Voices from the Shadows

ME, CFS and Research

Dr Montoya

Dr Jose Montoya

An overview of Infection Associated ME/CFS can be found on the  Stanford Medical School website.

A recording with slides of the research presentations from the Stanford ME/CFS Symposium 20014, (as well as video of the Media Portrayal of ME/CFS panel discussion with a 30 min screening of Voices from the Shadows) can be found at http://mecfs.stanford.edu/2014SymposiumVideo.html

There are also two Youtube video presentations  by Dr. Jose Montoya, the Director of the Infection Associated Chronic Fatigue Initiative at Stanford Medical School. The longer one can can be seen here  and the short Stanford Medical Minutes video is here.

 

The most recent International Association for CFS/ME Conference 2014 was summarised by Prof Komaroff – Professor of Medicine at Harvard Medical School and Senior Physician at Brigham and Women’s Hospital in Boston. It can be heard here or a report read here.

A previous seminar by Prof Komaroff  given to the Massachusetts CFIDS/ME &CFS Association in 2013, giving a very clear account of research evidence about ME and CFS and can be watched on line on their website at www.masscfids.org/videofiles/Komaroff_Youtube_2013/Komaroff_Lecture_Presentation.html

 

Dr David Bell

Dr David Bell

A very clear 5 min video  by Dr David Bell which clearly describes the main symptoms of ME/CFS can  be found at http://vimeo.com/34099309

Lecture in 2011 for the  Massachusets CFIDS organisation by the very knowledgeable  paediatrician Dr David Bell who has followed the 1985 CFS outbreak among children at Lyndenville New York. http://www.masscfids.org/videofiles/BellApril2011/Bell.html

 

 

“Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research” by Prof Malcolm Hooper is published in the Journal of Clinical Pathology. May 2007. A clear and simple 6 page explanation by Prof Hooper with the conclusion; “There can be little doubt now that myalgic encephalomyelitis is correctly described as an encephalitis associated with upregulation of pro‐inflammatory immune responses, with downregulation of suppressor cytokines. This, coupled with the association of NTE gene, validates the WHO nomenclature and classification under neurology that allows the alternative name of post‐viral fatigue syndrome.”

Denise Lopez-Majano

Denise Lopez-Majano

 

An accurate and vivid description of the nature of the illness as experienced by one young person, by his mother, can found here. This is the testimony his mother Denise Lopez-Majano gave to the  Institute of Medicine Study on Diagnostic Criteria for Myalgic Encephalomyelitis on May 5th 2014.

 

 

Screen Shot 2013-05-18 at 20.07.27An overview, written in 2005, of  the Canadian Consensus Document – ‘A Clinical Case definition and Guidelines for Medical Practitioners‘  can be down loaded here. This definition has been supported by 50 world medical and research experts in ME/CFS.

Guidelines for diagnosis and treatment/management of ME/CFS produced by doctors and researchers of the International Association for CFS/ME 2012 can be downloaded from the IACFS/ME website here.

The ‘International Consensus Primer (ICP) for ME ‘ 2012 was  produced  (following on from the International Consensus Criteria for diagnosis and research 2011)  by a panel of specialists which includes those involved in writing the Canadian Consensus Criteria. Marj van de Sande  says it “is a one stop, user-friendly reference that specifically targets primary care physicians and specialists in internal medicine.” It is available from   http://hetalternatief.org/ICC%20primer%202012.pdf 

 

 

Myalgic Encephalomyelitis in context 

World Health Organisation (WHO)

Since 1969 ME has been formally classified by the World Health Organisation as a disorder of the central nervous system. Its classification in the International Classification of Diseases (WHO ICD G93.3) defines it as a physical disorder and not a psychiatric disorder. ME was originally called Benign Myalgic Encephalomyelitis in the UK, until it was realised over time that it actually was not benign! It was first identified and characterised through an understanding of the illness acquired during epidemics which frequently appeared to be caused by viruses closely related to the polio viruses (hence alternative names have been ‘atypical poliomyelitis’ or ‘posterior poliomyelitis’).

Myalgic Encephalomyelitis  is a descriptive name for the illness, describing and identifying a disease with inflammation of the brain and spinal cord with muscle pain. It is a chronic, complex, multi-system disorder. It involves demonstrable pathology, not only of the central and autonomic nervous systems but also of the immune, cardiovascular and endocrine systems. There is ongoing inflammation, with damage to skeletal and cardiac muscle as well as to other organs including the pancreas and liver. Although there is as yet no simple definitive test, there are numerous accredited biomarkers of pathology in ME/CFS, all of which lend support to the diagnosis. It is now most commonly thought of by experts as being an inflammatory neuro-immune disease.

CFS is the abbreviation for Chronic Fatigue Syndrome, the name given in the USA to the same or very similar conditions (including several epidemics which occurred in the USA in the 1980s), but more recently expanded tenfold by the CDC to cover a broad range of generally unexplained fatigue states. There is a lot of confusion around these names and the initials ME, CFS, CFS/ME, ME/CFS, CF and PVFS  are often used rather arbitrarily to refer to a variety of chronic fatigue conditions. Chronic fatigue is a very common symptom caused by many types of physical and psychological illness, ranging from flu, thyroid disease, cancer and AIDS to burnout, depression and anxiety. In fact many if not most severe illnesses cause fatigue. Because there are no clear cut tests for ME or CFS, research programmes will, depending on which criteria are used, actually be investigating different groups of people with a different mix of physical and psychological conditions.

A paper by Leonard Jason et al which examines some differences between CFS and ME  is called “Contrasting chronic fatigue syndrome versus myalgic encephalomyelitis/chronic fatigue syndrome”  and can be found here.  “Consistent findings indicated that the ME/CFS criteria, when compared to the CFS criteria, selected a group of patients who had more severe functional impairments and symptoms” A further study “found that the Myalgic Encephalomyelitis International Consensus Criteria identified more impaired individuals with more severe symptomatology” than those with CFS (Fukuda).

In the UK CFS, or even CFS/ME  as it is now often referred to by psychiatrists wishing to be all inclusive,  signifies a very different spectrum of conditions from Myalgic Encephalomyelitis, (called CFS in the USA as an equivalent for ME). The NICE description for CFS depends on four months of fatigue as the major symptom with at least one other symptom from a list. A  prevalence rate of  .2% – .4% is suggested by NICE (2007) and is consistent with previous estimates.  However the new 2013 Research Collaborative has increased this proportion up to ten fold and publicity material claims that the illnesses they are investigating affect up to 2.5% of the population! This suggests that either there has been a massive increase in cases – or the criteria for including patients within this category of CFS/ME   has been broadened to include people with other conditions, who would not previously have come under the more characteristic ME/CFS illness umbrella.  As the Research Collaborative Launch publicity material linked the illness to “functional somatic syndromes, and prior mood disorders”  this is the more likely optionThese are not characteristics of the illness ME and suggest that research based on these broader criteria (reflected in a larger prevalence)  is likely to include a significantly large  majority of patients who do not have Myalgic Encephalomyelitis. Research results from studies such as the PACE Trial will not be applicable to patients with the severe physical illness known historically as ME.

Symptoms.

One of the main symptom of Myalgic Encephalomyelitis is  that the illness can cause abnormal, delayed reactions to both physical and mental over-activity, resulting in deterioration and amplification of most symptoms. These delayed deteriorations may occur two or three days later and involve long recovery times. Major relapses can last for years, with the patient never recovering the former level of functioning. Another major symptom can be orthostatic intolerance, so that just standing upright for a few minutes can result in a drop in blood pressure and tachycardia (very fast heart beat), leading to the patient becoming incapable to staying upright and even blacking out. This means that patients are only able to sustain activity for short periods of time in a day.  Co-ordination and balance are very difficult. Cognitive problems affecting concentration and memory are characteristic of the illness and are particularly bad in environments where there are multiple stimuli. Pain can be widespread, variable and of different types, with some people suffering very severely. Problems with sleep are a major aspect of the illness. Minor infections can cause prolonged relapses because of an imbalance of the immune system. Physical and psychological stressors as well as the everyday stimuli of sound, smells and chemicals, some foods and even light can cause an exacerbation of illness. There is a talk by Prof Mark VanNess about the consequences of aerobic activity for ME patients. http://voicesfromtheshadowsfilm.co.uk/exercise-mecfs-event/

Perceptions of the illness impact on research and treatment.

During the last 30 years there has been little or no Government funding for biomedical research into the causes and mechanisms of ME and ME/CFS in the UK, and indeed in most countries. This has been caused by widespread trivialisation of the illness, ignorance and conflict over whether ME or ME/CFS is really a severe physical illness, as was previously acknowledged, or whether we are talking about a psychological or behavioural condition as asserted by some psychiatrists. (Influential medical text books have been changed to support this claim and even the government has on occasion been given false information about the WHO listing). Recently the evidence from biomedical  research, showing pathology consistent with a complex serious physical illness has become more and more compelling. The illness can now be more clearly identified by new diagnostic and research criteria – the Canadian Criteria  and the Myalgic Encephalomyelitis: International Consensus Criteria). Research into this illness is at last becoming “respectable”. The MRC has recently allocated funds for medical research into CFS/ME and new research initiatives are springing up at major universities such as Stanford Medical School (chronicfatigue.stanford.edu).  Dr Montoya, an Associate Professor there, is interested in the role of viruses and other pathogens and in the innate immune response. He explains in a video clip from Mill Valley here, that, at Stanford Medical School Infectious diseases department, he is working with doctors and researchers from Harvard, Cornell and Columbia Universities. New and esteemed international scientists, first attracted to the field by evidence of immune abnormalities in patients which were initially thought to be associated with a new retrovirus, are beginning to realise that this is an intriguing area of research where exciting discoveries can be made and patients helped. Funds for this research are very gradually becoming available. Other research initiatives can be seen at www.research1st.com or in the UK at www.meresearch.org.uk

In the UK a welcome major change occurred in December 2011 when the Medical Research Council or MRC (the public funding body for medical research in the UK) announced that more than 1.6 million pounds would be allocated to biomedical research projects for ME/CFS, or for research into other conditions whose pathology might shed some light on the pathology of ME. see here   Prof Julia Newton and Dr Wan Ng at Newcastle University were recently awarded nearly one million pounds  by the Medical Research Council for projects investigating ‘Autonomic Dysfunction’ and ‘Immune Dysregulation’. This research follows on from many years preliminary work funded by private donations through ME Research UK. An interview with Julia Newton can be seen here on ProHealth.

The dominant view promoted by the UK Government through its National Health Service, Medical Research Council and the Science Media Centre, has long been that although ME/CFS might initially be caused by a virus, accident or stress, the long lasting debilitating illness these patients suffer is, they say, merely the result of physical de-conditioning caused by a fear of activity or exercise and over-attention to symptoms. This claim ignores the large and growing body of research demonstrating a severe neuro-immune physical illness. It has had devastating consequences for patients as well as for doctors and researchers supporting a physical understanding of the illness who have been threatened with losing their jobs and in some cases have lost their jobs. An explanation of these contrasting views can be found in “Chronic fatigue syndrome: Harvey and Wessely’s (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways” by Michael Maes and Frank NM Twisk at www.biomedcentral.com

For many years several million pounds worth of MRC research funding for ME/CFS has been allocated to studies run by psychiatrists and psychologists examining the usefulness of different combinations of management programmes more appropriate for behavioural and psychological conditions. These are cognitive behavioural therapy (CBT), which was  originally developed to treat depression, and graded exercise therapy (GET) which is also considered to be a valuable treatment for depression and de-conditioning. These ‘treatments’ for ME are actually management programmes. They are used extensively to support patients receiving medical treatment for illnesses such as cancer, whereas in ME/CFS these behavioural management programmes are being used as a substitute for proper medical treatment. Alarmingly these recommended ‘treatments’, particularly GET, has been found to exacerbate illness and increase disability in many ME patients, sometimes resulting in lifelong total incapacity. (Further reading can be found here: www.ncbi.nlm.nih.gov & www.iacfsme.org) There is a video from the ‘FDA: Development of safe and effective Drug Therapies for CFS and ME’ workshop with Prof Chris Snell an exercise physiologist talking about the objective measures that can be used to assess patients severe disability. Here on Day 2 Panel 3 

Voices from the Shadows shows the devastating impact that these misguided beliefs have had on the lives of so many people. Children have been particularly at risk since they are vulnerable to persuasion and their views are often overridden by professionals, but both men and women have been harmed too. Many adults and children continue to suffer at the hands of a medical system which has for too long denied the severity of their physical illness, has abandoned biomedical research for decades in the UK, and has hounded professionals who tried to promote understanding of ME as a physical illness with supportive medical treatment for patients.

 

Prof Komaroff ended the 2014 IACFS/ME conference in San Francisco by saying;

“In summary, I would conclude that the last three days and the science that’s been reported over the last twenty years shows repeatedly that when patients with CFS are compared to various comparison groups—healthy subjects and in many cases, other fatiguing diseases, what you find is robust evidence for an underlying biological process that involves the brain, autonomic nervous system, immune system, energy metabolism and although we didn’t hear a lot about it at this meeting, oxidative and nitrosative stress. 

In summary, the illness is not simply the expression of somatic symptoms by people with a primary psychological disorder. It was a fair question thirty years ago to ask whether people with these symptoms might not just be expressing psychiatric stress, amplifying normal body sensations, or even fabricating for secondary gain—was a fair question thirty years ago, but today it’s no longer a fair question.” 

This repeated in essence what he said eight years previously at a 2006 Centre for Disease Control Press conference:

“There are now over 4,000 published studies that show underlying biological abnormalities in patients with this illness ((ME)CFS). It’s not an illness that people can simply imagine that they have and it’s not a psychological illness. In my view, that debate, which was waged for 20 years, should now be over. A whole bunch of studies show that the hormone system is different in patients with (ME)CFS than in healthy people, people with depression and other diseases. Brain imaging studies have shown inflammation, reduced blood flow and impaired cellular function in different locations of the brain. Many studies have found that the immune system appears to be in a state of chronic activation (and) genes that control the activation of the immune system are abnormally expressed in patients with this illness. A number of studies have shown that there probably are abnormalities of energy metabolism in patients with this illness”. 

In January 2008, Prof Nancy Klimas went on record:

As an immunologist, I once would have said (ME)CFS is clearly an immune dysfunction state, while an endocrinologist would have called attention to the adrenal gland irregularities, and a specialist in the autonomic nervous system would be convinced (ME)CFS is all about blood pressure abnormalities. Given what we’ve discovered about the illness, I now tell people (ME)CFS is all of these things.  We know that (ME)CFS has identifiable biologic underpinnings because we now have research documenting a number of pathophysiological processes involving the brain, the immune system, the neuroendocrine system and the autonomic nervous system”  ( In:  “Defining Moments – 20 years of making CFS History”, published by the CFIDS Association of America, January 2008).

 

Research and Treatment Initiatives

Just a very few examples of people involved in significant biomedical research initiatives and treatment trials with patients with ME or CFS.

The new Chronic Fatigue Initiative funded by the Hutchins Family Foundation involves the Center for Infection and Immunity at Columbia University, Harvard School of Public Health, Harvard Medical School, Duke University, NewYork-Presbyterian/Columbia University Medical Center, Brigham & Women’s Hospital, Massachusetts General Hospital, University of Miami and University of Utah.

Dan Peterson http://simmaronresearch.org  www.bond.edu.au

Martin Lerner www.treatmentcenterforcfs.com

Jose Montoya Infection Associated Chronic Fatigue Initiative,  Stanford Medical School. http://chronicfatigue.stanford.edu

Ronald W. Davis  Stanford Genome Technology Center,  Stanford University. http://med.stanford.edu/sgtc/donation.html

Ian Lipkin & Mady Hornig Center for Infection and Immunity , MailmanSchool of Public Health,  Columbia University.  Chronic Fatigue Initiative 

Nancy Klimas http://cfinitiative.org  Nova Southeastern University

Øystein Fluge & Olav Mella  http://bergento.no/2011/11/summary-media-coverage-cfs/ Haukeland University

John Chia www.enterovirusfoundation.org

Staci Stevens, Chris Snell & Mark VanNess www.workwellfoundation.org

Julia Newton   Newcastle University UK    MRC Award

Sonya Marshall-Gradisnik   http://works.bepress.com/sonya_marshall/ Griffith University

Andreas Kogelnik  Open Medicine Institute 

 

Many people continue to research the involvement of a number of viruses and other pathogens implicated in ME/CFS.  When carefully identified subsets associated with different viruses and pathogens are treated with appropriate anti-virals and anti-microbials there has been a very high level of success.

Recent treatment research in Norway using a cancer drug – rituximab – has resulted in some of the most promising success rates seen yet, and suggests the likelihood of an autoimmune or autoinflammatory process as the cause of illness in at least some some patients with ME/CFS. www.meassociation.org.uk

In the UK research into ‘Biochemical and vascular aspects of pediatric chronic fatigue syndrome‘ by Prof Jill Belch at Dundee University, supported by MERUK & TYMES Trust, has been important in showing that CFS or ME in children is essentially the same as CFS or ME in adults, with blood changes that suggest chronic inflammation and evidence of a persistent or reactivation of viral infection.  see here

This is consistent with the work of David Bell in the US who for decades studied an epidemic affecting children which  caused long term illness. The Dundee research is particularly relevant because it is evidence of the physical and inflammatory nature of the disease in children in the UK. This is inconsistent with the underlying assumptions of the The PACE trial, which was criticised by most adult charities for being unscientific and (being part funded by the Department of Work and Pensions) politically driven. However, in spite of this the PACE Trial has, along with the SMILE study, been endorsed by an influential children’s charity!

Research and articles which put the the findings of the PACE Trial into perspective can be found here (Nunez),   here (Maes & Twisk) and here (Kindlon). A helpful critique by Maes and Twisk of  the biopsychosocial ideas underpinning current management approaches can be found here.