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Myalgic Encephalomyelitis (ME) or What? An Operational Definition, 2018, Frank Twisk

Discussion in 'BioMedical ME/CFS Research' started by strategist, Sep 8, 2018.

  1. strategist

    strategist Senior Member (Voting Rights)

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    http://www.mdpi.com/2075-4418/8/3/64
     
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  2. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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    So is this yet another set of criteria?
     
  3. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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  4. lansbergen

    lansbergen Senior Member (Voting Rights)

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    Is Frank Twist a member here?
     
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  5. Trish

    Trish Moderator Staff Member

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    I've only read the abstract so far.

    I like the fact that he removes 'fatigue' as a core symptom and replaces it with ''muscle fatigability/prolonged muscle weakness after trivial exertion''. For me that sort of distinction is essential in explaining the difference between whatever it is I suffer from and other 'fatiguing conditions'.

    I also like that he talks about ''neurological disturbance, especially of cognitive, autonomic and sensory functions'' rather than calling it a neurological condition, because we don't yet know whether there are any permanent structural neurological changes, or whether it is disturbed function which could be reversed if a biomedical cure were found.

    What seems to be missing from the abstract is a clear description of PEM which is a lot more than prolonged muscle weakness.

    The paper is open access, and likely to be worth reading, I think.

    Sometimes I feel overwhelmed by all the stuff I want to read and understand...
     
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  6. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I think this is misconceived and tends to take things in the wrong direction.

    It is this sort of analysis that makes me think we should stop referring to 'outbreaks of ME' documented in the past, because they probably tell us nothing important about the illness people suffer from today. The 'neurology' of the Royal Free outbreak turned out to be not very much that could be pinned down with objective evidence.

    The core of the definition given in this proposal is:

    ME is a multi-systemic illness, which (1) often has a sudden onset, in most cases a respiratory and/or gastro-intestinal infection, but a gradual or more dramatic onset is also possible; (2) has an epidemic and an endemic form; (3) has an unique clinical pattern deviating from other post-viral states; (4) is distinguished by muscle fatigability/prolonged muscle weakness after trivial exertion; (5) is accompanied by symptoms relating to neurological disturbance, especially of cognitive, autonomic, and sensory functions; (6) can be accompanied by symptoms associated with cardiac and other systems; (7) is characterized by fluctuation of symptoms (within and between “episodes”); (8) has a prolonged relapsing course; and (9) has a tendency to become chronic.

    The usual term is multi-system, rather than multi-systemic but that does not matter. The problem in using the term is that multi-system implies not just symptoms but pathology in several systems and we do not have that as yet.

    The criteria themselves are not of much practical value.
    1. If the onset can be sudden or gradual then a description of onset may be of interest but does not contribute usefully to a definition - because it does not narrow down possibilities. Th occurrence after infection is relevant but EBV is not really either respiratory or GI.
    2. I do not think that it helps to talk of an 'epidemic form'. Of the hundreds of thousands of documented cases of ME maybe 1000 at most were documented as part of multiple case clusters. Since infections often come in epidemics and ME follows infections I cannot see that these clusters add anything useful.
    3. ME may have a unique clinical pattern but we need to know what that is.
    4. The idea of muscle fatiguability/weakness comes from Ramsay, I think. Ramsay was not a neurologist and I do not think neurologists would consider this a very helpful part of a definition because it is too vague and ambiguous. Fatiguability and weakness are different. Moreover, as far as I know no objective evidence has been documented for either muscle weakness or fatiguability in the sense that it has for myasthenia gravis.
    5. ME is certainly associated with cognitive disturbance symptoms. Attributing symptoms to autonomic problems is a bit more tricky. I am not sure that any sensory abnormalities have been shown to be more common in PWME. I think from the neurological point of view it would be much more useful to focus on the cognitive deficit.
    6. This is too vague to be useful. ME is not as far as I know associated with cardiac abnormalities per se, although there is a suggestion of low cardiac volume.
    7. Fluctuation is also hard to use as a criterion. Moreover, I understand that for some people there is not much fluctuation.
    8. A prolonged relapsing course is not very helpful as a definition that identifies people until it is a bit late!
    9. This seems to add nothing to 8.

    I appreciate that Frank Twisk has produced this in good faith as an attempt to document his conception of ME. However, it is not in a form that is going to be of use to medical practitioners, or to researchers.
     
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  7. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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  8. Trish

    Trish Moderator Staff Member

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    Thank you @Jonathan Edwards. You have spelled out clearly a lot of the misgivings I had about it from the abstract.

    I admit my initial positive reaction was largely based on his discarding of the phrase 'chronic fatigue' that seems to appear in every other definition of ME/CFS as the core symptom, and which I find pretty meaningless. I prefer replacing it with muscle fatiguability which seems to much better describe my experience.

    I suffered chronic fatigue (tired all the time, drained, exhausted) when I was feeding young babies and not getting enough sleep, but I was perfectly healthy and could do all my normal daily activities. My muscles functioned perfectly normally.

    The feeling in my muscles and rapid onset of weakness/fatigue/pain in my muscles after a small amount of activity since I've had ME is completely different. Although perfectly fit at onset, I was suddenly unable to walk normal distances or climb stairs without stopping and sitting down. My legs would give way. That's not normal.

    Is there a medical way of describing this difference?
     
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  9. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    There should be but I am not sure there is.
    When Ramsay talked of fatiguability he was obviously noting a real symptom. However, my understanding is that electrophysiological studies do not demonstrate nerve of muscle impairment. The closest thing that I can think of that might explain what is going on is the involuntary inhibition of muscle action that occurs with pain and probably with fever. There is no doubt that during 'flu' one can often not stand. These days I sometimes fall because my left knee refuses to support my because of inhibition that occurs even before pain is noticeable. Yet I suspect that electrophysiology would equally show that nerve and muscle are OK. Richard Edwards did some work on this but not in the context of ME.
     
  10. strategist

    strategist Senior Member (Voting Rights)

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    Is it possible that at the time of Ramsay, a patient with problems sustaining a certain activity would be described as having muscle fatiguability? Whereas today a specific reference to muscles might be avoided unless evidence of a muscle problem existed.
     
  11. Sarah

    Sarah Senior Member (Voting Rights)

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    When you say you aren't sure sensory abnormalities have been shown to be 'more' common in PWME, with what group as it were are you making the comparison?
     
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  12. Hutan

    Hutan Moderator Staff Member

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    Obviously ME's clinical pattern isn't the same as some of the more clearly understood post-viral states like Guillain-Barre. But I don't think that there is evidence that ME is essentially different from the type of post viral state common after an EBV infection (or from post-Ebola syndrome). The 6 month time requirement is a construct with little to do with how the disease process works.

    Twisk seems to be suggesting that ME is a post-viral state but there is quite a lot of evidence to suggest that a viral infection is not a necessary trigger. For example, bacterial infections (e.g. Q fever) and protozoan infections (e.g. giardia) seem to be able to induce ME. And there may be other triggers or combinations of triggers (of different kinds and/or possibly with cumulative effect until a threshold is reached).

    I'm with @Trish on this, there is something real going on with muscle weakness. Sometimes, I can walk up the two steps of my deck without thinking about it. Other times it requires conscious effort to muster the explosive power required to do that. Walking up a flight of stairs is, at times, extremely difficult. I can't believe that it is not possible to collect objective evidence of this, it's just that it hasn't yet been done under the right conditions.

    Perhaps the muscle itself is indeed perfectly healthy, but the outcome of some process is muscle weakness, just as an eye can be healthy but a person can (temporarily or permanently) have no sight.

    Re autonomic problems - there are problems with temperature control, and orthostatic intolerance seems to be very common. Are these not necessarily autonomic problems? (genuine question).
    There has been some good preliminary work on vision problems in PWME. Certainly I have blurred vision when suffering PEM.
     
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  13. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Was thinking of a randomly chosen cohort, to see whether the incidence of sensory symptoms in ME could be considered more than one would find by chance in a random selection of people. If not there would be no reason to think it was part of the ME.
     
  14. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Temperature control is hypothalamic but I am not sure it is autonomic. The response of the hypothalamus involves things like changing thyroid hormone secretion and shivering (which is somatic rather than autonomic).

    Orthostatic intolerance is often attributed to autonomic dysfunction but there are lots of puzzles with that. As some of the people who study this have pointed out, if you have a poor autonomic response then you expect to get no tachycardia on standing. You might well get loss of cerebral perfusion but last time we discussed this my impression was that OI is often a bit different from a standard faint. And unfortunately certain physicians have made broad claims about autonomic dysfunction without there being much well documented evidence in the literature.
     
  15. Barry

    Barry Senior Member (Voting Rights)

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    The trouble with ME it seems, is that other than PEM, just about every other symptom seems to present in various other illnesses also. So without any biomarkers, the symptoms alone are incredibly difficult to use as a unique signature of ME. When I talk to my wife about her tiredness / fatigue / weakness / symptom-without-a-name, she, same as @Trish, has trouble describing it, but is clear that it is very unlike any normal kind of fatigue / tiredness she ever used to experience ... and indeed she wishes that's all it was. As someone not suffering from ME, although I obviously do not wish it on myself, I really wish I understood what the symptom feels like. It seems like it might well be a distinguishing feature of ME, but no-one knows how to adequately describe it!
     
  16. Sarah

    Sarah Senior Member (Voting Rights)

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    I'm surprised by this. It seems to me that sensory abnormalities are well documented in PWME and I would have thought them a pretty uncontroversial aspect of the potential symptomatology a given PWME may develop. I'm thinking of hyperacusis and photophobia in particular, but no less other sensory issues. Would you not find onset of sensory abnormalities coinciding with onset of ME and/or degree of severity coinciding with ME status in PWME claiming sensory involvement in any sense persuasive? If not, isn't it therefore as arguable that cognitive dysfunction may be cropping up incidentally and not in fact due to the ME?

    To be fair, I'm not sure sensory abnormalities have been shown to be more common than cognitive dysfunction, or deficit, in PWME either. But I'm also not sure cognitive dysfunction has been shown to be more common than sensory abnormalities.

    Edited - clarity
     
    Last edited: Sep 8, 2018
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  17. Trish

    Trish Moderator Staff Member

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    Thank you @Jonathan Edwards. It is very puzzling.

    The only way my simplistic view of biology can explain my muscle fatiguability is that it's like a battery gradually going flat and the motor it is powering slowing down. The motor (muscle cell) may be structurally perfectly normal, but if the power input (mitochondrial energy production) has slowed down or can't keep up with demand, it can't function at normal levels until the battery has had time to recharge.
     
  18. alex3619

    alex3619 Senior Member (Voting Rights)

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    Recent research using invasive CPET indicates possible low oxygen use and low cardiac preload. Not enough blood is being returned to the heart and it has too much oxygen. This involves CPET with an arterial catheter loaded with sensors. There is some association of this with small fiber polyneuropathy and orthostatic intolerance. There are some research biases here, I think the group is loaded with OI patients, and it needs further replication, but it might explain a lot for about sixty percent of patients.
     
  19. Barry

    Barry Senior Member (Voting Rights)

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    I sometimes have minor back issues, and have occasionally had referred pain / weakness in my legs as a result. There have been times I have found myself feeling silly because my leg has "backed off" before anything has really happened, and left me thinking "well it didn't even hurt, am I just being silly here!". But it happens nonetheless. Not really been able to work out if it really is involuntary, or voluntary but needing lots of self control.
     
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  20. dreampop

    dreampop Senior Member (Voting Rights)

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    To me that was one of the reason why the definition was unsuitable - I suffer from [very] extreme fatigue of sudden, post-viral onset. Best explained by the IOM defnition. It might fit in as a neurological symptom or whatever, but both it's suddenness and severity are what make the illness so distinct and insufferable. Simply avoiding provocations does not, strangely, eliminate the fatigue. If it's meant to just refer to PEM, it would also be unsuitable, as I have an overall worsening of symptoms, esp. fatigue, but not what I understand to be true clinical muscle weakness. In any case other definitions provide for both fatigue as well as PEM as core criteria, so this could be a dramatic difference.

    But perhaps unequival for me is 7, since I am stable, as are my symptoms w/o the provocation of PEM. Sure there's some very minor changes from day to day, but I am sick, and when I do more I get more sick. This must be an optional requirement. 8 seems like total speculation.

    I appreciate the effort to try to tweak the defintion, and I understand how important it is, so I respect the author's intent. I think w/ definitions we are at the point where we really need some luck in the research to help us sort this out further. Else this feels like working backwards to avoid BPS stereotypes w/o letting the evidence guide us. Paticularly, I don't understand this need to go back and try to shoehorn epidemics. We don't know what they were and we don't know what's wrong with us. There was a post-viral illness w/ fatigue at Tahoe an somehwere along the way people saw the similarities and started applying the name to a broad range of patients with unexplained symptoms.
     
    Last edited: Sep 9, 2018
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