New Dr Snell paper on exercise and CFS

[Bob]

Just read Firestormm's post on Jennie's blog, and noticed an interesting point that I hadn't picked up on before:
"What of other diseases for whom patients report similar feelings of a general ‘worsening’ of symptoms post-exertion? Does the above serve to make PEM unique to ME? Does it even have to?"

Dr Snell only compared CFS patients to healthy controls, and did not compare against any other diseases.
(Perhaps the significance of this is obvious, but I can be a bit slow on the uptake sometimes!)
So we don't actually know if the results are unique to CFS patients.
The tests might be able to distinguish CFS patients from healthy people, but may not necessarily distinguish CFS from other illnesses.
More research needed, as always!

 

[Firestormm]

Bob you mean she published my comments! Oh crap

 

[Bob]

Bob you mean she published my comments! Oh crap

 

[alex3619]

o

Just read Firestormm's post on Jennie's blog, and noticed an interesting point that I hadn't picked up on before:
"What of other diseases for whom patients report similar feelings of a general ‘worsening’ of symptoms post-exertion? Does the above serve to make PEM unique to ME? Does it even have to?"

Dr Snell only compared CFS patients to healthy controls, and did not compare against any other diseases.
(Perhaps the significance of this is obvious, but I can be a bit slow on the uptake sometimes!)
So we don't actually know if the results are unique to CFS patients.
The tests might be able to distinguish CFS patients from healthy people, but may not necessarily distinguish CFS from other illnesses.
More research needed, as always!

More research is indeed need, as always. Its almost my mantra. However they have vast experience at testing other diseases involving cardiopulmonary dysfunction. This is a standard test. What is not known is how this goes with non-cardiopulmonary diseases, like MS.

 

[biophile]

Was there a strong correlation shown between objective measures and subjective reports of post-exertional symptoms?

Non-cardiopulmonary disease controls are not good enough on their own, I also want to see chronic depression and chronic anxiety controls too. No matter what biological difference are found between CFS and healthy sedentary controls and select disease controls, someone will always come along and suggest that the same findings could be psychosomatic and found in those experiencing psychological stress and psychiatric morbidity, or that CFS is an extreme form of burnout.

Even then some people would not be satisfied, as it will then be (has already been) argued that idiopathic chronic fatigue itself is an interdependent psychiatric category in its own right along side anxiety and depression. So, (obviously) more research also needs to be done on what exactly is causing the dramatic drop in performance.

 

[Firestormm]

biophile and as we said earlier this needs to be carried out as a longitudinal study I think. Can people recover sufficiently to perform the test on day 3, day 4, day 12 etc.

Not sure we can include everybody in such a study we might like to - but more can certainly be done.

Mind you I much prefer subjecting our cells to this kind of testing than our entire bodies. As Alex said I think above - Julia Newton's muscle gym is a beginning in this respect.

If that is enough to demonstrate the same then great. I can see a relatively simple test being performed at the point of diagnosis. But I doubt very much it will be able to test the range of abnormalities that this kind of exercise testing can - at least not perhaps on muscle cells alone.

And anyway - for this to work and be objective wouldn't a possible diagnosee have to be tested constantly - or can it be assumed that once is enough and that the other symptoms will be sufficient to diagnose ME?

Interesting and thought-provoking thread

 

[alex3619]

Was there a strong correlation shown between objective measures and subjective reports of post-exertional symptoms?

Non-cardiopulmonary disease controls are not good enough on their own, I also want to see chronic depression and chronic anxiety controls too. No matter what biological difference are found between CFS and healthy sedentary controls and select disease controls, someone will always come along and suggest that the same findings could be psychosomatic and found in those experiencing psychological stress and psychiatric morbidity, or that CFS is an extreme form of burnout.

Even then some people would not be satisfied, as it will then be (has already been) argued that idiopathic chronic fatigue itself is an interdependent psychiatric category in its own right along side anxiety and depression. So, (obviously) more research also needs to be done on what exactly is causing the dramatic drop in performance.

I both disagree with this and agree with this, for different reasons. At some point the medical world will wake up and realize that this test shows a marked abnormality in ME, and it does not matter if it is or is not diagnostic, it explains our problems. At that point the psychs will only have comorbid illness claims left to them, which they may claim no matter what the testing in ME shows.

In one sense psychogenic proponents will always find things they want to claim - as you exclude one thing, they will claim others. Thats the history of this going back to the nineteenth century. Historically they have been proved wrong time and time again, and have yet to be proved right once, but it doesn't stop them. Its like a fanatical cult: reason, evidence and repeated failure doesn't seem to reach them. Moreover this cult is deeply entrenched in western culture: we have to change the culture to prevent the cult from influencing medical treatment.

I don't know that I consider patients with anxiety as desirable controls, but I consider MS, RA and depression to be desirable controls. This in part comes down to money though - the more control groups you have the higher the cost if you want a statistically significant size to those groups. Once this is done enough then at some point anyone wanting to claim that disease X is the same, then will have the burden of proof on them: they have to do the study comparing the two. Since by that time there will be established protocols and methodologies in place, anyone using substandard protocols and methodologies will stand out. They will not have credibility unless they can establish their methods as better.

One thing that might work in our favour is a change in general medical research. As these findings about exercise and ME become more widely known, researchers in other disorders might do pilot studies to see if this kind of thing applies to those disorders. So RA, MS etc. might well be studied. So might many other conditions. The burden of establishing evidence might shift from ME researchers, to those investigating other diseases.

In addition the VO2max test and performance drop are only some of the changes we are seeing. Other findings may well be compared to this, like increased muscle lactic acid. If those patients showing exercise abnormalities also show other characteristic abnormalities, then the specificity and usefulness of alternative tests will be more easily validated. In time I am guessing we will wind up with combination tests, and then as the science evolves a specific test or test schedule will develop.

 

[Bob]

This is an interesting study that WillowJ posted on another thread.
It looks at post-exertional 'haematic lactate' levels in patients with polymyositis and dermatomyositis.
I don't know anything about those illnesses, but it says that they are "inflammatory and autoimmune skeletal muscle disorders characterized by reduced muscle strength, fatigue and myalgia."
It goes on to say: "metabolic alterations such as an impairment of oxidative metabolism seem to be responsible for the disability in the chronic phase of the disease."
So they seem to have some similarities to ME, and perhaps these are illnesses that might have similar results in CPET tests to CFS/ME patients?

'Haematic lactate' seems to be a measure of lactic acid in the blood.
So, considering Julia Newton's study, it might be appropriate to measure 'haematic lactate' levels in (the blood of) CFS/ME patients after exercise.
Perhaps this might give useful or interesting results after just one exercise test?
I wonder if anyone has done any research in this area on CFS/ME patients?

Wikipedia states that L-lactate is an alternative term for lactic acid, and says that, during 'power exercise' "lactate is produced from the pyruvate faster than the tissues can remove it, so lactate concentration begins to rise"; "It does not increase in concentration until the rate of lactate production exceeds the rate of lactate removal", and "The concentration of blood lactate is usually 1–2 mmol/L at rest, but can rise to over 20 mmol/L during intense exertion."

 

[MeSci]

This is an interesting study that WillowJ posted on another thread.
It looks at post-exertional 'haematic lactate' levels in patients with polymyositis and dermatomyositis.
I don't know anything about those illnesses, but it says that they are "inflammatory and autoimmune skeletal muscle disorders characterized by reduced muscle strength, fatigue and myalgia."
It goes on to say: "metabolic alterations such as an impairment of oxidative metabolism seem to be responsible for the disability in the chronic phase of the disease."
So they seem to have some similarities to ME, and perhaps these are illnesses that might have similar results in CPET tests to CFS/ME patients?

'Haematic lactate' seems to be a measure of lactic acid in the blood.
So, considering Julia Newton's study, it might be appropriate to measure 'haematic lactate' levels in (the blood of) CFS/ME patients after exercise.
Perhaps this might give useful or interesting results after just one exercise test?
I wonder if anyone has done any research in this area on CFS/ME patients?

Wikipedia states that L-lactate is an alternative term for lactic acid, and says that, during 'power exercise' "lactate is produced from the pyruvate faster than the tissues can remove it, so lactate concentration begins to rise"; "It does not increase in concentration until the rate of lactate production exceeds the rate of lactate removal", and "The concentration of blood lactate is usually 1–2 mmol/L at rest, but can rise to over 20 mmol/L during intense exertion."

Here's one on CSF lactate in people with CFS, anxiety and depression respectively but I can't see any mention of exercise:

http://www.ncbi.nlm.nih.gov/pubmed/20661876

and here is a related one:

http://www.cfids-cab.org/MESA/Mathew.pdf

This one states that high lactate can be assumed from the fact that the patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls:

http://www.translational-medicine.com/content/8/1/93

There is a seriously-weird one here that interprets a post-intervention decrease in systolic blood pressure and an increase in blood lactate, after graded exercise, as positive. I understand that most people with ME actually have trouble keeping their bp UP rather than down (although I am an exception):

https://www.mja.com.au/journal/2004...rial-graded-exercise-chronic-fatigue-syndrome

You may find more if you do a word search of the huge file of research abstracts that can be downloaded here:

http://www.meresearch.org.uk/information/researchdbase/ResearchPublications1956-2012.pdf

as I did.

 

[urbantravels]

Bear in mind that the Pacific Fatigue Lab Workwell Foundation (dang, I keep forgetting this) has very little money. They are not in a position to conduct multiple-arm studies of patients with multiple other conditions. I don't know the ins and outs of their funding situation, especially now that they're no longer supported by the University of the Pacific.

Other groups are using the two-day Stevens Protocol in other studies, which is all to the good. I think it is not practical to write up a lengthy list of other conditions that we'd like to prove we don't have, and try to eliminate them all based on this method. Perhaps major depression would be the one condition I'd pick for a direct comparison, simply because that is one of the top misdiagnoses that ME/CFS patients are labeled with, if not #1.

I can't dig up the Snell et. al. papers at this moment but I believe they reference other CPET studies for other conditions. Whether the CPET results obtained in other studies are directly comparable to the Stevens Protocol results I cannot say.

 

[WillowJ]

This is an interesting study that WillowJ posted on another thread.
It looks at post-exertional 'haematic lactate' levels in patients with polymyositis and dermatomyositis.
I don't know anything about those illnesses, but it says that they are "inflammatory and autoimmune skeletal muscle disorders characterized by reduced muscle strength, fatigue and myalgia."
It goes on to say: "metabolic alterations such as an impairment of oxidative metabolism seem to be responsible for the disability in the chronic phase of the disease."
So they seem to have some similarities to ME, and perhaps these are illnesses that might have similar results in CPET tests to CFS/ME patients?

'Haematic lactate' seems to be a measure of lactic acid in the blood.
So, considering Julia Newton's study, it might be appropriate to measure 'haematic lactate' levels in (the blood of) CFS/ME patients after exercise.
Perhaps this might give useful or interesting results after just one exercise test?
I wonder if anyone has done any research in this area on CFS/ME patients?

Wikipedia states that L-lactate is an alternative term for lactic acid, and says that, during 'power exercise' "lactate is produced from the pyruvate faster than the tissues can remove it, so lactate concentration begins to rise"; "It does not increase in concentration until the rate of lactate production exceeds the rate of lactate removal", and "The concentration of blood lactate is usually 1–2 mmol/L at rest, but can rise to over 20 mmol/L during intense exertion."

thanks.

yes, I thought that was interesting also. From the (very limited) information in that study, it seems unlikely they would have similar (repeat) CPET results because the 4 people they tested with exercise appeared to improve in lactate levels in these myopathies. of course 4 isn't much to go on.

I posted it for comparason, e.g. using objective testing, and because, as you mentioned, some of the theory might be applicable (oxidative damage theory, and the same kind of lactate testing; MeSci found one paper with blood lactate reported increased [my guess is that the authors know nothing and thought this was good because it was evidence of the patients doing more, not realizing it meant their bodies couldn't cope, physiologically, with doing more] and I think Dr. Myhill's work might show this kind of blood lactate increase also, though I didn't double check). It would be nice to get the full text of the paper on inflammatory myopathies.

 

[alex3619]

One of the issues with blood lactate is that it is a sign of a problem, but not the cause of the problem. Some might well respond to exercise, but others with a different cause might not. However even the Workwell Foundation ( urbantravels I have the same problem with the old name you do, and a similar issue with PHANU - darn, whats the new name again?) use exercise to improve patients, they just use it according to established exercise principles - always work under the AT and have plenty of rest. In us the AT is so low that the exercise has to be kept very very light, and not increased at any kind of rate that would resemble graded exercise.

 

[Bob]

Looks like Dr Enlander is doing interesting post-exertional tests in his exercise study:
https://www.facebook.com/PANDORAORG/posts/10151444436882371

"The study requires exercise on a stationary bicycle for 25 minutes on a Monday (approx 2 hours total in the hospital by the time all the bookwork is done) , blood is drawn on Tuesday, Wednesday and Thursday mornings (approx 30 mins) The study will demonstrate the effect of exercise on the ME CFS patient, confirming or denying the PACE report that exercise GET is a good treatment of ME CFS. In my opinion this is a most important study related to the PACE report."

 

[SOC]

"The study requires exercise on a stationary bicycle for 25 minutes..."

I did maximal exercise testing and I wasn't on the bike anything like 25 mins. I don't think I could do 25 mins now, even though I'm doing a lot better.

 

[Bob]

I did maximal exercise testing and I wasn't on the bike anything like 25 mins. I don't think I could do 25 mins now, even though I'm doing a lot better.

Perhaps they don't require maximal exercise for the whole 25 mins. They might be doing some submaximal testing, and perhaps some time might be spent calibrating the equipment?

 

[WillowJ]

Looks like Dr Enlander is doing interesting post-exertional tests in his exercise study:
https://www.facebook.com/PANDORAORG/posts/10151444436882371

"The study requires exercise on a stationary bicycle for 25 minutes on a Monday (approx 2 hours total in the hospital by the time all the bookwork is done) , blood is drawn on Tuesday, Wednesday and Thursday mornings (approx 30 mins) The study will demonstrate the effect of exercise on the ME CFS patient, confirming or denying the PACE report that exercise GET is a good treatment of ME CFS. In my opinion this is a most important study related to the PACE report."

they are looking for healthy controls in the area, if anyone has contacts there.

 

[Ember]

Dr. Snell explains in the videos below that a range of conditions have been assessed for disability in their lab, including CFS, FMS, Lyme, Thyroiditis, Neurocognitive dysfunction, Multiple chemical sensitivities, HHV6, Low back pain, Autoimmune collagen disorder, HIV, Crohn's Disease, Multiple Sclerosis, Undifferentiated autoimmune disease, Sarcoidosis, Chronic active EBV, Spasmodic dysphonia, Sjogren's disease, POTS/orthostatic intolerance, Toxic chemical exposure and Congestive heart failure.

So far, exercise intolerance has been demonstrated only in CFS patients. In an experiment that employed a single-subject design and included a low-functioning CFS patient, a high-functioning CFS patient, a sedentary control, an active control, an MS patient and an immuno-deficiency (HIV) patient, a decrease in oxygen-consumption function, workload capacity and ventilation was found during the second-day test only in the CFS patients.

“Cardiopulmonary exercise testing can clarify the etiology of exercise intolerance and unexplained dyspnea in patients with multiple chronic comorbidities,” according to Dr. Snell. “Certainly with ME," he says, "you can come up with an autonomic subgroup and an immune subgroup” for research purposes.

A sample report states that the findings are “inconsistent with deconditioning, poor effort or primary depressive disorder.” Oxygen use is measured via expired gas exchange indicating oxygen utilization at the cellular level, i.e., mitochondria. Results are used to confirm diagnosis, identify systems with abnormal function, rule out cardiac and pulmonary reasons for fatigue, determine if treatments are objectively improving functional capacity and provide guidance on activity management programs using ATHR with an HR monitor:

 

[biophile]

Is there an equivalent serial stress test for neurocognitive function? There may even be a shared mechanism.

 

[Simon]

Is there an equivalent serial stress test for neurocognitive function? There may even be a shared mechanism.

Amazingly - given the huge issue with fatigability in this illness - no one really seems to have tried. Most studies focusing on patients vs controls without stressing

Rayhan and Baraniuk measured cognitive function after a repeat 2-day exercise test (like Snell) - and found no difference in cognitive performance, though they did find some evidence of different brain activation in GWI patients (who also met CFS criteria) vs controls post-exercise. See this blog. (Cognitive performance was worse in patients, but no different before/after exercise).

A very interesting study in 2011 found that for CFS patients with POTS, cognitive performance was normal when supine but declined with increasing tilt angle. A follow-up study last year found evidence this was due to problems with brain blood flow.

I think the fatigability and PEM with both mental and physical tasks might be unique to ME, and i've always wondered if there was a common mechanism. do hope someone will try to find outl

 

[alex3619]

Is there an equivalent serial stress test for neurocognitive function? There may even be a shared mechanism.

A few years ago at CFSAC they were using a three hour neurocognitive battery of tests. I think combining a shorter test with repeat exercise, or just two neurocognitive tests two days running might lead to interesting results.