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Wolfe Hypothesis ~ Key causative processes involved in CFS/CFIDS/M.E.

Discussion in 'General ME/CFS Discussion' started by John H Wolfe, Sep 13, 2012.

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Does this theory seem plausible?

  1. Yes

    9 vote(s)
    24.3%
  2. Didn't read it

    5 vote(s)
    13.5%
  3. Not sure I fully understand it

    5 vote(s)
    13.5%
  4. No

    18 vote(s)
    48.6%
  1. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Better run or hide, John H Wolfe - the Hulk approaches..:aghhh::D

    Just please promise us that your next project is not "The Wolfe Therapy"...at a (high) price. If it is, you may find an army of Hulks after you...

    Oh - and please test it on yourself first before presenting it to the world.
    Snowdrop and Valentijn like this.
  2. John H Wolfe

    John H Wolfe Senior Member

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    Never made such a link myself but I'm interested in differential presentations :)

    Oops, should have been psychopathological!

    (although I'm not sure even that term is really suitable for what I'm trying to encapsulate)
  3. John H Wolfe

    John H Wolfe Senior Member

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    Just noting some interesting observations. Personally I have no problem talking about my own sub-disorders (e.g. compulsive behaviours, above) but I have no history of depressive/anxiety disorders :)

    You'd have to ask the study organisers these things (I'm guessing not re: your 2nd question though)

    At some stage I will critically evaluate as many references as possible but as I'm still writing the 1st draft of the paper and the references amount to over 150 papers

    If you take the time to read my discussion with MeSci you'll note my thoughts on psychophysiology

    That would be handy to know for the purposes of relative comparison aye

    I'm afraid not, anyone following my work will note that I keep moving the goal posts re: my theories the more I learn about different pathophysiological explanations and their possible interplay
  4. John H Wolfe

    John H Wolfe Senior Member

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    I've always helped people for free but what's wrong with folks providing therapy (at any price)?

    Giving false hope/lending credence to psychobabble/unsustainable GET is of course hazardous, but otherwise.. people are free to pick and chose/take or leave the various therapies out there, and we are lucky we're living in the internet age where word of mouth/reviews are relatively easy to come by :)

    I am not a (qualified) health practitioner, and have no plans to/am not currently in a position to/interested in delivering therapy in a professional setting. My main aims are:

    1) To construct this systems biology disease model that provides a platform for better understanding of the illness by all (especially medical researchers/trial designers)

    2) Off the back of that, to provide insights/ideas for protocol design that may enhance wellness, chances of remission and possibly recovery
  5. Valentijn

    Valentijn Activity Level: 3

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    You can't rely on bad sources ... it's not good enough to say "well it got published, so it must check out." If you read it thoroughly, and basic questions like the ones above are not answered, then the conclusions drawn by that paper simply cannot be trusted and used to support any theories or arguments.
    Snowdrop likes this.
  6. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    What's wrong is when the 'therapy' is based on poor evidence or no evidence and has the potential to cause harm. For example, at your second link you say

    Many people with ME are deficient in minerals/electrolytes due to passing large quantities in urine - osmotic or solute diuresis. Drinking water - a hypotonic fluid - will further dilute the blood and exacerbate the deficiency. I ended up seriously ill in hospital from hyponatraemia, for example. I was not far off dying. People with this type of osmotic diuresis/polyuria need to drink fluids that are at least isotonic and ideally hypertonic. In any case, I believe that the advice to drink 2 litres a day is based on poor evidence, even for healthy people.
    leela, helen1, peggy-sue and 2 others like this.
  7. John H Wolfe

    John H Wolfe Senior Member

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    No evidence and potential harm are of course an undesirable basis for any treatment. However evidence for efficacy is often limited (nature of the beast) and owing to the complex and enigmatic nature of the illness, plus the wide variety of presentations and relationships with changes in this or that parameter, the potential for harm cannot ever fully be removed

    I have responded to your other points in the appropriate thread
  8. John H Wolfe

    John H Wolfe Senior Member

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    Indeed..

    "The detection of ATP activity by receptors on ATP potassium channels determines glutamate and GABA production and hence the glutamate:GABA ratio. ATP depletion is associated with NMDA stimulation and when cells containing NMDA receptors become ATP depleted, these receptors become hypersensitive to further stimulation.(Pall, 2003) Furthermore, low neuronal energy production markedly increases sensitivity to glutamate excitotoxicity.(Blaylock & Maroon, 2012)" ~ Draft paper

    This rudimentary/rough (unfinished) diagram I put together just yesterday to help illustrate the central component of my disease model may be of interest here (elements on the right hand side relate to what you mentioned)
  9. John H Wolfe

    John H Wolfe Senior Member

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    Updated working draft abstract:

    A NEUROIMMUNE MODEL FOR THE ETIOPATHOGENESIS OF MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) a debilitating condition of unknown aetiology, classified as a disease of the central nervous system by the World Health Organisation. In recent years the disease has been linked to neural sensitivity and sensitisation. In this speculative article I describe a new neuroimmune model for the etiopathogenesis of ME/CFS in this context

    Drawing upon relevant findings from the neurology literature, and in the light of the reported efficacy of Rituximab and Naltrexone, as well as purported overlaps with migraine pathophysiology, I present a rudimentary model for the etiopathogenesis of ME/CFS centred on glial activity and neural (hyper)sensitivity. The model holds the following as central to etiopathogenesis: glial priming, and possible gliopathy - relating to a synergistic (neuro-glial) dysfunction and/or (fungal) glio-toxin exposure, in the context of persistent pathogenic and/or biomechanical sources of chronic peripheral nerve infection/inflammation/nociceptive signalling. This results ultimately in neural sensitivity and central sensitisation effects

    [​IMG]

    Neural sensitivity associated with excitotoxicity, neuroinflammation, and possibly also central sensitisation and subsequent sensory gating irregularities, enhances the potential for pathogen activation and adverse neuroimmune responses including glial dysfunction and autoimmunity, as well as the central initiation of ‘sickness behaviour’ and dysautonomia

    This neuroimmunological model may explain why only a small proportion of the general population infected with pathogens commonly associated with ME/CFS go on to develop the condition. The model provides a platform, and suggestions for, future exploration and testing of component pathophysiological links, as well as insights into the efficacy of existing treatment strategies and ideas for the development of fresh approaches

    Keywords
    ME/CFS; Myalgic encephalomyelitis; M.E; Chronic fatigue syndrome; CFS; Neural sensitivity; Microglial activation; Neuroimmune; Neuroexcitation; Excitotoxicity; Neuroinflammation; Neural sensitivity; Central sensitisation; Etiopathogenesis; Pathophysiology;

    Wolfe Hypothesis © John H Wolfe (2013)​
    beaverfury likes this.
  10. beaverfury

    beaverfury beaverfury

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    Looks good! Well done. A lot of work.

    Theoretically, microglial inhibitors could have a useful role to play in this model. Especially at onset.

    There doesn't seem to be much evidence of their use or effectiveness in me/cfs at the moment.
    Maybe low dose naltrexone for fibro. http://www.ncbi.nlm.nih.gov/pubmed/23359310

    Probably early days yet.
  11. John H Wolfe

    John H Wolfe Senior Member

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    Thanks, yes indeed, getting that diagram alone worked out/put together took me the best part of an afternoon! hehe

    Aye

    Do you know if there is any?

    From my infection and immune status section:

    "One or more of these themes [B cells/microglial autoantibody relations] may, in part, help explain why Rituximab and Low-dose naltrexone (LDN) have been shown to improve symptoms in ME/CFS (Fluge et al, 2011) and the overlapping condition fibromyalgia [FM] (Younger et al. 2013) respectively in early trials.

    Naltrexone is a drug that blocks the opioid/endorphin receptors in the brain, apparently resulting in increased compensatory endorphin production, and inhibits microglial activation.(Younger et al. 2013) Endorphins relieve pain and are produced by the hypothalamic pituitary adrenal (HPA) axis, a glandular system broadly held as being dysfunctional among patients with ME/CFS and FM.(Papadopoulos, 2012)" ~ Draft paper
  12. beaverfury

    beaverfury beaverfury

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    Good point.
    I took a quick lazy look through the ncbi pubmed archives and couldn't find any. I'm out of my league here though.

    Ibudilast, a drug used for asthma, has been mentioned as a possibilty, http://www.mecfsforums.com/index.php?topic=4512.0
    but i can't find any research directly relating it to me/cfs treatment.

    Cort and Marco, over at Healthrising have done a good job of discussing possible neuroinflammation models, with microglial activation in me/cfs.
    http://www.cortjohnson.org/blog/201...py-implications-for-chronic-fatigue-syndrome/
  13. John H Wolfe

    John H Wolfe Senior Member

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    Me either, and me too really (not as learned or in the loop as professional/qualified experts)

    I'll look into that, thanks - very interesting!

    Yes indeed, speaking to Marco/incorporating bits and bobs from his series into my discussion, and Cort's site more generally, has been extremely helpful indeed :)
  14. John H Wolfe

    John H Wolfe Senior Member

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    The 2nd draft of the paper I am writing off the back of this work is now complete. Updated abstract:

    A NEUROIMMUNE MODEL FOR THE ETIOPATHOGENESIS OF MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) a debilitating condition of unknown aetiology, classified as a disease of the central nervous system by the World Health Organisation. In recent years the disease has been linked to neural sensitivity and sensitisation. In this speculative article I describe a new neuroimmune model for the etiopathogenesis of ME/CFS, in this context.

    Drawing upon relevant findings from a diverse literature, I present a rudimentary model for the etiopathogenesis of ME/CFS, centred on glial activity, neuronal hypersensitivity, and related neuroinflammation. The model holds the following as central to etiopathogenesis: glial priming, and possible synergistic neuro-glial dysfunction, in the context of (fungal) glio-toxin exposure, and/or persistent pathogenic and/or biomechanical sources of chronic peripheral nerve infection/inflammation and associated distortions, and chronicity, in nociceptive and ‘sickness behaviour’ signalling.

    [​IMG]

    Neural sensitivity and central sensitisation effects associated with cytokine and excitotoxic products of glial activation enhance the potential for pathogen activation and adverse neuroimmune responses including immune dysregulation, glial dysfunction and autoimmunity. Central initiation of sickness behaviour, neuroendocrine dysfunction, and related hypothalamic pituitary adrenal (HPA) axis dysfunction and dysautonomia, are also a corollary.

    This neuroimmunological model may explain why only a small proportion of the general population infected with pathogens commonly associated with ME/CFS go on to develop the condition. It provides a platform to help direct more focused future research into component pathological thematics, and elucidates important probable pathophysiological links within those thematics, as well as conceptual insights into the efficacy of existing treatment strategies and a broad array of ideas for the development of fresh approaches.

    Keywords
    ME/CFS; Myalgic encephalomyelitis; M.E; Chronic fatigue syndrome; CFS; Neural sensitivity; Microglial activation; Neuroimmune; Neuroexcitation; Excitotoxicity; Neuroinflammation; Neural sensitivity; Central sensitisation; Etiopathogenesis; Pathophysiology;
  15. John H Wolfe

    John H Wolfe Senior Member

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    Updated abstract:

    A PSYCHONEUROIMMUNOLOGICAL MODEL FOR THE AETIOPATHOGENESIS OF MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) a debilitating condition of unknown aetiology, classified as a disease of the central nervous system by the World Health Organisation. In recent years the disease has been linked theoretically to neural sensitivity and sensitisation. In this speculative article I describe a new neuroimmune model for the etiopathogenesis of ME/CFS, in line with this increasingly prevalent conception.

    Drawing upon relevant findings from a diverse literature, I present a rudimentary model for the etiopathogenesis of ME/CFS, centred on glial activity, neuronal hypersensitivity, and related neuroinflammation. The model holds the following as central to etiopathogenesis: glial priming, neuroinflammation, and possible synergistic neuro-glial dysfunction, in the context of (fungal) glio-toxin exposure, and/or biomechanical and/or persistent pathogenic sources of chronic peripheral nerve inflammation/infection and associated distortions, and chronicity, in nociceptive and ‘sickness behaviour’ signalling.
    [​IMG]

    Neural sensitivity and central sensitisation effects associated with products of glial activation enhance the potential for pathogen activation and adverse neuroimmune responses including immune dysregulation, glial dysfunction and autoimmunity. Central initiation of sickness behaviour, neuroendocrine dysfunction, and related hypothalamic pituitary adrenal (HPA) axis dysfunction and dysautonomia, are also a corollary.

    The proposed model may explain why only a small proportion of the general population infected with pathogens commonly associated with ME/CFS go on to develop the condition. It provides a platform intended to help direct future research towards potentially key component pathological thematics, and elucidates important probable pathophysiological links within those thematics, as well as conceptual insights into the efficacy of existing treatment strategies and a broad array of ideas for the development of fresh approaches.

    Keywords
    ME/CFS; Myalgic encephalomyelitis; M.E; Chronic fatigue syndrome; CFS; Neuronal sensitivity; Microglial activation; Neuroimmune; Neuroexcitation; Excitotoxicity; Neuroinflammation; Central sensitisation; Etiopathogenesis; Pathophysiology; Etiology.​
  16. philpot

    philpot

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    http://www.nhs.uk/Livewell/Goodfood/Pages/water-drinks.aspx

    "The European Food Safety Authority recommends that women should drink about 1.6 litres of fluid and men should drink about 2.0 litres of fluid per day. That's about eight 200ml glasses for a woman and 10 200ml glasses for a man."

    Regards.
  17. philpot

    philpot

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    John, you write some good stuff and there are some thought provoking items in there and for me this as it should be. Until someone has a clear cut answer on the cause of ME/CFS and which can be scientifically proven we should stimulate discussion and different ways of thinking about things.

    Regards.
  18. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    That's not evidence, but advice, and it refers to fluid, not water.

    Here is the rest of my post that you quoted from:

  19. philpot

    philpot

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    Thank you for replying to my post. :) The link etc., is from a National Health Service and which is regulated by the Government. Actually there are lots of such links and we have all over the internet doctors saying things one year which are then found to be nonsense years later and so on.

    So if these people cannot even get it right over a simple thing like water then how can we really ever be sure about 'evidence' on the things related to ME/CFS? All the scientific evidence would appear to be 'dodgy', all of it.

    Are we going to wait for some doctor to come up with a solution and then provide umpteen scientific studies in order to prove that pill/operation will work before we take it? If we do then decades of our lives will be gone because that is how long it is going to take......do you want to waste your life?

    You have an MSc, so do tell me what is missing here and what opportunity exists to do something about it? I believe we have here a group of people who have a vested interest in getting better and we have an illness or illnesses which are a little bit complicated. How do we solve complicated? Shall we formulate an approach to solving complicated and then work together collectively on it and in a more organised way?

    I believe we can do this but I do think in order for us to do so we have to also be prepared to critically analyse ourselves along the way and proceed with open minds, logic and reason and not be going into running each other down. If in the meantime some doctor comes up with the magic pill then great we'll take it.

    Regards.
  20. philpot

    philpot

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    Let us discuss 'critical thinking' because this is something which is applied, or should be, by those who have the highest qualifications, i.e., doctors. In order to research you have to be able to critically analyse and also be objective, of course this also means ourself in order to remove our own bias from the subject we are researching.

    This is sometimes difficult when people have been ill for a long time because they bring thier own biases into the things they report.

    Doctors even critically analyse each other's work, after all that is what researchers are taught to do. I think one of the issues we ill people have is that we tend to want to sometimes lash out at others who present ideas, experiences, theories, etc., and maybe tell them what they suggest is insulting to us whilst actually it is not, it's just an idea or thery for discussion and to be critically analysed.

    Let us discuss this thing called 'evidence' and get rid of the myth that many people seem keep alive. Let us say that Me Sci were to tell me that she had a pain in her muscle, i.e., her brain was registering a pain, she would not be able to offer any peer reviewed scientific evidence at all to prove she had that pain. Therefore if I were to always ask for evidence then of course I would have to conclude the pain was a figment of her imagination.

    Rather like ME/CFS, yes it's all a figment of the imagination, or is it! Funny how we who are often accused of making up our illness often then often ask everyone else for evidence for many things they suggest. :)

    It's good to ask for evidence of course but let's not forget that sometimes we just need to be open minded and discuss things through and see where we end up. We landed on the moon because someone had the initial idea; the evidence for it did not exist until we had made the idea work. People made that idea work by working together as a team, drawing on each others strengths.

    Now my point is that Me Sci knows 100% and without any doubt that she has this pain and therefore she knows something to be true that the outside world cannot prove either way. Now let us say that philpot was then to say 'hey guys' Me Sci has a pain in her muscle. Again I would have no peer reviewed scientific proof and yet Me Sci would know 100% and without any doubt that I was 100% correct about something which I had no evidence for.

    My point is that it is perfectly possible and reasonable for someone to be 100% correct about something even though they cannot provide peer reviewed science/evidence to back it up. So on the basis that there is no peer reviewed science which states without any doubt what is the cause of ME/CFS or else what the solution is then all the theories and ideas etc., proposed by all people in these forums could be 100% correct, we do not know.

    If everytime we who are often accused of inventing our illness start going on about evidence we should remember two things:

    1. We may well be asked to provide the scientific peer reviewed evidence to prove we are ill.
    2. We may just snub out the idea/theory which may have otherwise ended up leading to the road to our cure.

    I am all about hearing people's ideas and theories and discussing them openly and honestly and collectively and without thowing my dummy out of the pram or prentending to be offended or insulted just because someone suggests something may be in my mind; because this also needs to be explored and discussed.

    I am also not about asking for peer reviewed science on everything because this is an area where the science thus far does not amount to much. It may be our discussion which develops the evidence and this will not happen if we 'shout' people down.

    Also for each of us when we try something ourselves in order to improve our lives so we need to think critically about the other things which may be happening and which may have instead improved things, we need to be careful about this because otherwise we may ourselves miss the thing which actually helped because we were blinded by the particular thing we were trying.

    Regards.
    Last edited: Feb 26, 2014

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