myasthenia gravis. This affects the post-synaptic neuromuscular junction. So there's a bimodal distribution here. We've got young women, typically third decade, and older men over the age of 50. Those are the most common populations that we'll see myasthenia show up in.
Speaker 1:Very often the first symptoms will be things like ptosis, diplopia, but about half of those may develop generalized symptoms within a couple of years and about 10% will present with bulbar weakness and some cervical involvement, that is, the neck. So it's not uncommon for these people to be seen by optometry or ophthalmology first due to the ocular symptoms that can be so common. At presentation. Diagnosis wise these days the antibody testing is really good. About 90% of patients will be antibody positive. 85% are going to be the more typical binding blocking or modulating antibodies. 5% of those might be musk, which is going to be a little bit more bulbar onset. They tend to have more respiratory involvement, more facial weakness, so a little more aggressive course, and they don't respond as well to treatment as the people who are positive for the other antibodies. Sometimes you may still need to do neuroconduction studies and that'll show a decremental change on repetitive stim. So that may show up in a question stem.
Speaker 1:There is some debate about initial treatment. So symptomatic treatment is usually with periodostigmine, aka mestinone, which is a cholinesterase inhibitor. You do have to watch out it will increase secretions right, saliva, diarrhea, tearing things like that. So any place that makes fluid making more fluid. And there is some debate about whether to start disease modifying treatment when people have purely ocular symptoms. If periodostigmine is able to keep things under wraps, I tend to be of the party that I think maybe disease modifying treatment is more appropriate to start at beginning, just because of so many people developing generalized symptoms over time.
Speaker 1:So our typical disease modifying paradigm, first line is very often prednisone and you titrate up slowly. If you start at too high of a dose it can paradoxically worsen things and cause a myasthenic exacerbation. If you're not able to get someone down to a low dose of maintenance prednisone, you're going to be using steroid sparing therapy and those are again classically mycophenolate and azathioprine. You can also use things like IVIG or plasma exchange and there are a number of new monoclonal antibodies and other types of disease-modifying treatments out there. I don't know if those are starting to hit the test just yet, so we're not going to go into them too much.
Speaker 1:A word about a myasthenic crisis. So this can present with very sudden worsening weakness of the bulbar muscles, respiratory muscles, and this can be triggered by stress, different kinds of antibiotics such as aminoglycosides, infections, recent surgery, certain medications, as we mentioned aminoglycosides, quinolones, magnesium, beta blockers, hydroxychloroquine. So people definitely need to know before they start a new medication whether or not it is going to be safe for them with myasthenia. And you may need sometimes, to quote medically optimize someone with myasthenia prior to having an elective surgery, and that may mean giving them a short course of IVIG or some other kind of treatment. So that just really depends on the context and your particular patient that you're taking care of. Another treatment that is out there is thymectomy. So if they have a thymoma, obviously we're going to remove that. For people who don't have a thymoma, there may still be some benefit, not immediately per se, but over time. They generally require less immune suppressive medication.
Speaker 1:Next up in our NMJ is Lambert-Eaton-Myasthenic syndrome. So this is a presynaptic neuromuscular junction disorder and it's associated with antibodies against voltage-gated calcium channels. So very often this will be associated with small cell lung cancer, although there can be perineoplastic versions as well. So if they have the cancer, treat the cancer. If they have no cancer, then you treat with immunosuppression, ivig, plasma exchange, kind of the usual things at this point.
Speaker 1:So typically if this is a man, you'll get some autonomic symptoms, including erectile dysfunction very commonly, and they'll get some kinds of weakness. You can see hyporeflexia as well and you can see this phenomenon called augmentation, where if you have them flex a muscle and then you check the reflex before and after activating that muscle, the reflexes will often be brisker after you have them use that muscle for a short period of time. And you'll see a similar thing on nerve conduction studies as well, with repetitive stimulation. We are in the home stretch, we are at the muscles. So let's talk about myopathies. So the classic pattern for a myopathic process is going to be weakness, typically proximal more than distal, and obviously, because it's the muscle, you usually shouldn't have sensory involvement unless there's something else going on. Lab-wise you're going to be checking a CK level, maybe an aldolase. Very often you'll be doing EMGs and nerve conductions on these and this will show typical patterns. The typical pattern for a myopathy on needle EMG is going to be low amplitude, polyphasic and early recruitment, which is kind of the opposite of what we normally see for a neuropathic process. So in some severe cases you may also need a muscle biopsy. Now a word about EMGs and muscle biopsies and CK levels. You want to check your CK before you poke the muscle, right, you poke the muscle with a needle, it may raise the CK and similarly the muscle biopsy itself may cause an elevation in CK as well. You also don't want to biopsy the muscle that you also poked a needle into, because that microtrauma may influence the pathology a little bit, so it may be a little less reliable.
Speaker 1:So, moving on, our first family is inflammatory myopathies. Now some of these are going to sound really familiar Polymyositis, dermatomyositis and inclusion body myositis. Then you also have immune mediated necrotizing myopathy. So polymyositis and inclusion body myositis. Then you also have immune-mediated necrotizing myopathy. So polymyositis, right, you tend to have that classic pattern of weakness, elevated CKs, dermatomyositis, elevated CKs, strong association with different kinds of cancers. So you need to check out for that and you're looking for that skin involvement, that rash, that shawl sign. Immune-mediated necrotizing myopathy very often will be triggered by statins, may have an association with HMG-CoA reductase antibodies and again you'll treat this with immunotherapy. Inclusion body myositis often has a very slow course. Typically you'll have early weakness of the distal upper extremity flexors, the quads, bulbar muscles potentially, and on muscle biopsy you'll get, obviously, inclusion bodies. That's kind of the big takeaway there, so that can be very helpful in that case.
Speaker 1:Moving on to endocrine-related myopathies so different endocrine disorders can cause myopathic changes. So hypothyroidism can cause myalgias, proximal weakness, myxedema changes. So hypothyroidism can cause myalgias, proximal weakness, myxedema, hyperthyroidism you can get fasciculations, ophthalmoplegia, hyperreflexia and then, as we mentioned earlier, you know, kind of the looks like an endocrine related myopathy. Is the diabetic amyotrophy no-transcript getting weaker again, more in their shoulders and legs, and it's like this isn't the same kind of weakness they had before. Well, you might need to back off on the steroids. So you will oftentimes check a CK. It's going to be normal. Emg very often will be normal. Some steroids are more likely to do this than others Dexamethasone more so than prednisone or hydrocortisone. So you do have to watch out when you're using steroids to treat one other condition as that may cause this kind of paradoxical new problem.
Speaker 1:Moving on to toxic myopathies. So the poster child for this family are statins, which can cause pain, very often in the shoulders and the thighs, and in more severe cases, weakness as well. In those severe cases, the really severe cases, it'll go to that necrotizing myopathy that we mentioned earlier. Other medications can also cause a toxic myopathy. Ck levels may be mildly or significantly elevated. Typically remove the offending agent and most people should get better.
Speaker 1:Finally, inherited myopathies so a lot of these will present early in life. There are some that will present in adulthood, so a couple that I want to touch on. So myotonic dystrophy very often is associated with some other systemic disorders. You can see myotonia, which is this impaired relaxation of muscles. So for instance, you go to shake somebody's hand, they can't open their hand right away and you can use sometimes like sodium channel blockers, like phenytoin or other types of things to help with that. So type 1 myotonic dystrophy you typically have distal weakness, they have cataracts, frontal balding, they'll also have some cardiac and endocrine associated disease and they might have some mild cognitive issues as well.
Speaker 1:Mitochondrial myopathy this is kind of a wide category, significant variability depending on the syndrome. But whenever you have a mitochondrial disease you expect multi-organ involvement. So myalgias, ophthalmoplegia, other organs, and obviously it tends to be maternally transmitted due to the mitochondria. Some of the classic metabolic adult-onset myopathies may present with exercise-induced weakness, cramps, myoglobinuria right, you get that dark urine myocardial disease, carnitine, palatoyl transferase II deficiency are probably the two most common. You can also see Pompe disease or acid maltase deficiency. So it has an adult onset form with proximal weakness and respiratory muscle weakness. And you can check the alpha glucosidase activity as well as genetic testing. There is a treatment alglucosidase alpha, and just like that we have made it to the end of the muscle category and we have finished our rapid survey through the peripheral nervous system. If you made it to the end, good on you.
Speaker 1:Thank you so much for spending your time listening to me rattle on about neuromuscular diseases. I know this is a lot of information and it's still a little bit longer than I would have liked it to be, but it's just such a broad category. Obviously, we will have to revisit some of these topics in more depth in the future. I hope this was at least edifying in some fashion and will help you on some of your exams and hopefully even more so in real life when you're taking care of patients. If you found this podcast helpful, educational, leave us a five-star review, leave us some feedback. You can check out our past work at theneurotransmitterscom. You can also find me on Twitter. Slash x at drkentris d-r-K-E-N-T-R-I-S, or the podcast itself at neuro underscore podcast. Again, thank you for listening and if you have any show suggestions, ideas, you can always get a hold of us through our website.
