Primer for journalists

Myalgic Encephalomyelitis (M.E.), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF) are widely misunderstood. In this primer, we provide evidence-based statements (with links to further reading & sources) to support journalists writing about the disease. Chronic Fatigue Syndrome must never be shortened to Chronic Fatigue in the body of an article or its headline. This has caused much confusion for readers who do not understand CFS is a debilitating lifelong illness and it is not the same as CF which is a symptom.

What do we know?
ME is a debilitating illness that has been recognized 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, the disability of 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.

Disease onset and course of illness
The disease ME/CFS is diagnosed when a person does not recover from a flu-like illness, EBV, mononucleosis, HHV, Q fever, Virus or other infections and meets one or more diagnostic criteria for either ME, CFS or ME/CFS. "Occasionally, ME/CFS has been triggered by environmental toxins, the receipt of an immunizing injection, or surviving a major trauma." Patient health is never the same and they experience numerous symptoms and disease severity which fluctuate day to day, week to week, month to month, year to year and decade to decade as well as varying symptoms and disease severity among patients.

Pediatric ME/CFS
Children are also afflicted with ME/CFS. See: Pediatric.

Prognosis
Prognosis for ME/CFS is generally poor. See: Prognosis

Female to male ratio
Like many auto-immune and neuro-immune diseases where mostly women are afflicted, the ME/CFS female/male patient ratio is 6:1. Fibromyalgia has a F/M 7:1 ratio and some ME/CFS patients have this additional diagnosis.

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) 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. See: Definitions of ME and CFS.

The name Chronic Fatigue Syndrome is itself controversial, as many consider it stigmatizing. 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 trivializes and stigmatizes 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: anemia, 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 exasperate 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 dysfunction
 * 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 or practical 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. Three major brain abnormalities.
 * Immune findings: Mady Hornig & Ian Lipkin
 * Metabolic features of chronic fatigue syndrome
 * 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 arthritis, chronic renal failure, sclerosis, schizophrenia, COPH, etc)

Causes & triggers

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

Persistence hypotheses

 * Immune findings

Three stages
Dr. David Bell, who serves on the Scientific Advisory Board for the Open Medicine Foundation, discusses three stages of the disease in the article Prognosis of ME/CFS.


 * At the first stage, there is an 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. He adds "in a person with a gradual onset of symptoms, this stage would be different."
 * 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."

Poor long-term prognosis
Dr. David Bell has great concern for patients 35 years old who had become ill as teens and has been studying a group that first became ill in 1985. "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."

Few Return to Pre-illness State of Functioning

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.

Severely ill
It is estimated that 25% of ME/CFS patients are severely ill and are housebound or bedbound.

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, produced by Hemispherx Biopharma, 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. Argentina has approved the use of Ampligen in 2016. Also in 2016, it was made available on a limited basis in Europe. July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the United States, known as AMP-511, to new enrollees for the first time in more than a year."

Rituximab, a lymphoma drug, had shown promising results in initial trials in Norway, and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. Øystein Fluge and Olav Mella announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The Drs. will publish a paper next year with the specifics of the failed trial.

Jarred Younger announced in March 2016 that he will be undertaking a trial of Low dose naltrexone (LDN) in ME/CFS.

Exercise as treatment
Previously, two common treatment recommendations for ME/CFS were 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 hypothesized 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 to 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 Graded Exercise Therapy 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. From 2015 to present day, the study was the subject of a series of investigative pieces that were highly critical of the trial by journalist Dr. David Tuller, science writer Julie Rehmeyer, patient advocate Tom Kindlon, Dr. Keith Geraghty , psychologist Dr. Carolyn Wilshire and others. 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 organizations 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 heart rate 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 traveling to laboratories for required testing. The Open Medicine Foundation's ME/CFS Severely Ill, Big Data Study will be the first in-depth study of people with a severe form of ME/CFS. This study has so far produced the groundbreaking paper Metabolic features of chronic fatigue syndrome.

Notable patients with severe or very severe ME/CFS include Whitney Dafoe, Karina Hansen, Lynn Gilderdale, Laura Hillenbrand, Tom Kindlon, Vanessa Li, Doctor Speedy, Naomi Whittingham, Jamison Hill and Jessica Taylor-Bearman.

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

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?"

Working with government to move forward
Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the NIH, the CDC reinstating and increasing funding and education based on IOM recommendations and the HHS funding to develop Centers of Excellence. MEAction reports on this ongoing process.

CDC Website updates

 * July 3 2017, the CDC's Chronic Fatigue Syndrome page has been changed to Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and GET and CBT recomendations have been removed.


 * July 12 2018, the "Information for Healthcare Providers" tab and its subtabs were updated.

MEAction input
 * Jul 29, 2018, CDC Revises its Information on ME MEAction report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from the feedback of patients about these updates as well as asking for further patient input.

Quotes from ME/CFS experts and patients

 * Thoughts About ME - List of Quotes
 * Individual Quotes

Doctors for expert opinions
Daniel Peterson, Nancy Klimas, Ronald Tompkins, Ron Davis, Lucinda Bateman, Alan Pocinki, Susan Levine, Jose Montoya, Anthony Komaroff, Benjamin Natelson, Lily Chu, Peter Rowe For others: see

Researchers
Leonard Jason, Mady Hornig, Ian Lipkin, Maureen Hanson, Betsy Keller, Jarred Younger, Neil McGregor, Gunnar Gottschalk, Suzanne Vernon, Staci Stevens For others: see

U.S.

 * Jennifer Brea
 * Ryan Prior
 * Julie Rehmeyer

U.K.

 * Jessica Taylor-Bearman

Ireland

 * Tom Kindlon

Patient groups & charities
Patient groups
 * American patient groups
 * Australian patient groups
 * Belgian patient groups
 * British patient groups
 * Canadian patient groups
 * Dutch patient groups
 * Irish patient groups
 * Italian patient groups
 * New Zealand patient groups
 * Norwegian patient groups
 * Swedish patient groups

History

 * Osler's Web is a book by Hillary Johnson on the early history of CFS.
 * Thirty Years of Disdain by Mary Dimmock and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.
 * List of news articles on ME and CFS
 * Sophia Mirza's life ended due to CFS and Merryn Crofts death is attributed to ME. Other deaths in the UK, United States, and Australia have also recorded deaths due to ME or CFS. See Editor's Note
 * UK agencies involved in the implementation of the PACE trial. Disabled in Tory Britain - PACE trial
 * Important events timeline

Other tips

 * Always interview a patient
 * Interview more than one researcher (not just from the psychological etiology 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 at their computer or students with a pile of books sleeping at their desk. Solve ME/CFS Initiative's Times Square Public Awareness Ad shows the reality of the disease ME/CFS. Using photos of patients whether chronically ill yet functioning or a severely ill patient or stock photos that reflect life with this disease is necessary.

Learn more

 * Caring for People with Myalgic Encephalomyelitis (2018) Guide for Caretakers
 * What is ME/CFS? By the Open Medicine Foundation
 * 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
 * Unrest (2017)
 * Jessica Taylor-Bearman
 * Forgotten Plague (2015) (see trailer)
 * Notable studies