My understanding is that coffee is an anticholinesterase, like Mestinon but milder. Coffee makes me stronger when I'm weak.* Mestinon doesn't. What does that suggest? All I can think of is that I've been taking Mestinon in doses that are much too large (I've tried 60mg at a time and 30). I'm going to try quartering the pills and see what happens. Any other thoughts?

Abby
*I love coffee so much that I have to use big words like "anticholinesterase" to convince my family that I'm not just joking about how good for me coffee is.

I am not aware of coffee being an anticholinestrase. It does have a direct effect on the muscle more similar to theophyline or ventolin.

It is interesting that coffee works for you better then mestinon. Have you been tested for MuSK? or other antibodies?

Alice, after I posted that I looked it up and found out that that little factoid was a figment of my imagination. I will look into the other drugs you mention.

I tested negative for the AChR antibodies three times, and negative for the MuSK and LEMS antibodies once each. I would like to know what is going on with me.

Thanks.

Abby

Alice, a quick google brings up the old specter of CMS. I am 45 years old, and have had symptoms of MG for less than two years. I have seven children (ages 7 to 21), none with unusual weakness. I also have seven siblings, none with unusual weakness. My seven siblings have, among them, 27 children--all fine.

With a history like that, does it even make sense for me to look into this? I do remember being tired as a child--in fact, it's sort of my overwhelming impression of childhood: slogging home from school, pushing through gym class--but nothing really out of the ordinary. I could keep up with my friends, and I did do a lot of biking.

I'm going to ask my neuro, though, at the next appointment, if he'll try me on albuterol.

Abby

And, one more clue: my symptoms are predominantly limb-girdle. I have almost no eye involvement (just a bit of eyestrain now and then). I sometimes have mild bulbar symptoms. I have weakness in my neck, arms and legs. My first and worst symptom, though, is truncal weakness. This puzzled the doctors and delayed my diagnosis. I often have trouble holding my upper body upright.

All of this would sound like a dok-7 CMS except for the little fact that I didn't notice any symptoms until I was 43.

Abby

Abby, Here's my old post on that.

http://neurotalk.psychcentral.com/thread80534.html

Here are a few articles.

http://www.ncbi.nlm.nih.gov/pubmed/2003276

http://jpet.aspetjournals.org/content/273/2/637.short

http://www.ncbi.nlm.nih.gov/pubmed/89675

Sorry if I'm repeating myself but I didn't read through the original post. Caffeine has been shown to be a cholinesterase inhibitor, like Mestinon. They inhibit acetylcholinesterase, the enzyme whose job it is to "clean up" after acetylcholine is done of it's job making muscles strong. If it didn't, muscles may become too weak from too much acetylcholine (in people with or without MG).

Coffee and Mestinon aren't, obviously, the same animal. Until coffee is thorough evaluated, it's hard to say what other properties are at work. Caffeine does increase dopamine, which is why caffeine makes people feel more alert. Coffee has large amounts of potassium too, which you have been low on in the past.

Calcium may be more at play here than ACh. Perhaps you have a CMS, who knows. "Channelopathies" involve electrolytes like calcium. I can't remember, did they try IVIG on you? Sometimes with "seronegs," they do IVIG or plasmapheresis to look for improvement. If there is, they know it's autoimmune MG.

Well, those are my thoughts. I know you want more proof but don't beat yourself up trying to find it.

Annie

Oh, and about that not noticing thing. Are you SURE you didn't? Were there any physical activities you couldn't do as a child? Any that you did less of than others? Did you nap in the afternoons (past the time you "took" naps)? I had so many clues growing up that I simply ignored. I thought I just had to try harder.

Abby, Coffee really helps me in the mornings. Usually takes 2 cups and my legs feel a whole lot better. In the morning my legs are so tired I feel I can't make it to end of driveway to get the paper.
Mike

Thanks for the links, Annie. I'll study them. Now I remember where I heard that coffee is an acetylcholinesterase inhibitor--from you!

Re: IVIG improvement: I was convinced at the time that it helped, but in retrospect I'm not so sure. The crash that put me in the hospital was triggered by a progesterone drop, as usual. I got better when the progesterone started building up (as usual). I did have two very strong weeks, but I've had those before and since. If the IVIG did help, it took two weeks before it kicked in. Then the end of my cycle hit, and I got worse as usual.

I was a very unathletic child--picked last for every team (but I'm OK now! Really!). I've always been clumsy. Gym class exhausted me. And I spent a ton of time in bed in the daytime, with books. So I guess it's a possibility, but none of this was to such an extreme that anyone though something was wrong with me--they just thought I liked to read, which was true and also typical in my family (my father was a librarian, and we were raised without TV). But I think anyone would have described me as a lazy child.

Thanks for remembering my potassium troubles. I have been taking great care to get lots of potassium. I ate beet greens today from the garden, planted just for me.

Thanks, Annie.

Abby

Abby, When I figured out that I had fatigable ptosis in eyelids and eyebrows since I was a kid (looking at K-12 photos in 2006), I knew that all those years of "adapting" were MG. I had close calls with breathing, like during the flu in 1968, but if you don't know something is wrong, you can easily pass it off as something else. The "funniest" memory was of looking through our binoculars. Objects always looked blurry, even with glasses on that corrected my astigmatism. I had to close one eye to see things clearly. Yeah, MG double vision. It didn't matter which eye I closed either.

So, write down memories, look at childhood photos and really think about all this. CMS's can be mild, though even mild ones can get severe. I have antibodies but I can't completely rule out CMS. My MG got worse when I had my B12 deficiency. That's when I began noticing all of my symptoms like ptosis (figured it out in 3-2000). You can't make acetylcholine well without B12.

Like Mike, I rely on coffee every day. I stopped it when I stopped working in 1998 and restarted in 2007. Should've kept having it. I only have one cup, in the afternoon, to give me a boost to get some things done.

Annie

And because I'm like a dog with a bone . . .

http://www.ncbi.nlm.nih.gov/pubmed/20030211

http://onlinelibrary.wiley.com/doi/1...1.00841.x/full

http://www.pierce-antibodies.com/Ant...l--MA3916.html

This has the "opposite" clinical presentation of you.

http://www.ncbi.nlm.nih.gov/pubmed/17539937

Has anyone been tested for Titin or Ryanodine?! I think you should be tested for both.

http://www.ncbi.nlm.nih.gov/pubmed/21034627

And, no, you're not a cow but this is a very interesting article!

onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0705348/pdf

Thanks for this Annie. I didn't know that. It just shows how complex the human body is and how many effects pharmacological agents can have, apart from their well-known mode of action.

The known mode of action of caffeine is inhibition of an enzyme-phosphodiesterase. This leads to increased levels of cAMP, which is a very important secondary messenger, in many cells. But, it also has a direct effect on the ryanodine receptor.

http://www.ncbi.nlm.nih.gov/pmc/arti...00432-0219.pdf
And possibly other effects we are not yet aware of?

I agree with that. There is adult onset CMS. I believe that it is there from birth, but very mild. There is a normal distribution of strength and endurance in the population, so it can be seen as the bottom of normal, even though it is abnormal.
To complicate matters, it is quite possible to have both-a mild genetic abnormality, combined with an autoimmune MG.
Also, there is more and more evidence showing that MuSK (and possibly other types) autoimmune MG, is caused by a different mechanism than "classical MG". This is why the response to mestinon is less clear and optimal, but could also be that the response to other agents (such as ventolin, ephedrine etc.) would be better.

Ephedrine was in fact the first treatment for MG. It was found incidentally by a physician (Harriet Edgewood) who had MG, and was given Ephedrine for some other minor medical problem. She noticed that it made her MG much better and shared this with her physicians (who actually listened to her and were ready to check it out).
http://qjmed.oxfordjournals.org/content/5/1/21.full.pdf


I wish physicians were as meticulous today, as those who have written this paper. I also wish that medical journals and the medical community would appreciate more the importance of a single case study.