New Atmosphere, New Vision: Gibson and Whittemore Kick Off Invest in ME Conference 2016
Mark Berry reports on Dr. Gibson's introduction and Dr. Whittemore's keynote speech, at the 11th Invest in ME International ME Conference in London.
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Abstract: Does CFS Have a neurological origin?

Discussion in 'Latest ME/CFS Research' started by minkeygirl, Feb 4, 2016.

  1. minkeygirl

    minkeygirl But I Look So Good.

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    Does chronic fatigue syndrome have a neurological origin?

    Barnden, Leighton


    "Abstract: Chronic Fatigue Syndrome (CFS) is distinguished by a persistent malaise and lethargy that physical or mental exertion exacerbates for a period of several days. Sufferers can identify a clear-cut beginning to their condition. In many, it follows a viral infection such as glandular fever. Sufferers also experience cognitive difficulties and, sometimes, autonomic disturbances such as dizziness on standing, gastrointestinal upsets, cardiovascular irregularities and immune system dysfunction."




    http://search.informit.com.au/documentSummary;dn=789240893533647;res=IELAPA
     
    Last edited: Feb 4, 2016
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  2. jimells

    jimells Senior Member

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    Apparently this is a review article. I wonder why it is not indexed in Pubmed. I did find his study of brain MRIs

    http://www.ncbi.nlm.nih.gov/pubmed/25702943
    This looks really interesting. I wonder what it all means. I think it suggests that we have the opposite of MS - too much myelination (is "nerve insulation" a fair description?) is disrupting brain signal processing.

    The full text is available for free, for folks able to understand this stuff.
     
    Last edited: Feb 5, 2016
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  3. JaimeS

    JaimeS Senior Member

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    Fascinating. For those of us who've had MRIs especially.
     
  4. jimells

    jimells Senior Member

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    Yes, my MRI shows "several punctate subcortical T2 hyperintensities" ("bright spots"), but since no one knows what they mean, they apparently mean nothing. It would be interesting to have it reviewed by someone like Dr Barnden.
     
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  5. JaimeS

    JaimeS Senior Member

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    Ditto. Punctate white-matter lesions. My docs admitted they didn't know what it was, but they did not act unworried. Two separate reports stated in almost identical language what amounted to "looks kind-of sort-of like migraine damage." Neither report was exchanged (i.e. Doctor 1 didn't see Doctor 2's report, and vice-versa). I said to Doctor 1, "this language is equivocal. You say 'may be' migraine, but that's just the closest thing to what you're looking at, right? It looks kind of like migraine, but not really?"

    He was a pretty honest guy, and after a minute, he nodded. "Yes, it's almost like that but not quite." He signed me up to run an MRI for 6 mo. later, but given he didn't know what it was, I think it was a try for peace of mind. If they hadn't increased in number or grown any larger, he could say, "we don't know what it is -- but at least it's not progressing."

    @jimells , we seem to be exchanging a lot of these sorts of stories, lately. ;)

    -J
     
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  6. duncan

    duncan Senior Member

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    Curious as to what strength MRI people have used, i.e., 1.5 vs 3.0.
     
  7. JaimeS

    JaimeS Senior Member

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    Sorry, @duncan -- as Lestrade says, "not my area". All I know is that they used gadolinium as the contrast medium, and that (for once) I didn't react to a new chemical unfavorably!

    -J
     
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  8. jimells

    jimells Senior Member

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    So far, I haven't been brave enough to try any contrast agents. If a doctor really expected to see something useful that can't be seen any other way, then maybe I would try it.
     
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  9. duncan

    duncan Senior Member

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    Perhaps intensity matters.

    I had two 1.5's with contrast and they evidenced no foci or hyperintensities. Sandwiched in between those two I had a 3.0 with contrast and they found multiple points.

    I tried to get another 3.0 approved, but was refused.

    So, maybe the testing some pwME are being directed to is insufficient...?

    I suppose I need to read this study in its entirety to find out what strength its researchers used.
     
  10. JaimeS

    JaimeS Senior Member

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    @ duncan -- here's what I've learned so far.

    1) The researchers used voxel-based regressions. This is a very subtle, sensitive way of gauging differences in brain anatomy using scans + statistics. Read the introduction in this Wikipedia article for more.

    2) In addition to voxel-based morphometry, they did T1 and T2-weighed spin echoes.
    • T1w shows changes in levels of myelin.
    • T2w shows blood volume in that region
    3) They used 25 subjects who met BOTH Fukuda and CCC definitions, ages 19-47. They discontinued meds for the purposes of the study. Those who were too ill to stop their meds were excluded. Therefore it's viable to assume that, like the vast majority of ME/CFS studies, this one only ended up testing people who have minor-moderate form of the illness.

    Study period was delayed if the patient was too ill to get the scan, and then resumed once they were well enough to continue -- I think that's good practice, really, or you could lose a lot of subjects in a patient pop like this.

    There were 25 age-, gender- and even weight-matched, non-related controls. They were not on meds and had no major illnesses.

    4) Three CFS severity scores were used:
    • Bell's CFS disability scale
    • Somatic Symptom Score
      • Fatigue
      • Change in sleep pattern
      • Dizziness on standing
      • Muscle pain
      • stomach symptoms
      • overall level of function
    • Neurological Symptom Score
      • change in concentration
      • change in short-term memory
      • headaches
      • emotional swings
    (For these, low scores = higher severity)

    They also carried out a Hospital Anxiety and Depression Scale (HADS) questionnaire.

    5) @duncan , these MR images were acquired on a Philips 1.5-T scanner.

    6) They DID correct for multiple regressions (bless them).

    7) Correlations were found between:
    • CFS disability and somatic SS ; CFS disability and neuro SS; CFS disability and depression
    • Somatic SS and Neuro SS; Somatic SS and depression
    • Anxiety and depression (que surprise!)
    There was no correlation between CFS disability and anxiety, or somatic symptoms and anxiety.

    8) Nerve conduction through the midbrain appears to be impaired in CFS. This was shown through an increase in prefrontal myelination (via T1w) in sickest patients, and volume loss in midbrain white matter (via T2w).

    9) CFS severity effects are not directly related to depression or anxiety (even though depression is correlated, it's not causative.) Anxiety and depression were included as 'nuisance' covariates in order to remove any apparent contribution to severity correlations.

    If this appeared to weaken the correlation of damage to that part of the brain with CFS severity, one could feel more confident in saying that depression is at least a strong part of what drives CFS symptom severity; that is, it is a somatoform disorder.

    Instead, both T1w imaging and T2w imaging with depression and anxiety 'removed' from the picture showed a stronger correlation to CFS severity rather than a weaker one. In other words, if you removed the 'white noise' caused by depression/anxiety, it strengthened the association between brain abnormalities and CFS severity.

    Thus,

    10) Volume loss might be due to astrocyte shrinkage; it's definitely not due to oligodendrocytes.

    Overall conclusions:

    Elevation of myelination is severity-dependent. There are midbrain nerve conduction issues in CFS, as defined by CCC, with midbrain volume loss and midbrain neuroinflammation. This might help explain autonomic and cognitive issues experienced by PWME. Despite the fact that severity of the illness correlates to depression, the neuroimaging studies don't support that CFS is caused by depression; in fact, when depression is eliminated as a 'possibility', the correlation between midbrain damage and CFS severity increases rather than disappears. CFS is therefore a distinct disorder rather than a form of depression.

    Guys, please read this study for yourself. I am an absolute novice at both statistics and MRI, and, er...

    That was the two topics. So.

    -J
     
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  11. duncan

    duncan Senior Member

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    @JaimeS - based on what you've just written, I suspect no one would consider you a novice. :)

    You say a 1.5? Imagine what they possibly could have found with double that. Or with PET or SPECT scans (different data).

    If one technology uncovers footprints, shouldn't someone try to complement the effort with other technologies to generate a comprehensive image of what is going on in our brains?

    Rhetorical, as I know that money will be one reason why this does not happen, even though it should.
     
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  12. jimells

    jimells Senior Member

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    There have been a number of studies that use various brain imaging techniques. Unfortunately they have all been small numbers of patients and the results have been buried under the noise generated by the PACE propaganda machine.
     
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  13. duncan

    duncan Senior Member

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    Yes, @jimells. It is unfortunate.

    I was in a US govt sponsored study. I demonstrated neurological symptoms. They found subtle abnormalities with a 1.5 philips. Another group with a 3.0 found several not-so-subtle problems. I pushed the original group for a 3.0 AND a PET AND a SPECT - and was turned down for all three. Not part of the protocol, I was told.

    My response was if you are interested in discerning neurological abnormalities, then start walking the walk and cough up the money and LOOK.

    They refused.

    I took them off my Xmas card list.
     
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  14. Scarecrow

    Scarecrow Revolting Peasant

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  15. JaimeS

    JaimeS Senior Member

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    Thanks, @Scarecrow ! How's about we move the discussion there, guys?
     
  16. jimells

    jimells Senior Member

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    Oh yeah, we're supposed to be discussing a review article, if only we had access to it...
     
  17. Scarecrow

    Scarecrow Revolting Peasant

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    o_O

    It's free at the link you provided.
     
  18. jimells

    jimells Senior Member

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  19. Scarecrow

    Scarecrow Revolting Peasant

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    Oops! :redface:

    I didn't even notice that they were different......
     
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  20. JaimeS

    JaimeS Senior Member

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    Can't find it on Research Gate at all, either. Weird...

    -J
     

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