Thank you for this very interesting thread,
Every time I think I am done thinking about MG, I realize that there is still something new to think about.
This is a question that has been bothering me for a long time.
Physicians, after reaching a diagnosis have to make management decisions. Those are based on the severity of the disease/prognosis without treatment/ability to monitor response (or lack of response) to treatment and effectiveness of treatment.
My encounter with numerous neurologists made me realize that those are very muddy waters in MG, as even leading experts are unable to answer any of those questions.
How do you define severity of MG? And is it possible to do that?
From this paper it seems that the answer is-not. As this is what leading experts in an MGFA task force think:
The fluctuating extent and severity of MG, and the variable predominance of the muscle groups involved, makes it extremely difficult to classify these patients.
The Task Force sees no alternative but to accept the inherent imprecision of a clinical classification
In general, these classifications use subjective assessments and lack quantification. What one physician may regard as "mild," another might regard as "moderate" or "severe." Furthermore, some experienced clinicians believe that oropharyngeal involvement is more dangerous, and perhaps different than limb weakness, and thus should be identified by the classification system. Some feel that "crisis" (respiratory insufficiency necessitating intubation and assisted ventilation) is the result of coincidental infection or other stress in susceptible patients, whereas others regard crisis as defining the ultimate in disease severity.
I then looked at what a few MG patients said about their own experiences:
So a flare up means symptoms become more severe
With me it's just so confusing am I getting better cos I can do more or is it cos the weather is much better for me I've never been able to go out for five days in a row which I have now I guess being able to talk breath swallow must be good thou I have felt better when I've felt bad again and that doesn't make sense
using 3 quantitive scores total for MG from 3 different sources I will have gone from a severe to mild in two of those categories
So, both physicians and patients are totally confused regarding the severity of this illness.
The question is: are they looking at the right thing, or possibly because they are looking at the wrong thing, it appears totally arbitrary, makes no sense and goes from severe to mild within a short period and sometimes back again.
My answer to this question is that they are not looking at the right thing. They are looking at the wrong parameters and that is why it is so confusing.
8 years ago (before I was ill) I had two patients with leukemia. They both received high dose chemotherapy.
One was in the ICU with severe pneumonia, intubated and nearly paralyzed.
The other was sitting in her bed and cheerfully chatting with me.
Which of them had a more severe illness?
You would probably say that the first.
But, you can't answer this question without a very important parameter-the results of the bone marrow examination.
The first had a completely normal bone marrow, whereas the second had residual leukemia.
That is why the first patient is now alive and well (after a very rocky course and recovery), whereas the second patient died a year later.
What made the difference?-the nature of their leukemia and how well it responded to the currently available treatment.
30 years ago, both patients would have died. But, now we can cure nearly 50% of those patients, because we can diagnose, classify and adjust the treatment.
As we learn more about the underlying mechanism of the disease, we can better stratify and better adjust treatment. Some types of leukemias can now be fully controlled in the vast majority of the patients, whereas for others we still do not have effective treatment. But, we know quite early in the course of the illness which patient will quite likely do well with a given treatment and which patients should be referred for experimental approaches.
The first patient was transiently ill, because of a severe infection which temporarily endangered his life. The second patient did not have such a complication, but this did not make her underlying illness less severe.
The reason this is not so in MG, is mostly because there are no tools by which neurologists can clearly stratify patients. Because, as I said, they look at the wrong parameters.
MG is not a disease of muscle paralysis or even weakness. It is a disease of muscle endurance. Muscle strength changes and fluctuates, but muscle endurance does not, or at least it changes much less.
So, assessing strength doesn't make much sense.
Likewise, assessing the severity of an illness, based on a transient complication doesn't make sense. (just like it doesn't make sense to asses the prognosis of leukemia based on the severity of infectious complications).
In my opinion:
There are two parameter which defines the severity of MG: one is the extent of involvement (how many muscle groups are involved) and the other is endurance and exercise tolerance.
No neurologist I have met ever measures it and most patients don't either.
In my opinion the following should be assessed:
1. The maximal amount of activity an MG patient can do. This should best be done on a treadmill with a full cardiorespiratory exercise test. But, it can also be done with a simple walking or bicycle test.
2. The time it takes to recover after maximal exercise, 70% of maximal exercise and 50% of maximal exercise.
In patients who have involvement of only one group of muscles the same should be assessed on that one group.
For instance if there is only arm involvement-the arms should be exercised to fatigue instead of the entire body.
The other important parameter (just like in leukemia or any other disease) is response to currently available treatment.
Once disease severity can be measured accurately, response to treatment will also be better monitored and the time to assess response will be better defined.
If someone could only walk 100 meters and it would take them 2 days to recover before treatment, and one week after treatment can walk 120 meters and it takes them 1.5 days to recover, it would be a significant response which could easily be missed if all you do is a rapid assessment of strength and even QMG score in the physician's office.
If you follow the right parameters you will see improvement, instead of becoming confused when receiving effective treatment. You will also not have so many "remissions" and "flare ups".