Re-inventing ‘CFS’- the International Consensus Criteria for ME: the Marj Van de Sande Interview

September 16, 2011

Posted by Cort Johnson

Just M.E. 

“The Month Of ME’ – in response to a challenge and in recognition of the important role the term myalgic encephalomyelitis (ME) has played and continues to play in this disorder, August, 2011 will be the ‘Month of ME’ on Phoenix Rising. We examine ME’s role in this disorder throughout the month. All articles, blogs and posts produced by Phoenix Rising only used the term myalgic encephalomyelitis or ‘ME’ unless ME/CFS or CFS was absolutely required..

In reward for doing so, GregF, a Forum member, contributed $1,000 to the Whittemore Peterson Institute. Although it was not in the bargain he also generously contributed $320 to Phoenix Rising.

The International Consensus Criteria for…what? Not CFS… not ME/CFS but ME (myalgic encephalomyelitis) – hit the internet with a bang. This wasn’t just an attempt to give CFS a new and better name – it was far bolder than that; this was an attempt to introduce a ‘new’ disorder to the medical community – a disorder the authors feel has been subsumed under an overly broad definition for chronic fatigue syndrome for decades.

Make no mistake about who this definition is focused on; it’s you – the CFS or ME/CFS or ME patients (call it what you will) these physicians and researchers have treating and studying for decades. ‘ME 2011’ is nothing more than CFS plus 25 years of research and treatment. Call it a new version of CFS or what you will – this definition is the most up to date understanding of the illness you have – and it may differ quite a bit from the illness the CDC is studying.

Make no mistake about how new the term ME will be; for most of the medical community, myalgic encephalomyelitis – the termed coined to portray what some believe to be the outbreak version of CFS over 50 years ago – with its few research citations, is an entirely new concept.

Marj Van de Sande

That Marj Van de Sande helped lead the way for this ‘new’ disorder was no surprise. The world is rife with great ideas but most of us lack a bit in the follow through department but follow through is clearly no problem for Marg. An ME patient for over 20 years, she and Dr. Carruthers have, through their editorship of two important papers, the Canadian Consensus Criteria for ME/CFS, and the International Consensus Criteria for ME/CFS, played a seminal role in promoting not one but two of the most important ideas to hit the ME community in the last decade into play:

  1. that ME researchers and physicians can band together to thwart the stranglehold that the fatigue based CDC sponsored definition of CFS has had on the disorder for decades.
  2. that ME is a disorder whose hallmark symptom is not ordinary fatigue but a uniquely negative response to exertion

A past Director of Education and Advisor for the advocacy group that spearheaded the drive for the guidelines, the National ME/FM Action Network, Marg also developed overviews of the Canadian Consensus Criteria that have been translated into 8 languages.

I asked Marg what her history with ME was and how she came to work with Dr. Carruthers.

I was in a car accident in 1984 that caused whiplash and spinal injury and triggered fibromyalgia. When I had cancer in 1986-87, I got an upper respiratory infection and became overwhelmingly exhausted. Naturally I thought my energy would be restored after I recuperated from surgery; however, it was ME. Until 1995 I didn’t know anyone else who had ME or FM. I was a director of the National ME/FM Action Network from 1995 – 2004 and then an advisor until 2010. As Director of Education, one of my main responsibilities was developing educational materials. In 2003 and 2006, my son Bob built and donated new websites to the Network and I developed/edited the content and was webmaster from 2003-2010.
CCC: The Network spearheaded the drive for guidelines. Dr. Carruthers, a specialist in internal medicine, was known as a compassionate doctor who was very knowledgeable about ME & FM. He kindly agreed to work on developing clinical definitions and guidelines. Dr. Carruthers and I began working together drafting the Canadian Consensus Documents for ME and FM in 1999. After publication in 2003, the Canadian College of Family Physicians suggested that short versions of the consensus documents may further assist busy medical practitioners. Subsequently, Dr. Carruthers and I wrote Overviews of the Consensus Documents (2005/6), which are independent of any organization and are not-for-profit projects.I have enjoyed working with organizations in many countries regarding printing and translation of the Overviews – now in eight languages. Dr. Carruthers and I also wrote the first two chapters of TEACH-ME: A Sourcebook for Teachers of Young People with ME/CFS and FMS (2nd edition – 2005) – a Network publication.

Rewriting ‘CFS’: The Two Tracks - Change the Name or Re-invent the Disorder – The search for legitimacy and Funding for ‘CFS’ has taken several paths. There is the ‘change the name’ pathway which leaves the disorder essentially intact but with a better name, and the ‘re-invent the disorder’ track which attempts to rewrite the entire playing field.

The Name Change Track - In the most recent iteration of the Name Change scenario the 2007 Fair Name Campaign
http://www.afairname.org/index.cfm, which included such luminaries as Drs. Klimas, Peterson, Cheney, Komaroff, Lapp, Bateman and Bell, called for a name change to ME/CFS in the hope that the ME would push the CFS as much as possible out of the spotlight. Citing the need for research continuity and the need to maintain social security and other benefits, the Fair Name Campaign argued that it was not yet the right time for ‘ME’ to stand alone.

ME/CFS proved to be a good transition name with several organizations in the US and abroadpicking up the name and the Department of Health and Human Services (DHH) using it on their CFS website (and putting the name under official consideration.) Combining the two names did bring myalgic encephalomyelitis back into the mix but that ‘CFS’ was still there and that was a problem. As Marj noted

Although introducing the term ME/CFS in the Canadian consensus document served to reintroduce the name ‘ME’, it presented its own problem because those who believe there is a psychiatric basis put CFS first and those who believe there is a physiological basis put ME first.”

ME/CFS did help but some people felt the two, like oil and water, did not mix. For Marj the adding ME to CFS was helpful but it also meant “The water ‘kept’ getting muddier and muddier”. Marj noted some of the problems ‘CFS’ had caused.

There have been concerns about the broad-based term CFS since it was coined in the 1980s. Patients who have myalgic encephalomyelitis (ME) are only one of many groups placed under the CFS umbrella. In the UK, they distinguish ME from CFS. In many other countries they use the term CFS, which usually includes both patients who meet the criteria of ME and those who are chronically fatigued.
The Re-invent the Disorder Track: A New Start for ME - Dr. Carruthers, Marj and the 23 other co-authors of the ICC felt what was needed was not just a new name but a new start. Given the vagueness of the CFS definition and the large group of patients it delineated it was difficult to simply lather ‘ME’ over CFS….
ME, after all, was a more exclusive illness which generally referred to an exertion based disorder usually triggered by an infectious event.The gulf between what was considered ‘CFS’ and what was considered ‘ME’ had caused some to resist any attempt to combine ME in any way with CFS. Indeed, a core objective of several of the ME definitions proposed over time has been to differentiate it from the definition of ‘CFS’ that permeated the research landscape.

 

Fatigue was and is present in ME but its usefulness as an adequate descriptive term for this disorder was long past – something the CDC has failed to recognize. In the end, however, the name (chronic fatigue syndrome) coined by the CDC sponsored group was secondary; the big problem was the vague original definition of CFS which resulted in heterogeneous sets of patients in research studies.

Marj noted a key goal of the new criteria is for researchers to study ‘homogeneous patient sets’ ie; groups of patients who all have same disorder – something that many believe has never happened in the history of CFS. Indeed, the authors of the definition (Fukuda 1994) used in the vast majority of CFS research studies referred, over 20 years ago, to the subsets of different disorders that their definition would allow to show up and pressed for studies that would reveal them. If that had been taken care of the bad name (‘CFS’) might very well have have been replaced long ago but unfortunately paltry funding and disinterest on the federal level never allowed those studies to take place.

As Marj noted that left the research field to muddle along examining an uncertain mix of patients – making it unlikely that the field would progress with any speed.

 

The Jason et al. study of the Reeves empirical criteria indicated that 38% of patients diagnosed with Major Depressive Disorder were misclassified as having CFS, it was possible to be diagnosed with CFS without any physical symptoms and only 10% of those diagnosed with CFS actually had CFS. Definitions based on chronic general fatigue or a general state of unwellness do not select ME patients or distinguish it from depression. This results in such heterogeneous groups of patients that it is impossible to determine whether or not research findings apply to ME.

By all rights this problem was the CDC’s to remedy. The CDC oversaw the creation of the Fukuda definition now used in almost all research studies and then its update, the Empirical definition, which flopped in the research world. A year and a half ago the CDC announced that a CDC- sponsored international conference on the definition was imminent but nothing more on that has been heard.

Many researchers and physicians have grumbled about the CDC’s vision of CFS but until recently, few (other than Dr. Jason), have attempted to challenge it directly. Largely perceived as a kind of outlier in the CFS research community, the withdrawl of an out-of-sync CDC from a leadership role left an opening that Dr. Carruthers, Marj van Sande, Dr. Jason and the co-authors of first the CCC, then the Pediatric Definition and now the ICC, have filled.

These actions demonstrate that ME researchers have the willingness to take matters into their own hands and they illustrate the huge gap that has opened up between the conception of the lead federal agency on CFS – the CDC – and the much of rest of the ME research community.

In the end, the flaws of the Fukuda definition were considered too great for the group to consider something as superficial as a name change; what was needed was an entire rewrite of the illness to get the patients ME physicians were seeing back into the research agenda.

An Audacious Goal - The twenty-five co-authors of the International Consensus Criteria (ICC) decided on an audacious goal – to distinguish a new disorder to the medical community. They would introduce a new updated definition that identified a unique exertion based disorder which they elected to call ‘ME’. They would buttress their claim by identifying what they felt was a unique characteristic – post exertional neuroimmune exhaustion (PENE).

This ‘ME’ wasn’t exactly the same as some earlier definitions of ME – no mention of outbreaks or contagion was present and an infectious onset wasn’t necessary – but many of the core elements including a neurological basis of the disorder – remained the same. The ultimate goal was clarity…Marg stated

The solution is to identify those who have ME, which is recognized as a neurological disease by the WHO, remove them from broad-based criteria and simply stop using the term ‘chronic fatigue syndrome’.

For some people, of course, lopping the CFS off ME/CFS was part of the grand scheme all along….first you slip ME in there in the form of ME/CFS, and when the research community has gotten comfortable with that – drop the CFS. It may have worked out that way but the real reasons for the switch were far more mundane. Marj reported that ME – standing alone – was in the mix for both definitions.

The draft of the Canadian Consensus Criteria (CCC) used the name “myalgic encephalomyelitis” (ME). However, we changed it to ME/CFS because a member of the panel felt that some American patients were not familiar with the name ‘ME’. At the time we did the CCC, we didn’t have plans to do another definition in the future. In retrospect, it did serve as a good transition period.
The reappearance of ‘ME’ appeared, however, to many to be years in the future and whether ‘ME’ would make it in the long run was questionable – given that it was describing an inflammatory situation in the brain, that at least thus far, has not shown up in dramatic fashion. But a nice chunk of the physician and research community serving ‘CFS’ patients obviously begs to differ. Now is the time, they say, for a dramatic shift in how the medical profession views this group of patients. People with ME have lumped together with other types of patients in research studies for too long. We have the studies, they say, we have the evidence that a unique disorder exists and it’s time to make our case – and they have.
With the publication of the International Consensus Criteria for Myalgic Encephalomyelitis (ICC) they have drawn a line in the sand; there is a disorder called ME and it is different from CFS and it is time to start splitting them apart. Marj stated

 

Broad-based criteria such as the Oxford, NICE and Reeves criteria have led to confusion, bothclinically and in research. Definitions based on chronic general fatigue or a general state of unwellness do not select ME patients or distinguish it from depression. This results in such heterogeneous groups of patients that it is impossible to determine whether or not research findings apply to ME.

Working with patient organizations in several countries regarding the printing or translation of the overview of the Canadian ME Consensus Document, now in 8 languages, gave me a deeper appreciation of the struggles of patients in other countries. In some countries patients are denied most medical tests and treatments; doctors treating ME as a patho-physiological disease have been sued. It is time for this to stop.

The Precursor - The Canadian Consensus Criteria developed in 2003 by Carruthers, Van Sande and others began the process that lead to the ICC. The CCC demonstrated that ME researchers could band together outside of traditional channels (ie the CDC, NIH) to put their own stamp on this disorder. Above all the CCC stamped out a divergent point of view of CFS from the officially accepted one at the CDC. At a time when the CDC was putting less and less emphasis on exertion based relapse the CCC made it a core part of the criteria. Not long before the CDC began to incorporate emotional distress into the CFS equation, the CCC focused on

A very long document providing lists of symptoms, lab tests, differentiating factors between ME/CFS and mood disorders and FM, plus sections on diagnosis, treatment and disability, the CCC was something of a one-stop shop for physicians wanting to learn more about ME/CFS. The document was well received in ME circles and had overviews published in eight languages.

The CCC’s impact outside of the community, however, was dampened because of it’s publication in a journal (Journal of Chronic Fatigue Syndrome) which was not indexed by medical journal search engines. There was a reason for that – Marj pointed out that few if any other journals would be willing to publish an 110 page document but the ICC, a much shorter document, was engineered to reach out to a broader audience.

This time we wanted to write a paper for publication that was limited to the criteria for ME and their application in both clinical and research settings. We thought it was important to publish the criteria in a journal with broader readership in order to give them credibility and reach more of the medical community including clinicians.

This time not only have Carruthers and Van Sande managed to gather much more support for the ICC (26 co-authors) than for the CCC did (12 co-authors) across a much larger geographical range (12 countries) but the criteria were also published in a prominent journal (Journal of Internal Medicine) marking the first time in over 50 years that ME will get its chance with mainstream research community.

A co-editor for both the CCC and the ICC, Marj explained how the process differed in both. One was developed under the aegis of Health Canada which imposed some standards.

Canadian Consensus Criteria: The Terms of Reference for both the ME/CFS and FM Canadian Consensus Panels established by Health Canada, required that each panel consisted of at least 10 members, 4 of which could come from outside Canada. We were working with 2 panels at the same time – the ME had 12 co-authors and the FM had 14 co-authors. The most difficult thing was to find enough doctors in Canada who were knowledge about ME.

 

The ICC was different. Finding ME knowledgeable doctors was no problem this time.

 

There is a huge amount of work liaising back and forth with panel members and integrating information so I knew from being consensus coordinator for the two Canadian consensus documents that about 20 – 25 members would be good. It was not difficult to get excellent clinicians and researchers to serve on the International Consensus Panel.
Even though our panel members are heavily committed and frequently travel, they indicated the project was very important and were eager to contribute their expertise and time. The logistics of getting information back and forth to busy panel members, incorporating various suggestions and hopefully still being able to coordinate a consensus among the panel members largely determined the size of the panel.

The co-authors of the ICC ended up being a nice mix of old and new. Five of the 12 co-authors of the CCC returned and 20 new authors came on board. There were the stalwarts – researchers/physicians engaged in this disorder for decades such as Dr’s. De Meirlier, Lapp, Bell and Vallings as well as relative newcomers such as Gordon Broderick, Alan Light, and Judy Mikovits.

Not only did the publication of the ICC in the Journal of Internal Medicine indicate the Journal editors considered it a timely and significant issue (a big change!) but it guaranteed the outside research community would get engaged as well. I asked Marj if they had anticipated difficulty in getting the Criteria published in a major journal. It turns out that they had not.

Not being a researcher I didn’t know what to expect, but was pleased by the confidence expressed by panel members regarding publication. I can only speculate that the growing body of research and some of the excellent research papers published in the past few years, including those of members of our panel, opened the door. Naturally, all of us are very pleased that it was accepted for publication by the Journal of Internal Medicine.

A Neurological Disorder - The old name “chronic fatigue syndrome” may have reflected uncertainty about the nature of the disorder 25 years ago but things have changed, and now, the ICC co-authors assert that the bulk of the scientific evidence points in a broad but still clear direction: a neurological disorder with ‘widespread inflammation’ and ‘multisystemic neuropathology’. Neurology is the key focus with pain and sleep problems now being firmly ensconced within the neurological symptom category now.

Historical factors obviously played a large role in this attempt to return ‘myalgic encephalomyelitis’ to prominence but does the science support a name that refers to inflammation in the brain? Marj felt it does. She also pointed how difficult it was to gather direct evidence to support kind of injury occurring in ME.

Obviously the ethical implications and medical risks of taking biopsies of the brain and spinal cord for research purposes prevent a lot of direct evidence. Dr. Chaudhuri’s three spinal autopsies identified neuro-inflammation of the dorsal root ganglia, which are the gatekeepers of peripheral sensory information traveling to the brain. There is evidence of chronic immune activation and an imbalance between inflammatory and anti-inflammatory immune mediators. Dr. Natelson’s study on cerebrospinal fluid proteomes and Drs. Light et al recent study suggesting infected and injured dorsal root ganglia are important. (Note how recent some of the studies she refers to are; the Light, Natelson and Klimas (cytokine) studies have all been done within the past year and a half.)

 

Ultimately Marj felt “ The name ‘myalgic encephalomyelitis’ is the most accurate and appropriate name and indicates underlying pathophysiology. It is recognized by the WHO and is consistent their neurological disease classification of ME (ICD G93.3). Even though the name ME came into use in the 1960s, recent research findings further support the name ‘myalgic encephalomyelitis’.”


The CORE of the definition – PENE – the Symptom Not the Noodle (penne) 

This version of ME is largely identified by a core symptom – something so unique to the medical field that the authors felt the need to make up a new name for it – PENE. The ICC states PENE refers to a state of

‘neuroimmune exhaustion with a pathological low threshold of fatiguability and symptom flare in response to exertion….e.g. post-exertional neuroimmune exhaustion’

The only compulsory symptom of ME, PENE is marked by rapid, physical and/or cognitive fatigability in response to exertion which causes worsened symptoms, exhaustion within hours or days with a recovery period of 24 hours or longer and which can cause relapses lasting from days to weeks or longer. (The definition also requires 3 immune, 3 neurological and 1 energy transport symptom to be present.)

Attempting to introduce a new term into the medical lexicon is a bold move. I asked Marj why the group felt now was the time to take such a step? It turned out that it was due to nothing more than the march of time and science, particularly in the last few years.

It was the accumulation of research and clinical knowledge that influenced the decision to develop new criteria, however, a few studies come to mind….The 2005 Snell et al study, the first test-retest exercise study, reported that some patients had a dramatic drop in their ability to produce energy following the second test. More exciting post- exertional studies followed – the Pacific Fatigue Lab, Drs. Light, White, Van Oosterwijck, de Meirleir, etc. The test-retest studies not only confirmed that ME patients had pathological responses to exertion, but the abnormalities were greater than expected in many cases. Genetic, neurological, immune, mitochondria and ion transport studies brought greater clarity. (Kerr, Broderick, Klimas, Myhill, etc.)

The authors statement that ‘post-exertional neuroimmune exhaustion is part of the body’s global protection response’ suggests they believe the fatigue, pain and other symptoms are largely produced in order to get the body to slow down in order to avoid further injury.

Research 

Research studies incorporating patients meeting the criteria for ME is the long term goal of the ICC and the paper is larded with research citations. Since no studies have been done on the ICC designated ME patients, no one really knows what an ICC ME patient looks like ‘under the hood’. (Ironically, this means that all the research citations for ‘ME’ are based on studies on ‘CFS’).

For the criteria to succeed research studies will need to show that people with ‘ME’ are different from people with ‘CFS’. That will take work but the path may not be too difficult . Since the core difference between the ICC and other CFS definitions is the requirement for exertion based relapse (or PENE), studies that use exercise tests to highlight exertion based abnormalities should be able to differentiate the two disorders. These kind of studies could examine the Lights pain and fatigue receptor findings, the Pacific Fatigue Lab (and other) VO2 max and other abnormalities, the complement and NO alterations, cerebral blood flow problems, etc. If Byron Hyde is right exercise tests should easily show reduced blood flows to the brains of ME patients (according to Hyde) but not CFS patients.

One thing at a time, though; the ICC group is presently focused on developing comprehensive Physician Guidelines.

The Physicians Guidelines will be based on the ICC but will be more comprehensive. We felt it was important to publish the criteria to give them credibility prior to developing the guidelines. They will include the ICC, steps in diagnosis, biotests, treatment and management protocols, the International Consensus Symptoms Scale and other useful appendices, etc. The goal is to develop concise but comprehensive user-friendly physician guidelines (handbook), which include the ICC and are specifically designed to complement them.

That’s not all -this group is busy; they are also developing an International Consensus Symptom Scale (ICSS). The CDC has developed their own symptom scale for ‘CFS’ for use in their Empirical Definition. The ICC’s Symptom Scale will be a partner to their criteria as well and it’ll be interesting to compare the two. Marj noted that the

The International Consensus Symptom Scale (ICSS) will coincide with the ICC. They are ‘partners’ and can be used as a questionnaire or as a structured interview. The ICSS has different applications in clinical and research settings.
We are not advising that the ICSS be used in the initial clinical assessment because it may alter the weighting of symptoms. It is important for the clinician to focus on the presentation and interaction of symptoms, and their impact on the individual patient. Primary symptoms need to be separated from secondary symptoms or aggravators. In the clinical setting, the ICSS is a valuable tool to be used periodically for help position the patient within the group, determine symptom severity hierarchy, and orient and monitor treatment.
For clinicians who are new to diagnosing ME, the ICSS can serve as a check tool.Every patient should complete the ICSS as close to the time that blood samples, etc. are taken prior to entering a ME research study. Only patients who meet the full criteria for ME, unless the study states otherwise, should be used in research studies. Researchers can also check their findings against the patients’ ICSS profile to help determine which abnormalities coincide with which symptoms.

The Future

Finally I asked Marj to look to the future. In five years what do you hope will happen with these criteria? Looking back from the future how would you complete this sentence? The 2011 myalgic encephalomyelitis ICC definition lead to………

2016: Everyone remembers that the use of broad criteria led to general confusion and conflicting research results. Even studies that were scientifically excellent but used broad-based criteria, left one wondering, “To whom do these research findings apply?”

Clinical: The 2011 myalgic encephalomyelitis ICC led to the ability to identify and select patients who have profound dysregulation of the neurological and immune systems, post-exertional neuroimmune exhaustion (PENE) and a pathological inability to produce sufficient energy on demand, which is a giant step forward. The emphasis on looking at the dynamical interaction of symptom pattern clusters and their underlying causal relationships enhanced the understanding of ME. The ICC brought clarity in diagnosis internationally.

Research: The ICC and the use of the ICSS when entering research studies ensured the selection of homogeneous subsets of patients, which resulted in greater consistency of research findings around the world. Analyzing the contextual and dynamical interaction of combined patterns expressed in broader panels, introduced by Dr. Broderick, led to a more comprehensive approach to research. Huge advances in technology combined with homogeneous patient subsets led to breakthrough research, effective biomarkers and sub-type identification. The practice of comparing research results with prominent symptom clusters of the patients as indicated in their ICSS brought mutual confirmation and better treatment strategies.

Dr. Carruthers joins me in thanking all members of the international panel, representing 13 countries, for graciously giving their time and expertise without recompense and working together to bring the International Consensus Criteria for Myalgic Encephalomyelitis to fruition.

(Reviewed by Bruce Carruthers, MD, CM, FRCPC (co-editor/co-author)

Marj van de Sande, B Ed, Grad Dip Ed (co-editor/co-author/consensus coordinator)

2 comments

{ 2 comments… read them below or add one }

Dr. Speedy September 18, 2011 at 10:05 am

Marj Van de Sande: “When I had cancer in 1986-87, I got an upper respiratory infection and became overwhelmingly exhausted. Naturally I thought my energy would be restored after I recuperated from surgery; however, it was ME.”

Dr. Ramsay: The main characteristic of ME is an abnormally delayed muscle recovery after doing trivial things, if you don’t have that, you don’t have ME
http://niceguidelines.blogspot.com/2011/06/main-characteristic-of-me-is-abnormally.html

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Raindrop November 16, 2013 at 1:43 am

I was just told by a member of Phoenix Rising that it might be possible to get a *hard cover*
copy of the ME/CFS Primer from you. Is this true? If so, can you let me know how I would do
so (your order info) and what each copy would cost? VERY much appreciated,
Raindrop

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