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New paper: Inability of ME patients to reproduce VO2 max indicates functional impairment

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Exercise intolerance is present in hundreds of disorders. It usually shows up on day one of CPET. To date only ME and CFS patients, with the exception of one HIV patient, are clearly known to have the massive day two crash. I think there might have been two healthy controls who have shown a crash though ... but they might have undiagnosed (subclinical) CFS or ME.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Post concussion syndrome is new to me. I was aware of GWI, its why I want them included in testing. Of course its also possible GWI is similar to, or even just a symptom variant of, ME.

I appreciate its not the 2 day CPET but here's a few links on GWI :

The Baraniuk brain study which should be familiar (not the paper)

http://www.medicalnewstoday.com/articles/262010.php

Autonomic dysfunction supports self reported post exertional 'fatigue' in GWI

http://journal.frontiersin.org/Journal/10.3389/fnins.2013.00269/full

Its difficult to pick out one specific paper for post concussion syndrome. One recent development is the use of early exercise to prevent acute concussion developing into post concussion syndrome which sounds like GET but the key to the approach in PCS is that its individually tailored with the primary intention of avoiding (not ignoring) aggravating symptoms.

This is a general overview of post concussion syndrome but touches on symptoms following exertion (bottom of page 7 - can't copy and paste from this document). On a more general note there are many similarities between this syndrome and ME/CFS not least that when you fail to recover 'as expected' then predisposing usually 'personality' factors start entering the discussion.

Postconcussion Syndrome: A Physiatrist’s :)Approach

http://now.aapmr.org/PMRJournals/201110_S396_PostconsussionSyndromeAPhysiatrists.pdf
 

SOC

Senior Member
Messages
7,849
Do Sjorgen's and Lupus not include PEM?
I didn't think we were totally exclusive on this.
I have seen no indication that PEM is a feature of either Sjogren's or Lupus. Fatigue, yes. Exercise intolerance, maybe. PEM is neither of those.

Nevertheless, it would be advantageous to all patients of fatiguing illnesses to do research using 2-day CPET to determine whether the decline after exercise is present.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
I appreciate its not the 2 day CPET but here's a few links on GWI :

The Baraniuk brain study which should be familiar (not the paper)

http://www.medicalnewstoday.com/articles/262010.php

Autonomic dysfunction supports self reported post exertional 'fatigue' in GWI

http://journal.frontiersin.org/Journal/10.3389/fnins.2013.00269/full

Its difficult to pick out one specific paper for post concussion syndrome. One recent development is the use of early exercise to prevent acute concussion developing into post concussion syndrome which sounds like GET but the key to the approach in PCS is that its individually tailored with the primary intention of avoiding (not ignoring) aggravating symptoms.

This is a general overview of post concussion syndrome but touches on symptoms following exertion (bottom of page 7 - can't copy and paste from this document). On a more general note there are many similarities between this syndrome and ME/CFS not least that when you fail to recover 'as expected' then predisposing usually 'personality' factors start entering the discussion.

Postconcussion Syndrome: A Physiatrist’s :)Approach

http://now.aapmr.org/PMRJournals/201110_S396_PostconsussionSyndromeAPhysiatrists.pdf

As concussion can be associated with damage to the blood-brain barrier and notably to the pituitary gland, the symptoms and signs would appear likely to resemble ME. Indeed, maybe head trauma (even mild) could be a cause of ME in some people. There has been a little discussion of this in other threads.
 

SOC

Senior Member
Messages
7,849
I agree absolutely, @SOC that all "fatigue" related illnesses should be studied using the 2 day test - to be absolutely sure that is is or isn't specific to ME. :thumbsup:
Maybe that will happen someday, but I doubt it. Unless there's clinical evidence of post-exercise exacerbation of symptoms, there's no motivation for anyone to study it. Exercise intolerance intolerance is a different beast and is already studied in conditions where it exists.
 

bambi

Guest
Messages
56
This is a very important paper. It is not only about exercise intolerance, but actually points to the cause of exercise intolerance, heart (muscle inflamation), low oxygen - muscle and a loot more. Keep this paper close. Very important piece of the puzzle indeed.
 

SOC

Senior Member
Messages
7,849
This is a very important paper. It is not only about exercise intolerance, but actually points to the cause of exercise intolerance, heart (muscle inflamation), low oxygen - muscle and a loot more. Keep this paper close. Very important piece of the puzzle indeed.
I know I'm repeating this over and over, but I think it's important that we patients make this distinction. PEM is NOT exercise intolerance.
Exercise intolerance (functional aerobic impairment) is defined as an abnormally low Vo2max. This can occur with any factor that affects one or more of the four variables of the Fick equation that determine Vo2max: a reduction in maximal heart rate, maximal stroke volume, or maximal Cao2; or an increase in rest Cvo2.

This paper is not about an abnormally low VO2max on a single CPET (exercise intolerance). It is about the inability to reproduce VO2max and other measures on the second day CPET. This is the feature that, so far, sets us apart from all other illnesses and is likely, therefore, to be diagnostic.

Exercise intolerance is an known symptom of a number of different conditions for which graded exercise is often (not always) prescribed. Treatments for exercise intolerance are not necessarily appropriate for PEM.

We patients need to be careful that we properly characterize this feature of our illness or we will perpetuate a number of damaging misconceptions about our illness.
 

NK17

Senior Member
Messages
592
How many of us reading this thread had the 2 days CEPT?

I really wanted to do it last summer, but my ME dr. advised me against it and told me to save every penny.

Now I regret not doing it back then when I was way more "functional". Doing it now would be pure suicide ;(.
 

Kati

Patient in training
Messages
5,497
What is the current situation with Dr Unger and 2 day CPET? Does this paper give us leverage?
OTH

i have maintained that doing one day VO2max test would give an opportunity to the CDC to say I am just deconditioned. i am hoping that after many delays, 2 days will be the protocol. Going to the clinic will set me back 1000$ (and a prolonged relapse) so it's better be worth it.
 
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bambi

Guest
Messages
56
I know I'm repeating this over and over, but I think it's important that we patients make this distinction. PEM is NOT exercise intolerance.


This paper is not about an abnormally low VO2max on a single CPET (exercise intolerance). It is about the inability to reproduce VO2max and other measures on the second day CPET. This is the feature that, so far, sets us apart from all other illnesses and is likely, therefore, to be diagnostic.

Exercise intolerance is an known symptom of a number of different conditions for which graded exercise is often (not always) prescribed. Treatments for exercise intolerance are not necessarily appropriate for PEM.

We patients need to be careful that we properly characterize this feature of our illness or we will perpetuate a number of damaging misconceptions about our illness.

I agree with you that we should differentiate. And I agree with you that they are differences between PEM , PENNE and exercise intolerance and the probable causes and mechanism to each. I don't agree that this study will ONLY useful to aid diagnosis and it does not set us apart from other illnesses. The opposite is true, it will place us with in a range of disease which not previously considered to be relevant to me. You will see - things will fall into place.
 

SOC

Senior Member
Messages
7,849
I agree with you that we should differentiate. And I agree with you that they are differences between PEM , PENNE and exercise intolerance and the probable causes and mechanism to each. I don't agree that this study will ONLY useful to aid diagnosis and it does not set us apart from other illnesses. The opposite is true, it will place us with in a range of disease which not previously considered to be relevant to me. You will see - things will fall into place.
I do not suggest that it will ONLY be useful for diagnosis. This research has value in understanding the nature of the illness and consequently politics as well. It will be important for developing treatments. It is critical for disability evaluations. I'm sure there are many more ways this research will be useful.

Why do you say this does not set us apart from other illnesses? Do you know of other illnesses that show a decrease in multiple measures on the second day CPET testing?

What do you mean by "place us with in a range of disease which not previously considered to be relevant to me"? I don't understand this phrase. Do you mean it will show that we belong in a known already established illness group? If so, which one?
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
As concussion can be associated with damage to the blood-brain barrier and notably to the pituitary gland, the symptoms and signs would appear likely to resemble ME. Indeed, maybe head trauma (even mild) could be a cause of ME in some people. There has been a little discussion of this in other threads.

In the case of post concussion syndrome we at least know unambiguously what the trigger was - an initial 'mild' traumatic brain injury but only a minority then go on to develop the syndrome after the point where the initial injury should have healed and neuroinflammation 'should have' ceased. This suggests to me that there may be an increased tendency to develop sustained neuroinflammation in some individuals and this appears to be the case as regards gene polymorphisms and microglial activation.

The fact that a constellation of symptoms closely resembling those that lead to a diagnosis of ME/CFS can result in the absence of infection suggests to me that an initial or continuing infection isn't necessary for a 'state' such as ME/CFS to develop.

Microglia are the critical convergence point for the many diverse triggers that elicit an adaptive immune response (Figure 1). Stroke, hypoxia, and trauma compromise neuronal survival and indirectly trigger neuroinflammation as microglia become activated in response to the insult in an attempt to limit further injury. Infectious agents activate microglia either through damage to infected cells or direct recognition of foreign (viral or bacterial) proteins. Following exposure to neurotoxins such as the mitochondrial complex I inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the dopamine analog 6-hydroxydopamine (6-OHDA), or the pesticide paraquat, microglia become activated and primed. Microglial responses to these toxins may contribute to neuronal dysfunction and eventually hasten neurodegeneration (Czlonkowska et al., 1996; Kohutnicka et al., 1998; Liberatore et al., 1999; Dehmer et al., 2000; Vila et al., 2001). In addition, genetic mutations that give rise to increased production of toxic oligomeric, aggregated/truncated, or oxidized protein species promote sustained activation of microglia and may prime the immune system for aberrant responses to subsequent insults. Regardless of the initiating factor, all of these external or internal stimuli have the potential to trigger a self-perpetuating inflammatory response that, if left unresolved, may contribute to death of vulnerable neuronal populations.

(my bolding).


http://www.molecularneurodegeneration.com/content/4/1/47
 

beaker

ME/cfs 1986
Messages
773
Location
USA
I know I have posted this before in some long ago thread on the matter, but I think it bears repeating. Or at least it helps me vent;-)
This work was done -- perhaps not to the degree of specificity-- but the 2 day tests were done and data collected 25+ years ago by HEM{or whatever incarnation of their company name is now}
It was done on the Ampligen patients. At least on the early studies. All that data is sitting in some box in storage somewhere. A shame they don't pull it up and analyze it and share it. Shame nothing was done w/ it all those years ago. The focus was on approval via the shortest route, and no one was paying attention. Heck not many are now.
Where are the WSJ articles ? Where is the NYT ? It's not as sexy as mass hysteria, yuppie flu or XMRV, but it's damned important.
 

beaker

ME/cfs 1986
Messages
773
Location
USA
@beaker, do you have a reference for 2 day CPET 25 years ago? OR was it just exercise testing? What was measured?

I have my own test results, that's it. I'd have to dig out the papers to tell you every little thing on it.
They measure anaerobic threshold, the various gas exchange stuff, it was on treadmill. how long lasted how long to exceed AT, HR, BP that sort of thing. And they did a second day test. Doesn't really sound any different from what I understand these tests to be.
They also retested half way mark of the study and at the end of the study.
And yes, they had sedentary controls. At least in the very beginning of the study they did. But it wasn't blinded. Physiologist came in and did the initial testing/set it up . Then later the clinic staff took over.

Maybe the Investigators{Cheney, Peterson} would have some of that. They were using it as a marker for Ampligen efficaciousness. But they sure knew enough to do a 2 day.

I guess I just get upset at all the wasted time. Half my life, ya know ? Yes. I 'm sure you do.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
I have my own test results, that's it. I'd have to dig out the papers to tell you every little thing on it.
They measure anaerobic threshold, the various gas exchange stuff, it was on treadmill. how long lasted how long to exceed AT, HR, BP that sort of thing. And they did a second day test. Doesn't really sound any different from what I understand these tests to be.
They also retested half way mark of the study and at the end of the study.
And yes, they had sedentary controls. At least in the very beginning of the study they did. But it wasn't blinded. Physiologist came in and did the initial testing/set it up . Then later the clinic staff took over.

Maybe the Investigators{Cheney, Peterson} would have some of that. They were using it as a marker for Ampligen efficaciousness. But they sure knew enough to do a 2 day.

I guess I just get upset at all the wasted time. Half my life, ya know ? Yes. I 'm sure you do.

Can anyone get the full text for this paper, or is it perhaps already in the 'filled paper requests' thread? I wonder whether the info is in there. If not, someone could ask in this thread.