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My thoughts on why I think ME/CFS is not, at its root, a putative neuroinflammatory disease

Discussion in 'General ME/CFS Discussion' started by leokitten, May 31, 2015.

  1. leokitten

    leokitten Senior Member

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    Continuing on the very nice discussions and debate we've been having as to whether ME/CFS is more infectious or autoimmune I want to throw out this controversial opinion based on my own treatment results and in light of the rituximab findings.

    Let me be clear I totally believe that there is some neuroinflammation in ME/CFS and it's been proven (Shungu et al, Nakatomi et al). I just think that it's a secondary effect to peripheral immune activation and this is also seen in a number of autoimmune diseases.

    I used to think that the root cause of ME/CFS could be neuroinflammation so i decided very early on in my treatment protocol to do aggressive treatment to combat this with the following combo:

    Valcyte*
    Famvir
    Immunovir
    Doxycycline*
    LDN*
    Memantine*
    Celecoxib*
    Gabapentin*
    Clonidine*
    Tiagabine*
    A bunch of anti-inflammatory supplements (curcumin, resveratrol, alpha lipoic acid, etc)

    The starred (*) drugs have been shown inhibit neuroinflammation.

    Even with long-term aggressive treatment using the above potent combo of anti-neuroinflammatory drugs it has not improved the core symptoms of this disease.

    I know there are other anti-neuroinflammatory drugs such as Ibudilast (which i cannot get and would try if I could) but honestly if the root cause was neuroinflammation then the above combo should've worked after taking it more than 1.5 years?!? I'm pretty sure I don't have any neuroinflammation going on anymore but nothing has changed.

    I just feel in my body that there is something else going on that is driving this disease.

    Could it be that this combo isn't working because I've been working full-time since I got sick and am in a pretty much constant state of PEM and crashing often?
     
    Last edited: Jun 1, 2015
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  2. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    well it seems 2/3 or half of cases is indeed autoimmune. The rest of the cases may be related to some other disease mechanism, maybe involving the the interaction between microglia and the immune system. Some are misdiagnosed, and some seem to have immune dysfunctions leading to constant infections (and some of these cases are even autoimmune). Just my gut feeling based on what ive read
     
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  3. Sidereal

    Sidereal Senior Member

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    It's very easy to obtain this from a reputable Japanese online pharmacy. I have tried it. It did next to nothing.
     
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  4. duncan

    duncan Senior Member

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    This is such a vexing question to answer.

    I can speak to the fact - or appearance? - that abx regimens have helped me historically. However, they are not now, and I feel worse than ever. No combination of abx seems to offer me even temporary sanctuary anymore.

    I have mentioned the problems that present, for patients, when you know researchers in a given field are misrepresenting a disease and its patient population. This compounds the complexity of trying to resolve the active infection question.

    For me, it does not help that my personal history only seems to underscore the difficulties. It could be the putative agent(s) behind my symptoms are not adequately being addressed. It could be that my immune system has burned out. It could be that there is an autoimmune variable at play. After all these years, I am no closer to knowing which is right.
     
    leokitten likes this.
  5. SOC

    SOC

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    That seems likely to me. In my case, the improvement with treatment plateaued as soon as I tried to work more because I felt better... and I only added 5-6 hrs a week for a total of 10 hrs a week of work. As soon as I dropped the extra work and went back to aggressive rest, my improvement started up again. I had to wait until I had a lot of improvement before I could put in a significant number of hours. The improvement had to come first, then the work.

    Certainly extensive anecdotal evidence indicates that constant PEM and frequent crashing causes a continued deterioration. It may be that your treatment is allowing you to maintain your condition rather than deteriorate from the on-going PEM, which I suppose should be considered a plus. However, to improve from where you are you may need to stop PEMing yourself. The best treatment in the world probably can't make you better if you keep damaging your body.
     
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  6. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    What do you call 'neuroinflammation' @leokitten? We discussed this at the IiME workshop and a number of people are unhappy with this broad brush term. There does not seem to be inflammation in the sense of vascular permeability changes (which should show on MRI). There may be microglial activation - the Japanese study suggests that. But people are trying to block microglial activation in a range of other diseases like Alzheimer's and I am not aware that there is any very effective agent available yet. We did not get shown any scans losing orange spots after treatment in our seminar.

    What sort of inflammation did Shungu show? I am not up on this study - although I just looked at a study of lactate levels which looks a bit weird to me.

    I think your main question is spot on though. We spent two days circling round this this week and there was quite a lot to support your position.
     
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  7. Hip

    Hip Senior Member

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    leokitten likes this.
  8. leokitten

    leokitten Senior Member

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    A good point, I've been thinking about this possibility for a long time, but here in the U.S. you know we don't have much of a choice.

    They will never give me disability because I can work full-time still even though it's at a huge cost, they don't care about what is doing to my health or life outside of work. I basically have to get to the point where you and many others did where you work yourselves to the ground and the CFS gets so bad that you then require disability.

    What sucks is that they won't give me "preemptive" disability for a period of like one year to improve. That's what's so terrible about ME/CFS, it breaks all the rules and what we need to get out of this disease just goes against anything insursance or disability would allow.
     
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  9. Marco

    Marco Grrrrrrr!

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    My personal feeling is that 'neuroinflammation' is the key 'axis' of the problem but have been puzzling for a long time over whether or not an ongoing peripheral stimulus is necessary to sustain it or that it becomes self-sustaining.

    There appeared to be a reasonable consensus that there was a degree of ongoing low grade peripheral inflammation involving IL1-b, IL6 and TNF-a but other reviews refute this.

    I now lean to the view that sensitised microglia react to normal physiological levels of everyday metabolites etc (i.e. normal everyday life). I can appreciate that various trigger 'stressors' could prime and activate microglia but why does this happen in PWME and not in the majority subjected to the same environmental insults?

    Autoimmunity is one possibility as are genetic/epigenetic influences ( as per polymorphisms affecting TNF-a levels effecting sickness behaviour in PBC).

    We also don't know enough about ME/CFS pathophysiology to know whether 'neuroinflammation' if it is a feature is pathogenic or appropriate.
     
    leokitten likes this.
  10. SOC

    SOC

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    I hear ya. :( It's both stupid and unjust to require a sick person to work full-time until they deteriorate to the point where they may never recover.

    Is there any hope you could get by working part-time for a while? Could you afford it and might your employer allow it? Is there any more you could do in terms of pacing and activity management that could reduce the PEM? Are you HR monitoring? Working with your feet up? Have you got a power chair or scooter? Do you nap over lunch? Do you shower sitting? Do you minimize at-home activity in deference to resting? These are all things that might allow you to keep working to some extent while reducing PEM.

    Activity management is everything when you have no choice but to work. It's not easy and requires religious attention to all kinds of petty little details, but it's worth it to preserve some amount of your health... and your job.

    In the worst case, you should be able to get a 2-day CPET test which would demonstrate sufficient disability now to allow you to stop working and get disability payments. They won't be anything like what you earn now, but it might keep you going while you allow your treatments to work.
     
  11. Scarecrow

    Scarecrow Revolting Peasant

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    Oh, how I wish this was possible.
     
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  12. halcyon

    halcyon Senior Member

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    Have you thought about trying an FMLA leave? Obviously this doesn't help your financial situation but you could rest for a few months and see if there is any improvement.
     
    Valentijn likes this.
  13. geraldt52

    geraldt52 Senior Member

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    A bit off topic, but one should really think twice about working part time as a way to keep working, while coping with worsening CFS.

    I went from working 5 days a week, to 3 days a week, to 2 days a week over several years...finally being let go, being unable to reliably manage even two days. At my Social Security Disability hearing the judge told me that my history seemed to demonstrate that I no longer wished to work full time, and had applied for Disability just because I couldn't find a job working so few hours. He also pointed out that Soc Sec didn't need to consider that I wasn't able to maintain full time employment, only part time employment, because I had already demonstrated that I was able to live on part time employment. The "Employment Expert", who was hired by the judge for the hearing, suggested that I could probably find a job working just a day or two a week, albeit a hundred miles from my home, as a "lampshade assembler"...ANY job theoretically available in the workplace can be used by Soc Sec to deny your claim. I am/was a Mechanical Engineer with 30 years experience.

    None of my testimony, none of my 2 inch thick file, from a doctor specializing in CFS, made even the slightest difference. The judge simply made up his mind, by making up the "facts" where necessary. It took 7 years to have that overturned. I should have quit when I was first unable to work full time.
     
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  14. leokitten

    leokitten Senior Member

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    In the case of ME/CFS I believe the neuroinflammation discussed is microglial activation.

    Apologies yes all three of Shungu's papers found markers of increased oxidative stress in the ME/CFS brain. I implied that if there is increased oxidative stress then this would also over time trigger neuroinflammation.
     
  15. halcyon

    halcyon Senior Member

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    What is your interpretation of the SPECT/SPET findings in ME patients showing impaired perfusion? 1 What else could explain these findings other than some sort of vascular dysfunction?
     
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  16. leokitten

    leokitten Senior Member

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    I got an FMLA in late 2014 because I ran out of personal leave, but I've been too afraid to even use it. I have hidden my illness from everyone at work because honestly no one would understand and I'm afraid all my colleagues at the NIH will think I'm a quack. This is just such a misunderstood disease.
     
    Last edited: May 31, 2015
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  17. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Hypoperfusion would be the opposite of inflammation (where the 'flame' part is the redness of increased perfusion). This is why I think we need to disentangle the various component physiologic changes because they may not be working together in the way they do in typical inflammation. As far as I can tell microglial activation can occur without any perfusion changes. There was lots of microglial activation in the brainstem areas where that paper reports hypoperfusion. Maybe they are linked but if so we need a new word for this combination I think.
     
  18. duncan

    duncan Senior Member

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    What about neuroinflammation tied into vasculitis? Couldn't the end result be hypoperfusion that shows up on SPECT scans, or even MRIs if the damage is severe enough?
     
  19. halcyon

    halcyon Senior Member

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    Agreed. Looking at the relatively little autopsy data we have to go by, it seems the consistent findings are nerve root inflammation and damage to cerebral capillaries.
     
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  20. leokitten

    leokitten Senior Member

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    In my current position at NIH I could never request this. And to make matters worse I'm work for the NIH via a contractor (which most federal jobs are like now), so I'm totally afraid that if I try to request something like this they will find some way to let me go because it's so easy to lay off a contractor for no reason at all.

    I could do a lot better with this, it's been really hard though. In addition to full time work I'm in a relationship and live with my partner. Those of you who are married or in relationships living together know how hard it is, I can't have everything revolving around me and the entire relationship constantly being about this disease.

    Where would be the best place in the U.S. to get this?
     

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