I am trying to compile anecdotal evidence to present to my neurologist to support my requests to do further investigation for a few different diagnoses.

For myasthenia gravis, I want to ask for a Tensilon test, even though I'm seronegative and EMG was negative. suev, I found a great, concise post of yours about Mestinon helping you even though you are seronegative and your EMGs were not conclusive. Is it okay if I print it and take it to my appointment?

Also, can anyone else share your story for me to use, or point me in the direction of any similar stories about EMG's being normal? I was sure I'd seen at least one or two others, but am having trouble locating them. Maybe I'm search impaired

Thanks,
Tatia

My EMG was negative as was my first blood panel taken by my local neurologist. I had double vision so I was referred to a Neuro-opto who diagnosed me with MG. He said he did not care that those tests were negative he was positive I had MG. Six months later my blood work came back positive. I have not had the single fiber test so I can help you there. My sister had the single fiber test at the University of North Carolina and it was negative however we are still convinced she has MG. She is going to Duke in June and maybe she will get a diagnosis there.
Mike

Tatia,

Absolutely you can print what I wrote...I hope it helps in some small way! Let us know how it goes with your neuro.

You have more than anecdotal evidence.

There is very limited data regarding the utility of the SFEMG in AchR ab. negative patients.
The data which is available, suggests that patients who are seronegative are more likely to have a normal SFEMG.

http://www.springerlink.com/content/w916713q36h18333/

In fact there is more and more evidence that AchR MG , MuSK/ seronegative MG are not exactly the same disease and are caused by different mechanisms.

There is more and more direct and in-direct evidence that abnormal coupling of the electric signal with muscle contraction is of importance in the pathophysiology of myasthenia.

http://www.ncbi.nlm.nih.gov/pubmed/22386321

And possibly may be the only important mechanism in some patients leading to normal electrical signal (as seen by the EMG) in the face of abnormal repetitive muscle contraction.

There are tests which can test muscle fatiguability (and not muscle exitability), but for some reason those are not widely used.

In fact the diagnosis of MG was initially done by such a test, called the Jolly test. The idea that myasthenia has to be due to abnormal transmission of the electrical signal at the NMJ was never proven by any acceptable evidence based research.

you can read about it here (page 5-6).

http://www.mga-charity.org/informati...inter-mga-news

A tensilon test may not provide the answer either, as it can be negative in MuSK MG.

Last but not least, I am sorry that you have to go through this.
But, hopefully your determination will help pave the road for others.

Hope this helps,

Alice

Hi. I would like to be of support to anyone out there with myasthenic weakness despite negative test results and am also looking for some closure as well...

Neurophysiologist and MG researcher October 2011:
´Despite your negative blood tests & negative SFEMG (September 2011) I believe you have had an atypical presentation of seronegative myasthenia which went into a sudden and spontaneous drug free remission (May 2011) which may last up to 2 years. You should take an RNS and retake the SFEMG on a weak muscle (frontalis & deltoid) when symptoms return. I do not believe your symptoms are psychosomatic or that sedatives are the cause of your weakness´

My own conclusions about symptoms after pregnancy are as follows:
1) Zoplicone/antibiotics + heat + repetitive muscle use = severe muscle weakness in an MG pattern. (during an already existing flare up)
2) Reduced medication + cold temperatures + reduced specific muscle use + REST = greatly alleviated muscle weakness.
3) Zoplicone caused 11 months of bulbar & respiratory problems 12-16 hours after each dose was taken (1.25mg daily…. and symptoms reappeared with each challenge dose a total of 10)

Most notable ´episodes´ of fatiguability:
Unable to…..... turn the pages of a book; writing looks like someone else´s at the bottom of the page (that´s still the case); grasp things; strum guitar to end of song; finish a round of applause; almost drowning from sudden deltoid weakness, hold a door open for someone; put make up on with elbows pressed into stomach, piece of rice stuck 20 minutes; tongue weakness; choking on liquids and even toothpaste fumes; epiglottis forgets to do its job; lungs rattling unable to clear; severe breathlessness on repeating same sentence; reading bedtime story like a drunk; chewing stopping halfway through a meal; voice and eyes going in and out of focus; neck weakness; thighs like rubber bands; falling into my dinner plate as the meal progresses........

Some questions:

1) From 2009 until 2011 there was a predictable, almost perfectly exponential progression of fluctuating symptoms yet with such erratic and unpredictable exacerbators from the outside. How does the myasthenia remember or know exactly which position to go back to every time (plus an increment of severity) if there is no permanent damage recorded by an SFEMG?
2) If a sedative could be responsible for 3 years of fluctuating, progressive and fatiguable weakness (mostly upper body and bulbar) then is it possible for someone to go into a significant myasthenic remission whilst ACTUALLY TAKING regular doses of the offending substance?
3) Why would sedatives (Zoplicone & Ambien) cause similar symptoms to antibiotics? (9 prescriptions during 2009)
4) Why might sedatives cause respiratory problems and bulbar weakness 12-16 hours consistently after taking only a 1.25 mg dose?
5) Do normal drug induced side effects follow a fluctuating and PROGRESSIVE pattern?
6) Why, after challenge doses of sedatives, would breathing weakness always precede muscle weakness.
7) Why during flare ups would weakness appear in other totally unrelated sets of muscles than those that were used repetively?

Thank you so very much.......

Hi,

I will start with- I don't think anyone can give you a clear and scientific answer. Also, you give many details but a lot are also missing.

But, based on my knowledge and understanding of this illness, autoimmune diseases in general, and my own experience I am ready to speculate.

1. You don't clearly say, but I assume that you are a young healthy fit woman, and that your symptoms started during pregnancy/childbirth, lasted for over a year and then gradually got better.

If this is the case, you most likely have autoimmune MG and it is not rare for autoimmune diseases to be effected by pregnancy. The reasons for that are not entirely clear, but we know that pregnancy effects the immune system locally in the placenta (or else you would "reject" the fetus, which is 50% dissimilar to you).

2. spontaneous remissions in MG (as any other autoimmune disease) have been described and can even last for many years. So, assuming that you had complete disappearance of all MG symptoms, and it was pregnancy related possibly (and hopefully) you will never suffer from it again.

3. You do not mention why, if you had significant symptoms for a long period, you were only seen by the MG expert after they resolved. Did you have any tests during that time? were you given any treatment (such as mestinon)? what was your response to it?

4. Any medication that has an effect on muscle contraction or neuromuscular transmission (and there are many) can make MG symptoms worse.

5. MG is usually fluctuative and without treatment it may also be progressive.
So, there is nothing unusual in that.

6. when you use a muscle repetitively to the extent that you reach the anearobic threshold of that muscle, there are two consequences-one is that this specific muscle becomes fatigued and the other that it leads to systemic changes. (such as increased lactate levels in the blood etc).
In some MG patients, other muscles can be sensitive to those effects. This phenomenon has been described by Marry Walker who noticed that when MG patients used their arm repetitively it caused ptosis and generalized weakness.

7. relatively mild weakness in respiratory muscles will be symptomatic (you will feel shortness of breath), the same degree of weakness in other muscles may be less noticeable (unless you try to do some heavy work, but this will also effect your respiratory muscles more).

8. Many times the result of a triggering even will only be seen later (this is why it is so hard to know what causes diseases). Theoretically, the medication could have caused a decrease in the activity of a certain protein, this in turn could lead to abnormal production of another protein and that protein may be what is responsible for the clinical symptoms. It can take time for this to happen.

9. MG doesn't cause permanent damage. that is why, when given proper treatment, someone can go from being on a respirator in the ICU to being completely normal.

10. As I have mentioned in a previous post, the SFEMG may be normal in myasthenia, because quite likely in some patients the problems is not in the transmission of the electrical signal (which is what the SFEMG measures) but in the contraction of the muscle itself.

Alice md...

RE: your #9

In your experience/opinion/belief, is this statement true of any type of MG...ie. that there is no permanent damage? I know this may not be able to be scientifically proven (am I right in saying this?), but I wonder for the following reason.

My neuro has offered to put me on pred to prevent 'further stress' to the NMJs and with the possible hope of remission. Since I do just fine on Mestinon, I have always refused the offer (for 3 years now). My thinking is that I don't want to use a hammer on something that can be handled with a fly swatter. And, worse case, I could always use the pred later if necessary.

Thanks for your thoughts

Yes thank you Alice, I was an extraordinarily healthy person before pregnancy with incredible stamina & strong muscles, I wouldn´t recognize my doctor if I passed him on the street! Muscle weakness really started gradually one year after childbirth....actually in the deltoids whilst changing diapers! This snowballed to a high peak 3 years later. Antibiotics in the blood stream for most of 2009 did not help matters very much at all. And with each returning´flare up´during those 3 years a muscle would perform less well and fatigue much faster each time. And also with each flare up a new set of muscles would also be affected. The last flare up lasted 3 months escalating to a point where I could no longer hold up a drink to my child for longer than 2 seconds. Just one increment more and I would have needed help brushing my teeth at bedtime. I also lost that anacrusis that comes just before executing any movement, and no one really knows exactly what that is until they´ve actually lost it……

The gross motor´remission´ as I call it came immediately after this peak and it took all of 5 days. On the first day I could not lift a pillow without being out of breath and by the 5th day I could manage to carry a 10 kilo boom box. I got a little over excited and decided to use a lawn mower after 2 weeks. Well the deltoid muscles ended up feeling like two broken sticks with tape around them being pushed from both ends at the same time. Today they look really skinny and everyone notices. (Biceps are quite pronounced)
The fine motor skill ´remission´ is taking much much longer. Only a month ago did I change bedsheets for the first time in 4 years!! (Grasping a duvet then manipulating the pillow into its cover is quite the chore!)

The reason I wasn´t seen by anyone before remission is that my doctor diagnosed me with psychosomatic fatigue syndrome (and so I was determined I would be able to fix that with my own mind); the psychiatrist thought it was drug induced; the physiotherapist thought it was neurological and the neurologist (who could only give me an appointment 5 days after the sudden remission) thought pretty much that I was lazy and should just use my muscles more…
I ended up wasting a lot of time researching other countries and then traveling abroad to find knowledgeable neurologists thinking all the while that at any given moment all my symptoms would return. Anyway if I would have traveled during worst peak then I would have literally folded over onto the floor in the check-in line with weak trunk muscles.

It seemed as though gross motor went into sudden significant remission last May but the dreadfully laborious breathing in afternoons and bulbar problems (which may have started after a trigger finger operation January 2011) had a separate life; lingering on many months afterwards with the use of sedatives until the challenge doses 3 months ago which put a full stop to all medication.

Since the point of the thread was about negative SFEMG´s. It was interesting that my revered neurologist abroad wanted to actually reanalyze my already negative SFEMG performed by another neurophysiologist…as he put it himself...´to look for any individual escapee myasthenic signals.´

Thank you for this helpful and fascinating information, Alice. I´m feeling much closer to closure now.
I´ve recently felt inspired to write a paper called ´The effectiveness of brain rewiring in fluctuating diseases´…..but may start with another version …....´The effectiveness of brain rewiring during fluctuating diagnosis´

Sending good energy to anyone who might read this.......

PS.....Never been on Mestinon - had only short rest techniques that worked to temporarily alleviate severest muscle weakness

No permanent damage to the NMJ, does not mean that there is no evolution of the immune disorder leading to the production of auto-antibodies.
Physiological and pathological immune responses are a dynamic and evolving process.
This is a somewhat simplistic explanation-but, when there is an exposure to a foreign antigen, there is production of relatively non-specific antibodies (which are not very effective) within a few hours to days. This is then followed by a series of changes in immune cells which lead to the production of more effective antibodies as well as memory cells which will "remember" the antigen if there is another encounter. Those antibodies are much more effective in attacking the offending pathogen. And also the cells which produce them are much more resistant and long-lived.
The dynamics of the immune system when there are autoantigens and not foreign antigens is less well understood, but there are studies which suggest a similar type of evolution of the immune system.

Even if this is the case, quite likely after 3 years, you have reached the peak of the severity of your illness. So, if you do well with mestinon and don't require any further treatment, you have probably made a good and reasonable choice. Of course there is no way to tell for sure. But, as prednisone carries its own price, it may not be worth it in your specific case and more reasonable to take some risk.