Originally Posted by alice md

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