The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
Discuss the article on the Forums.

New Exercise Study Brings Both Illumination and Questions

Discussion in 'Phoenix Rising Articles' started by Simon, Aug 20, 2014.

  1. Christian Godbout

    Christian Godbout

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    I really salute your emphasis on the issue of safety … This test in my view ought to be a means for research alone, and not a means to prove disability to insurers. Have a few hundred courageous ME/CFS sufferers undergo the test for the sake of science, and for that sake alone. It would be terrible if insurers were one day to demand it systematically to thousands of sufferers... As you have pointed, the moderately ill run the risk of worsening their state, and the severely ill could not even perform the test in the first place. (If one is to prove that one has a heart condition, do you demand that he or she go through a near- heart attack experience?!...) That is why I find the merging of the two studies - the CPET and the Lights' on gene expression - so harmonious. The CPET provides "hard core" and damaging data, so to speak, that backs up the softer gene expression studies, which take the lead from there in direction of biomarkers. Let's just hope that some day soon with the latter we can prove the pathology underlying post-exertional exhaustion, without having to go through it to prove it...
     
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  2. Sea

    Sea Senior Member

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    Alex, there is an email address for Workwell listed on their Facebook page. I have emailed them previously and gotten a response from Jared Stevens within a couple of days
     
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  3. Gingergrrl

    Gingergrrl Senior Member

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    @PNR2008 I am so sorry to hear all that you are going through and admire your strength and perseverance with all those tests. Hopefully your results on Mon will bring clarity and a solid plan. :hug:
     
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  4. Simon

    Simon

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    Thanks for raising that and I'm sorry it wasn't clear: yes, I did get in touch with Betsy Keller, who was very helpful.

    It would have no effect on the main effect observed here, the drop off on day two. I think it could affect the basic day one level of the anaerobic threshold in particular, but I'm really not too sure.
     
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  5. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    Two O2 consumption test on a treadmill in two consecutive days (10 minutes with last 2 being uphill and fast) left me almost useless for a week. But something interesting: both test showed abnormally low anaerobic threshold and the second test showed lower oxygen consumption than the first, 24 hours later. It weas hard to get those tests done since I'm from Argentina and nobody here knows much about ME and let alone these scientific studies. What do you think?
     
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  6. JKN

    JKN

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    I feel like a stranger in a strange land with all of this exercise testing. I had a mild case of ME/CFS for 10+ years prior to taking a cardiac stress test 9 years ago, which caused very severe disease progression and heart damage. I am now in Stage 2 diastolic heart dysfunction with Stage 4 heart failure symptoms as a result of this stress test. I also lost my ability to talk after the stress test. I had no heart problems or problems with my voice before the stress test. I am now almost entirely bed and wheelchair bound.

    "Findings which suggest mitochondrial metabolic dysfunction similar to mitochondrial encephalomyopathy in CFS patients led CFS expert Professor Paul Cheney to comment. ‘The most important thing about exercise is not to have patients do aerobic exercise. I believe that even progressive aerobic exercise is counter-productive. If you have a defect in mitochondrial function and you push the mitochondria by exercise, you kill the DNA.’ Numerous heart, lung, brain and other abnormalities also show strong evidence that exercise can have extremely harmful effects on CFS patients in many different bodily systems, permanent damage may be caused, as well as disease progression." (Williams 2004, [online]).

    "In CFS physical overexertion causes relapses of symptoms and continued physical overexertion can lead to disease progression - which may be irreversible." The Hummingbirds' Foundation for M.E.

    "As well as long-term effects on disease progression, exertion can also have serious (and sometimes fatal) effects which are more immediate (cardiac complications for example)." The Hummingbirds' Foundation for M.E.

    "Not only is it inappropriate for CFS patients to undergo a treadmill stress test or be pushed toward age-predicted target heart rates, but this is potentially dangerous." Philipa Corning, Ph D, Vice President Quest 61, 2003

    So I am totally shocked by the growth of these exercise studies, and PWCs standing in line. Unless I have a different disease, or there is a difference between ME and CFS, or most of the PWCs taking these tests have been misdiagnosed, then I don't understand why PWCs taking these exercise tests aren't having the same horrific results that I've had. So I would warn all PWCs that taking a stress or exercise test could destroy your life and possibly lead to severe permanent disease progression and death from heart failure.

    Furthermore, I don't understand why there are no mainstream research studies going on today reg. the effects that ME/CFS has on the heart, i.e. this is one of the main causes of death from ME/CFS.
     
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  7. CaronR

    CaronR

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    I would be interested to see how results for patients with dysautonomia (including POTS) respond to this excerise test and how the results compare with ME patients. Once of most infuriating things I've found about ME and CFS is how quickly doctors are to slap a CFS diagnosis on patients (my daughter in our case), which means it's unlikely they'll investigate further, and getting any sort of treatment, other than seeing a psychologist is nearly impossible. But many patients orginally diagnosed with CFS have POTS or another form of dysautonomia, amongst other conditions, either alongside their ME or CFS or instead of, but this is rarely investigated, despite there being treatment that can significantly improve their quality of life and functionality.

    Patients with POTS (just POTS with no ME) also complain of post exertional malaise and payback for pushing beyond their limits, so it would be interesting to find out if one of the subsets relates to autonomic dysfunction (rather than ME) and if another was specific to ME (and not to patients with 'just' autonomic problems).

    At the moment, I suspect the exercise tests also pull patients with dysautonomia, and not necessarily ME, into the pot and also includes people with ME, who do not have dysautonomia. This begs the question, what other conditions would also show these sorts of results.
     
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  8. Valentijn

    Valentijn Senior Member

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    For many patients a 2-day CPET result can make the difference between getting government or insurance benefits, versus being homeless, unable to feed themselves, and/or shunned by family, friends and doctors.

    We know it's a risk, which is why we want it to be a central aspect of research looking for additional biomarkers which won't risk maiming or killing us in the process of collecting them :p
     
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  9. Valentijn

    Valentijn Senior Member

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    Exercise intolerance is what hits OI patients during and immediately after exertion. PEM has a substantial delay and exacerbation of the ME symptoms. I think you might be assuming that Exercise Intolerance and PEM are the same - they aren't.

    ME patients often have both OI and PEM, so will get hit twice: once during or immediately after exertion, and then a day or two later. If an OI patient has ME symptoms and PEM, they probably need a new diagnosis (or not, if it means an end to helpful treatment).

    An OI patient should be able to exercise lying down without problems, and can often build up muscles to help with OI and resulting exercise intolerance. That doesn't work at all for ME patients.
     
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  10. PNR2008

    PNR2008 Senior Member

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    In 1992 I had a spect scan through Jay Goldstein which showed " diminished perfusion in the right frontotemporal lobes and incomplete response of regional cerebral blood flow to exercise". As far as he was concerned the first day of exercise and the spect scan showed the abnormality and said the second day was up to me but it could provoke an exacerbation of symptoms which wasn't necessary. I did not do the second day testing. I really miss that man and this was in 1992!

    Now in 2014 I'm in worse shape than ever but being put to tests that may pinpoint problems with POTS and hopefully make my later years of life better or not? That is if I have enough time to get over the PEM these tests caused. This is a double-edged sword which just might pierce my heart literally.
     
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  11. voner

    voner Senior Member

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    CaronR,

    Well said.

    One research group who is starting to delineate subgroups are the Lights and Dr. Bateman. They delineated a unique group that had ME/CFS, fibromyalgia and "Orthostatic intolerance" and had a unique gene expression following a single exertion test.

    Here is a summary from Kathleen Light:

    There used to be a good summary of this research over at the CFIDS (now Solve ME/CFS initiative) website, but I can no longer find it. I wrote a rambling blog about the study over at Cort Johnson site, focusing on the subgroup. (http://www.cortjohnson.org/blog/201...yndrome-subset-if-doctors-will-just-look-for/). As Simon has said, the Drs. Lights and Dr. Bateman have embarked on a much larger study that was supposed to be published somewhere around this time frame this year. So, hopefully they'll publish soon and There will be more detailed information about Gene expressions, sub-groupings and???
     
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  12. Valentijn

    Valentijn Senior Member

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    α-2A is ADRA2A (Adrenergic Receptor Alpha 2A), which can cause low norepinephrine when over-expressed, and thereby low blood pressure and/or low pulse pressure. I've tested low in blood norepinephrine, and have very good results with a low dose of Yohimbe, an ADRA2A antagonist. I think someone else here is on it as well, and mentioned good results.

    But the smaller group has a large decrease in ADRA2A, which might explain the rarer hyperadrenergic POTS patients with orthostatic hypertension which we have here. I know @taniaaust1 has that issue, and tests high in norepinephrine, rather than low. I've seen someone else mention that problem recently as well in a thread.
     
    Last edited: Aug 23, 2014
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  13. Gingergrrl

    Gingergrrl Senior Member

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    @JKN I am so sorry you had that experience and was wondering if the doctor ever explained to you how the exercise stress test (I am assuming it was on a treadmill?) led to heart failure and losing your voice. I believe you and am only asking b/c I just did the exercise echo (treadmill test) a few days ago myself and curious to learn more from your experience. Have you found any treatments that brought you any improvement and did your doctors offer any suggestions? Again, I am so sorry to hear how much you have suffered with this and wish you peace moving forward.
     
  14. voner

    voner Senior Member

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    @Valentijn,

    So, The smaller group (the one with the large decrease) might be affected by mechanisms described in this paper,

    http://atvb.ahajournals.org/content/32/8/1910.long

    Where they find:



    Or am I confused?
     
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  15. Valentijn

    Valentijn Senior Member

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    I think it would be a different pathway into the same (or similar) symptoms. Unless the way that ADRA2A reduces norepinephrine is by reducing SLC6A2, in which case it could be the same problem. I need to read more about the mechanism for how ADRA2A is impacting norepinephrine!
     
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  16. Stretched

    Stretched Senior Member

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    Nice reporting but I feel the researchers are barking up the wrong tree... .

    If the purpose of exercise testing results in help PWMEs get financial help then more power to the researchers for correlating the subject findings . However, wouldn't similar respiratory-exertion findings be common to any serious long term sickness?
    Assuming that's the case then these experiments might prove embarrassing, like publishing results tantamount to 'when it rains things get wet!'

    I am under the impression that adrenaline rising (rushing) is a shared, sic felt, causative symptom from physical OR mental effort (exertion) and that it ultimately leads to malaise, even perhaps severity of the malaise (>adrenaline production) is directly correlated to a measure of that exertion?

    If this is the case then wouldn't measuring epinephrine and its analogs before and during exertion yield more significance, in that an autonomic immune system dysfunction is a resultant of ME (albeit likely initiated from variant causes)? I'm not aware of the HEPA axis dynamics having been ruled out as causative of the kind of malaise we all suffer.
     
  17. voner

    voner Senior Member

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    Dr. Alan Light, et. al., have done these gene expression studies on patients with ME/CFS, ME/CFS with fms, patients with only fibromyalgia, prostrate cancer, and patients with multiple sclerosis only. The patient subsets with ME/CFS, and ME/CFS with fibromyalgia each have unique signatures.

    If you type this into the pub med search engine, you can see a listing of their publications, and are well worth perusing:

    (Chronic fatigue syndrome) AND Light ar[Author]

    Their color-coded gene expression graphs are pretty spectacular.
     
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  18. alex3619

    alex3619 Senior Member

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    The answer appears to be no. Its certainly not the case for cardiac or respiratory patients that I am aware of, nor MS patients. One patient with HIV does test this way though, but I suspect this person is unfortunate enough to have both HIV and ME. Its also not seen in deconditioning. There is some question of whether or not its seen in things like POTS or post-cancer fatigue however. We do not know yet.

    The results re so unique to ME (so far) that two separate research teams were at first convinced their machine was broken or needed calibration.

    There are three benefits to the 2 day CPET:

    1. As a research finding it gives us another direction and clearly shows severe pathophysiology in many patients, and so is a biomarker for ME even if its not diagnostic. It currently is best thought of as an outcome marker in my opinion, and indeed it has been used this way I think.

    2. It can assist patients obtaining disability or insurance payouts. Its hard for anyone to dispute this finding, at least at present.

    3. It can provide information on a patient's anaerobic threshold and current recovery status ... whether or not their treatment is working. This can help plan treatment changes.

    However, it may also have the following issues.

    A. Insurance companies may decide to mandate testing. I wonder if they will accept responsibility if this forces a crash.

    B. Most patients do somewhat to a lot worse after testing. Some go into serious crashes. I would not recommend this for anyone as a routine test, its something that should be up to the individual, their doctor, and their current needs.

    C. More severe patients cannot do this kind of testing. Its limited to mild to perhaps the low end of severe (depending on what you mean by severe), and the more severe the patient the less desirable this testing might be.

    I think this kind of technology will be necessary for a while for some patients, but I also suspect it will be superseded. However even the Light's testing requires one bout of exercise, though perhaps at lower intensity. Its also the case that lower intensity testing might suffice for determining anaerobic threshold, and even that gas analysis for metabolic rate testing is all that is needed in some cases, particularly severe cases.

    Despite this technology being around since at least 1949, and docs using it for ME since the 80s at least, its still very early in the research for us to have a good grip on what this tech should be used for.
     
  19. Simon

    Simon

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    Glad you liked the article :)

    As the article mentions, a lot of testing has been done on on patients with heart and lung diseases - that's been the main medical use of these exercise tests (CPET - cardiopulmonary exercise testing in the jargon). For example, angina patients were found to be able to repeat the test reliably three times in 3 days. There's a lack of data other fatiguing illnesses, though Workwell have set the ball rolling with tests on one MS & one HIV patients - more data is needed, though the fact that people with serious heart and lung disorders can repeat the test strongly suggests to me this isn't a generic feature of chronic illness. Though to be honest, before I'd seen the data for other illnesses I'd assumed, like you, that it would be.
     
    Last edited: Aug 30, 2014
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  20. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    Try this thread. Title "Functional characterization of muscle fibres from patients with CFS" :)
     

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