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Evidence of Neurological Abnormalities in ME Suppressed in the IOM "ME/CFS" R

taniaaust1

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@zzz thank you for the above post. I am curious though re: dysautonomia (which I definitely have!) why I can have extreme shortness of breath and chest pain even in the absence of tachycardia and low BP?

Sometimes I have severe tachycardia and low BP and then I know it is dysautonomia behind the SOB and chest pain. But other times my HR and BP are okay (like today) but the breathing and chest pain are still very severe.

Would this still be dysautonomia or would it be a feature of the ME/CFS itself that my body just cannot create enough metabolic energy or oxygen to do basic functioning?
I cant say that I know the answer but even when we aren't showing the tachycardia and low BP we still have the other things which go along with the dysautonomia such as low blood volume, so maybe its something like that leading to pain etc.
 

zzz

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@zzz thank you for the above post. I am curious though re: dysautonomia (which I definitely have!) why I can have extreme shortness of breath and chest pain even in the absence of tachycardia and low BP?

Sometimes I have severe tachycardia and low BP and then I know it is dysautonomia behind the SOB and chest pain. But other times my HR and BP are okay (like today) but the breathing and chest pain are still very severe.

Would this still be dysautonomia or would it be a feature of the ME/CFS itself that my body just cannot create enough metabolic energy or oxygen to do basic functioning?
I originally sent my reply to @Gingergrrl as a PM in order to avoid sidetracking this thread. But as further questions have come up here on this subject, I might as well repeat my answer and also address A.B.'s question. I would suggest that further questions on this topic (which is an important one) be put into their own thread.

Here's my answer to @Gingergrrl:

This is just a milder form of dysautonomia than POTS, but it is still dysautonomia. In fact, the symptoms you describe are exactly what I had when I began my magnesium nebulizer treatment a year ago. The fact that magnesium gradually cured it indicates that it’s entirely neurological (for reasons that I elaborate on below).
Apologies for going off topic. Re. dysautonomia, I'm wondering about a certain breathing symptom. During episodes of increased exhaustion, my breathing is shallow and it feels like I'm not getting enough oxygen, so I have to make a conscious effort to breath more deeply. Shouldn't my body make some adjustments to breathing, such as increasing frequency or depth when it feels that there isn't enough oxygen? Is this some form of dysautonomia?
The answer is the basically the same as the answer to @Gingergrrl's question. To elaborate a bit more, excess noise in the NMDA receptors creates a low signal-to-noise ratio, which makes it difficult for the brain to tell what's going on. As a result, its output to the autonomic nervous system is incorrect, resulting in dysautonomia. Magnesium is the most powerful NMDA antagonist, calming down these receptors and reducing their noisiness, thereby enhancing the signal-to-noise ratio, so that the brain can once again precisely detect what's going on with the autonomic nervous system and control it properly. For this reason, proper magnesium treatment is extremely effective as a treatment for dysautonomia.

Again, further discussions of this topic should probably go into a different thread.
 

Marco

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melamine

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@Sidereal @melamine @WillowJ (and anyone I missed) what do you mean when you say your "breathing muscles are weak?" Does this equate to "shortness of breath" and chest pressure and/or chest pain for you guys or something else?


@Gingergrrl
- I've tended to consider the loss of strength in my back muscles and the kind of rapid loss of muscle strength I've experienced in other muscles when I use them to be somewhat different than the "tiredness" of my lungs, which feels like a mitochondrial issue. My tendency to breath fatigue when I'm in an extended (or even short), sustained conversation, remains, even when chest tightness and lung-centered energy are not otherwise noticeable. I don't think the cause of all of these is necessarily mutually exclusive, but I had noticed the lung symptoms worsening over time and separately from other muscle symptoms, which had somewhat improved in certain respects.

A.B. and Sidereal have described the primary lung symptom I experience for periods of time, in conjunction with a feeling of pressure or tightness in the chest area -

During episodes of increased exhaustion, my breathing is shallow and it feels like I'm not getting enough oxygen, so I have to make a conscious effort to breath more deeply.
Breathing became a conscious effort for me. It wasn't the usual chest pain and dyspnea on exertion. It was a sensation of weakness in the chest even when resting and if I didn't force myself to keep taking breaths it's as if my body forgot to do so. I'm not doing a good job explaining it.
@Sidereal - you've described it well. ;)
 

Sidereal

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These are classic symptoms of dysautonomia. It is not a problem with your breathing muscles or your heart.


And this is CNS depression, as you indicated. The difference is very clear. With dysautonomia, you are huffing and puffing away, as if you just ran a marathon. The breathing muscles are working fine; you just can't seem to get enough air. It is brought on or exacerbated by activity. In CNS depression, as you mentioned, @Sidereal (and I think you gave a very good explanation), it's like you have to force yourself to breathe, or else your diaphragm just won't move. It is not brought on by activity, and ceasing activity doesn't make it go away. Your description of its lasting 12 hours fits in totally here.

Strong magnesium supplementation can help dysautonomia, such as yours, @Gingergrrl, but too much for a given person will bring on CNS depression, as in @Sidereal's case.

In some people, CNS depression can be brought on by very small doses of magnesium, as when it happened to @Sidereal when she took a quarter tablet of a magnesium pill. This is a result of extremely hypersensitive NMDA receptors. Magnesium lessens the hypersensitivity of NMDA receptors, so if any signs of CNS depression occur (and they typically include drowsiness and excess sleepiness in combination with continual muscle weakness), starting with a lower dose that is tolerable and letting the body adjust will allow higher doses to be tolerated.

Paradoxically, an extreme reaction to magnesium, such as @Sidereal's, is typically evidence of magnesium deficiency, manifesting in the form of hypersensitive NMDA receptors. Gradually increased amounts of magnesium will cause this hypersensitivity to lessen or disappear, often along with other hypersensitivity reactions (such as dysautonomia).
I agree with the general thrust of your argument but I do think that in severe and very severe ME, even though the patient has an underlying severe deficiency, magnesium supplementation can be detrimental due to muscle weakness and vasodilation.

I would also add that Dr Goldstein spoke of the fact that if every ME/CFS case was having glutamate/NMDA excess then everyone would have a positive response to ketamine which quite clearly they do not. Some do well with NMDA agonists (though I would question whether that reflects a true improvement or just short-term stimulation / fake energy while worsening the underlying redox problem).
 

snowathlete

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This is probably right, but double edged. We are not driving this process. We can however respond to it. Hence the debate on how best to do that.

We did and still do need better engagement with the politics. Its been one of our huge failings, and that includes our researchers.

I am completely for using this as much as possible to advance a research and medical education agenda. Yet such an agenda needs to be examined just as much as everything else in ME. Is a process.

Its not irrelevant because it was premature, because we have to keep in mind that its all temporary: SEID, the definition, most of the concerns we have now. We need to remember that this may all change very rapidly. Where we gain the most is from more research funding, any centers of excellence, and better medical awareness. If nothing else, just like XMRV did, this raises the public profile of the disease.
This is the main immediate benefit of the IOM report in my view. Regarding validation of the IOM criteria, I agree it's needed. But if we waited for it to be validated before adopting it, by the time it was validated it would likely be obsolete as the science is moving forward. As you said in an earlier post, A biomarker changes everything.
 

snowathlete

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Maybe that is what we should be putting focus on with our advocacy, getting research started ASAP in the areas which were discluded in the IOM due to lack of patients in the studies showing promise.

It would be good if these studies could be done larger before the review happens within 5 years, so is something we need to start pushing to be done now as doing a study takes quite a while often years to organise and publish. Just imagine how much better that IOM report would of been if those small studies had more weight.

ME patients could work to fundraise for these studies and work to find scientists interested in doing a bigger follow up studies on these. These areas should be made priority areas which need big studies done.
Not only would a larger study like that carry more weight in a review but it might be enough to trigger that review in itself.

I think we need to focus on research full stop because that is what will ultimately take us forward, and if this is considered to be one important yet under researched area then that would certainly be one place to focus.
 

Gingergrrl

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I originally sent my reply to @Gingergrrl as a PM in order to avoid sidetracking this thread. But as further questions have come up here on this subject, I might as well repeat my answer and also address A.B.'s question. I would suggest that further questions on this topic (which is an important one) be put into their own thread.
@zzz I agree that this needs a separate thread but don't want to create more work for the moderators! I wasn't going to respond here further either on this topic but since you guys did, I have some more questions. Also, indirectly I do think it relates to this thread as it is about neurological & autonomic stuff not being in the IOM report when these seem to be core symptoms for many people.

This is just a milder form of dysautonomia than POTS, but it is still dysautonomia. In fact, the symptoms you describe are exactly what I had when I began my magnesium nebulizer treatment a year ago. The fact that magnesium gradually cured it indicates that it’s entirely neurological (for reasons that I elaborate on below).
I increased my magnesium dose in the nebulizer to 1/2 tsp (from 1/3 tsp) last night to see if this will help my shortness of breath and chest pressure. I still can't tell though what is autonomic dysfunction versus my cells cannot make energy at a mitochondria level when I do any exertion and therefore cannot breathe.

A.B. and Sidereal have described the primary lung symptom I experience for periods of time, in conjunction with a feeling of pressure or tightness in the chest area -
@melamine Do you feel breathless as if you have run up a flight of stairs when all you did is lift a plate out of a cabinet?

I agree with the general thrust of your argument but I do think that in severe and very severe ME, even though the patient has an underlying severe deficiency, magnesium supplementation can be detrimental due to muscle weakness and vasodilation.
@Sidereal I do have a Magnesium deficiency on the intracellular Mag test (in spite of massive supplementation with pills, nebulizer and skin oil.) How would I know if what I am doing is detrimental due to muscle weakness and vasodilation?

I would also add that Dr Goldstein spoke of the fact that if every ME/CFS case was having glutamate/NMDA excess then everyone would have a positive response to ketamine which quite clearly they do not. Some do well with NMDA agonists (though I would question whether that reflects a true improvement or just short-term stimulation / fake energy while worsening the underlying redox problem).
I wish I understood this part but do not retain the meaning of a lot of the words like NMDA and redox even though I have asked about them a hundred times. Maybe we could start a new thread on this topic and I apologize we shifted the topic!
 

A.B.

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Like Sidereal I have experienced a distinct sensation of weakness in the chest. Also some chest pain and tachycardia (but only after a bronchitis). And magnesium does help - no chance of a mistake. I don't know how much I'm taking, about a teaspoon full of magnesium sulfate. I'm guessing that's about 1g?
 

melamine

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@melamine Do you feel breathless as if you have run up a flight of stairs when all you did is lift a plate out of a cabinet?
@Gingergrrl - In that kind of situation, my symptoms tend to be more localized - to my arms in your example, as well as contributing to overall exhaustion and PEM to one degree or another. My lung symptoms seem to have become part of low level background noise in the past year or so, but when they're more noticeable they can remain so for weeks or more and have tended to be at least as bad when I lie down as any other time.
 
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Sidereal

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Do you feel breathless as if you have run up a flight of stairs when all you did is lift a plate out of a cabinet?
My weakness only got that bad if I tried supplementing something that forces energy production on a system that can't handle it, stuff you see people here frequently keeling over from, like methylfolate, methyl B12, CoQ10, D-ribose etc.
 

zzz

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This is obviously a complex issue. On one hand, magnesium has clearly helped @A.B., by his own testimony, yet magnesium made @Sidereal's symptoms worse. This in itself is understandable, but then @melamine says:
A.B. and Sidereal have described the primary lung symptom I experience for periods of time, in conjunction with a feeling of pressure or tightness in the chest area -
This seems to be confusing, as these symptoms are due to opposite causes. @melamine also questions the role of mitochondrial function here, which is a very reasonable question, and certainly enters into the picture.

It is possible to sort all this out into a coherent picture, though, and I will attempt to do so.
I agree with the general thrust of your argument but I do think that in severe and very severe ME, even though the patient has an underlying severe deficiency, magnesium supplementation can be detrimental due to muscle weakness and vasodilation.
This occurs only with an overdose of magnesium - one that causes severe CNS side effects. It's important to remember that multiple studies have shown that the majority of the U.S. population is deficient in magnesium. There's no reason to believe that this is any different in other parts of the Western world, or that ME/CFS patients suffer from this less. To the contrary, Dr. Myhill found that intracellular RBC magnesium tests showed her patients uniformly deficient in magnesium. That is why she has stated that magnesium injections "are so helpful that it is pointless progressing onto other things without trying these first." It is due to her statements that I started magnesium by nebulizer, and have experienced great improvements over the last year as a result.

EDIT: I should add, as I mention later, that not everyone can tolerate these injections, and that for many, the starting dose that Dr. Myhill recommends is too high. I elaborate on this in this post.

It's also important to note that muscle weakness is often caused at least partially by magnesium deficiency, as magnesium is necessary for proper mitochondrial operation, as well as the generation of new mitochondria. Although not all mitochondrial problems are due to magnesium deficiency, without sufficient magnesium, it is impossible for mitochondria to work properly.
I would also add that Dr Goldstein spoke of the fact that if every ME/CFS case was having glutamate/NMDA excess then everyone would have a positive response to ketamine which quite clearly they do not.
Do you have a reference here? In any case, ketamine is very different from magnesium. Magnesium is required for proper neurological functioning; ketamine is not. You can live fine without ketamine (most people do), but you can't live without magnesium. Ketamine's functions are purely neurological, at least as far as we know, while magnesium plays multiple essential roles in bodily function. People can become tolerant to ketamine to the point where it's no longer effective; this does not happen with magnesium, due to its essential role in body chemistry.
Some do well with NMDA agonists (though I would question whether that reflects a true improvement or just short-term stimulation / fake energy while worsening the underlying redox problem).
It's important to note that different NMDA agonists have different effects. For example, glutamate is the most powerful NMDA agonist. Yet no one does well by ingesting excess glutamate, such as MSG. Yet many people do well on Provigil, which is another NMDA agonist. Provigil also helps in the production of ATP in the mitochondria, which undoubtedly contributes to its beneficial effects.

NMDA agonism in and of itself does not provide lasting benefits. But if combined with treatments that address the fundamental energy deficit in ME/CFS, it can provide impressive symptomatic relief. (Provigil helped me lead a near-normal life for over eight years.) However, many people are too sensitive to tolerate any NMDA agonists at all, and for these people, such drugs can easily worsen their condition.
I still can't tell though what is autonomic dysfunction versus my cells cannot make energy at a mitochondria level when I do any exertion and therefore cannot breathe.
Fortunately, magnesium addresses both problems simultaneously.
Like Sidereal I have experienced a distinct sensation of weakness in the chest. Also some chest pain and tachycardia (but only after a bronchitis). And magnesium does help - no chance of a mistake.
The symptoms of CNS depression and dysautonomia can be very similar, and this is where it can get confusing. The former is made worse by extra magnesium, while the latter is improved by adding magnesium.

CNS depression is not a typical symptom of ME/CFS, and in all the cases we've been talking about, it's been caused by excess magnesium intake. So I think it's quite safe to say that breathing problems experienced by someone who is not supplementing their magnesium are not a symptom of CNS depression. In these cases, such as @A.B.'s, proper magnesium supplementation will typically help (as he found).
I don't know how much I'm taking, about a teaspoon full of magnesium sulfate. I'm guessing that's about 1g?
One teaspoon of magnesium sulfate is 1.5 grams. The effect it has depends on the method of administration. How are you taking it?
@Gingergrrl - In that kind of situation, my symptoms tend to be more localized - to my arms in your example, as well as contributing to overall exhaustion and PEM to one degree or another. My lung symptoms seem to have become part of low level background noise in the past year or so, but when they're more noticeable they can remain so for weeks or more and have tended to be at least as bad when I lie down as any other time.
Due to the near universal magnesium deficiency in our population, as noted by Dr. Myhill, I think that at least some of your problem can be attributed to lack of magnesium, and that a gradually increasing magnesium therapy would be something that would be very worthwhile to try. I would expect it to help significantly.
My weakness only got that bad if I tried supplementing something that forces energy production on a system that can't handle it, stuff you see people here frequently keeling over from, like methylfolate, methyl B12, CoQ10, D-ribose etc.
As I noted in my previous post, a hypersensitivity to magnesium as you have described is typically indicative of a severe magnesium deficiency. Due to the hypersensitivity of the NMDA receptors that this implies, this can result in hypersensitivity to all sorts of drugs and supplements, including all the ones you list.

@Sidereal, as yours is a rather complex case, we should probably talk more about this via PM.
 
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Gingergrrl

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@SOC if we start a new thread, how do I quote from the old thread into the new thread? I am temporarily not at home with access to my regular computer so probably will not figure it out!
 

Gingergrrl

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Okay, I will try it and was asking the questions in order to create the new thread (to get this one back on topic) so hoping to solve this problem if I can!
 

Gingergrrl

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Drop me a PM when you get the new thread created and you and I can come back here and delete these last few OT posts.
@SOC I created a new thread titled "Dysautonmia, shortness of breath, and Magnesium." I put this here so others can find it but I will send you a PM too.
 

WillowJ

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I didn't see the same kind of "this study doesn't meet criteria for being a 'worthy' study to be included" way of sorting out papers like was done in P2P and in other EBM reviews. Instead they just said it was a difficult field due to low funding & etc., lots of studies were small, and said what the specific limitations of the studies were as they reviewed them.
Evidently they did exclude a lot of studies due to poor quality. Yet they did include some small studies, case-control studies, etc. And they did include some that covered sleep problems, cognition problems,