What are seminal studies in ME research?

[Alvin2]

Since Dr Davis' research is unpublished you can add a section on current research linking some of his key videos

 

[Londinium]

Are you planning to include the important BPS studies or are you focussing on the seminal biomedical studies only? If the former, I think McEvedy & Beard (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700895/) is the first case of the psychiatric interpretation of ME labelling us all delicate flowers who don't have a real physical disease. It's also a great example of how easy and pernicious it is that a group of vulnerable patients can be labelled as mentally ill on nothing more than a hunch and have that interpretation accepted without question by the wider medical community.

 

[JoanDublin]

@ScottTriGuy - This is a great compendium of studies! Did you put this together?

A patient called Paul Watton from the UK put this together. It's a great little resource

 

[Forbin]

This 2014 brain study from Stanford University Medical School seems like something of a watershed, but I'm not sure about follow-up and replication.

Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome
http://pubs.rsna.org/doi/abs/10.1148/radiol.14141079

https://med.stanford.edu/news/all-n...bnormalities-in-chronic-fatigue-patients.html

Also, this 2011 paper by Komaroff, et al. was able to correctly identify patients and controls about 90% of time.

EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients-A case control study
https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-11-82

 

[arewenearlythereyet]

Have you covered off Intracellular magnesium @JamieS. I'm not sure of how much scientific credibility the below have but they might reference something more meaningful?

1 Howard J. Muscle action, trace elements and related elements: the myothermogram. In Chazot Gea; ed. Current Trends in Trace Element Research. Smith-Gordon, 1989

2 Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2:1-16.

3 Booth NE, Myhill S, McLaren-Howard J. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med. 2012;5(3):208-20.

4 Myhill S, Booth NE, McLaren-Howard J.
Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit. Int J Clin Exp Med. 2013;6:1-15.

 

[Londinium]

The only other comment I would have is whether it's possible to highlight which papers have been replicated successfully. There's a lot of papers out there that have interesting findings on ME/CFS but, due to the paucity of research in the field, have never been subject to attempted replication. As a lot of papers rely heavily on post-hoc subgroup analysis and/or are statistically underpowered, I do wonder how many studies can truly be considered seminal if they haven't been repeated elsewhere?

 

[RogerBlack]

I do wonder how many studies can truly be considered seminal if they haven't been repeated elsewhere?

Most of them haven't been directly replicated, due to reasons of funding mostly.
The ones that come closest are GET/CBT studies, but replication doesn't do much if you start out with a biased trial design.

 

[Londinium]

Most of them haven't been directly replicated, due to reasons of funding mostly.
The ones that come closest are GET/CBT studies, but replication doesn't do much if you start out with a biased trial design.

Agreed. Repeating a poorly designed trial gives equally poor results.

The closest I can find to properly replicated (or at least consistent) results is the work of Fluge & Mella, who have found similar findings in different cohorts. But even that will benefit from the UK or other trials planned by outside research teams to demonstrate the result is rigorous. Many of the studies listed here may well be seminal, but we should be cautious unless they are replicated elsewhere (e.g. I find a lot of the stuff from Ian Lipkin's lab fascinating, but it often relies on subgroup analysis and could really do with a validation cohort). Basically, because of funding and the general neglect from the medical research community, we don't know whether a lot of these papers are 'the answer' or are the result of fluke.

 

[Alvin2]

A pillar of science is reproducability, but with very limited resources we can either replicate what has been done or keep going forward, i wish we could do both but that will take a lot more money which we do not have.

 

[JaimeS]

I do wonder how many studies can truly be considered seminal if they haven't been repeated elsewhere?

NK cell work has been repeated like crazy. Got to get at least one of those in there.

 

[Jenny TipsforME]

Are there any seminal studies effectively demonstrating "ME is not deconditioning" ?

 

[Gemini]

NK cell work has been repeated like crazy. Got to get at least one of those in there.

@JaimeS great project, thanks for all your work! Apologies if you've already considered these...

NK research evolved from renowned immunologist Jay Levy's 1991 seminal study "Chronic Fatigue Syndrome: Clinical Condition Associated with Immune Activation"

https://ncbi.nlm.nih.gov/pubmed/1679864

As for general historic studies, the 1990 Ramsay "Myalgic Encephalomyelitis: A Persistent Enteroviral Infection?" study:

https://ncbi.nlm.nih.gov/pubmed/2170962

 

[RogerBlack]

Are there any seminal studies effectively demonstrating "ME is not deconditioning" ?

https://www.ncbi.nlm.nih.gov/pubmed/24456560 seems to be one, though I'm unsure how seminal it is.

CONCLUSION:
Low oxygen uptake by muscle cells causes exercise intolerance in a majority of CFS patients, indicating insufficient metabolic adaptation to incremental exercise. The high increase of the cardiac output relative to the increase of oxygen uptake argues against deconditioning as a cause for physical impairment in these patients.

https://www.ncbi.nlm.nih.gov/pubmed/23813081

The lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, the results from the second test indicated the presence of CFS-related postexertion fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in people with CFS. A second test might be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.

I don't understand this first sentence. Do they perhaps mean 'do not support' and it's a typo?
However, the finding that there is no significant difference for this group kind of ridicules the claim that it is deconditioning surely. Unless they mean by 'deconditioning' not classical deconditioning, but 'fear-avoidance-deconditioning loop, boom-bust and...'

 

[Jenny TipsforME]

@RogerBlack thanks. No I don't understand that first sentence either :thumbdown:

 

[jimells]

I don't understand this first sentence.

It means that a one-day exercise test can not discriminate between ME patients and deconditioned controls - it takes another exercise test on day 2 to see differences between the groups.


Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders.

This is the most important study I have read regarding my illness, because it informs treatment. I still have orthostatic hypotension, and ME, but no more hyperadrenergic POTS crashes since starting an anti-histamine.

 

[RogerBlack]

@RogerBlack thanks. No I don't understand that first sentence either :thumbdown:

Reading the actual paper, I can't find justification, though I've skimmed it.
Interesting facts popped out - the control group was 'sedentary' - 'not participating in a regular exercise program, or not accumulating more than 30 minutes or more of moderate physical activity on most days of the week'.

Despite this, there was no deconditioning found of Fuduka criteria CFS patients that was significant.

 

[RogerBlack]

It means that a one-day exercise test can not discriminate between ME patients and deconditioned controls - it takes another exercise test on day 2 to see differences between the groups.

I understand the rest of the paragraph.
However how does that

appear to support a deconditioning hypothesis for CFS symptoms.

when according to the deconditioning-symptoms-on-exercise-fear-avoidance hypothesis all patients with long-lasting CFS are in a fear-avoidance-deconditioning loop and therefore should be deconditioned.

My understanding of the BPS model is that the sole reason for perpetuating the symptoms is classical conditioning to avoid exercise due to this loop.

 

[JaimeS]

Are there any seminal studies effectively demonstrating "ME is not deconditioning" ?

Yes:

Vermeulen, R. C., & Vermeulen van Eck, I. W. (2014). Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome. Journal of Translational Medicine, 12, 20. http://doi.org/10.1186/1479-5876-12-20

 

[JaimeS]

https://www.ncbi.nlm.nih.gov/pubmed/24456560 seems to be one, though I'm unsure how seminal it is.

@RogerBlack you and I crossed! Yes, this is a good study demonstrating the difference between ME/CFS and deconditioning.

according to the deconditioning-symptoms-on-exercise-fear-avoidance hypothesis all patients with long-lasting CFS are in a fear-avoidance-deconditioning loop and therefore should be deconditioned.

American researchers and clinicians would not necessarily agree, even if they did believe deconditioning was part of the illness-picture. I've heard lots of US physicians pushing patients to exercise more because they fear their genuinely exhausted patients will also become deconditioned, which to their uninformed knowledge, would worsen matters. This is totally separate from the paradigm of "movement phobia".

For example, my mom (CFS via EBV in the 1990s) was prodded into exercising gently every day, but no one ever figured that it was a lack of exercise that caused her illness or that an irrational phobia of standing and walking was what was keeping her sick -- so there was a difference in both etiological and maintenance philosophies as compared to the BPS school of thought.

 

[Jenny TipsforME]

Thanks. I do also myself worry about becoming deconditioned. It feels like the desire to hammer a stake into the ground and refuse to give up that territory. But mixing metaphors, I remember someone on here saying it's like worrying about a lit candle when there's already a raging forest fire. i.e. We have much bigger problems to deal with and if we do deal with them, then deconditioning will also be easy to deal with.

But that reference is good for showing the problem itself isn't deconditioning