Myopathy Junction and Dystrophinopathies

by Carlo Raj, MD

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    00:01 Once again, I’ll bring this illustration to your attention because I want you to know where we are and what we’re dealing with.

    00:09 So, we’re doing neuromuscular diseases, and we spent an awful lot of time with peripheral neuropathy and such.

    00:15 And we talked about diseases of the anterior horn, motor neuron diseases such as amyotrophic lateral sclerosis.

    00:21 With peripheral neuropathy, we went through plexopathies, we went through mononeuropathy, mononeuritis multiplex, and walked through polyneuropathies.

    00:30 And then what we have left now is going to be neuromuscular junction diseases, and then we’ll have our myopathies including our, what’s known as your muscular dystrophies, Duchenne and company.

    00:41 At this junction, pun intended, it was the neuromuscular junction.

    00:46 Let’s begin.

    00:49 With neuromuscular junction, well, what are we looking at? What if the problem was presynaptically? And that’s where the disease was.

    00:56 So, think about where you are first.

    00:58 Neuromuscular junction.

    01:00 You’re going to release what at the neuromuscular junction? Acetylcholine.

    01:04 What does it bind to? Your acetylcholine receptors, a.k.a., nicotinic receptors.

    01:09 These are ligand-gated.

    01:10 This then opens up your sodium channel, and in comes the sodium, right? But in order for you to release that acetylcholine, what do you need to bring in presynaptically so you can release it? Ah! Voltage-gated calcium channel.

    01:22 So, presynaptic disease, Lambert-Eaton myasthenic syndrome.

    01:26 We have already talked about this as being possibly paraneoplastic with small cell lung cancer.

    01:32 Botulism, what does that do? Well, if you’re injecting botulinum, right? Why? Because you heard Botox, right? That’s amazing to me.

    01:44 But you’re trying to iron out the wrinkles by inhibiting the release of acetylcholine presynaptically.

    01:53 And something called tick paralysis, presynaptic.

    01:56 Postsynaptically, the infamous myasthenia gravis.

    02:01 That’s where we’ll begin is myasthenia gravis.

    02:03 Clinical features: What happens here? Well, most likely, an autoimmune disease automatically puts you into to the gender or sex of females, right? In addition to that, what else might you find here? The thymus in a 40-year-old female.

    02:19 Well, normally, it should be non-existent.

    02:22 But then they give you a chest x-ray or you’ve been shown a chest x-ray, and then all of a sudden, in this 40-year-old female, you’ll find a thymic shadow.

    02:31 Fascinating! A thymic shadow in a 40-year-old? Why in the world was there a thymoma to begin with? Well, maybe because this female had myasthenia gravis.

    02:42 And what happened? Well, she had fatigable weakness.

    02:45 What kind of muscles? The proximal versus the distal.

    02:49 And you have different types of muscles, don’t you? You have type 1 and type 2.

    02:54 The fast-twitch will be type 2, that you’ll have to memorize in your own special way.

    02:58 But type 2 will be the fast muscle fiber.

    03:00 They require quite a bit of energy, so therefore, think about the eyelids, huh? Fast-twitch.

    03:06 So, your patient is now complaining of, “Hey, doc, I wake up in the morning.

    03:10 Hey, I feel great and I go to work.

    03:14 And man, around lunchtime, I’m having a hard time seeing.

    03:18 And by the time four o’clock rolls out, I am barely able to get out of my chair.” So, prominent ocular involvement, because the first type of muscle fibers that would be affected will be fast-twitch.

    03:29 Ptosis and diplopia.

    03:32 Continue.

    03:33 Pupils never get involved, because why? This is neuromuscular junction, is that clear? It has nothing to do with oculomotor parasympathetic.

    03:41 Bulbar musculature frequently involved, and deep tendon reflexes usually preserved.

    03:47 Around four o’clock, why does the patient feel so incredibly tired? Because now, the pathogenesis, which we’ll talk about in a second, the acetylcholine receptors, type 2 hypersensitivity, had been destroyed.

    04:00 If you don’t have these receptors, it might be difficult for you to move, huh? How in the world are you supposed to have an action potential in the neuromuscular junction if your receptors are obliterated? The pathophysio, what is it? Antibodies directed against the postsynaptic acetylcholine receptors.

    04:18 Where? On the muscle fiber.

    04:21 Hence, the oculomotor was not affected, right? What was affected? Oh, the muscle, that’s right, the type 2 muscle fibers.

    04:31 Frequently associated with thymic hyperplasia.

    04:33 Stop there, absorb that.

    04:34 I told you about this female who had a thymic shadow at the age of 40.

    04:39 Remember, the thymus is responsible for educating our T-cells.

    04:44 And once the T-cells are educated and then the soft T-cells undergo apoptosis, then really, the thymus undergoes involution itself.

    04:55 Next, the thymomas, older onset, which may need to be removed, and that’s what I was referring to.

    05:01 The thymectomy on your chest X-ray would then reveal a thymic shadow.

    05:07 Next, well, what happens on your nerve conduction test, NCS? Decremental response with low frequency repetitive stimulation.

    05:16 Increased jitter on single fiber EMG.

    05:20 So, what do you think you might want to do in which you can increase the strength of the muscle? If the problem is that the acetylcholine receptor is never worked, why not increase the concentration of acetylcholine? “That sounds like a fantastic idea, Dr. Raj.” It is, because if you do increase the concentration of acetylcholine, guess what? You might actually get a response where the muscle fiber might increase in strength.

    05:45 You’re going to use this for your diagnostic purposes, and actually, long-term management of your patient.

    05:51 Are you having fun yet? Let’s do this.

    05:55 Management: Now, myasthenia gravis, what do you want to do? Increase the concentration of acetylcholine in the synaptic cleft.

    06:01 Can you picture that? Are you there? A wonderful place to be.

    06:05 You inhibit the acetylcholinesterase.

    06:07 Think about drugs such as pyridostigmine.

    06:10 Pyridostigmine.

    06:11 Steroids, possibly.

    06:14 And steroids-sparing agents.

    06:16 And so here, immunomodulators, right? Azathioprine, if necessary, methotrexate and company.

    06:23 IVIG and plasmapheresis, especially if there’s a crisis.

    06:28 Remember, this is an autoimmune disease, huh? And so therefore, attacking the acetylcholine receptors, and if you start getting to a point where it’s refractory and it’s really not responding, then you’re really not left with much of a choice, and then it is shown that by removing the thymus, this hyperplastic thymus or a thymoma, that the patient’s symptoms might subside.

    About the Lecture

    The lecture Myopathy Junction and Dystrophinopathies by Carlo Raj, MD is from the course Polyneuropathy. It contains the following chapters:

    • Myopathy Junction
    • Dystrophinopathies

    Included Quiz Questions

    1. Charcot Marie tooth disease
    2. Duchenne dystrophy
    3. Limb-girdle dystrophy
    4. Myotonic dystrophy
    5. Becker dystrophy
    1. Fibrofatty tissue accumulation
    2. Muscle hypertrophy
    3. Nerve enlargement
    4. Inflammation and edema
    5. Accumulation of blood
    1. Dilated cardiomyopathy
    2. Restrictive cardiomyopathy
    3. Hypertrophic cardiomyopathy
    4. Mitral valve prolapse
    5. Myocardial infarction
    1. X chromosome
    2. Chromosome 5
    3. Chromosome 16
    4. Chromosome 20
    5. Chromosome 3
    1. Frameshift mutation
    2. Point mutation
    3. Copy number variation
    4. Missense mutation
    5. Nonsense mutation

    Author of lecture Myopathy Junction and Dystrophinopathies

     Carlo Raj, MD

    Carlo Raj, MD

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    By Hannah B. on 06. December 2017 for Myopathy Junction and Dystrophinopathies

    very good video. Did not not know the relation to floppy baby and botulinum toxin.