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Objective assessment of diverse types of MS related fatigue and fatiguability (Lurija Institute)

Discussion in 'Health News and Research unrelated to ME/CFS' started by MSEsperanza, May 20, 2018.

  1. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

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    The following list of trials and other papers could be helpful arguing about the differences between the PACE trial methodology on the one side, and trials studying fatigue in other neurological conditions on the other side. Investigators of the latter developed objective measurement tools. I can't judge their quality, but perhaps other forum members are interested?

    There was a short (beginning of a) discussion on this topic in a thread I drove off topic a while ago:
    The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis by @Marco

    Recent research on diverse types of MS related fatigue and fatigability

    1) Lurija Institute


    1.1 Spiteri S, Hassa T, Claros-Salinas D, Dettmers C, Schoenfeld MA. Neural correlates of task-dependent and independent fatigue components in patients with Multiple Sclerosis. Neurobiol Aging. 2017,, http://journals.sagepub.com/doi/10.1177/1352458517743090

    Abstract

    1.2 Vieten MM, Sehle A, Jensen RL. A novel approach to quantify time series differences of gait data using attractor attributes. PloS one. 2013, 8 (8): e71824, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0071824
    (full text)

    1.3 Sehle A, Vieten M, Sailer S, Mundermann A, Dettmers C. Objective assessment of motor fatigue in multiple sclerosis: the Fatigue index Kliniken Schmieder (FKS). Journal of Neurology. 2014, 261 (9): 1752-62, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233503/ (full text)

    1.4 Sehle A, Vieten M, Mundermann A, Dettmers C. Difference in Motor Fatigue between Patients with Stroke and Patients with Multiple Sclerosis: A Pilot Study. Frontiers in Neurology. 2014, 5: 279, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273629/ (full text)

    1.5 Claros-Salinas D, Dittmer N, Neumann M, Sehle A, Spiteri S, Willmes K et al.
    Induction of cognitive fatigue in MS patients through cognitive and physical load. Neuropsychol Rehabil. 2013, 23 (2): 182-201, https://www.ncbi.nlm.nih.gov/pubmed/23153337

    1.6 Neumann M, Sterr A, Claros-Salinas D, Gutler R, Ulrich R, Dettmers C. Modulation of alertness by sustained cognitive demand in MS as surrogate measure of fatigue and fatigability. Journal of the neurological sciences. 2014, 340 (1-2): 178-82, https://www.ncbi.nlm.nih.gov/pubmed/24703580

    Abstract
    1.7 Claros-Salinas D, Koch E, Dettmers C, Schoenberger M. Fatigue-related restrictions of participation in MS and stroke patients six months after rehabilitation (submitted)

    Source:
    http://www.kliniken-schmieder.de/lu...schungsprojekte/fatigue-und-fatigability.html?
    (then click "Literatur" on the right-sided menu)


    2) Papers by authors unrelated to the Lurija Institute:

    2.1 Kluger BM, Krupp LB, Enoka RM. Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology. 2013, 80 (4): 409-16, https://www.ncbi.nlm.nih.gov/pubmed/23339207

    2.2 Rudroff, Thorsten, Kindred, John H, Ketelhut, Nathaniel B.; Fatigue in Multiple Sclerosis: Misconceptions and Future Research Directions, Frontiers in Neurology 2016 Aug 2;7:122. doi: 10.3389/fneur.2016.00122,
    (fulll text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969300/ )


    [edited 2018-07-22: sorted, added 2.2]
     
    Last edited: Mar 10, 2019
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  2. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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    Nice. Thanks.
     
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  3. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

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    Last edited: Mar 11, 2019
  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    @MSEsperanza,
    I think this sort of line of thinking is very relevant and worth exploring.

    One caveat I can think of is that the reason why we look for 'objective' markers is that we want reliability of evidence. If the subjective symptom is of key importance to the patient then objective measures are there to confirm the reliability of subjective reports as indicating a relevant underlying biological change. There is a lot to be said for requiring both a subjective score and an objective measure that confirms that.

    The measures given here are objective in the sense of being direct measures of biological events that correlate with types of fatigue. However, do they increase the reliability of the fatigue reports? If the objective findings just correlate reasonably well then in cases where they disagree what do you believe? Is the person fatigued if they say they are but the scan does not show it?

    I think to be of use these objective measures actually need to be based on good reasons for thinking that they are a more reliable indicator of a key underlying process than the subjective report. It is reasonable to think that a serum CRP is a more reliable indicator of cytokine based inflammation than a report of tenderness. Or at least it is a reliable indicator that the tenderness is likely to be due to cytokines. I am not sure that fMRI is at a stage where it provides that sort of clear indication of an underlying process. What if the fMRI just reflects different conscious thoughts that arise from the persons subjective feelings about things at the time rather than the underlying mechanisms that give rise to those feelings?
     
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  5. Graham

    Graham Senior Member (Voting Rights)

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    Subjective assessment can be more "reliable" if the trial is truly double-blinded. An easy one would be in homeopathy, where the homeopathist could prescribe a certain mixture, but the patient could easily be presented with plain water (that is, as opposed to water that had been shaken and diluted with water).

    It could be difficult to agree upon measures that correlate with fatigue, but surely it would be easier to agree upon measures that correlate with the consequences of fatigue? If I claim that my fatigue is greatly reduced, but, even over a period of time, the distance that I can walk remains severely restricted, it would sensibly throw doubt on my claim (assuming that I do not have another restricting condition).
     
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  6. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Yes, that would be an objective indicator of a relevant underlying physical process - the ability to do exercise. I guess it does not matter whether the indicator indicates something upstream or downstream of the subjective reported symptom, as long as it suggests that the symptom reflects something worth trying to modify. I had not really thought of it but for tender joints rheumatoid factor antibodies would be upstream in a relevant process and CRP would be downstream but both are good indicators that the symptom reflects something you want to treat.
     
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  7. Barry

    Barry Senior Member (Voting Rights)

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    I'm intrigued by the idea of reaction time being used as an indicator of cognitive fatigue - just feels like a valid correlation. Certainly it's recognised that driving when mentally fatigued impairs reaction times. Have any such studies been done for PwME? And it's easy to measure, with a bit of care.
     
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  8. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I would be interested to know if anyone has looked at something simple like a blink reflex or a tensor tympani reflex where the brain responds to sound by adjusting the tension of the ear drum unconsciously.
     
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  9. Graham

    Graham Senior Member (Voting Rights)

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    Well you live and learn. There's me thinking that I'm not remotely musical, and it appears I've got a tensor timpani reflex.
     
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  10. Sean

    Sean Senior Member (Voting Rights)

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    A question both tongue-in-cheek, and serious:

    How does the researcher tell the difference between the 'active' water and the 'inactive' control water?

    All water has been in contact with some other substance at some point, and subsequently diluted to the nth degree (thus rendering it mightily potent, according to homeopathy). Even distilled water has been in contact with the distilling apparatus, which is never 100% inert.
     
  11. Graham

    Graham Senior Member (Voting Rights)

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    The explanation that I heard was that the shaking and diluting process enables the water to retain a memory of the shape of the molecules of the added substance.

    Give me credit, I kept a straight face, which was necessary in the cirumstances.
     
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  12. Sean

    Sean Senior Member (Voting Rights)

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    Admirable restraint, sir.
     
  13. Sasha

    Sasha Senior Member (Voting Rights)

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    A quick google shows that various aspects of blinking have been examined in relation to fatigue (and sleepiness) but I didn't find an up-to-date review (which doesn't mean there isn't one, because I didn't do a thorough search).

    The tensor tympani reflex has also been looked at, but on another shallow and incompetent google, I didn't see a review. I did find, for example, a study in which the reflex helped distinguish patients with myasthenia gravis from healthy controls:

    https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.410090604
     
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  14. Marco

    Marco Senior Member (Voting Rights)

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    There have been a (very) few studies on pre-pulse inhibition (PPI) of the startle reflex and event related potential (ERP) responses to sensory stimuli which are a similar thing and at the early procssing stage are pre attention/pre-conscious.
     
    Last edited: Jul 2, 2018
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  15. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

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    Thanks to all who have contributed to this thread so far. I hope I will be able to come back to some questions soon.

    In the meantime, just to get a more complete picture, I added the following paper to the OP:

    The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue
    https://www.ncbi.nlm.nih.gov/pubmed/19995840

    edit: I have not read this yet - might be a bad example. i.e rather subjective measure?
     
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  16. Woolie

    Woolie Committee member

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    I just saw this. Having only read the summary so far (the one in the OP), my first worry is that these neural correlates they've found - which are just that, correlates - could easily morph into causes, and ultimately, feed the view that fatigue is a construct created entirely in the mind.

    Yes, fatigue is a construct created in the mind, just as is perceiving a fast approaching train. But the best way to deal with both is not to modify the perception, but rather the external conditions giving rise to it. Like, get off the damn train tracks!

    Maybe I worry too much?
     
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  17. Hutan

    Hutan Moderator Staff Member

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    I agree @Barry. I used some software ( http://www.sleepdisordersflorida.com/pvt1.html#responseOut ) to measure my reaction time, tracking it daily for quite a while. Reaction time was longer on the days when I felt worse and found it harder to focus and concentrate.

    For example, on a day of slow reaction time (459), there was a difference of 41 beats per minute in the orthostatic intolerance standing test (i.e. positive for POTS), my pulse pressure was bad (low - 23), shock index high (1.1). As well as all the usual symptoms, there were extra symptoms of muscle twitches, a warm feeling on my foot, and cramps. That day, deep fatigue didn't hit until the evening, but the following day fatigue was particularly bad from the morning.

    On a day of faster reaction time (307), the OI standing test had a difference of 19 beats per minute (negative for POTS), my pulse pressure was fine (36), my shock index was fine (0.7). Fatigue was moderate that day and the next day.

    I would really like to see a study done correlating reaction time (and those other suggested measures of blink and ear drum reflex) with subjective measures of fatigue.
     
    Last edited: Jul 22, 2018
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  18. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

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    Unfortunately some of the listed papers do not seem to reflect the premise I found so promising: to differentiate clearly between specific types of fatigue when writing about fatigue. Have to read them yet.

    The abstract and first paragraphs of one of the now added papers however sound quite good to me.

    Could be helpful to relate to this paper when arguing with NICE re: objective measurements?

    from: Rudroff,
    Thorsten, Kindred, John H, Ketelhut, Nathaniel B.; Fatigue in Multiple Sclerosis: Misconceptions and Future Research Directions, Frontiers in Neurology 2016 Aug 2;7:122. doi: 10.3389/fneur.2016.00122, (fulll text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969300/ )]

    Abstract:
    Intro:
    re: exercise therapy:

    re: objective measures and need to specify fatigue:

     
    Last edited: Jul 22, 2018
  19. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

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    @Woolie, I thought this article might be of interest for your question posted in an related thread re: MS related fatigue:

    from: Rudroff, Thorsten, Kindred, John H, Ketelhut, Nathaniel B.; Fatigue in Multiple Sclerosis: Misconceptions and Future Research Directions, Frontiers in Neurology 2016 Aug 2;7:122. doi: 10.3389/fneur.2016.00122, (fulll text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969300/ )]

    re: Peripheral Factors

     
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  20. Woolie

    Woolie Committee member

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