How ME/CFS Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS Nacul et al 2019

Discussion in 'ME/CFS research' started by John Mac, Sep 17, 2019.

  1. John Mac

    John Mac Senior Member (Voting Rights)

    spinoza577, Nellie, Lidia and 23 others like this.
  2. Hoopoe

    Hoopoe Senior Member (Voting Rights)

    Neuro-immune would mean related to the brain's immune system. Neuro-immune as used in the ME/CFS community seems to be a buzzword with little substance behind it.

    We also have no idea how the metabolism changes over time, or whether the currently in some instances contradictory metabolic findings are contradictory because patients are being examined at different stages of an illness that progresses from one metabolic state to a different one. It could also be that these differences are due to sample processing and testing methods or due to the existence of subgroups.

    However I would agree that my illness seems to change and evolve over time.

    That seems to be a sensible approach.
    Last edited: Sep 17, 2019
  3. Trish

    Trish Moderator Staff Member

    The PDF of the article is open access. It's 16 pages of detailed biomedical information and hypotheses that I don't have the brain to read today but looks interesting. The point that ME seems to change over time and go through different biomedical stages is interesting, and their longitudinal study seems a very good idea. A pity that, by definition, it will take a long time.
    obeat, Lidia, Annamaria and 21 others like this.
  4. Cinders66

    Cinders66 Senior Member (Voting Rights)

    This might be a very worthy document and like @Trish I simply don’t have the brain power to read a long very dense document at present so I skipped to the severe sections. Whilst I agree with idea of the illness advancing and compounding with cumulative effects of abnormalities I did notice the word rehabilitation cropping up a lot???

    I also saw this
    “Looking at other models of disease that include ‘invisible stages’ of illness brings us to the change in focus that evolved in the study of Alzheimer’s disease. Over the past decade, a conceptual shift to consider the disease as a continuum has occurred and, along with the discovery of biomarkers, has re-focused the research agenda towards the pre-clinical stage and early intervention (Dubois et al., 2016)Similarly, we suggest that a re-focus of the ME/CFS research agenda towards the pre-clinical stage by way of larger cohort studies, may contribute to revealing potential risk factors to support primary prevention efforts.”

    Which frankly gives me the shivers because I feel like an end stage Alzheimer’s or MS patient might feel ie oh dear you’re too screwed to do anything with let’s focus on prevention instead. I’ve no problem with a general broad increased research effort but the word refocus if it means redirection to the easier option of preventative care would to me in context of tiNY existing biomedical research effort be unfortunate

    Edit i also think nihr & uk generally would Lap up early intervention possibly behavioral versus biomedical research of more serious cases research
    Last edited: Sep 17, 2019
    feeb, Annamaria, Ravn and 7 others like this.
  5. DokaGirl

    DokaGirl Senior Member (Voting Rights)

    The evolves through stages theory of ME is not new, but thank you to the authors for looking at this.

    Although how to prevent ME seems to me impossible, given the number of "insults" out there: chemicals, toxic metals, viruses, bacteria, surgeries, accidents etc.

    My own experience indicates to me at least, there are stages. However, this might just be n=1.

    Early on I read Katrina Berne's Running on Empty: The Complete Guide to Chronic Fatigue Syndrome (CFIDS).

    In her book, Dr. Berne talks about the progression to cognitive dysfunction following physical dysfunction.

    That was partly how it was in my case: first significant physical problems, then added in cognitive problems.

    However, problems with short term memory started quite early on before the brain fog/confusion, dizziness, problems with speech, headaches, etc. became issues.

    Here is the MEpedia site about Dr. Berne, and her work:


    Pre-clinical - scientists may want to look at pwIBS. There may be some potential there, as many with ME had IBS prior to ME.
    obeat, Chezboo, Mij and 11 others like this.
  6. InitialConditions

    InitialConditions Senior Member (Voting Rights)

    North-West England
    I also had physical symptoms before any cognitive symptoms. And IBS many years before that.
    wigglethemouse, alex3619, Mij and 7 others like this.
  7. ladycatlover

    ladycatlover Senior Member (Voting Rights)

    Liverpool, UK
    I thought I had IBS, symptoms were similar anyway. But then (long story) found in fact I had diverticulosis.

    Was diagnosed with diverticulitis on a trip to visit daughter in London, and the nature of the pain I had then was exactly what I'd felt before when I thought IBS was playing up. So best to try get this checked out - diverticulitis can be serious, I'm very grateful to St Thomas's Hospital for diagnosing and treating me.
    JemPD, Annamaria, alktipping and 2 others like this.
  8. Barry

    Barry Senior Member (Voting Rights)

    Prevention might well of course involve avoidance of "pushing through" possible very early symptoms, the significance of which may not be understood. As yet we do not know if the observed onset is when someone's ME really starts, or if it is simply a "final straw" threshold that is finally breached, after what might have been months or years of some unrecognised developing physiological change. If the latter, and if the unrecognised changes could be detected earlier on, then it might just be that careful energy management could prevent the final straw stage being reached. All conjecture on my part of course.
    obeat, JemPD, feeb and 11 others like this.
  9. ScottTriGuy

    ScottTriGuy Senior Member (Voting Rights)


    Given the current predominant response of the majority of physicians, either pushing exercise, and/or traumatizing, many ME patients would not be as sick as they are.
    obeat, rainy, JemPD and 12 others like this.
  10. Simbindi

    Simbindi Senior Member (Voting Rights)

    Somerset, England
    But not possible if you have caring or parenting demands (for example). Additionally, the 'final straw' may be an acute infection or other disease, an accident etc.
    obeat, MarcNotMark, JemPD and 8 others like this.
  11. NelliePledge

    NelliePledge Moderator Staff Member

    UK West Midlands
    As gradual onset likely at least 8 years undiagnosed this is definitely a needle/needles in a haystack situation trying to identify what actually contributed and what was completely irrelevant. You don’t pick up the drip drip worsening as anything remarkable until it has stacked up into something big enough to register as not normal. How you would pick up on it sooner would take a change of thinking from medics and public awareness i don’t see how that would work without some kind of test that could be carried out on people who have flu type illness symptoms to say oh you haven’t got flu you’ve got mild ME.
  12. Barry

    Barry Senior Member (Voting Rights)

    Onset of diabetes, as I understand it, is a tipping point following physiological changes that may have been developing for years. Once upon a time those pre-onset changes were not understood, but now they are, and are detectable.
    Last edited: Sep 18, 2019
    Annamaria, DokaGirl, Ravn and 2 others like this.
  13. Amw66

    Amw66 Senior Member (Voting Rights)

    Wearables will come into their own for this. Chemistry of anode/ cathode tweakable to be sensitive to different compounds. There is a plethora of PhD students doing such projects.

    Kraft assay test picks up pre diabetes stage, devised decades ago but not used clinically.
  14. Ravn

    Ravn Senior Member (Voting Rights)

    Aotearoa New Zealand
    Yes, I noticed that, too. They don't actually say anything 'wrong' about rehabilitation. Their definition of rehabilitation is broad, e.g. gentle physio to improve range of motion counts just as much as rehab as a gradual return to work. And they intend rehab to be adapted based on the stage the patient is at, e.g. an already recovering patient can carefully increase activity, a deteriorating one cannot. Unfortunately the sheer number of times the word rehabilitation is used is highly likely to cause a non-expert reader to conclude that most ME patients can be rehabilitated to health. If only!

    Too much emphasis on fatigue, again. Compare to other fatiguing illnesses, study fatigued patients after acute illness to see who goes on to develop ME, etc. For the 517th time: think fatiguability, not fatigue!!!

    But a lot of good in there, too.

    I like the suggestion of making an early, provisional diagnosis and telling patients to rest and pace already then. It may just help them recover or at least to not deteriorate as much.

    Many good suggestions, too, for improving ME research in the future, from the types of studies needed to patient selection criteria and stratification. Sadly no mention of where to get the money from to do it all (not the authors' fault I hasten to add).
  15. Ravn

    Ravn Senior Member (Voting Rights)

    Aotearoa New Zealand
    The paper refers to a presentation given by Schweitzer in 1998 about phases in ME. Not sure we've made any progress in further investigating the observations made back then.
    obeat, ladycatlover, rvallee and 5 others like this.
  16. Cinders66

    Cinders66 Senior Member (Voting Rights)

    Chrome might have been a useful resource but it makes me cringe that we could identify the housebound for the purposes of observation and natural course investigation but didn’t proceed to do any further research on the severe community for years.
    obeat, Annamaria, Ravn and 2 others like this.
  17. DokaGirl

    DokaGirl Senior Member (Voting Rights)

    Regarding phases of ME ("cfs"), in 1989 Health and Welfare Canada held a workshop, and published the results in 1991.

    The introduction says: "The purpose of this meeting is to review what we know about CFS, make recommendations and prepare guidelines concerning the diagnosis and management of CFS, and discuss various approaches for future research."

    Of particular interest are pages 59 to 71 of this link.

    On page 59 discussion included the issue of clarifying how "chronic psychiatric disease", and "malingering" featured, or did not feature in the Holmes' definition:

    This workshop and the ensuing publication concluded "CFS is a triphasic syndrome: Phase 1 - (lasting 3-6 months), an acute phase of greatest illness. Phase 2 - (lasting 3-24 months), a phase of slow improvement. Phase 3 - stability at an improved functional level usually subjectively less than 100% (no inexorable downhill course)."

    Based on the above government information, I was told I would recover in one to three years. I waited, puzzled, and concerned that I didn't seem to be improving, and the three year deadline was fast approaching. Over 30 years on I know this information is at best extremely optimistic for many pwME. We are still waiting for more definitive information about the natural course of this disease.

    In August 2009, CFIDS of America reported on a survey of 1,784 respondents: " Only 4.4% have been ill less than two years; 62.1% have been ill more than 10 years....63.3% are fully or partially disabled or retired from work..."

    Several other questions including work, full or part-time, receipt of disability income, number of medical consults etc. were also included in the survey.

    I have been unable to find the link to the above. I have a photocopy of the info without a link noted. It would be interesting to see more survey results like this one.

    The gap between what pwME experience and what policy and decision makers portray is very difficult to describe in positive terms.

    However, thirty years on we finally have some good news in Canada.

    I hope this more enlightened policy catches on in the UK and elsewhere!

    ETA: Also, looking back, by the time I was told I would recover in one to three years, I had been very much worsening for two years, and had had a total of about 6 years of gradual onset with new and increasing health issues added on over time.

    Initially, my gradual onset could have been seen as mild ME. With continuing to work, and press on as usual, which included lots of exercise, the ME worsened.

    ETA #2: quotation marks added.
    Last edited: Sep 18, 2019
    Simbindi, Annamaria, Ravn and 4 others like this.
  18. Mij

    Mij Senior Member (Voting Rights)

    I respect physicians who admit that they don't know and support the patient.
    ukxmrv, Annamaria, Barry and 4 others like this.
  19. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

    I wonder, do these authors intend to publish this in a scholarly journal?
    DokaGirl, ukxmrv and ScottTriGuy like this.
  20. Mithriel

    Mithriel Senior Member (Voting Rights)

    This is a description of typical EBV infection which the Americans were obsessed with at that time. Stephen Straus was brought into the CDC and given overall control of the Incline Village outbreak because he was an expert in EBV. The disease was originally thought to be chronic epstein barr disease which was his pet theory and which is described above.

    When it turned out that some of the patients had no EBV he was furious and the name was changed to CFS but the definition remained that for EBV with reference to that virus removed.

    Regardless, EBV continued to be a focus. There is confusion because EBV may lead to ME but it can also take years to resolve in itself. Like all herpes viruses it can remain in the body for years. Most of the cases of complete recovery I have read have started with being very ill with EBV then improving.

    ME as in the epidemics starts with a common infection which seems to be going but then gets worse, often with a relapsing remitting course until it either plateaus or gets worse.

Share This Page