A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
Mark Berry presents the first in a series of articles on the 11th Invest in ME International ME Conference in London ...
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New paper: Progressive brain changes in CFS

Discussion in 'Latest ME/CFS Research' started by Countrygirl, Apr 29, 2016.

  1. Countrygirl

    Countrygirl Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/27123773

    I have just seen this and hoped that some of our scientists here could judge whether it has any significance. The abstract doesn't state which diagnostic criteria were used.


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  2. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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  3. Keith Geraghty

    Keith Geraghty Senior Member

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    This evidence is just part of the vast evidence base Dr OSullivan ignored in her book - but then again she did say Neurologists have turned their backs on ME
     
  4. Hutan

    Hutan Senior Member

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    This is work done by NCNED, among others. The selection of the patients was probably done pretty well.

     
    Last edited: Apr 29, 2016
  5. Bob

    Bob

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    I think NCNED usually use Fukuda.
     
  6. Hutan

    Hutan Senior Member

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    Yes, somewhat.
    That matches.

    That's different.
     
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  7. Hutan

    Hutan Senior Member

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    Yes, but I think we have discussed NCNED's patient selection in relation to some of their other papers. They seem to be aware of the Canadian criteria and are probably doing a reasonable job of selecting patients. @alex3619 or others with direct experience with NCNED, maybe you have a comment?

    Possibly the fact that this study is rescanning patients first scanned 6 years ago and the involvement of the SA institutions may mean they haven't been quite so stringent about screening patients.

    It's hard to know much with just the abstract.
     
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  8. Sea

    Sea Senior Member

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    The full paper is available, it says patients met both Fukuda and Canadian Consensus Criteria
     
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  9. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Full paper: http://onlinelibrary.wiley.com/doi/10.1002/jmri.25283/full

    It seems really thorough. Surely they are on to something important here.

    From the conclusion:

    "this study detected continuing shrinkage of WM in the left IFOF in patients with CFS, but not in NCs. This result was consolidated by the pooled inter group comparisons revealing decreased regional WM volumes in adjacent regions and decreased GM and blood volumes in contralateral regions and by regression analysis showing significant correlations of WM and GM volumes and T2w intensities with CFS symptom scores in those regions. The superficial and dorsal subcomponent of the IFOF connects the frontal lobe with the superior parietal lobe and the ventral subcomponent of the IFOF connects the frontal lobe with the inferior occipital lobe and temporo-basal area.[26] Therefore, our findings are consistent with the decreased intrinsic connectivity in CFS within left fronto-parietal networks (FPN) found in a resting-state functional connectivity study.[27] Similarly, a diffusion tensor imaging (DTI) study reported bilateral white matter atrophy and increased fractional anisotropy in the arcuate fasciculus, possibly reflecting degeneration of cross fibers.[8]
    The IFOF connects networks of cognitive control, attention, language processing, and working memory[28] and links the bilateral insular regions and anterior cingulate cortex.[29] Considerable evidence suggested that the IFOF plays a pivotal role as the connectivity substrate in goal-directed cognition, mediating the dynamic balance between default mode network and dorsal attention networks.[30] Therefore, symptoms experienced by CFS patients, such as impaired concentration, working memory loss, inability to focus vision, and poor motor coordination could be explained, in part at least, by our finding of continuing shrinkage of WM in the IFOF. Our finding of IFOF WM shrinkage in CFS, together with consistent findings by us and others above, warrants more investigations to understand the pathomechanism of this deficit.

    Compared with NC, CFS patients also showed decreased GM volume and increased T1w and T2w signal intensities near the contralateral ILOF. The absence of corresponding longitudinal findings in the right hemisphere may be a result of lower sensitivity in longitudinal studies and/or because the changes in CFS occurred soon after onset (before the first scan) and did not progress appreciably thereafter. The increased T2w signal intensities suggest possible decreased blood volume in these regions.[31] Indeed, previous studies have found decreased regional cerebral blood flow in frontal and temporal lobes[32] and decreased frontal oxygenation[33] in patients with CFS. Thus, a gradual and chronic hypoperfusion of the brain may contribute to this continuing WM shrinkage.

    Additionally, chronic functional hypoxia due to dysfunction of the neurovascular unit could also cause neurodegeneration.[34] Of interest, a recent study found seventeen single nucleotide polymorphisms (SNPs) were significantly associated with CFS.[35] Nine of these SNPs were associated with muscarinic acetylcholine receptors and eight with nicotinic ACh receptors (nAChRs). ACh, a neuromodulator in the brain, changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs. Control of synaptic Ca2+ concentration following nAChR stimulation is a major pathway for ACh to influence neuronal networks.[36] Furthermore, nAChRs are also present in the cerebral vascular endothelium and smooth muscles.[37] Thus, aberrant AChR function may impair cerebrovascular autoregulation and cause chronic functional hypoxia. Distribution of moderate nAChR density in temporal parietal cortices and low levels in white matter tracts could make IFOF more vulnerable to aberrant AChR function. Furthermore, the IFOF is in a brain region that undergoes continued organization in early adulthood[38] and is particularly vulnerable to vascular risk factors.
    [39]"
     
  10. CFS_for_19_years

    CFS_for_19_years Hoarder of biscuits

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    I tweeted the link to O'Sullivan - I sense a blocked Twitter account coming on soon.

     
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  11. Kati

    Kati Patient in training

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    i love this :D:rolleyes::whistle::woot::angel::cool:
     
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  12. Woolie

    Woolie Senior Member

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    The patients seem to have met both Fukuda and CCC criteria.

    The study is rather well done, and its good that they compared the same patients across two timepoints, rather than just across groups (where there could be all sorts of confounding factors). The MRI machine they used is pretty low resolution (1.5 Tesla). But to be honest, I don't think you need enormous resolution for this kind of study.

    The IFOF is one of the longest white matter tracts that connects cortical regions with one another. So it makes sense that its the first place you might see any atrophy (shrinkage). The authors suggest the atrophy may be caused by poor blood supply, although I'm not sure why they think this.

    There is not a hint of psychobabble.

    Limitations are that only the left IFOF showed a reliable effect, and you would expect both sides to show it. So it could just be a chance effect after all. Also, a lot of measures were obtained. Tthey said they corrected for the total number of measures (there's an increased chance of getting a significant result just by chance alone when you do a huge number of tests). But its a worry that not all the measures obtained seemed to be consistent with one another. One comparison even showed an effect in the opposite direction to that predicted (some white matter volume measures were positively correlated with Somatic symptoms scores - that is greater volume was associated with more - not less - symptoms).

    There's not a lot of consideration of individuals, so its unclear how many people showed the group effects. This si important, because some CCC people might actually have something like MS, but it hasn't yet shown up on any conventional tests.

    I'm not sure why they didn't do more people. That would have helped a lot (and this stuff isn't that expensive any more).
     
    Last edited: May 1, 2016
  13. Kati

    Kati Patient in training

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    Thank you @Woolie
     
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  14. Sea

    Sea Senior Member

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    Money is certainly one of the limiting factors. Another is finding enough suitable applicants. Not only do they screen carefully to make sure people do have ME/CFS, they also rule out for their study co-morbid disorders and anyone taking medication that they can't/choose not to stop for a week before the test. I was a subject in one of the earlier MRI studies by Barnden and Kwiatek.
     
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  15. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    It seems that chronic severe ME may be a risk factor for vascular dementia in later life.
    (One sign of dementia is reduced blood flow to the brain).

    Does it surprise us from this new reseach, that if PWME have brainstem hypoperfusion (hypoperfusion shown by Costa et al in the 1990's on neuroimaging), and are then left for 30 years told to do CBT/GET and take antidepressants that some of us will end up with dementia? No it doesn't, sadly.

    21 years ago, this was discovered....

    It won't surprise me at all to learn 'brain fog' (cognitive defect worsened by 'thinking') is a form of post infectious brain damage either, especially more prominent cognitive dysfunction in severe cases in which the patient was without this symptom, became very ill from an infection, and then never lost this neurological symptom from that day onwards.

    What makes me mad is this long term neglect of patients lives, was avoidable:

    Diagnosing but then leaving patients to fend for themselves from 1988 with a diagnosis based on tiredness is incredibly reckless of the CDC to do, by creating CFS and incorporating many misdiagnoses within
    the CFS umbrella.

    I imagine this finding, if it becomes a biomarker for some (or all) will be just one physical test that although we will finally appreciate being taken seriously, we won't appreciate how this all happened.

    For once, I will end there but my suspicions of all this lie with Borrelia/Bartonella (infects lining of blood vessels) and other neuroinvasive infection that crosses the blood brain barrier -due to these classes of infection. A permeable BBB explains many of the problems PWME PWCFS suffer from including hyper drug sensitivity and susceptibility to infections.

    Inviting in psychiatry to look after us during all this, well...what could possibly go wrong?

    [​IMG][/quote][/quote]
     
    Last edited: May 1, 2016
  16. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    I don`t think there`s any evidence for a heightened dementia risk, at least i can`t remember reading of such a thing..;)
     
  17. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    Progressive white matter loss, over decades, due to low grade inflammation will increase your risk of neurodegnerative disease, however, it depends how severe it is and where it is.of course, but the key risk factor here is the patient experiencing cognitive decline.

    Severe grade PWME can have cognitive decline, some report it in childhood, others adolescence - fast forward these people 30 years, untreated. I am confident they will have significant problems in their 50's and 60's, if in their 20's they are putting their car keys in the fridge and not remembering how to spell and experience confusion out a familiar environment.

    Back to this study:

    This study was over 6 years in people well enough to attend brain scanning.The results may have been the same, or worse in people much more ill. We don't know.

    In my opinion chronic severe ME is potentially linked to increased risk of vascular dementia in the severely affected because of the multiple infections they carry, which likely causes chronic low grade neuroinflammation in the brain and oxidative stress damaging to the brain, ageing it either directly or indirectly via autoimmunity.

    Why am I confident this new study isn't a red herring and 'fluke' that two different countries found similar results?:

    Its not published and may not be published at all, if the early findings aren't found in others, but I know this from a group looking at dementia in ME. When I said severe ME and risk of vascular dementia in my other post, I mean Chronic Lyme (Chronic Lyme, not being Lyme but a different condition) but I can't say that yet as there's no 'proof', I just know it exists behind closed doors.

    Have you been able or considered checking your PrPC? I have, and it barely exists, it's around 20+ lower than my elderly father - not good! I've also tested controls and my family. What I found was, the more severe the 'CFS', the less PrPC present. Is this definitive proof of much, no. A Lumbar Puncture PrPC test to my knowledge is not available though - now that would be a deciding factor to prove PWME have absent PrPC, because if they have absent PrpC the inference is, it's possibly transcribed to a deranged form, and then all hell can break loose as from rogue prions you can get amyloid and from amyloidosis you can get dementia.

    From above...MS + SLE are two autoimmune diseases. HIV (retrovirus), Lyme (Bacteria). The common denominator? Inflammation.

    I'm not suggesting PWME 'catch' ME and end up demented, I'm suggesting some severe PWME will likely increase their risk of dementias in later life, because of the chronic low grade brain inflammation that occurs, left for decades, unchecked. This may be related to loss of PrPC protecting the brain, my opinion, not proven.

    That's why I think this study is interesting as it's not in very severe or extreme severe ME patients who are wearing headphones and ear defenders who can die in their 30's (I've seen them), and who before they die have massive neurosensory derangement to the extent they don't even drink or can't be touched. And yes they have ME and not the wrong diagnosis,they just have an extreme accelerated form of it. Sometimes the 1% of patients can help explain the 99% of others, because in the others, the 'damage' is too slow to measure during a life time (slow burning).


    I feel this is all totally predictable if the authorities leave people with teenage onset ME + cognitive dysfunction with 'new headache', who say their brain feels on fire, feel like their head is empty of blood (as it is) and leave them without researching their disease extensively at a biomedical level. Well that's happened.

    Unchecked, chronic, neuroinflammation,will age your brain over decades Vs Healthy Controls of the same age and by ageing it with ROS you will increase your risk of brain damage such as dementia and risk having a premature CVA too.

    This study shows progressive brain damage (white matter loss) in 6 years, in people who aren't severe.
    I'd love to see it over 30 years in the severely affected Vs Healthy Controls, patients who are borderline 'Mild Cognitive Impairment' especially.
     
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  18. Woolie

    Woolie Senior Member

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    @Marky90, I haven't seen this either, but vascular dementia has a very different disease process from Alzheimer's etc. Basically, its what happens when a person has a series of mini strokes that over a long period.

    Just thought I'd mention that, cos it wouldn't necessarily mean more dementia overall.
     
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  19. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Gotccha! I`m just thinking that the rtx-responders seems to show that our cognitive impairments are revversible, and I doubt our underlying disease mechanism restricts blood flow so much in the brain that it leads to vascular dementia; cause that`s usually not completely revversible is it?
     
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  20. Sea

    Sea Senior Member

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    I have had ME/CFS for 30 years this June. My cognitive function is significantly impaired but I don't think there is a decline. It gets worse with PEM and stabilises back to my baseline when I'm not pushing too much.
     
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