Understanding Myasthenia Gravis: Diagnosis & Management

Please signin to watch the full session

Understanding Myasthenia Gravis: Diagnosis & Management

17 Jul, 5:30 AM

[Music] good morning everybody i'm dr marat [Music] student so it's a pleasure to host a session where sciencer is conducting and uh to introduce say sir scissors was the professor of internal medicine let's say jsmc and kmh where we were all the students and always an enthusiast in teaching students now he is working as a professor at diwa battle medical college and consultant physician at apollo hospital navi mumbai today's session is about myasthenia gravis its diagnosis and management i think uh we can start with uh already people have joined it so i think so over to you you can start oh thank you everybody so now this is about understanding my senior so how would you define it those who are using it for uh preparation they can use these definitions so my mycenaea is a autoimmune neurological disorder affecting the neuromuscular junction [Music] and what causes it okay is and as i said it's an autoimmune disorder so antibodies produced against receptors which are style volume receptors so to understand this better i'll just go through quickly the normal physiology of muscle contraction if you understand that then it is easy to conceptualize what is my thing so what is the normal physiology of muscle contraction this we need to know so when an impulse travels down the peripheral nerve and reaches the neuromuscular junction at the junction there is there are neurotransmitters a style choline is the neurotransmitter so when a single impulse travels down a style choline is released from vesicles at the end plate with the pre-synaptic it is the synapse now with one end and the muscle at the other so from the knob terminal we call that pre-synaptic part of the neuromuscular junction so style choline is released now this style stimulates the style cooling receptors which are at the postsynaptic that means the muscle end of the synapse so these receptors sense the style and there are pores in the style choline receptors which open up and this allows sodium ion to enter into the muscle right so entrance of this cation causes depolarization of the muscle if the depolarization is sufficiently strong an action potential will generate and the muscle will contract so this is the usual day a single impulse traveling is received like this way by the neuromuscular ejection and the muscle contracts now once the muscle has got depolarized it has to immediately get re-polarized so therefore there are there is a chemical there polynesia rays which metabolizes the released style right and then the muscle gets repolarized it comes in the resting state okay so this is the usual way a muscle contracts by a single impulse now there is this these receptors are of vital importance to sense the style coding now these receptors are there their subunits are around the core of the receptor which is normally closed and opens when their style cooling interacts with the style cooling receptors so these clustering of acetylcholine receptors is absolutely essential so there are other factors which influence these clustering of the style cooling receptors so factors like there is a protein of enzymatic protein called muscle specific kinase then there is lipoprotein receptor related protein so these substances help in aggregation of the acetylcholine receptors right now once the muscle contracts action potential develops the style cooling is metabolized by cholinesterase right now just imagine if there is repeated impulse coming down when you do repeated movement when repeated movements that means repeated impulses are traveling down the receptor there is a phenomena called pre-synaptic run down three synaptic random this has to be understood so what happens in this if repeated impulses travel down the nerve the amount of action the style colleen released progressively decreases okay so this pre-synaptic rundown is a normal phenomena on repeated stimulation now with understanding of this we can understand how mycelia gravis occurs and what is the problem in this right so what is the etiology or etio pathogenesis okay why this autoimmunity leads to neuromuscular junction disorder so being autoimmune there is release of antibodies auto antibodies to self protein auto anti autoimmunity can occur due to an external protein like in infections but it may occur to internal matters as well so there is some protein within the body which causes activation of antibodies which are directed against acetylcholine receptors so the basic problem in mycelial gravis is that the number of actile choline receptors decrease because of production of auto antibodies and these antibodies are actile choline receptor antibodies so 85 percent of patients who have mycelia have these style choline receptor antibodies now of the remaining 15 percent okay about 10 percent have muscle specific kinase antibodies right so what is left to explain the five percent so in these there are antibodies against the other proteins which help in aggregation of style cooling receptors like i told you lipoprotein receptor related protein it's got lrp4 so for antibodies very small fraction and about one percent you would not know what has caused this mycenaes but on the whole it is well understood which is common to have so that's the pathology the production of style cooling receptor antibodies or musk antibodies in a small part of small fraction of the patients so we are doing we are trying to understand why mycenea occurs so what is the etiology the pathogenesis is this style volume receptor antibodies but then why they are produced so in study patients with mycenae it was found so that we attribute as the etiology that 75 percent patients of mycenea dramas have thymus abnormal so thymic abnormality is the most common reason to get this autoimmunity now what is wrong with the thymus gland the thymus gland is functional in childhood okay in adults it becomes non-functional but in 75 patients of my senior it is found that there is thymic abnormality most have thymic hyperplasia and about 10 percent of patients of mycelia have frank thymoma tumor of the thymus plant now how is the thymus responsible here so on biopsy of the thymus gland it is found that on the surface of the thymus gland they are muscle like cells similar structure proteins it's called myoid cells muscle like cells on the surface so this is expressed in thymomas and thymic hyperplasies so these muscle like cells have also have acetylcholine receptors so the system gets exposed to acetylcholine receptors on the thymus gland which is hyper plastic or thymo okay frank hylon therefore the body in response produces antibodies against style going into the surface so this is clearly understood now this explains why there is this neuromuscular disorder where there is decreased amount of hostile choline receptors now in the pathology of the neuromuscular junction in which is there in myasthenia gravis it is found that the number of hostile holy receptors are less than normal one the other factor which is seen which is also attributed to these style interceptor antibodies is that these antibodies cause some destruction the postsynaptic membrane for synaptic membrane on the muscle side okay which harbors the style coolant receptors so these postsynaptic membrane is in form of folds the peaks and troughs that folds on the postsynaptic intake and these style receptors are present on the peaks of the force and cholinesterase in the clips so this folding at the of the postsynaptic membrane is also destroyed there is flattening of the postsynaptic the less number of peaks and troughs so these two features have been pathologically studied but on the whole to understand what we can take home from today is that there are decreased number of established centers so as the number is less so the amount of acetylcholine is not sensed appropriately in my senior grammars there is no defect in secretion of a style the defect is in sensing it because of less number of style cooling receptors so neat questions like that okay so that's the pathology now what is the chief feature how is this disease if in case you are defining mycenae so it is an autoimmune disorder of the neuromuscular junction and it is characterized by what is the main specific clinical feature which i am going to tell you in the future so my senior gravis this autoimmune disorder of the neuromuscular junction is characterized by weakness and fatigue of muscles so fitting what is important here so what we understand with fatigue is that when a repeated movement is done there is progressive weakness so a repetitive movement will induce weakness that is the characteristic of my signatures now why this happens it should be at this stage of understanding it should be clear that because there are nests less number of receptors and on repetitive movement as i told you the pre-synaptic run down so progressively less amount of style cooling is released therefore less and less amount are sensed by the limited number of style cooling receptors because of those presynaptic run down there is fatigue that means repeated movement will cause progressive decrease right so this is the so this normal physiology of muscle contraction what is the pathology in my senior gravity having understood that proceeding now to what would be the clinical feature [Music] in this before we go to the actual manifestation other things to be understood for students is that what is the epidemiology how does it affect the population so as i told you it is not an uncommon condition 200 per 1 lakh population okay that is quite a sizable amount now females are affected more than males the ratio of three is to two [Music] right now younger females in 20s and 30s are commonly affected whereas men are affected in later stage in the 50s and 60s so this is okay how the population is affected now what is the clinical feature if you have to tell in one sentence the specific clinical feature is that fatigue and muscle weakness is the main manifestation of myself fading would mean repeated movement would cause progressive weakness [Music] therefore the weakness is maximally manifested at the end of the day right so people complain by evening there is more weakness if a person sleeps who is affected sleeps or takes a risk finds that the power is improved right so patient is best after sleep and worst after having worked so generally people complain of these manifestations by eb now what are the early features from here so what is characteristic here is that creating cranial muscles that means muscles supplied by the cranial nerves are involved earliest so granular motor cranial manifestations are not used in this the first to be involved and most common presentation is third nerve involvement patient complains of ptosis and diplopia so the third involvement is just a patient complaining of doses or simply diplopia should be considered okay and this should be ruled out other cranium of involvement which also characterizes after third this ocular muscles okay if only ocular muscles are involved that condition is known as ocular moisturizers but more than 80 percent patient who have machining will later over a period of two to three years will develop muscle involvement as well because tip now so concerned with chewing so this is a repeated movement chewing patient will complain like person is chewing gum so first few movements are okay but after chewing for few movements they find that it's difficult to chew them or like eating their food is to be true tough food meat okay chewable food so first few bites are okay but after that the patient starts having weakness of cueing so that the facial facial nerve environment also quite common okay so like person wants to smile so he will not be able to do this it's called snarling smile patient wants to show his teeth so he'll just lift his lips so snarling smile is manifestation then there's muscles of swallowing when they start getting involved the patient has difficulty in depletion but how he expresses it mostly on swallowing liquids there is there is nasal regurgitation of fluids so this is another point to be taken into account while drinking water water comes out of my nose especially after lunch or dinner i have chewed for longer it's a nasal regurgitation of liquids the voice changes that is patient becomes dysarthric that is because like that you say the tongue movement becomes less therefore patient being tends to get disarted so by evening patients voice changes and it's called mushy voice like you're talking to a child so that kind of voice okay so this is the early feature earliest being ocular process and diplopia later leave muscle weakness now it is purely motor mycelica there is no sensory involvement no bladder involvement the higher functions are all intact except for the speed becomes this r3 so this is the major manifestation so when this kind of complaints are there how to confirm so investigations now invasive clinically it would almost be clear that this looks like my seniors an experienced person from now on you people as well would be able to pick up okay clinically what is my thing but you can't start treatment unless you confirm because the treatment requires many aspects long-term treatment surgical intervention is there which is recommended for myself so the treatment okay is to be done only after having confirmed so what are the investigations easy ones so the gold standard is demonstration of the antibodies so antibody to a style choline receptor acid that is available everywhere now the style columns separate antibody assay so that would come positive in most patients those who have negative acetylcholine receptor doesn't mean that there's no masonic so they must be investigated further musk antibodies muscle specific kindness antibodies so that fifteen percent patient that is present lrp4 as i told you okay this is not commercially available at the moment so these two antibodies can be done you will miss in case that you just miss two or three percent patience so that is this is the confirmatory investigation but bedside assessment website testing can be done there is something called ice pack test ice pack test is done in initially the patient has got ptosis so that can be done in the clinic or at bedside you can do if the patient has closes ice pack is placed on the protic eye right and placing ice improves the ptosis that is because holiness stress gets inhibited by cold so the amount of style increases therefore patient has transient improvement in the power [Music] what else can be done is nerve conduction test as i told you there is fatigue so repeated impulses passed down the nerve will cause progressive weakness in the evoked response right normally there isn't more than 10 percent decrease in the force power of contraction on repeated movement on electromyography is suggestive of icd right so that that's how you diagnose now as i told you there is thymic involvement so therefore the thymic involvement is best demonstrated okay ct scan of the chest so in the interior mediastina a hyperplastic or a thymum hyperplastic thymus or thymoma which is essential because that involves the treatment so these investigations confirm my senior gravis right and after that one can proceed now there is one more bad test which is not done present times because of the assay of the antibodies are present but earlier time this was a good test it can be done now also we have done this is called androphonium test hydrophone so it involves anti-colonist rays this is also known as the anticholinesterase so the idea is you choose a muscle okay target muscle which is weak glycosis or the speech abnormality due to tongue weakness or you ask the patient to extend his arms the arms start dropping because it's a fading ability cannot sustain the activity so hydrophonium is used in this hydrophonium is a very short acting anti-holy nester is it blocks the pollinator stress so the amount of style cooling increases okay and causes improvement in the muscle power so your target muscle like ptosis tongue or extended arm is chosen and two milligram of hydrophonium is given interestingly immediate improvement in the power this come confirms that the patient has got a neuromuscular junction disorder involving the involving since style cooling okay so by raising a stimulation power is improving if two milligrams would be given intravenously fails to evoke the test the test is repeated using eight milligrams so this can be done if there is still doubt or you want to show magic in the world so it's right so but now this is not necessary if just a stack only receptor antibody level being raised is diagnostic okay so this is an investigation which we immediate attacks immediately and the action passes the two minutes okay so that's why hydrophonium is used right now what is the management how to manage the simple immediate improvement okay in manage before understanding management in clinical manifestation you understand one thing that i told you about fatigue ability involving cranial muscles and then the muscles but the respiratory muscles when they get involved okay then that will cause a life-threatening situation so if the respiratory muscle is involved in mycelia which would occur okay after a few years of adding machining this situation is known as myosthenic crisis because it just created a crisis situation in the sense that such patients will require respiratory assistance okay involving positive pressure ventilation so such a situation called mycenae crisis that is the severe form of mycelium the most the least severe okay in of course almost form of mycenia is ocular mycelium but then process is hazardous the person doing work driving in this situation so these two extremes ocular mycenaean and the other one being mycenae crisis which requires ventilatory assistance so these we need to understand before we enter into money so treatment how to treat okay the easiest way to treat is the raise the amount of the stock only in the neuromuscular things therefore anti-polina stress drugs are used like hydrophonic but androphonium is very short-acting is just used for diagnosis so the best drug is spiritual stigma so anticholinesterase drug used is pyridostic 30 to 60 milligram three to four times a day now this has to be tailored if we start with the minimum goals and then gradually it can be increasing the dose of above 200 milligram okay it's not beneficial means it has a plateau effect okay and the side effects should be too much patient will get muscarinic side effects of acetylcholine so just like organophosphorus so 60 milligram three to four times a day is adequate those who are treated theoretically now timing is used in such a way that activities which get affected by mycenaean like well patient cannot eat properly because of inability to chew fatigue and mastication so it is given half an hour paradise treatment given half an hour before the action the onset of action of paradise treatment occurs in 30 minutes maximum and will last to three to four hours so therefore your time so that is that that is used now what else is an autoimmune condition so immunosuppression that is the actually the backbone if you [Music] tied over the crisis by increasing your steroid remission is what is your designing so the removal of the offending structure that is the thymus is absolutely essential in fact all patients with style volume receptor antibodies are should be subjected to if it is just an ocular mycenaean then it is not missing but if somatic muscle weakness is occurring then thymectomy is so after and this time antipolynesia is drug the second approach should be get a thyme immediately but this should be done at the proper place where okay surgeons are experiencing the second aspect of the treatment now as it is an autoimmune disease okay so the immunosuppression is what is right neurosuppression is initiated before thyme and then there is improvement then the patient is subjected to thymus so here we need to understand okay so this can be used in other situations of immunosuppression so how to achieve immunosuppression so there is this can be divided into three parts an immediate immune suppression sometimes you may want immediate how do we achieve immediate immunosuppression in which situation in my senior so if there is a my senior crisis because respiratory muscles are getting involved you want immediately to immunosuppress the patient the only way of achieving immunosuppression immediate is by intravenous immunoglobulin iv igg in the standard dose 2 gram per kg divided into five doses given over five days per time okay this is a non-intervention way of achieving so this is done in my scenic crisis or also be before thyme also this immediate immunosuppression the other way of doing this is like plasmapheresis but it is an intervention so immediate immunosuppression for any situation not only mycenea these are the two methods iv igg intravenous immunoglobulin and plasma ferrous this people think that by giving corticosteroids immediately so next way of and in my senior it is usually not indicated to do immediately the separation unless there is a crisis or before time so what is desired required here is intermediate term but this is sufficient in fact nicely aggressive intermediate duration immunosuppression call it immediate intermediate immunosuppression okay because during the intervening period thymectomy is done and 70 patients they have remissions so immunosuppression mostly can be withdrawn so intermediate immunosuppression the drug of choice and well tested so this is the temperature glucose vertical steroid therapy for intermediate right so when you starting derived oral previous alone generally the usual standard dose of one milligram per kg body weight should be initiated and you have to wait for six weeks for immunosuppression to occur so that patience and experience okay in having patience is required so this dose of glucocorticoid previous loan is given and one has to be patient and one has to wait to see the result so it may take at least six weeks that's when glucocorticoid induces immunosuppression right like here the audience is young and wanting to learn so what is to be understood is that when you give particular steroids for anything any other disorder [Music] don't get frightened that it will cause immune suppression i've seen very senior intensive ways and physicians and neurologists scared of using corticosteroids infection [Music] particular steroid is basically used as anti-inflammatory because the immune system will take six weeks to work right so not to be afraid so that here is used that you don't expect immunosuppression to occur before six weeks so this is continued once the immunosuppression begins you get to know that there is improvement in the patient so gradually the dose of insulin can be decreased but that is attempted okay quantum not more than 10 milligram per month slowly and then minimal dose in which immunosuppression maintained is continued for two to three years okay so intermediate immunosuppression with the risk of immunosuppression [Music] but not very well experienced but then they are people in my senior people use these suppressions because there is an opportunity to see how they affect like cyclosporine or tacrolimus so these three glucocorticoids across cyclosporine these are used for intermediate immunosuppression understood the glucocorticoid is limited by its side effect okay so you want to know how to manage the side of it many people use because i'm talking about if you just listen many people will be many of you would be using google cards for other so when you use glucocorticoid the immediate side effect is muscle weakness so that's why in my senior many people are afraid of using a very high dose initially so it's they increase the dose okay the standard 30 milligram and then this this can be done okay so immediate muscle weakness earliest side effect of corticosteroid you give and patient gets this is because of hypokalemia that occurs with glucocorticoid so one should be aware when you are using large growth so when those who are aware there is no problem all right then other side effects long-term metabolic side effects therefore you can use if you are using corticosteroid for immune suppression two to three years safely but long-term immunosuppression one time before thymectomy long-term immune suppression but that was the standard way of treating icd or for any long-term human suppression so long-term immunosuppression the drug of choice is microphenolate so because it is devoid of side effects but then it takes longer for immunosuppression to occur so there is a crossover overlapping particles to ride with microfinance now as i told you it will use many other means of immunosuppression here because of the subject so other drug and which is quite effective is as a thyroid for long term okay now one more drug is a monoclonal antibody which is now used with the semen used for other rheumatoid arthritis lymphoma so due to map is basically where it is indicated in my senior is muscle specific kind is antibody positive so in musk all these thyme activity and um pirate of paradise treatment are not so effective and in this the best immune suppression for must positive so for those who so that's it so this is the the other thing is if there is a mycenae crisis you are in intensive care you get a physician managing my senior so if the patient has come in crisis state what has to be done is and now why my senior crisis is precipitated the usual usually an inter current infection patient my scenic patient getting an inception so that is the commonest reason to get myself crisis so such in such patients ventilatory support is essential okay so tied over the crisis number two you do an immediate immunosuppression using iv igg or plasmapheresis but other standard procedures is that you stop anti-colinos residual because excessive or anti-choliner stress will also cause muscle weakness like the they got any side effect of full energy so that so the anticoagulant drug is stopped infection is treated okay now other reasons why my scenic crisis may be precipitated or you can worsen my senior is because of infections i told you infection use of drugs so certain drugs cause increased in the manifestations of mycenae like usually is to antibiotics amino glycosides you should not use things the manufactures may induce myasthenic crisis or even fluoroquinolones so commonly used so these main don't use these three groups of antibody easy to remember aminoglycosides fluoroquinolones and macrolides not to be used beta blockers to be not used avoided so these are stopped myosthenic crisis ventilatory support you give an immediate immunosuppression using ivig which is an expensive proposition so if that is a limiting factor you do a plasmapheresis okay the patient improves and after that the treatment is same like any standard mycelium okay so that takes care of management also you have understood my senior graphics how to investigate how to treat now here no just because you have 10 minutes more time just one more condition which can be made my senior is and commonly academically you know is lambert eaton syndrome okay so lamberty mycenic syndrome usually seen with small cell carcinoma okay same muscle weakness people get confused but how do you differentiate that theoretically you know and that you can use practically to differentiate in fact number eight in my scenic weakness will precede any manifestation of bromogenic customer before that okay so lambert return is a pre-synaptic disorder my seniors are personable so in this condition number two there is decreased release of a style there are antibodies against calcium channels so calcium channel antibodies which inhibit release of the style so therefore how the patient can so this is pathological difference okay difference in clinical manifestation is that repeated movement will cause progressive improvement in the power unlike my signal there is decreasing power now one the neurological findings of my signatures pay attention this can be used is that all signs of neuromuscular junction disorder without sensory involvement without bladder involvement and in examination of the nervous system when you do motor examination deep tendon reflexes are preserved you do a deep tendon reflex so this is one defining question or motor expression this is easy to understand so in the first movement there is no problems when you do deep tendon reflex you do one movement so the first movement occurs normally if you have to repeat the deep tendon reflex then it may become absent when doing repeatedly so the deep tendon reflex is preserved in my ceiling whereas in lambert eaton syndrome okay because the first response is v okay so that's to be understood other condition to be differentiated is thyroid oxygen paratoxic periodic weakness that is not difficult to diagnose right so that's it if there is any question and even having any questions can post it in the comments all right no questions uh sir i have one question sir if a patient who is on uh redness alone who is already taking it started recently now comes in my aesthetic crisis then what should be done with the uh dose of prednisone one and uh second is uh the role of uh methyl prednisolon pulse uh in a in the myasthenic ground the second one is easy to answer basically [Music] now [Music] is that as this led to infection immunosuppression itself can lead to infection so it has to be treated but your objective is already achieved of inner suppression so these two have to be collected in place so this may suggest that long term now the side effects of immunosuppression is occurring in this question you have to manage so this suggestion should be after the crisis is over this kind of interactive and active way of managing so there is a question from sadhar sani differentiate portalism what do you remember [Music] for the first time with crisis okay then you need to differentiate whether this is bottling causing poisoning so this problem may arise in patients with mystery crisis so a dietary history the drug history has to be taken and there is test modeling toxin level can be done in fear that's a differentiator okay so swish is asking can thymic hyperplasia be detected on ct is thymectomy performed only for thymoma or even [Music] women would like [Music] is [Music] that depth has shown that thamectomy definitely leads to complete remission or lesser use of immunosuppressants the only way as i told you intermediate suppression you do with particular steroids in the hope that there will be lifelong emission so this can be achieved not just for thymo but even for [Music] so there is a question how to prevent progression from ocular to generalized masternode [Music] [Music] it cannot be prevented [Music] because there is no way um so can neostigment be used instead of pyritos statement side effects because the side effects and crossing deployment so you all have been used so finally it is and ingrow suppression has improved the last century it was a severe disease categorizes now one person there is no way to prevent that [Music] did most questions have been covered till now yeah right yes thank you

Description

The most prevalent condition affecting the neuromuscular junction (NMJ) of the skeletal muscles is myasthenia gravis (MG). The classic presentation is a variable weakness, more pronounced in the late afternoon. Usually, the muscles in the eyes, throat, and extremities are involved. Muscle weakness results from the diminished electrical impulse transmission across the neuromuscular junction caused by the development of autoantibodies against the particular postsynaptic membrane proteins. MG can be triggered by a wide range of factors, including infections, vaccinations, operations, and medications. Numerous difficulties are brought on by myasthenia gravis. The acute respiratory paralysis known as myasthenic crisis, which necessitates critical care, as well as side effects from long-term pharmaceutical use, such as opportunistic infections and lymphoproliferative cancers, are among them. A complete understanding of the pathophysiologic mechanisms, clinical manifestations, treatment strategies, and complications of myasthenia gravis is necessary for better patient care and outcomes. Join us live with Dr. Sahay for this blockbuster live to understand about MG in depth.

Speakers

About Medflix

Medflix is a new platform by PlexusMD, India's most active and trusted doctor community. On Medflix, you can discover live surgeries, discussions, conferences and courses from some of the top doctors and institutions across the world. Join clubs in your areas of interest and access hundreds of amazing live discussions everyday.

Contact us

support@medflix.app

+91 9023-729662

Medflix Logo

© 2022 Plexus Professionals Network Pvt Ltd

InstagramFacebookTwitter