Cook, Light, Light, Broderick et al: Neural Consequences of Post-Exertion Malaise in ME/CFS

mango

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Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Dane B. Cook, Alan R. Light, Kathleen C. Light, Gordon Broderick, Morgan R. Shields, Ryan J. Dougherty, Jacob D. Meyer, Stephanie VanRiper, Aaron J. Stegner, Laura D. Ellingson, Suzanne D. Vernon

Highlights
  • Acute exercise affects symptoms, cognitive performance and brain function in ME/CFS.
  • Symptom provocation by exercise is a useful model to study post-exertion malaise.
  • Objective neurophysiological evidence of the phenomenon of post-exertion malaise.
Abstract
Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored.

The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging.

Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 minutes of submaximal exercise (70% of peak heart rate) on a cycle ergometer.

Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 hours following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping.

Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05).

For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan.

For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices.

Changes in brain activity were significantly related to symptoms for patients (p<0.05).

Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.


http://www.sciencedirect.com/science/article/pii/S088915911730051X
 

Mohawk1995

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Here is a separate link: http://dx.doi.org/10.1016/j.bbi.2017.02.009

Because cognitive functions are only the tip of the ice berg (maybe 10% of brain resources), one has to wonder what deeper subconscious and "nonconscious" neurophysiological processes are impacted? When we can tie the threads that connect neurophysiology to biochemistry to metabolism to hormonal factors to genetics and ultimately functional expression of these factors we will be well on the road to defeating ME. This is yet another step in that direction in my opinion.
 

RogerBlack

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If you want to induce PEM, do the exercise two days in a row. Everything becomes much more obvious after the second day.
And may also cause in some people long-term reduction in ability. Working-> not. Not working -> housebound. Housebound-> bedbound.

This is not to say I quite disagree with a study that may cause some of the trial participants long term disability.
But getting meaningful consent, or even working out the likelyhood of that is hard.
I guess CEPT performed twice has been done on other studies.
 

*GG*

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If you want to induce PEM, do the exercise two days in a row. Everything becomes much more obvious after the second day.
Sure does, why I don't usually exercise 2 days in a row!

GG
 

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Daisymay

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CPET is 1949 technology. Neuroimaging of the kind that might be useful really dates from some time in the 70s, but has improved since then.
It's very shocking when you think how much further forward research should have been in the understanding of ME.

OK we wouldn't have had metabolomics and the more recent immunological testing etc BUT we could have been legitimately physically ill, not subjected to the psychiatric paradigm and all the physical, mental and emotional abuse that comes with that.
 

*GG*

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It's very shocking when you think how much further forward research should have been in the understanding of ME.

OK we wouldn't have had metabolomics and the more recent immunological testing etc BUT we could have been legitimately physically ill, not subjected to the psychiatric paradigm and all the physical, mental and emotional abuse that comes with that.
Yeah, whats up with those societies that lock up people with our illness, not very civilized :( That has not been my experience.

GG
 

Solstice

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It's very shocking when you think how much further forward research should have been in the understanding of ME.

OK we wouldn't have had metabolomics and the more recent immunological testing etc BUT we could have been legitimately physically ill, not subjected to the psychiatric paradigm and all the physical, mental and emotional abuse that comes with that.
Probably wouldn't be pretty much homebound if I had known more about this disease from the getgo. The amounts I've exercised and worked that were all to my detriment.....
 

ash0787

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I have this effect at the moment, I know what my limits are but sometimes I can't stop myself from trying VR games, did this one for 3 hours ( standing up ) https://gfycat.com/SelfishRealGnat
and 2 days on I feel like my IQ has dropped 50 points and all I want to do is watch really stupid videos on youtube.

Its annoying because I bought into the VR idea before 99% of people and now everything seems to be slowly moving in that direction but I cant make proper use of it or give it a fair assessment.

https://uploadvr.com/man-loses-50-pounds-playing-soundboxing/
 
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Many of you already know this, but this study also demonstrates that the symptoms and cognitive defects are not due to accumulation of lactate.
Could you explain why the issues couldn't be due to lactate? I find this very interesting and I want to understand it better.
 
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Could you explain why the issues couldn't be due to lactate? I find this very interesting and I want to understand it better.
I should probably clarify to say the differences are not due to accumulation of lactate in the muscles. The level of exertion was still (mostly) below the ventilatory threshold and there were no significant differences in amount of lactate between patients and controls.
 

BurnA

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Would it be accurate to say this study provides objective evidence that exercise cases an exacerbation of symptoms for ME patients?

Would it also support the claim that exercise should not be prescribed to or undertaken by ME patients?

There seems to be so many things measured objectively in this study that could easily have been done in any previous GET study. There is no excuse for future GET studies ( if there are any) not to include objective measurements of cognitive decline post exercise now.
 

Mohawk1995

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Would it be accurate to say this study provides objective evidence that exercise cases an exacerbation of symptoms for ME patients?

Would it also support the claim that exercise should not be prescribed to or undertaken by ME patients?

There seems to be so many things measured objectively in this study that could easily have been done in any previous GET study. There is no excuse for future GET studies ( if there are any) not to include objective measurements of cognitive decline post exercise now.
It would be accurate to state that 25 min of exercise at 70% of Peak Heart Rate causes an exacerbation of symptoms in a vast majority of ME patients. The sample size is too small to say all ME patients. At the same time, the significant discrepancy between ME and Control patients is startling. Any clinician considering GET with ME patients should look at this as a huge negative in pursuing this as an effective form of treatment.

There is enough (although again the sample size is small) support to say that any form of activity including "exercise" at this level should be pursued with extreme caution. Your second question appears to be based on an absolute statement. One thing about the practice and delivery of medicine is that there are very few if any absolutes.

Unfortunately it is not only the form of treatment that can create adverse affects on patients, it can also be how that form of treatment is delivered. GET as defined "is physical activity that starts very slowly and gradually increases over time." It is not just the "level of exercise" as demonstrated in this study. In fact, I would argue this study does not translate well to the actual definition of GET. GET or "Functional Restoration" as it has been used in Physical Rehab is well proven to be successful in other areas of medicine. It's application to ME is very questionable at best, although I would argue that it is more in how it has been applied or delivered that is most questionable.

The other question then becomes, what level of activity is a person with ME able to tolerate and would there be benefit in a "GET" program that spreads the "gradual" increase over weeks, months or even years? Because no one has studied this, there is not an answer as of yet. Although it is anecdotal, our experience was that once our son was able to tolerate an increase in activity, it required 3 years of gradual increase of activity to reach his level today (attending school and working in warehouse loading trucks).