coffee and Mestinon
 

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.

This is sort of on-topic, Abby, so please indulge me. I did some research at the local university after my B12 deficiency. I found unbelievable amounts of detailed "doctoring" a century ago. People like Addison, who truly looked at every angle of a disease and documented it. I agree with Alice. There is not as much looking and thinking now days. And putting pieces together. Dr. Andrew Weil said in a lecture I saw over a decade ago that pathophysiology is not even taught in medical school anymore. There's no time for it. How sad.

Sure seems like a lot of us here are - as Alice has said - zebras.

Annie

Annie,

(forgive me if this is a bit off-topic).

B12 deficiency was sort of my first clue to understanding my illness.

No, I do not personally have B12 deficiency. But, quite a few years ago (shortly after I finished my fellowship in hematology), I was called in the middle of the night to see a patient who the resident thought had leukemia.

On first seeing her this is what I thought too. she was very pale, slightly jaundiced, with an enlarged spleen. All her blood counts were at ground level and she looked very ill.

On first site her bone-marrow also looked as if she had leukemia, but the more I looked at it, the more I realized that this was not what she had. It looked more and more like she had severe B12 deficiency such as I have never seen before. ( I had to open all the atlases and text-books to find similar BM findings, and be convinced in what I thought).

It turned out that she was not only a vegetarian, but also never went to see her physicians. She did feel a bit tired, but only when she started to have bruising and collapsed was she brought into the hospital by her family.
I realized that I was seeing the natural history of an illness that should no longer have a natural history. I also realized why it is called "pernicious anemia". Until the discovery of vitamin B12 it was a fatal illness, just like leukemia. I knew this theoretically, but now saw it in front of my own eyes.

Within a few months of receiving treatment with B12 she fully recovered, and even her liver and spleen went back to normal size. I went back to the original descriptions of pernicious anemia and found it all described.
I wrote a case report about it-Pernicious anemia-revisited (as I thought it is important that other physicians will know how to recognize it), but it was not accepted.

When I was nearly bed-ridden and required nearly constant respiratory support, I started thinking why so many neurologists told me that my symptoms were "impossible" and that they have never seen something like that. And I thought to myself that maybe (just like me with the patient who had pernicious anemia), they are seeing the natural history of an illness that rarely has a natural history nowadays.

So, I asked my husband to find me everything that was written about myasthenia before there was effective immunomodulatory treatment.
This is how I got to Osserman, Mary Walker etc. Who have indeed describe each and every one of my "impossible" symptoms.

In fact I recently came across a paper (and found it quite amusing) that one of my "impossible" symptoms was called the "Mary Walker Phenomenon". This phenomenon was required (then) in order to confidently make the diagnosis of MG. It is probably not seen much now, because patients receive effective treatment long before they reach this state. And also because physicians are many times much less observant and meticulous in their examination than when they had very limited tools other then their own clinical skills, so probably wouldn't even notice it, if patients did have it.

I was thinking if I should send this paper to the neurologist who told me it is "impossible" but then decided not to.

So, in a way you can say that B12 deficiency probably saved my life.

Abby, Sorry if my question for Alice or Annie hijacks your thread!

I start my day with Mestinon and a nice hot cup of coffee or two!! It makes a world of difference in my morning.

Alice or Annie, Do either of you know of any medical literature showing a direct correlation between B12 deficiency? I was dx'd with B12 deficiency last June and went on to be dx'd with sero-negative MG not long after.

Thank you,
Rachel

http://ajpendo.physiology.org/conten...1/E31.abstract

Abby, Read that. ;)

And because of the darn medical journals, I can't put an article on here, at least yet, that shows this info:

80% of ACh antibodies are cell bound and 20% are circulating antibodies.

As I suspected. If the little suckers are having fun destroying your cells/tissues, then why would they have any interest in being drawn out by a lab tech to engage in a test?!

Abby,

I also find coffee more helpful than Mestinon for my symptoms currently. It hasn't always been this way, but I am now taking 1/8th of a Mestinon pill every day and a cup of coffee in the afternoons (or a cup of tea if my symptoms are only mild).

I prefer the coffee to Mestinon when my symptoms are mild. The Mestinon makes me feel horribly nervous.

I think it is the heat that reduces my symptoms somehow. When it gets cold again I expect that I will be back to taking more Mestinon and having lots of bad days.

:hug:

I am going through the diagnosis, probable, possible, see another doctor, eye rolling, etc. that almost everyone that is seronegative goes through. But thought these memories might be interesting to people who are drumming up things from childhood. By the way, my aunt looked and acted very much like the woman in the Mary Walker clip and my father had MG diagnosed at age 80, my aunt, his sister, died at 42 and I believe she was untreated. I am 65, but here's what I remember from my childhood: at 4 I used my weak r eyelid to tell left from right and school pictures were a nightmare due to having one eye closed for many of the shots, I was extremely active and loved the out of doors, but always had scratches and scabs, especially on my elbows and knees, I was usually king of the mountain and hung by my knees from the merry go round but not fast or the best at jump rope and too stiff to do acrobatics for the first grade circus, I had no thirst, could play tennis all day in the summer without drinking and win, in swimming I was first across the pool if everyone was not allowed to kick and last if we couldn't use our arms, drove the swim instructor crazy and unlike my brothers, not fast enough for the swim team, played high school basketball for four years, shortest on team, handicapped by height, lack of speed, jumping ability, aim (left eye dominant, right handed). Was on the traveling team all four years, which did not mean I got to play, only that I was determined reliable and yelled loudly from the bench. It was the only sport for girls. I have been on pyridostigmine for less than a year which was like magic to begin with, but requiring more until I need more help than I can get without another work up scheduled for October. Maybe it's just as well, because I only recently realized that my problem could be CMS, although I am 65, and of course this is important for all blood relatives. Thanks for being here and bringing some of this research to our attention. Besides the seronegative testing, a lot of the eye rolling is because I am so strong and at the same time from the same office the diagnosis code reads lethargy, malaise, and fatigue. Hopefully this time someone will have some compassion and good sense! I am just as competitive as I was when I was a child, I am just losing.