I realized that in some of my posts I may be using too much medical terminology.

So, I decided to try and explain this in a more simple, Alice-way.

I have a disclaimer: This is an imaginary story. I don't think there are aliens that abduct people and talk to them (although if I did, it could fit with some of the "diagnoses" given to me over the last few years).

Also, take into account that the graphics I use are a bit limited, so use your imagination to fill in the gaps. I had to divide it to different posts and also use less repeats than I wanted, because you can't use so many graphics in one.

Chapter I: A small factory-getting to know the workers.

This is Mo.

His job is to operate a machine which moves "thing" from one place to the other.
But, he is not alone because his small machine doesn't have enough power to move much, so he has to operate his machine at the exact same time that others Mo's do so together they can move "things". If they don't work together at the exact same time, they will not be able to move much and will waste their energy doing nothing.


But, how can we make them all work together at the same time?
That is why we have Co.
His job is to pour a special fuel into their machine. Once he has done that they can push the button and operate it. This way they all do it together at the same time.

So, if each Co. puts the fuel at the same time into the machine of each Mo. every-thing is nicely coordinated and "things" move properly.




But, wait a minute. How do we make all those Co's put the fuel in the machine at the same time?

That's easy, For that we have Ao.
Ao. gives an order to Co. And then Co. puts in the fuel so that Mo. can operate his little machine.

Chapter II: coordinating it all.


But (I know what you are going to ask now).
How do we make all those Ao's tell all the Co's to put in the fuel at the same time?

This is were Jo. comes in.
There is only one Jo.
He has a special laptop on which he writes orders. Those are printed in numerous copies and sent flying over to Ao's, so they all reach the Ao's at the exact same time. Also, to make sure that orders are given correctly, Jo had a few extra Ao's, so if a few didn't see the orders there were still enough to make sure that all the Co's and Mo's worked properly. ( I remind that you have to multiply this many times. I just don't have enough graphics).

Chapter III: extra precautions.


Those pieces of paper on which the orders are written are magic pieces of paper that dissolve within minutes after they are printed. Why is that? because we don't want an Ao. to get confused and think that an old piece of paper is a new order.
And then he would get a Co. putting fuel into a Mo's machine so that when the come times and there is a new order this Mo. will be too tired to operate his machine and if that happens with a few Mo's at the same time, "things" will not move properly.




::

When there are no orders to give Jo. Rests quietly.
And so does everyone else. The Ao's, Co's and Mo's all work very efficiently, but only if they are given proper time to relax and rest.
This way they are all full of energy when a new order comes. And "things" move very well.

This nice little factory worked very well for many years with "things" always moving nicely.

Chapter IV: A sad thing happens.

One day something very sad happened. Aliens from outer space came and abducted some of the Ao's. This was a great shame, because now only some Ao's were working properly and so only very few Co's and very few Mo's could do the job.

Jo noticed that even though he kept on giving orders, "things" did't move as smoothly as they did before. So, he called the police to check out what happened. The police had to tell him the sad truth. Quite a few Ao's were no longer there. That is why sometimes his orders would get over properly, but many times not.

But, Jo, a resourceful guy had a great idea

He made his magic pieces of paper last a bit longer. This way some of Ao's who didn't get the order would now get it and all would be nice and well. Thank's goodness he was smart enough to get some extra Ao's in the first place.

This worked well for quite a while, but the aliens didn't stop coming and another group of Ao's was abducted. So, even thought Jo. managed to recruit more Ao's it was not enough.

Jo. was now very angry. He called the police again. This time, he said angrily, I want you to find why the Ao's are disappearing and do something about it.

No problem, the police said. It took them a while but they figured out what happened and gave Jo a special weapon he could use against the aliens
so that they would stop coming again and again.

This was a very happy ending for the little factory and every hugged and kissed and celebrated. And "things" again moved nicely.

Chapter II: A different story, with somewhat similar consequences, but very puzzling this time.

For many years Bo's little factory was working very well and 'things" were moving nicely.






Until one day, total Chaos took over Jo's nice little factory.

Bo gave his orders just as before. But, sometimes they worked very well and other times with no good reason nothing happened or "things" were moving but very inefficiently.

Bo remembered, that his friend Jo's factory was once attacked by aliens who abducted some of the Ao's. He remembered that Jo told him of his excellent idea-making the magic pieces of paper last longer.

So, even those this was a little different, Bo now did the same. And this little trick seemed to work, but to his surprise sometimes it worked very well (just like it did for Jo) but other times instead of all the Mos working together there was total Chaos. Some would work very hard while others would just rest doing nothing. And then "things" hardly moved despite the Mo's putting a lot of energy. And then the Mo's which worked were so tired that the few who could still work could really do nothing.






Bo decided that this is the time to call the police, because he can't do much on his own.

The police came on a very good day, in which everything went smoothly. They were angry at Joe for calling them and explained that they are busy taking care of important problems and don't have time to fool around.

But Bo didn't give up. He knew there were days in which things weren't moving as they should, so after a while he called them back again. This time they too could see the chaos. They did some investigations and told Bo that they could not find any problem. None of the Ao's were missing, so there was no reason for things not to work properly.

We are sorry, they said, we thought it could be another case of abduction by aliens, but we were wrong. You will have to figure it out on your own. Maybe you just didn't train your Ao's properly. You have to better organize your factory. People here seem to be very lazy.

And Bo had to admit that they were right. Most of the Mo's were sleeping most of the time. For a short while, it would seem that all is in order again. His orders went through. The Ao's passed them to the Co's and those put fuel in the little machines and the Mo's did their work.

Sometimes making the magic papers last longer seemed to make the work more efficient, but other times it seemed to do the opposite. It seemed as if the Ao's were abducted by aliens for a very brief period and then put back again in their place. So, when they were missing the longer lasting magic papers worked very well, but then when they suddenly came back it created enormous chaos because too many Ao's were working at the same time, leading to disorganized orders to the poor Co's (who didn't have time to rest) and the poor Mo's who were so exhausted by now that they could hardly do their work any more.

Bo knew that he had an excellent team of workers. He was not ready to accept the police's criticism. He knew they were very obedient and never lazy. In fact they even won a prize a few years before.

He called the policeman again. By now they were impatient and angry, as "things" were moving even if a bit more slowly than they should. Look, they said-stop wasting our time. We told you before there is noting wrong. You just have lazy and in-obedient people working for you. If you bother us one more time with your nuisance we will file a complaint against you for interfering with police work.

Chapter VI: trying to find help elsewhere.


So, poor Bo decided to call a private detective to try and get to the bottom of what was going on. The private detective repeated the same steps the police did.

Look, he said, you have a perfect number of Ao's, no one is missing. I have checked a few times and I know for sure. Also, he said they receive the pieces of paper in a timely manner. No problem with that either.

Then what is going on? Bo asked being on the verge of despair. What happened to my nice little factory.

Don't worry, the private detective said. I will keep on working on this until we understand. Would it be OK if I go and interview you Ao's? he asked.

Sure, Bo said, and wondered why the police didn't think of doing the same.

The next day, the private detective walked into Jo's office and said- I have bad news for you. What is it? Bo asked? Any news bad or good is better than not knowing what is going on.

Well, the detective said- Some of your Ao's seemed to have lost their ability to give proper orders to the Co's. instead of giving their orders they start screaming at them. So, you have a proper number of Ao's but they have gone bezerk. It seems like the aliens instead of abducting them are making them behave in a very weird way.





Now, Bo understood why what worked for Jo, didn't work so well for him. The longer lasting magic pieces of paper would sometimes reach the healthy Ao's (and then everything worked well), but sometimes they reached the alien-effected Ao's and then it created even more chaos.

What can be done? he asked the private detective. Well, we could still try using the weapon against aliens, but I am afraid it will not work as well, because those are much more sophisticated aliens than the ones Jo had. They are much better in disguising themselves.

Chapter VII: Not giving up.

But, Bo, a resourceful guy, was not ready to give up.
He too had an idea

What if, he said, I will bypass the Ao's and give the orders straight to the Co's .

Hmmm. the detective said, I believe that could work, but how would you do that?

It took Bo a few weeks to figure it out, but he finally found Po.

Po. gave orders in an old fashioned way-he wrote them down.

He also had bloops, who received his orders, and then transferred them (very nicely and gently with a kiss and a hug) to the Co's .

So, now the little factory had a new team, of wonderful workers.
Things did go a bit more slowly, but everything was back in order.

The Ao's still did some work, but much less than before. So together they managed to make things work most of the time.







And "things" were again moving smoothly (even if more slowly).

And, hopefully one day, there will be a better and more efficient way to fight those aliens.

The moral of the story

Now if you think that Jo/Bo=nerve cell
Magic paper=Acetyl-choline
Longer lasting magic paper=using mestinon etc.
Ao=acetyl-choline-receptor (AchR)
Co=Calcium signaling
Mo=myosin and the machinery of muscle contraction.
Abducting aliens=anti AchR antibodies
Police investigation=Single Fiber EMG.
Ao. receiving orders= transmission of the electrical signal from the nerve to the muscle at the NMJ.
Sophisticated aliens=anti MuSK (and possibly other not yet recognized Abs.)
Private detective investigations= direct measurement of muscle contraction and fatigability. (not done routinely)
Po=adrenergic receptor.
Bloops=salbutamol etc.

You can ( I hope) understand better the different types of MG.
Why even with severe disease there is normal SFEMG in certain types.
Why mestinon works in an ackward manner in certain types.
And what is the role of salbutamol etc.

The AchR antibodies indeed "abduct" the AchR. They lead to their destruction by an inflammatory process. Those antibodies belong to a sub-type called IgG1 which promote the inflammatory response.

The anti-MuSK antibodies belong to a different sub-type called IgG4. They do not lead to destruction but impair function. That is why there is a very small decrease in the number of AchR, many times they are able to receive the electric stimulation properly (hence a completely normal SFEMG) but they are severely impaired (the exact mechanism is not clear yet) in their ability to transmit this signal in a way that will create a normal muscle contraction.
Giving them more Acetyl-choline may sometimes help, but can also cause them to give signals at the wrong time. Making small parts of the muscle contract in a very inefficient way. This is called "fasiculations".

As opposed to "classical" MG in which the severity of the illness is in direct correlation to the number of preserved AchR, this is not so in MuSK MG, therefore the disease tends to be much less predictable and stable. It also (for the above reasons) has a much less predictable response to medications like mestinon. The same dose can lead to improvement, worsening or do nothing. This (in my opinion) led to the wrong notion of "cholinergic crisis" which many neurologists think doesn't exist. And also to the term "brittle myasthenia" in which patients can go from having too little to having too much mestinon within minutes. (those phenomena were described in the 60s and refuted by many modern neurologists, who gladly attributed this instability to "emotional problems").

I love that story, Alice!…...Hiring a private detective when your case hasn´t been resolved and been dismissed by police seems like the way to go if you want to get to the bottom of things in MG!… Chapters 5 & 6 were my absolute favorites.

Actually ever since being a student, graphics have always been the way I´ve understood and retained the most important info I´ve ever learned!

Thank you

Anacrusis