Hi,

first, I want to apologize for not having a lot of time to come here, and chat.

I am thinking of you, and of how we can improve the understanding and managment of this illness, and am trying to do something about it. slowly, but hopefully surely, though it is very hard to know.

as part of that, I have discussed with my neuro that he will start writing about some unusual observations, that are considered "impossible" in MG.

one of those is the worsening (instead of improving) of MG with steroids. and I am not talking a about a transient worsening initially, but of continous worsening with treatment, and gradual improvement with the tapering down of the steroids.

I was wondering if any of you have experienced this? obviously, it is quite rare (he has only one more patient apart from me that has this problem), but existent.

my "story" with steroids was that 5 years ago, I recieved high dose steroids during my crisis, and once the PLEX was stopped, I went into another crisis again, about 4 weeks after starting the steroids. my neurologist at that time thought it was "impossible", but fortunately my pulmonologist/anastheisologist didn't give a *******about what he thought, and I had PLEX again, the steroids were stopped and within a few weeks I gradually recovered to some extent.

about 2 years ago, after my illness progressed to the extent that I was intermitently respirator dep. , I was seen by one of the leading experts, who thought I should be given steroids. he explained to me that what happened before was the well recognized transient worsening of MG with steroids. (obviously, he had very little respect for the neurologist that took care of me before, assuming that he didn't know that, and not there was something unusual about the way my illness got worse).

I was so desperate at that time, that I was ready to do what ever he recomended. again, I had PLEX, with significant (and very short lived) improvement, followed by a gradual increase in the dose of the steroids. again I had the exact same response. but, this time I was told that it was transient and I will be much better when I go home. I was also told (again) that the pattern of worsening that I had was "impossible", and the fact that my SFEMG at a time of profound weakness and respiratory insuff. was completely normal gave support to that.

so, (stupid me) , I put my trust in him, and kept on taking the steroids, until I nearly died, and then decided to start trusting my own clinical judgement, and began to taper them down.

it took a very long time, because by then I had supression of my adrenal gland with fairly significant addissonian symtpoms, so I could only decrease them very slowly.

so 2 weeks ago, I was finally able to stop taking them. I still have addissonian symptoms, which combined with the symtptoms of MG are not easy to handle, but they are gradually becoming less. I am still not back to what I was before this treatment (which wasn't that great either) but possibly will get there eventually, and be well enough to tolerate other treatments, that are now too dangerous for me.

so I was wondering if any of you have had similar problems with steroids?

alice

No, Alice, BUT, I knew NOT to take steroids BECAUSE I have have previously suffered from steroid psychosis (suicidal). I had to FIGHT with several neuros over this -- who were convinced that the ONLY way I would "survive" was IF I immediately started Prednisone.

I suspect that the problem "may" lie IN the anxiety that Prednisone produces in the susceptible -- and that anxiety RAMPS up the antibodies -- actually making us worse.

I don't know about everyone else, but ANXIETY is my enemy number one and VIRAL/BACTERIAL INFECTION is enemy number two.

http://www.drrichardhall.com/steroid.htm

Alice,

in1991 I was put on high doses of Pred and after months of misery I told my Dr I wanted off of them, he was against it so I started tapering myself off, it took a year but it was oh so worth it, in fact I went into a drug free remission for 17 years.

My MG is back now and my Dr. says no pred for me {and I agree} I had a "Power Port" put in and after surgery had a bad reaction to the meds they gave me and the surgeon pumped me full of steroids.. BIG mistake. My blood tests showed imminant heart attack and liver function off the charts, it was all due to the steroids.

So I can't take pred and to be honest I think it made my MG worse back in 1991.

Actually, now that you mention it, Alice, I developed additional MG symptoms since starting steroids. My left eyelid gets droopy a bit since I started them, and my upper body weakness is worse. It also seems like my speech is more dysarthric when I'm really weak now, as opposed to before.

sorry to hear about the steroid psychosis that you had. it is very rare and I am sure quite scary. I have seen one patient that had it. it was when I was a med. student, but still remember it. she was a very sweet young woman, who was started on steroids due to lymphoma and a few days later she was brought to the hospital after she ran naked in the street.

it is good that you managed to fight those neuros that thought they know what's good for you, better then you do.

the worsening of MG I am talking about though, has nothing to do with anxiety, nor with the immune system. it is most likely due to a direct metabolic effect on the muscle fiber. in fact, it was one of the pieces of the puzzle that I had to understand my illness, the reason for the normal SFEMG, hypersensitivity to calcium etc.

alice

what you say is very interesting and also gives a lot of hope.

do you remember how long it took since you stopped taking the steroids all, together, until you were symptom free?

my feeling is that since I stopped taking them about two weeks ago, after having some fairly bad withdrawl symptoms, including total lack of mental and not only physical energy, I am gradually doing better each day. it is a very minimal, hardly noticable improvement so I am not sure if it is just wishful thinking or could this be real?

Nicky,

my thoughts are that the reason steroids make MG worse, is that it decreases the entry of calcium into the muscle cell. (this is well known and has actually been utilized in the treatment of Duchene's muscular dystrophy).

when there is activation of the acetyl-choline receptor, it leads to depolarization of the membrane (which is what is detected by the SFEMG), this in turn leads to entry of calcium into the cell. the calcium that enters the cell, eventully leads to release of calciium from stores inside the cell. ( the exact steps of this process are not clearly known, but most likely involve various proteins that are related to the synapse, such as DOK7, MuSk etc. ).

the protein that governs the release of calcium from the intracellular stores is our "good ole friend" the ryanodine receptor, which is activated to release the calcium by calcium that enters the cell, but also by adrenergic receptors (such as with ventolin or ephedrine), and caffeine etc.

so my thought on the matter are, that if you do have worsening of your symtpoms with steroids it could be due to some malfunction in one of those proteins, possibly the ryanodine receptor itself. so once there is impairment of calcium entry into the cell (due to the steroids) combined with the abnormal ryanodineR, it could lead to further impairment of muscle contraction. this could also explain why your response to mestinon is not so good (if I remember correctly).

I personally think that those events are much more important then the depolarization of the membrane. and that's also why, there are patients that have very minimal MG symptoms with a very abnormal SFEMG and vice versa.

and possibly also the reason why there is no correlation between the titer of the achetyl-choline receptor antibodies and the severity of the symptoms. because this is not the right antibody, that leads to those symtpoms.

al lot of what I am saying is theoretical, so maybe it is not correct.
but, at least it should provoke some thinking.

alice

Wow...It seems like you're right on!

It's funny you mention Duchenne's...I looked up 'prednisone + DHEA' because I was thinking that I should maybe take DHEA since it's suppressed while on steroids, and I came across info. on how Duchenne's is treated with prednisone which I didn't understand why, but now do...

When I was reading postings by Cowgirlup, I felt that she must have the same antibody as me- the one that causes my strange symptoms because our sx are sorta similar, at least from what she described...I agree that I don't think that the achr antibody is causing at least the majority of my sx. My titre is 2.88, and my MG is severe. I know that the docs. say that the titre, at least when it comes to MG, is not related to severity of sx, but the titre of antibodies in other illnesses is, so it seems that maybe something else is going on.

I asked my neuro. yesterday if I was tested for the ryr and titin antibodies, and he said that I wasn't because it wasn't necessary in diagnosing the MG (I also suspect that they never suspected that I had a thymoma either...I think they thought that I had the MuSK type).

Anyway, I think that you are definately right on the money...What you say makes perfect sense, and yes, I was convinced that I had some other illness for the longest time because the mestinon didn't work for me at all, it seemed...I have to admit that it does work now, especially the time-release, so I'm still wondering what's up with that...It all is very complicated, but keep doing what you're doing...If people have the ryr antibody, then prednisone shouldn't be prescribed to them because it just makes things worst!

P.S. My SFEMG was very abnormal..It was done in my forehead (where I didn't seem to have any sx).

Nicky

Alice it could be real....

It took a year to tapper off for me, I went real slow and slowly started feeling improvements. A year later, I packed my car with everything that would fit, sold everything else and took my young sons and drove from NY to FL to start a new life. I was in complete remission. So I guess it took one year. I was DXed in 91 complete remission in 93.

And let me tell you, I lived every moment that I could, from bike riding to hiking to swimming.. anything and everything I could!

But remember this too... I had the mental drive, so I also believe that may have played a part in it. I honestly didn't think of going into remission but I felt I wouldn't let MG beat me. The remission was an added bonus, but now that you bring up the steroids I think you are onto something there!

My neuro that I have now.. refuses to use steroids, and God love him for it

Nicky, If you want to become even dizzier with information, read this.

http://www.ihop-net.org/UniPub/iHOP/gs/91954.html

Or this.

http://www.neurology.org/cgi/content...act/62/10/1894

There's a lot of info out there, but who's pulling it all together?

If you want more info, just do this search: myasthenia gravis RyR1

Alice, I did not really get better on steroids (they make me feel nutty too) but whether that was due to the dose or length of use who knows. I know they are useful but I doubt if they are good for everyone too. Hope you are doing ok.

Annie