Damage From no treatment
 

I get it a lot isnt understood about nmj but has it been determined that living with MG without treatment (undiagnosed) for many years causes damage that cannot be repaired? If yes is damage due to "pushing through" symptoms and doing ore than should or due to lack of medication to assist or both?

I was told that mestinon only helps when you are taking it. If that is true, it doesn't seem like it would make a long term difference one way or the other whether you take it. My neurologist gave me the impression that it just helps me get through the day (and life in general).

I am interested to hear what others have to say on this for sure.

I ran out of my 180mg time release Mestinon about 2 weeks ago and missed 4 days of it and saw no difference. When that happened I just stopped taking it and it has been 2 weeks with no changes good or bad.
Mike

Mike

You are also taking other med's too right? If my recollection is correct, you didn't get much relief from mestinon as compared to someone like me who has noticeable relief when I take mestinon.

Stephanie

It's weird this post came up today.

I took my first mestinon, prednisone and cellcept in two days just 1/2 hr. ago. Just before signing in here. Friday and Saturday I did not take any medication.

I did not feel any difference with the exception that I got a couple of nights of pretty good sleep and no headache. I was afraid to go any longer without my meds.

I have an appointment in November with another Neuro for another opinion on whether there may be some other treatment option for me. Specifically Cytoxin.

scrubbs

Scrubbs
I would be VERY careful with the prednisone. I missed a dose and it really knocked me for a loop. My dr is slowly reducing mine. I'm down to 20mg.

I feel the same way. Mestinon has no effect on me and I have tried Imuran which only made me sick as a dog. I am currently on Cellcept with no effect for 7 months. I have had so many IVIG's I have lost count with zero effect. I'm like you, I need to look at another approach. I'm considering going to Wake Forest for a second opinion. I would never ditch my Neuro I love him. He suggested Wake Forest a few months ago. I do have positive Striational antibodies plus 3 others which I have been told is the most severe form of MG.
Mike

The answer to your first question-No, there is no clear data which show that.

I believe (from the limited data there is) that it is more likely that the severity of the illness is determined by its nature to begin with. So, some patients will have a relatively mild illness which will never progress, whereas others will have a more progressive course. It is not clear if response or lack of response to treatment is also predetermined.

As to your second question, I think that it can cause damage.
In fact even trained and healthy athletes have some damage when they exceed their abilities. Trained marathon runners do not run faster than what they can with 70% of their VO2 max.

Mike;

Prednisone seems to be my bread and butter too.

scrubbs

Oh, and it's my Neuro sending me for another opinion.

scrubbs

See I believe Neuros send us for second opinions because they do not have the expertise to deal with difficult cases. That being said I appreciate my Neuro doing that. That's just one reason I like him. Most of them have ego's that will not allow that. I have already been for one second opinion and he was the one who found out I was positive for 4 antibodies but did not offer any plan of attack.

Prednisone almost ruined me. I was on 60mg and the muscles in my legs got so weak I almost needed a wheelchair. The second opinion doctor (neuro-muscular) said I was one of those people that can't take Prednisone and started tapering me that day.
Mike

Mestinon - an acetylcholinesterase inhibitor - does nothing to improve or slow the progress of MG. It simply allows our muscles to take up more acetylcholine than they are able to (due to the atrophy of ACh receptors on our muscles).

I think Alice described it best in another post - our bodies release a constant level of acetylcholine, and our muscles take up what they need. Acetylcholinesterase comes along behind and "mops up" any ACh that hasn't been taken up. This is necessary because a human's muscles cannot handle too much ACh.

For people with MG, the fact that our receptors are damaged means that we aren't able to take up an amount of ACh which will allow our muscles to work well. The AChE mops up the excess, regardless of if we have enough in our muscles or not. It isn't a "variable" process, it is a constant, level process.

Mestinon allows us to "cheat" that process by slowing the rate at which the AChE is released by our body.

So in that regard, Mestinon is not a "cure"; rather, it is a "booster". It works differently in every person who takes it (however, a person who doesn't have MG will not be able to tolerate it because there is nothing wrong with their ACh/AChE process in the first place).

It is the immunosuppressants which seem to help us more, as they stop the PROGRESS of the damage which is being done to our receptors.

Most Drs. will start their MG patients off on the lowest possible dosage of an immunosuppressant precisely because of the side effects. For most patients, those side effects that are so common with medications like Prednisone tend to not show up until a patient is taking more than 20 mg/day.

I've been on 10 mg/day for over a year and haven't noticed any adverse side effects; however, for a couple of weeks when I had to be hospitalized, my doctor put me on 60 mg/day, and it was horrid. I was eating anything that wasn't nailed down, and I was "hell on wheels", as my family put it.

Of the two, the immunosuppressant appears to be the one that is more important in terms of "helping" MG patients (and it doesn't work for everyone), because it slows the progression of the disease. Mestinon doesn't have to be taken, but it will generally allow us to function day-to-day more efficiently than we could without it.

Obviously, you are not required to take ANY medications if you don't want to - you just need to be aware of the REASONS that your doctor is suggesting these medications.

....living with MG without treatment (undiagnosed) for many years causes damage that cannot be repaired? If yes is damage due to "pushing through" symptoms and doing ore than should or due to lack of medication to assist or both?

And I realize that I didn't answer your original question.....

The damage is ONLY caused by the autoimmune response - our body, for whatever reason, attacks itself and damages/destroys the biochemical receptors on our muscles. By the time we realize that damage has been done, we are experiencing pretty noticable symptoms.

My neuro said that because the progression of the disease is so slow, most people have been "living with" MG for many, many years before they are diagnosed.

I thought that my "symptoms" were common for a person my age who didn't exercise and was overweight - it never occurred to me that I had it exactly backwards. I wasn't able to exercise because it wore me out; I never would have imagined that I was getting worn out because my muscles weren't getting the "juice" that they needed due to an illness that I didn't realize I had.

By the time that we are diagnosed with MG, the medications that are prescribed are to try and slow the rate at which the disease progresses. There isn't a "cure" for MG - doctors can only hope to slow things down (immunosuppressants) and/or make our current condition more manageable (biochemical inhibitors).

Nobody knows what CAUSES an MGer's immune system to go wonky in the first place, and it since it takes so long for symptoms to start causing problems, there really isn't any way to prevent the damage from being done. But once it's done, it's done - there isn't any way to regenerate those receptors.

By the time we are diagnosed, we are pretty much at the point where all we can do is hope to minimize further damage.

I started 10 mg prednisone day three weeks ago and have seen no improvement, effect at all...how long does it typically take to see if low dose is going to help or not? I am contemplating asking dr to increase to 20 per day as my current condition is generally crummy all the time which some time in between mestinon doses that I feel ok, not great, not strong, just ok but by end of day my legs feel like 200 pounds of brick! And my vision is really bad.

Steph,

It would be reasonable to try 20 mgs a day. It's when the dosage gets into the 60 mg and up that it gets into "high dose" territory where side effects can really get problematic quickly.

I've been on and off of pred many times in the 14 years I've had MG. I find that 20 is my upper limit as the mental/emotional side effects are much more problematic if I go higher than that. It would be worth a call to your doctor.

Good luck and hang in there.

How long after taking dose did you notice effect?

The very first time I took it I did 10 for 1 week, then 20 for one week and that is when I noticed the effects. I didn't go higher at that time....but did need to after a post-thymectomy crash a few months later.

Now it just takes a few days to notice an improvement, but I'm at the point where I don't wait and see what might happen; I just take care of it. My neuro trusts me to use pred as needed, due to my prolonged "experience" with it. I am also on other medications (but don't use mestinon).

Hope this helps (and hope the pred helps, too!):)

Hi Steph,

I was too tired yesterday to give you a more elaborate answer, but I have been researching this question quite a bit, as many things in MG appear unreasonable (such as people having improvement in their symptoms after a year of taking a medication which leads to improvement within 12 weeks in other diseases; the notion that MG is a "nice, easy to treat" illness, when not all patients respond to treatment and left untreated it can be fatal; the fact that so little is known and understood about this disease and yet there is so little research).


To answer your question seriously, you need to know the natural history of the disease. Most MG patients nowadays are treated, so the natural history can only be found in historical studies from the 60s and before.

There are very few and quite methodologically flawed, but do give some idea of what this illness was like (before there was any treatment other then symptomatic).

Interestingly, as opposed to diseases in my field of practice (in which we try to stratify patients according to risk/benefit of treatment vs. no treatment) this is not done in MG and all patients (mild ocular MG to severe generalized MG) are treated the same. Although many neurologists are aware of the possibility that there are different sub-types of MG.

So, the data I was able to extract from those studies is quite limited, but summarized below:

20% of MG patients will have a spontaneous remission (=complete disappearance of all their symptoms with no treatment) which can last for quite a few years. All will eventually have a relapse of their illness and the severity of the disease when it relapses is unrelated to what it initially was.
So, having a spontaneous remission is not a prognostic factor.

about 3/4 of MG patients have mild to moderate disease over the entire course of their illness. Most of those patients will have a slow gradual improvement in their symptoms over the years. (I believe, as opposed to the authors of the paper, that most of it is due to adjustment and not a change in the activity of the illness).

About 20% of the patients will have a severe disease, requiring respiratory support. 90% of them died in the early 60s and this gradually decreased to less than 5% who die nowadays. This is mostly due to a combination of ICUs, much more effective supportive care and possibly also better treatment for the illness. (I believe this will go down to nearly 0, once non-invasive respiratory support is used more often).

Further more, some of those who died of respiratory complications in the past had a relatively mild illness which was complicated by a severe infection. Such patients will do very well nowadays even if they do have a more severe exacerbation and quite likely not have another "crisis". So, the notion of neurologists that this is "the most rewarding illness to treat, in which patients can go from being respiratory dependent to normalcy" is probably correct in a significant number of patients.

Most patients who have a severe disease will have severe symptoms within the first years of the illness.

There is no way to predict the course of a given patient, in the early days of the illness. Statistically most will probably do well even without treatment.
There are small studies which suggest that treatment within the first year after the first symptoms leads to a better chance for response. But, it is also possible that patients in which there is a delay in diagnosis (and therefore in initiation of treatment) have a different sub-type of MG which makes them less likely to respond.

So, to answer your question-from the data I have it seems that a delay in diagnosis doesn't lead to damage which can not be repaired. It is more likely that a delay in diagnosis is because it is a less typical variant of the illness.

It also seems that (like in many other diseases) the nature of the illness is determined from the start. So, some people have a mild illness and quite likely will never progress. Whereas others have a more progressive course and will probably require more aggressive treatment to put it under control.
Some have a disease which tends to respond to the currently used treatments and others have a disease which is less likely to respond. (and hence the urgent need for more research).

Like I have said, most MG studies lump all the patients together, so it is very hard to know what is related to the nature of the illness and what should be attributed to treatment. Also, most of the significant improvement in survival was due to better supportive care and not treatment of the disease itself. Although, one study shows that treatment with Prednisone/Imuran of patients who had a crisis, decreased their risk of another crisis.

The bottom like is that there is very little data regarding the optimal management approach of MG; Limited understanding regarding its mechanism and minimal attempts to improve this.
The good news is that most patients will probably do well, regardless of what management approach is chosen :). (and this is probably the reason why most experts in the field are so lay-back about this illness, because in the majority of the patients it is an easy to diagnose/treat "nice" illness).

Some neurologists will honestly admit that, and try to find the best management approach combining your understanding, knowledge and experience with theirs, based on the nature of your illness and your life preferences and values. Others will give you answers with the self confidence of a dictator, with very little data to base it on.

Alice that was another of your wonderful insights to this complicated disease.
Thank You
Mike

I totally agree Mike – this makes for a wonderful read and the most amazing information. Thanks for researching and sharing all of it, Alice!

(Celeste – I have been given the green light for taking Mestinon only when I need it and have got it working with my fluctuations because that works for me. Now suddenly it has turned quite cold where I live and surprise surprise I can take even less of it)

Anacrusis

I hope that means you are feeling better!
Steph

Alice

Thanks for the (as always) thoughtful response. I realized although I like my neuro, truth is only thing he actually told me was he said I think you have MG beyond that anything I know about it is what I read which is quite amazing to me.

Also another thing I noted about neuro in general is they do tests, exams that suggest to me that unless I am literally incapacitated at time of the exam, ar sort of useless...ie..sure I can walk, touch my nose and puff my cheeks but that doesn't mean I am ok. Perhaps something that actually compares your performance to your own baseline would be more helpful?

Steph

My neurologist tests me (for example) by having me push on his arm, and my strength always seems normal. But the neurologist who finally diagnosed me (I had to travel) used the same tests, but he kept me pushing much longer. At that point in my illness, I wasn't noticing weakness in my arms, so I was surprised when the muscles gave out--in a way I had never experienced before. Now that's a neurologist who knows what he's doing! He said, "Hmm. That's pretty good. It's not normal, but it's pretty good." I was so glad to hear those words, because it was the first time a doctor had anything to go on besides my description of symptoms.

Abby

Well certainly today I feel extremely normal! I hope this lasts and am not getting overexcited about nothing! Hard to believe a few weeks ago I was choking on my spit during SFEMG – But surely cold temperatures can not possibly give such dramatic improvements? It´s as if suddenly no´damage´ is present even after all these years. I doubt that I will ever return to my original pre-myasthenia activity level but if I can find an electric cooling jacket, take Mestinon when needed and stay away from antibiotics then I think I´m good! (I do know you can´t do that with other medications)

Hope you get the minimum spreading of MG and maximum effects from your medications, Steph

By the way - I landed probably the one neuro on the planet who didn´t test me for fatigable weakness.....and I wondered why a neuro wouldn´t ask which were your weakest muscles :Scratch-Head: when that is the whole point of your visit.

The fact of the matter is that only around 600 people in the US are diagnosed with MG per year - it's not a common disease by any stretch of the imagination. The best neuros out there are the ones who are willing to LEARN about the disease and listen to their patients.

If you are lucky enough to live in/near a larger population center, chances are that at least one neuro in the area has had experience with more than one MG patient.

And yes, it is hard for a doctor to know what our day-to-day lives are like when they only see us for 1 hour (or less) every 3-6 months. If we "appear" fine at the office visit, they will naturally assume that we are like that all the time.

Some people have found that - as hard as it is on their body - it is sometimes best to not take their medication before their office visit. Some of them find that an appointment later in the day (when muscles are weaker) "helps" as well. Keeping a daily journal can help, too - it gives their doctor better insight into what's going on day-to-day.

Most doctors want to help us as much as possible, but they can only work with the information they are given/what they see. They're only human, and they don't have the time to do the in-depth research that we can do - they have more patients than just us, and most of them have families who want to spend time with them after their work day is done.

A good doctor is one who is willing to work WITH their patients, and who understands that we have access to information that might be helpful to our individual situation.

Totally and utterly agree with that. I now have a doctor who sees me and treats me as one of the ´5%´ SFEMG negatives in MG which is quite amazing. This was effortless on his part and made me realize that a relationship with a doctor doesn´t have to be a laborious arduous task.

It wasn´t difficult to respect but SO MUCH hard work trying to work with the wrong doctor over 2 years when you already have debilitating symptoms. I personally am a much´harder´ patient now than what I was. Just like running a business - at the same time as still respecting all of my present doctors I expect no nonsense both in and outside of the doctor´s office.

I may be wrong, but I do not think MG is that rare. Also, neurologists see all MG patients, not only the newly diagnosed ones. So, in a chronic illness the exposure of physicians is determined by the prevalence (the number of patients in total) more than the incidence (the number of newly diagnosed).

There are about 25,000 MG patients in the US.

According to Google, there are 13,5000 practicing neurologists in the US.

So, on average every neurologists sees 2 MG patients over his/her life-time.
This number is of course much higher for neuromuscular specialists.
In fact, most leading MG experts see a few hundred patients.
So, not having enough exposure to patients is not the reason for lack of understanding and knowledge, nor does it explain why there is such limited research.

I am sorry, but I do not agree with that. Part of a physician's job is to have a good and deep knowledge and keep updated with the research in his/her field of practice. Physicians should also try and find answers and better ways to manage their patient's illness by doing well conducted research.

I think most neurologists do know the medical literature on MG, with reasonable depth. It's just that there isn't much to know. The way MG was diagnosed and treated 20 years ago is very similar to the way it is diagnosed and treated now.

I agree with that. I think it is very hard to think that someone who looks so well in the office can be so ill at other times. They know this illness can be confusing and fluctuating but they find it hard to imagine how much. (even we, who live with it 24/7 find it hard to comprehend, so can't blame them for that).

I fully agree with that. I think it is even more true in this "crazy" illness and not every physician has the personality which is required for that. So, even if they have the best intentions they end up stepping on our toes during this complex dance.

no treatment
 

I am not very experienced with this, but I went apprx 4 years un treated , because of no diagxx and mine did not get worse. I stayed about the same, hard to chew, hard to speak sometimes, and droopy eyelids. Mestinon has completly taken that away, but I wasn't getting worse before.
Thanks all

FredH

Which brings to mind a question I have had in my mind for some time. As a practical matter how long can a person stay on 60-80 mg's of Prednisone without causing serious damage to the body...muscular, skeletal, organs, etc. Of course it will vary depending on the initial state of health when the Pred is started...but on average I wonder. I have been on 80 a day for one month and am now beginning to drop to 60 every other day. Presumably this is the beginning of a long taper during which my Neuro will look for signs of success or failure in getting those hooligan antibodies to stop destroying and/or blocking my ACh receptors. But I have to wonder how long I can keep taking this sledgehammer drug, it's already taking a toll. Just now reaching the "puffy face" stage...and weak? Oh yeah. Oops and one more question. At a sustained 60 or 80 mg level of Pred, just how much of a person's immune system has really been put out of business? It can't be a total shutdown, or we'd all die of a common cold. Any thoughts?

Very articulate and accurate explanation. Thank you. I'm familiar with the hell on wheels thing at 80mg, which was my starting dose 30 days ago. Some start high and then go down, others the opposite. I think my Neuro looked at my exacerbated symptoms and anti-body count and decided that my MG needed to be to hit hard right out of the starting gate. The Pred tends to make me more hostile and sensitive, then the 60-4x Mestinon wires me up tighter still. I have to admit that there are times when I'm not fun to be around. Or could it be the Peet's coffee that I'm addicted to? No wonder my pupils are constricted, along with some other things. -Mark

80 mg of prednisone a day will most definitely cause some issues. It would kill me due to high blood pressure. How long it takes will probably depend on you.

I don't know that much about humans, but I had a 100 pound dog that took 40 mg of prednisone every other day for 7 years. He died eventually, but he was 14 old which is about as long as any 100 dog is going to live.

When I was on 60mg I had the fat face, swollen ankles, hump on the back of my neck plus a huge neck BUT the worse was it was destroying the muscles in my legs. I got to the point where I could only lift my foot 2 inches. I went to my neuro-muscular Dr and he said I had to get off Prednisone right away. I am currently on 20mg but slowly still reducing it. Never did see a benefit from it.
Mike

Mike, a lot of people (and dogs) do have a lot of side effects from prednisone. If it is not helping (and for that matter helping a lot), I think that you are doing the right thing to wean off of it. The only reason to put up with horrible side effects from any drug is if it does so much good that it is worth it. Side effects like you are telling us about are too bad to tolerate. I would think that it could kill you if you kept it up. Other people may do ok on that much.

I think that the fluid retention would kill me. If I eat pizza, my blood pressure will soar. If I took a drug that caused fluid retention, I don't think I would make it.

I am very glad you are getting off of it.