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Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Discussion in 'General ME/CFS Discussion' started by cfsStevew, Feb 11, 2015.

  1. cfsStevew

    cfsStevew

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    Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

    http://jnm.snmjournals.org/content/55/6/945/F3.expansion.html

    Hi All

    Im writing this due to the recent IOM suggested name change to SEID. I guess they decided to change the name due to lack of evidence of inflammation...?

    I know the trial posted above was only based on 9 CFS/ME patients - but having reviewed it - apart from a increase in sample size - I cannot understand how it could have been much better as an example of neuroinflammation in CFS and ME:

    Between 45% and up to 199% increase in microglial activation levels from control to patient (depending on brain area)

    Fairly clear correlation between reported symptoms via questionnaire and recorded brain inflammation levels...This to me is a really key point I think the medical profession ought to reflect on. There is evidence for a physical marker which increases in line with a patients reported fatigue and illness levels...in a climate of disbelief where psychiatrists are still sectioning patients - should this information not be shouted from the rooftops?

    Its a little frustrating I think for patients when there is evidence like this however it seems the momentum of the medical system is barely bothered by it...and I KEEP reading about neurologists who state there is no evidence for inflammation...

    It comes back to my question I made to Dr Shepherd - which is - how much evidence do you need to make a difference? In the western world we have to rely on small charity run studies and hard fought piecemeal government efforts...how long is it going to take to provide the quantity of evidence needed to make a real difference?
     
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  2. adreno

    adreno PR activist

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    I don't know when it's enough; it looks like a good study, and certainly at least a basis for larger trials.

    PET studies are expensive, though. They are also quite invasive. Funding?
     
  3. Sasha

    Sasha Fine, thank you

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    That's it, though... 9 patients... not enough to hang a $1m name-change on.
     
  4. cfsStevew

    cfsStevew

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    maybe they should spend that $1m on finding out what the illness is before they try again to rename it?! ;)

    In fairness the rest of the report is excellent...

    but lets not forget many people around the world refer to ME which is inflammation of the brain and spinal cord...so in many areas its a retrograde step...
     
  5. A.B.

    A.B. Senior Member

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    I think ME is mainly used in the UK, where it's mostly seen as behavioral disorder. The name doesn't mean much.
     
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  6. charles shepherd

    charles shepherd Senior Member

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    Reply

    I suspect that you may have missed one of my fairly regular responses in relation to neuroinflammation and the relationship to a diagnosis of encephalomyelitis

    Neuroinflammation occurs in a number of inflammatory and infective diseases. Examples include hepatitis C, HIV and lupus.

    The presence of neuroinflammation in the well publicised Japanese study does NOT mean that these patients have what neurologists and neuropathologists would recognise or define as an encephalomyelitis.

    Encephalomyelitis refers to widespread and significant inflammation involving both the brain and spinal cord.

    From a clinical point of view, encephalomyelitis presents with severe neurological symptoms and signs, which may be life threatening.

    There is, at present, no pathological or neuroradiological evidence to show that people with ME/CFS have an encephalomyelitis, and that incudes the findings from the post mortem research group that I am a member of.

    Like everyone else, I want to establish what the neuropathology of ME actually is - but there is no point in coming to flawed conclusions about cause unless there is sound scientific evidence to demonstrate what you are claiming.

    Abstract from our paper in the Journal of Neurological Sciences on post-mortem findings which have also
    demonstatred neuroinflammation in the form of dorsal root ganglionitis:

    Pathology of Chronic Fatigue Syndrome: Pilot Study of Four Autopsy Cases

    DG O’Donovan1, 2, T Harrower3, S Cader2, LJ Findley2, C Shepherd4, A Chaudhuri2
    1Addenbrooke’s Hospital Cambridge UK
    2Queen’s Hospital Romford Essex UK
    3Royal Devon & Exeter Hospitals UK
    4Honorary Medical Advisor to ME Association UK

    Chronic Fatigue Syndrome / Myalgic Encephalomyelitis is a disorder characterised by chronic exercise induced fatigue, cognitive dysfunction, sensory disturbances and often pain. The aetiology and pathogenesis are not understood.

    We report the post mortem pathology of four cases of CFS diagnosed by specialists.

    The causes of death were all unnatural and included: suicidal overdose, renal failure due to lack of food and water, assisted suicide and probable poisoning.

    Selected portions of tissue were made available by the various Coroners in the UK and with the assent of the persons in a qualifying relationship.

    The cases were 1 male, and 3 female. Ages (years) M32, F32, F43 & F31.

    One case showed a vast excess of corpora amylacea in spinal cord and brain of unknown significance but Polyglucosan Body Disease was not supported by clinicopathologial review. No ganglionitis was identified.
    One case showed a marked dorsal root ganglionitis and two other cases showed mild excess of lymphocytes with nodules of nageotte in the dorsal root ganglia.

    This raises the hypothesis that dysfunction of the sensory and probably also the autonomic nervous system may lead to abnormal neural activity eg hyperalgesia & allodynia rather than anaesthesia and may explain some of the symptoms of CFS / ME such as pain, hypotension, hyperacusis and photophobia. However, the syndrome may be heterogeneous.

    Nevertheless, the precise relationship of fatigue, which may be either peripheral or central, to abnormalities in the peripheral nervous system (PNS) needs to be studied.

    The differential diagnosis of ganglionitis should be investigated in CFS / ME patients hence Varicella Zoster, Lyme disease, HIV, Sjogren’s disease, paraneoplastic sensory ganglionopathy should be excluded by appropriate history and tests.

    Thorough histopathological study of cases coming to autopsy may help to confirm or refute the hypothesis, that CFS is a disease process, and whether the symptomatology may be explained by inflammation of the sensory and autonomic divisions of the PNS.

    A specific CFS / ME brain and tissue bank in the UK is proposed.

    Further CS notes:

    The dorsal root ganglia (DRG) are, in very simple terms, minute bundles of nerve cell bodies that lie outside the spinal cord - and so form part of the peripheral nervous system.

    So inflammation of the DRG is not the same as myelitis in ME. Myelitis refers to inflammation of the spinal cord.

    The DRG appear to be involved in the transmission of sensory information, and so disturbances in function may result in sensory disturbances and pain

    Dorsal root ganglionitis, inflammation of the DRG, can be caused by infection such as chickenpox

    But it can be associated with specific conditions such as Sjogren's Syndrome - which has some interesting overlaps with ME/CFS, including debilitating fatigue.

    In the case of SS, the presence of DRG-itis has been linked to the sensory neuropathy that occurs.

    As far as ME/CFS is concerned, we just don't know at this stage whether DRG-itis is part of the disease process, or whether it could just be the result of a triggering infection such as herpes

    As we do more post mortems the position may become more clear.


    Dr Charles Shepherd Hon Medical Adviser, MEA
     
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  7. charles shepherd

    charles shepherd Senior Member

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  8. anciendaze

    anciendaze Senior Member

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    Question concerning clinical precision: What acronyms do you use in place of malaria and influenza?
     
  9. alex3619

    alex3619 Senior Member

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    I concur with @charles shepherd , the definitions of inflammation and what we are seeing in microglia do not match up. We have immune activation of some kind, but what kind of inlfammatory state it is has not been properly determined. Those claims will depend on future research.

    However its already been discussed that this disorder might be called Limbic Encephalitis. That is, an alternative kind of encephalitis. Its less intense, and instead of acute issues its chronic. This however is still only an unproven hypothesis.

    The reason encephalomyelitis is indefensible as its usually identified by brain or spinal lesions which are permanent. We have lesions, but its unclear these are consistently permanent.

    I have had bone fide encephalitis and its not fun. People die. In fact that is when I put the start of my ME, uhhhh, possible SEID - measles encephalitis, age 7, 1968.

    The IOM panel would have been very careful not to say too many things that can easily be challenged. This is one of those.

    I still like ME though. It has gravitas. That is a personal thing, and due to its link to the primary symptom of post exertional malaise. Which SEID has.
     
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  10. charles shepherd

    charles shepherd Senior Member

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    Wiki has quite a good entry on neuroinflammation:

    http://en.wikipedia.org/wiki/Neuroinflammation

    and the comment on exercise, which I have discussed with a colleague working in experimental neuropathology, is quite intesting:

    Role as a Therapeutic Target
    Drug Therapy
    Because neuroinflammation has been associated with a variety of neurodegenerative diseases, there is increasing interest to determine whether reducing inflammation will reverse neurodegeneration. Inhibiting inflammatory cytokines, such as IL-1β, decreases neuronal loss seen in neurodegenerative diseases. Current treatments for multiple sclerosis include interferon-B, Glatiramer actetate, and Mitoxantrone, which function by reducing or inhibiting T Cell activation, but have the side effect of systemic immunosuppression [15] In Alzheimer's disease, the use of non-steroidal anti-inflammatory drugs decreases the risk of developing the disease. Current treatments for Alzheimer's disease include NSAIDs and glucocorticoids. NSAIDs function by blocking conversion of prostaglandin H2 into other prostaglandins (PGs) and thromboxane (TX). Prostoglandins and thromboxane act as inflammatory mediators and increase microvascular permeability.

    Exercise
    Exercise is a promising mechanism of prevention and treatment for various diseases characterized by neuroinflammation.[9] Aerobic exercise is used widely to reduce inflammation in the periphery. Exercise has been shown to decreases proliferation of microglia in the brain, decrease hippocampal expression of immune-related genes, and reduce expression of inflammatory cytokines such as TNF-α.
     
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  11. charles shepherd

    charles shepherd Senior Member

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    Thanks - as my personal experience of ME was triggered by chickenpox encephalitis, I have a lot of sympathy with people who want to use the term encephalomyelitis. I just don't believe on the evidence we have that this a pathologically correct term to describe what is happening once this illness enters a chronic stage.
     
  12. physicsstudent13

    physicsstudent13 Senior Member

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    I have terrible neuro degeneration with blindness, facial palsy, loss of hearing and taste and terrible severe brain fog and diabetes damage. aspirin has many beneficial. I recently think I may have had a stroke. are any of these drugs safe to try?
     
  13. cfsStevew

    cfsStevew

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    thanks - yes it makes sense - I replied on the other thread.

    http://forums.phoenixrising.me/index.php?threads/new-name-for-me-cfs.35440/page-2#post-557309

    I suppose it makes sense why the ME community has received a bit of a short shrift (anecdotally) from neurologists - because they may see a very severe and critical encephelitis.

    Still the japanese study is mentioned because at least if offers something positive that could be replicated...and perhaps an additional direction...the low grade inflammation seems quite plausible to me as part of the picture.
     
    Last edited: Feb 11, 2015
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  14. physicsstudent13

    physicsstudent13 Senior Member

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    what about valcyte, are there any cheap places to buy it, since I'm sure some doctor won't prescribe it unless I was in the ER dying
     
  15. charles shepherd

    charles shepherd Senior Member

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    Valcyte has a potential to cause serious side effects - so should only be used under medical supervision and where there are good reasons for doing so. It is not a 'do it yourself' treatment. Please don't try to treat yourself with antiviral drugs such as this purchased via the internet.
     
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  16. physicsstudent13

    physicsstudent13 Senior Member

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    http://en.wikipedia.org/wiki/Valganciclovir#Side_effects
    I do have the chicken pox virus or herpes zoster. The retinal detachment and myelosupression side effects seem really serious. Especially since I'm already going blind from glaucoma and have blurry vision just from diabetes and high sugar

    I think rocephin may help neuro inflammation
     
  17. picante

    picante Senior Member

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    I was hiking up 12,000-ft. mountains, back-country skiing, working summers in Yellowstone and Alaska, figure skating, and dancing up a storm. Before EBV crashed my metabolism. Prevention??? Maybe... I'm more functional than a lot of people here, at activity level 5-6.

    Trouble is, all that "prevention" couldn't compete with a jillion toxins and pathogens:
    • Perchlorate (ages 8 to 17) – there was rocket fuel in our municipal drinking water
    • Mercury (amalgams)
    • Lead – I lived in extreme smog from age 0 to 17
    • Fluoride, bromide, chlorine
    • Polio vaccine during the years it was contaminated with SV 40 (1955-1963).
     
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  18. physicsstudent13

    physicsstudent13 Senior Member

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    ANYWAY I started tinidazole+doxycycline and I think my breathing is improving from mycoplasma/tuberculosis granuloma infection and I can exhale a little bit better

    what should I do? I'm so damaged from hypoxic low oxygen stroke and diabetes destroying my brain and eyes and kidneys and blood vessels and heart
    I take metformin which is a cheap and AFAIK safe medication for diabetes
     
  19. brenda

    brenda Senior Member

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    I would not like to shut down my liver's production of insulin with Metformin. I have been reducing my glucose with Vanadium and Chromium plus a sugarless and no fruit diet and my l;evels are coming down to normal.
     
  20. physicsstudent13

    physicsstudent13 Senior Member

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    well I was on metformin and then went off and drank lots of sugary drinks and didn't exercise and then I had this stroke with confusion trouble pronounincing and really blurry visiona nd dizziness.
    I don't think that's a good idea, even metformin isn't enough for many patients, many diabetics are on insulin and there is byetta and FGF1 now
    why is shutting down liver's production of insulin a bad idea? does it not regain production levels after metformin? I thought metformin suppose to stop liver production of glucose
     

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