Primer for journalists

Myalgic Encephalomyelitis (M.E.), Chronic Fatigue Syndrome (CFS) and chronic fatigue are widely misunderstood. In this primer we provide evidence-based statements (with links to further reading & sources) to support journalists writing about the disease.

What do we know?
ME is a debilitating illness that has been recognised as a neurological condition by the World Health Organisation (WHO) since 1969.

It is a systemic neuroimmune condition characterized by post-exertional malaise (a severe worsening of symptoms after even minimal exertion). It causes dysregulation of both the immune system and the nervous system. The effects of ME are devastating enough to leave 25% of patients housebound or bedbound. For moderate to severe patients, living with ME is like living with late-stage cancer, advanced stage AIDS, or congestive heart failure for decades.

In many parts of the world, it is commonly called Chronic Fatigue Syndrome.

ME/CFS costs the US economy up to $24 billion per year in direct medical costs, and lost production. Despite this, funding for research is not commensurate with the level of disease burden. In the 2015 financial year, the National Institutes of Health (NIH) provided only $5 million in research funding for ME/CFS, which is less funding than hayfever. This is in stark contrast to funding levels for other similarly disabling illnesses, like Multiple Sclerosis ($105 million) and HIV/AIDS ($3 billion). The Institute of Medicine, a special advisory committee of the U.S. Department of Health and Human Services (HHS) (ref: CFSAC recommendations) and NIH expert advisory panel agree that it is imperative to increase research funding into ME/CFS.

ME vs CFS vs CF
The name Myalgic Encephalomyelitis (ME) was coined following an outbreak of an illness at the Royal Free Hospital in the UK, in 1955. The name Chronic Fatigue Syndrome (CFS) was coined by the Centers for Disease Control (CDC)l following an outbreak of a flu-like illness at Incline Village, at Lake Tahoe, in the 1980s. There is disagreement as to whether (ME) and (CFS) are the same condition, entirely separate conditions, or whether ME constitutes a more severe subset of CFS. Adding to the confusion, the diagnostic name given to patients is more often dependent on the country in which they live, than differing characteristics of their condition, as some countries use CFS (eg: US, Australia), and other countries (particularly in Europe) use ME. At this point in time, there is no clear biological evidence to resolve whether the conditions are the same or different, and there is unlikely to be a resolution until firm biomarkers have been identified. As such, many patients and researchers use the term ME/CFS.

The name Chronic Fatigue Syndrome is itself controversial, as many consider it stigmatising. In February 2016, Dr Anthony Komaroff, who was part of the Centers for Disease Control (CDC) group of clinicians who coined the name Chronic Fatigue Syndrome, said of it:

"I think that was a big mistake because the name, in my opinion, and the opinion of a lot of people, it both trivialises and stigmatises the illness. It makes it seem unimportant, maybe not even real"

It is important to distinguish between ME/CFS and "chronic fatigue" (CF), which is a symptom of many different medical conditions (eg: anaemia, Hepatitis, Multiple Sclerosis, hypothyroidism, depression, ME/CFS). "Chronic fatigue" is not a condition in its own right and it is incorrect and misleading to refer to ME/CFS as "chronic fatigue". Whilst fatigue is a component of ME/CFS, many consider Post-exertional malaise (PEM) to be the cardinal feature of ME/CFS.

Symptoms
Symptom presentation varies enormously between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear. There are many symptoms which people with ME/CFS experience, though those listed below are arguably the most common:
 * Post-exertional malaise (PEM) is the hallmark symptom of ME/CFS. After physical or mental exertion (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program) there is a payback which can be delayed 24-48 hours and can last 24 hours or more. The patient will experience even greater fatigue as well as exasperating the flu-like symptoms and body pain.  Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.


 * Regarding PEM the CFIDS Association of America states: "This is a term which describes a symptom in which exercise or exertion can bring on malaise (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold)."


 * Chronic fatigue
 * Chronic pain
 * Cognitive dysfunction
 * Unrefreshing sleep, and sleep disturbance
 * Orthostatic intolerance, such as Postural orthostatic tachycardia syndrome (POTS) or Neurally mediated hypotension (NMH)
 * Neuroinflammation
 * Neurological disturbances such as muscle spasms, numbness/tingling, sensory overload

Biological abnormalities
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the condition. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. Whilst it is true that the condition is poorly understood, many biological abnormalities have been found in a range of different body systems that have been found in ME/CFS, particularly in the Central Nervous System, Autonomic Nervous System, Immune system and energy metabolism. Unfortunately, none have yet proved to be specific enough to ME/CFS as to be useful as a biomarker of the condition, and many were identified in small studies, which are in need of replication. Whilst there have been abnormalities which have been identified to be associated with the condition, it cannot yet be determined whether these are a cause or consequence of the condition.


 * Neuroinflammation Japanese Neuroinflammation study, Younger's Leptin study
 * Reduced brain white matter study by Stanford ME/CFS Initiative New York Times Article with brain images.
 * Immune findings: Mady Hornig & Ian Lipkin
 * Autonomic nervous system:
 * Natural killer cell findings
 * Gut dysbiosis
 * Rituximab

Epidemiology
Prevalence estimates for ME/CFS range between 0.2-2.5%, depending on the definition of the condition used. In the US, estimates range between 836,000 and 2.5 million people with the condition, though true numbers are under reported. It is estimated that 84-91% of people with the condition remain undiagnosed.


 * Level of disability (Norwegian study HRQoL) (suggests quality of life is LOWER than for many cancers, heart diseases, brain stroke, diabetes I & II, rheumatoid arthiritis, chronic renal failure, sclerosis, schizophenia, COPH, etc)

Causes & triggers

 * Outbreaks - see List of outbreaks
 * Possible infectious triggers: Enteroviruses, Epstein-Barr virus, Q Fever , Ross River Virus , (Ebola?)
 * Non-viral triggers - trauma, chemical

Persistence hypotheses

 * Immune findings

Prognosis
In about 40% of people with ME/CFS the condition will improve over time, though recovery rates from the condition are generally quite low (less than 10%). The condition may also take a relapsing/remitting course, so individuals who appear to have recovered, may actually be in remission. For 5-20% of people, the condition is degenerative. Some studies suggest that prognosis is better for those with less severe symptoms, and who developed the condition at a younger age (childhood-young adulthood), though these findings are not consistent. It is clear that few people will return to their pre-illness state of health and functioning.

Dr. David Bell, who serves on the Scientific Advisory Board for the Open Medicine Foundation, speaks of three stages of the disease; First stage: acute illness where EBV is likely responsible for most adolescents but there is no standard viral illness. The initial virus likely fades away in a week and the patient feels better and is ready for regular activities. ..."in a person with a gradual onset of symptoms, this stage would be different"; "The second stage occurs when the symptoms do not disappear, but persist for months to years in roughly the same severity. There is little variation day-to-day, and this time is very confusing. Many medical providers are contacted, most giving conflicting opinions varying from psychological disorders to possible exotic infections, but the tests come back normal."; in the third stage patients will have mild, gradual improvements over years and patients adjust their lives to the symptoms. Patients may look well and recovery is thought to have taken place. Some patients will make a full recovery in 3-4 years but "recovery and improvement are completely different." Dr. Bell has great concern for patients 35 years old who had become ill as teens. "Some of the young adults rated their health as “good,” while the amount of activity they could perform was minimal. They had become so used to their performance level, they accepted it as their new normal. Unfortunately, many of them, while they described their health as good, they were unable to work full time or carry on other duties." It is now understood that persons with ME/CFS do not have a good long term prognosis and it is actually poor as "full recovery from untreated CFS is rare."

Treatments
There are currently no FDA approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many potential treatments, though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.

Two treatments that have garnered much attention are Ampligen and Rituximab. Many people have reported enormous benefit from Ampligen, some doctors have been prescribing it for ME/CFS for decades. Attempts to obtain FDA approval for Ampligen in the US have failed so, despite its usefulness, it is unavailable to many. Rituximab, a lymphoma drug, has shown promising results in initial trials in Norway, and there are groups crowdsourcing funding for further trials in other countries. Jarred Younger announced in March 2016 that he will be undertaking a trial of Low dose naltrexone (LDN) in ME/CFS.

Exercise as treatment
Two common treatment recommendations for ME/CFS are Graded Exercise Therapy (GET) and Cognitive behavioral therapy (CBT). These treatments are based on the hypothesis that the condition might have begun with a viral infection, but has been perpetuated by deconditioning from lack of activity, and fear and avoidance of activity. GET & CBT are aimed at addressing these hypothesised causes by challenging the unhelpful thoughts that result in avoidance of activity, and reconditioning through a gradual increase in exercise. These treatments are controversial, and are at odds with much of the research literature, which suggests that exercise may actually be harmful for people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened, which is consistent with other patient surveys.

The PACE trial, published in 2011, is the largest GET trial ever conducted. It has received much publicity as a result of its claims of recovery rates, though it has come under strong criticism from within both the scientific and patient community, for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow up studies. The study was the subject of a series of investigative pieces by journalist David Tuller in late 2015, that were highly critical of the trial. A petition signed by almost 12,000 ME/CFS patients and allies, and an open letter signed by 42 ME/CFS experts from around the world, were sent to The Lancet, both calling for the data to be reanalysed. Twenty four ME/CFS organisations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis. To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the PACE trial continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.

One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of Post-exertional malaise (PEM), which is an exacerbation of symptoms following physical, mental or even emotional exertion. Studies have revealed immunological, muscular, neurological, autonomic and cardiovascular abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary controls, the adverse effects of exercise cannot be said to be due to deconditioning.

People with ME/CFS should approach exercise with caution, as there is much potential for harm.

Anaerobic threshold, use of HR monitors for activity and pacing. Analeptic, not aerobic. Energy envelope/pacing - people do better if stay within their envelope, than push to increase activity

Severely ill patients
Considerable variation exists in the severity of the condition. The International Consensus Criteria lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):


 * Mild = 50% reduction in pre-illness activity levels
 * Moderate = mostly housebound
 * Severe = mostly bedridden
 * Very Severe = totally bedridden, and needing help with basic functions.

At least 25% of people with ME/CFS are bedbound or housebound, often for years or even decades, so are largely an invisible population. So invisible in fact, that they have rarely been included as part of research, because their level of debility precludes them from travelling to laboratories for required testing. The Open Medicine Foundation's Severely Ill Big Data Study will be the first in depth study into people with a severe form of ME/CFS.

Notable patients with severe ME/CFS include Whitney Dafoe, Karina Hansen, Lynn Gilderdale, Laura Hillenbrand, Tom Kindlon, Vanessa Li, Doctor Speedy, Naomi Whittingham.

Though uncommon, there have been instances of deaths which have been attributed to the condition (see Sophia Mirza).

Patients & psychiatry/psychology

 * Objections & scope
 * Mind-body dualism
 * The PACE trial. See Patient view of the PACE Trial controversy
 * Patient mental health

Stigmatization

 * Pretty young women slumped on desk
 * Yuppie Flu
 * Accusations of laziness/lethargy
 * Epidemiological evidence - age, gender, demographic, racial/cultural

Accusations of harassment

 * Tiny %
 * No arrests or convictions
 * Poor treatment of patients not mentioned. Ean Proctor and "The Mental Health Movement: Persecution of Patients?"

Quotes from ME/CFS experts and patients

 * Thoughts About ME - List of Quotes
 * Individual Quotes

Doctors for expert opinions


Researchers


U.S.

 * Jennifer Brea
 * Ryan Prior

Ireland

 * Tom Kindlon

Patient groups & charities
Patient Groups Australia: Emerge Australia, ME/CFS Australia (SA) Inc, ME/CFS Society of Western Australia, ME/CFS Society of NSW, ME/CFS Society of ACT

Patient Groups Belgium: Wake Up Call Beweging

Patient Groups Canada: National ME/FM Action Network, May12th.org, Action CIND

Patient Groups Ireland: Irish ME/CFS Association, Irish ME Trust

Patient Groups Italy: Associazione Malati CFS onlus, CFS Associazione Italiana onlus, CFS Italia

Patient Groups Netherlands: Steungroep ME en Arbeidsongeschiktheid, ME/cvs Vereniging, ME/CVS Stichting Nederland, ME Vereniging Nederland

Patient Groups New Zealand: Associated New Zealand ME Society (ANZMES)

Patient Groups Norway: ME-Forskning

Patient Groups Sweden: Riksföreningen för ME-patienter

Patient Groups UK: Action for ME, Invest in ME, Change For M.E. Change For Us, ME Association, Tymes Trust, MEActionUK, Forward-ME, Hope 4 ME & Fibro NI, Welsh Association of ME & CFS Support, Sussex & Kent ME/CFS Society, Association of Young People with ME, Tyne and Wear ME/CFS Support Group, Edinburgh MESH, Leeds ME Network, The York ME Community, 25 Percent ME Group

Patient Groups USA: #MEAction, ME Advocacy, National Alliance for Myalgic Encephalomyelitis, Massachusetts CFIDS/ME & FM Association, May12.org

Other tips

 * Always interview a patient
 * Interview more than one researcher (not just from the psychological aetiology view)
 * Avoid using derogatory, outdated & incorrect term "Yuppie Flu"
 * Never shorten the disease name Chronic Fatigue Syndrome (CFS) to the symptom chronic fatigue (CF). CFS, ME or ME/CFS can be used to save print space.
 * Use photographic imagery that represents the reality for patients - serious illness & disability (not well-groomed & slightly tired office workers). There is a curated set of images here.

Learn more

 * ME/CFS Diagnosis and Name with Dr Nancy Klimas (video)
 * Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education (CDC Video, 2016)
 * Institute of Medicine report
 * Canary in a Coal Mine (2017) (see trailer)
 * Forgotten Plague (2015) (see trailer)