arrow29 Comments
  1. Marilyn
    Apr 23 - 12:45 pm

    This is such an important topic! Thanks so much Cort for covering it. I also had a very in between sort of onset. First I had extremely subtle symptoms, then it got worse and I took some time off from grad school and got almost well. Then I had a series of stressors- trouble with my research project, major surgery, a major bicycle accident and my dad diagnosed with cancer. After that I had a day when things suddenly went very wrong. As to symptoms, I don’t have any cognitive problems, but do have classic PEM.

    • Cort Johnson
      Apr 23 - 1:12 pm

      Aha! What an interesting subset you are. We should do a poll about subsets…I imagine there’s a large variety of onset subsets….

      Hmmm…….

  2. Barbara
    Apr 23 - 1:36 pm

    This is critically important – how can you study a disease effectively if no-one can agree on what it is? How can you effectively treat a disease if you are confusing it with others?

    The conflation of M.E., CFS and FM holds us all back, researchers and patients both. I have classic M.E. and it isn’t the same as CFS.

    Thank you Cort, for covering this.

  3. Arlene Smith
    Apr 23 - 2:12 pm

    Hummingbirds’ Foundation for M.E. (HFME.org) ~ explains everything about this devastating disease from which I have suffered for 38 years. Cort you’re so up to date on things I hope you’ve heard about this organization plus I don’t understand why all the researchers in this country don’t subscribe to this instead of wasting so much precious time on “cfs” research which I now know doesn’t even exist.

    • geoffrey keith brown
      Apr 23 - 9:54 pm

      Arlene it isw so simple isn’t it but it took me 27 year4s the p3enny to drop
      humming birds for me myalgic encephalomyelitis ie or a diagnoses of post viral syndrome
      sudden onset that means overnight
      cfs for the rest
      cheers geoffrey k brown

      • Claire
        Apr 24 - 6:11 pm

        I don’t understand what all the controversy is about ME versus CFS. Am I missing something? ( yes I’m sure I am ). Dr, Hyde is actually my doctor and he has never mentioned this Hummingbird site in all my many hours of doctor visits with him. I also notice he doesn’t really put down the word CFS although he, at one time, said it wasn’t really a diagnosis. He doesn’t say much about ME either and certainly doesn’t say things such as “you have ME but not CFS ” or “you have CFS but not ME”. I wonder if, with all the recent developments, he is changing his mind? I’ll have to ask him and get back to you all.

        I think a lot of us, depending upon what definition you use, fit into both ME and CFS categories. I for one, fit both ME, according to this Hummingbird site , and CFS but use the term ME/CFS or even CFS more often, just for simplicity. Aren’t we doing ourselves a huge disservice and wasting our precious energy by arguing amongst ourselves as to which of us has “true ME” versus what some people consider “not ME” or “CFS”. Isn’t the whole point of needing a better definition and needing a diagnostic test to avoid having this type of discussion? I just hope that we get some really good bio-markers soon so all this talk of definitions and who fits where and who has what can not be such a combative subject. Then we can be all one happy family…..with multiple sub-groups.

        Thanks Cort for this blog. I missed this talk and now wished I hadn’t. I didn’t realize the subject of a definition for ME/CFS ( or ME or CFS or whatever)_ was so interesting :)

  4. Caron Ryalls
    Apr 23 - 2:13 pm

    My 16year old daughter was diagnosed with ME/CFS 3 years ago after her HPV vaccination and then after 18 months it was discovered she was suffering from POTS. I’m still no wiser as to whether she has ME/CFS or indeed has ever had ME/CFS since her POTS specialists maintain her symptoms can all be attributed to POTS/Dysautonomia, including PEM. Lots of POTS patients refer to a delayed ‘payback’ after overdoing things and overdoing something one day can leave them bedbound for days afterwards – is this not considered the cardinal symptom of ME/CFS. Sleep distruption,
    unrefreshed sleep and cognitive problems are also considered POTS symptoms. So are there a great many ME/CFS patients wrongly diagnosed and actually suffering from ‘just’ POTS, or are there a great many POTS patients who are wrongly attributing symptoms and are really suffering from ME/CFS or are ME/CFS and POTS two separate and different disorders that one can suffer with at the same time. Still very, very confused and not sure how accurate the De Paul questionnaire will be at weeding out other conditions.

    • Cort Johnson
      Apr 23 - 5:47 pm

      It’s such a great question. Weeding out the intermingling is going to be fascinating. This study suggests there is a distinct POTS subset in ME/CFS that is younger (Natelson suspects that POTS may transform into hyperventilation as the person ages in some cases), less fatigued and has more autonomic issues.

      Who knows which comes first – which is the chicken or the egg or if there are such things. With all the autonomic issues in ME/CFS my guess is that its all one group with lots of different variations.

      J Intern Med. 2013 May;273(5):501-10. doi: 10.1111/joim.12022. Epub 2013 Jan 7.
      Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome.

      Lewis I1, Pairman J, Spickett G, Newton JL.
      Author information
      Abstract
      OBJECTIVES:
      A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia +syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.
      METHODS:
      A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.
      RESULTS:
      CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.

      CONCLUSIONS:

      The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.

      There’s also this study which shows that POTS shows up in multiple sclerosis – http://www.ncbi.nlm.nih.gov/pubmed/20309394

      Int J Med Sci. 2010 Mar 11;7:62-7.
      Autonomic dysfunction presenting as postural orthostatic tachycardia syndrome in patients with multiple sclerosis.
      Kanjwal K1, Karabin B, Kanjwal Y, Grubb BP.

      and this study which shows that ME/CFS is common in POTS and that POTS patients with ME/CFS are similar to POTS patients without ME/CFS. I’ll bet there’s a continuim that stretches all the way into CFS patients not diagnosed with POTS.

      Clin Sci (Lond). 2012 Feb;122(4):183-92. doi: 10.1042/CS20110200.
      Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes.
      Okamoto LE1, Raj SR, Peltier A, Gamboa A, Shibao C, Diedrich A, Black BK, Robertson D, Biaggioni I.

      Abstract
      Several studies recognized an overlap between CFS (chronic fatigue syndrome) and POTS (postural tachycardia syndrome). We compared the autonomic and neurohormonal phenotype of POTS patients with CFS (CFS-POTS) to those without CFS (non-CFS-POTS), to determine whether CFS-POTS represents a unique clinical entity with a distinct pathophysiology. We recruited 58 patients with POTS, of which 47 were eligible to participate. A total of 93% of them reported severe fatigue [CIS (Checklist of Individual Strength), fatigue subscale >36], and 64% (n=30) fulfilled criteria for CFS (CFS-POTS).

      The prevalence of CFS symptoms (Centers for Disease Control and Prevention criteria) was greater in the CFS-POTS group, but the pattern of symptoms was similar in both groups. Physical functioning was low in both groups (RAND-36 Health Survey, 40±4 compared with 33±3; P=0.153), despite more severe fatigue in CFS-POTS patients (CIS fatigue subscale 51±1 compared with 43±3; P=0.016). CFS-POTS patients had greater orthostatic tachycardia than the non-CFS-POTS group (51±3 compared with 40±4 beats/min; P=0.030), greater low-frequency variability of BP (blood pressure; 6.3±0.7 compared with 4.8±1.0 mmHg2; P=0.019), greater BP recovery from early to late phase II of the Valsalva manoeuvre (18±3 compared with 11±2 mmHg; P=0.041) and a higher supine (1.5±0.2 compared with 1.0±0.3 ng/ml per·h; P=0.033) and upright (5.4±0.6 compared with 3.5±0.8 ng/ml per h; P=0.032) PRA (plasma renin activity).

      In conclusion, fatigue and CFS-defining symptoms are common in POTS patients. The majority of them met criteria for CFS. CFS-POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients.

  5. John Gabor
    Apr 23 - 3:29 pm

    There are many subsets and likely subsets of subsets. One that has bugged me is that there is a significant number of people with ME who do not get the common cold or flu virus. It is now over 4 years and I have not had the flu or a cold at all. I use to be petrified at the cold or the flu making me sicker. My wife is a preschool teacher who often gets sick and brings home whatever new virus has made it into the preschool. I have 3 teenagers in school too. Everyone in the family gets sick from these viruses – except me. I have asked other people with ME about this many times on Facebook groups and on Forums. There is always two clearly defined groups. One that gets sick from the slightest infectious contact and the other that rarely gets any flu or cold infections. That said, my symptoms are constantly highly viral (according to my MD) and every time my immune activation is measured it seems to be getting worse. I think there is a lot of value at recognizing and studying subsets in terms of giving us a better understanding of ME and how we might effectively treat it/cure it – not that I am naive enough to think that any drug company wants to develop a cure for any illness.

    • Anon
      Apr 25 - 7:05 am

      The phenomenon of *not* getting that cold or flu that’s going around . . .

      You may want to do some research on the concept of anergy. (Not energy; it’s anergy with an “a”.)

      Wikipedia says,

      “Anergy is a term in immunobiology that describes a lack of reaction by the body’s defense mechanisms to foreign substances, and consists of a direct induction of peripheral lymphocyte tolerance. An individual in a state of anergy often indicates that the immune system is unable to mount a normal immune response against a specific antigen . . . “

  6. Christian Godbout
    Apr 23 - 3:57 pm

    I do not see the CCC or the ICC as the sacred Scriptures, but I am not at all comfortable with Dr. Jason’s view on these! I agree that a too long list of required symptoms can be problem; but a far greater problem to me is symptom hierarchy. Fukuda had fewer symptoms than the CCC or ICC? So what! PEM, though present in Fukuda, not only does not come first hierarchically but , worse, it is optional! And that is it’s greatest flaw. That was certainly rectified by the CCC, who puts PEM as the second criteria (following “fatigue”), and radically more so by the ICC which bumps fatigue out all together and sets PENE right on top as the very first compulsory symptom and the only one in this list which is not an option among other symptoms (to me that is a clear-cut criteria that rules-out right from the start most other fatigue-associated illnesses). Nothing vague here. Actually If you read the ICC carefully, it only requires 4 symptoms, no more. However much I admire Dr. Jason’s Work, I must say I have reservations about his reservations towards the CCC and ICC.

  7. Gregory G Cutler DVM
    Apr 23 - 5:16 pm

    Key to all these issues and questions are two missed topics Dr Jason discusses but doesn’t highlight -but are essential to quality medicine. 1) A proper medical History which involves quality questions. 2) Algorithms to determine the stated “Assessment” eg., cognitive disfunction- does indeed fit the definition for the specific disease.
    As I have written to the IOM ( and I’m sure was immediately put in the round file cabinet!). What the ME/CFS case definition lacks, but all other medical conditions contain, are Algorithms leading to a diagnosis.

    • Cort Johnson
      Apr 24 - 12:05 pm

      I think he would agree completely.

  8. Lisa Petrison
    Apr 23 - 6:14 pm

    Of course, I appreciate Dr. Jason’s work and am grateful to him for his dedication.

    Still, if our goal is to really get a handle on this disease, we need be approaching the situation as described in the following comment (made by a highly respected epidemiologist who focused his attention on ME/CFS during a recent presentation about issues with the disease at the Santa Fe Institute):

    >There’s a science that studies the causes of disease, epidemiology. A way that you could use a lot of these ideas is that you come up with an adequate case definition. That’s hard. You start by identifying true cases and matched controls, and you can go through and create hypotheses. For instance, about mold exposure. Where you’ve lived in the past ten years. Then you come up with nice identifiable risk factors for this disease. Like with the AIDS epidemic. You had this collection of individuals who had Kaposi’s sarcoma and pneumocystis, but you had no idea what caused it. They sat down and had this clear case definition that you can try to tease apart from there. It’s surprising to me, and I guess it’s because it’s such a nebulous thing, that no one’s ever sat down and done this.

    http://paradigmchange.me/wp/?p=672

    Until we actually go through this process of focusing on and then profiling the clear cases (which should have been done in 1986 and which instead has not ever been done by anyone), we’re never going to get a clear handle on “Who’s In” and “Who’s Out.” It’s all going to be based on speculation and algorithms — which, though both have their place, should not be the driving force in the study of the disease.

    I have found few knowledgeable people in this community who do not agree with this, in theory. It thus is frustrating that no one, to my knowledge, is actually pursuing this sort of project.

    I elaborate a bit on the importance of this with regard to understanding ME/CFS in this brief talk (transcript in the comments section).

    Best,

    Lisa Petrison, Ph.D.
    Executive Director
    Paradigm Change
    http://www.paradigmchange.me

  9. MsJustice
    Apr 24 - 4:23 am

    Much as I respect some of Jason’s work and his empathy, I don’t think the answer is narrowing the list of symptoms IF the list of symptoms are vague and undefinable symptoms (often found in other conditions together and some in the general population). Just because sleep dysfunction and fatigue are common symptoms in CFS and ME, doesn’t mean these should be the core symptoms. Many people with clearlt defined ME and advocates, liked the CCC and ICC: ME because they felt it described their illness better. More about the neurological, immunological, autonomic problems and less fatigue/sleep/lack of concentration vagueness.

    For example; we’ve moved from Ramsay’s muscle fatigue on exertion and delayed recovery, to generalised fatigue (often undefined) with post-exertional generalised fatigue (often undefined and optional in some criteria).

    I like the idea of studying the most severe, acute onset patients with Ramsay defined ME, then getting objective findings. I’m not a scientist or epidemiologist though and know nothing about how other established definitions/criteria came about. Worrying to know that insurance industry input and politics can influence these.

    In summary: We need stricter criteria based on objective findings and if that means people don’t fit the criteria, an additional Atypical Syndrome, can be a looser definition, that protects patients’ rights to care, insurance and benefits…if needed.

    • Cort Johnson
      Apr 24 - 12:09 pm

      Jason is finding that study evidence indicates that if you pick the right symptoms then you can differentiate this disease from other disorders and that adding symptoms doesn’t really make you more effective at that; instead it can bring other types of patients. Jason is using a long list of symptoms to find the ones that are most characteristic of ME/CFS; he’s not choosing the symptoms that ‘make it'; the statistical program is determining that.

      Interestingly, the London Definition of ME only uses a couple of symptoms; it’s the closest to the putative Jason definition that we have at present.

      Intuitively, it doesn’t makes sense that a shorter definition would be better but it seems to work out that way.

  10. MsJustice
    Apr 24 - 5:24 am

    How about a strict set of core serious symptoms, at least 50% reduction compared to pre-illness activity levels and objective findings for criteria for research, at least? They should have loss of normal muscle power that causes significant reduction in activity, for days after exertion. More research on the severe. If scientists are concerned about deconditioned patients muddying the waters, they can have severe patients who are not bedbound and compare to sedentary, healthy controls. Also, circulatory phenomena-feeling cold, cold extremeties, orthostatic intolerance.

    • Cort Johnson
      Apr 24 - 12:13 pm

      I think that’s what Jason did in general; he added frequency and severity to the equation and that changed everything. Once he did that he was able to eliminate non-ME/CFS patients from the ME/CFS and keep the ME/CFS patients in there.

  11. Gijs
    Apr 24 - 6:16 am

    I think that a PET scan can make an end of this ‘discussion’. I put my money on this :-)

  12. Simon McGrath
    Apr 24 - 9:06 am

    Terrific article, Cort, thank you. I think Lenny Jason has long been at the forefront of case definition research and like his emphasis on empirical use of data to validate case definitions. This is exactly the point stressed by Tony Komaroff in his excellent IACFS/ME Conference round up: consensus is not enough.

    Also, I seem to remember you writing a piece a few years back about how CCC criteria were ‘flexlibly” applied by researchers in order not to exclude everyone eg if someone had a symptom at the beginning, that would count, even if they no longer had it? I thought this was you reporting back on a ’round table’ discussion at some conference, but my memory is rubbish.

    “About 10% of severely impaired individuals with ME/CFS do not experience much fatigue, apparently, because they’re rigorously staying within their energy envelope. Unless that’s made clear, those individuals could fall out of a research study.”
    I’m pleased he’s looking at this. The problem with using a scoring system based on frequency and severity is that patients use pacing precisely to reduce the severity and frequency of their symptoms. One way round this is to ask people what happens if they exceed their limits.

    Good to hear the CDC are using his questionnaire as that will allow Jason to make hay with the results from the CDC multi-site clinic. And it was interesting to hear Nancy Klimas talk about the value of the new CFI cohort, and how early results supported the Canadian criteria. It seems we are getting the tools and the data needed to refine case definitions.

  13. Guido den Broeder
    Apr 24 - 1:09 pm

    Doesn’t work.

    Many patients with Lyme, Parkinson, Lupus, mito’s, cardiomyopathy, Ehlers-Danlos, and so on, have the same reply to these three questions as ME patients.

    Your understanding ME won’t begin until you accept that it’s not some CFS, and that patients need to be medically examined to get the diagnosis.

  14. Eilidh Hewitt
    Apr 25 - 12:06 am

    I am a fan of lenny Jason I think he’s doing great work for ME patients but I am dismayed that he wants to add yet another definition to the already enormous and confusing collection.

    It seems to me that it would be far better to support the CCC and the ICC that does the job and already has a great deal of support from both patients and researchers. lets get one good definition established and as the proponents suggested refine it as it goes along.

    I would just like to add that CFS is an umbrella term that contains many different conditions that have fatigue as a component (practically every condition). ME hoewever is a single distinct entity and just like in other disease like MS or AIDS it affects each patient differently. An MS patient might have eye problems as a main feature or leg problems or cognitive problems or bowel and bladder problems. These differences in how it affects each patients does not make it a different disease or a subgroup.

    • Cort Johnson
      Apr 25 - 8:38 am

      Lenny Jason’s work suggests that both the CCC and the ICC will select out patients with high rates of psychological disorders. If that’s what you want in a definition then by all support them, but that’s probably the last thing I want to see associated with ME/CFS.

      I know people love the CCC/ICC and I loved the CCC/ICC but I’m dismayed that so many people support a definition that could conceivably end up with ME/CFS more likely being determined a psychological disorder. If there’s even the hint of that I would run for the woods.

      There is no easy fix for those definitions; the problem is the number of symptoms – you either have to shave off symptoms or leave them as they are.

      Yes, there is a lot of support for those definitions but since they’re rarely used in research you’re not losing anything on that front by adding a new definition. Jason, by the way, supports the use of the CCC for the clinical definition. It’s just the research definition.

      So, for me – yes to the CCC/ICC for the clinical definition and no to it for the research definition and yes, to a definition that includes ME/CFS patients but does not fill ME/CFS with patients with mood disorders while excluding many who do not have mood disorders.

      • Eilidh Hewitt
        Apr 26 - 8:28 am

        Thank you Cort for that explanation and it’s reasuring to know that the CCC/ICC would still have their place as part of the scheme and not be entirely abandoned.

        Having carefully read over the article again and I think I can see where Lenny Jason is coming from with his proposal for a more rigerous definition. Though it’s very confusing when the CCC/ICC definitions were brought in to better define ME and weed out psychiatric and psychological cases and every one thought they did that.

        I really hope he’s right in thinking that it’s possible to accurately pick out ME patients with just two or three core symptoms and that researchers would be able to make it work well. It’s what we all want, the confusion to end and ME to take it’s rightful place as a well defined disease along with others of a comparable nature such as MS.

        • Cort Johnson
          Apr 26 - 10:11 am

          Dr. Jason appears to strongly endorse the CCC/ICC as a definition for doctors – whom it was originally created for. A research definition is really a different can of worms so to speak.

          The CCC/ICC very much do define people with ME/CFS better in many ways. They filter out a group with more severe symptoms and I’ll bet with their focus on post-exertional that they weed out people who have depression and don’t have ME/CFS. Several studies suggest, however, that those ME/CFS patients who met the criteria tend to have more mood disorders on the whole. I think they’re getting ME/CFS patients – they’re just selecting out a subset of them.

          Of course not everybody who meets the CCC has a mood disorder! I imagine that most do not but the prevalence overall is increased. Lenny, who is a psychologist, I believe, also said that he felt that structured psychiatric interviews were very important -apparently so that doctors can catch mood disorders that they might otherwise miss.

          I think it’s all about taking a very rigorous approach to ME/CFS – not leaving any stone unturned.

  15. keeto
    Apr 27 - 7:35 am

    Very interesting l.Jason talk-as he states it isn’t in the interest of the psycho ‘researchers’ to clarify this situation and they realistically won’t. If they do not believe that ME could be a neurological disease then why would they seek clarification- it isn’t in their interest or their inclination. Goes to show how flawed humans can be, especially when they have influence and power. Respect to Lenny!

  16. Anne Ö
    May 04 - 9:30 am

    I agree with the worries MsJustice and Guido den Broeder have expressed: If the definition is cut down to only three core symptoms (post-exertional malaise, sleep dysfunction and cognitive dysfunction), how is that going to weed out other undiagnosed diseases which have these same symptoms at a high degree and frequency? For example, my friend who has been through a burn-out syndrome (due to extreme work hours for a long period of time) would likely have been included, though her illness was very different from ME/CFS when you look at the big picture.

    How to ensure such a limited definition doesn’t include other diseases/illnesses?

    • Cort Johnson
      May 04 - 10:31 am

      I don’t know but according to Lenny, it as as effective as the CCC/ICC at differentiating ME/CFS from other disorders and it doesn’t come with the problem of delineating a mood disorder subset. (I wonder if while she was in her burnt out state she would have met the CCC anyway (?). She probably had PEM, poor sleep, cognitive problems, sensitivities ????.) My guess is that no symptom based definition is ever going to be very satisfactory; we need biomarkers that delineate the different subsets.

      Lenny noted that people who are burnt out but then recover after a suitable rest period obviously don’t have ME/CFS. The Fukuda definition comes along with a bunch of other filters – one of them is, if I remember correctly, that rest does not significantly improve ones functioning. Operationalizing the definition so that they don’t get included in research studies will be important.

      • Anne Ö
        May 04 - 11:21 am

        Thanks for the reply, Cort. I’m pretty sure my friend would not have met the CCC definition, but she would have fit this “three symptoms only version”.

        Difficult, this!

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