Caffeine Boost to Acetylcholine in NMJ?

[AtopicGuy]

After many years, I still have no diagnosis. I have all the symptoms of PMR, but no detectable inflammation (which is the usual cause). I also have half the amount of anti-AChR antibodies that is considered borderline for MG. I'm told this "is of no consequence".

A while back I noticed that taking 1200mg of aspirin to head-off a migraine had the strange side effect of allowing my upper arms to rise above the horizontal (against gravity) for a short while. After reading up on myasthenia gravis and other neuromuscular junction disorders (NMJDs) I just tried another experiment. I attempted to boost my levels of acetylcholine by taking 8 heaped teaspoons of instant coffee and two Kit Kats in one go (apparently, caffeine is known to temporarily boost acetylcholine levels). After about 30 minutes, I started feeling jittery, but my symptoms were unchanged. After one hour, however, my arms were just about up to my ears! Even better than aspirin! After 2 hours, the effect was starting to wear off and my arms were almost back to (ab)normal. The jitteriness and queasiness were subsiding, too.

As a retired scientist, I know the next logical step is to try an acetylcholinesterase inhibitor, such as pyridostigmine. From what I read, this seems to be a standard way of confirming NMJDs in the USA, but not the UK. I've already suggested it to my rheumatologist and neurologist, but they weren't keen. Hence my experiment.

Has anyone in the UK been prescribed pyridostigmine (or similar) on the way to a diagnosis, rather than a treatment?

I'm awaiting nerve conduction studies, so I'll throw this new clue into the pot. It's a sad reflection that I have to resort to home experimentation, but I can't stand much more of this low quality of life.

[CDreamer]

I was diagnosed on clinical exam & symptom/health history - lifting arms and doing the ‘chicken wings’ fatigue exercise + eye test as I had double vision. I was put on Pyridostigamine immediately, way before AChR array came back positive - high number. That was 10 years ago and diagnosed by neuro experienced in Mg, they weren’t going to wait for the bloods to come back and leave me untreated. From what I can gather, it really varies from neuro to neuro. It was my chiropractor who first diagnosed me and told me to see someone ASAP.

I was treated with Mycophenolate as steroid sparing drug alongside Pyridostigamine for symptom control only now just starting to titrate down from maximum doses. It took a good 6 months of treatment to make any difference and about 3 years to stabilise. I had my driving license revoked during that time because of the double vision, thankfully got it back but only under 3 year medical licence so have to have full medical every 3 years.

I have noticed that caffeine helps fatigue and as eggs also help so tend to have boiled eggs for breakfast quite a lot but I have to be careful with coffee because of heart arrhythmia so no way would I touch dehydrated coffee, especially that much!

Hope you get a diagnosis soon. Have you been in contact with the Myasthenia charity in US? They used to have an excellent help resource.

[AtopicGuy in reply to CDreamer]

Thank you, once again, for your detailed and helpful reply. I can't drive, now I'm off steroids, as I'm too weak and make mistakes when fatigued. I am envious of your outcome, but also glad I've not yet had such terrible things as double vision and near-paralysis. I can't help but believe remission should come easier to me, in the long run.

I'm in the Kafkaesque position where my symptoms are severe enough to ruin my quality of life, but too indistinct to get a diagnosis or treatment. For example, my upper arms won't go much above the horizontal (unless I remove gravity by lying on my back first). However, I can flap my elbows like a chicken, or raise my outstretched arms through 90 degrees like a penguin, about 50 times: it's increasingly sore from the outset, and I feel exhausted by the 50th, but not paralysed. Given a short break, I can do them again, but I don't know for how many/few cycles. It is this ability to exercise in short bursts that allowed me to keep working, and even to take up skiing and (social) tennis in middle-age (after my atopy became well controlled, but before the PMR-like fatigue became too severe). I have always paid for doing any exercise through pain and stiffness for a few days afterwards. When I push myself too hard, I can become seriously ill and collapse; so I've learned not to, the hard way.

I felt it safe to do the high-dose caffeine trial because I paid for a full cardiac check up and stress test last year. That was all clear, despite the almost immediate onset of fatigue while merely walking on the treadmill. I've always blamed the ease with which I get out of breath on my asthma, despite the fact it has been fully controlled by a twice-a-day preventer inhaler for decades. Now I wonder whether this, too, is a symptom of my low, 0.12 nmol titre of anti-AChR antibodies weakening my chest muscles?

Despite resting 23 hours a day, either in bed or in a reclining chair, the PMR-like pain and stiffness has spread from the shoulders to my hands. Reaching for a mug and gripping it instantly makes the muscles just below my elbows complain, and often causes acute, cramp-like pains in my hands. My right hand is noticeably swollen and the fingers will no longer straighten properly, yet none of the joints are inflamed. Lack of exercise might be partially to blame, but I almost always manage to get up, shower, wash my hair, and dress by lunchtime, no matter how exhausted it makes me. I count that as 90 minutes' light work, these days!

I stumbled across this excellent Practical Neurology website yesterday, while looking for life-long NMJDs. Some form of CMS ( CHRNE?) would fit much of my experience, except only rarely do they respond well to steroids (and get confused with MG). Depending on my nerve test results, genetic testing might be an option. I still think a trial of pyridostigmine should come first.

practicalneurology.com/arti...

Thanks for the opportunity to vent! Oh, and the egg tip. They've always been part of my diet, along with meat, fish, beans and cruciferous vegetables. Lack of choline shouldn't be a problem.

[stiff19]

Hi I am also undiagnosed but continue to struggle. I cannot get ice test done even though ive experimented with this test and my eye will open be it temporarily, I have no antibodies but not had musk test. one neurologist said he thought it was mg and that the nerve and blood tests dont rule it out as I can be sero or even triple sero. The past few years were the worst before high dose steroids for a week but I had not been seen for years before and not tests or seen before the steroids or after so pointless as they have no sense of difference. still problems continue but lesser and fear their neglect for years missed the worst as I believe diagnosis becomes harder if not diagnosed appropriately from beginning.i have not been seen by a muscular neurologist or one with any experience in mg . im sure my thymus is involved and thyroid.

I wish someone would let me try pyrodostigime here , I will try anything but I am ignored simply because of negative bloods despite clinical presentation, well the body improved a lot after steroid re weakness but not the eye and still get weak if do much. like you I am sick of this and empathise and relate as I feel also low quality life but one doc just said sorry about that. Its a lot of money to go private and I cant afford it or im sure id get a diagnosis and its sad that it boils down to cost with health, especially when my docs seen know nothing of and say they dont know enough about myasthenia to diagnose.

Why do you mention pmr please? I was asked was has anyone ever mentioned pmr to me ,the one time I was seen, and no one had mentioned but I have had symptoms of that and hyper/hypo thyroid in the second or third year of this, I think the steroids helped this🤷‍♀️im not a scientist or a doc just a sufferer with no help

best wishes🙏

[AtopicGuy in reply to stiff19]

I mentioned PMR (polymyalgia rheumatica) because my GP suggested I might have it, 5 or 6 years ago, when the weakness in my upper arms became absurd. Blood tests showed no inflammation, but she reluctantly agreed to try corticosteroids to see whether they had any effect. I'm grateful she did, because prednisolone massively restored my quality of life and confirmed I probably have an autoimmune condition. The problem is, the symptoms always return as I taper the dose.

To my amazement, I now know PMR is not alone: MG is another autoimmune disease that can also cause this bizarre weakness in the upper arms and also responds to prednisolone. There are many other clues that point more towards MG than PMR, but doctors won't take it seriously until an eye lid droops or my diaphragm seizes up.

[stiff19]

ive had very bad ptosis fluctuating for years and all I get is we dont know but systemic symptoms too. the rashes and such cleared with prednisone and some weakness but by no way near enough and fluctuating with breathlessness also.🤷‍♀️I understand where you're coming from.