Gut Microbiota research funding needed

Invest in ME invites people to donate to their UK Gut Microbiota Research project, which  aims to find whether there is evidence of a leaky gut in ME patients.

Goal                         £200,000
Raised 15/7/15     £153,000
Donate online

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World Federation of Neurology writes about ME/CFS

Article extract:

In summary, ME/CFS (SEID) is a serious, chronic, complex and systemic disease that often significantly limits the day-to-day activities of those affected.

It is characterized by a prolonged, significant decrease in function; fatigue; post-exertional
malaise; unrefreshing sleep; difficulties with information processing, especially under time pressure; and orthostatic intolerance. A thorough history, physical examination and targeted evaluation are necessary and can be sufficient to make a diagnosis.

Despite the  high prevalence of this condition with associated high economic burden, little research has been conducted to study the etiology, pathophysiology and effective treatment of this disease. Moving forward, it will be vital to distinguish this disease against other complex fatiguing disorders as the majority of previous research has compared ME/CFS (SEID) patients to healthy controls.

Additional research into ME/ CFS (SEID) is essential for further progress to be made, and the term “chronic fatigue syndrome” should no longer be used due to the associated stigma, which often precludes patients from receiving appropriate care. It is critical that we do our part to help stop the stigma associated with this condition and provide optimal care of these patients.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A New Name & Diagnostic Criteria, by Maggie L. McNulty (assistant professor at Rush University Medical Center, Department of Neurological Sciences) in World Neurology, the Official Newsletter of the World Federation of Neurology, Vol. 30 No. 3, June 2015

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Accurate diagnosis of ME and CFS based on objective test methods for characteristic symptoms

Article abstract:

Although myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are considered to be synonymous, the definitional criteria for ME and CFS define two distinct, partially overlapping, clinical entities. ME, whether defined by the original criteria or by the recently proposed criteria, is not equivalent to CFS, let alone a severe variant of incapacitating chronic fatigue.

Distinctive features of ME are: muscle weakness and easy muscle fatigability, cognitive impairment, circulatory deficits, a marked variability of the symptoms in presence and severity, but above all, post-exertional “malaise”: a (delayed) prolonged aggravation of symptoms after a minor exertion.

In contrast, CFS is primarily defined by (unexplained) chronic fatigue, which should be accompanied by four out of a list of 8 symptoms, e.g., headaches. Due to the subjective nature of several symptoms of ME and CFS, researchers and clinicians have questioned the physiological origin of these symptoms and qualified ME and CFS as functional somatic syndromes.

However, various characteristic symptoms, e.g., post-exertional “malaise” and muscle weakness, can be assessed objectively using well-accepted methods, e.g., cardiopulmonary exercise tests and cognitive tests. The objective measures acquired by these methods should be used to accurately diagnose patients, to evaluate the severity and impact of the illness objectively and to assess the positive and negative effects of proposed therapies impartially.

Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms by Frank NM Twisk in World J Methodol, 2015 Jun 26; 5(2): 68-87.

 

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Stanford University’s ME/CFS research

Researchers are making headway toward finding evidence of chronic fatigue syndrome and how it may change the brain.

Ronald W. Davis, a Stanford University genetics researcher who was instrumental in the Human Genome Project, is heading up a new research center at Stanford University, The Chronic Fatigue Syndrome Research Center (CFSRC), which is rapidly becoming a nexus for chronic fatigue research.

Davis – whose son, Whitney Dafoe, has severe chronic fatigue syndrome – believes the answers lie in finding molecular biomarkers, which are characteristics or substances that indicate the person has a particular biological condition or disease. A specific marker might lead to a blood test that can definitively diagnose and potentially treat chronic fatigue, Davis said. So far, chronic fatigue has not shown its face through conventional blood markers that indicate inflammation in the body or that show the presence of a specific infection.

Davis and his team plan to use technologies developed for the Human Genome Project to sequence the entire genome of chronic fatigue patients, including 1,600 mitochondrial genes, more than 20,000 other genes and control regions that regulate genes. They hope to identify proteins that are found in immune cells, blood and spinal fluid; search for infectious agents in blood, bone marrow, spinal fluid and saliva and changes to gastrointestinal tract flora; and find evidence of autoimmune responses. The research could reveal DNA sequences that are altered in chronic fatigue patients.

The detailed approach is more comprehensive than that of other research, which has only looked at a fraction of the genes, according to the center’s website.

The center’s research will also focus on a large number of the most severely ill patients, who often have disruptions to multiple body systems where a pathogen or genetic alteration may be lurking, Davis said. The research will look at patients who have responded positively to drug treatments and those who have failed to respond, he said.

Researchers have known for many years that the onset of chronic fatigue is often preceded by a viral or infection-like illness, according to the Stanford University School of Medicine’s Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Initiative, another university research arm.

The disease may have multiple causes. Two main theories are that the disease is caused by a pathogen or by an immune-system reaction to a pathogen, according to a Stanford research team led by Dr. Jose G. Montoya, professor of medicine in the Division of Infectious Diseases. Montoya has studied chronic fatigue patients for seven years through the ME/CFS Initiative.

Focusing on organs and body systems most likely to be involved in the disease, Montoya and his team work with researchers and physicians in departments such as immunology, brain research, cardiology, genetics and pathogen discovery to pursue clues, he said.

In one study, Montoya and lead researcher Mady Hornig of Columbia University looked at 298 chronic fatigue patients and 348 people without the disease, and what they found was surprising: inflammation

Patients in the early stages of chronic fatigue had elevated levels of certain cytokines — chemical messengers that regulate inflammation. The most prevalent cytokine was interferon gamma, which has been associated with fatigue from viral infections, including mononucleosis.

Patients who had the disease for three years or less had the elevated immune molecules, but persons with the disease for more than three years showed low levels of the cytokines, which could be evidence that the immune system is exhausted, according to the research.

Finding the cytokines provided proof that chronic fatigue is biological and not merely psychological, and it offers hope that early treatment might affect the outcome of the disease.

In a separate study, Montoya and Michael Zeineh, Stanford associate professor of radiology, found significant differences between the brains of chronic fatigue patients and persons without the disease. Brain-imaging studies showed that overall “white matter” – long nerves that carry signals to the “gray matter” parts of the brain, which process information – were abnormal. Chronic fatigue syndrome appeared to involve chronic inflammation, according to their research.

The abnormality was located in the right hemisphere of the brain, which connects to the frontal and temporal lobes. The amount of abnormality also correlated to the severity of the patient’s condition, they said.

The gray matter in those areas of the brain was also thickened, according to their Oct. 29, 2014, study, which was published in the journal Radiology.

But Montoya said they do not know if the left side of the brain is also inflamed, and the right-side aberrations are thickened because of a compensatory reaction, he said.

There are also two schools of thought regarding whether chronic fatigue is caused by a single disease that causes multiple symptoms or if there are subsets of patients afflicted by are variety of agents, he said.

“With AIDS, there are different manifestations of the disease, but they are all caused by a single virus,” he said by way of example.

Several infectious diseases have been associated with the onset of chronic fatigue in some patients, including Epstein-Barr virus (glandular fever), which is associated with mononucleosis, Coxiella burnett (Q fever), enteroviruses (which affect the gastrointestinal tract) and Herpesvirus 6. Montoya said he has had several patients whose chronic fatigue started with the H1N1 influenza.

“There’s no question that different agents have been found,” he said.

Montoya and Dr. Andreas Kogelnik of the Open Medicine Institute in Mountain View have also looked at the use of anti-viral medications in some chronic fatigue patients. Their 2012 study of 61 patients given the anti-viral drug valganciclovir found that 52 percent experienced at least a 30 percent improvement in physical or cognitive functioning. Among these, 59 percent had physical improvements and 81 percent improved cognitively.

Their 2013 double-blind study with valganciclovir against a placebo involved 30 chronic fatigue patients who had elevated antibodies against human herpesvirus 6 and Epstein-Barr, found that patients who received the drug had a greater improvement in mental fatigue, fatigue severity and cognitive function within the first three months. The benefits continued for the remaining nine months. The patients’ white blood cells and other immune-system responses also improved, according to the study, which was published in the Journal of Medical Virology.

Davis is working with numerous collaborators across many fields, hoping the collaborative effort will attract the best minds in their fields.

“This is probably one of the last major diseases we know nothing about. This is your last chance to be a pioneer,” he said.

Unraveling the mystery of chronic fatigue syndrome –  Scientists take small steps toward understanding a devastating disease, by Sue Dremann in Palo Alto Weekly

This is probably one the last major diseases we nothing about, by Lisa Steakly

Invisible Illness – Stories of Chronic Fatigue Syndrome – video of 2 people with CFS, including Whitney Dafoe

 

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Progressive ME or a new disease?

Case study abstract:

This is a report on a patient with a history of increasing dizziness and muscle weakness after minimal exertion. In her twenties, the symptoms became more pronounced following glandular fever. After excluding other diseases, her physician diagnosed myalgic encephalomyelitis (ME), now commonly referred to as chronic fatigue syndrome (CFS).

The condition followed a relapsing-remitting course until about five years ago, when she experienced a sudden deterioration and developed new symptoms such as blurred vision in one eye and urinary incontinence. Whether this is a case of progressive ME or a new disease remains uncertain. Research is required both to increase diagnostic clarity and to establish whether the recommended behavioural interventions designed for CFS are appropriate for the subset of patients with neurological symptoms and abnormalities on MRI.

Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report, by Sandra Howes and Ellen M Goudsmit in Physical Medicine and Rehabilitation – International Vol. 2, no.6, p 1052, July 9, 2015

 

 

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HPV Vaccine, POTS and ME/CFS

The HPV Vaccine, POTS and ME/CFS and FM – Is There An Issue?, by Cort Johnson, Health Rising, July 1, 2015

Through their ability to virtually eradicate infectious diseases such as polio, smallpox and measles, vaccines have produced incalculable good over time. Measles is a case in point. In 1958, 763,094 cases of measles were reported in the U.S.:  in 2008 less than seventy were.  Recent research suggests that damage to the immune system following the measles infection probably resulted in many health issues later as well.  It’s almost impossible to calculate how much disease and suffering vaccinations have prevented.

That’s why it’s been difficult to write a blog suggesting that a specific vaccine may have problems. Put the studies indicating that it’s as safe as any vaccine against anecdotal reports that it’s causing harm, and you don’t have much.  Parents of autistic children were sure that the mercury in the vaccinations their children were taking was causing autism. It took millions of dollars to prove it wasn’t. Meanwhile many unvaccinated children were left in harms way.

The state of California is concerned enough about dropping rates of vaccinations that a  bill that would bar children who are not vaccinated from attending public schools, is on the brink of passing. I do not in any way wish to be a part of any general anti-vaccination promotion.

Designed to prevent infections associated with the development of cervical cancer, genital warts, and other cancers, the human papillomavirus vaccine is the latest vaccine to come to market.

The Upside

HPV vaccines have received widespread approval from major health organizations. The World Health Organization (WHO) and public health officials in Australia, Canada, Europe, and the United States have recommended vaccination of young women against HPV. ( The U.S. also recommends vaccination in young males).

The two vaccines approved in the U.S., Gardasil and Cervarix, protect against two types of human papilloma virus responsible for  70% of cervical cancers, 80% of anal cancers, 60% of  vaginal cancers, 40% of vulvar cancers, and 90% of genital warts.

The efficacy of the vaccine is not clear yet but it may be able to significantly reduce the rates of cervical cancer. It is the fourth most common cause of death from cancer. (The introduction of the pap smear has reduced number of deaths, they have dropped significantly over time.) The National Cancer Institute has stated that

“Widespread vaccination has the potential to reduce cervical cancer deaths around the world by as much as two-thirds, if all women were to take the vaccine and if protection turns out to be long-term. In addition, the vaccines can reduce the need for medical care, biopsies, and invasive procedures associated with the follow-up from abnormal Pap tests, thus helping to reduce health care costs and anxieties related to abnormal Pap tests and follow-up procedures.”

By 2014 almost 40% of teenage females in the U.S. had received at least one shot of the three shot protocols. In Australia the percentage is almost 70%. Statistics suggested the vaccine was working. The prevalence of HPV infections among teenagers aged 14–19 had been cut in half with an 88% reduction among vaccinated women in the U.S.. The infections were down threefold in Australia.

The National Cancer Institute reported that tens of thousands of vaccinations were done prior to licensing and that a recent CDC and FDA safety review found adverse events were no higher than in other vaccines.  (It did note that a higher proportion of syncope (fainting) was seen in Gardasil.)  While studies have found that the incidence of serious adverse effects is  low (<1 in a 1,000) anecdotal reports have emerged of the vaccine triggering autonomic nervous system dysfunction including postural orthstatic tachycardia syndrome (POTS).

A Downside?

The case against the HPV vaccine having an  unusual number of side-effects is quite strong. Some dissenting reports have emerged, however. A small Japanese study recently reported increased rates of orthostatic intolerance and an complex regional syndrome-like disease in young women, who associated their symptoms with HPV  vaccination. The young girls, some of whom were unable to attend school, tended to be diagnosed as having a psychosomatic disorder.  The study suggested abnormal peripheral sympathetic responses were present.

A media outlet recently published a report from a U.K. agency indicating that many more adverse side-effects have been reported for the HPV vaccine than for other vaccines. Since the vaccine was not given until three years in the reporting period the report understates the incidence of negative side effects of the HPV  vaccine relative to other vaccines.  It should be noted that this report stands at odds with reports from other countries.

The media report followed the case of a young girl experiencing a very ME/CFS like illness progression.

Two weeks after her first HPV injection, a previously healthy and active 13-year old teenager experienced dizziness and nausea.  She eventually ended up in the emergency room with severe chest and abdominal pains and difficulty breathing. Suggestions that the vaccinations were responsible were met with hostility and ridicule and predictably she was told to push herself to get back to normal. Two years later, now able to attend school only 3-4 hours a week, she was finally diagnosed with postural orthostatic tachycardia syndrome (POTS).

When people come down with POTS and ME/CFS and FM they often do so suddenly; there’s no way to tell that her POTS was caused by it or by another factor.

In the HPV category alone, however, ADRs numbered 8,228, of which 2,587 were classified as “serious”; i.e. resulting in hospitalization or deemed life threatening.

It should be noted that adverse effects “associated with” or occurring around the time of vaccination are to be expected. For instance the thirty-two deaths and 12,424 adverse reactions ranging from dizziness to autoimmune disorders reported with HPV vaccinations in a CDC study came after 23 million doses.  Those numbers are in line with safety studies of other vaccines.

In 2013 the Japanese government, pending an analysis of reports of long-term pain associated with the vaccine, withdrew its recommendation that young girls receive the vaccine.  It noted that while still very low (12.8 serious cases of adverse events per 1 million inoculation) the reports of adverse events were higher than for some other vaccines.

Hypothesis: Human papillomavirus vaccination syndrome—small fiber neuropathy and dysautonomia could be its underlying pathogenesis. Manuel Martínez-Lavín. Clin Rheumatol, July 2015, Volume 34, Issue 7, pp 1165-1169

Dr. Martinez-Lavin has produced a hypothesis paper proposing that HPV vaccines may cause sympathetic nervous system dysfunction in very small proportion of those being vaccinated.  Calling these issues “rare” Martinez-Lavin speculated the aluminium adjuvant in combination with the inactivated virus may play a role.

Martinez-Lavin believes the multi-symptom nature of the complaints may have made it difficult to determine causality and lead to under-reporting of harms. He started worrying about the vaccine after several girls now under his treatment developed fibromyalgia shortly after being vaccinated.

Conclusions

On the balance the evidence suggests HPV vaccinations are safe. They may help reduce the incidence of cervical cancer and genital warts.  Pending further analysis – and counter to other nations – the Japanese government, however, withdrew it’s recommendations that young girls be vaccinated. One recent report suggests rates of adverse effects, while still rare, may be higher than in other vaccines.

 

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Challenge & defence of name SEID and IOM’s definition

Fink and Schröder challenge the validity of the IoM’s new name and definition of ME/CFS:

Redefining Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

To the Editor: The Institute of Medicine (IOM) proposed a new name (systemic exertion intolerance disease) and diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).’ The IOM
panel aimed to develop evidence based clinical diagnostic criteria  for ME/CFS for use by clinicians, using a consensus-building  methodology.”

We agree that more valid diagnostic criteria for ME/CFS are needed and welcome the panel’s effort to improve patient care through better diagnostic tools. However, we do not believe that a new consensus-driven proposal added to the many existing ones will help reach these important aims. The poor acceptance of ME/CFS in the scientific community is due to a lack of convincing evidence that
ME/CFS is a distinct syndrome that can be delimited from other similar syndromes.

Even though the panel’s comprehensive literature review revealed important data indicating the difficult experiences of patients with ME/CFS, the crucial question regarding the nosological status of ME/CFS remains unsolved2 and can be solved only through new scientific studies, not by consensus.

To identify a distinct syndrome, 2 prerequisites need to be proved. First, studies need to show that symptoms cluster (ie, appear together more often than randomly), which can be done using a cluster or factor analysis.1 None of the reported analyses show that the suggested symptoms cluster (postexertion malaise, unrefreshing sleep, cognitive impairment, and orthostatic intolerance).

Second, boundaries or points of rarity between the syndrome and related syndromes need to be identified, which can be achieved with latent class analysis or similar statistical techniques.3 This type of analysis is not reported. Because the suggested symptoms are common in numerous conditions, identifying these boundaries are of paramount importance.

Patients with ME/CFS have multiple symptoms and many fulfill criteria for multiple syndromes.2 4 The new diagnostic proposal does not answer the important question of whether patients who have multisymptomatic ME/CFS have the same illness as patients with few symptoms.

Is ME/CFS a distinct syndrome or part of a spectrum? To answer that question, we need more research that complies with the basic rules on how to establish and validate diagnoses.

Per Fink, PhD. DMSc
Andreas Schroder, MD, PhD

1. Clayton EW. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: an IOM report on redefining an illness JAMA. 2015:313(11) 1101 1102.
2. Wessely S. Nimnuan C. Sharpe M. Functional somatic syndromes: one or mny? Lancet. 1999:354<9182):936-939.
3. Kendell RF. Clinical validity. PsycholMed 1989;19{1) 45-55.
4. Fink P. Schroder A One single diagnosis, bodily distress syndrome,
succeeded to capture 10 diagnostic categories of functional somatic syndromes and somatoform disorders. /Psychosom Res, 2010;68<5) 415
-126.

Ellen Wright Clayton defend the IOM’s process:

In Reply I concur with Drs Fink and Schroder that more research is  needed to understand the etiology and refine the diagnosis of  systemic exertion intolerance disease. I, however, cannot agree with  their conclusion that the IOM  Committee’s case definition fails because it was not based on a cluster or factor analysis or latent class analysis or by using similar sta¬tistical techniques.

The Committee examined the existing literature that used these techniques1(pp60-66) and found those studies inadequate for several reasons. The committee also recognized that the framing of salient case definitions frequently relies on a variety of inputs, including expert consensus, input from pa¬tients and stakeholders, and evidence-based review of the lit¬erature that addresses etiology, pathophysiology, and discrimi¬nating clinical characteristics.

The Committee cited 2 examples, the Jones criteria for rheumatic fever and the Diagnostic and Statistical Manual of Mental Disorders, in which case definitions had been made in the absence of clear understanding of etiology.1(p38) In its com¬prehensive literature review, which assessed the quality of available evidence, the Committee focused on identifying symptoms that are found in virtually every patient, with an emphasis on those that have objective findings
on testing in cases of ambiguity. The criteria set forth in the report reflect that analysis. As directed by the statement of task, the criteria and the recommendations also reflect the voices of patients, advocates, and experts inside and outside the Committee who were eloquent in their statements about the seriousness, complexity, and chronicity of this disease, and the misunderstanding and dismissiveness of clinicians and others. I stand by the major contribution of the Committee’s work for these patients.

Ellen Wright Clayton. MD, JD

Read more about the IoM and their report.

Read Dr Lucinda Bateman’s answers to questions about the report

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Circulating cytokines & CFS

Research abstract:

There has been much interest in the role of the immune system in the pathophysiology of chronic fatigue syndrome (CFS), as CFS may develop following an infection and cytokines are known to induce acute sickness behaviour, with similar symptoms to CFS.

Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a search was conducted on PubMed, Web of Science, Embase and PsycINFO, for CFS related-terms in combination with cytokine-related terms. Cases had to meet established criteria for CFS and be compared with healthy controls. Papers retrieved were assessed for both inclusionary criteria and quality. 38 papers met the inclusionary criteria.

The quality of the studies varied. 77 serum or plasma cytokines were measured without immune stimulation. Cases of CFS had significantly elevated concentrations of Transforming Growth Factor-beta (TGF-) in five out of eight (63%) studies. No other cytokines were present in abnormal concentrations in the majority of studies, although insufficient data were available for some cytokines.

Following physical exercise there were no differences in circulating cytokine levels between cases and controls and exercise made no difference to already elevated TGF-β concentrations. The finding of elevated TGF-β concentration, at biologically relevant levels, needs further exploration, but circulating cytokines do not seem to explain the core characteristic of post-exertional fatigue.

Chronic fatigue syndrome and circulating cytokines: a systematic review, by S Blundell, KK Ray, M Buckland, PD White in Brain Behav Immun. 2015 Jul 3. pii: S0889-1591(15)00238-X [Epub ahead of print]

 

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Mendus: patient driven research projects

Mendus is an online research lab where patients can take part in research trials and even suggest topics for study.

The aim of Mendus is to bring research within reach of those who need it.
patients can unite, discuss, and with the guidance of experienced research scientists, conduct their own research.

So far there are 4 patient communities:

  • Pernicious Anaemia / B12 deficiency
  • CFS
  • FM (Fibromyalgia)
  • MS (Multiple Sclerosis)

There are 4 active CFS studies:

  • CFS Diet Study
  • D-Ribose Study
  • Chocolate
  • Whey protein

6 studies are proposed:

  • Low Dose Naltrexone (LDN)
  • Vitamin B12
  • AHCC (mushroom) StudyVitamin B1 Study
  • Anaerobic Threshold Study
  • Vitamin B1
  • CFS Genetic Study(s)

Mendus is run by Joshua Grant, a neuroscientist with CFS, who has spent hours surfing the net looking for possible treatments that might help him. He discovered that many of the research studies are based on a modest number of participants. He decided that larger scale trials were needed and not all research needs to cost a lot of time and money.

How to get involved:

  • Register anonymously on the site – all you need is an email address
  • You will be asked to Complete the DePaul Symptom Questionnaire (devised by Dr Leonard Jason from the DePaul University, Chicago)
  • You will be given an ID number and you can begin a study at any time, though may have to purchase items in order to take part.

Mendus website

 

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Meanings of ME

Book abstract:

Chronic fatigue syndrome (CFS or ME) is a problematic diagnosis, and much of the existing writing on the topic is dominated by questions of biology, psychology and causation.

The focus on personal, interpersonal and public meanings in Meanings of ME signals a paradigm shift in thinking about CFS/ME. Contributions from clinicians and academics as well as from those who have personal knowledge of CFS/ME
highlight the varied experiences of the illness.

Rather than insisting on a specific theory of the illness, the authors provide fresh
perspectives on the sometimes conflicting ways in which the diagnosis and symptoms of CFS/ME are interpreted by doctors, patients and others. The book’s early chapters survey four different ways in which CFS/ME can be presented: as lived experience, as a scientific phenomenon, as a medical diagnostic classification, and as a product of culture.

The personal, interpersonal and public meanings of CFS/ME are then discussed before an exploration of stigma and identity from both personal and professional standpoints.

Meanings of ME: Interpersonal and Social Dimensions of Chronic Fatigue, ed by Christopher D. Ward. Palgrave Macmillan, July 15, 2015

Christopher Ward is Emeritus Professor of Rehabilitation Medicine at the University of Nottingham, UK. His clinical interests as a physician were in long-term conditions including chronic fatigue syndrome/ME. Most of his publications have been in the fields of neurology and rehabilitation. He now practices as an accredited Family and Systemic Psychotherapist.

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