DIP Episode 435 - Diseases of The Neuromuscular Junction (for Step 1-3)

All right, welcome. My name is divine. This is episode 435 of the divine intervention podcasts and into these podcasts I'm going to be addressing the diseases of the neuromuscular junction diseases of the neuromuscular junction This should be a short podcast, but it should be a podcast that's pretty high yield for your exam Let's just get right into it. So what if they give you a question about a lady in her 30s and They tell you that she comes to the physician because she has been having trouble keeping an eye open at work and they tell you that on physical exam she has like a droopy eyelid and You're told that when you tell her when you do the heathen space test multiple times It gets harder and harder for her to keep her eye open In fact, they may tell you that as you do the heathen space test more and more and more and more and more the degree of droopingness gets worse and They also tell you that oh this person has you know like proximal muscle weakness and They tell you that this person has no deficits of light touch, pain, break, vibratory sensation and They also tell you that this person's reflexes are completely normal reflexes are normal and they can even tell you that when the person Is told to walk in a straight line. They would walk normally without etaxia If you see something like this what should you be thinking about?

I really hope you're saying or divine this person has my senior gravies The thing is some distractors they can try to trip you up with on your exam They can put something like polio dramatic myocides as an answer Just because of that one thing I said about proximal muscle weakness and Then they can also just put a bunch of other things like lupus Some rheumatoid logic thing like rheumatoid arthritis don't fall for those things again Put the whole clinical picture together in the right way not a diagnosis So this person has my senior gravies remembering people that have my senior gravies essentially They have anti acetylcholine receptor antibodies. They literally have auto antibodies Against the nicotinic acetylcholine receptor So since they've made auto antibodies against that receptor That receptor which we find that the neuromuscular junction cannot work So the ultimately getting trouble and Because you're basically blocking the ability of acetylcholine to bind to the nicotinic receptor Which we find out the neuromuscular junction especially with skeletal muscle So that can ultimately cause problems in these in these people Now how do we diagnose this?

Well, typically we're gonna diagnose this by looking for anti acetylcholine receptor antibodies In the person's serum we look for anti acetylcholine receptor antibodies in the person's serum If you don't find those you can look for the anti-musk Antibodies you can look for the anti-musk MUSK MUSK antibodies And What would you expect if the person were to undergo repetitive nerve stimulation?

Well, I really hope you're saying out of line this person is gonna have a decremental response To be honest with you the NBME is one thing they're very smart about is Instead of making this a straightforward question they can just pick some muscle in the body They can pick um like I don't know just literally any muscle they can literally pick any muscle And then they will show you Nerve stimulation they'll show you time one seconds two seconds three seconds five seconds ten seconds And then you'll notice that the amplitude With initial stimulation is like two and then it raises to like five And then you notice that man after that initial burst up it is that's trending down You see like wow the amplitude of the muscle contraction or the tension that's generated by the muscle is like three Two One it keeps dropping dropping dropping When you see that pattern you want to think about my esteem nervous Again one big thing about the USML exams these days Is a lot of it is based on application this something I was telling people during their step-on review course last week The USML is you can know all the information you want you can memorize everything that you want But you need to be able to use that information you need to be good at data analysis to do well on the USML exams So that's why again, it's good to do practice problems especially thoughtful practice problems So that you can actually like money try to manipulate that material in very unique ways So these people are going to have a decremental response to repetitive nerve stimulation That's something you may find on an on an EMG Now what other kind of diagnostic testing should be done in a person that has my esteem nervous on your test I would really hope you're saying oh divine we're going to get a CT of the chest We're going to get a CT of the chest Well why in the world are we going to be getting a CT of the c

hest we're going to be doing that Because remember people that have my esteem nervous can absolutely have fine warmers People that have my esteem nervous they can definitely have fine moments And some in some people that have my esteem nervous for is selecting those fine moments Can be very helpful in actually improving the symptoms of their disease And again our friends at the EMG is instead of putting fine momas and answer One thing they can easily easily easily do as a Throwing as an answer is they can just put anterior medius thinoma And anterior medius thinoma can be a thinoma remember your terrible teas that love to shop in the anterior medius thinoma Like thymomas Tera tomas and they don't forget like lymphomas and things like that And don't forget the sales sign with the thymus in a newborn Obviously it's going to be absente at a child that has the George syndrome Because the third and fourth bulge is do not form and also the child that has skin severe combined immunodeficiency So how do we actually treat people to have my esteem nervous?

Well typically you're going to give them an acetylcholinesteria inhibitor So something like pyrididol steaming for example you get red My steining of gravity is red pyrididol steaming with pyrididol steaming Because it's an acetylcholinesteria inhibitor So it's going to bump up your levels of acetylcholine by doing that It's going to outcompose those mastian antibodies that we find on the surface of the person's Necotinic acetylcholine receptors And you can also give steroids you can give steroids You can again do a thymectomy if a thymoma is discovered those people should absolutely get a thymectomy And if you notice that an acetylcholinesteria inhibitor is not co-ordinated for this person anymore And they say what's going to be your next best step in management I really hope you're picking an answer That involves some kind of immunosuppressant So something like is a thyloprene, mycophylophotel Those are things you have to do Now Many times diseases have chronic presentations And what I like to call an acute exacerbation So if they give you a question about a person that you know has a history of my stenographies And they notice over a few hours over a few days Did you really study compensating You'll notice that these people are getting more respiratory and more so weakness They're getting lots and lots and lots of issues Then in that case I want you to think of a monastening crisis When a person has a monastening crisis You cannot do usual therapy for them The thing that's going to rescue those people The thing that's literally going to rescue those people Is those people getting plasma ferrisis or getting IVIG They get plasma ferrisis or they get IVIG That's literally the thing that's going to rescue them in those circumstances And remember people that have my stenographies I think maybe one thing that I'd be helpful to you Is being able to compare and contrast my

stenographies With lumbar etymisthenic syndrome So my stenographies Typically these people will have no more reflexes They will not have any issues with their reflexes But people that have lumbar etymisthenic syndrome Do you usually have some degree of hyporeflexia Or some degree of air reflexia Some degree of air reflexia Some degree of air reflexia And typically people that have lumbar etymisthenic syndrome They tend to have other like autonomic symptoms They'll have like dry mouth They'll have blurry vision You know they can have constipation They can have importance They can have all those things And I know some of you may be like divine But why is that the case?

Why do we know necessarily find this in my stenographies I can remember my stenographies is a pure problem At the level of the nicotinic acetylcholine receptor But in people that have lumbar etymisthenic syndrome The problem is with a presynaptic Votage-gated calcium channel Is with a presynaptic Votage-gated calcium channel Presynaptic Votage-gated calcium channel Think about it That it seems like a subtle difference But it's a very important difference Because that presynaptic Votage-gated calcium channel Is not only found At the neuromuscular junction It's found in many other parts of the body So you can have just more diffuse symptoms In those circumstances Pretty much any synapse that releases Like neurotransmitter Very likely has that presynaptic Votage-gated calcium channel And remember people that have lumbar etymisthenic syndrome Is classically associated with Long cancer Especially small cell long cancer But I said my stenographies is classically associated With a thymoma With a thymoma And remember the response to the repetitive nerve stimulation People that have my stenographies I said that they have a decremental response With repetitive nerve stimulation But people that have lumbar etymisthenic syndrome They have an incremental response With repetitive nerve stimulation Basically The more you keep stimulating the nerve, stimulating the nerve The better the amplitude you'll get with your muscle contraction So you may start off with like one Two What over time is going to have these big jumps three Four or five One because by stimulating the muscle more and more By stimulating the nerve You're going to recruit more calcium To that Votage-gated calcium channel And that's going to outcompete those race Those antibodies And when it outcompete those antibodies Then you have better neuromuscular transmission You have better neuromuscular transmission You get be

tter neuromuscular transmission And remember one old test that we do For people that have my stenographies Is the tensileant test Sometimes they call it the edrophonium test Is basically an acetylcholinecerase inhibitor Androphonium is an acetylcholinecerase inhibitor When the inhibitor acetylcholinecerase It's going to bump up your levels of acetylcholine And that's going to cause a transient improvement in muscle weakness And then another thing they can also do is They can give you like an ice pack test Or something like that They can give you an ice pack An ice pack test They can even show you like a picture of someone Like a woman because don't get me wrong My stenographies can affect men But they almost exclusively pull those in women on exams So they can give you a question about a person And they will show you images Again remember the MBM is these throwing pictures every now and then On exams I'm just trying to show you the different ways That they like to test information They will show you a person They will see before and after You see the before You see a person having like just Terrible terrible terrible Drupia elite And then you then notice that after an ice pack is placed on your eye You notice that boom Everything just improves So what's the mechanism there Well the mechanism there Is that an ice pack When you pull down the temperature of the neuromuscular junction Acetylcholine estuaries does not work as well When you pull down because remember Many enzymes in the body are temperature sensitive They work best at certain temperatures They don't work as well at such temperatures So when you ice up a person's neuromuscular junction That decreases the activity of acetylcholine estuaries That's going to cause a temporary bump In the person's levels of acetylcholine And when that happens When that happens You're going to notice that the person is going to h

ave And improvement in their muscle Weakness Person is going to have an improvement in their muscle Weakness And again remember People that have myestinogram is It typically affects bulbor muscles So they usually have issues with swallowing They usually have issues with your eye muscles They usually have a lot of proximal weakness Many times when they give you a lumbar Itemisthenics syndrome question They are not really going to give you anything About bulbor weakness like trouble swallowing Or eye issues No People that have a lumbar Item They usually have just proximal muscle weakness And many times You know they will have the decrease The deep tendon reflexes That's not necessarily something we find in myestinia Gravis It's not something we're necessarily finding in myestinia Gravis And again if you like the way I'm like oh going over this material But not just throwing the knowledge at you Actually showing you okay This is the way this may be tested when you examine Now you may be interested in the review courses that I offer My review courses are not lectures They're not lectures There are problem solving situations Where I teach you how to problem solve But as I'm teaching how to problem solve You learn the material at the same time And I tend to integrate content across multiple disciplines I have an MBA me testing strategies class For step two and step three That's going to be taking place next week Friday It's going to be from 5 to 7 30 p.m.

Mountain standard time And then the week after that From pretty much from During that week For four days during that week I'm going to be holding the 20 hour review course For step two and step three And obviously for complex level two and three And then the week after that Towards the tail end of that The next week after that I'm having a four hour biostatistics bootcamp And a five hour social sciences and ethics review The biostatistics bootcamp The social sciences and ethics review Is for step one to step three complex one to three We know that the USML is these these About 10 to 20% of the questions Are based on social sciences and ethics So I decided to design a separate course That addresses that And then I have a step one class That's going to be taking place Next month in the month of February We just have one very simply Very very high yield Again It's just The USML is not just all about memorization They are more about very deep Detailed understanding And also being able to see these concepts in scenarios So if you want to be well versed in those things And get a very solid content review And not just a content review But a review that shows you Hmm This is how you approach questions on your exam This is how this material most likely presents If you want something that is not going to be A bunch of lectures lectures lectures But it's going to be like Tons and tons and tons of clinical scenarios Then these review courses Maybe things that will work really well for you And then finally What if they give you a question About a 25 year old male And they tell you that for the past three days He has been having a lot of Constipation They tell you that Hmm He has a lot of muscle weakness And they tell you that Physical exam he has decreased deep tenderness reflexes And They tell you that this guy Has a history of injecting Black tar heroin Black tar heroin If you s

ee something like this What should you be thinking about I would really hope you're saying Botulism So maybe maybe like Huh Botulism Yes Botulism Botulism is actually pretty high You'll to know for exams Obviously there's the classic exposures Like Child on their age 12 That did this I mean under Under 12 months Under a year of age That his mom decided to dip his pacifier in honey Or they can give you some question about some adult That consumes home kind goods Or you know they can give you those scenarios But again the NBM is Same concept just different scenarios This is actually one of the more common causes Believe it or not Of botulism When you inject Black tar heroin That can cause like a wound-based botulism But the common final pathway is the same Although I want to maybe comment Kind of specifically about some of these things When you see an adult with botulism Usually they're going to have Really anyone with botulism is going to have flassey paralysis I'll explain why But remember people that have botulism as adults Is usually from the toxin If you ingest the spores as an adult That's usually not going to cause a significant issue for you To be honest why Because again your intestinal flora is very well versed In dealing with the spores So you have to consume the actual toxin In like a home kind good to get in trouble But a child on their age one year Cannot really deal with The spores Because the child does not have enough of an intestinal flora So if the child consumes the spores Even if they don't consume the toxin Just consume the spores Those spores will germinate in their GI tracks Elaborate toxin And in those cases will get in trouble Again Is the same common final pathway But the mechanism of disease is different You've got to make sure you understand that stuff Don't forget this As usual Black tar heroin Very very high yield to know For example Very

very high yield to know for exams So what's the pathophys Well the pathophysiology typically Is the botulinum toxin Cleaves a snare protein on a snap 25 It cleaves a snare protein on a snap 25 By cleaning those snare proteins You're basically going to decrease the release Of acetylcholine at the neuromuscular junction If you decrease the release of acetylcholine At the neuromuscular junction Then you're not going to have any kind of muscle contraction And you're absolutely Positively going to get flasset paralysis You're going to get flasset paralysis Flasset flasset flasset paralysis Descending flasset paralysis And how do we treat botulism Although we treat botulism Is by giving the anti toxin We can give the botulinum anti toxin It actually can really really help those people Again, our friends at the Mbimis can write a question Where a person gets an anti toxin And then you notice that With repetitive stimulation They're now getting a better response An incremental response That will be botulism Because the anti toxin basically Bound up the toxin And fix those people's problems Now make sure you can Compare and contrast botulism with tetanus When people have tetanus Tetanus, the toxin Also again, please snare proteins Would that prevent the release of inhibitory neurotransmitters Like GABA and glycine If you cannot release inhibitory neurotransmitters Like GABA and glycine From racial cells Then you're going to have a spastic paralysis Because you have less release Of inhibitory neurotransmitters You're going to have a net Neuromusculic citation And they can put you in a lot of trouble They can put you in a lot of trouble Now, the one thing I just want to say Let me actually help you on exams Is when a person takes botulinum anti toxin What if they give you a question and detail That the person starts having these fevers Because usually when you have tetanus When

you have tetanus actually You can have fevers I mean when you have botulism sorry You can have fevers Because your sweat glands They work based on acetylcholine So if acetylcholine is not released Then your sweat glands will not work So you're not going to be able to We're distributed very well So you can become hyperthermic As a result of that But please don't forget That's the botulinum anti toxin So they tell you the person gets it The person starts feeling better initially But after a while They start having fevers They start having like constitutional symptoms If you see that What should you be thinking about I really hope you're seeing oodivine This person has developed Some kind of serum sickness Remember anti toxin Are very prime candidates For causing serum sickness You can absolutely positively Cause serum sickness It's a type 3 hypersensitivity reaction From antigen antibody complexes This bot cause by the way again It's really short But it's really really high yield I will encourage you to make sure you actually understand Notice I wasn't just three facts at you I was giving you context and scenarios But also trying to explain pathophys This pathophys You do actually have to understand it for change Okay, so make sure you understand these things And I really hope you find this podcast To be helpful I also want to want you to learn for step 1 to step 3 Preclinical medical exams, 30th of exams I help with your application More interviews, personal statements, and rec letters I also have these podcasts on the major apps Apple, Google podcasts and Spotify Then I have a You Tube channel Divine Intervention Life, US-Vili podcasts and videos Divine Intervention, US-Vili podcasts and videos That's why I post the videos that I make And then I also offer review courses for step 1 For step 2, step 3 For biostatistics and for social sciences And ethics And then I also

have a new website called Divine Intervention Lifelessens.com That's why I post the life lessons that I make Many of you know I'm a Christian Many people have told me Ooh, Divine, I absolutely love the life lessons that you You put at the end of some of your podcasts So I decided to start a new website for that There is actually an Apple podcast associated with that The Divine Intervention Life lessons podcast And basically it's two podcasts every week About 10 to 20 minutes long And from a biblical perspective I try to address a common problem that's faced by people So I'll encourage you to check it out I think you're going to find it to be really helpful So thank you for listening to me I'll see you in the next episode Have a wonderful rest of your week God bless you Bye for now Thank you

Fluctuating weakness and fatigability (e.g., ptosis worsening throughout the day).

A decremental response to repetitive nerve stimulation (RNS).

LEMS patients typically have hyporeflexia, and the RNS shows an incremental response.

It cleaves SNARE proteins on SNAP-25, preventing acetylcholine release at the neuromuscular junction.

Tetanus causes spastic paralysis (due to failure to inhibit neurotransmitters); Botulism causes flaccid paralysis (due to failure to release A Ch).

Serum sickness, which is a Type III hypersensitivity reaction.

Nicotinic acetylcholine receptor (A ChR).

Anti-acetylcholine receptor (A ChR) antibodies and anti-MuSK antibodies.

Small cell lung carcinoma (SCLC).

Proximal muscle weakness; Autonomic symptoms include dry mouth, constipation, and blurry vision.

Botulism causes flaccid paralysis by preventing A Ch release (cleaving SNARE proteins); Tetanus causes spastic paralysis by inhibiting inhibitory neurotransmitters (GABA/Glycine).

It temporarily improves muscle weakness because cooling decreases acetylcholinesterase activity, leading to a temporary buildup of acetylcholine.

IVIG or Plasmaferesis (immunomodulatory therapy).

Nicotinic acetylcholine receptor (A ChR).

Anti-acetylcholine receptor (A ChR) antibodies and anti-MuSK antibodies.

Small cell lung carcinoma (SCLC).

Proximal muscle weakness; Autonomic symptoms include dry mouth, constipation, and blurry vision.

Botulism causes flaccid paralysis by preventing A Ch release (cleaving SNARE proteins); Tetanus causes spastic paralysis by inhibiting inhibitory neurotransmitters (GABA/Glycine).

It temporarily improves muscle weakness because cooling decreases acetylcholinesterase activity, leading to a temporary buildup of acetylcholine.

IVIG or Plasmaferesis (immunomodulatory therapy).