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