“This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in ME/CFS and diagnostic biomarkers for disease” W. Ian Lipkin
Big study – big results
Distinct plasma immune signatures in ME/CFS are present early in the illness. Hornig. M. Monotoya, J, Levine, S., Felsenstein, D., Bateman, L, Gottshalk, G….Likpin. L. Sci Adv 27 Feb. 2015.
It’s a major study indeed – the first, I believe, to come out of the Hutchins Foundation’s Chronic Fatigue Initiative and the media is picking it up quickly. The Hutchins Foundation doesn’t mess around. They’re putting $10 million into researching chronic fatigue syndrome. They do big rigorous studies with top researchers.
This study with its carefully selected patients from across the country was loaded with ME/CFS expertise. Besides Mady Hornig and Ian Lipkin of Columbia, Dr. Montoya, Dr. Peterson, Dr. Klimas, Dr. Bateman, Dr. Levine and Dr. Komaroff were listed as co-authors.
It’s Biological
“These immune signatures represent the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder, and the first evidence that the disease has distinct stages.” Columbia University Press Release
Once again we see claims made that finally, finally we have proof that ME/CFS is a biological illness. (The head of the CDC said something similar regarding their study about ten years ago at a National Press Club event.) This time the claim is a bit different, however. This time they have not just evidence but “robust” evidence that ME/CFS is a biological illness.
If the study size is any indicator of robustness – and in a well-designed study it is – their evidence is robust, indeed.
It’s So Big!
This wasn’t just a big study – it was a huge study containing almost 650 patients and healthy controls (298 ME/CFS patients and 348 healthy controls). (A similarly large study is underway at Stanford).
All the patients met both the Fukuda and Canadian Consensus Criteria.
The study wasn’t just big in size – the 51 immune factors it measured meant it was deep as well, and leptin was one of the immune factors measured.
Different But Not Substantive
The study started off on a bit of a downer. Differences in immune factors between the ME/CFS patients and the healthy controls were present, but not “substantive”.
Note, however, almost all the immune factors are lowered – not increased – in the chronic fatigue syndrome patients. We’ll come to a reason for that later.
- Pro-inflammatory – IL171A (p<.0043), CXLC10 (p<.04), TNF-B (p<.0028), Il-6 (p<.04), sFasL (p<.01)
- Anti-inflammatory – Il-10 (p<.024), CSF1 (p<.025)
The one immune factor moderately increased in ME/CFS was leptin (p<.03).
That didn’t mean many in the group hadn’t experienced profound immune alterations, though. They had – earlier…
Hit and Run
“The immunopathology of ME/CFS is not static” the authors.
Further analyses uncovered something the authors freely admitted surprised them. The ME/CFS patient’s immune measures didn’t differ by triggering factor or age or even by sex – they differed by time.
The key factor for the immune system – was time
Alterations in over half the immune measures found (combined with some very, very low probability factors that the results weren’t correct) (p< >0002-.0008) indicated that “substantive” differences in immune functioning had existed at one point in time. The short duration patients showed signs of intense immune activation not found in the other groups.
Both the pro and anti-inflammatory sides of the immune system were on high alert early on in ME/CFS.
Immune Differences Between Short-term ME/CFS patients and Healthy Controls:
- • Increased levels in ME/CFS: IL1A, IL1B, IL-6, IL-12, IL-17a, Il-17f, IL-8, TNF-a, sFasL, TRAIL, IFN-y, CCL2, TGFa, CSF, resistin, CCL-11, CSF2, IL1RA, IL-13.
• Reduced Levels in ME/CFS – PDGFBB, CD40L
Cytokine results have been spotty in ME/CFS and that’s been a problem. A few up or down regulated cytokines just don’t raise many eyebrows in the research world. They’re looking for evidence of broad immune alteration – and here it is. I don’t think anybody has seen this kind of sweeping immune activation in ME/CFS before.
Viral Fighter Stands Out
A logistic regression suggested that IFN-y played a particularly significant role in the immune system activation. Produced mostly by natural killer and cytotoxic T-cells – two cells with similar problems in ME/CFS – IFN-y is both an immune stimulator and pathogen inhibitor. (Microglia are big IFN-y producers in the central nervous system).
The IFN-y findings suggest either a pathogen attack or an autoimmune shift may be triggering the immune upregulation seen early in the disease.
Bug alert! The early immune findings were consonant with a pathogen attack.
High IFN-y levels are associated with Th2 dominance in the immune system and an increased risk of autoimmune processes. Post-viral fatigue has been associated with high IFN-y levels, and alterations in the IFN-y gene have been associated with increased fatigue following infection as well.
IFN-y also showed up in Broderick’s small study examining 16 cytokine levels in adolescents in the first two years after coming down with infectious mononucleosis. Four cytokines IL-8, Il-23, IL-5 and IL-2 were significantly altered or nearly significantly altered.
IFN-y levels were not increased but a computer model suggested it and four other cytokines constituted an immune signature that differentiated people who came down with ME/FS after IM and those who recovered.
Mady Hornig on the Study
IL-5 levels were significantly decreased in ME/CFS patients but IL-5 did not, interestingly enough, make it into the computer model. Further analysis indicated that IL-5 levels were significantly correlated with Il-23 and IFN-y: two cytokines that did make into the model. These cytokines were essentially analogues for IL-5 in the body.
THE Pathway???
IFN-y also accelerates tryptophan degradation by activating the indoleamine-2,3 deoxygenase enzyme in the kynurenine pathway – Mady Hornig’s favorite pathway. That pathway produces neurotoxic substances that increase production of the excitatory neurotransmitter glutamate that some researchers believe is in play in both fibromyalgia and ME/CFS. Andrew Miller of Emory University has earmarked the kynurenine pathway in ME/CFS.
Could the kynurenine pathway be it for ME/CFS?
Cognitive problems and mood changes have been associated with up-r egulation of the kynurenine pathway in diseases ranging from Alzheimer’s to depression. In fact, disruption of the one part or other of the kynurenine pathway occurs in many neurological and psychological disorders.
The authors were confident enough to hypothesize that lesions produced by high IFN-y levels early in the disease are producing the cognitive slowing and depression found in ME/CFS. Andrew Lloyd of the Dubbo project has been suggesting for years that high cytokine loads early in the disease process had disrupted brain functioning, but nobody has gotten this specific before. Now Hornig and Lipkin et. al are proposing a specific mechanism for that: IFN-y produced lesions.
“We propose that IFN-y mediated lesions in kynurenine metabolism may culminate in the depression and psychomotor tardiness (slowed information processing) that contribute to disability in some patients with ME/CFS”.
That kynurenine pathway gets more intriguing when we consider that IFN-y activation and tryptophan degradation has been associated with chronic Epstein-Barr virus infection. Epstein-Barr virus is often associated with infectious mononucleosis – a common trigger of ME/CFS.
CD40L
CD40L appears to be another early key immune factor. A clear driver of immune functioning in the healthy controls and longer-term ME/CFS patients, CD40l was found to be reduced and strangely disengaged from the immune system in shorter-term ME/CFS patients.
A B-cell maturation regulator, deficiencies in CD40L are associated with recurrent infections and unexplained cognitive issues and CD40 deficient mice exhibit major immune deficiencies. Citing the Fluge/Mella Rituximab study the authors suggested the collapse of this immune factor early in this disease could be important.
Nice Fit
One scenario proposed by this study – natural killer and cytotoxic T-cells pumping out IFN-y early in the disease only to collapse later on–appears to fill in some holes that smaller studies would have missed. If this study is representative maybe 20% of the patients in any study have probably had ME/CFS for three years or less. That would mean that the typical low NK dysfunction will show up but the up-regulation early in the disease the authors believe may be contributing to that doesn’t.
Flipping the Switch
That suggests that somewhere around the 3rd year of illness major immune shift occurs. The immune system flips from being hyperactive not to being normal but to being somewhat under active.
Dr. Hornig described a condition of immune system burnout:
“It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop.”
Does the immune system get burned out in longer duration ME/CFS patients?
There’s something very right about “immune exhaustion” being associated with this disease The fact that many cytokines increased in the early stages of ME/CFS are decreased in the later stages suggests a kind of burnout process is occurring.
Poor natural killer cell functioning in ME/CFS is often described as a type of immune system “burnout” and evidence is emerging of similar cytotoxic T-cell problems as well.
Leptin Again
It’s hard for me parse how leptin showed up in this study. The only immune factor increased in the whole ME/CFS group vs the controls, leptin was highlighted in one network analysis of early duration patients and showed up moderately in two others. The authors noted that it was tightly correlated with most of the immune factors later in the disease but not early.
Another cytokine called PDGFBB appeared to be the main driver of the immune reductions later in the disease.
Hit and Run
That suggests the disease has in some way moved on from the immune system. The authors of the paper didn’t have a great explanation for why people remained ill after their immune system activation had died down or had become decreased. If Younger’s findings pan out perhaps the lone elevated immune marker – leptin – found is enough.
The findings suggested ME/CFS is a hit and run disease.
A email to Jarred Younger gave a quick answer and a warning that it was not based on a close reading of the paper. He suggested systemic inflammation may drive ME/CFS early on but sensitized microglia and astrocytes in the central nervous system drive it in its later stages. Because we don’t have good ways to test central nervous system inflammation at that point the disease mostly becomes invisible to testing afterwards.
In fact, the authors tantalizingly noted because ME/CFS appears at least in part to be a central nervous disorder cerebral spinal fluid may very well be a better medium to investigate than peripheral blood. That could suggest we’re due some more important findings in a couple of weeks when the Simmaron Research Foundation/Chronic Fatigue Initiative CSF study is published.
The High Cytokine Longer Duration Patients
The study doesn’t make any mention of longer duration patients ME/CFS patients with high cytokine levels. Anecdotal reports from patients indicate they are definitely out there, but this study – involving many quite ill patients being seen at ME/CFS practitioners – suggests that they probably constitute a relatively small subset of patients.
Conclusion
“We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn’t psychological,” Mady Hornig, MD
This large study presents what appears to be almost novel finding in medicine: distinct before and after stages early in a chronic illness. In the early stages of ME/CFS (first 3 years) a distinct and impressive immune activation is present that is followed by modest immune deactivation.
The early immune activation is highly suggested of an infection or some other immune altering process.
The study may ultimately open up possibilities for treating patients with recent onset but provides no possible treatment options at this point for patients who have been sick longer. The more modest immune deactivation found later in the disease suggests that the core causes of the disease are either found elsewhere or were not illuminated by the study.
A major question facing researchers now is finding ways to translate this hit and run immune activation or viral infection into long lasting central nervous system problems. Microglia sensitized by chronic immune activation/kynurenine pathway activity is one possible answer.
Ian Lipkin’s statement that they hope to find important answers in their microbiome study suggests he believes a permanently altered microbiome could provide an answer to that question.
“The question we are trying to address in a parallel microbiome project is what triggers this dysfunction.”Ian Lipkin
The authors statement that cerebral spinal fluid may provide a better medium for understanding this disease could mean we’re in for some interesting findings in a couple of weeks.
Stay tuned!
Wow….I hope they are right….we will see…we have been here before and I am the great skeptic. .lets wait and see…This will bring other researchers out of the woodwork. a very good thing in itself no matter the out come….but you never make policy on the basis of a single study…
Nice point. When people of Lipkin’s and Hornig’s ilk publish big studies like this – people notice them….
right..a great start ..but it need to be reproduced. and researchers all over the world will be trying to do just this. ..this study design is a bit of data mining in a case control study…and they are notorious for associations that prove to be not valid. just a cautionary note from a scientist…and one with our thing who has been through 25 years of exciting starts..
check out this analysis of of biomakers found over the years for schizophrenia..absolutely a physiological disease and years of publications of biomakers proved to be wrong. a cautionary tale.
Neurosci Biobehav Rev. 2014 Sep;45:134-41. doi: 10.1016/j.neubiorev.2014.05.010.
Clinically meaningful biomarkers for psychosis: a systematic and quantitative review.
Prata D1, Mechelli A2, Kapur S2.
I agree with you Cort my intuition is saying now were going on that path to knowing soon enough within a year or so to the answer of how to cure this. We are getting real close. I have hope & faith. I read was reading the start of this article and said,”Amen 3x”. Great hope and news. I am excited about the news.
The good studies and reports just keep on coming! It’s an exiting time for all of us. The thing I wonder is why, after 21 years of this illness, do I still have a bunch of high to very high cytokines?
The good studies and reports just keep on coming! It’s an exciting time for us all. The thing I want to know is, why after 21 years of this illness, I still have a bunch of high to very high cytokines?
Ok, I am very brain fogged right now, and i skimmed the article, so I may be missing or repeating something really obvious, but as far as I can tell, I’m not…….if the immune system is first over active and then gets burned out and becomes under active, but the illness continues, perhaps the immune system is not the underlying cause, but another effect.
And, if that’s the case, then a few things that could be the cause are: a gene or genes, something to do with the mitochondria, something to do with the nervous system, something in the endocrine system, or the vagus nerve infection that (I can’t remember his name rt now) proposed. The nervous system, endocrine system, and mitochondria I mention, because they have all been considered part of this illness somehow, and a gene or genes would be pretty obvious a possibility, too.
The vagus nerve infection makes the most sense to me, though, because not only would it be hard to find, and not only does it fit with the gut issues that so many of us have, but also because there is nothing that I have read about this illness thus far that would not fit with a vagus nerve infection starting all this, including this study.
If it were to start there, the ramped up immune system would make sense, and then after enough time of being ramped up, the burn out would also make sense, but then since the vagus nerve infection still would be there (it’s hard to find and hard to get rid of), it would still be driving the other symptoms…….and even though the immune system would be burned out by that pt, it would still be trying to get rid of the vagus nerve infection; just not doing much of a good job because it has nothing left to give.
That would also explain why symptoms fluctuate and change a lot over the yrs…..esp things like the sore throats at the start that often disappear after yrs of illness, and the sleep patterns that often start with way too much sleep and then wind up changing to too little, the fact that some catch colds and flues and stuff very easily, and others seem to never get anything else, etc, etc.
I have had M.E. for over 50 years and are now more or less bed bound, although with 48 hours rest I can get out and about for a couple of hours, for which I am thankful. I used to get viral flu type infections which would last for 6 months and often end up with a bacterial chest infection and coughing up of blood. I find taking vitamin D or using a vitamin D lamp helps enormously with that aspect. Of course I still get a type of infection if I over do things, which feels the same but it goes quicker and I feel is different. I have recently started again with sore throats I haven’t had since a child.
I’m happy that Vit D has helped you, though I am not sure why you wrote this in reply to my comment (perhaps because of the immune system issues?). Anyway, that said, my vit D levels are really good, because I go tanning regularly and have had them checked to see if that helps them.
“This could be a really big deal and I hope they are right. Real biomarkers for ME/CFS. We know they have to exist somewhere. We will need a lot more work on this and this study will bring researchers out of the woodwork. That in itself is a great thing.
However you dont make policy on the basis of one study. We have been here before and I am the great skeptic, in fact all good scientists are. But maybe..just maybe…we have to wait and see.
and remember even if these finding are substantiated….”Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.”
This is a very amateur shot at it – my own nearly 30 years experience of this illness has been characterised by a very gradual and fluctuating improvement, and from the very beginning it was evident to me that worsening of symptoms followed physical exertion, but I also had a couple of experiences of worsening following cognitive exertion, and of extreme emotional responses (sobbing from fatigue after having had an exciting and rewarding day on a workshop and was perfectly happy!). My later history has included being worse for about a year after having followed the advice of my chiropracter to start riding my bike, so I rode it to work for a few weeks. It took me about a year of resting to get over it, and I had a similar year’s relapse after looking after a dog over the Christmas holidays.
I believe that ultimately we are going to find that there is a latent virus which is stimulated by exertion. In HIV, the retrovirus resides in immune system cells, and when a minor illness such as a cold stimulates the immune response, the infected immune cells produce lots more of the HIV. I think that muscle cells may harbour a hidden virus, so that when muscles are used, the virus multiplies.
It also seems evident that Ramsay’s prescription of complete rest from the inception allows the body (the immune system) to mount a response to this situation, and likewise that intensive resting allows the same process to take place….my experience, and that of other patients (also reported in a paper by Jason et al) is that serious resting results in improvement, over the long term. The ‘envelope’ theory, pacing, involving keeping activity levels within perceived energy levels, seems to result in increased energy levels over the long term.
For these reasons, I believe that as this recent biological evidence continues to accumulate, we need now to campaign for Ramsay’s prescription of rest to become the highest treatment priority. No one is researching rest as a treatment…after all, it puts doctors out of a job, and no pharmaceutical company will make any money from it. The psychiatrists campaign against it. SEID seems to say that exertion of any kind can do harm to organ systems, so avoiding exertion seems the obvious way to avoid harm…but it does more than that, according to Ramsay. The IOM must be encouraged now to make treatment recommendations which are in line with their definition.
Nancy,
We’re CFS sisters! I’m in the midst of a complete relapse after (Foolishly!) taking care of someone’s puppy for a week at Christmas. I’ve had this illness for over 20 years and find I too relapse from too much physical, cognitive or emotional exertion.
Rest is interesting. Early on, I heard from various sources that a subset of sufferers completely recovers within 5 years. I have been very jealous of at least one woman I know for whom this was the case. (She climbed Mt. Kilimanjaro at the 5 year mark to celebrate). She believes her recovery was from having the resources to be able to do little more than rest and sleep. She had little kids at the time but also had an extremely active husband and a lot of other outside help, which allowed her a daily schedule of: morning breakfast with kids, rest, lunch, rest, dinner with family, sleep.
I have been somewhat bitter about the fact that I live alone and have few outside resources. The exertion from simply driving to the supermarket (less than a mile away!) or doing other bare necessities of life keeps me in a seemingly never-ending bed bound existence.
So, for the thousands of us without the financial or other means that would allow us the significant rest that would help, we need the gov’t to step up and get the medical community to help us have lives!
There are definitely some people for whom complete and careful rest works- yes, indeed….I’ve never been able to accomplish that. I do wonder if I’d just done if things would be different
There are many people I imagine for whom it did not work unfortunately as well
Rest….(I actually hate that word!!) Conservation of exertion. If we become experts….use every possible aid for minimising exertion. Lawn recliner in the living room (or every room) so that one can be completely physically relaxed while phoning, talking to a visitor, watching TV, working on a (well supported) laptop or ipad. Always, always keep your head supported, it weighs 10lb. Use a wheelchair (and I mean use, you can push it along with parcels in it, sit in it when you feel like it, use it as a tool). Lie down whenever you can, sit whenever you can, don’t carry things (put them in your wheelchair!). Be really clever about outwitting this illness. Use plastic plates instead of ceramic, take water to the kettle, not kettle to the water. Help anyone around you understand that every bit of physical help they give is like giving you a pill to make you better. If you are very clever about minimising exertion, then you will free up energy for the things that are really important, the most important being getting better. Your immune system needs all the energy you can save for it to figure out what to do about this hidden invader. The thing is, I don’t believe it is ‘too late’, I think that a program of exertion-conservation may just offer that extra that you need, and over time gradually extend the range of what you can do. I call it slotting an invalid life-style into as normal a life as possible. Students shouldn’t walk anywhere if they can avoid it, and do everything needed to keep head supported in classes – save energy for the cognitive task of learning. And so on….Back to the recliner – if you have one, you can take a complete rest or sleep whenever and for as little or as long as you need – just by moving the arms a little bit to change the slant. You can slot being a complete invalid into getting on with your life – The immediacy and minimal change from complete rest to normal functioning allows you to adapt instantly to the changing requirements of your illness, more or less with a flick of the wrist.
And as far as shopping is concerned, we now get as much as possible delivered – most big shops now, at least in the UK, have delivery service, which can be quite inexpensive. Internet shopping is a godsend, you can order most things and get them delivered, saving exhausting hours of going round shops looking for something, finding it, bringing it home.
I don’t think many people have worked out how physically demanding most women’s lives are…take a supermarket shop, involving 50 to 100 lb of stuff in total. By the time you have taken it off the shelves, put it your trolley, put it on the cash-out counter, put it back in the basket, taken it out and loaded it into the car, driven home and then taken it into the house, and then stored each item individually where it is needed. you have moved 50-100 lb a total of seven times. And they say we need exercise!! So one delivery can save that much exertion, or most of it. Ramsay does recognise this when he says that women who have children and unavoidable physical demands have little chance of being able to get enough rest to recover. (www.name-us should take you to the site where you can find his article ‘Myalgic Encephalitis – A Baffling Syndrome with a Tragic Aftermath’. We need a major campaign for his recommendations.
Hi Nancy,
I call it the ‘grocery hokey-pokey’ to make it a little more entertaining. it goes like this……you put your groceries in (the trolley), you take your groceries out, you put your groceries in (the trolley again) and shake them all about (in the trolley…then you get to the car)…..you take your groceries out, you put your groceries in and shake them all about (in the boot), then you take your groceries out, you put your groceries in (the cupboard)
….and hopefully that the end of the song cause you don’t want them shaking about in your pantry!
Cheers
Linda
Have been very ill since diagnosis in the early nineties. Not aware then, of effects of rest as a primary treatment at onset; I continued to work harder in medical career (even returning to school so I could work at a desk job) which only compromised my ability to heal in those first years. Something viral was occurring in my brain causing migraines which disappeared after those first years (inflammatory period/inflammation in brain seems most likely, as evidenced in EEG/brain mapping done) So many losses that many of us have experienced of career, friends, good healthcare, self esteem and more. Been relapsing since March of last year when one too many cold viruses stressed my already compromised immune system.. Have read the new research. Have also participated in research via a New York physician, to attempt to contribute. Now, aging, mostly homebound, minimal income w/out means to progress w/a healthier lifestyle, it has left me with limited hope for the future. When a dignified name could not even be given in all these years, what could be discovered and agreed on that would modify those lives of sufferers and provide a semblance of peace and validation? Am grateful to the dedicated doctors and researchers, and those like Cort w/his blog, who have provided time and effort, expertise. Once so optimistic, I have sadly become indifferent…. I am also bitter, live alone, w/out the many resources of previous years. Now it is more a state of accepting that I am a spiritual being in this exhausted physical body that lives for quality of life in my remaining time. This is my reality.
that is not amatuer nancy just accurate common sense i pleasant change to reading corts bullshit over the years he has learnt that you can say anything about me just add the invented cfs he is a traitor to all us genuine me sufferers
I appreciate your positive response to my comments, but need to say that I do not share any hostility to Cort Johnson. He seems to me to be providing a useful service even if one does not always share in some of his interpretations or responses. Would we be better off without his work in following research and media reports? He seems to be a hate figure with some, and I suppose that if our real enemies can play divide and rule with advocates and bloggers, it strengthens their position. We have problems with limits on energy enough without dispersing it in attacks on each other. Maybe that’s just another naive view!
Thank you, Ms Nancy, for discouraging attacks on each other. It IS a total waste of energy and only spreads the negative kind none of us need.
Sounds like your having a SUPER BAD day Geoffrey Brown.
Cort is giving us info Which Most Of Us appreciate. Otherwise, delete your account or delete when it comes. You have that choices,GEOFFREY. HOPE YOU FEEL BETTER.
“Bug alert! The early immune findings were consonant with a pathogen attack.”
************
The genetic predisposition and many, many guns … while many patients developed ME/CFS after a flu, virus or infectious agent, don’t rule out other environmental, or toxic exposures as triggers. ME/CFS for many of us was triggered after a chemical exposure, a vaccination, prolonged physical exertion, or a physical trauma etc. Although sufferers differ in what caused their ME/CFS, the common feature is that physical, emotional or cognitive activities will cause their autoimmune illness to flare.
I agree completely – particularly since I did not come down with ME/CFS after a pathogen attack…
I believe I didn’t come down with it after an obvious & acute pathogen attack either. I’m def. in the gradual onset category. I wonder how the study will incorporate pediatric cases, or maybe they have – as their long term sufferers.
Thank you for the write-up Cort!
Just to say that as Dr Chia has pointed out you may have come down with a pathogen attack and not know it because many healthy people have pathogens inside us already. Then due to whatever circumstances , the pathogen stirs up and activates- but it hasn’t come from outside but is endogenous- therefore you assume it’s nothing to do with a virus/pathogen.
Zip, One thing I don’t believe about my illness ME/CFS is that my immune system is stuck in permanent overdrive because it can’t rid itself of a virus that is lurking/hiding somewhere in my body. Any virus that attempts to enter my body is quickly eliminated by my quick acting immune system. There’s absolutely nothing down-regulated about my immunity and my immune system is quite capable of launching a suitable attack to eliminate pathogens.
I had exactly this experience with my illness- didn’t get anything that was going around, or a very mild version. I interpreted this as that my immune system was constantly on red alert, looking for a pathogen that it couldn’t find, so it really zapped anything else that was coming in.
I even toyed with the idea that a parasite might be involved because apparently there are some parasites that can ramp up the bits of the immune system that deal with bacteria/viruses while damping down the parts that would attack parasites. But we already know that some viruses become latent until stimulated by some trigger, and for sure, whatever it is we have is triggered by exertion.
I continue to regret and be puzzled by the general rejection of Les Simpson’s work on blood flow. One of the things that goes on in ME is that the red cell population becomes dominated by irregular shaped cells that can’t get through the capillaries which serve muscles and the brain. This accounts for the inability to use oxygen and immediate switch to the anaerobic metabolism when muscles are used, also ‘brain fog’ due to lack of oxygen and build up of metabolites which are usually removed by the red blood cells. This can be alleviated by taking things which improve blood flow – fish oil, EPO, B12 injections, Trental – but his work is ignored. It’s not either cause or cure, just one piece of the jigsaw, but many of us, not all, could benefit if this was recognised and his recommendations tried out.
“But we already know that some viruses become latent until stimulated by some trigger, and for sure, whatever it is we have is triggered by exertion.”
****************
For some of us with ME/CFS, I believe an autoimmune response is triggered by exertion because exertion depletes dopamine stores. When dopamine stores are depleted prolactin levels rise. If you are low on dopamine and your body has lost the ability to restore dopamine levels exercise, stress, exertion etc, anything that eats up your small reserve will cause more fatigue, “flu-like-symptoms”, pain etc. Dopamine can act like a brake and without it the immune system becomes hyper-responsive.
Prolactin is a cytokine. Prolactin is also a growth factor for lymphocytes with the potential to stimulate immune responses at many levels.
It is an immunostimulating peptide hormone linked with a number of autoimmune illnesses. Hyperprolactinemia stimulates autoimmune disease, and this stimulation is determined by genetics.
So, my theory is that in my case of ME/CFS exertion is depleting my small dopamine reserves causing prolactin levels to rise initiating an autoimmune response. This over-reaction of my immune system is not just against some dormant virus that suddenly re-activates, but to anything and everything my body deems foreign.
you dont actually know that- how on earth can anyone given that the immune system is so very complex- scientists dont understand fully the workings of it so a lay person cant.Viruses are tiny and may find a home where the immune system cant attack- there was research (cant think specifically now) showing that it doesnt always recognise pathogens. wHAT aboiut the hiv virus- ,most people can shake that off or autoimmune conditions. Or indeed MS now thought to have virus involvment.
I knew I had been infected with Epstein-Barr virus years ago but after having in-depth blood analysis done I also have HPV-6 and c-pneumonia active and causing havoc. The HPV-6 virus is the same as what causes roseola using contracted when we were kids. So, yes, my immune system has been in over-drive all these 15 years of having ME plus FM (although I believe I had ME and not FM years ago, I had to diagnose myself then a complex disease clinic started and I was confirmed ME/FM)
The point being, I am an RN (retired) and would never have known without reading research papers, how involved my immune system really is, all blood tests have been normal except maybe 15 years ago and it was written off as a tropical flu I picked up when in Myanmar. After the “flu” was gone I had episodes of being “well” and not. Becoming very weak, not able to climb stairs, severe double vision. Then after 5-6 months I got better, but not quite. I had a major cycling (bicycle) accident and the following winter a very bad skiing accident and that did me in for good. For years I was encouraged and attempted to get back to exercising and I tried so hard but I think everyone knows what happens with that. I’m now house-bound-reclining chair and bed. Boring 🙂
Except: THANK YOU CORT, with this site I know I am not alone
ditto; to that,Rachel…I have no more a problem(likely less) with cold/ flue, etc than the average person; however me/cfs has made me somewhat of a recluse, and the rare occasion that I do “venture forth” I am always “aware” of my surroundings’ have all the usual symptoms; on morphine for pain since 1998….ME/CFS;my constant”companion”since 1986
So if many people can have these hidden pathogens but only a few get CFS it means that the problem is not the pathogens.. it is maybe defective genes/metabolism, the real cause
Sorry, forgot to mention I was put on Valtrex (anti-viral) twice. The first time I noticed a drastic upturn. My head was clearer than had been for years and I had a bit more energy. Unfortunately it didn’t last and the 2nd time it didn’t seem to do anything.
I aslo want to mention if anyone is put on anti-virals or anti-bx than often you feel worse for a week or two then turn around. This is called Herxing, your body needs a lot of energy to rid itself of these bacteria and viruses.
To Analucia and Ivan,
Yes, I believe for me fibromyalgia was passed down from my mom,& from me to one of my sons IBS so we are both on Gluten Free.
Ivan yes people like us become reclusive because not feeling like 100% like we use to be makes us want the alone time & quite. Noise is hard to take. I already have the noise(ringing in the ears) 24/7 plus pressure in the head of headaches. So alone time/quite time is what we get use to in order to stay calmer. Plus for me with me/cfs for 36 yrs. at the age when it started I was 34 & it was so hard to be a hair dresser with the noise and physicalness of the job was unbearable at times wear I wanted to run out of the shop and scream out of frustration of pain and tiredness. So now
after all these’s years especially the last 2 yrs. I retired so I have more quite time to myself & because of my little chihuahua I motivate myself to shower and take her for a 40 min. walk. We both socialize and sit when I need to. I walk on the esplanade on the beach. Which I love to hear the ocean which claims me with the sun shinning.
I take a lot of supplements holistic M.D. recommended to keep the VIRUS’S away has helped a lot is 1.) “Ecological Formulas” Monolaurin 600mg. 4 a day of these. Started with two a day & kept increasing as time goes on. A most for me. 2.)For CFS Ayush Herbs Ashwagandha 2 a day.
3.)Vit.D-3 10,000 a day ( also helps for viruses)& 4.) on an empty stomach HPN Nr Niagen Nad+Booster helps with energy. Grape seed extract also is more powerful then reg. vitamin C. These is what I have learned in the last 2 yrs. which is helpful to me. Even if I don’t do to much I am ok with it but on sunny days I want to walk myself and my dog. Even if you walk slowly for 10 min. one way sit and 10 back. Baby steps is the key & then you can go more as time goes on. I seem to have more energy later in the afternoon after a good dinner. Salmon,salad,avacado/stringbeans with almonds & olive oil. So I went to the market to shop having this energy. So pass yourself. Finding each day what will work for you.
Being retired has helped me to choice wisely. Eat healthy is also the key. Gluten free helps a lot also but somethings stay the same like enjoying your own company with my dog:)
Thank you for commenting, Danielle; the onset of infection and duration you have experienced is very similar to mine. For the first years after diagnosis I spent much precious energy and money pursuing any and all methods and/or treatments; supplements, and drugs.In the end what proved beneficial was a “proper” diet; I am now vegetarian; some supplements (vitamin,herb protocol,melatonin etc). Unfortunately I am still unable to get proper sleep; I “live” on less than 4 hrs. a day; and that 4 hrs is intermittent. It amazes me just how much “abuse” the human body can tolerate….and….also, unfortunately I have to take morphine for my pain. It works, and without it I would be dead. It has its side effects, but I have learned to cope with them. For those, who do not have to take a “heavy” pain medication…consider this a small blessing…I hope they never do.
Hi Ivan,
Yes, I have spent so much money on doctors threw the years myself.
Does anyone have a dizziness or drunken feeling “all the time”?? Which never seems to go away.
For sleeping for myself I just recently found FibroSleep by Pro Health taken 2-3 capsules with ibuprofen 600-800mg. per night in order for me to sleep & wake up 3-6x a night but I manage to relax and fall back to sleep. When a virus is going I am in bed 11-12 hrs.
I noticed to much sugar like ice cream also lowers the immune system. I love ice cream 80% of the time I don’t buy it but when I do. I have a quart a night. Not good for me it’s like a bad drug. Want more!
God Bless Ivan,Danielle:)
Change is the only constant with this thing. It started out with my right side feeling weak but not “testing” weak. Very MS-like symptoms like loss of vision in left eye but nothing from the opthamologist except a suggestion to put eyedrops in. Disequilibrium initially and a few years later….gone! But the lack of refreshing sleep has never gone away. Now it’s more cognitive and memory impairment so how will they EVER pin this “guy” down? It’s really multiple hit and runs that leave one extremely vulnerable to stress as this will bring new neurological symptoms. If they can figure out how to fix the sleep architecture anomalies, I will be happy. To pop out of bed refreshed!
Thanks to Cort for bringing all this wonderful news so expeditiously!
Thanks Kathleen. I’ve had a few similar weird neurological abnormalities that came – and thankfully went…
Hmm… I mean it’s not really earth-shaking, if you think it’s an infectious process. Consider…
Forsberg P, Ernerudh J, Ekerfelt C, Roberg M, Vrethem M, Bergstrom S (September 1995). “The outer surface proteins of Lyme disease Borrelia spirochetes stimulate T cells to secrete interferon-gamma (IFN-gamma): diagnostic and pathogenic implications”. Clin Exp Immunol. 101 (3): 453–460. doi:10.1111/j.1365-2249.1995.tb03134.x. PMC 1553228. PMID 7664493. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1553228/?page=5)
Borrelia-Specific Interferon-γ and Interleukin-4 Secretion in Cerebrospinal Fluid and Blood during Lyme Borreliosis in Humans: Association with Clinical Outcome
Mona Widhe1,2,4, Sara Jarefors1,2,4, Christina Ekerfelt1,4, Magnus Vrethem3, Sven Bergström5, Pia Forsberg2,4 and Jan Ernerudh4 (http://jid.oxfordjournals.org/content/189/10/1881.full)
Inflammatory Cytokine Production Predominates in Early Lyme Disease in Patients with Erythema Migrans
Lisa Glickstein,* Brian Moore,† Tara Bledsoe,‡ Nitin Damle,§ Vijay Sikand,‖ and Allen C. Steere#
Author information ► Article notes ► Copyright and License information ►
This article has been cited by other articles in PMC.
Go to:
ABSTRACT
In a study of cytokine production ex vivo by Borrelia burgdorferi-stimulated peripheral blood mononuclear cells from 27 patients with culture-positive erythema migrans, production of inflammatory cytokines predominated, particularly gamma interferon and, to a lesser degree, tumor necrosis factor alpha. In contrast, with the exception of interleukin-13, anti-inflammatory cytokine production was negligible. Thus, B. burgdorferi antigens in early Lyme disease often induce a strong inflammatory response. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC201073/)
Vlynx,
My brain has shut down for the evening but I noticed your citing of Lyme related articles. Any chance you could give a quick lay person synopsis? It’s most likely I had Lyme prior to getting CFS so I’m curious. Thanks!
Sorry. Reason I just posted articles is my brain is shut down as well.
I think my basic point is that the findings Cort is describing are likely duplicated in Lyme disease. Or maybe any infection. But Lyme is so similar to the disease formerly known as ME/CFS that they may be looking at the same thing. I think Montoya is aware of this. Whether Lyme is “hit and run” or persistent infection is the big question, isn’t it?
Lyme is epidemic, transmissible by any number of pencil-dot size tiny insects plus animals whose destroyed habitats have caused them to mingle more with humans and pets; it is also transmissible by any type of body fluids, and the blood supply is not tested for LD and and its frequent, numerous co-infections. Entire families get infected from one outdoors excursion and may not notice any symptoms until years later, when rheumatoid arthritis or some other secondary falling health domino starts to manifest long after the spirochetes are hiding inside bone burrows, where they cannot be detected by serum blood tests.
This post may or may not be helpful to Kira. Like M.E., CLD numbers have been always greatly underreported. Accurate tests still do not exist (why?). One existed, but was taken off the market by some political machinations, as was explained to me. The Igenex test is said to be widely misread and misinterpreted by different groups of doctors due to “the battle of the bands,” missing at least half (?) the valid cases. M.E. doctors are usually severely uninformed about CLD and its relationship to all neuroendocrine diseases, especially Chronic LD, and usually use the government stats and info of the same bogus, disinfo quality as that given for M.E. This ignorance does not lower the PTSD numbers among neuroendocrine experiencers.
Many M.E. doctors are often loathe to connect M.E. with CLD; after I was diagnosed with CLD by a Northeast expert, one conventional Florida immune doc said in an accusatory voice when I asked about being retested: “WHY DO YOU WANT TO HAVE LYME!! ” (twice, in a quite unfriendly way for such a nice clinic). Now is the time to widely publicize all the relationships among CLD/co-infections and CIRS; some in this group surely are familiar with the peer-reviewed data that exists. There is a serious scandal regarding CLD; coverups exist as they do re: M.E. and all related neuroendocrine diseases involving both endogenous and exogenous/environmental toxins.
Becca,
thanks for this info. quick question. what is CIRS?
Also, are you comfortable saying who the doc in the northeast is that you saw? I may consider seeing them. I used to live in the Boston area as well as NJ, where people seemed to have been significantly more informed than the medical community here in Florida where I now live. 🙁
Kira,
Why don’t you see Dr. Nancy Klimas, who is near Miami, I think?
Thanks. I’ve tried. Dr. Klimas is not seeing any new patients.
Cort, just want to give more of my heart felt thanks for all your hard work on this website. It has been a godsend for me!
Kira
Glad to hear it! 🙂
I want to say, with Kira, that this website has kept me going when I was ready to give up and let the docs have their way with ‘there’s nothing wrong with you’ and ‘your tests all came back normal’ even though they were only standard blood tests. We sometimes just don’t have the energy to keep fighting. This website is what I need and this article is SUCH good news!
Thank you from the bottom of my heart, Cort!
My fellow Australian Andrew Lloyd has been on this path for more than 5 years. ‘Hit and run’ immune insult. Then damage to brain / CNS.
This study is well behind Andrew’s work.
The USA has more than 15x the Australia population and should be doing better.
But still a good study. We need to work out the why/how the brain is affected after the initial insult.
I believe Andrew is studying that.
I hope he is…It’s the hardest place to study – otherwise I think more would have been done.
That’s right. My son is his patient and Hit and Run is what he proposed and studied nany years ago. His new study will be fantastic, building on the Japanese one with 500 people uses complex new PET techniques including special dye fluid which will highlight microglial activation. He’d hope to have it underway but is still waiting for the grant approval.
btw, consistent with this study my immune system has definitely changed during course of illness. First 3-4 years I was awful, lots and lots of allergies. Allergies have subsided over time. 90% of health regained. But still lack energy and exercise tolerance.
It still cannot be stressed enough that any single ‘model’ or finding that does not take into account the presence of putative subtypes is most likely fatally flawed from the outset. If there were one subtype of ME/CFS which consisted of a persistent enteroviral infection, another with some sort of autoimmune reaction to a previous infection, maybe one with a genetic inability to suppress herpes virus infections, etc, then it’s no wonder that the results from any given study would be all over the place.
Yes – the bulk of the patients in this study remain a mystery.
Until we get extroardinary amounts of money to do the very large and very comprehensive study or studies needed to do that, though,this is pretty darn good.
Prayers for all of us and for my doc’s group at Nova, Ft. Laud. Dr. Rey, Dr. Klimas, etc. and all the others that are working so hard to help us. 32 years for me and don’t know how much more of this assault I can take.
Times running out for those of us that were sick at the onset. Thought it was so bad in 1982 and looking back, that was a walk in the park. This is progressive and has attacked all organs and systems.
News sounds better and just need to hold on till better treatments are found.
Cort,
This study was completed due to some very dedicated people: Mady Hornig, José G. Montoya, Nancy G. Klimas, Susan Levine, Donna Felsenstein, Lucinda Bateman, Daniel Peterson, Gunnar Gottschalk, Andrew F. Schultz, Xiaoyu Che, Meredith Eddy, Anthon Komaroff, and
Ian Lipkin. But there are the patients and the controls who were willing to be lab rats…We don’t know the controls names who volunteered, but I hope that the word gets out how much we appreciate them. Also, at the expert clinicians offices, all the working staff carry an extra load of work to make studies like this happen, so if you are a patient at any of these practices, please thank the nursing staff, medical records, receptionists, office managers, and volunteers. It takes a Village… There is more to be done and more coming, but this is Hope for our patient population…Thanks for the breakdown of the paper.
Well said Bob.
I couldn’t agree more.
We simply don’t get such studies in the UK, so are extremely grateful to our fellow patients in America who took part in this study.
Only large and careful studies like this one will shift the goalposts.
Many thanks to all involved and of course, in particular, the researchers and support staff.
Amazing news, amazing article!
I wonder how and why would RITUXIMAB be well suited for both groups (before and after the 3 years mark) as they are inclined to think it is.
They referred to the Rituximab study and an autoantibody study in the paragraph on CD40L which appears to play a role in the shorter duration patients. It was more, I got the impression, that there’s evidence that B-cells and CD40L may be involved in ME/CFS.
If EBV is the key drive which i believe, EBV hides in B-cells. Rituximab kills these cells.
Oh, I’ve lost that paragraph.
Still I wonder about 2 things:
1. I remembered Rituximab being first proposed as a hope to severe patients. Perhaps the severity has nothing to do with the stage? You might be severe ill for too much action against your body or for too less action perhaps?
2. Gijs, that’s interesting, but why would the response to the treatment be so delayed? (they say it can be up to 6 months till the first results right?)
Good question. Maybe this article is interesting for you;
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085387
Hi, lots of the scientific terminology is overwhelming, but I try to grasp what I can. My daughter ended up with CFS after a severe virus and exaccerbated by a school administered vaccination whist she was still unwell. Interestingly we had two tests done by Metametrix over the time….BOTH showed irregularities in her kynurenate pathways…tests were done about 4 years apart! Hopefully they are on to something! And can tell us what to do for it.
Thanks Cort, and good luck to all of you out there.
If it is of any ‘consolation’ to anyone out there….my daughter did noting but rest for weeks at the outset and has still never been rid of the symptoms, though she does manage to function at a very basic level. Part time Uni (she is now 19) but no work or exertion. Have managd to keep very good control of her diet also, so despite 6years of ‘no physical activity’ she is not becoming overweight. I think diet has an influence.
It sounds like you did a fantastic job for your daughter in allowiing her to rest right from the beginning…of course you regret that she is only well enough to do a part time university course – but had you pushed her, she might well now be living in a darkened room, completely disabled. Conserving physical exertion in every possible way is her best chance of managing the cognitive exertion needed for a university course, and hopefully to continue to improve. Best wishes..
Hi Nancy,
Thanks for the comments.
Noted your information about the blood flow and other contributor comments about visual disturbances and inexplicable changes to blood pressure and heart rates on exertion. All are applicable to my daughter.
I keep looking for help and have tried many avenues…. I will not stop.
Will be on to the RBC issue TODAY.
Thanks again for the ‘red blood cell’ comments.
Cheers from Australia
Linda
For anyone interested in following up Les Simpson’s work on the red blood cell problems in ME/CFS…If you can access the very first Journal of Invest in ME, there is an article by him in that. My little book, ‘A Beginner’s Guide to ME/CFS’ has two short chapters on his work. Our joint book, Ramsay’s Disease has a very detailed account of his research as well as much more information. If you went onto my website and accessed Positive Health via it, you possibly could access the article he wrote for them. The Invest in ME journal would probably be the best way of getting a summary of his work. I also have some copies of his book ‘Blood Viscosity Factors – the Missing Dimension in Modern Medicine’ which I could send to anyone interested. In that he discusses red blood cell problems in diabetes, Huntingdons, MS, as well as ME/CFS. It seems that attention to blood flow problems in diabetics can help to prevent the secondary problems caused by circulatory failure in limbs and eyes. If you have access to medical journals from the 90’s and earlier, he has published about 120 papers on the subject…but sadly, hemorheology (the study of the physical properties of blood) isn’t included in medical school curricula, and Les is a Ph.D. in biological research, not an MD, which may be why his work is ignored.
Thanks for covering this in such detail, Cort!
As you’ll have seen, this is getting a lot of media coverage. As a community, we should be jumping in on those media stories and leaving comments encouraging people to donate to research, pressure the NIH and write to congress. It’s a great opportunity for outreach.
I’ve been putting the Columbia donation link around when I can:
https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677
There are commentable stories on Yahoo News, Medical Express, possibly the WSJ (I’m not a subscriber and can’t see the article by Amy Dockser Marcus), and the UK Telegraph, Independent and Daily Mail.
We can expect more today – please post comments and let’s leverage this coverage to our advantage. We can advocate and grow our research donation base at the same time!
Cort, could this study fit with the results of Lipkin?
Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085387
Everything points out to EBV in my view….
I truly believe ALL we have some how is related to what my father was exposed to during his time in WAR for the USA. He was deployed overseas. I will never forget hearing about the U.S. government telling GULF War Syndrome suffers that what they have was fibromyalgia and they weren’t going to give benefits TO THOSE suffering. HONESTLY I DON’T KNOW BUT COULD IT BE POSSIBLE THAT INOCULATION AND AGENT ORANGE AND WHATEVER ELSE PEOPLE ARE BEING EXPOSED TO COULD BE EFFECTING THEM AND/OR THEIR OFFSPRING???
I’ve been pretty sick my entire life. I have more diagnosis than any nursing home patient I ever came across in all the years I did medical records. Never know, I could go on for days but I’ll stop now but this might just be that motivation I’ve needed to finally write a book. THANKS AND TO ALL US SUFFERING GENTLE HUGS ,BUTTERFLY KISSES AND BEST OF HEALTH !!
What about those of us whose onset was gradual? When I first got sick, it manifested as fibromyalgia mainly, and the fatigue and other issues were much less of a problem. I was able to work for, however erratically and only part-time. Gradually the fatigue became more and more dominant, with many of the typical symptoms developing until I became homebound. I don’t see this pattern discussed in these sorts of articles.
That pattern is not excluded in this study. The findings could refer to an abrupt infectious onset or they could refer to something else – even a gradual onset.
They simply state that in the early years many people with ME/CFS have a revved up immune system. Infection is probably the most likely culprit but I imagine that that could be triggered in a number of ways – perhaps even a non-obvious infection (???)
This study really resonates with me. In the early years of my illness, all blood tests showed increased white cells (if I remember correctly), but no cause was ever determined. Later, my white blood cell count returned to normal. But, my symptoms/disability remained the same. Another piece of the puzzle, it seems.
This is the same with me Ellen hopefully someone will enlighten us 🙂
The IOM can change there name:
Systemic Exertion INFLAMATION Disease 🙂
SEID……
I’ll bet cytokines are skyhigh after exertion CPET.
Neat. Bit premature but then Montoya was also pronouncing earlier in the week about this being inflammatory, and now Lipkin/Hornig too 🙂
I simply have to defend Cort as I am new to this but only know that he does this and no one else HAS. Who is bringing all his information to us but him? Why on earth would anyone want to beat him down and call his reporting “bullshit”? So let’s just celebrate that fact that we are being VALIDATED by all this recent research. Over the past 20+ years I’ve been tested for MS using MRI’s about 6 times and a spinal tap. This thing does neurological, endocrine and cardiac damage. Some repairable, some not. Has anyone been stress tested on a treadmill and the cardiologist said ” you reacted paradoxically: your BP went up when it should have went down.” Also, does anyone’s heart rate rise quickly when any uphill challenge is presented? When the treadmill speed was increased and the elevation raised a Small amount my heart rate rose so quickly so they failed me. The first test I ever failed! And the eye stuff. When fatigued does anybody start having blurry vision or a “film” on the eye that doesn’t go away until one rests? When I used to hike in my 20’s when I would be going uphill and it was hot ,I would stop, hold onto an obliging aspen and would see all the other trees “retreating”. They looked like THEY were moving! I knew I was really neurologically screwed up when this happened! Something right out of the Shining….ugh!
So I wish all you folks in early stage ME/CFS a good day and hope your symptoms feel a little better today than you did yesterday. Watch out for stressful lifestyles(a major bogeyman in my journey with this illness as a nervous breakdown preceded my initial symptoms)!
…Remember what Steven Hawking said about where there is life, there is Hope. Thanks Cort and may the Force be will you!
P.S.How about naming this thing: Global multi-systemic Inflammatory Disease?
GMSID?
I’m very tired today so perhaps more pessimistic than usual – but while this is offering some interesting insight into what starts the disease of it doesn’t seem to offer much for why it continues.
That’s an excellent point Tatt.
I think it’s pretty clear for most people CFS starts with a really nasty infection.
but why is it perpetuated?
I think its permanent neuroinflammation.Which hopefully can be targeted by treatment
Occasionally someone relates that their symptoms began after surgery. Since that seems to be my pattern, I am interested to know other’s stories who have experienced the same onset of fatigue. I had several minor surgeries ( 2 carpal tunnel, torn rotator cuff in shoulder-twice, torn meniscus in both knees…then the “biggie”; open spine …fusion requiring 3 incisions).
I complained of having “anesthesia brain fog” and extreme fatigue as well as feeling “sick”. It has been three years and my condition has gotten progressively worse. For at least two years, I pushed myself to get things done even when I hurt, felt sick and could hardly accomplish the task because of no energy.
I am now basically homebound because I just can’t push anymore. With the least exertion…like having lunch with friends at a restaurant puts me to bed for a day or two. I never feel good and I am sick and tired of feeling sick and tired. I do better if I rest after each thing I do…like brushing my teeth. The bath routine is exhausting and puts me to bed.
What a life!!!
I am 80 years old and have had a very active life…32 years as a school administrator…long days and many evening meetings.
Regards to the long-sufferers.
Mary Lee
Mary Lee, I am nearly 80 and have had ME since 1986. My consistent experience is that if you treat rest as a treatment, and do it as much as possible, you can set a path towards gradual improvement. It is so sad that so many ME sufferers, being energetic, positive, caring people, do go on pushing themselves when they get sick. And get sicker. I think if you take resting and conservation of exertion very seriously, eliminating any unnecessary physical exertion (like supporting the weight of your head, make sure you are always resting your head on something, it weighs 10lb and takes muscular exertion to keep it upright)….Become an exertion-conservation expert, and help those around you to understand that rest is your medicine, so every physical task they help you with or do for you is positive help towards your getting better. Try this approach for six weeks…six months…it doesn’t cost money!!! I do hope you can try this advice out and find it helpful…
I got that cough thing this winter, and have been having to spend half each day in bed for weeks. All of a sudden – as my friend put it – I’m acting like a normal person. It’s like being let out of prison. But I know I need to spend tomorrow resting, and be really careful to keep resting in my schedule. It really does help, over the long term.
Cort,
Cort in your opinion what are the implications of this new study of Ampligen and its chances of being approved by the FDA
I think it and the publicity around ME/CFS can only helpat the FDA but I have no idea how much. I hope it creates more urgency for everyone to find creative ways to get things done..
I do believe Hemispherx Biopharma and the FDA are talking.
I have gotten thru a lot of life, not even aware of such a disease as ME-now I am 78! I started looking up ME info by searching the internet about 7-8 years ago, and discovering the Hummingbird site. Everything in it matched me!! I had been complaining about fatigue to my dr. for a long time and had no results or reactions-work too hard!! Yes, I have been an energizer bunny all my life!! Recently, I found letters from my college years, finding I was complaining all the time of “being tired”-I had even been put in the infirmary. Then, I noticed something else on some site–ME being called atypical polio. Our tiny town had been struck by a polio “epidemic” in the 1950’s-leaving one girl on crutches for the rest of her life, and one boy died. Could I have possibly picked up something similar in my system which would plague me the rest of my life, but never severe enough to stop me. I have had most all the symptoms listed for ME at one time or other in my lifetime. But the last 10 years has brought on some more severe symptoms-old age?? But the most noticeable has been the slow but sure lack of energy after any tasks-work, home, family, etc. Things I had no trouble handling even 5 years ago, according to my diaries, I can no longer do-no strength!! Even 1 year is now appearing very different. I must sit and sit, not able to do anything here in the house-it all just sits here waiting. I must do this in order to be able to go to work-yes, I still work! And take care of an extremely disabled husband whose condition is worsening. And none of the doctors I see have any idea about ME. How I would love to be tested for some of the advances now being done!! I would love to know if this is what has been plaguing me all these years! But I have no financial way to get anything like that done. All I can hope is that there now will be more testing and research on ME (will NOT use “new name”) for those coming up behind me, or have had ME affect them at a much younger age than when it has finally taken over my life!! Thanks for listening!!
Yes, Cindy, I diagnosed myself initially also via the Hummingbird website. I had been diagnosed with FM x 10 years but I was getting worse and worse, more and more exhausted and house-bound. I’d always felt something wasn’t quite right with the diagnosis. I stumbled upon the Hummingbird site and got all excited when I realized I probably have ME. I then went to the Canadian Consensus and read through that. Finally a clinic for Complex Disease, including ME, FM and Lyme disease opened and I was diagnosed with ME/FM. Unfortunately the clinic is so over-whelmed with new patients it’s in a bit of turmoil and patients like me who were seen when the clinic opened a year and half ago have to fight to get an app’t for continuing care.
I keep up with Cort’s blog, thanks Cort, which constantly gives me hope as well as interaction with other suffers. I have truly felt I’ve battled this disease alone, which we all do in a way, but it’s good to hear the same issues from others.
I did a similar thing.. had diagnosis for Fibromyalgia 13 years ago, but some symptoms didn’t make sense. I found the symptoms list on the Hummingbird site and then I knew that what I had was more than Fibromyalgia. I am now mostly bed bound and believe I have ME.
But the clinic near me in the UK is run by a doctor who says that Fibromyalgia patients can’t be admitted, as he says Fibromyalgia is at the opposite end of the spectrum from ME, which really makes no sense to me. In any case, I don’t take his word for anything as I’ve looked at his published article and research, which are based on the PACE trial!
So for me, the self-diagnosis has to be it. My GPs (I’ve had 3 now) do not want to discuss ME unless I will go to the Rheumatologist to have it diagnosed. To me that seems like going down the road to hell, since they all treat with CBT and GET, and are determined that we make ourselves continuously and progressively ill by being deconditioned and having wrong illness beliefs.
So, I just have to rely on this website and thank goodness I have Social Service funding for carers now. Too bad I didn’t have the care I needed back when I was still able to walk a bit and not bed bound. That is the trouble that needs to be addressed immediately with moderately ill patients. As long as people show some ability to function, they will be denied benefits and care. They will get worse, because they are not able to rest.
I have often been so angry and defiant at being told that my tests are normal (routine blood tests and nothing more are all they will ever do), that I pushed myself and willed myself to get well. We know how that turns out. I still have a lot of difficulty stopping when I am tired, as I have so much creative energy. I just want to keep at a project, a letter, reading, talking to a friend online, etc. until I am wasted from the effort.
I hope it’s not too late for me. 62 yrs old and have been ill for over 13 years.
I too have this awful disease and recovered from it the first time which came on
Overnight after a period of about a year.
But I have now had it twenty years,But perhaps their is still hope for us
Long sufferers.
I used to feel better sometimes when I had Flu I don’t know why.
Wish I could remember the reason I recovered first time.
The second time was directly after a weekend with a sore throat and Glands
Enlarged.
One Question I would an answer to is the “Royal Free Disease” where a number of
Doctors And Nurses Died in a London Hospital in I think 1955.
HOW!!!
Gordon,
It’s interesting what you said about feeling better when you have the flu. I’m a longtime sufferer (18 yrs). This study puzzles me bc of my experience. Over the years I have definitely lashed out against this disease only to be slapped down by it again & again. My course has followed one of ups & downs: every up being shorter & not as high as the last, every down being lower & lasting longer. But all during this time when I am down I catch nothing going around. When I start to come up a little I will start catching everything but still feel better!?? Anyone else w this pattern? How does this fit in w this study as I have continued to have this up to at least the 17 yr mark?
Thanks Cort for your always illuminating update. I will be much happier when they come up with a way to first of all prove with the seemingly necessary empirical data that those of us who have been variously diagnosed with (I won’t list the truly rude and dismissive things my GP told me at first) ME, PVS, CFS and finally FMS have been waiting for. I’m rather concerned by what they can apparently easily prove in early illness and how easy it would be to focus on these still young people and forget about 20+ years veterans like myself. I still have 20 years of good working life in front of me – I hope.
I for one don’t want another 20 years of this. If these group of illnesses cannot be ‘cured’ soon – I’ll be campaigning for the right to die.
Sorry to sound negative but I’m becoming overwhelmed by all the new research. Don’t get me wrong. I’m glad the research is happening but despite a Masters in Public health, my brain can no longer process the methods or even results of the research. That leaves me relying on their interpretations – once they have been explained in letters of no more than three syllables! Are they going to find a ‘final stage’ to this condition? Am I already in it? Is there anyway back!
Thank you so much, Cort! and to all the other responders, too. The Fog is too strong to write much of anything else at this time. I’m 63 and first Dx in 1986 with FMS then self-Dx SEID (ME/CFS); pretty much home bound, can no longer do, think, say what I used to. So frustrating, especially after reading posts from those in their 80’s. I can’t last 20 more years with this.
A couple of notes I jotted down while reading
vagus nerve infection? : my vagus nerve -> vertigo, syncope, gut problems, sneezing after eating
central nervous system : many drugs I’ve taken cause CNS adverse effects
Wishing us all the very best!
Does anyone know a doctor in the Atlanta Georgia area taking new patients? Diagnosed with CFS/Fibromyalgia in 2002 after birth of first child. Narcolepsy more recent. Desperate to get relief from a doctor that really understands these diseases. Thanks in advance.
Stephanie,
There is a Holtorf clinic in your area. A large focus of their’s is on the endocrine system & the part hormones play in this disease. Google holtorf clinic… Wishing you the best!
Look up Dr. Satesh Cuddapah. I saw him when I first became ill with SEID/CFS/ME in 2006. His manner is wonderful and his understanding of fatigue and its many comorbid disorders and diagnoses is superb. I don’t see him any more as I live 8 hours away, but I’d go back in a heartbeat if he lived closer.
do the lesions mean irrepairable damage- the thought of not being able to read a book again is too upsetting
Iwatched a Japanese television program on chronic fatigue which went through all the research that’s been done in Japan. They found that the brain of chronicbfatigue patients is impaired but will return to normal once they recover. I have had fibromyalgia since 2008 with fatigue but had a sudden, severe, and debilitating onset of fatigue in May 2013 and was subsequently diagnosed with CFS. Until a few weeks ago I couldn’t read a book. But suddenly and magically, although I was told at a aCFS clinic that cognitive function is the last thing to return to normal, my brain for has largely gone and I don’t seem to be experiencing the severe cognitive fatigue that would come on even after physical exertion. I think there’s definitely hope, though I’m spending my time reading as much as I can lest I completely relapse.
The only change I made was to put all treatment on hold and stop seeing doctors for anything. I’m completely burnt out after all these years and the stress of constantly thinking about and monitoring my condition got too much. I’m sure this reduction in stress hashed a bbeneficial effect.
I wish you all the best and I truly hope you’ll exhaust entire libraries in time.
Zip:
Don’t give up hope about the books. I’ve been sick nearly 11 years, now, and for the first nine or so I could only listen to books on CD or Audible.com. The good news is that in the last 18 months, I have rediscovered my ability to read and write (I freelance) and it is wonderful. I can’t read five books at a time like I used to, but I CAN read them and I am so grateful. I am also now addicted to audio books, too, though!
I simply have to defend Cort as I am new to this but only know that he does this and no one else HAS. Who is bringing all his information to us but him? Why on earth would anyone want to beat him down and call his reporting “bullshit”? So let’s just celebrate that fact that we are being VALIDATED by all this recent research. Over the past 20+ years I’ve been tested for MS using MRI’s about 6 times and a spinal tap. This thing does neurological, endocrine and cardiac damage. Some repairable, some not. Has anyone been stress tested on a treadmill and the cardiologist said ” you reacted paradoxically: your BP went up when it should have went down.” Also, does anyone’s heart rate rise quickly when any uphill challenge is presented? When the treadmill speed was increased and the elevation raised a Small amount my heart rate rose so quickly so they failed me. The first test I ever failed! And the eye stuff. When fatigued does anybody start having blurry vision or a “film” on the eye that doesn’t go away until one rests? When I used to hike in my 20’s when I would be going uphill and it was hot ,I would stop, hold onto an obliging aspen and would see all the other trees “retreating”. They looked like THEY were moving! I knew I was really neurologically screwed up when this happened! Something right out of the Shining….ugh!
So I wish all you folks in early stage ME/CFS a good day and hope your symptoms feel a little better today than you did yesterday. Watch out for stressful lifestyles(a major bogeyman in my journey with this illness as a nervous breakdown preceded my initial symptoms)!
…Remember what Steven Hawking said about where there is life, there is Hope. Thanks Cort and may the Force be will you!
Yes I get the blurred vision (I called it lazy eye as a child) when I am fatigued, often before I feel fatigued in other areas of mind or body. I always put it down to eye muscles lacking the energy to focus.
Kathleen,
Yes, my heart rate rises almost immediately with any uphill challenge, even one so slight it is hardly noticeable.
I, too, experience blurry vision or a greasy “film” over my eyes. I know from experience that I must rest for an extended period of time before getting my eyes checked for glasses. Otherwise, it’s a wasted appointment because I can’t focus, regardless of how the optometrist sets his equipment.
And, one of the scariest indications that I am “neurologically screwed up” is when driving (or a passenger) and it seems cars in adjoining lanes are veering towards my lane. Even worse, when especially fatigued and moving slowly through a parking lot, it appears as if all of the stationary (parked) cars are backing up into my lane.
Hi,
Thank you for your great article.
I wanted to check the following: am I right to assume that by ‘IFN-y’ above you mean IFN-gamma, a symbol that looks a lot like a y?
I’ve seen this ‘interferon gamma’ hilighted in other reports of this study so I was wondering if you are agreeing with these hilights or commenting on something different entirely.
Thanks again 🙂
Yes – IFN-gamma
I wonder what this research could mean for FM. Many believe that FM and CFS/ME are one and the same. Any comments??
I think it could mean a lot for FM. FM often starts with an infection. We know that the central nervous system is on overdrive in FM – why not a a period of immune activation for a time to send the brain spinning?
I can definitely see the same process having somewhat (but not very) different effects in FM.
thank you for this….btw; looking after my 2 cats(or is it the other way around) is the only thing giving me a will to live……LITERALLY; if there is no cure….when they’re gone, I’m gone; ENOUGH !
I think a lot of us know exactly how you feel. For me it’s my grandkids, but there are times that even the thought of them fades when I’m in intractable pain or have no strength left what-so-ever.
My suggestion: get another kitty when your other cats are old…there are lots of stay kitties that need our love. That need your love and care.
thank you for commenting Katie; I have”adopted” many rescues over the years; all have been the most precious gifts I have ever received…perhaps the only “good” to come from this disease(for me), is a greater empathy for the suffering of others; this includes(other) animals; the most exploited, abused and tormented sentient beings on this planet;… and,we know, that abuse, is a human”invention”… my concern / fear, that I may outlive my “companions”, is at odds with the joy I have in sharing my”life”with them…the thought of what may befall them, should they survive me, is very disturbing, as I don’t really have the means to guarantee an acceptable life for them, once I am “gone” .
Ivan whilst all of us that have this horrible disease feel as you do at times.
We have to stay positive and hope research will yield perhaps a cure or help
In bearing up with this disease.
It is essential we do this if not for the growing number of young people
Who may be viewing this discussion.
Keep hope alive.
Since 1994, hard to look at that in black and white type. I am overwhelmed by the absolute randomness of symptoms and seemingly conflictive news and research on this illness. I tried hepapressin and after after some months, went back to a state much like the first year. I was doing much much better for a good ten years. To me, this illness is hugely neurological. I’ve had so many really scary neurological symptoms and in my worst crashes, after taking a stron sleep med, my brain is interrupted and there is a short time (before sleep) of reversal of symptoms….
How long before there is consensus and thus treatment that works?!?!
Didn’t Jay Levy of UCSF already showed 20 years ago that the immune system of CFS patients were hyperactive? I don’t think this study from Colombia will amount to anything other than perhaps serving as a biomarker for short term patients if replicated. For one thing, all patients, both short and long term, exhibit PEM. That makes me think that the hyperactive/underactive immune system is a victim, or symptom, of CFS rather than the cause.
I’m so glad that more thorough research time is being spent on looking at possible viral and pathogenic causes. I have had FM for 15 years now, and for 15 years I have told every doctor and specialist that will listen to me that I was once a very healthy active person, then I was hospitalized and treated for meningitis.
At the time I had 3 spinal taps, and every time, all they could say was my spinal fluid was not normal, and cloudy, with an excess of white blood cells.. but they couldn’t tell if I had viral or bacterial meningitis conclusively.
I thought after being treated, I would just get well, and return to my normal life.
I don’t make a very good patient!
Instead, by whole health, flipped upside down, starting suddenly not being able to walk for more than a block or two, and being so exhausted I couldn’t stay awake or focus enough to function. I was a single mom, and part time student.. I had to drop out of school, and my mother had to step in and help me take care of my own children, because I was completely debilitated. Over the years I have fought to get proper care from doctors who can’t even say the word fibromyalgia. I’ve been prescribed antidepressants several times, and have since gained 60 pounds, with doctor trying to reassure me this is the best and only treatment available. I have learned through trial and error, that antidepressants make me mentally worse, as I truly am not depressed on going, only feel defeated and blue once in a while because of the toll this has taken on my life.
I really hope so much this leads to some kind of treatment. Its been a difficult ride, with too few doctors wanted to see it as anything but depression or not getting out more and socializing!!
The ripping burning pain I feel daily, the exhaustion and sleep deprivation… my kids have had to suffer with having half a mother.. I pray for a cure, or at least a test my doctor will actually accept as being real medical proof.
I have had active symptoms of fibromyalgia since I was 8 years old and am now 73. That means to me that I probably have always had it. My mother had FM too which makes me wonder about the genetic connection. I am so grateful to those involved in searching for answers for us…finally! I don’t think it will happen in my remaining years because there is still a long way to go but it would be lovely to sit across from a doctor…any doctor.. and know that they no longer believe that everything is in my head. Forget the pain, that has been the cruelest thing of all. Good luck to all of us, patients and researchers alike!
Replying to Judy & everyone else,
I have had the FM/CFS for 36 yrs. Now this yr. I will be 70. My mom also had FM but I don’t know if she also had CFS. We both have had the constant dizziness a feeling of having alcohol but I don’t drink neither did she. We also experienced lot’s of head aches & for me almost every day.
She passed from multiple strokes…I wonder how it’s going to go for me? Super stress has played a part with also infections for when it started when going threw a divorce in 1975 & four yrs later. I was sensitive to alcohol before Fm/cfs started..Hang overs lasting 3 or so days plus anxiety sometimes. Then in 1979 it came with hives and fainting. Hives lasted for days & the hives were large. In emergency the dr.’s could not figure it out.
I do eat a healthy diet & I just came off my diabetic meds cause I feel I can control that with Cinnamon and chromium 1,000 mg ea. I was having the nerve pain in the feet and hands. Now just in the hands. I feel I was being over medicated with this stuff after 16 yrs. I believe in holistic medicine.
Yes, I believe it can be in the DNA. CFS/FM.
Thanks to Cort Johnson:) God Bless Everyone.
Bless you Danielle. I have had this curse for more than two decades and that is bad enough.
It’s good to read that we never give up searching for answers. I swear off and just try to accept from time to time but who can accept the neglect and cynicism of science, doctors, health insurers, governments, friends and non sufferers at large. It is only now that science, medicine and (at least the US) establishment are taking notice. I hope that the many questions will be answered in our lifetime – maybe not effective treatment let alone a cure – but enough evidence to validate the illness. I’d like to live long enough for personal and public apologies.
The flame burns brightly in us despite what we exist with. Long may it burn.
Christine
Hello Christine,
I agree with you on so many Doctors did not & some still don’t believe in CFS. I went to an infectious disease Dr. for more insight in 2012. Well, he said nicely. I don’t doubt your go threw all this but I see no evidence of this being a real thing & don’t believe in this. I was shocked ! In 2012 this all does not exist in the science world. Wow, I thought to myself. He was a young Dr. I would of thought would be open minded. NOT:)
Well we can’t give up even when I have days like yesterday. I crashed by sleeping all day. Today was a good day thou. I have not crashed like that since 2012 when I took care of my fiancé with cancer stage 4. That was very stressful for me so I had a lot’s of crash days more often.
Keep the fire burning & praying that more scientist “Nail it on the Head” with the right answer’s….Blessing’s to you…Danielle