Muscle atrophy not related to disuse

[viggster]

@RYO @viggster

I was wondering whether the NIH study has decided to include muscle biopsies.

I had a biopsy done at the end of last year which revealed severe typeII muscle atrophy. I am bedbound with severe muscle weakness. I was shocked to find that a study in the early 90's showed 39 of 50 ME/CFS patients had type II atrophy and this target has never been looked at again.

Hi...I recently had a muscle biopsy at Stanford that showed inflammatory myopathy and type II fiber atrophy. I will be going back to NIH March 3 for part 2 of the study. NIH is going to look at the slides from Stanford but they may decide to do another biopsy too because their procedures are different. The good news is that we have ruled out inclusion body myositis, which is untreatable. The doc at Stanford suggested IVIG for the inflammatory myopathy.

Do you have the reference to the study of muscle atrophy in ME patients?

Thanks.

 

[Gingergrrl]

The good news is that we have ruled out inclusion body myositis, which is untreatable. The doc at Stanford suggested IVIG for the inflammatory myopathy.

That is so interesting @viggster and high dose IVIG completely reversed the muscle weakness in my arms and upper body (even though I still have autonomic problems). I had a few questions (when you have time of course) and I apologize if you have told me any of this info before!

- Did your doctor explain HOW the IVIG does this?
- Can you remind me what your muscle weakness was like and how it affected you?
- Do you test positive for any specific autoantibodies?

Thanks in advance and best wishes with the study!

 

[Rossy191276]

Hi...I recently had a muscle biopsy at Stanford that showed inflammatory myopathy and type II fiber atrophy. I will be going back to NIH March 3 for part 2 of the study. NIH is going to look at the slides from Stanford but they may decide to do another biopsy too because their procedures are different. The good news is that we have ruled out inclusion body myositis, which is untreatable. The doc at Stanford suggested IVIG for the inflammatory myopathy.

Do you have the reference to the study of muscle atrophy in ME patients?

Thanks.

Hi @viggster . Great news about the NIH including biopsies. I also have a couple of questions when you get a chance I would be most grateful if you could reply.

@Gingergrrl you might also be interested in the information I share in this post.

As well as the type II atrophy my biopsy also revealed myositis but it was only in one fascicle so the report did not make any conclusions on this. I am wondering if you could give more details on what inflammatory myopathy was shown and how they ruled out the inclusion myositis (and I assume polymyositis) as I have been finding it difficult to get info on that finding... At the end of my hospital stay the overseeing doctor also suggested the possibility of IVIG trial but since the myositis was only in one fascicle and they haven't found any auto-antibodies so far I haven't been able to get any progress with doctors regarding this.

Also my other consistent finding is high ferritin and low transferrin which my doctor attributes to an inflammatory process-- have you had your iron panel tested and if so would you share your results?

The reference for the type II fibre atrophy is:
Mitochondrial abnormalities in the postviral fatigue syndrome* W. M. H. Behan1, I. A. R. More1, and P. O. Behan2

My doctor and I have since been researching as to why type II rather than I atrophy might be part of ME or at least a subset. The following is a good article which explains these possibilities and points towards malnutrition/inflammation (one key to share with relevant people is that disuse causes more type I atrophy so the type II findings aren't caused by disuse):
Mechanisms for fiber-type specificity of skeletal muscle atrophy.
Wang Y1, Pessin JE.

Additionally, I experience chest and breathing weakness (I can't pass a Spirometry test) and cant talk much of the time. This paper on respiratory muscles explains that each fast twitch (type II) exertion uses 3-4 times the ATP of a slow twitch (type I) exertion so my hypothesis is this might contribute to why type II fibre atrophies in ME/CFS or whatever subset of disease causes type II muscle atrophy and potentially inflammation:
Respiratory Muscle Fibres: Specialisation and Plasticity Polla, Bottinelli, Regianni

For your information @Gingergrrl I would describe my muscle weakness as a burning weakness with discomfort but not particularly painful that can affect different areas of the body more or less so at different times usually the worst being upper legs and chest but currently it is also bad in my arms/hands.

 

[Gingergrrl]

@Gingergrrl you might also be interested in the information I share in this post.

Rossy, thank you for tagging me and I will keep following this thread to learn more.

At the end of my hospital stay the overseeing doctor also suggested the possibility of IVIG trial but since the myositis was only in one fascicle and they haven't found any auto-antibodies so far I haven't been able to get any progress with doctors regarding this.

What is a fascicle? I Googled it but didn't really understand what I was reading to apply it to your case (or my case). How do fascicles relate to autoantibodies? I am so curious if high dose IVIG would help you. It is so expensive (literally more than 3x the price of my Rituximab) and my insurance has tried every tactic known to man to cut me off but so far I keep prevailing.

Also my other consistent finding is high ferritin and low transferrin which my doctor attributes to an inflammatory process-- have you had your iron panel tested and if so would you share your results?

I tend to have low iron and ferritin (for whatever that may be worth?) but am not sure about "transferrin" or if I have been tested for that. I know I had an entire "iron panel" done at one point but don't remember anything too irregular re: the results except that the iron on the low side (but I was slightly anemic at that time overall).

Additionally, I experience chest and breathing weakness (I can't pass a Spirometry test) and cant talk much of the time.

I could not pass a spirometry test for several years and I experienced breathing weakness but I was always able to talk. Although there was a point that I could get out of breath from talking (but this is completely gone now). I can pass a spirometry test now but it is still much lower than where it should be in a normal person.

Can you remind me (if you know) does your spirometry show pulmonary restriction (like mine) or obstruction? Mine still shows restriction, just not as severe as before.

For your information @Gingergrrl I would describe my muscle weakness as a burning weakness with discomfort but not particularly painful that can affect different areas of the body more or less so at different times usually the worst being upper legs and chest but currently it is also bad in my arms/hands.

My muscle weakness was never burning and I would describe it as pure weakness. Mine never affected my legs and was concentrated in my upper body (lungs, chest, arms, neck, etc). It is dramatically better now but is not gone. But so far every gain I have made with IVIG and Rituximab has been permanent. Meaning once I could open a water bottle or a pill bottle, turn on the shower faucets, cut paper with a scissors, open a box, carry my purse, etc, it has stayed and never reversed.

There are still things that I cannot do (but they are more autonomic dysfunction than weakness at present). I also have no idea what will happen to me once my treatments stop which really scares me. The treatments may have "re-set" my immune system back to pre-illness but we do not know yet. They put my MCAS/allergic reactions into remission which will be two years in July.

 

[Rossy191276]

Rossy, thank you for tagging me and I will keep following this thread to learn more.

Great...I followed your case and you were the reason I got cell trend tests done but I was negative to all.

What is a fascicle? I Googled it but didn't really understand what I was reading to apply it to your case (or my case). How do fascicles relate to autoantibodies? I am so curious if high dose IVIG would help you. It is so expensive (literally more than 3x the price of my Rituximab) and my insurance has tried every tactic known to man to cut me off but so far I keep prevailing.

A fascicle contains the muscle fibres. So for example when they do a muscle biopsy it might have 10 fascicles which each contain 10 fibres (this number is a total guess and why I don't know how big of a deal it is to have just one fascicle show myositis and whether this rules out the myositis diseases or whether this could occur in those diseases). It doesn't have anything to do with autoantibodies except I guess that autoantibodies could potentially cause problems that end up damaging muscle fibres (e.g., polymyositis I think is thought to be autoimmune).

I tend to have low iron and ferritin (for whatever that may be worth?) but am not sure about "transferrin" or if I have been tested for that. I know I had an entire "iron panel" done at one point but don't remember anything too irregular re: the results except that the iron on the low side (but I was slightly anemic at that time overall).

Yes my doctor says high ferritin is common in his patients with ME but it seems rare on forums

I could not pass a spirometry test for several years and I experienced breathing weakness but I was always able to talk. Although there was a point that I could get out of breath from talking (but this is completely gone now). I can pass a spirometry test now but it is still much lower than where it should be in a normal person. Can you remind me (if you know) does your spirometry show pulmonary restriction (like mine) or obstruction? Mine still shows restriction, just not as severe as before.

I literally couldn't blow enough air for them to get a recording. My report from neurologist when I was in hospital simply says "He had respiratory tests completed and has not been able to provide any sustained force with his breathing".

My muscle weakness was never burning and I would describe it as pure weakness. Mine never affected my legs and was concentrated in my upper body (lungs, chest, arms, neck, etc). It is dramatically better now but is not gone. But so far every gain I have made with IVIG and Rituximab has been permanent. Meaning once I could open a water bottle or a pill bottle, turn on the shower faucets, cut paper with a scissors, open a box, carry my purse, etc, it has stayed and never reversed.

Very interesting... yes particularly in legs and arms mine comes with a burning sensation and when it has hit in past it has huge effects quickly. So I have gone from walking in apartment to not being able to walk at all within 3 days. Or typing for several hours a day to not being able to type more than a couple of minutes within a few days. Thats how Ive always known that the cause has nothing to do with deconditioning.

There are still things that I cannot do (but they are more autonomic dysfunction than weakness at present). I also have no idea what will happen to me once my treatments stop which really scares me. The treatments may have "re-set" my immune system back to pre-illness but we do not know yet. They put my MCAS/allergic reactions into remission which will be two years in July.

Really happy to hear of your progress and hope it continues. I live in Australia so if I was able to get IVIG it would be free as part of medicare but up to the doctor as to how long I would get it.

 

[Gingergrrl]

Really happy to hear of your progress and hope it continues. I live in Australia so if I was able to get IVIG it would be free as part of medicare but up to the doctor as to how long I would get it.

It is also up to the doctor here (and without a doctor's prescription I would not be able to get it) but regardless of the doctor, the ultimate decision for approval is from the insurance company. I have two doctors saying that I need it, so my prescription is not at risk, but my insurance company can deny me at any time which has been a constant battle.

Sorry to be a pest with this last question but do you know if your spirometry test showed restriction or obstruction? I am trying to compare your situation to mine and am very curious!

 

[Rossy191276]

It is also up to the doctor here (and without a doctor's prescription I would not be able to get it) but regardless of the doctor, the ultimate decision for approval is from the insurance company. I have two doctors saying that I need it, so my prescription is not at risk, but my insurance company can deny me at any time which has been a constant battle.

Sorry to be a pest with this last question but do you know if your spirometry test showed restriction or obstruction? I am trying to compare your situation to mine and am very curious!

You're not being a pest at all Ive found your posts very helpful. Re Spirometry I am not sure. To give you context I did it during a hospital stay after presenting to ER with severe tachachardia (I have severe dysautonomia) that at the time I didnt understand so thought I was having a heart attack. It was chaotic and I just remember at some stage someone came and took me to do the test. All I remember is them saying you need to blow harder as I was not registering enough force but each time I did it I was getting worse and worse and they said they couldn't get a proper recording as I didnt blow hard enough. After this I literally thought I would die as I got severe chest pains for days and became so weak I couldn't eat. And then the report I have just says what I wrote above. I would be petrified to do another one because I still have such inability to blow any air out that I know I wouldn't be able to get a reading. They never mentioned anything about restriction or obstruction.

What makes most sense to me is that the type II atrophy I have in my thigh I also have in whatever muscles are required to blow air and talk and I'm not sure how that would be classed on tests. I can breathe quite normally at rest as long as I'm not in a crash but can't do anything else but that...

 

[Gingergrrl]

Re Spirometry I am not sure. To give you context I did it during a hospital stay after presenting to ER with severe tachachardia (I have severe dysautonomia) that at the time I didnt understand so thought I was having a heart attack. It was chaotic and I just remember at some stage someone came and took me to do the test. All I remember is them saying you need to blow harder as I was not registering enough force but each time I did it I was getting worse and worse and they said they couldn't get a proper recording as I didnt blow hard enough. After this I literally thought I would die as I got severe chest pains for days and became so weak I couldn't eat. And then the report I have just says what I wrote above.

Thank you (and I apologize if you already told me all of this before)! From what you describe re: the extreme difficulty exhaling/ blowing out and then having chest pain for days afterward, my guess is that you would have shown a pulmonary restriction from muscle weakness. When I was hospitalized on a cardiac unit in 2014, I attempted to blow into the spirometry machine but absolutely nothing registered like you.

When I was hospitalized again in 2015 (this time for allergic/ anaphylactic reactions), I attempted the basic spirometry test again and was able to register on the machine and showed a pulmonary restriction with my best effort at 69%. The only logical explanation was muscle weakness (since three consecutive lung cat scans show my lungs are clear), but we did not learn of all my autoantibodies until 2016.

But I have never had such severe chest pain in my life as the attempted spirometry (and PFT) tests prior to high dose IVIG. Now I can "pass" the test with FVC (forced vital capacity) at 84% (in April 2017) and I suspect I would have an even better score if I were to attempt it again now almost one year later. I also have severe dysautonomia like you.

I would be petrified to do another one because I still have such inability to blow any air out that I know I wouldn't be able to get a reading.

I agree and I don't think you should do one now. It literally took me days to recover from it when I was at my worst and felt like someone had kicked me in the chest and squeezed my heart muscle. Vs. I had no negative after effects from the test in 2017.

What makes most sense to me is that the type II atrophy I have in my thigh I also have in whatever muscles are required to blow air and talk and I'm not sure how that would be classed on tests. I can breathe quite normally at rest as long as I'm not in a crash but can't do anything else but that...

I have not had any weakness in my thighs or legs (which is why they felt I did not match with LEMS even though I have the calcium autoantibody) but I had unbelievable weakness in my arms. To be able to use a hairdryer again to dry my hair after a shower still shocks me b/c I never believed that I would do it again.

Does your breathing get worse if you raise your arms over your head or bend down from a standing position to pick up something from the floor (nothing heavy, just doing that motion)?

 

[Rossy191276]

Thank you (and I apologize if you already told me all of this before)! From what you describe re: the extreme difficulty exhaling/ blowing out and then having chest pain for days afterward, my guess is that you would have shown a pulmonary restriction from muscle weakness. When I was hospitalized on a cardiac unit in 2014, I attempted to blow into the spirometry machine but absolutely nothing registered like you.

Thanks for your reply Yes that makes sense...

 

[Rossy191276]

Thank you (and I apologize if you already told me all of this before)! From what you describe re: the extreme difficulty exhaling/ blowing out and then having chest pain for days afterward, my guess is that you would have shown a pulmonary restriction from muscle weakness. When I was hospitalized on a cardiac unit in 2014, I attempted to blow into the spirometry machine but absolutely nothing registered like you.

When I was hospitalized again in 2015 (this time for allergic/ anaphylactic reactions), I attempted the basic spirometry test again and was able to register on the machine and showed a pulmonary restriction with my best effort at 69%. The only logical explanation was muscle weakness (since three consecutive lung cat scans show my lungs are clear), but we did not learn of all my autoantibodies until 2016.

But I have never had such severe chest pain in my life as the attempted spirometry (and PFT) tests prior to high dose IVIG. Now I can "pass" the test with FVC (forced vital capacity) at 84% (in April 2017) and I suspect I would have an even better score if I were to attempt it again now almost one year later. I also have severe dysautonomia like you.



I agree and I don't think you should do one now. It literally took me days to recover from it when I was at my worst and felt like someone had kicked me in the chest and squeezed my heart muscle. Vs. I had no negative after effects from the test in 2017.



I have not had any weakness in my thighs or legs (which is why they felt I did not match with LEMS even though I have the calcium autoantibody) but I had unbelievable weakness in my arms. To be able to use a hairdryer again to dry my hair after a shower still shocks me b/c I never believed that I would do it again.

Does your breathing get worse if you raise your arms over your head or bend down from a standing position to pick up something from the floor (nothing heavy, just doing that motion)?

No I have no plans to take another one unless I was in much better condition. Traditionally my worst weakness has been in my upper legs and chest and much less so my arms. I went into severe crash in March last year and from that time I haven't been able to leave bed (except for bowel movements in bed side commode). I did improve slightly in June and so they transported me to hospital in ambulance and at that time I was able to talk again and they treated me for Dysautonomia but the standing HR tests was too much and I haven't been able to leave bed again. I did get back talking in November but then got an infection and have been too weak to talk since then. So I haven't tried picking anything off floor for over a year but before March last year I would use a wheelchair when outside but function pretty well indoors.

 

[pattismith]

@Rossy191276

do you know more about your type 2 atrophy muscle fiber?

I found this:

"Type 2 fibers contain more Na+-K+ exchange pump and atrophy of type 2 fibers predominated over type 1 in muscles of PPs patients"

This is from a scientific paper with one patient with Periodic paralysis who recovered with CoQ10, and the other recovered with Idebenone:


http://forums.phoenixrising.me/inde...elopathy-with-coenzyme-q10.56835/#post-944206

I have myself big muscle problems, and a low T3 syndrome, and I feel almost normal with T3 + Idebenone;

(I suspect my muscles problems are coming from impaired ion channels)

 

[Rossy191276]

Thanks for this @pattismith ... I think there must be a reason that people with muscle weakness in ME seem to be predominantly Type II atrophy.

 

[pattismith]

Thanks for this @pattismith ... I think there must be a reason that people with muscle weakness in ME seem to be predominantly Type II atrophy.

My investigations make me think that it could be a dysfunction of ion channels, because type 2 atrophy is a non specific myopathy that can be seen in several diseases, like hypothyroidism and periodic paralysis, that are linked to ion channels dysfunction.

I can instantly rescue my own muscles with both T3 + Idebenone, two drugs that have an effect on ion channels as seen in several studies I quoted, so it may be that they could be useful for some other ME/CFS sufferers with muscle symptoms and particularly for those with type 2 atrophy.

 

[Gingergrrl]

My investigations make me think that it could be a dysfunction of ion channels, because type 2 atrophy is a non specific myopathy that can be seen in several diseases, like hypothyroidism and periodic paralysis, that are linked to ion channels dysfunction.

Hi Patti, I am still trying to determine if this pertains to me since I have a calcium channelopathy and had severe muscle weakness (which is better now with treatment). I never had a muscle biopsy and have no idea if I ever had type 2 atrophy. But I do have hypothyroidism (Hashimoto's). Do you think this is worth pursuing or would it not change anything in my case?

 

[pattismith]

Hi Patti, I am still trying to determine if this pertains to me since I have a calcium channelopathy and had severe muscle weakness (which is better now with treatment). I never had a muscle biopsy and have no idea if I ever had type 2 atrophy. But I do have hypothyroidism (Hashimoto's). Do you think this is worth pursuing or would it not change anything in my case?

As you already have some evidences that you have both a channelopathy and hypothyroidism, a muscle biopsy may show you a type 2 atrophy, but I 'm not sure if it will be really usefull to know it, because you already know the cause, and you receive proper treatment for it.

I surely would go for a muscle biopsy if I had myself the opportunity to do so, because in my case, a low T3 syndrome is not supposed to receive any treatment by doctors, although I benefit strongly from T3 drug, and can't do without.

I would go, just to show them it is not all in my head, even though I read it is a painful test

 

[Gingergrrl]

As you already have some evidences that you have both a channelopathy and hypothyroidism, a muscle biopsy may show you a type 2 atrophy, but I 'm not sure if it will be really usefull to know it, because you already know the cause, and you receive proper treatment for it.

I have limited medical knowledge (even though it sometimes appears otherwise)! Do you mean that the cause of the muscle and breathing weakness in my case was the channelopathy, or the hypothyroidism, or both? Also, from your research, does it confirm that high dose IVIG and Rituximab (what I am doing) is the proper treatment.

My doctors feel that it is, and my improvements so far have exceeded my expectations, but I was wondering if this matched with your research when you said that I am already receiving the "proper treatment". Thank you in advance for your info on this!

 

[pattismith]

I have limited medical knowledge (even though it sometimes appears otherwise)! Do you mean that the cause of the muscle and breathing weakness in my case was the channelopathy, or the hypothyroidism, or both? Also, from your research, does it confirm that high dose IVIG and Rituximab (what I am doing) is the proper treatment.

My doctors feel that it is, and my improvements so far have exceeded my expectations, but I was wondering if this matched with your research when you said that I am already receiving the "proper treatment". Thank you in advance for your info on this!

Ginger, there is no doubt that you are receiving the right treatments, your improvement gives you evidence for it!

Do you receive a T4 treatment for your hypothyroidism? Was it before Ivig and Ritux?

 

[Gingergrrl]

Ginger, there is no doubt that you are receiving the right treatments, your improvement gives you evidence for it!

I have no doubt they are working and neither does anyone who knew me pre-illness, when I was near death in 2015, and sees me now. But I wish I understood exactly how and why they were working and what percent of my improvement is from IVIG and what from Rituximab. When you mentioned muscle weakness, hypothyroid, and ion channelopathy it is 100% my situation (plus POTS, MCAS and other factors) and I want to crack the code but afraid I never will.

Do you receive a T4 treatment for your hypothyroidism? Was it before Ivig and Ritux?

I have taken Armour Thyroid for Hashimoto's (which I believe is T3 and T4) since end of Oct 2013. I did not start IVIG until July 2016 and did not start Ritux until July 2017.

Edit: The Armour has kept my thyroid numbers in the normal range (minus the Hashi's autoantibodies which fluctuate but usually remain high). But the Armour alone did not bring about any symptom improvement and I got progressively worse until I began IVIG.

 

[pattismith]

I have taken Armour Thyroid for Hashimoto's (which I believe is T3 and T4) since end of Oct 2013. I did not start IVIG until July 2016 and did not start Ritux until July 2017.

Edit: The Armour has kept my thyroid numbers in the normal range (minus the Hashi's autoantibodies which fluctuate but usually remain high). But the Armour alone did not bring about any symptom improvement and I got progressively worse until I began IVIG.

The treatment with T4 (and T3) is not for Hashimoto (Hashimoto is an auto-immune thyroiditis), it is for hypothyroidism which is not exactely the same. I suppose Hashimoto may be part of your over active immune system, I saw on internet that some hypothyroid patients also suffer from POTS, althought there is not a direct link between the two, so I suppose auto-immunity could be a link.

Endocrinologists just give T4 to treat hypothyroidism, so I suppose you were given Amour by an american integrative doctor (is it Dr Kaufman?).

I would be interested to know your thyroid panel before you took Amour, even we are not in the right thread to do so...

But I am happy you are getting involved in this thread, because I do believe @viggster and @Rossy191276 should have their auto-immunity checked against their voltage-gated calcium channels just like you were checked yourself.

Auto-immunity against these channels would be able to trigger the muscle type 2 atrophy, at less in theory.
(all the auto-antibodies against ion channels would be indicated in fact)

If auto-immunity is responsible for their type 2 atrophy, they could benefit from IVIG and Ritux like you do.

If I was in their situation I would have also an extensive thyroid panel done regularly including reverse T3

 

[Gingergrrl]

I saw on internet that some hypothyroid patients also suffer from POTS

I don't think I have heard of that before (a link between Hashi's and POTS) and would be curious to learn more about it. I was diagnosed with Autoimmune POTS, and of course Hashi's is autoimmune thyroiditis, so there is definitely the autoimmune link (in my case).

Endocrinologists just give T4 to treat hypothyroidism, so I suppose you were given Amour by an american integrative doctor (is it Dr Kaufman?).

Dr. K is my main doctor but I have a separate endocrinologist who treats my thyroid and monitors my other hormones. My Endo is American but I would not call him integrative in any way and is a standard Endo. Is Armour considered "integrative" outside of the US? I have two other very close local friends with Hypothyroid (one with Hashi's and one without) and both of their doctors also prescribe them Armour (one is an Endo and one just a PCP).

I would be interested to know your thyroid panel before you took Amour, even we are not in the right thread to do so...

I could probably find the original thyroid panel for you (done in Oct 2013) if it would be helpful.

Auto-immunity against these channels would be able to trigger the muscle type 2 atrophy, at less in theory. (all the auto-antibodies against ion channels would be indicated in fact)

I wish I understood this all better as much as I try . I know that the CA+ Channel autoantibody that I have can weaken muscle strength (I believe along with the anti muscarinic/cholinergic autoantibodies which I also have) but I don't really understand HOW they do this even though it has been explained to me before. All I know is that IVIG and Ritux greatly improved my muscle strength.

If auto-immunity is responsible for their type 2 atrophy, they could benefit from IVIG and Ritux like you do.

Does type 2 atrophy only show up on a muscle biopsy or are there other ways to test for it? I never had a muscle biopsy but there was a point in 2015 for my disability exam in which the doctor measured my grip strength on a machine and I squeezed the handles as hard as I could and absolutely nothing registered. While it helped my disability case, I was very upset about it at the time and was convinced I could make something register if I tried harder but I could not (at that time).