Primer for the public

Primer for the public offers a broad audience detailed information on myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS), complex, chronic, and poorly understood medical conditions. ME was first categorized as a neurological disease by the World Health Organization (WHO) in 1969. CFS was first formally defined by the United States Centers for Disease Control and Prevention (CDC) in 1988 as a framework for researching unexplained chronic fatigue (CF) associated with a mononucleosis-like syndrome. There remains a lack of consensus among members of the medical and research communities regarding the equivalence of ME and CFS. Some believe that CFS is intended to describe the same disease entity as ME, while others believe that they are distinct conditions but with overlapping symptom profiles. In deference to this lack of consensus, the combined term ME/CFS is often used.

https://www.youtube.com/watch?v=pqDubEeIBtA

The core ME/CFS symptoms are: chronic fatigue (CF); post-exertional malaise (PEM); unrefreshing sleep/sleep problems; and cognitive impairment/brain fog and/or orthostatic intolerance (OI). A patient can have many more symptoms and meet different criteria. Systemic Exertion Intolerance Disease (SEID), an ME/CFS criteria, allows for a patient to be diagnosed with the minimum core symptoms  and the patient may have other symptoms. The Canadian Consensus Criteria (CCC) requires the core symptoms and neurological, autonomic, neuroendocrine, immune system, and myalgia symptoms to meet its ME/CFS diagnostic criteria. The International Consensus Criteria (ICC) is used to diagnose myalgic encephalomyelitis (ME) which requires the core symptoms and neurological, immune/gastrointestinal/genitourinary impairment, and energy metabolism/ion transport impairment symptoms for a diagnosis.

Although the Fukuda and the Oxford Criteria are used for diagnosing chronic fatigue syndrome (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having CFS when in fact they are suffering from the symptom chronic fatigue (CF). There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had overtraining syndrome (which has the symptom of CF) and not ME, CFS, or ME/CFS. CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients. "The most common overlapping condition with ME/CFS is fibromyalgia."

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. Graded exercise therapy (GET) and cognitive behavioral therapy (CBT) are used in the UK inappropriately for treating ME/CFS. The CDC website states "ME/CFS is a biological illness, not a psychologic disorder" and impacts multiple body systems. The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity.



Disease onset and course of illness
ME/CFS can onset from many acute/sudden triggers: usually viral or bacterial, but also trauma, surgery or childbirth, allergic reaction, and stress. There is also a gradual onset not attributed to any one or multiple triggers. Myalgic encephalomyelitis (ME) is said to always have an acute/sudden infectious onset.

The disease ME/CFS is diagnosed when a person does not recover from a flu-like illness, such as mononucleosis or another herpesvirus, Q fever, 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.

The CDC recognizes that there can be different causes and it is possible two or more triggers could cause the illness. Areas of research are infections, immune system changes, stress affecting body chemistry, changes in energy production, and a possible genetic link.

In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems." The CDC notes there are abnormalities with the immune system, cellular metabolism, and blood pressure or heart rate regulation.

Blood donation
Blood donation prohibition had been exacted in the United States (US) and United Kingdom (UK) at one time due to the incorrect research of XMRV as being the infectious trigger of CFS and that patients carried the virus. Two papers on XMRV were retracted as it was a laboratory contamination. The US American Red Cross and UK National Health Service Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS. Australia has a prohibition as a precaution.

Mini-Docs
https://www.youtube.com/watch?v=Fb3yp4uJhq0 What happens when you have a disease doctors can't diagnose By Jen Brea/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.

https://www.youtube.com/watch?v=9_HwOUiImvw

Invisible Illness - Stories of Chronic Fatigue Syndrome By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by Chronic Fatigue Syndrome - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online

https://www.youtube.com/watch?v=RC9TjgE_PlU

Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome By Dr. David Kaufman/Unrest

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is part of the Unrest Continuing Education module, made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch Unrest online for free and receive Continuing Education credit.

Epidemiology
In the United States, 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually." Some CFS patients can work with job accommodations but 1/3 to 1/2 become unemployed and many rely on SSDI/SSI.
 * Epidemiology
 * All races and cultures are afflicted with ME/CFS. Children and adolescents are also diagnosed.


 * Female predominant diseases
 * Like many autoimmune and neuro-immune diseases where mostly women are afflicted, the ME/CFS female/male patient ratio per Capelli et al. is 6:1 while the CDC states 4:1.


 * Pediatric
 * Pediatric ME/CFS is defined by the CDC and the National Academy of Medicine (NAM) although it is usually diagnosed in adults. "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults." The prognosis in adolescents is considered to be better than in adults. Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.


 * Prevalence
 * "An estimated 17-20 million people suffer from ME/CFS worldwide, and 25% of them have a very severe form of it."  25% of patients are severely ill and are either bed-bound, wheelchair bound, or are housebound or nearly so.  The ME/CFS Severely Ill, Big Data Study is focused on this 25%. 90% of patients are undiagnosed.


 * Prognosis
 * The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning. The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.

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 the core symptoms found in all patients. "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)."
 * 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 of worsening ME/CFS symptoms which can be delayed 24-72 hours or more  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:
 * Chronic fatigue


 * Cognitive dysfunction


 * Orthostatic intolerance (OI) such as postural orthostatic tachycardia syndrome (POTS) or neurally mediated hypotension (NMH)
 * Unrefreshing sleep See also: sleep disturbance

Other possible symptoms

 * Chronic pain is a mandatory symptom in the Canadian Consensus Criteria.
 * Gastrointestinal/Irritable bowel syndrome
 * Immune system
 * Neurological signs and symptoms See Also: neuroinflammation.
 * List of symptoms in ME/CFS

Expanded lists of symptoms

 * Symptoms of Chronic Fatigue Syndrome
 * What are the symptoms of ME/CFS?

Comorbids

 * Fibromyalgia (FMS), irritable bowel syndrome (IBS), temporomandibular joint disorder (TMJ) and multiple chemical sensitivity (MCS)

Government guides on symptoms
US Government guides on symptoms
 * Clinicians Guide via The Institute of Medicine report
 * CDC - ME/CFS Symptoms

Canada guides on symptoms
 * Alberta Clinicians Guide

Tests

 * Natural killer cell (NKC) Blood Test


 * Sleep study for sleep apnea, restless leg syndrome, and other sleep disturbances.
 * Tilt table test for OI or POTS.

Drugs, treatments, and therapies
There are currently no Food and Drug Administration (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 unsuccessful psychological approaches to treatment.

Drugs
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 United States have failed so it is unavailable to many. Argentina has approved the use of Ampligen for severe ME/CFS 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." AMP-511 "will allow treatment of up to 100 ME/CFS patients at any one time at approved clinical infusion therapy sites."

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 doctors 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.

Treating other conditions
Different forms of OI are treated with Beta-blockers (Metopropol), Fludrocortisone (Florinef), and Pyridostigmine. When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are sensitive to medications. The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the central nervous system, such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient." For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI.

Controversy
Psychiatry has taken an inappropriate lead and treatment path for a biological disease. In the UK, graded exercise therapy (GET) and cognitive behavioral therapy (CBT) are employed by ME Clinics. Exercise exacerbates symptoms and can further injure patients. Depression and anxiety drugs are utilized usually with poor and even damaging results.

Treating a biological disease as a mental illness is seen as cost-effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance, having clauses excluding a mental health illness/disease, stop any payment or shorten the payout time-frame.

Graded exercise therapy & Cognitive behavioral therapy
GET and CBT are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed PACE trial which used the flawed Oxford criteria to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

Exercise, especially GET, can injure an ME/CFS patient further.


 * Jennifer Brea walked home from her Neurologist's office and became wheelchair bound.
 * This is an experience of serious injury due to GET shared by K. Miles, via Tom Kindlon on Twitter.
 * Emma Shorter was able to walk a few minutes a day until GET put her in a wheelchair.
 * Doctor Speedy was also seriously injured by GET.

Claims of curative treatments
Charlatans claim they can cure CFS (per the CDC "there is no cure" ) when in reality they may be able to treat chronic fatigue (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from overtraining syndrome, a condition they sometimes acquire,  while some people with adrenal fatigue are sometimes diagnosed with CFS.

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 National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC) reinstating and increasing funding and education based on Institute of Medicine report recommendations and the Health and Human Services (HHS) funding to develop Centers of Excellence. #MEAction reports on this ongoing process.

CDC Website updates

 * Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and GET and CBT recommendations have been removed.


 * Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs 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 patient feedback on the updates as well as asking for further patient input.

Documentary
Films
 * Forgotten Plague is a US documentary about Ryan Prior, an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for streaming and DVD purchase. (2015)
 * Unrest is a US documentary film that aired on PBS's Independent Lens in 2018 and is available for streaming and DVD purchase. Jennifer Brea, a person with ME, directs. (2017)

Short film

 * The Last Great Medical Cover Up is a UK short Film on Vimeo with several patient interviews. (2015)

News media

 * Chronic Fatigue: Missing Millions (Carte Blanche DSTV) TV report, South Africa (2017)

Talks and interviews

 * Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film Canary in a Coal Mine (now called Unrest) at 5:30 and 10:20. (2016)

Government health organizations

 * US


 * Centers for Disease Control (CDC)
 * ME/CFS in Children Fact Sheets (2017) Fact Sheets for Healthcare Professionals, Parents/Guardians, Education Professionals


 * National Institutes of Health (NIH)
 * Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)


 * Institute of Medicine (IOM)
 * Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts From the Institute of Medicine report. (2015)


 * Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness Report Brief on the Institute of Medicine report. (2015)

ME/CFS research foundations

 * UK


 * Invest in ME
 * Frequently Asked Questions


 * US


 * Open Medicine Foundation (OMF)
 * What is ME/CFS?

ME/CFS organizations

 * Australia


 * Emerge Australia
 * What is ME/CFS?


 * UK


 * ME Association
 * What is ME/CFS?


 * Tymes Trust (Pediatric)
 * Pediatric ME, CFS, SEID for Families and their GPs (2016)


 * US
 * Massachusetts CFIDS/ME & FM Association
 * About ME/CFS


 * Solve ME/CFS
 * What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS? (2017)


 * Get the Facts about ME/CFS (2016)


 * What is ME/CFS? (2013)


 * International
 * MEAction
 * Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS) (2015)


 * Reports and Fact Sheets (2015)

Other organizations

 * National Organization for Rare Disorders (NORD) has a section for Myalgic Encephalomyelitis

Other reading

 * What Do You Do When a Loved One Becomes Chronically Ill? By Suzan Jackson

1980's to present day

 * 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.

Deaths of ME/CFS patients

 * Causes of death
 * Suicide

Death certificates with ME or CFS
 * Merryn Crofts' death is attributed to ME.
 * Sophia Mirza's death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS. See Editor's Note

Disease names and acronyms around the world
The United States and Australia usually refer to the disease as CFS, (chronic fatigue syndrome). Many European countries, the United Kingdom and Ireland mostly use the name ME, (Myalgic Encephalomyelitis). Most countries, as well as doctors and researchers worldwide, will also use the acronym ME/CFS and a few CFS/ME. See: Definitions of ME and CFS.

The symptom chronic fatigue (CF) should not be used in place of the name chronic fatigue syndrome (CFS); this has been a source of confusion of CF the symptom and CFS the disease. CFS is a grossly misnamed disease whereas CF is a symptom of many diseases, illnesses and drug therapies. Dr. Jarred Younger explains chronic fatigue and begins by stating "Fatigue is not a disease and it is not even a symptom. So fatigue is a alarm system and the most general alarm system the body has." Webinar with Jarred Younger, Ph.D. (@6:04-7:54)

Myalgic Encephalomyelitis (ME)
Although many similar diseases have occurred for centuries, in the 1920s - 1940s there were sporadic outbreaks around the world, of both poliomyelitis, and what Dr. Melvin Ramsay called 'Benign Myalgic Encephalomyelitis' ('benign because it is disabling but not usually fatal). In 1969, the World Health Organisation included "Myalgic Encephalitis' in its 'International Classification of Diseases' (ICD), under the category 'Diseases of the Nervous System', code G93.3.

From ME to CFS
Incline Village, Lake Tahoe, NV, USA experienced an outbreak during 1984-1985. The CDC were sent to investigate. Dr. Anthony Komaroff studied cases from the outbreak and eventually he and a body of clinicians settled on the name "Chronic Fatigue Syndrome". Dr. Komaroff discusses the name emerging in the documentary film Forgotten Plague.

From CFS to 'any unexplained fatigue'
Various groups invented new definitions, that required only 'medically unexplained fatigue' such as Reeves criteria and Oxford criteria. Fatigue is a common symptom in any population, with many different causes. These new definitions allowed some psychiatrists to claim that CFS could be 'cured' through exercise and positive thinking which has been promoted through the PACE trial and that this 'cure' also applied to people who are severely ill with Myalgic Encephalomyelitis. Postviral fatigue syndrome (PVFS) is the next frontier of the psychological paradigm keeping control of an organic disease and have been laying groundwork to do so.

SEID name and diagnostic criteria
Systemic Exertion Intolerance Disease (SEID) is a diagnostic criteria proposed by the Institute of Medicine (IOM) in the Institute of Medicine report. This clinical criteria was developed for doctors in the United States to diagnose at 6 months instead of years or even decades. Doctors are encouraged to perform tests prior to six months, such as a Tilt table test or sleep study if symptoms require further investigation. Treating symptoms such as orthostatic intolerance or a sleep disorder can begin prior to the six months needed to diagnose.

Currently used

 * Canadian Consensus Criteria (CCC)
 * Fukuda criteria (Sometimes referred to as CDC Criteria)
 * International Consensus Criteria (ICC)
 * Oxford criteria
 * Reeves criteria (Sometimes called Empirical definition)
 * SEID or IOM 2015 (Used by CDC on their ME/CFS Diagnostic Criteria for Healthcare providers page.)

Currently not in use

 * Holmes criteria
 * London criteria
 * Nightingale definition
 * NIOF
 * Ramsay definition

The different criteria used from one doctor to another and researcher to researcher results in confusion for doctors trying to diagnose, poor research and discord between patients, medical professionals, and charitable organizations. Adding to the confusion is a clinical criteria will at times be used in research and a research criteria used by a clinician to diagnose. Many US researchers will use Fukuda (using the PEM "option") and CCC in a single research project. The NIH Post-Infectious ME/CFS Study will be using four: SEID, Fukuda, CCC and Reeves. The ME/CFS community wanted to participate in this study's design.

Notable studies
"Bilateral white matter atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS."
 * 2014, Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome
 * 2014, Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder By David Tuller - New York Times: Well


 * Cytokine ("Notable studies")
 * List of enterovirus infection studies
 * 2016, Metabolic features of chronic fatigue syndrome


 * 2019, Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy
 * 2018, ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study (TALK)

Learn more
Potential treatments and research Guides and reports
 * Ampligen Used in Argentina for the treatment of severe ME/CFS.
 * Brain imaging
 * Natural killer cell
 * Vagus nerve infection hypothesis
 * Caring for People with Myalgic Encephalomyelitis (2018) Guide for Caretakers
 * "In the Expectation of Recovery" by Centre for Welfare Reform UK

Patient mental health


 * Patients that had been deemed as suffering from mental health and not a biological illness.
 * Karina Hansen is a young Danish woman taken from her family for 3 1/2 years due to Per Fink's insistence her ME was due to mental health issues.
 * Sophia Mirza was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
 * Ean Proctor was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.

Outbreaks
 * ME/CFS is not depression. It is a lack of energy, not desire.
 * Incline Village outbreak of 1984 began the research that led to the diagnostic construct Fukuda and name of chronic fatigue syndrome


 * List of outbreaks

Other resources

 * Verywell FMS/CFS Well written articles on ME/CFS and Fibromyalgia.