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

[WillowJ]

Same here. Breathing muscles became weak next. I'd love to hear how the deconditioning hypothesis can account for that.

my breathing muscles also. and my neck muscles, which I use all the time. Pretty difficult for neck to be deconditioning.

 

[snowathlete]

The Nakatomi et al. PET study quoted was carried out on just 9 patients. I think it's pretty difficult to include something like that as a key part of your evidence review if you want the world to take you seriously. Not necesarily because the study isn't right, but because it's just too easy for people to attack.

I think if we could get that study replicated to 50 patients minimum, it would be a much stronger case that would hard to ignore. And I don't think there is any conspiracy here: I don't think it would be ignored if we got that. It's frustating because there is a lack of funds to get these studies going at all, and that's no doubt why the study quoted was just 9 people in the first place. But I do think we have to acknowledge that the reality of studies like this being so small is that it severely limits their strength as evidence for decision making purposes.

 

[Gingergrrl]

@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?

This is my #1 most debilitating symptom and is why I can no longer walk more than a few feet or carry anything. Today I had a horrible episode after lifting a plate of food. I should have stopped but proceeded to take a shower and became so short of breath any normal person would be going to the ER but I am used to it even though it is very scary.

Does this mean my breathing muscles are no longer working versus a cardiac or autonomic issue? My BP was actually good today so this was not the cause (although it is normally very low.)

Thanks for any info and I apologize this is off topic but three of you mentioned it so it must be a common part if the illness and I wish it had been mentioned in the report and criteria.

 

[alex3619]

Were any of the various criteria for ME/CFS tested before they were published?

To me it seems pretty normal for them to just publish whatever they think some committee thinks is worthwhile.

No, they were not. However, and this is the real key, neither were they operating under an "evidence based" mandate. That is a huge part of it. Also, they were published as research, and not proposed to be adopted without further ado.

Edit: I am writing about CCC and ICC, obviously. The exceptions were Holmes, Fukuda, Australian and Oxford definitions, which were rolled out without any testing. Look how they turned out. Its a mistake to not plan to initiate a serious validation protocol as part of any new definition.

The "evidence based" part was in the evidence review, and I suspect only patchily followed after that. For example, one key source of data that informed them was the CDC multisite study. Yet it cannot even be ranked on an EB hierarchy as its not even published yet!

The CCC became the defacto standard only because of more than a decade of use in research. It was not adopted overnight. SEID could be adopted rapidly, without full consideration.

Now after reflection I do not have any huge issues with the definition of SEID, though more than a few minor ones, and I don't care about the name (though a name change is premature, and ME is acceptable to me), but adoption of sweeping changes does need careful reflection and research over time by researchers, patients, advocates and doctors.

The biggest positive is we can use the report to support advocacy. The biggest negative is its premature to be sure it captures an accurate diagnostic protocol. I think Nancy Klimas got it right when she said the report was premature by a few years.

The research is changing the landscape fast. By 2017 we might know if Rituximab is what we hope it may be. We might find biomarkers, or even causative agents. Other treatments might get into phase 3 trials. Even one validated and robust diagnostic biomarker will change everything. All definitions will be up for review then. So will the name.

PS The core of science, to call something science, requires rigorous testing of the ideas. So at best the report is a collection of hypotheses. Its a position statement, with recommendations ... which is management. Its not science, but it uses scientific findings. The science part comes later when things get published in appropriate journals. Finally, anything derived by consensus is not scientific in itself. It needs validation, it needs to be tested.

 

[alex3619]

Does this mean my breathing muscles are no longer working versus a cardiac or autonomic issue?

We can get muscle weakness but I think there are many other factors leading to a feeling of shortness of breath, including neurologic, metabolic, vascular and autonomic issues.

 

[Esther12]

Any criteria is going to be a bit dodgy at the moment imo. Fair enough for people to be wary about them all, but I don't want to hold this one to a higher standard than others. Also, it did seem that they were open about the likelihood of change in the future, so this doesn't seem to be something that they are trying to set in stone.

 

[Sidereal]

@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?

This is my #1 most debilitating symptom and is why I can no longer walk more than a few feet or carry anything. Today I had a horrible episode after lifting a plate of food. I should have stopped but proceeded to take a shower and became so short of breath any normal person would be going to the ER but I am used to it even though it is very scary.

Does this mean my breathing muscles are no longer working versus a cardiac or autonomic issue? My BP was actually good today so this was not the cause (although it is normally very low.)

Thanks for any info and I apologize this is off topic but three of you mentioned it so it must be a common part if the illness and I wish it had been mentioned in the report and criteria.

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. I can't remember much from that period, it was death's door stuff.

If you're finding yourself with worsening weakness it may be due to magnesium from aggressive supplementation. At the time when this was happening to me if I took a quarter of a Mg pill I'd get severe muscle weakness and CNS depression lasting for like 12 hours.

 

[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?

Muscles actually weak, probably neurological. I did have shortness of breath but the key to this was sensation of the muscles being weak/ worn out. I will send more info to your inbox, as the details are probably off-topic in this thread.

I wasn't taking any supplements at the time, except maybe Vitamin D.

 

[alex3619]

it did seem that they were open about the likelihood of change in the future, so this doesn't seem to be something that they are trying to set in stone.

Yes, its one of the good things about the report. It will indeed need a review in only a few years.

 

[alex3619]

Fair enough for people to be wary about them all, but I don't want to hold this one to a higher standard than others.

I think we should hold this to a higher standard, and all further reviews. Its time. We had lower standards in the past because its the best we could do. That is changing. We need standards for definitions, research, reviews, recommendations, etc. If we ever want to see ME get fully researched we need to up our game, not operate by the standards of the past. This is particularly important if we want a medical specialty to adopt the illness.

If we had minimum research standards for example, would so much of the poor quality research (think PACE) ever be acceptable?

This is in part the problem with the neurological evidence. There is data. Its highly suggestive. It looks very very interesting. Yet there is, so far, insufficient robust evidence for most of it. This is a primarily a funding and resource issue as others have said. We have important evidence, we need those bigger and better designed studies!

What I do like about the research data on neurological issues is that study after study, using different methods, is finding things that seem to fit together with other findings. This is encouraging, its not proof.

 

[Esther12]

re higher standards for the development of criteria: given the current state of research, I'm a bit unsure how much can be done here. While there is so much uncertainty, any of the criteria could be of value if used responsibility. The trouble with something like Oxford is largely in the way it has been used.

 

[zzz]

@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?

This is my #1 most debilitating symptom and is why I can no longer walk more than a few feet or carry anything. Today I had a horrible episode after lifting a plate of food. I should have stopped but proceeded to take a shower and became so short of breath any normal person would be going to the ER but I am used to it even though it is very scary.

Does this mean my breathing muscles are no longer working versus a cardiac or autonomic issue? My BP was actually good today so this was not the cause (although it is normally very low.)

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

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. I can't remember much from that period, it was death's door stuff.

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).

 

[Gingergrrl]

@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?

 

[Sean]

That is the trick. It is NOT science. Its a managerial review.

In effect, but a firmly science based one.

The IOM is working the interface between science and politics, which is what we need.

I think Nancy Klimas got it right when she said the report was premature by a few years.

There is some truth in that, though whether it ends up being a significantly bad thing remains to be seen, and we can always say we should just wait for the next round of studies.

But more importantly, even if it was premature that is also now irrelevant. The report has been done and we have to deal with it as is, and use it as best we can.

If funding for biomedical studies increases substantially over the next 2-3 years, at least partly as a result of this report (plus the P2P and AHQR reports), will people still be saying we should have waited a few years?

 

[Sidereal]

The Nakatomi et al. PET study quoted was carried out on just 9 patients. I think it's pretty difficult to include something like that as a key part of your evidence review if you want the world to take you seriously. Not necesarily because the study isn't right, but because it's just too easy for people to attack.

Couldn't agree more. I'd just add that this sort of low-grade inflammation also occurs in disorders that are generally regarded as neuropsychiatric so it doesn't constitute evidence of "neurological abnormalities" being suppressed in the IOM report.

 

[alex3619]

The IOM is working the interface between science and politics, which is what we need.

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.

 

[taniaaust1]

The Nakatomi et al. PET study quoted was carried out on just 9 patients. I think it's pretty difficult to include something like that as a key part of your evidence review if you want the world to take you seriously. Not necesarily because the study isn't right, but because it's just too easy for people to attack.

I think if we could get that study replicated to 50 patients minimum, it would be a much stronger case that would hard to ignore. And I don't think there is any conspiracy here: I don't think it would be ignored if we got that. It's frustating because there is a lack of funds to get these studies going at all, and that's no doubt why the study quoted was just 9 people in the first place. But I do think we have to acknowledge that the reality of studies like this being so small is that it severely limits their strength as evidence for decision making purposes.

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.

 

[A.B.]

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?

 

[taniaaust1]

Yes, its one of the good things about the report. It will indeed need a review in only a few years.

Issue is, can we trust the government to do the review then. There is nothing to say that they wont put it off for however long they want to do so.

 

[alex3619]

Issue is, can we trust the government to do the review then. There is nothing to say that they wont put it off for however long they want to do so.

The issue is not just whether or not we can trust the government and agencies, its about trusting the process. This kind of process is for well developed areas of research. However for all we know in a few years we will have definitive studies. So its a concern, and something we need to watch as this all unfolds.

At least the P2P and IOM made clear there has been inadequate research.