Transcript for:
MGFA Southeast Conference Summary

um good morning everybody happy saturday uh welcome to the mgfa southeast regional conference we have a very exciting program today we actually have three volunteer organizers uh we have kathy timothy who will be moderating today and pam alec they are the co-support group leaders in saint petersburg and we also have another volunteer jenny clark we definitely want to first start off by thanking our sponsors who make this possible alexion argenex jansen ucb immunovance horizon a credo and sanofi we have a really exciting program today this is our agenda and what we like to ask is i think everyone's pretty good at at after all these months and months of doing zoom calls please stay on mute when we have our q and a's we will ask you to put your questions at any time you have questions put it in the chat and we will be um watching the chat and we'll be moderating the questions so how's that i am going to stop sharing and i'm going to allow dr rosario to pull up his slides and kathy it is all yours thank you good morning everyone we're so lucky to have dr rosario with us today dr rosario was born in puerto rico he initiated medical school in guadalajara mexico before transferring to new york medical college where he successfully completed medical training he then completed a neurology residency at university of connecticut in 2012 where the interest in neuromuscular disease was started he then transitioned to duke university in north carolina where he completed a neuromuscular disease fellowship in 2013 followed by an advanced neuromuscular disease fellowship in 2014. he then moved to st petersburg florida where he has been faculty with bay care neurology group and the tampa bay muscular dystrophy care center dr rosario and by the way dr zario go huskies that's right all right um good morning everyone um this is a lengthy topic and we only have 45 minutes so i'm just gonna go ahead and get into it can can everybody hear me well yes okay and can anybody see the slides well yes okay goals for today we're going to learn what are the treatment options in myasthenia gravis above all we i i really would like to show how do they work in the mechanism and why do they work why do we choose these medicines for myasthenia how do they work in the pathophysiology of this disease there are different treatments in myasthenia gravis things like lifestyle modifications some exercise i believe this is going to be touch more later today part of treatment is understanding your body and understanding what things to avoid what things to do what things not to do recognizing some of the early symptoms to avoid worsening there's also pharmacological treatments there's symptomatic management with with medication like methanol for example there's also immune immunomodulatory medications like prednisone and there's some oral other oral ones like cellsep imuran we're going to be touching on these later today there's also some iv minimal relatory medications like solaris ultimates or vip guard in addition to the pharmacological treatment there is also interventional procedures typically done in emergency settings and that will be plasmapheresis or ivig finally there is surgically mentioned myasthenia with thymectomy um but from all these treatments on today's uh chat we're going to be focusing on pharmacological treatment and the emergent management in myasthetic let's start with meston but to understand how methanol works we really need to know about the neuromuscular junction physiology and these are very complex topics um and i i'm gonna i'm gonna use language and i'm gonna use pictures that hopefully i will be easy uh to to understand hopefully i can transmit a complicated topic into something easily understandable but to your left you see here this is the neuromuscular junction down here can everybody see my pointer as it move anywhere you can see my mouse yes i mean dr rosario so this is uh this is your nerve okay and this down here is the muscle and between the nerve and the muscle we have the neuromuscular junction when we decide when when when we decide to contract a muscle either voluntarily or involuntary when we do this our brain sinks down signals through the brain through the brainstem into the spinal cord from the spinal cord into the nerve and travel down down down down down here once it gets here the nerve releases these vesicles these are acetylcholine vesicles and these vesicles now are going to flood that that that junction the neuromuscular junction and these are all these red dots and hopefully they're going to find an available uh acetylcholine receptor these receptors are in the muscle membrane so like this one for example okay this one red one here finds this closed receptor and once it binds it it opens it up and then there's some chemical reactions that occurs eventually that will lead to muscle contraction and that's the normal physiology of the neuromuscular junction what happens inside within this junction right here within this space we have this enzyme here in the corner it's called the acetylcholine esterase and this enzyme here that looks like a little pacman the job of that enzyme is to eat away all of these pebbles all of the acetylcholine vesicles right here okay here in this other picture we have the receptor and this is the the myasthenia antibody in green basically it is covering the spot where the acetylcholine should bind so that it opens it so when we have the receptor right in the middle covering the site then the acetylcholine will not will not activate that receptor to open up and follow the chemical reactions that leads to contraction that leads to weakness so how mestino works is the following you remember this enzyme we just talked about the acetylcholine esterase and the job of this enzyme is to eat all that is to eat all of these vesicles of acetylcholine right here so what messed it on or pre-dos technique what it does is it pretty much blocks it it shoves it in the mouth it blocks it and when this enzyme is blocked when this acetylcholine esterase is blocked it can no longer eat all of the little pebbles all the acetylcholine and that creates more acetylcholine available in the cleft in that space i'm sorry it will leave more of those now now our junction is going to be full of acetylcholine because the pacmans that eats them it's blocked by the mastodon when we have a lot of them that say now we have a lot because all the pacmans have been blocked and they're not eating them they accumulate they aggregate and then eventually they will gang up and they will take the receptor and they will push it away and that leaves the open site so that the vesicle or the acetylcholine reach it and eventually leads to contracture and that's how and why mastodon works it blocks the acetylcholine esterase when it blocks it now it leaves a lot of acetylcholine in the junction and all that acetylcholine will gang up and will scare away and push away the bad antibody from the receptor leading to improvement in strength mustang comes in 60 milligram tablets they're often scored there's a time span option which is like a extender release option there's also a syrup option liquid and there it also is a iv or intramuscular option that one's left pretty much if you are unable to take any oral medications don't let anyone give you iv mesting on please if you cannot take any oral messing on then you want to do intramuscular vest masculine the reason is iv methadone can cause cardiovascular complications mesoderm works at the neuromuscular junction we just talked about that and it provides temporary improvement in strength starts working in about 20 minutes or so then peaks in about 45 to 60 minutes and it lasts anywhere between four to six hours so that predictability on how it works when it peaks and how long it lasts it helps us uh the clinicians to better to guide your treatment help us understand what kind of dosing how often how high of a dose or how frequent of a dose the patient will need it does not have long-term side effects it does have short-term side effects while the medication is in you and most common are being gastro things like diarrhea abdominal discomfort you could also have salivation lacrimation muscle twitches etc the dose is individualized and standard dose varies between patients um some some dogs start at 30 milligram three times a day but that might be too much or that might not even touch you everybody is different and it is advanced as tolerated as discussed some of these common side effects or nausea how many abdominal cramps lacrimation salivation muscle twitches please be mind be mindful a lot of methanol is bad okay about 45 minutes to an hour during the peak dose if if if you take too much it can worsen myosin it can cause a weakness it can also slows down your heart rate and it's it could be dangerous so too much methanol can be very dangerous also we're talking of messing on working at a neuromuscular junction uh level meaning that really does not alter your immune system being mycena and autoimmune disease it does not affect it doesn't stop your immune system from making the bad antibodies you can take all the medicine in the world your immune system is still producing those bad antibodies to understand how immunosuppressants work to understand how to reduce those that antibody production we we need to have some knowledge of immunology basic immunology because it is very complex but as you all know from when you get your cbcs in your blood work you have different type of cell lines you have the red blood cells you also have the platelets you also have the white blood cells and within the white blood cells there's other cell lines the important ones here are the lymphocytes and these are the the when we're talking about myasthenia these are the important ones and that b cell right here this b cell lymphocyte will transform into plasma cell will change into a plasma cell and the function of plasma cells is to produce immunoglobulins immunoglobulins can be used interchangeably with antibodies but it produces immunoglobulins and and there's different types of immunoglobulin there's igg there's ige igm g i g a etc n and all these igs or all these immunoglobulins have different functions for example iga has to do with the immune function of mucus membranes like your lungs or your gastro ige has to it has to do with the parasites or asthma um pretty much parasites and and that sort of stuff but the important one here i want to bring to your attention is igg the myasthenia gravis antibody is an igg our plasma cell produce iggs which protect us against bacterias viruses toxins etc so we have the plasma cell here as the b cell converts into plasma cell once we get a virus or a bacteria this plasma cell produces iggs so this right here in green is our plasma cell that produces the igg which is a good antibody fighting against this guy however that same plasma cell can get confused and can do and can form and will also be the one that forms the bad antibodies or reactive antibodies or auto antibodies these are all synonyms and these are the bad antibodies and these are the antibodies that don't target the virus or bacteria it's now targeting a part of your own body in this case the acetylcholine receptor now the immunosuppressant some of which are listed here they work in different ways right they all have different mechanisms of action we're not going to go through all of them but the end result is that they kill that plasma cell or they low or or they reduce the ability of that plasma cell or that b cell to produce it reduces the levels of plasma cell so in other words all these medications simplified will reduce or kill or eliminate try to eliminate this guy so that it does not produce the bad antibodies unfortunately remember that this guy also produces the good antibodies that's why all of these medicines they cause immunosuppression meaning they lower your immune system and that's how all those medications work they reduce the b cell population or the plasma cell so that we get less less of the bad antibodies a little quickly on prednisone it's oral there is an iv alternative in case you can't swallow it is relatively cheap and it is it is it works it's high it's very effective in myasthenia it does not work fast does take several weeks to start working and um it you know the recommended dose is high dose if you have generals my astina gravis and you can't swallow you're having problems eating [Music] chewing and you get started on prednisone five milligrams that's that's not appropriate really we should use high dose prednisone and uh ocular myasthenia might be less than 60 milligrams but it should be a high dose pregnancy okay and then it gets reassessed over over some time and then eventually once you're all better we start a tapering process and with prednisone you you need to expect side effects and these are some of the side effects of messing on your left it's a it's a whole list of of of there are short-term side effects like insomnia jitteriness anxiety reflux and then there's some other longer-term term side effects like perhaps weight gain or osteoporosis cataract etc here on your left side there's a list of some of the most common immunosuppressants used they're also norm uh coined as steroid tapering agents you might you might hear that term also cell sep which is mycophenolate immune which is acetharaprine rituxan solaris ultimarus vivcard and when do we use these well we use those when [Music] once when we cannot taper down that prednisone right so you start with the mesting on which does not have long-term side effect if you still have symptoms when we add prednisone and then once you're better we reduce prednisone but if we are unable to taper off that chromosome then we institute these medications and which one to use that's that's a shared um consent right that's a shared decision with uh with a clinician the one we use it depends on many things it depends on the side effect profile of the medication um it depends on the frequency of administration let's say you're not used to taking a medicine twice a day like cells but even urine can be taken once a day for example also depends on your comorbidities let's say you have history of meningitis then i wouldn't use solaris or old tumors well let's say you have a history of pancreatitis then i wouldn't use immune because so depends on what kind of comorbidities you have will help me choose an agent that's safer also depends on how severe is your illness because some of these like mycophenolate and insect fibrin particularly as a therapy they take many months to start working and perhaps we need something of a faster onset ultimately the insurance has a lot to say and i may want to start something but your insurance might not approve it i just want to spend this slide on rituxin in case there's anyone with musk in the audience or or on on retoxin i mean it can be used also for refractory generalized myasthenia and retoxin is a monoclonal antibody against cd20 and and i'm going to unpack what what that means a monoclonal antibody many of these medicines are monoclonal antibodies and and you know what an antibody is so so a monoclonal antibody is an antibody that has been created engineered in a lab by intelligent people that actually makes it okay and this antibody which is up here and this antibody binds cd20 and cd20 is a protein that is in the surface of the b cells all the b cells have in the surface this little yellow cd20s and city 20 allows an optimal immune response cd20 is the one that guides and move around that b cell same way a jockey uh moves a horse in the direction where you want the horse to go well that cd20 is kind of the jockey of the of the b cell without uh without properly function cd20 the cell the cell dies okay and if the cell if the b cell dies then the b cell does not convert into plasma cell the plasma cell does not produce antibodies if it does not produce antibodies then the myosin agravis antibodies are not produced and that is how how retoxin works is an iv medication and is every six months works well musk also used in refractory uh gmg ultimatus or solaris to understand these two medications we need to know a little bit about the complement system and our immune system not only has the iggs and the ant and not only have the antibodies and different type of antibodies but it also have this little circulating proteins around and they're called complement and they're called complement because they actually complement our immune system they're not it but they are part of it okay so they improve the ability of the antibodies and those immune cells to get rid of pathogens they they they improve the the antibodies and immune cells to reach target organs same way a police officer directs the traffic the traffic and helps those vehicles come in and out and move safely around and help vehicles get to their destinations in that same way the complement system aids all of our immune cells and our antibodies to reach their target and this picture here this red is our muscle and our muscle have our folds here and within this surface with the folds you we have the receptors these are the acetylcholine receptors okay and this in blue is a myasthenia antibody in here it is blocking it is blocking one of the receptors so acetylcholine cannot reach this guy this receptor here what happens when the antibody reaches the receptor it activates the complement system and i see the complement system like a snitch the complement system will say will activate the whole a whole cascade of of immune cells i will tell them hey guys come down here let's kill this muscle membrane so once this binding occurs it activates the complement system the complement system now calls all this army of immune cells to kill or to destroy the muscle membrane on the right side here we see a muscle membrane that is now less functional the deep folds here have now simplify they're not as deep and now the recep that reduces the number of receptors you can count there's a lot of receptors here and this side here there's less receptors and those receptors not working well so the immune system the complement system calls bad cells to come and attack the membrane where the receptor lives what solaris or ultima is what they do is they bind the complement system so when the myasthenia antibody attaches to the receptor now these complement system they are shut up they the solaris prevents them from calling all those bad guys to attack the muscle membrane and that's how solaris and altimeters work notice that they work at the complement level so they really do not reduce your your cells your b cell ability to produce antibodies to produce myostina antibodies as such they don't lower your immune system and they can't even be used in combination with immunosuppressants briefly on these they're both iv they have the same mechanism of action the efficacy between those are the same the clinical trials the difference is on the dosing solaris is every two weeks after an initial induction dosing and then ultimarus is a longer acting one it's done every eight weeks there's really no no reason why to be on solaris when when when you can be on altimarus the efficacy and the mechanism of action is the same they're both for adults serve positives and general myasthenia gravis and they both require a meningococcal vaccination two weeks prior to treatment event card now let's talk about vip guard to understand how vip guard works we need to know about the concept of igg recycling as you remember our plasma cells comes from b cells they produce antibodies now those antibodies they don't live forever they they're around for about 14-21 days in our bloodstream and while they're around our bloodstream if if they're good antibodies they protect us but they're bad antibodies they're attacking our neuromuscular junction in about two to three weeks these antibodies are removed from our body and how are they removed there's a cell called lysosome and the lysosome will degrade it it will eat them it will melt it down but it will not eat all of our iggs some of the iggs will have a second chance to live and go back into circulation and that's called igg recycling and i've created this so it's easier for you to understand here up here is our this is a blood vessel in your blood vessel this is just our bloodstream we see here that we have eight iggs two of them myasthenia and the other ones normal iggs okay and it's been two to three weeks so now it's their time to die go away the way this happens is our cells this is a cell of the body could be a cell from this lining right here our cell will take those eight iggs into a endosome here and once they come in they will play musical chairs within this endosome and the the chairs are called fcrns and some iggs will find fcrns and some of them will not find fcrn those that are unbounded to the scrn those that could not find the musical chairs they will get degraded or eliminated eaten by the lysosome now those four that actually found the fcrn the musical chair they will get a second chance and they will get thrown back into our circulation now that's fantastic because that's a way our body prevents us from not having enough igg now we have a lot of ig even when we are immunocompromised temporarily our body is not eliminating all of our iggs but if you have myasthenia gravis you do not want your own body to throw back the bad antibiotics into your circulation you really want to get rid of all these bad antibodies so that's where vip guard comes in what vivgar does is wants these eight antibodies right here iggs once they come into our endosome once it's time to find the musical chair these chairs will be occupied by vip guard vivgar has a higher affinity to these fcrn receptors it will attach to them before these igg's attached to them so we'll they will occupy the majority not all but the majority of these fcrms so now more iggs are unbounded more iggs are free and remember all the iggs are free will get eaten away by the lysosome and the ones that get bounded this lucky one he gets thrown back into circulation along with some of the vip car that's why vip car is it's a long acting and that's how viper works it binds to the fc receptor so that the antibodies both the good and the bad so that the iggs do not get recycled and they don't and and they go and die into the lysosome notice that it does not eliminate all of the anti all of the iggs the majority but not all of them as such it does not suppress completely our immune system also it only affects iggs so all the other iggs are not affected all the other i'm sorry all the other igs all the other immunoglobulins the m the a right all of those are intact okay so our immune system would not be compromised with vip guard because it does not eliminate all of the immunoglobulins it will eliminate majority of iggs it is approved for adults surpositive and generalized myasthenia it is also an iv medication and it is once a week for four weeks and that constitutes a cycle once you complete a cycle then subsequent cycle will be on a as needed basis and that varies between patients for some patients they will need a second cycle in two months for some patient will be in three months or some patient will be more so so that it varies between patients there's no vaccination needed prior to each treatment and some of the most common side effects are headaches there are reports of respiratory tract infections and urinary tract infections now let's move let's move on to uh we just completed the immunomodulatory treatment now let's move on to the emergent treatment and this is plasmapheresis and ivig and plasmapheresis is not a medicine it's a process and basically you get hooked to a machine and your blood will go into this machine and once it's inside that machine it will centrifugate which this is what it looks like it spins around really really really really really really fast and once it spins around it will divide your blood into plasma and cells this the plasma gets thrown out and the cells go back into your body this is how it looks like when it comes out of the center of the centrifuge down here you have the cells and up here you have the plasma why is so important to get rid of this plasma because in that plasma that's where the mg antibodies live so mechanically you are removing the the igg the myasthenia antibodies from your body and that's how plasma freezes work it removes the antibodies the bad iggs the batter the the myasthenia and how it removes them how by removing the plasma from your body from your blood and removing the antibodies translate to less neuromuscular junction blockade so that improves strength plasmophoresis is very effective in my opinion one of the most effective treatments and typically every other day for five treatments and and the onset of improvement is viable generally after second or third exchange we start seeing an improvement now this is short-term improvement okay that benefit will wear off after several weeks so there there has to be a back-up plan when you're doing plasma phrases a long-term backup plan because plasmapheresis is short-term treatment it's indicated for mg exacerbations crisis also for surgical pre-op and and an exception is not the rule but sometimes some patient will need it will need plasmapheresis as a chronic management again the standard doors the standard dosing is five exchanges you could do more depending on certain things that we look into you should not get plasma freezes if you're actively infected if you're septic okay if you have a fever if you have a low blood pressure some of the side effects of plasmapheresis are complications from the central line placement and complication from the procedure itself some institution uses central line some institutions do it peripherally if you get a central line the needle can collapse your lung or you can get infections in the lying or even cardiac arrhythmia from the tip of the line tickling your heart can cause arrhythmia if there are a complication from the cer from the procedure itself includes low blood pressure and bleeding ivig iv means intravenous so the treatment goes through your vein it's not all and igr immunoglobulin so these are intravenous immunoglobulin immunoglobulins are antibodies iggs [Music] and a bottle of of of of of ivig like here hanging here that that comes from the plasma of thousands of donors okay and they make up this super concentrated collection of antibodies and this is how it works this up this right here is your nerve this down here in blue is your muscle and this red things here are your receptors and these smiley faces are the acetylcholine vesicles okay so as we've discussed before the the the acetylcholine reaches the receptor and once it reaches the receptor a contraction occur okay now we have our b cells in our bloodstream and they're making the good iggs in orange however this b cell is confused and it's also making the bad reactive antibody or outer antibody the myasthenia one in teal when you get ivig this is what happens the ivig will bind it will prevent okay it will avoid hopefully those bad antibodies reaching to the target which is a receptor so so that's that's that's part of how it works it will bind the it will prevent the bad antibodies to reach to the receptor in addition you guys remember that compliment that we talked about this niche that tells our immune system hey let's come and attack our muscle membrane well ivig also binds that guy and that's how ivig works it bad it binds the bad antibodies so they don't reach to their target and it also inhibits the complement activation ivig is also short-term treatment it wears off after a couple weeks so a backup plan is also needed also indicated for exacerbations and crisis it can be used for surgical preparation if someone's a poor candidate for plasmaphrases it it's not typically used for chronic management but it could be used in again as an exception not the rule let's say someone has contraindication or refractory to all the other you know multory medications and the dose depends on if this is the first time you get it or if it's more maintenance though the those will depend ivig is used on a number of neuromuscular diseases but it's also used on other other autoimmune diseases as well you should be checked to make sure that you do not have iga deficiency if you have iga deficiency you can have anaphylaxis with ivig anaphylaxis is a bad allergic reaction potentially life threatening it can also cause cv it's also contraindicated in someone who has kidney disease and that's because ivig is a large solute and that can cause pro so and that can cause problems in your kidneys also should not be used in patients who have cardiomyopathy a big heart which a weak heart and that's because ivigs are large volumes a lot of waters a lot of volume that goes in so your heart needs to pump more if you have a weak heart that can lead to pulmonary edema or water in your lungs side effects there are severe side effects that can occur like anaphylaxis that can cause that could be potentially life threatening renal failure as we mentioned it can cause thrombotic events things like stroke okay heart attacks etc it can cause symbolic uh arterial and embolism to an arm you can lose an arm okay um it can cause meningitis and there's also some infusion related reactions like headaches hive nausea flushing vomiting etc some of the infusion reaction can easily be treated with with reducing the infusion rate just making the the iv goes down slower and also the use of pre-medications to avoid headaches and nausea etc there is also subcutaneous ig called hyzentra that's not approved for myasthenia gravis and currently is an investigation over several uh clinical trials and open trials for for hyacinthra so hopefully maybe in the future it will be a fda approve option but for now it's fda approved for other neuromuscular conditions but not myosin or rabbits and this is the last slide and this slide shows pretty much all the mg treatments throughout the the mechanism on the pathophysiology are the different mechanism of how these medications work in this cascade of of areas that we can treat myasthenia so let's start from the right side here at the neuromuscular junction this is where mesting on our periodontal signal it's not here it should be but it's not here but this is where messenger is working okay um moving now to the bloodstream we have the myasthenia antibodies and these could be mechanically removed by plasmapheresis or they can be bound so that they prove so by the ivig so that it prevents it from reaching the target also in our circulation we have the complement and the complement is the one that calls our immune cells to go in and attack our membrane that complement can be shut off by solaris right here also in our bloodstream we have our immune cells our immune cells can be reduced with medications like mycophenolate cellsep or emuran in addition remember in our b cells we have this in the surface of our b cells we have the cd20s c20s is the yawkey of the horse moves the b cell around that one right there can be can be uh blocked by rituximab also here we have the remember the fc rn which is the musical chair that recycling of iggs into our bloodstream can be inhibited or prevented with fcartigamod which is vidguard finally all of our bloodstream all of our blood cell lines are comes from different immune areas in our body including our bone marrow and thymus so that's why phytomectomy can also help in the in as part of the it's also part of the treatment of myasthenia and that's it thank you very much thank you dr rosario that was we've got a lot of good feedback excellent we do have some questions dr zaria and i want to be mindful of your time because i know you have a another meeting um so i'm going to kind of generalize questions so we can get them in groups um how long can you be on an immunosuppressant like in iran can you stay on it the rest of your life if you need to um ideally our goal is to have you be on the best you can be with the least amount of medication if you're on immuran you should i mean obviously you're being monitored you're being examined okay and there are some tools that we use in planning to monitor progress and once you're better and that improvement is sustained then we want to start tapering your medicine slowly cautiously judiciously over over time and and continue evaluating you and see what's the least amount of medicine or treatment that you need to keep you at that at that decent level and that might be some form of immunosuppression or immunomodulatory medicine forever some patients were able to taper everything away after some time what medications are best used for extreme fatigue well that's a um that's a look that's a different off topic fatigue in myasthenia you will get muscle fatigue but fatigue can occur for many many other reasons things like anemia vitamin deficiencies hypothyroidism sleep apnea etc so just because you have myasthenia you cannot just say that the fatigue is from the myasthenia you need to have a medical workup to see if there's anything that can be treated let's say you have apnea well getting that treated might help the fatigue now if the fatigue is if the muscle fatigue is from myasthenia meaning you're using your muscles and you're getting a little all higher generalized weakness from activity then treating the myasthenia should improve the fatigue um what um i have two more kind of generalized questions too um what is available for and we knew this would come up to your negative patients besides prednisone and methadone um well all all of the discussed treatments except for solaris multimeris and vivcard so emiran cellsept mestron prednisone ritoxin ivig plasmapheresis they can all be used in severe negatives hopefully hopefully in the future hopefully near future we can use vip guard in server negatives in their clinical trial sero-negative patients were used as such there is a chance that the fda will approve it for certain negatives as opposed to solaris where seronegatives were not included in their trials so it's less likely that that medicine be approved for certain negatives in the future thank you how about research being done on cannabis mg have you seen anything oh me personally i have not seen it i haven't looked into it either so i am not i am not aware of any research in that field however i have not looked into it either so i i don't know if there's any i don't know if there's any uh research going on with with with cannabis okay um i know we weren't talking about thymectomy but a question came up if somebody is seronegative cannot take an immunosuppressant um is thymectomy then a viable option can you explain what would make that a viable option so if if you have generalized weakness i'm sorry generalized minus senior gravis and sir negative it it it is if it's if it's only ocular or or if it's generalized but mild then thymectomy might not be appropriate it's an invasive treatment um it's a surgery and yeah would not use it if you are only have mild symptoms will not will not recommend plasmaphrases for ocular myasthenia or if you have well control let's say you have general eyes but with initial treatment now you're doing very well you're only on messing on monotherapy maybe on an astonishing basis and you're doing fantastic you do not need a time maximum okay we had a question coming and you know sometimes we forget that let's have it on the journey for a little bit that we do have new people um joining and we want to make sure we educate them can you please explain what zero negative means and why would somebody not take this guard sure um some patients with myasthenia gravis will have the presence of acetylcholine receptor antibodies in their bloodstream not everybody it is believed that about 80 percent of patients with generalized myasthene aggravates will have presence of acetylcholine receptor antibodies in their bloodstream that's a blood work that can be known as lab core quests etc if if a patient with myasthenia gravis tests negative for those antibodies then they're considered seronegatives with time we have find out that they're of course there's other antibodies that causes this condition but technology hasn't we do not know all the antibodies that causes myasthenia we've identified one called musk muscle specific kinase musk antibody and there's another one the lrp4 that's a newer one we're testing for those now um still there's patients that test negative for acetylcholine receptors musk and lrp4 so if you don't have the presence of an identifier any of those then you have seronegative myosin around us and the reason why some of these medications are approved only for several positive is because during their clinical trial the majority or only several positive patients were were allowed to participate certain negatives either were not allowed or they constitute a smaller percentage of the patients that were the medication was studied on thank you if anybody has any questions we could probably take one more um hold on i have one more dr um highest um compliment you got was the best presentation they've seen in 50 years so thank you thank you so much for that um somebody wanted well and this is an objective is vivgart better than than mestino if you're doing well with mestano okay then you then you should not then then messing on is better than this car i mean you want to start with methanol as a reminder mestadon does not have long-term side effects messing on is relatively cheap vip car is very expensive this car is iv and it has side effects mestron is cheap it's oral and does not have long-term side effect so from a side effect perspective and from a a accessibility or access messenger is much cheaper and easily accessible now at the end of the day we use what works so we start with methanol and if mestron helps if methadone achieves our goal then we really don't need to go and go beyond that if we use medicine on a we're still having symptoms that's when we go to tier two or phase two that's when we start adding some of the other ones and vip guard is one of the options thank you very much everybody thank you uh dr rosario that was truly a very great explanation very clear for us and um as dover put in the chat this will be available on um myasthenia.org so you can go back and re-review it if you would like to and we really appreciate your time dr rosario thank you everybody happy to be here now i'm going to introduce dr elizabeth liz plowman she's the owner of the pain boss physical therapy and an assistant clinical professor at texas woman's university school of physical therapy in houston texas she began her career as an active duty physical therapist in the united states navy in 2019 she was medically retired from the navy due to a disability related to myasthenia gravis at which point she opened her own private practice and joined the faculty of texas women's university school of physical therapy dr plowman is a board-certified orthopedic clinical specialist and a therapeutic pain specialist she is dedicated to the successful integration of technology into rehabilitation practice improving access to care for patients with disabilities and helping to move the profession forward into today's tech savvy world thank you so much i am so pleased and honored for the invitation to be here today and to be able to see you i see some friends some familiar faces out there so nice to see you again and thank you very much donna for the wonderful introduction i am um actually i'm gonna go ahead and share my screen so i get going get some slides going here for you but i am um very pleased to chat today hopefully this comes up um about exercise with myasthenia gravis um there are going to be some subtitles here so for those of um for those of you who um need the subtitles just to help with a little bit of accessibility that's there for you my disclaimer is that i it is entirely voice recognized and sometimes powerpoint does not get all the terminology correct so that's my disclaimer on the closed captioning association in orthopedics also in in pain science same science education and most recently i've done a specialty specialty training in neuromuscular disorders and rehabilitation for that because of course it's very personal to me um i was an active duty therapist in the united states navy so i'm working with a wide variety of folks i do have i am now in private practice working with chronic pain conditions and neuromuscular disorders specifically specifically myasthenia honored to be on the faculty at texas women's university and doing research with them into mycena and rehabilitation implications and exercise implications which is fueling a lot of this presentation today and then i think i'm branded on the internet as to my aesthetic pt um so that is me that is my little my little story in pictures here um as a disclosure i have nothing nothing else to disclose and i do want to acknowledge i have a fabulous group of research students at texas women's university working on the projects that i previously described and and they have helped contribute to the content of this presentation so i do want to acknowledge them so coming up we're going to talk about exercise so what is it um we're going to talk about the health benefits mg concerns with exercise and then of course how to exercise safely in the context of myasthenia so this is with working with um any of the myosthenics that i have ever worked with before this is probably the universal question that i get is can i exercise with myasthenia gravis and the answer is yes with the asterisk mark that there are some very special considerations with specific to myasthenia that is different from just about every other condition that might limit exercise yes exercise is absolutely possible and there are wonderful health benefits from it but it has to be approached carefully and likely with direction to avoid any of the complications from myasthenia so in using the word exercise exercise can sometimes be a rather intimidating word and a lot of times when we think of the word exercise certain images come to mind most likely something like that right um but that is not um that is a type of exercise um probably not one that the vast majority of us would be engaged in but exercise can mean a lot of different things so it can be walking um gardening swimming or water water type aerobics which i will get to i will talk about a little bit more in this presentation yoga pilates stretching tai chi and and things in that family are wonderful forms of exercise and movement so aerobic stability court um core training i am from texas so i'm obligated to put some dancing in there um and then just simply things that we don't aren't necessarily organized exercise but um you know spending time playing around with kids pets grandkids um things that require just a little bit of activity there um so maybe in term maybe instead of exercise even though i'm going to use the word as to go through um think um instead if that word evokes that very first image that i put up there the you know heavy weightlifting and that's an intimidating word think instead of thinking exercise think of activity think of movement um all of which are are vital um to to a relatively normal quality of life to doing activities that are important to us and then also to staying to staying healthy so health benefits and i am i'm gonna go fairly quickly on this slide because um i'm not i'm probably telling you nothing that you do not already know so there are a mountain um of hell there's a mountain of health benefits related to to exercise in general not even talking about mg but just in general and the research that supports physical activity for health benefit is staggering i could probably if i had listed every single reference that talks about the health benefits of exercise i think i might have blown up powerpoint so so health benefits it prevents deconditioning so deconditioning is where you know after prolonged sedentary time you get at muscle atrophy and you get various cardiopulmonary related issues too just related to being to being deconditioned exercise improves cardiopulmonary health and heart disease if um as a reminder is one of um is one of the biggest killers in our country and it is the leading killer among women so cardiopulmonary health is is understated but so very important um and exercise is one of the best things to improving cardiopulmonary health mobility and function so um and now now we're getting into mg right um so being able being able to move being able to do your daily tasks things that are um um important to your into your life all of the inwards so dressing eating bathing generally functioning balance and stability you have muscle tone is required for that and and then that leads into decreasing fall risk improving metabolism the physical activity is probably one of the best things to do to improve improve metabolism bone and joint health especially as we age bone bones and joints require loading in order to maintain good health which requires physical activity and movement and um there's a lovely batch of chemicals that get released by the brain um uh serotonin to uh probably to be number one there which will improve mood so hosts lots and lots and lots of health benefits to exercise but there's always the butt right um there are exercise concerns with myasthenia gravis so um mg symptoms um are um exacerbated by um repeated contraction of affected voluntary muscle fiber so voluntary muscle fibers are um those types of muscles skeletal muscle things that you think about okay i want to voluntarily move if you can voluntarily move it you're likely talking about a skeletal muscle um some of those are of course more affected in myasthenia than others so the ones that tend to be closer to closer to your trunk so shoulders and hips tend to be a little bit more affected ones that are further away so hands and feet tend to be less affected but that being said mycena can affect any voluntary muscle in the body so you have your the nerve signal so the nerve sends a signal releases acetylcholine and i'm glossing over this because this is of course information you've already received but acetylcholine releases at the neuromuscular junction and with that repeated voluntary contraction of muscle fibers um if you kind of get enough of that the with myocena being that autoimmune disorder those anti-acetylcholine antibodies are going to be released and then that communication between the nerve and the muscle is impaired and so that muscle firing becomes impaired excessive muscle firing demand can lead to an increase in those mg symptoms um and then if you keep you know keep going of course that can cause flare-up or even crisis um but so typical exercise exercise regimes exercise instructions are generally not compatible with the presentation of mycena so things like push through fatigue pain is um no pain no gain more is better feel the burn those sorts of things those um probably exercise instructions that we have been we've had drilled into us for our for all of our life and i think back to think back to junior high um pe classes um that that type of approach to exercise does not work with mycenium that's that is where um we can run into some danger that is where we run into some caution because um now we're uh causing basically causing that that cascade of anti-acetylcholine antibodies to be released decreasing that muscle performance and then even to have an increase in symptoms and then where it really gets dangerous of course is where you start losing that connection the the communication to the diaphragm and you start having impaired breathing so um so i do want to put that out there that these are the big exercise concerns with mg however you know we have to kind of sit here and weigh right there are benefits of exercise and there are there are health risks if you if you don't move and you don't exercise and then there's a practical issue where you know you need to you know live your life and that requires being able to move around that requires being able to to lift and carry that requires being able to do functional things so um you know we're kind of sitting here with a balance so what does the research say um there's um within i would say within the past decade um there has actually been some decent research done on physical activity in myasthenia gravis and i've just i've pulled out um pulled out some of them there's there are more but these are these are some of the highlights so there were two papers um by westerberg at all and between the two of them they concluded physical exercise in mg is safe and it does improve neuromuscular parameters and physical performance-based measures so they found that in their study wong it all found that specifically doing balanced strategy training will improve balance and decrease fall risk in patients with mg um then he's in it all in 2020 determined that an independent exercise program will improve community participation so being able to do things out and out in the community and interact and um and such like that in patients with neuromuscular disease and they actually broke it up and they did look at subsets of various neuromuscular diseases and mg specifically was one of them and then um and these um and this guy found that directed exercise programs with a neuromuscular disease is safe and that was another one where of course they broke into different the different categories of neuromuscular disease and mg was one of those so so the research shows us that you know basically to sum this slide up that that um directed directed exercise in in mg with with considerations of the of the disorder um is safe and um has those health benefits that we talked about so how do i find the middle path between things safe with mg and reaping those health benefits and on the converse side of that not having those deleterious effects of not of not exercising or not doing physical activity well the good news yes there's a middle path so um exercise very specific exercise considerations for mg so things to think about first and foremost and i'm gonna sound like like a like a commercial but um please consult a health care provider before engaging in exercise or physical activity beyond what you currently do so if you are already participating in an exercise program or you have a certain level of physical activity and you're controlled and you're safe in doing that please continue doing that but if you either are not engaged in an exercise activity plan and you want to be or you want to up where you are because of mg i highly highly recommend that you do consult your health care provider um and this is possibly a little shameless plug for my profession but consider working with a physical therapist and specifically those this is a little lesser known in our field but physical therapists specialize just like um other professions do so there are physical therapists specialized in neurology there are physical therapist specialized in orthopedics or both as case with me so you want to definitely work with one who is specialized in neurology and neuromuscular disorders you want to consider your symptoms so your mg should be reasonably well controlled um and that would be a determination that between you and your neurologist likely with medications of course some people do go into remission which is fabulous but the vast majority of us are on some sort of a medication um so you want like i said work with your neurologist to make sure that your your symptoms are reasonably well controlled before starting or increasing exercise you want to exercise or engage in more strenuous physical activities when you're at your best so three things to think about one time of day think of the time of days when you tend to when you tend to be at your best your energy levels at its peak so for most people this tends to be on the earlier side of the day than the late but perhaps maybe not first thing in the morning again it's going to vary from person to person um but for me for i'm just going to use me as an example um my peak time of day is 10 am and so trying to plan and budget if you're going to have a more strenuous physical activity try to plan a budget at that time of day where you're going to be at your best um also think about medication timing so if you happen to take something like um like methanol or peristic meaning bromide um the the uh the non-extended release one so the they're usually 60 milligram tablets um and taken as needed or every three to four hours typically um so think about your medication timing so that generally takes around about half an hour or so to kick in so you want to plan basically to plan your exercise you know maybe um maybe 30 minutes to an hour after you've taken that nest and on dose since you're getting um the best effect of it and then also and i think this is particularly pertinent right now while the majority of our country is baking avoid overheating so especially in summertime that's going to be a lot of indoor activity especially if you are like i said i'm hailing from houston texas right now and um i think we're very excited this is our one day of not having a high over 100 um but so those um outside outside actually try that again outside exercise activities um can be particularly dangerous so definitely avoid overheating pool exercises you want to go on a cooler pool so you know you basically you want to stay under 90 degrees in the pool closer to 85 is actually better but so those are considerations there let me go things to avoid all right so you want to avoid um repeated contraction of the same muscle group so this photograph down here of the guy doing the bicep curl so that same bicep curl um 10 reps 20 reps 30 reps that can repeated contraction of the same muscle group that you want to you want to avoid you also want to avoid sustained muscle contraction so that's basically where you contract the muscle and you hold it for a long period of time and there's a lot certain types of yoga do a lot of sustained muscle contractions which can be a little which can be a little tricky and mg um so instead of that um we can perhaps think about doing a circuit so instead of doing the same contraction of the same muscle group you might do for example a bicep curl and then an overhead press and then maybe lift up on the triceps so you're using different muscles but you're kind of cycling through them that's a way that we get around that and then how we get around sustained muscle contraction is um and i'm going to use again i'm going to harp on yoga a little bit just because that's probably the best example that most people are familiar with um so instead of you know holding that tree pose for example or or holding the downward dog pose i like to do yoga flows where you flow through and go from one position to another to another to another so that you are getting the benefit of the movement the muscles are contracting so you are using them but you're staying you're not overly contracting so you're kind of trying to stay under that threshold of where the um the autoimmune characteristic of mg is going to kick in and start releasing those anti-acetylcholine antibodies um you also want to avoid too much too fast um so you know if you've if you are at a you know if you're at a certain level where you know a walk around the block might be as much as you do and and i'm only using that as an example so please don't think that that's a baseline some people may be way above that some people a walk maybe a walk down the driveway is is is what is normal for you but if think about where you are um so the walk around the block is your thing um running a 5k is going to be too much too fast so um so you want to to gradually kind of gradually increase making sure that you're saying that you're staying at a level that is comfortable that is safe you also want to avoid um what i like to call pushing through and so that's where you start feeling muscle fatigue um and again that's going back to going against all the things we've been taught right we've been taught you want to push through muscle fatigue because that's where the gains are that's that's not true um and it can be potentially dangerous you can start having increased symptoms and mg if you start pushing through muscle fatigue and then also keeping up with others and i want to put the caveat in here keeping up with yourself um because um for a lot of us um we developed myasthenia some at some point in adulthood and so prior to myasthenia we had we may have had an increased level of fitness um so speaking personally right i was active duty in the military i was very physically active and um you know i did i was deployed on aircraft carrier and we had a exercise group we'd go run on the flight deck and we would do the insanity programs up on the flight deck and post myasthenia that level of activity um may or may not be attainable um and it certainly um if i set that kind of bar for myself or trying to keep up with myself or what i was pre-mg i am potentially setting myself up for failure so um so keeping up with others remember we are all people with mycenea are all at different points in the in the disease and we all have different levels so um so just just caution with that all right so here's some of the how to's i've touched on this a little bit in the um in that first slide but um so exercising safely start ridiculously easy and i mean absolutely ridiculously easy if you're already at a certain level let me put this kv on in there if you're already if you are already exercising and you already have a safe nice comfortable level that is where you start if you if physical activity is not part of your normal life you want to start with something that you absolutely know that you can attain because you know that you're going to be safe at that level okay and then you start ridiculously easy and then you um so you start start low and go slow so you increase um once you're comfortable at a certain level then you might um increase just a little bit so for example if you were comfortable um if you were comfortable walking um or or writing let's say riding a bicycle for 10 minutes that's where you're comfortable then um after you know after of course rest um the next time you try that activity you were very comfortable at 10 minutes the next time you might try 11 because it so it's a small incremental increase um but likely one that is going to still keep you under that muscle fatigue threshold under that autoimmune firing threshold and it's going to be something that is safe and attainable for you you want low impact and low resistance activity so you want good movement but you want to be easy on your muscles you want to basically get the best bang for your buck without causing a lot of that that muscle fatigue or that that excessive use of affected muscle so that's going to be achieved through some low impact and low resistance activities um low reps low sets frequent rest breaks so the american college of sports medicine talks about when we dose exercise or prescribed exercise depending on what your goal is right there's you know do i use high weight or low weight so the um the traditional recommendation is that if you're trying to increase strength you want to or increase muscle bulk or power you want a higher weight or higher resistance with a with lower lower repetitions and then on the flip side of that if you're trying to increase endurance you want low resistance with higher repetitions well both of those are they kind of go against the the initial mg exercise guidelines so there was um there's actually there's a study done that looked at doing low low resistance and low reps with frequent rest breaks um in myasthenic patients and they did ultrasound imaging of of the muscle and over over time it's about a six month course they are able to see an increase in the width of the muscle which indicates that there's muscle hypertrophy which basically means that muscle's bulking up in layman's terms and there isn't there was an increase in increase in strength so um so the low res low reps and low weight with frequent breast break it takes longer than the quote unquote traditional exercise prescription but the research shows that it is still effective and it's safe with myasthenia um no extra weight is required unless you are already at a level where you might be lifting weights or having some extra resistance if you're just getting started no extra weight is required simply by by raising um raising a limb against gravity um that is you have the weight of that limb plus or times the distance of um the distance of that limb from your trunk um and that is um sorry i'm bringing physics back here so let me let me get off of physics um but basically that is that is enough resistance and that is enough work on that muscle so you don't have to lift heavy weights to get um to get muscle the muscles to work the weight of the arm or the leg is is perfectly adequate swimming or aquatic exercise is fabulous with myasthenia with caution of course so you want to stay in shallow water when you can touch the bottom or hole to the side floatation aids are very helpful too because the the danger with water is that it is deceptively easy and you will actually you don't you can't feel that the muscles are fatiguing until then they either quit working or you get out of the water and then you really feel it so you can get a lot more work done in the water because you don't have as much strain on the muscles and so you can basically stretch what the muscle is going to be capable of before before that myosthetic muscle fatigue but sometimes that that easiness of the water can can mask um can mask that muscle fatigue so safety considerations there shallow water flotation aid and then also it's not on the slide but don't be alone either so those are some cautions with that and then and then cooler water too cycle through movements and body regions to present excessive prevent excessive fatigue i touched about touched on this on the previous slide um so that you can you're still getting movement um but you're basically giving um you're giving different muscle groups rest as you move through so i with mg i love circuits um or i so i love you know you know a little bit exercise once maybe maybe the arm and then do a little exercise down on the leg and then maybe do something for poor stability and then and then cycle through so you're not you're you're getting work and you're getting endurance there but you're not excessively fatiguing any one region of the body and then most important stop before you feel tired so rest before you think you need to um and so these are my uh guidelines research based um for safe exercise with myasthenia and then the stop before you're tired that's going to lead me right into this rate of perceived exertion scale which is very very important with with any exercise but with specifically with myasthenia you want to kind of keep a keep a feel on where you are on this scale as you're as you are exercising or doing physical activity um and with myasthenia i say stay in the green so one is a very light activity basically anything other than just completely lying flat in bed um two and three is light activity and one reason i love this scale is because with mg breath is it is a very important thing and this talks about what your breath feels like um so you should be it should be very very easy to breathe you can carry on a conversation if you're doing levels two to three four to five um you could still do the activity for a longer period of time and you can talk while you're doing it and be able to hold short conversations and that is for for mg that is where you want to stay you want to aim to be in that four to five beyond that that is where you start you are on the verge of becoming uncomfortable you start getting short of breath you can maybe get a sentence out you start getting breathy that is um that is where you need to scale back your activity so this is a really really important scale and then of course please don't get into the orange or the red so so i go for green with this particular scale it's called the rate of perceived exertion scale some resources for getting started um this is um i'm going to to acknowledge my research students at texas women's university they put together um a research based exercise um some exercise videos um so this is the link is here um the link is on the slide and i believe this presentation is going to be available but if you if you just go and search on youtube safe exercise with mg this video series should come up it is from texas women's university um it has three exercise videos where they go through all of these um basically exercises and exercise variations so sitting and standing easier and harder um with and specific to mg so exercise flows lots of rest breaks and there's a safety video in the beginning which reiterates a lot of what i talked about and then the very last video in the series is yoga so they go through a couple of different yoga flows where you're recycling through different activities so um i i'm really pleased with my students they did a lovely job and they're actually going to prove they're presenting a poster on this at a research conference coming up um next february so i'm really excited about that but great great resource if you're getting started or just need some considerations for exercise with mg so these are some of my references and these are my these are my my children uh my daughter when she was in this uh in this picture she's about 10 months old in this picture she can she could do better push-ups than i ever could so um these are these are my little ones and then this is me so if you do need to feel please feel free to reach out contact me um i am more than welcome to um to entertain um any and all queries to help you be more physically active thank you liz we've got several comments about the fact that you have motivated people to seek out some more exercise now that they know the right way to do some of that yeah and a few questions for us with mg is light weights or resistance bands a better option it depends on what you're doing so um so so either are fine um but i would be honest if you um if you're just getting started i would try the movement with nothing at all just just the weight of just the weight of the limb against gravity to start like i said start ridiculously low and slow um light weight um lightweight is fine and lighter resistance bands are fine too um you're just kind of working different muscle groups the difference with with weight is that you're going to have a sustained a sustained resistance throughout as you as you complete the movement with resistance bands it's of course going to get easier and harder at different points in the movement there are benefits to both there so i guess it really really depends on what you're doing but if you stay with um either are fine but if you stay with that um start low and go slow um mantra um you'd be fine with either of those so you want so the lighter colors on the on the um on the exercise band so um yellow universally tends to be pretty easy um and then it kind of goes up from there um where blue and black are up toward the hardest um and then lighter weights but yeah start low and go slow if i can exercise one day but the next day i end up barely being able to do anything is that normal am i doing too much that is not normal you are doing too much um so that means that you need to basically whatever level you were at on that on the day that you did exercise um if it's if it's causing you to be completely wiped out later later that day or the next day that was that was too much um so i would i would absolutely scale back whatever it was you were doing and that goes back to my start apps start ridiculously easy so if you think what you're doing is easy go easier than that and make sure that it is that is safe and sustainable for you and that you are not wiped out the next day and you'll know that that's a good safe baseline and that's where you start from any tips to help differentiate between mg weakness and deconditioning mg weakness is going to fluctuate so and mg mg type weakness um will um will come on quickly so for example a muscle that is just generally deconditioned um you're going to have difficulty um either doing the movement or maintaining contraction from the beginning and and then it'll it will of course decline but it'll be hard in the beginning whereas mg affected muscles the first couple contractions you do are fine and then you get a and then you get a steep drop off um okay which then recovers with rest so that's that's really how you differentiate the two how do you choose a any tips on how to choose a pt that's knowledgeable or willing to learn about mg so there are a couple of ways to do that um there are if you go to the american physical therapy association website apta.org and i'm i'm not a phil i mean other than being board certified and a member i'm not promoting them um there is a there's a link on there called find a pt um and you can search by various specialties um you can also kind of look around in your in your community um and basically search them out on the community and a lot of times on their websites they'll say um just like physicians do they'll say these are my areas of interest or these are the things that i that i tend to treat and so you want to look for you want to look for neurology type you want to look for neuromuscular if you might be hard-pressed to find someone who specifically lists myasthenia um i do but i'm strange um i'm a rarity in that um just because it's a rare disease um so you want to look for more like the the neuromuscular family you want to look for someone who's perhaps uncomfortable working with things like um multiple sclerosis or guillain-barre syndrome or als um which it's a little it's different but it's in the right family um and then also interview um there is absolutely nothing that says you have to um you know just take the physical therapist assigned to you um you should be able to call a practice and and see if you can have um have a chat with with the pt before you book with them if the practice isn't willing to let you do that i would find the next practice is there any that you know of ongoing or current researcher doing research about exercise and mg remission um specifically in mg remission i am not familiar with any ongoing research right now um i am [Music] i personally have ongoing research um in exercise with myasthenia um so i and um and there are new some new studies that are coming out um as it becomes a topic of greater awareness but specifically of exercise in remission um i would have to go do some more research that i am not i am not familiar with anything right now at the moment most of the studies are either in well-controlled which may include people in remission or may include people who are essentially in medicated remission if you will or with a milder presentation of the disease that's where most of the research has come although there is some with with moderate um moderate forms the disease as well cold therapy seems to be getting more popular is there anything that we should be we're aware of or any studies being done on cold therapy and mg cold therapy um so there have been some studies that have come out about um basically doing um resistance type training with um with cold with with cold packs um and um and that is getting some good um some good initial initial review and initial feedback um but um i think there's more a lot more to be done i'm not um other than um uh then that one and that one exercise study coming um that's been going on i'm not familiar with any others although that's a great area for future research so thank you for that little tip i'm going to put that on my list for my students lucky them um muscle soreness do mg patients have any different delayed onset of muscle soreness over non-mg patients from the research i can't speak to that because that has not an area that has been studied however anecdotally um in a lot of the clients that i have worked with um that is the the the overall report is that um muscle soreness may take a little bit longer and and also just post exercise fatigue um like the in the previous question where you know you're not necessarily wiped out that day but the next day it really hits you um so post exercise fatigue and post-exercise performance anecdotally um a lot of my clients tell me that they get um it's you know they get sore maybe maybe even not the next day but two days later is when they start feeling it and then it the time to recovery um is is more than that kind of 24 to 36 hours it's kind of more doubled than that but um to my knowledge there's not been any formal research on it another great ad to the list for my students is what about relatively long distance slow walking say one to two miles at a time every couple of days is that more beneficial than doing the faster paced um it is again it depends on your individual level um so that's not a recommendation that i could make a blanket across the board um because you know someone you know walking you know across the house might be their limit but um but yes well um but generally speaking kind of you know a lower pace so kind of lower intensity over a longer period of time would be um certainly would be beneficial although if you do want to up that rate basically there's kind of a changeover so if you're gonna you know more you know go more quickly or kind of do this interval a little fast a little slow then you definitely want to shorten up your time um but you know just in terms of um you know for for heart benefits kind of the you know the more the more um you know the more you're the more you can be out and doing the better so if that's um if that is the exercise that is sustainable for you you can if you can walk a mile or two but at a lower pace and you can kind of cover more mileage that way um then and do that safely then yes i would certainly recommend that what about using a personal trainer i'm saying um certainly very helpful but with my caveat that you know just like with any any professional that you're going to consult you want to make sure that they're very knowledgeable about mg and that they can work with the exercise considerations are very specific to mg so kind of just like you know you wouldn't you wouldn't expect your dentist to help you with your mg you wouldn't expect right a personal trainer who's never heard of it to be able to advise you there so there are um there are personal trainers who do kind of specialize in working with um with people with with various um disorders so so you want to find someone who is fully understandable of what's going on with mg and they're not going to go that you know push through no pain no gain come on just actually just just do a few more reps and you'll get it stronger um if if that's what you're seeing with a personal trainer then just like with any with anyone that you'd be working with that's that's a sign you want to change but personal trainers if they're knowledgeable and understanding willing to work with mg it is they have a good background in exercise science and that would be a great great resource and our last questions um what about massage and mg will that make my mg worse um again i'm not familiar with with particular with scientific research on this topic um but um massage in general um is you know should not should not increase mg symptoms um unless it is a very aggressive massage where it's actually causing pain or discomfort which causes you to contract the muscle as a kind of a muscle guarding then then that could potentially exacerbate energy symptoms such as general swedish massage in a um without being overheated so a lot of massage therapists like to warm their table up which feels amazing but if you have a if you have heat intolerance that could be an issue too so i would not have a heated table or heated blankets or things like that that they do to try to make make you comfy um and a general swedish massage that does not um cause muscle guarding but without you know getting uh too diggy pokey if that's that's not a technical term but i'm gonna use it without causing pain that causes that muscle guarding but otherwise yes massage there's health benefits to it as well um and it's yeah no reason why it should um complicate mg thank you dr plummen that was a great presentation and you've got a few more than a few people motivated to start doing some exercise with their mg fabulous well thank you so much for having me i'm i'm truly honored and now we're going to take a break guys we'll be back for dr pulley's presentation at noon so everyone stretch their legs and we'll see you back here in 15 minutes thank you pamela can you hear me yes we can hear you we're just going to wait till the top of the hour to start i know i just want to um so are you seeing the screen that shows the the title slide and the others on the side correct okay if i change it to if you go to slideshow um we can still see your notes if you go back no then on the top like you're on design if you go to slideshow and then do from current slide right there yep oh you still see okay that works let me see something i'm gonna try to cheat um we can see your notes on the side yeah i'm trying to switch these now and see if it will work let's see now if i do it um from current slide no no still seeing the notes yep um let me try same thing um i don't see anything right now i'm trying to go where is my sharing option now where did it go to hmm okay share screen let me do this let's try screen two share and now i'm gonna go to this from current slide so this works better than with the notes on the side oh that's perfect there we go we got it all right couple more minutes and we'll begin okay thank you all right okay three two [Music] three okay welcome back everybody it's 12 o'clock and our next speaker and it's our pleasure to have dr fully with us dr pulley is an associate professor of neurology and director of the emg laboratory at the university of florida health science center in jacksonville florida dr fuller dr pulley has expertise in diagnosis and management of neuromuscular disorders he has a special interest in the management of myasthenia gravis and follows nearly 400 patients with energy dr cooley is also experienced in electro diagnosis of nerve and muscle disorder and performs over 1 500 emg and nerve conduction studies each year dr pulley has participated in clinical research trials for myasthenia gravis lambert eaton myascenic syndrome lems hemiotrophic lateral sclerosis als multifocal motor neuropathy mmn dermatosis and chronic inflammatory demyelinating polyneuropathy cidp and have served on the medical advisory board for the mgfa welcome dr coley thank you very much everybody can hear me okay yes we can okay so um i'm just going to briefly recap um sort of the standard treatments that are used for myacenia very very briefly and then i'm going to talk about the new drugs that already are approved or are in the pipeline right now uh for myasthenia and um there's some that i won't touch on today um because there's still like not any data available i'm only going to talk about ones where there is data that's already available so um whenever we do a talk we should give our disclosures that i have participated in some medical advisory boards for these companies um so just to let you know now of course at the neuromuscular junction we have the antibodies against the acetylcholine receptor but of course there are other proteins right next to these acetylcholine receptors like the musk protein agreement and antibodies against those are sometimes seen in addition to or instead of the acetylcholine receptor antibodies and this is a really complicated slide this is where the business of this happens here this is the nerve terminal and these are the receptors and the antibodies are against the receptors what can happen is activation of this part of the immune system called complement that can cause destruction of the muscle on the opposite side where the receptors are located the antibodies activate this and it causes destruction and we're going to talk about some of the drugs that are targeting this the point of this slide is to look at where can we target the immune system along the way and in this case um you can target upstream or downstream so complement inhibition is fairly downstream for instance cholinesterase inhibitors like mestinon are downstream it's right here at where the nerve and the muscle are communicating with one another we can go back upstream to where the antibodies are and that's where the the drugs we're going to talk kind of extensively about the fcrn inhibitors i'll come back to them quite a bit um and then we can target actually the cells maybe that are producing antibodies i won't talk very much about that today so it's important to talk about this because as of now the only fda approved drugs are those that target um i'm sorry have been studied in people with acetylcholine receptor antibodies um there have been a little bit of study in terms of clinical trials in musk antibody positive and i'll talk briefly about that and there's other antibodies as well but they're much less frequent those are certainly the two most common and then there are peop there are people who don't have antibodies um to any of the things that we test for and we call that seronegative and i'll touch on that just a little bit with some of the drugs that we're going to talk about um so the standard treatments of course are initially to start a cholinesterase inhibitor pyridostigmine or mestanon most people will not get a good enough response and they have side effects um and mastadon has no effect whatsoever on the immune system and it almost always does not hold people steady so they need to have something that's going to target the immune system and although i'm going to talk about the new drugs i still always use the standard drugs first prednisone and plus or minus one of these nonsteroidal immunosuppressive drugs and i only move on if patients cannot tolerate these drugs or do not get a good enough response from them uh i i tend to evaluate that much quicker than some other people in terms of um the steroids and if i can skip the non-steroidal immunosuppressives if somebody doesn't respond to steroids i definitely try to do that let's say that somebody has not responded to this prednisone or i've not been able to taper it enough and they're having a lot of side effects in spite of trying these other non-steroidal immunosuppressives like cell cept or immuran or methotrexate then i will go to the next line and to me that's ivig why do i go to ivig first because it doesn't suppress the immune system at all it's the only one of the treatments that we're going to talk about that has no suppression of the immune system and so i i like to use it next i will do one single loading dose and if somebody gets a great response then i will put them on a maintenance and whenever we're talking about things from ivig onward i'm not looking for a little bit better i'm looking for a lot better i want patients to have a no doubt about it improvement and if they haven't had a no doubt about an improvement i'm not going to keep them on that treatment i'm going to try something else we have had um solairis the generic name is equilizumab approved for several years um and this is actually the first drug that was fda approved for myacenia besides mestanon um some neurologists and some neuromuscular specialists who manage a lot of myosinia patients like rituximab i personally don't like it that much for acetylcholine receptor antibody positive but i think it is the treatment of choice for people who are musk antibody positive i think we should never even bother treating them with steroids or other achievements we should just go straight to rituximab i have zero patients personally who are on chronic plasma exchange i think there are other ways to manage people and every patient gets a complication when they're on chronic plasma exchange and i'm not going to talk in depth about thymectomy but that's only a treatment for acetylcholine receptor antibody positive and probably in people who are younger than 60 and definitely people younger than 50. um so here's the the main topic of this talk what are the treatments on the horizon well some two of these treatments are now not no longer on the horizon they're actually available and those are vivgart also known as f gartigemon and it's in this category of drugs called the fcrn blockers and i'm going to get into that a little bit more detail in a second and then the second one second class of drugs are the complement inhibitors and that's the same class of drug that soliris is uh but there are two um newer drugs i actually misspelled this it's rav viewlisimap not rabbalism but it's called altomirus and zeleca plan and i'm going to go over all of these drugs with you all except for immune events because we don't really have much data and then nippocalymab we don't have much data on those yet um so this is the pathway what does fcrn do it's it's a pathway in your body that protects antibodies as they are being transported across a cell so if the antibody binds to the fcrm protein it is protected from going into the digestion chamber inside the cell and it comes back out of the cell on the other side if you block the fcrn by using an antibody or using a small molecule like f cartimod now the antibodies can't bind they're no longer protected and they get shuttled into the digestion chamber and destroyed so for antibody antibody-mediated diseases this mechanism is almost certain to work it's almost always going to have a an impact on the disease you're treating the the root cause of disease and myasthenia is what we call the prototypic autoimmune disease that antibody we know it causes weakness and we know if you take it out and you put it into an animal you can make the animal weak um so in the fcrm pathway i've kind of mentioned these already fcartijamod is one of the drugs i'm going to talk about rosano licizumab um it doesn't have a brand name yet and i'm not going to talk about the other two because we don't have enough data yet on those but to talk about these we kind of have to say what are the outcome measures that we look at in the clinical trials and two that are used most frequently are called the mgadl or activities of daily living score and the qmg or the quantitative myasthenia gravis score the other one that i think is pretty important is this thing called the quality of life the mgqol 15r i'm going to show these to you real briefly so i do the adl and the qol-15r in the clinic every day whenever i see patients this only takes a few minutes and we ask how have you been doing over the last week or so so we go across these rows you have any trouble talking they say no we're done they say yes then we say okay is it intermittent or is it constant and if it's constant then people have trouble understanding you so we get we do it that way with every one of these and this is how have you been doing in the last week or so um and so the the normal score is zero the maximum score because there's eight items there's 24 points that means you have really terrible disease the worst possible the qmg is not something that most people use in the clinic because it's very time consuming it's really not practical to do it on a on a daily basis as we're seeing patients in the clinic we do use it in research trials people feel it is more objective it's not just what patients are reporting if we go back to the activities of daily living score we have to use what the patient tells us so sometimes i'll see a patient say do you have a droopy eyelid they say no i look at them and their eyelids clearly drooping but we still have to write no if they tell us no so it's not quite as as reliable or as as objective as as something like uh the quantitative myosinia square and then i mentioned the quality of life score this one i also do in the clinic and this one is filled out by the patient so while they're waiting for me to come into the room my technician will hand them the clipboard and say fill this out for us and it says here over the past few weeks have you been doing um and so do i have this symptom not at all a little bit or very much it used to be five choices but they found that limiting it to three um actually didn't change the the uh sensitivity et cetera so now we're going to go on to talk about the drugs so efgartijamod the first drug studied in this fcrn pathway and it is now fda approved it's a smaller molecule the other end the other candidates in this pathway are all what are called monoclonal antibodies they tend to your body tends to react a little bit more to those so there's a little bit more side effects with those it is given as an iv infusion once a week there's four doses and then you wait to see when the symptoms begin to come back and then you treat as needed they've actually developed a new formulation that's not intravenous that's subcutaneous it's given at the same frequency um and they they've shown that that's just as effective and that's probably going to get approved too um i think i'm going to skip over this and get to some of the outcome measures and one of the things that people have looked at is this idea of what's called minimal symptom expression our goal is to make people as good as they can possibly be when we're treating their myasthenia and this is a good way of looking at that so to get that designation you had to go to a score of a zero or a one on the activities of daily living score and in this study 40 of the patients who got treated with the drug had that outcome and only 11 of the placebo patients so that's quite a dramatic difference um they did in their clinical trial actually study patients with zero negative myasthenia there was not a statistically significant difference because they only had 19 patients who were serial negative in the in this trial um but if they combine them together and looked at both the activities of daily living score and the quantitative uh myasthenia gravis score that was significant um the side effects of fgartijamod headache is a common side effect of all of these drugs actually this particular drug has the lowest incidence of only in the 20s in this case it wasn't even different than placebo but what is a little bit different is the upper respiratory tract infections and it didn't show up for some reason on this slide urinary tract infections so when you lower immunoglobulin levels it tends to potentially make you a little more likely to develop an infection there are people out there in the world who have immunodeficiency where their body just doesn't produce enough immunoglobulins and we have to give them ivig to prevent them from getting infected so this is the second one of the drugs that's in this pathway called the fcrn and now the clinical data is available for this it has not yet been fda approved but this is the data from their clinical trial it is a treatment that's given iv weekly and in their clinical trial they were looking at um six weeks after the onset of the study what was the outcome at that time they were looking at weekly infusions and this one is given one the evaluation at the six week mark and what they found was that there was a significant um drop in this activities of daily living score at day 43 with either of the two doses that they looked at and they were basically about the same difference um and this two and a half points or 2.6 points difference from the placebo is is actually pretty impressive and i'll show you some other data that might might kind of drive that home um they also looked at quantitative myasthenia gravis score and similarly um it had a significant impact this time there was a little bit more benefit with the higher dose than with the lower dose this is another outcome measure called the composite score and it also had an impact on that and then this this looks at what effect does it have on the antibodies in the blood all of these drugs that i'm going to talk about have have a similar kind of an impact some might have a little bit more lowering of the antibody levels in the blood and both the total amount of the of the igg and it's uh and the antibodies that were really interested in the acetylcholine receptor antibodies dropped by about 60 to 70 percent and all the drugs that i'm talking about in this class are have a similar level of impact on those antibodies if we look at um this drug it had a higher incidence of headache than the previous i think right here so headache was in um 45 percent of the patients on the highest dose 37.7 so about 40 overall um about 20 percent higher than the placebo group they say they're mild to moderate um and they can be managed with even with over-the-counter medications there was a higher incidence of infection just like with f cartichamod and similarly it's clearly a little bit different than with the placebo um this is an interesting way of sort of displaying the impact of these drugs on okay what effect does this have on on the improvement and so you say how many what's the percentage of patients who got the drug versus the placebo who had a specific amount of improvement on one of these scales and i told you i'm looking for big improvements when i give these medicines so let's say how many patients got a seven point improvement on the myasthenia gravis activities daily living square well a third of the patients got that big improvement but only 10 percent of the placebo so that difference is about 24 and if you look at all of these scores almost every one of them is about 20 percent different than placebo across the board it's pretty close almost all of them if we look at the similar data for f gartejomod um across the board the difference is closer to 30 percent and in some cases 40 percent higher with afghar tijumad than placebo um and so that's uh you can't it's not a good idea for us as doctors to to sort of make too much of a conclusion about the differences um across studies but this is the only way i know of to sort of have some idea okay is this drug more potent or not as potent as another drug it's to say what is the placebo subtracted response rates at given levels on these scores so i think this shows that this the f guarantee mod is probably a little bit more potent than um some of the uh than solaris which is the one i was showing you here [Music] this is the the new drug that is out now called altimirus it has been fda approved it's has basically the same mechanism as uh solerus um but it saliris is given every two weeks in its maintenance phase this drug is given every eight weeks in the in the maintenance phase both of those drugs and another one i'm going to talk about any of the drugs that are blocking the complement pathway you have to have a meningitis vaccination and you have to get that periodically in the raviolismapp study they showed that there was a significant difference between the drug and the placebo and how much change there was in the scores both the adl and the qmg score and this is just showing that um when they got to the end of the study which was at six months the patients who were on the placebo could cross over to the active drug and you see that right away they basically caught right up to the patients who have been on the drug all along and there's basically absolutely no difference in how they're doing compared to the people who've been on the drug all along so delaying start didn't really make a difference in how they're doing in the long run and then this is again looking at the difference between the drug and placebo and this looks pretty similar to what we had seen with soliris about a 20 point difference maybe a 15 point difference um at some levels this is for the quantitative myosinia gravis i don't think i have one for the adl score actually here we go yeah so this is the this is minimal manifestations status this drug had a 25 percent of patients who were on ultamiras had that outcome remember this is the one where you had to get down to a zero or a one score with f garciamod that was a forty percent versus ten with ultimates it's a 25 versus a 10. um and this is just sort of comparing across multiple different treatments and the one over here on the right is what i'm going to tell you about in just a second called zaluca plan and it's it's hard to see it but the differences there um were actually pretty impressive um and probably a little bit higher than what had been seen this is the saliris data this is the upgrade digimon data and this is the leukoplan data on the right that difference seems slightly more with the zeluko plan than it does with equilizumab the salires and this is just what is the absolute difference in some of these things this is the activities of daily living score and it was a two-point average difference from placebo at the end of 12 weeks um and you can see these drugs actually tend to work pretty quickly that people are already definitely better than the placebo group by the second uh by the second week uh by the first week even there's a statistically significant difference and then this is the other score the quantitative minus senior gravis score and the difference from the placebo group is about three points there and again that's significant and oh so here's a good uh slide where we're seeing that that um the difference from the placebo of like 24 here about 19 here so a little uh pretty similar to what we saw with solis but maybe just a little bit higher in some of these um and then again with the quantitative meiosina gravis score again looking at these differences we're seeing 28 percent here um 25 here difference from um from placebo i like looking at it this way as a way of saying okay what what how can i compare drug a b and c so there are some unanswered questions still remaining here so with these fcrn drugs we don't know what's the consequence of chronically low immunoglobulin levels are we going to create an immunodeficiency state i told you there are people out there who are born with problems in their immune system who have low immunoglobulin levels we are going to be lowering those levels with the fcr and drugs will these drugs work for rescue treatment well interestingly nobody has done a study yet i think it would be very brilliant for one of these companies to do this to say can we if somebody's in the hospital could we use this in place of ivig or in place of plasma exchange and i think that's going to be a role for those drugs later on and the other question is will other drugs be able to replicate f guaranteemod's success well the other drug the roseanne lexismab um the effectiveness of the drug look very similar to what was seen with efcartagemon one other unanswered question with with that drug in particular f cartegemont or vivgart as you guys may know it um in the study their criteria for retreatment were different than what we're going to be doing in the real world they were very strict about how they define re-treatment and because of that we are going to be using the drug more often so one of the things that i'm uncertain about still is how often will i need to give it to a patient when i start them on treatment we're going to give them that first cycle but when do i need to give them the second cycle well because the retreatment criteria were were not what we would do in the real world it's not going to be the same and it's almost certainly going to be more frequent than what was done in the clinical trial so that makes me a little bit uncertain about the safety data in terms of keeping immunoglobulin levels low what about the complement inhibitor drugs so the studies that were done with the with altimirus the newly approved drug and with the zeluca plan the other drug that's i i mentioned those are both also complement inhibitors they looked at less affected patients and that might have affected the impact um what is going to happen with solaris are they going to just get rid of it is it going to be totally replaced by altimira's i think it probably will be actually there's some other drugs that are being developed in this complement pathway i think once we have three drugs i don't know that there's any actual need to have other drugs in the complement pathway personally um so why should i pick one of these drugs against the other ones um what what reason would i choose a versus b versus c well you know it depends on what it is that's important to the patient is it i want the drug that's going to be the most potent one is that is that going to be the reason i pick it or is it going to be well i want something that's more convenient it isn't such a treatment burden so how often do i need to get this drug where do i have to get it do i have to go to some infusion center to get it done or can i get it at my home do i have to have these meningitis vaccinations how much of a burden is that on me etcetera and then there's the safety issue there's always a risk of suppressing the immune system our experience with using things like prednisone and cell cept and immuran has told us that these things probably aren't as big of an issue as we thought they might be because we almost never see people having severe infectious complications from these drugs i you notice i say almost never of course you can never say never once in a while it does happen um so this is still something that nobody is going to be able to give you a hard and fast answer and say you should go from a to b to c if you fail a go to b go to c i still think we should use ivig first um i'm looking for big effects of these drugs these drugs are very expensive um i'm not going to be satisfied giving somebody a very expensive drug and seeing only a little improvement in their disease activity i could probably get them better like that even without um using one of these expensive drugs just tweaking their other medicines so i'm looking for a big bang for my buck when i'm going to the later line treatments and i think we're right at the uh pretty much at the 30 minute mark so i'm going to stop there and then i'm gonna [Music] open it up to the questions all right thank you for your presentation that it was a wonderful presentation and we do have lots of questions in the chat said the first question is is if you're diagnosed with mild mg is a disease progress determined by hemostasis from the point of diagnosis or remain mild so um everyone's different um so there are some people whose disease never becomes severe there are some people who the very first time they are diagnosed they're doing terrible they show up and they're having trouble breathing swallowing etc when i see somebody who's doing terrible at the beginning i put them in the hospital immediately and i do a rescue treatment for them and i start them on high dose steroids all at the same time all at once if they've never had any kind of treatment before and they're really doing terrible i always choose plasma exchange in that situation because i think it's much more reliable um ivig usually works plasma exchange always works so that's my philosophy and um i say if i'm on the ventilator um because of my senior i don't want to probably get off the ventilator i want to definitely get off the valve later so that's why i do plasma exchange the exception is somebody has a history of being treated with ivig and they had an excellent response then okay i'll treat them the next time with ivig that's fine um so um if you have mild disease it certainly can progress and it can it can become more severe our job is to try to prevent that from happening with the treatments that we're going to give you okay next question is are there plans to expand lipguard study to include more sero-negative patients so this can get fda approved for serum negative patients so the short answer is i don't believe so um i think they're probably going to use what they call real world data they're going to rely on people like like me and other myasthenia experts saying well we do have some data and here's the data that we have from the study and if we look at the combination of these two outcome measures we can see there's there is a difference in the sero-negative patients and so um we're going to try to petition them and say look we want to try it in this patient and if they say no you can't do it then we appeal it and say look they've tried a and b and c um and they failed all of the above and so we really want to try it in this patient and you know we just have to keep advocating and presenting what the evidence that we do have i i'm not i don't work for the company so i can't say for sure what their plans are but i don't think that's likely when you say a drug is not approved for mg how is it that some patients are taking it is insurance not covering it so that's totally variable right so it depends a lot of course the big factor is cost so prednisone is not approved for myacenia but nobody cares because it's super cheap um and and even like azathioprine or methotrexate or drugs like that they're not approved but for the most part people don't care because they're not very expensive um there was a time where cell cept uh we had a hard times getting that we had to appeal and things like that we almost never have to do that anymore um but when it gets to the very expense of drugs yeah they're they're going to be uh very unlikely to say sure you can use this drug uh in a in a patient that doesn't fit the criteria they're going to fight your tooth and nail in that situation um the exceptions um of of a drug that's relatively expensive i would say is the rituximab for for musk mg where we've been pretty successful because i think there's pretty compelling data that it's actually in the best interest of the insurance companies to let people have it because otherwise the patient's going in the hospital repeatedly and having to get plasma exchange and things like that and they get rituximab and it like knocks their disease out and now they don't have to go to the hospital so it actually saves the insurance company a lot of money in the long run why is it mg patients react so differently to the medications that's a that's a good question um you know i think there are some treatments that you know work universally like plasma exchange i've never personally seen a patient get plasma exchange and not get better never never seen it happen if they have autoimmune myasthenia they don't respond to plasma exchange it makes me think they don't have autoimmune myasthenia i'm pretty convinced of that um but i don't know it's the short answer and i guess that's why they call it the snowflake disease you know that everybody's different um and how their disease behaves there are certain things about mg that tend to be pretty consistent and that is in a given patient the pattern of disease tends to repeat itself so if the first symptom was a droopy eyelid and now you know and you went on to have other symptoms you had slurred speech and you had choice of breath and you've gotten better the first symptom that you're getting weak again is usually the first one that you had in the beginning not a hundred percent you can't say you know it's always going to be true but in most people that it follows the same pattern in that individual person but everybody tends to be kind of different so some people it's slurred speech some people it's weakness in their arm or leg and some people it's most people it's it's eyes is the very first symptom why are sero-negative patients not included in clinical trials mainly because they are poorly defined um how do you how do you decide that somebody has myasthenia gravis who doesn't have antibodies so um so they have symptoms that fit so they have weakness that we fluctuate and fatigue so it has the classic pattern rest makes them better activity makes them worse it recovers with a little bit of rest in my opinion there has to be some responsiveness to a treatment targeted to the immune system if the if we try if somebody comes in and says i have seronegative myasthenia and i got plasma exchange and i didn't get better i don't believe they have myasthenia gravis they don't have autoimmune mystery grounds that's my my bias um i i like to say if everything about your disease is atypical you probably don't have that disease so if somebody comes in and they say they test me for antibodies and i don't have any of the antibodies okay well that's not typical but it definitely happens okay i tried mesting on it didn't didn't help me well that's not typical but it can happen okay i tried steroids they didn't they didn't help me at all and that's not typical but it could happen i got plasma exchange and it didn't make me better well that's not very typical at all and um as i said to me that's kind of the deal breaker and then there's electrical studies i had a a repetitive stimulation test where i had a single fiber emg and those were negative well if everything's on the atypical side of that equation you probably don't have the disease and that's true for any disease it's like everything about your quote disease is not typical then you probably don't have it so what about the ones that are typical myasthenia that are seronegative is there any research or future research that's going to be looked at to see if patients do eventually convert so it's interesting there so there's a different test for antibodies um than the one that's usually available in the united states called a cell-based assay um there's a lab in oxford england that's been doing this for like at least 10 years now not longer than that and now there's a lab in canada um that is doing it uh commercially theirs is a little bit different i understand than the oxford test but um so it's it's testing mainly for acetylcholine receptor antibodies and um i personally sent eight patients who were serial negative and three came back positive in that test um which can be really really important especially because these are now acetylcholine receptor antibody positive patients they were previously serum negative and now they're acetylcholine receptor antibody positive so now they can get all of these treatments that are only approved for um for acetylcholine receptor antibody positive so um that's that is a a um testing that is evolving and hopefully it'll be more widely available at some point in the near future so you know we can help out more of the previously serial negative patients a follow-up question does insurance cover that test no they don't as far as i know at least the one in oxford england they don't i'm not sure about the one in canada um so the patients that i they actually believe it or not the cost the biggest cost was shipping their blood across the pond uh it was extremely expensive so that's one of the reasons i waited until i had eight patients so they could split the cost of it um they had to pay for it out of pocket it ended up costing them like about 200 bucks a patient out of pocket uh or so somewhere in that range to get the test done what are the primary sources of your research are these studies a combination of trials provided or are they partially paid by pharmaceutical companies and independently analyzed so um drug studies that are for new products are of course going to be sponsored by the pharmaceutical company and they're going to be analyzed by the pharmaceutical company of course we as the clinicians we're the ones who recruit the patients into the clinical trials we're going to be sort of advising them on um you know how how should when we when we go to meet when they're they're doing these uh preliminary meetings for the studies and they're talking about how they're gonna design it we're giving them feedback and things of that nature no we don't think this is a good idea this is a great idea or whatever and in terms of analysis a lot of that is left up to kind of statisticians and how do you decide is this significant um one of the things i'll say there was too much focus i think in the upgrading mod the the vipart study on two-point improvement in the adl score being a clinically meaningful um difference um i when i'm using late line treatments two points is not enough for me on the adl score um so i didn't like that that they focused on that so much and that was one of the reasons i didn't like the way that they chose their re-treatment criteria in the study just a couple of follow-up questions about the cell-based analysis how can the provider order it and is there any drug companies that are paying for that test well somebody wrote here there is a drug company that is paying i don't know that i'm not aware that there is a drug company paying for the test personally but um there is i'd like to hear about that personally but um they so um anybody can order the test from the folks in oxford england you can go online and any doctor can do that it is it's a lot of work honestly to get it done um takes takes quite a bit of leg work on the part of the physician or their you know people who work with them uh so you're saying alexia on pacework i'm not aware of that honestly i i didn't know that that was true okay all of these mets are pretty much contraindicated for mg patients who have cvid already who have i'm sorry who patients who have i didn't get that part i think she froze can you hear me yeah i hear you are all of these medications pretty much contraindicated for mg patients who have cvid already so um i would have to defer that to an immunologist for them to say but um i would say a compliment inhibitor probably is not um i would say the fcrn drugs probably are but i don't know the exact definitions of the cvid i know there are the patients who have low immunoglobulin levels okay i don't i don't know all the categorizations and um designations of that but i can tell you if if your disease causes you to have low immunoglobulin levels then yes probably fcr and drugs should not be used in those patients all right now our last question will be will insurance company authorize emergency use um so i think that's on a case-by-case basis and even sometimes it's a hospital decision believe it or not so we have patients who are in the hospital who we just can't get them better no matter what we're doing we've done plasma exchange we've done ivig we've put them on high dose steroids and everything is failing this patient is stuck in the hospital can't get them off a ventilator they're on a feeding tube um there have been cases where the hospital in spite of the the big cost to them said it's cheaper for us if we can get this patient better and get them out of the hospital to give them this really expensive drug um and see if we can you know pull them out of this situation because patients who are in that scenario they actually the hospital loses a lot of money on those those kinds of patients so they they sort of have to take a gamble in some instances and say it's going to cost us a lot of money to do this but it may save us money instead of this patient just sitting here in the hospital and never getting better never getting better well thank you very much dr fully it was a wonderful topic and lots of discussion thank you very much [Music] okay our next speaker is melissa woolhurst melissa's career and volunteer efforts carry a recurring theme of finding proactive solutions to address challenging situations from her leadership in revitalizing blighted communities mediation and community consensus building as the executive director of west palm beach downtown development authority to our volunteerism as a crisis counselor homeless assistance advocate and as an mg friend peer-to-peer support volunteer melissa strives to find solutions that better communities and individuals she is an advocate for maya's genius awareness and assistance as moderator and administrator for several online support groups including zero negative myasthenia gravis with the help of her supportive family and friends plus an expert medical team melissa doesn't let her 35 her over 35 years with my estenia gravis stop her from embracing her life and being of service melissa we're going to turn it over to you thank you so much um thank you kathy and thank you to the mgfa for giving me the opportunity to speak today and for presenting um this these wonderful speakers it's it's been so helpful and there's been such valuable information from dr pulley dr plowman and dr rosario um i am before i really dig in i'm going to try to toggle my screen here and share a psa from some serial negative patients so if you bear with me i'm going to try to share my screen and open something up here um let's see i'm not as nimble as everybody else seems to be with this so um i have i have i have sarah negative negative i have zero negative my estimate i have zero negative i have zero negative myosthenia gravis myasthenia gravis is characterized by fluctuating weakness of the voluntary muscleworks the muscle weakness of mg increases with continued or repetitive activity and improves after periods of rest seronegative myasthenia gravis is a form of mg where antibodies like anti-achr and anti-musk are not detectable in our blood approximately 10 of all individuals with mg are seronegative individuals with serial negative mystery gravis are fighting the same war as individuals with detectable antibodies without the same arsenal of treatments available to us symptoms and response to treatments are often the same in seronegative mg as those with positive antibodies symptoms of myasthenia gravis can include treating of one or both eyelids double vision weakness in arms hands fingers neck face or legs or difficulty walking difficulty in chewing swallowing or talking shortness of breath difficulty taking a deep breath or coughing mask life or expressionless face or difficulty smiling and generalized sweetness sometimes antibodies for other proteins such as agaron or lrp4 auto antibodies are present more research is needed to further understand these antibodies and to find additional antibodies that have not yet been identified in zero negative individuals in a recent study eighteen point two percent of seronegative myasthenia patients actually tested positive for achr antibodies using cell-based assay testing published in the journal of neuroimmunology is the clinical need for clustered achr cell-based assay testing of seronegative mg unfortunately this test is not available in the us or most countries in the world [Music] [Music] mg i have serial negative mg serial negative serial negative zero negative i have stereo negative energy thank you so much for allowing me to share that very important message today um from the mg community i am just going to switch over okay i'll switch over to the presentation and thank you to um celia meyer bob ruff and alicia angel for putting together that content and many thanks to all in the energy community our c our serial negative patients that participated in that and continually participate in awareness and advocacy efforts um i bet as you know by now i have serial negative mg my name is melissa willis and um today um i'm going to be sharing my diagnostic journey with you um we're still seeing the screen with the with the movie with the video oh i'm so sorry okay let's see i'm seeing the other ones so let's see maybe if i go back to the zoom and stop sharing okay and then you'll reshare the others the other screen okay thanks so much dovah for one no problem um [Music] and for some reason oh okay let's see stop share and let's see and now we'll try this now try to share a screen okay how's that working nope nope okay uh one more bottom of the zoom you'll see the share screen when you when you scroll over it'll turn green um okay let me just go back to zoom thank you guys for your patience share screen and okay great thank you guys so much and here we go okay so as you know i have sarah negative my estenia gravis and i think dr rosario and dr pulley the other speakers really covered what seronegative mg is very very well although antibodies are not able to be seen in the blood work it doesn't mean that there are not other biomarkers or antibodies that have yet to be discovered or identified in this type of myasthenia gravis um so i'm here today really to share my diagnostic journey with you guys um because i have zero negative mg and because my symptoms started when i was a teen and were kind of mild and followed by other illnesses it took sec 16 years from the start of my symptoms to the actual diagnosis i've been officially diagnosed for 22 years which means i have been battling surviving and thriving with mg for 38 years which is 70 percent of my life so i've actually lived more of my years with mg than i have um not but today i want to focus on those first 16 years so you can get an idea of how symptoms might manifest particularly in kids teens and young adults i think there's so many um bodily changes that go on during that time there's changing life responsibilities so it's really easy for some of those symptoms to kind of be shrugged off fall through the cracks or maybe even be misdiagnosed at that stage um especially if you're seronegative of course much more is known now than 38 years ago when i first started showing symptoms but we still see patients that are experiencing these long lags in diagnosis and unfortunately in the sierra negative community we're also seeing patients that are diagnosed they start to do better maybe switch doctors maybe not then they're you know suddenly cured they get undiagnosed and then they start failing again and they get re-diagnosed again um so awareness and advocacy is is really key especially when dealing with zero negative mg so the first five years when my symptoms showed up um i see a little ptosis in this picture but uh but you know it wasn't anything that was noticeable um i did have mainly um voice changes i i that was really the most tangible um symptom that i had my voice became very very raspy i'd have to have this all the time um and it would go away if i would rest for you know a day or not speak for a day my voice would be fine and then if i spoke a lot it would start getting raspy and i'd have volume control issues which you know now i know to be it's it's a pretty classic mg symptoms i started getting really clumsy and i know you guys with mg can understand when you're walking down a hall and you're kind of bouncing off the walls to get somewhere or dropping things because you're you know your hands just aren't able to hold things up um i started getting this feeling that i would not have classified as weakness um it just felt like i it just it felt like i was carrying around you know another person or an extra 300 pounds on me it became very difficult to move at times i could not exercise um at all um and i'd be down and out for a couple of hours after i started missing classes in college um really because i i couldn't walk around the campus it was really really difficult for me um and i i i lived on the fourth floor in my dorm and to get up those stairs because they didn't have elevators then it was near impossible um i didn't tell anybody what was going on because i was i was really embarrassed i i didn't know if i was lazy or just inactive i just didn't understand that this could possibly be a neuromuscular disease um the other thing that i still do to this day um if i was out with friends at a party at an event i would find a quiet corner um or i'd even go out to my car sometimes and i still do this and i would lay down rest and after about an hour i'd be ready to go again but um i found that when i would rest um i could i could get up and do things again so um that continued that was kind of my life for five years i i figured out my own ways to accommodate for these mysterious symptoms that that were based in this neuromuscular disease um uh after those five years as a young adult i i had a bout of um mono and bronchitis i was given a whole bunch of antibiotics that probably weren't good for mg and i started experiencing what was likely an extreme exacerbation of the mg symptoms i had breathing issues very labored breathing i couldn't lay flat i was diagnosed with asthma i i guess i do have asthma but these um symptoms went far beyond asthma that heavy body feeling turned into a complete inability to walk at some time and sometimes i had to be guided to the bathroom or carried to the bathroom i was unable to chew i'd start eating something and my mouth wouldn't work which resulted in excessive weight loss and unfortunately doctors saying that i must be anorexic because i wasn't eating and i was losing weight um these are the types of of little of significant symptoms that can just fall through the cracks due to your due to age a lot of times i think um and what i found was that cold weather extreme cold made everything so much worse um i could not breathe outside at all i could i had a very difficult time walking the weight of clothing was just just too much of coats my parents would pick me up at my apartment and drive me to the front door of my office because i couldn't make it from the parking lot to the front door which was ridiculous that i tried to continue working but eventually i could not work anymore i saw countless doctors mostly infectious disease specialists because i had the mono and bronchitis thing um so i was i don't know if i was misdiagnosed or under diagnosed with chronic fatigue syndrome epstein-barr virus chronic lyme disease i went to mass general i lived in new england at the time and saw an amazing infectious disease doctor there and um and she um did just about every test she could possibly do and and came to me and and said the most compassionate thing she could say she said i really feel like you have an autoimmune disease but i can't identify it i've run all of these tests i can't identify it and it can take five to ten years for an autoimmune disease to manifest in such a way that it is identifiable i was frustrated she was frustrated but i felt seen and i figured gosh i just have to kind of wait this out but what am i going to do in the meantime until it shows up so um i became a little bit dr wary i felt like i had seen so many doctors so i kind of started out on a new path while i was waiting for this disease to kind of show up um i continued my rest and repair cycle i saw a therapist that specialized in chronic illness which was incredibly helpful and supportive i saw an acupuncturist that helped me make diet and lifestyle changes and this was 30 years ago so it was way before there was autoimmune paleo diets and tai chi and meditation you know those have really become part of our complement care now but this was before all that and i and i have to say it it definitely helped the changing lifestyle and dietary changes and acupuncture this acupuncturist also over time noticed that whenever i had my menstrual cycle whatever these symptoms were they would get much worse uh so he worked to kind of stabilize my hormones and things started slowly getting better but every time winter would hit it was just a mess again um i just did not take the extreme so i did the only thing i knew to do i was feeling a little bit better and uh packed up from new england and moved to florida um of course i didn't know about extreme heat and mg because i didn't know i had mg but i moved down to florida i felt great i started working again and all was well until my symptoms appeared in a new way i was diagnosed with graves disease which involves an overactive thyroid and can happen there's a little higher incidence of thyroid disease in people that have myasthenia gravis um so you know we added that to the mix just to confuse doctors a little bit more and because thyroid imbalances can impact mg um i became began having swallowing issues um which i had never had before and i assumed because if i'm eating and i can't swallow i must be having an allergic reaction to something so i would go to the er tell the er doctors that i must be having an allergic reaction they would do iv steroids give send me away with steroids and um and i would feel a little bit better but not completely better um i was kind of leading doctors wrong down the wrong path and instead of saying you know i can't swallow i don't know what's going on um but the only the only frame of reference that i had was that well i can't swallow i must be having an allergic reaction um except my doctors couldn't find any allergies so they were kind of perplexed my neck i started having really bad neck weakness and it was harder to hold up my head my arms and my hands were involved um i definitely started having a lot of anxiety around that time and my breathing problems increased and at this point no amount of natural remedies or alternative medicine was working rest was helping a little bit um prednisone was helping a little bit and um i was able to start working from home so doing breast and prednisone and working from home i kind of was able to get to a decent level of um functionality um and and the swallowing issues kind of resolved but i had doctors um that that were like you know something's not adding up here you have chronic fatigue syndrome but you can't walk sometimes and you can't swallow and one of my doctors said you know what i think you might have this thing called myasthenia gravis so i'm going to send you to a neurologist um and i was like gosh what is this you know and and i went to a neurologist and um i was 92 pounds and at 5'5 i was i was really really skinny um and that neuro basically berated me um for being there because i was wasting his time because my senior gravis is only an older person's disease and there was absolutely no way i could have it i was too fit you know i was 92 pounds and he felt that that looked too fit and i i i was too young and there was just no way that i had mg but he'd run the the um blood work anyway and of course because i'm so negative my blood work was negative so um my general doctor was really shocked um he he felt he had solved the puzzle all the signs for him were there but for the neurologists that i saw they weren't so i was just missing this one symptom and remember this uh this infectious disease doctor that i saw 11 years ago said that this autoimmune disease had to manifest in a certain way so that it was identifiable and very late to the party 16 years later mitosis shows up and it was um it was blatant um you know every doctor could see it i i didn't know what was going on and i went to my general doctor and this time he said okay i need to send you to a doctor that um is very familiar with mg and from there everything happened quickly it was crazy i went 16 years struggling and from that moment when one eyelid was you know practically shutting at night and the other was open it was pretty quick to get a diagnosis the neurologist that saw me diagnosed me preliminarily in about an hour um he followed up with some blood work for mg but he did not feel that i would um show up positive for the antibodies thankfully um 22 years ago he was seronegative aware and he knew that that antibody level didn't mean anything for him if i had all the symptoms and he gave me instructions for a mestand on trial after a week on mestanon everything started feeling better my eyes um started resolving um my body heaviness started going away um it was it was like a light bulb was turned on for me that neurologist did a repetitive nerve study but i was at that point i was on pretty high doses of mestanon and um and he had me on it while i was doing the study so it was kind of inconclusive and borderline so he sent me to a neuromuscular specialist in miami dr bradley who he considered to be an mg expert he had been working for years and years with mg patients um so dr bradley's office told me you know don't take any messing on before you come in he examined me um very thoroughly heard my history um had me take um i i think to mest it on um sent me out into the office for an hour or two and then brought me back and examined me again he confirmed after after 16 years he confirmed my diagnosis of seronegative mg he didn't want to put me through an additional repetitive nerve study or a single fiber emg because he felt that the exam and that trial of mestanon made it very very clear um so i was diagnosed 22 years ago and in those 22 years since diagnosis um i've lived a lot of life and a lot of it i i never dreamed when i was very ill in my when i was a young adult i i never dreamed of of the things that i would be able to do um i established a successful career um got married you know we bought cars we bought homes you know we weren't living lavishly we were just you know able to um you know i thought i would be living with my parents for the rest of my life and here i was living independently and able to have a life um most surprising of all i i i became pregnant at 40 i never thought that i would uh be able to have a child and raise a child with my physical state and i now have a 15 year old daughter um but life is not without its challenges and um and i'm just gonna spend a little time on this because i wanted to focus on the diagnosis part but um but because i was feeling better than ever i kind of thought i was invincible and i really worked myself to the bone and um i was a parent now so i was kind of burning the candles at both ends i was working really hard and i was trying to parent at the same time and my mg really went haywire um it was the worst it was the worst it had ever ever been i ended up hospitalized 12 times in 18 months and as you can tell in the photo on the right i had a very long-term relationship with high doses of steroids at that point because they worked they were the things that worked for me although they were really hard on my body they kept me alive my doctor in miami had since retired and i was referred to an incredible sero-negative friendly neurologist in st petersburg florida that i think a lot of you know and he works with dr rosario um i started seeing dr weiss um dr weiss suggested that i have a thymectomy and start on immune suppressants now i'd had scans in the past that didn't really show any any thymus issues so i had been kind of resistant to even consider thymectomy but at this point i had nothing to lose i had a two-year-old at home and i felt like i was losing the battle of my life and i'm still very emotional talking about it because it was it was a really hard time so i did have the thymectomy after the surgery pathology showed that i had several encapsulated thymomas in the tissue that was removed and the surgeon stated that i had hyperplasia which is an overgrowth of the thymus tissue and it was scattered from my jawline to my last rib um so he had to take out quite a bit of tissue um and he said it looked like my thymus had exploded in my chest he that was the only way he could describe it um so i am forever grateful to the expertise of dr weiss um which really allowed me to live and thrive in these past 12 years post-surgery and uh and i'm planning on a lot more years ahead too so my story is quite long my diagnostic journey is long and um i talk about about my diagnostic journey and my experiences in in hopes that others don't have to struggle for 16 years for a diagnosis um and from what i'm seeing um and hearing a lot in the community now there is hope um specifically seronegative mg um there's a lot of research in clinical there are clinical trials in mg right now and i i think i heard dr pulley and dr rosario say that there's one clinical trial that is including seronegative patients so that's encouraging but we all want to advocate for more of those and there is a serial negative mg-focused project research project that was initiated by the mgfa with the generous donation from susan johnson who is a fellow sure negative mg patient so we're so very grateful to her for her contributions and to the mgfa um and mgnet that is a um has been partially esta has been established by the national institute of health as a rare disease network for mg they're working with academic medical centers the mgfa and conquer mg to research biomarkers specifically for seronegative mg so we've got people doing the work so hopefully um you know we can have some sort of testing that can diagnose someone with with all of the symptoms but not the antibodies hopefully they can get diagnosed much sooner so if you are struggling with care or diagnosis do not delay in getting expert care i travel nine hours round trip to my neurologist and when i couldn't dress myself and i couldn't brush my teeth without going into crisis that was a really scary trip to take with my family it's a hardship to travel but it is 100 percent worthwhile especially if you're seronegative and especially if you're having a really hard time um with your mg if it's significant getting to an expert that understands this disease is very very important because you want to have proactive care to keep you out of the hospital you can go to the mgfa website for their partners in care information they have information on on neuromuscular doctors and then i also like to go into the support groups on facebook and regular support groups and kind of ask around because we're all patients we have the experiences directly with some of these doctors so that can be very helpful to just you know kind of cross-reference also make sure that you get educated on your disease um if you are not already and most of you that are here are here for for that reason so you're already ahead of the game um but make sure that you know what medications that if you take them they may flare your mg they have that is very important information to know know your triggers for you personally because they might not be the same it is the snowflake disease it could be stress extreme temperatures illness it can be having your period um it can be dehydration low potassium levels whatever it is you know see if you can kind of get in tune with your body and figure out what where your you know kryptonite is for lack of a better word and make sure your family knows and understands or and your friends and your loved ones um give them information have them join you at a doctor's appointment have them join in on some of these seminars make sure that they're supporting you in every way try not to self-diagnose as i did in some cases with going into the emergency room saying i can't swallow i have an allergy or i can't breathe it must be my asthma um you know give doctors a little leeway um that was some advice one of my doctors gave me you know tell me your symptoms so that way i can figure out what it is instead of you leading me in a certain direction um also um don't accept every issue as being mg you may be having breathing problems but that needs to be evaluated by a doctor because it could be your mg it could be something else and anytime you're having breathing problems you should be evaluated by your doctor anyway but um it could be something other than mg if you're having a swallowing issue it could be something other than mg so you just want to make sure that that you're not kind of brushing aside too many things saying oh it must be because i have energy if you have new symptoms that are showing up that they're new to you i personally call my neurologist anytime i've had a new symptom that just kind of pops up or a symptom i haven't had in a while that's showing up again i'll call my neurologist and see do i need to have some blood work done do i need to change something i'm doing or change my medication be a partner in your own care and get emotional support this is a long journey there are support groups on zoom as you guys know because you're here um there is an mg friends program through the mgfa where you can be connected with another patient that has mg and they can kind of walk in partnership with you and and help you through some rough patches um that's also available to caregivers which is very important i have found therapy to be extremely helpful so i will dip in now of of therapy of mental health therapy health therapy um you know this is long-term stuff um when i was first diagnosed i had never met anybody with mg um and i did feel very alone um now with the internet and strong patient advocacy advocacy groups we don't have to walk this path alone anymore so reach out build your community it makes all the difference and finally never give up if you are not diagnosed and you're struggling i see you and others see you because we understand we've walked this walk so hang in there don't give up um there is help available um you don't need to be on this journey alone i wish you guys all the best on your personal journeys and i thank you so much for your time today and if anyone has any questions unless that was a great presentation and i do have some questions um i just want to cover up by saying i have my grandson here so you need to hear some water running in the back he's taking this opportunity playing the sink well i can't talk right um what has been the most frustrating part of having sero-negative mg if you could define one part um i think it was going through the diagnostic process especially being young and going through the diagnostic process and and you know almost being treated as though i was crazy and that there was something mentally wrong with me and um you know i looked fit you know having people say things like that no you can't be sick you're you know look at you you look you look great there's no way there can be anything wrong with you um being dismissed i um it was it was really mentally grueling and i think that was the the hardest part um feeling unheard and not um and not believed we can i'm sure we can a lot of us can relate to that so um this is a great segue to the next one so what do you tell others um your loved ones your family friends medical professionals who may not believe in your diagnosis because you don't have that blood test that shows that you are that you have mg yeah i you know um it it's really challenging because um i people that were really close to me um you know things got got pretty severe for me a few times so people that were really close to me saw it and and they understood and um and it became evident and um the other people i i've i've made friends and i've lost friends and i've made the best friends in my life since my diagnosis with people that support me um i i i stopped trying to convince anybody that you know oh i can only do things you know during this time of day because i need to rest and you know um if they don't understand um and don't care to understand it's not my fight to you know to make them understand and that's a really hard truth um when i went through one of my really bad episodes i was engaged and um and the person that i was with was not supportive and it was you know so devastating to me i was i was young and in love and um and i had to let that relationship go but you know what it was the best thing for me because i moved on to people that truly are supportive i loved that quote it's not my fight love that thanks melissa so and on that same realm so you have said that you live quite a distance away from your um zero negative friendly physician how do you advocate for yourself if you need medical treatment closer to home um and before i started seeing my neurologist um not you know nine hours round trip away and um and so i'd get to the hospital and really nobody um wanted to put their hands on me or touch me um and and it it was really hard um you know i'd go in i couldn't breathe and would hear sometimes no you're just having a panic attack and i'm like well yeah because i can't breathe so kind of you get into a panic when you can't breathe um so my i was very fortunate that my lung doctor and i have a cardiologist and they got to talking when i was in the hospital one time and they said you know what you need doctors that come to the hospital and they worked to set up set me up with a general practitioner that goes to my local hospital a neurologist that goes to my local hospital that will defer to my um neurologist far away if necessary he'll confer with him and i only see him once a year um so they set up a local network for me um to make sure that when i went to my local hospital i had doctors there that knew me knew my case knew my history um and and could be called to bring in help because i was in the hospital once and i kept giving them dr weiss's phone number and nobody would call dr weiss and it was something that like my potassium was low and i just needed some hydration and potassium and he knew that but they would not call him so um so you really need to have a good home base in case you need it my doctor feels like part of his job is to keep me out of the hospital so that's what we try to do and we try to be very proactive and i stay in communication with him if i have if i have any issues so hopefully we can bypass that and it's been working for a while i think you're right communication is such a big part of this journey so how do you describe mg to other people ex like again especially sierra negative i think plays is another level um when there's commercials for viv guard on tv and all that how do you describe mg so i i very sim i try to keep it simple so i just say that there's a problem between my nerves and muscles and and there's a chemical between the two and it just doesn't work sometimes and we don't know why so so um things that my nervous system and my brain should be telling my muscles to do it just doesn't happen at times and and then i use examples of what it can impact so sometimes i can have trouble walking or i can have trouble you know opening things or lifting things up or you might hear my voice voice gets hoarse or it gets nasally sometimes i can't breathe sometimes i can't swallow so it's anything that's involved with your muscles there's just something there's a blockage between the connection so that's typically how i explain it it's a great explanation uh melissa i saw the news article they called you the downtown dynamo but i definitely think you're our myasthenic dynamo oh thank you appreciate all you've done for the community and it was a great presentation and you know thank you i think a lot of serial negative patients can relate and patients who are not seronegative have uh an understanding of that journey although we know for everybody mg can be a very difficult journey to diagnosis absolutely absolutely yes thank you so much for the time today oh thank you for sharing our saturday all right um so we are going to talk about um something new that is happening this year we um sorry i have to have notes the community health fairs are new to the mgfa and they will bring the mg community together in a different way than we've experienced before this year there are five venues um alexandria virginia which will be held on october 1st atlanta georgia november 6th austin texas area september 10th san francisco august 14th and then hopefully tampa bay on november 12th we're still seeking a venue for that one so what this is is to connect people share um and um to learn so hopefully patients that patients caregivers healthcare community general community at large will be able to um interact with the other mg patients and medical experts in the field of myasthenia gravis they're also going to be educational material available they'll be local businesses at each one who support the mg community things like medical devices um some of the healthcare providers things um medical alert companies anything that might support the mg community because this is all about the mg community and they'll be um the mg experience so you know we talked to melissa like how do you explain mg well the mg experience is one way that will help you to help somebody understand about mg this is a great event to bring a caregiver to or somebody who's maybe not understanding what you're going through so that they can experience somewhat what mg is like um there is registration on myasthenia.org and nova has brought that up to show us um it's under the event tab and i we will um these will be expanding as um the need is there over the next year we're hoping so i'm hoping this will be a great event for the mg community to get together for people who don't know about mg to learn about mg if you have any suggestions to somebody that you would like to see at the health fair please reach out there is a um a vendor form for any vendors there's also a volunteer form and there's a register form under each tab again florida doesn't have the dates sorry that's that's all i made still trying to find a venue um but i think these are really exciting i i wish i could travel to go see um one of them besides our own but and then the other thing we wanted to talk about was the support groups so there were a lot of questions that came up throughout the chat of how do i find a support group if you go on myasthenia.org under mg community you will be able to find support groups um most of them are still meeting via zoom it's it's just still a safer way in um communities with high covert numbers and what we found is during the zoom is that we've actually allowed people to join whatever meeting best meets their scheduling needs versus geographically so i think most support groups have really seen a growth during this time you can find the support groups and before i mention um two of the ones in florida there are also specialized support groups there is a spanish-speaking support group there is a caregiver support group um and that actually has two different meeting times in a month to try and help out with scheduling there's parents of children and there are the young adults um in florida we have the support group that pam and i co-lead and it is the first thursday of every month via zoom at seven o'clock and there's also dr fully support group which is the first saturday of even months from 9 to 11 and you can find the zoom link on myasthenia.org for now the boynton beach group is has joined the st petersburg support group um looking for a moderator for that group a leader for that group but in the meantime we welcome we welcome everybody we're so happy to have people join the group a lot of the support groups do a combination of education and sharing care so we tried to get speakers for every meeting we're not all we don't necessarily have one for every meeting so like our last support group we did um how to beat the heat how to how to take care of yourself in the heat with myasthenia gravis because we know most patients not all are bothered by the heat in myasthenia so um there are some good tips and tricks to do that we've had dr plowman who you saw today she's always very um willing to present at a support group we've had we have a nutritionist that we're working with now to talk about side effects of medication and how we can leverage our nutrition to help with those gi side effects or the hair loss with prednisone or the weight gainer friend zone so some pretty interesting things coming up and you are welcome to join groups so go on see what one better best meets your schedule and it'll tell you how to go ahead and join with that group any questions about support groups or health fair i know i kind of went through that pretty quickly okay um indova has placed the link for the health fair in the comments if anybody needs to see that link again myasthenia.org mg community find support group so we uh i know dovah has one announcement and then what we'd really like to do is there's anybody on here that's new and would like to have some sharing time um ask questions um we'd really encourage you this is a good time we're done a little early so this is a good time for us to spend time with anybody who would have some questions but first i'm going to turn it over to dovah thank you kathy um i just want to say thank you to our amazing volunteers today so thank you to kathy and pam and jenny for doing a tremendous job today uh hosting our event again i want to thank the sponsors um you guys have seen the we we have great sponsors and we've we have so many new activities um the health fairs are coming up and then also the online community is a new thing that we're that we've launched that should be really exciting so if everyone um if you go to our website it's it's on the home page and you can find the online community and we really it's something where we can share things and make it our own so it should be it's very exciting but take a look at it if you haven't already um i'm going to stop sharing at the screen and let you guys do your chat so i'm turning it back over to you kathy anyone that really wants to speak in mute anybody have any questions for i know melissa's still here so i have a question if i can ask go ahead christy hi i am also serial negative and i've um hearing melissa share her story definitely i could relate to most of of those experiences where the doctors weren't listening or you felt unheard and and things like that one of the challenges that i'm running into is the differences of opinion between neurologists so i have some neurologists who are telling me yes i should have a thymectomy i've got other neurologists telling me no you should run from any doctor that wants to give you a thymectomy so as a patient it's very confusing because there's such opposite opinions so i wondered how other people handle that i am running into exactly the same issues as you are because i i i'm nervous to do i had to have a very minor procedure where they gave me anesthesia and i responded very poorly to it and it completely kicked back in the myacenia portions that we had started to get under control so i'll be honest i'm very very scared of any kind of a surgery at this point based on that experience but if it gives me a hope of you know getting back some of my skills and some of my life i want to do everything i can but it is very very confusing to hear such different opinions and i and i honestly don't know what to do with the information when it when it happens because i have just as many people telling me to do it as i have people telling me not to do it um at that point yep i'm oh i'm sorry go ahead christy finish no i was thank you um so um i i understand uh the confusion and your concerns because before i went to dr weiss i i had my actually my local neurologist saying you should really get this thymectomy and then the one in miami saying you're too young don't don't do it um and because at that period of time and this is this is just my story i can't advise you how to do it because i don't know if i made the right decisions or not at that point um but i was on mestanon only and i was doing great so my thought at that time was well you know i've already gone this far with mgm i'm nesting on i'm doing great i don't need a thymectomy what do i need it for um and then and then when things got really really really bad um and i saw dr weiss and he said thymectomy i was like gosh you know i've gone i think it was like 19 years at that point and i'd never gotten one is this even going to work why am i going to do this i didn't have anything to lose at that point and it could only make improvements in my life um but i i did go i went online to the facebook community and and i asked i didn't ask dimectomy or not thymectomy i just asked like for those of you that had thymectomy did it help and um for me and and i'm not telling you what to do for me there was like this overwhelming response of people saying well i didn't go into remission but it helped um and again i was at a point that i didn't have anything to lose um so i i just went for it and i i was really really scared about it and it was really fear that always held me back on it um and in my case i had encapsulated thy moments so i'm i'm glad that i took that chance um and it did help it i'm not in remission i'm not near remission but um i couldn't brush my teeth without going into crisis before my thymectomy so for me it helped but i i think that it's really important you just have to make whatever decision um you know your instincts are telling you one thing you just it's really a soul-searching thing you gotta take all the facts and then go with your gut and and figure it out um i kind of came to a point where i'm like i can't let fear get in the way of me doing something that might be very helpful for me but again i i didn't have anything to lose i was already really bad so um i don't know what the right decision is for you but um you know that was kind of the process that i went through so i hope that helps okay thank you thanks melissa yeah it's so difficult because we're all so different so you know we do encourage conversations with your health care provider and if you think you aren't being heard then um like melissa said go on the mysteenia.org and look for partners and health care partners people have experience with myasthenia gravis because just because somebody's a neurologist does not mean they know myasthenia gravis i'm going to take one mountain tony can i put you on the spot i see you're on tony gittles is on and she runs the caregiver she's lead for the caregiver um support group so i wonder if you could talk to us about that yeah it's great um i am a patient that has ocular myosinia gravis but i also have led support groups for caregivers in the past so i am volunteering with mgfa to lead caregiver support groups you all have your stressors having the disease of which i am somewhat familiar though my situation is not really stressful i'm functional in everyday life and without difficulty um but the care the people that are in your life the loved ones that either live with you or provide some care support and love to you are going through a different type of experience completely and they i'm sure have your best interests at heart but sometimes as the care recipient we do not pay as much attention to what their needs are so and they do need to talk about it and they need a support group of people going through the same type of circumstances just like we as patients of with mg um can get a lot of value from support groups um with our people that are going through the same circumstances have the same disease so i would encourage you um to bring up uh the idea of your loved one who is caring for you to attend one of the support groups to check it out even if they feel like they don't need support there may be something very valuable in the conversation we are having for the first time a guest speaker who is going to talk about relaxation and stress techniques this coming tuesday july 19th as well as saturday july 30th it's something that i have been studying as well meditation mindfulness and relaxation i wish i had had it a long time ago when i was caring for my mother because the stress was unbearable so um this is something to explore for for everybody actually but the support group is for your your loved one who's caring for you um that's uh that's about i don't know anything else kathy that i'm missing um i did have i've had some people come that came once and then didn't come back but their loved ones said try it again so i now ask everybody we're gonna spend an hour and a half together what would be what would give you value why are you here so we do go through that conversation at the beginning people introduce themselves very briefly and they let me know what they need so that way it seems i can make everybody happy and they leave with some value so just let them know check it out a lot of people are coming on a regular basis and i really appreciate that and some people if you're going through a calm less stressful period you feel like you don't need it you don't need the support i would say come anyway you know encourage them um that you'll get techniques on communication and effectiveness and um just how to be a caregiver and relieve some of the stress between both of you that you're experiencing thanks kathy appreciate it welcome tony i always say our caregiver has the disease also just not the physical symptoms but they definitely suffer along with us um one of the patients was asking does anyone have seronegative mg and positive for voltage-gated channel antibody you can put it in the chat if you would like to if you feel comfortable and i do have a question as a support group leader and i think most support group leaders would really appreciate your input what type of educational opportunities or speakers would you like to see support groups do could you explain education please so where we could get a subject matter expert julie um somebody who knows a lot more about the topic than than i would know um you know like we've had dr plowman before speak about exercise um in energy conservation methods that type of topic because you know sometimes i i can't tell if i'm coming from my own perception my own point of view my own agenda and i want to make sure that as support groups we we are creating something for everybody and if you don't think of it now we could think of it later and maybe email one of us and just let us know that would be great any any kind of suggestions for the individual support groups um would be fantastic i had kathy i think i had mentioned to you that i had been studying positive psychology which is the science of happiness and i've started lecturing in my community to care caregivers about happiness and incorporating the principles and what we've learned over time is there are practices that you can put into place on a daily basis that don't take very long that actually increase your ability to find more happiness and joy in your life so this is something i'm very excited about um and whoever knew it was that easy i mean you can actually become a happier person no matter what your circumstances are and we certainly are engaged in challenging circumstances with this disease yeah i think melissa even mentioned that she's made some of her best friends through this journey thanks tony we may be we may be talking about that does anybody have anything else that they would like to ask bring up comment on you can take yourself off mute can i ask a question sure is there a place to find a listing of doctors who specifically believe in zero negative mg um we have our partners in careless and and and those are the doctors that the mgfa recommends um unfortunately that's not a specific question that we that we ask because they'll all tell you you know the same but it would be good to get a recommendation from someone in a support group about a you know a neurologist that they've gone to and had a good experience with that's probably our best recommendation for finding someone um you know who is more sero-negative friendly than than someone else might be we have a lot of support groups you know you they're all online and and through zoom you can attend a lot of different locations thank you great dovah do you have anything else before no i think we're good um thank you to everybody i'll let you close up um cathy can i ask one question one question please nandita go ahead julie um i'm sorry may i ask where you are located please louisiana ah okay i'm i was going to try and give you some lists of serial negative specialists but i don't have one in louisiana so it doesn't matter i will go anywhere to see someone i have seen about i've seen a few and everybody's giving me like a different answer regarding a thymic to i would really like something which will induce a remission without having to take an immunomodulating drug which is going to mess up my immune system i don't tolerate those medications well so i would take the name of any physician um and i too am i'm willing to travel i i hope the group will bear with us for just a minute i'll make this quick uh to travel to try and find somebody who's why don't you why don't you two exchange emails in even your that yeah yeah go ahead and exchange your emails in the chat i apologize okay no problem and i think um daryl has his hand up kathy i'm sorry uh yes daryl go ahead i just wanted to add a comment i found dr weiss by accident actually i lived near him and when my ophthalmologist suggested that i see a neurologist because he thought i had my opinion uh because i had through the eyelids and i knew a friend of mine's wife had myasthenia and i asked him what doctor his wife was being and he recommended dr white i had no knowledge at that time about dr weiss's reputation and i got an appointment with a very long waiting period to see doc actually i saw dr rosario first and he died mostly in 2016. and then later on that year i saw dr weiss switch to his uh care and i later on learned about his reputation by people in a facebook group when i saw people coming long distances to see him and i was quite amazed and but his he's been absolutely amazing for me um i've been really fortunate not to have been in crisis and i'm thankful for that although i really didn't have any serious symptoms until this last fall and i've been battling that since then trying to stay out of crisis i've got severe copd and i fight that as well but my doctors locally have been greatly cooperative with him um trying to keep me out of trouble and and i'm thankful for that as well and he's also very cooperative with them uh and i've questioned the thymectomy and i've gotten chest scans annually and i've had the radiologist pay particular attention to the finest land when they read those scans so i've really tried to advocate for myself and push them to pay attention to these things and be very careful about them and dr weiss has also been very cooperative about that i'm sorry we're going to have to close it out um daryl i'm so sorry we need to be our best advocates i think we heard that from melissa um just a note that if you are on a long waiting list to see a doctor asked to be put on their cancellation list as most doctors want that list worked especially with covid cancellations they don't want to lose newer patient slots so um with that we're going to have to close out but i want to thank dovah for always being so great with us and getting us where we need to be to get the information that we need and our speakers today dr rosario um dr plowman dr pulley and our um dynamic mgr melissa thank you everybody and we hope to see you at next year's conference thank you have a great day thank you