Jason and Evans: To PEM or not to PEM? That is the question for case definition

Hi waiting, for any piece of medical research to be of any use in distinguishing one illness from another, it has to fulfil two criteria first it must be done on patients that all have the same disease, and the tests must also be done on all other similar diseases to find out if these results are also found in any of these other diseases, and the findings have to be verified by other researchers.

Both the Pacific fatigue lab testing and the work of the Lights is done on patients diagnosed with CFS by using the CFS criteria, CFS is not ME, and it is not a disease it is a group of symptoms that could be caused by hundreds of different conditions. Neither the Pacific fatigue labs or the Lights extensively test their patients to make sure that every other possible illness is ruled out in the way that Dr Hyde dose, his patients have also been diagnosed with CFS by other doctors who are convinced that this is what they have, Dr Hyde finds that about 80% of these patients are misdiagnosed and have another known illness.

The findings of the Pacific fatigue Lab and the Lights has also not been tested on all other diseases that could be mistaken for ME to see if they are findings common to other diseases!

So what we have is research based on using CFS diagnostic criteria, which shows a lack of understanding that CFS is not ME, the patients that they are using have not been extensively tested to rule out all other diseases, raising the strong possibility that the research is being done on mixed cohorts, and research has not been done on all other conditions that could be mistaken for ME to see if these results can be found in other conditions. And none of this work has been verified by other researchers.

This work is interesting, but that is all, at the moment it means nothing, it will be at least a decade before enough research has been done to prove what if any relevance it has to ME, or if it will turn out just as it has been with NK cell, RnaseL and Mitochondrial dysfunction, etc, etc, all of which have been said to be exclusive to ME and then turned out to be common findings in many conditions.

The point that Im trying to make is that PEM the group of symptoms explained in the likes of the CCC is not exclusive to ME, it is a common symptom found in many conditions and this is not just my opinion it is a medical fact, and none of the writers of the CCC or any other definition have ever said that PEM is exclusive to ME they have said that it is a Cardinal not Exclusive symptom and have laid out an extensive list of other diseases that can cause it. Im not saying and nor are any of the diagnostic criteria that something like a CPETs test is or is not a measure of PEM or ME because the research has not been done to prove what relevance this has yet.

Please dont take this the wrong way, everyone is intituled to their own opinions, but you are saying that these findings are only found in ME based on a small amount of unverified research, with some serious potential flaws in it, that is going to need years of additional research to back up these claims and see if they do have any meaning for ME.

My concern with this is that a lot of people read what is written on this forum, if they have PEM and read your post without a full understanding of how unproven this research is, it may convince them that they could only have ME and stop looking for other potential causes, if their PEM is actually caused by something like Addisons, hemochromatosis, cancer, lupus etc, etc, which can and do cause PEM it could be disastrous for them. Please be careful about the way things are written peoples lives are at stake and the research has not been done sufficiently for anyone to be making definite claims about what it means yet.

All the best

Rlc, I totally agree with you on getting as many medical tests (even standard tests) done and explore other possibilities. There are two other considerations though: While ME might be rare, milder similar conditions such as mild CFS or FM or PVFS are actually very common and often produce similar symptoms, so chornic fatigue syndrome and fibromylagia is not rare but fairly common. The other consideration is that the path to these conditions could be combinations of other conditions worsening and basically leading to a functional breakdown of the body systems while strucurally theremight not be much wrong, so it might not be one condition at all, but multiple conditions with similar symptoms and multiple pathways to get there. I am also skeptical that researchers will ever come up with a single biomarker or reliable test for these conditions, as I suspect different co-morbidities and deficiencies can lead to similar symptoms and those symptoms can fluctuate and vary from very mild to very severe. What I don't get is why doctors need these clear cut single ICD diagnosis to treat patients, they should focus on treating the patients various deficiencies and always lookout for new/undiscovered ones. Not having a clear biomarker or fitness test that can diagnose CFS/FM/PVFS/ME might pose issues for various insurance coverages which will hopefully be addresses to the benefit of the patients in need but it should never make a doctor shrug their shoulder and turn you away or even worse steer you towards psychological treatments. Instead they should work hard to improve your quality of ife as they try and do for many other symptoms/conditions and constantly learn and update their research.

I do agree with a lot of what you said in your post.. have to comment thou on the above part to say that I disagree with it.

Most of us do keep searching for other answers. Most of us have been to specialist after specialist or doctor after doctor, trying to get answers and still do that as much as we are able. Most have spent a heck of a lot of money trying to work out what is going wrong in our bodies.

Ive probably seen well over 30 different doctors and specialists.

I personally dont see the patient community sitting back and not seeking answers. I dont think people are as naive and closed off to other possibilities as you think.

I had to have quite a few of the tests recommended for ME in which are known to show up abnormalities which often show up in ME (thou also do show up in some other illnesses too eg Postive Rombergs etc), before I was truely willing to believe that I "most likely" have ME.

I still do hold other illnesses in mind too.. I have two ideas of things I may have .. eg systemic mastocytosis is one of those, there is also a rare kind of cancer I wonder about but the issue is in doctors and the illness sometimes being impossible to find.

Sometimes no doctors are willing to do the tests one wants... it often isnt a case of we still arent seeking possible other answers.

I think most of us desperately search for other answers.. the fact we dont want to have ME/CFS pushes us along even more in trying to find other answers. If people arent getting other answers and things are being missed, it is usually the doctors at fault.

of cause you are entitled to your own opinion of how this community is.

Hmm, we seem to have a very heated debate going here - good! I'm a bit kanckered now after catching up on these latest posts and my brains gone a bit mushy so just a short reply. (edit - turned out long!)

From reading the posts and all the links to research etc - i still feel that PEM is a bit of a vague term. There are so may dsifferent types of 'malaise' that i and others suffer from that it ould be hard to pin them down to one term ie PEM or PENE. One thing that hasn't come up is the difference between post exertional malaise or exacerbation and DELAYED post exertional malaise. Could it be that what the lights etc are studying and seeing is Delayed PEM? I see this as being when the after effects of the activity are not seen immediately (or they may be immediate) but then the crash- for want of a better word - due to the overactivity comes on stronger the next day or up to 3 days later. This seems to me to be the phenomena we experience when in a good patch we may overdo our activity for a few days or more - only to have a serious relapse the next week that lasts days, weeks or months. Is this the defining feature of M.E PEM?

I agree that misdiagnosis is probably very high, and not often considered - once you have the CFS/anxety/depression stigma on your records it is hard to get any further help. M.e patients typically spend many years seeking a diagnosis and along the way our medical records reflect this constant seeking for answers. For me now, if i get sent to a new specialist for investigation i dont tell them i have been DX with M.E. I just say i have this problem and this and this and see what they say. Once you mention CFS you just get incomprehensible looks and blank stares then treated curtly to get you out the door.

I also think we would often be best of eliminating other dx if we can. For example, instead of spending any more money on M.E specialists (which has been of some help, but then may have helped whatever i actually had) I could spend my money on seeing a Lupus specialist for example and having that throughly ruled out. Of course in the UK - without being able to demand all this from the NHS i would have to pay for it privately which i cant actually afford. I agree very strongly that most other major illnesses have tests that are used to diagnose and that we do have tests that could be used - nobody tells a suspected MS patient that they can't have a brian scan becuase they are too expensive - in fact they are obliged by law to get you seen by a specialist within 6 weeks if they suspect it. I recently read the NICE guidelines on diagnosing and treating MS and they couldnt be in any more stark contrast to the M.E/CFS guidelines.

I'm going to push my doctor for a MRI scan - as my cognitive/brain problems are quite pronounced now - especially movement issues - neuropathic type pain etc. The way i see it is that it will rule out MS and IF they do see small lesions, then it helps to confirm M.E (As i said earlier i took part in the DE Paul University study and they said that i met the criteria for a diagnosis of M.E using ALL and every criteria from Oxford, FUKUDA etc to CCC and ICC)

I look forward to more of the debate, and take care all.
Justy

I would have expected certain changes on the Phoenix Rising site:

I've raised this issue before. But alas, Phoenix Rising's ME/CFS (Chronic fatigue syndrome) Forums and Chronic Fatigue Syndrome (ME/CFS) News remain...despite the CCC (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and the Myalgic encephalomyelitis: International Consensus Criteria. Now the Maes et al. abstract states, Fukuda's criteria are adequate to make a distinction between ME/CFS (sic) and CF....

I hope with PEM doesn't mean that case definitions for myalgic encephalomyelitis (ME...or ME/CFS) will be ignored. That's already been the CAA's approach for the SolveCFS BioBank (http://forums.phoenixrising.me/show...olster-CFS-Research-Field&p=245082#post245082). Unfortunately, I can't find any statement concerning how the CAA defines PEM, aside perhaps from the Jason and Evans definition posted by Research1st: prolonged restoration of muscle power following either mental or physical exertion.

Though still not much is know about the differentiators, I think PEM is NOT one of them and consider it absolutely wrong to distinguish ME from CFS through PEM. CFS and FM patients can experience PEM (days of flu-like aches and other pains, even some neurological nature) as well. My best guess to differentiate would be to call it ME if more severe neurological symptoms and symptoms of the nervous system are present (e.g. OI, POTS and severe brain fog and nerve pain). cheers

Getting back to the old name argument. Yes i believe it should be called M.E and more strictly defined. However, the political situation being what it is, and doctors being what they are, it will eman that all those who have been diagnosed with CFS - because thats what their govt or doctor calls it- will be stuck with the cfs diagnoses even if they actually have some other distinguishable M.E illness. My doctor writes cfs on my notes, despite the fact that it is M.E according to all criteria (apart from hydes because i havent had all the exclusionary testing - but then neither has anyone else)

This situation will leave thousands of patents ina limbo land, CFS will keep its 'psychological' meaning and those tiny group of people who can say they have M.E will have no organisations to fight for them.
I propse as a change over measure that M.E (cfs) be used for the time being, although i personally only use the term CFS when i dont want to alienate a patient who feels they have been diagnosed with CFS rather than M.E (or who perhaps arent interested in the argument about it all)
Justy.

Are you sure that patients who "only" have FM get PEM? My nanna has only FM and she dont even know what PEM is... she never gets it and hence could never understand it in me

She didnt understand how doing something one day would make me sick the next day... hence she was convinced she could help me by pushing me.. but all she ever did was make me very sick. The fact she has FM and hence dont understand ME/CFS due to not having PEM, made me have to cut off contact with her.

If a FM patient had PEM too who then how would one know they were just a FM patient? Many FM patients dont just have FM and have other things missed. One quarter to a third of FM patients end up with ME/CFS (those who get PEM probably fall in this catagory).

I think with FM overexercising causes prolonged pain and fatigue - but not exercising at all causes stiffness and pain as well - I think the cytokine expression for FM patients is a bit different than CFS (don't know about ME). You might be right that the threshold for PEM in FM is higher and it may be less severe, but I do think if you would push your nanna hard enough she would experience it as well. I think that it depends on how you pace and manage your condition with FM in regards to whether it will progress or not. I can totally understand the desire to distinguish and separate ME from the rest due to its apparent severity but I don't think this will help much and fear that those who are just getting into the boat with FM or mild/moderate CFS will continue being told to push on through since they have something less "serious" which can be cured by exercise only - I fear it will increase the amount of people ending up with severe CFS or ME if not treated right.

I agree with this, I don't know what definition is being widely used, but it is clearly possible to misunderstand this. My "typical" (in so far as anything with this condition is ever predictable) profile after a period of significant exertion is:

• to feel "normally" tired straight afterwards (I believe this is getting a little worse over time but that part only may actually be deconditioning). Note that if I totally overdo it I do get extreme symptoms at the time, but I am talking about exertion beyond my "long-term envelope" but stopping before reaching "short-term envelope".
• to feel more physically exhausted the next day with some flu-like symptoms and some neurological symptoms
• to feel worst physically two days after, muscle pains, flu-like symptoms, also neuro symptoms will be kicking in severely now
• by day three the physical side is fading but neurological side is severe
• gradual fade from that over anything from 1 to 3 further days

I have probably made it sound more exact than it really is, but I am quite concious of the neurological aspects as I work from home as a programmer and I know from quantifiable changes in output how well my brain is working (or not).

For example last weekend I took my family for a day out at a play centre (we normally have help with childcare at weekends but our helper was on holiday). It is Friday today so approximately day six and I am still suffering awful neurological symptoms (physically pretty much recovered to my baseline) almost completely preventing brain work.

Obviously healthy people can get some reaction to significant exertion, we all experienced that before we got ill. I am sure many conditions cause more extreme exhaustion and maybe the other symptoms also, but how many of them follow this strange bell curve response with a low initial reaction, a peak at 2-3 days after exercise, a tail of up to a week and this strange separation of physical and mental response profile? I have only ever come across anything like that on these forums and no-one I deal with in real life seems to understand that part. Of course I don't hang out on MS, FM etc. forums, so I can only ask the question...?

If PEM is indeed in any way unique to ME then it would have to be this version of PEM I imagine, "feeling ill/neurological symptoms after exercise" is not likely to be enough - so which PEM/PENE is the one being used in these studies and/or which version are people referring to here?

That is true.. but its also true that having all these illnesses lumped as one, is stopping ME/CFS associations which are supposed to cater for both ME and CFS from making the public aware that ME is even a serious illness.

Im quite annoyed right now at the Australian ME/CFS association as yet again they got someone on radio to talk about this illness who I dont think even had ME and who made this illness sound like it wasnt at all serious. See this thread http://forums.phoenixrising.me/showthread.php?17771-*-ME-CFS-Australia-Press-Release-* That is the damage lumping the two illnesses together is doing.

Its the ME patients which end up not being heard when they lump both ME and CFS together..as the ME ones are in the minority, so the ones with possibly more serious issues are going unheard.

All this is why there needs to be things broken down to different groups of patients.

eg My CFS specialist dont even know what symptoms are in ME as he thinks the illnesses are the same. Problems found in ME arent looked for as the doctors dont understand ME and just confuse it with CFS due to the two grouped illnesses.. this is very dangerous for many with ME who are at HIGH RISK of certain rare cancers due to it.

I worry about getting one of those cancers I believe due to ME Im at risk of but doctors are trivalising "ME/CFS"

This confusion will continue.. putting lives at risk until the illnesses are separated in some way. The big question is till there is a ME test.. is how does one separate. Which leads back to the post topic

I dont think you can seperate the illnesses according to severity. I have had mild, modearte and severe M.E at different times, with different symptoms at different times AND differing PEM experiences too.

I think that cfs and M.E are more or less synonymous. The people who could be weeded out are those with Chronic fatigue only and those with major depressive illness only. Basically the canadian criteria and now the ICC criteria seem adequate at the moment for describing M.E/CFS. BUT PENE or PEM should not be said to be exclusive to M.E, but a major part of the illness. For those that recover (i had a partial remission for some years) then PEM can be the only main symptom left. (feeling exhausted quicker than others and this exhaustion taking longer to ease and can be accompanied with other symptoms that mild M.E ers get.)

Hi Mellster RE While ME might be rare, milder similar conditions such as mild CFS or FM or PVFS are actually very common and often produce similar symptoms, so chornic fatigue syndrome and fibromylagia is not rare but fairly common.

What we have is three problems that have coincided with each other, in the last 30 years or so, doctors incomes have declined from what they were which has lead to them spending less and less time with patients in order to see more in a day to make more money, At the same time Governments have been making a mess of the hospital and health care systems throughout the world for a number of reasons and this has coincided with an increasingly aging population that is costing a lot in Health care, this has made it very hard for anyone who has a chronic health condition to get into the health system and get investigated, all the money and resources goes on Acute cases. If youve been smashed up in a car crash theyll spend millions on you, but if you have a chronic illness that shows no sign of killing you in the near future, then you will be lucky to get through the hospital door.

In the past not only would your doctor spend a great amount of time on you trying to figure out what was wrong with no finical restrictions on what they could test you for, but if they got stuck they would send you to the hospital and you would get every test under the sun done in an attempt to find what was wrong with you.

This has coincided with an alarming trend to invent diseases that are not diseases, they are just sets of symptoms that can be caused by many illnesses, Overworked doctors have embraced these syndromes because they are a very quick way to give the patient a diagnosis and then move on to the next patient and make more money. The last thing most doctors want is a patient that is complicated and going to take a lot of time, money and effort to work out, appalling I know but it is very common. Chronic fatigue syndrome is one of these non diseases.

Chronic fatigue syndrome is a nonexistent diseases, invented by the CDC in the 1980s, it was invented because they were under a lot of pressure from the press to explain ME epidemics that were happening at the time such as the one at Lake Tahoe, despite the fact that the CDC own investigation of lake Tahoe showed that it was not caused by the Epstein Barr virus the CDC doctors most of whom had never seen a ME patient, let alone examined them, invented the disease CFS and a criteria for it, that gave it the symptoms of a chronic Epstein Barr infection and deliberately left out important symptoms found at Tahoe like severe neurological symptoms and the fact that MRI tests done on Tahoe patients showed AIDS like lesions in the brain.

In 1994 (Fukuda) the CDC with help from the Wessely school reinvented this fictitious disease as one with no physical signs, removing symptoms like high temperature found in the first definition, and made it just a collection of extremely common symptoms found in hundreds of diseases, they also greatly reduced the amount of testing that someone had to have before they could get this diagnosis and specifically banned testing for all things that had been shown to be found in ME such as MRI and SPECT scans and testing for Enteroviruses. The doctors at the CDC knew that the disease that they had created wasnt real and therefore took all the money that had been allocated by the US government to research it and spent it on other projects until they were found guilty of doing this by a federal investigation in the late 90s.

The work of Dr Byron Hyde has shown that all patients diagnosed with CFS who dont have ME have another known illness, and that there is a very large number of diseases that are wrongly being diagnosed as CFS, which is why Dr Hyde refers to it as Garbage bag diseases, CFS does not exist, it is a man made fantasy,

Fibromyaligia is another one of these syndromes that can be caused by many illnesses and these illnesses should be looked for, found, and treated. Instead Doctors tend to diagnose it as if it is an actual disease and leave the patients to suffer. Dr Mirza has found that 70% of Fibromyaligia case are actually undiagnosed vitamin D deficiencies and when they are given enough vitamin D to get them to the levels recommended by modern research, they are cured, Hypothyroidism is another common cause of it, which is again being missed at alarming rates in patients due to the use of very wrong out of date reference ranges, it can also be caused by things like Polymytosis, polymyaligia rheumatic, spinal stenosis, whiplash etc

Irritable bowel syndrome is another one of these syndromes that people are being diagnosed with like it is a disease, but really it is caused by things like food allergies and intolerances, Celiac,s and a whole host of other gastrological illnesses.

PVS isnt used much as a diagnosis, but yes there are a number of viral conditions that can leave the patient ill for a long time such as EBV, they are usually self limiting, but if doctors get their act together these patients can normally be helped to recover with anti virals and nutritional support.

So what we have is a situation where for financial reasons the worlds health systems have largely given up on investigating chronically ill patients, and all the money and resources is going to acute patients, this has coincided with the invention of none existent disease like CFS, which is just a meaningless collection of symptoms that could be caused by hundreds of conditions. This has given doctors an easy out when dealing with chronically ill patients, just say that they have CFS or Fibro give them something like pain meds, sleep meds or anti depressants and leave them to get on with it.

The reality is that almost everyone with anyone of these kinds of syndromes could if they had doctors who took them seriously, were up to date and were prepared to take the time and effort to investigate them properly, could be given a real diagnosis, which in a lot of cases would be very treatable. Meanwhile the poor ME patients are caught up in this mess and cant even get their illness recognized as a separate illness, despite the fact it has been recognized as a separate neurological disease by the WHO since 1969!!

What is needed is for the medical community to stop diagnosing these syndromes as if they are diseases, and to investigate the patients to find out what is really wrong with them and where possible treat the real illnesses.

If only governments could get their heads round the fact that although investigating these kinds of patients is expensive it is far less expensive then the money they spend on benefits for these people and lost productivity! Then there would be a financial motive for helping these people and things would change.

All the best

Hi Tania, I wasnt aiming my comments at the patient community, there aimed at the information that is being provided on the internet to the patient community most of which is completely wrong and often very dangerous.

Most of the information available doesnt even describe ME, it is CFS propaganda that describes a disease that doesnt even exist, most of the information is full of blatant falsehoods such as PEM is exclusive to ME etc, there are hardly any sites that warn that the chances of misdiagnosis are extremely high or make any attempt to even provide basic information on what even the most common possibilities are. Instead there is vast amounts of information on bogus cures to try, which involve taking large amounts of expensive supplements and paying for alternative diagnostic tests that dont prove anything, achieving nothing but making other people rich, and endangering the lives of the patients who are trying these bogus cures while potentially fatal diseases are not being investigated.

Yes there is a part of the patient community who with a great amount of effort, which sick people shouldnt have to make, have waded through this vast amount of false information and realised that they may have other conditions and are doing what they can to investigate them often having to battle difficult doctors along the way, and are trying to let other people know that CFS is not ME and that other diseases have to be ruled out.

It shouldnt be this way ME sites should be providing accurate information on ME, warning people of the high chance of misdiagnosis and providing information on other diseases that should be investigated, I have tried to ask that warnings be put on this site about the risk of misdiagnosis, and that links to information on disease that can be misdiagnosed as ME be provided in a place visible to all that doesnt get lost in treads. Every time Im ignored without as much as a reply, I have asked that the correct name of the disease is used for the site, this also gets ignored. So we have a site that produces an endless stream of CFS propaganda articles, uses the wrong name for the disease and does nothing to raise the awareness of misdiagnosis, and has moved into advertising Prohealth supplements, how much does Cort get paid for this? And a group of patients on the forum using up large amounts of whay little energy they have constantly trying to correct this information and provide help to new patients on what other diseases their failed tests might be pointing to them having. It must be so hard for newbies to even begin to get an idea of what the truth is.

Best of luck with your doctors

All the best

Agreed, but for the patient it is irrelevant whether their chronic condition is given a basket case/garbage name or not, those chronic pain & fatigue conditions (whatever they are and whatever their origin is) are rampant these days and I do think that quite a lot do originate in the immune system. But it is indeed outrageous that the basket case definition is used by the docs to quickly get rid of the patient. cheers

I don't have the mental stamina to read all this, so my point may be off topic or something old. I just wanted to add that I just now read about PENE and the ICC. Wow, this really describes my illness so much better than all other definitions I have read.

For me, the "PENE" problems are worse than PEM (I have them both). Mental activity, things like talking, reading, etc. makes me physically ill, sometimes just a tiny amount, other times I do quite a bit more, but never on a consistent or predictable basis without feeling very ill.......either way it is my worst and most disabling symptom.

Again sorry if I am off topic or commenting on something old.....it is because I suffer from terrible PENE.

The ME-ICC cites Jason et al., claiming that some symptoms of the Fukuda criteria overlap with depression, whereas the Canadian Consensus Criteria differentiate patients with ME from those who are depressed and identify patients who are more physically debilitated and have greater physical and cognitive functional impairments. (See Comparing the Fukuda etal. Criteria and the Canadian case definition for chronic fatigue syndrome.)

Ember - we know it is possible to have mild M.E all the way through to very severe. Are you saying that only severe and very severe patients who have M.E should be considered to have M.E? what about those who improve from severe to modearte and mild or go into full or partial remmission - do they not have M.E?.

I don't know why you brought up depression, i am well aware that ther may be a group of patients wrongly diagn osed with CFS when they have major clinical depression, but that is not the issue here. I am just saying that M.E is an illness with a spectrum of ability and disability. It doesnt seem right to say all those on one side have M.E and all those on the other have CFS - especially when many do recover or improve over time.
All the best, Justy.

Here's the full quotation from the ME-ICC (as I probably should have posted it), Justy:

I found it interesting that Jason is cited here [21], given that his PEM article is the topic of this thread. But I haven't had time yet to search through the cited Jason et al. article, so I can't comment further on its significance.

I'm not sure I understand the meaning of side when you comment, It doesnt seem right to say all those on one side have M.E and all those on the other have CFS - especially when many do recover or improve over time. (Is one "side" severe and the other mild?) But again, I'm not so much making a claim as referencing Jason's.

Edit: Headaches might provide an appropriate analogy here. Even though migraines present a spectrum of ability and disability, they are considered to be more disabling than the average headache.

I think that depends for what purpose. I don't think many people would suggest discounting mild cases in clinical practice and/or refusing them treatment, however the single biggest issue we face is surely finding a treatment. When doing studies, tests, trials etc. if eliminating more mild cases significantly reduces the risk of including trial participants that are misdiagnosed then I absolutely think they should be excluded. That way we may actually find an effective treatment where we will not if trials continue to be run on excessively heterogeneous groups.