Myasthenia Gravis Support Group
Myasthenia gravis (MG) is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. The hallmark of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest. Although myasthenia gravis may affect any voluntary muscle, muscles that control eye and eyelid movement, facial expression, and...
I have been trying to find details about the time it takes for our muscle receptors (destroyed by our bad antibodies) to be replaced. I have assumed it is pretty fast for IVIG and PLEX to work so quickly but until now didn't find a reference. Here I found a good description of the whole process in
http://youmeandmg.com/YouMeAndMG-Chapter-1.pdf
It states "ACh receptors are constantly being replaced. There are two types
of AChRs. The majority are of the so-called stable type. At least 50%
of these are replaced every 12 - 13 days. The second type of receptors (called RTOs for rapid turnover) are replaced much more quickly.
Fifty percent of them break down and are replaced on a daily basis.
Although RTOs make up only 20 - 30% of the total number of
receptor sites they account for almost 70% of the overall turnover. Not
all RTOs break down this quickly, six to ten percent stabilize and
become the longer-lived type."
"Surprisingly, normal neuromuscular transmission requires that
only 25 - 30% of the total number of AChRs be functional at any one
time. Patients may have a 50 - 60% reduction of AChRs and still show
no clinical signs of inadequate neuromuscular transmission."
"AChR antibodies can cause problems in three ways; they can bind to
the AChR and block access by ACh, without damaging the receptor;
they can bind to AChRs and damage them, so that the AChRs break
down and are absorbed into the muscle; and they can bind
complement and damage the muscle endplate. As the number of
receptors decrease the NMJ becomes less responsive to ACh. There is
reduced transmission of the nerve signal, resulting in muscle
weakness."
I think that is why PLEX and IVIG are so fast at relieving MG (at least for many people). It is amazibg how rapid the replacement can be.
Another topic is permanent damage to our muscle receptors (to the end plate of the muscles where the receptors are).
from http://pmj.bmj.com/content/41/476/356.full.pdf
"Permanent "myopathic" changes may develop in affected muscles. Simpson recorded myopathic changes in 10% of the females and
20% of the males in his series (Simpson, 1958). These changes are most commonly found in the extra-ocular muscles, the triceps brachii, iliopsoas, quadriceps femoris and the tongue. Such changes are uncommon in muscles which have been affected for only a short time. The
duration of weakness is not the only factor, however, as muscles which have been affected for many years may never show myopathic
responses. When assessing the patient's reaction to anticholinesterase drugs, the possibility of permanent changes must be considered so that
a localised failure of response is not necessarily interpreted as a negative result."
(this says that if you don't respond to mestinon, it may be because you have damages too much to allow it to work and it is possible that the damages may be permanent)
My summary: Our receptors turn over rapidly and so we are often only a few days or weeks away from normal function (with IVIG or PLEX or maybe high doses of prednisone). However, there can be a point where the endplates and receptors are too far gone for repair.
Good Luck
http://youmeandmg.com/YouMeAndMG-Chapter-1.pdf
It states "ACh receptors are constantly being replaced. There are two types
of AChRs. The majority are of the so-called stable type. At least 50%
of these are replaced every 12 - 13 days. The second type of receptors (called RTOs for rapid turnover) are replaced much more quickly.
Fifty percent of them break down and are replaced on a daily basis.
Although RTOs make up only 20 - 30% of the total number of
receptor sites they account for almost 70% of the overall turnover. Not
all RTOs break down this quickly, six to ten percent stabilize and
become the longer-lived type."
"Surprisingly, normal neuromuscular transmission requires that
only 25 - 30% of the total number of AChRs be functional at any one
time. Patients may have a 50 - 60% reduction of AChRs and still show
no clinical signs of inadequate neuromuscular transmission."
"AChR antibodies can cause problems in three ways; they can bind to
the AChR and block access by ACh, without damaging the receptor;
they can bind to AChRs and damage them, so that the AChRs break
down and are absorbed into the muscle; and they can bind
complement and damage the muscle endplate. As the number of
receptors decrease the NMJ becomes less responsive to ACh. There is
reduced transmission of the nerve signal, resulting in muscle
weakness."
I think that is why PLEX and IVIG are so fast at relieving MG (at least for many people). It is amazibg how rapid the replacement can be.
Another topic is permanent damage to our muscle receptors (to the end plate of the muscles where the receptors are).
from http://pmj.bmj.com/content/41/476/356.full.pdf
"Permanent "myopathic" changes may develop in affected muscles. Simpson recorded myopathic changes in 10% of the females and
20% of the males in his series (Simpson, 1958). These changes are most commonly found in the extra-ocular muscles, the triceps brachii, iliopsoas, quadriceps femoris and the tongue. Such changes are uncommon in muscles which have been affected for only a short time. The
duration of weakness is not the only factor, however, as muscles which have been affected for many years may never show myopathic
responses. When assessing the patient's reaction to anticholinesterase drugs, the possibility of permanent changes must be considered so that
a localised failure of response is not necessarily interpreted as a negative result."
(this says that if you don't respond to mestinon, it may be because you have damages too much to allow it to work and it is possible that the damages may be permanent)
My summary: Our receptors turn over rapidly and so we are often only a few days or weeks away from normal function (with IVIG or PLEX or maybe high doses of prednisone). However, there can be a point where the endplates and receptors are too far gone for repair.
Good Luck
dezborme: plex is plasmapheresis (a treatment like dialysis that filters out the antibodies and relieves symptoms)
The statement about Mestinon is profound ; a non-response to Mestinon does NOT mean you don't have myasthenia gravis. In putting this puzzle together during the early days pre-diagnosis, I'm sure many physicians would rule-out MG based on a patient stating no benefit from Mestinon, when in reality their disease progression was too far to even benefit from the Mestinon at that point.
We are all different, snowflakes indeed.
I am not sure there is a clear answer for your questions--when you read about IVIG, the usual statement is that how it works it mostly unknown.
One of the ideas about IVIG is that with the influx of blood products, somehow our own immune system quits producing the bad antibodies (and maybe everything for a few weeks) as the overwhelming flush of new "stuff" overwhelms whatever is the driving impetus to make the bad stuff in the first place. So we get a break from bad antibodies and the fast regeneration of receptors quickly can bring normal receptor levels again.
PLEX -- blood filtering--is supposed to remove enough bad stuff to give the receptors a chance to regenerate before our immune system churns out more. In this case the immune system probably kicks into high gear as the lower level of antibodies probably pushes production to increase where as in IVIG the immune system may go to idle for a time.
Meds are slower, but also cut the attack and allow regeneration. Bug of course you have to live with a lowered immune system function overall just to get the bad stuff diminished. No selective switch for just one antibody.
I suppose the next question is How long do the bad antibodies persist in our blood and thus continue to attack the receptors? Since IVIG and PLEX seem to take about a week to be effective, maybe that hints at the time (I haven't tried either so am not sure about the time).
Anyway, I like the idea that not only we do regenerate receptors but it happens quickly and continuously with the right conditions. It is rather amazing that some receptors are replaced daily; and that we only need about 30% functioning to be normal. I like the idea we are one week or less away from being rebuilt to function normally if our immune system would turn off the bad stuff.