Myalgic encephalomyelitis/chronic fatigue syndrome

ME/CFS has been classified as a neurological disease by the World Health Organization (WHO) since 1969, initially under the name benign myalgic encephalomyelitis. The classification of ME/CFS as a neurological disease is based on symptoms which indicate a central role of the nervous system. Alternatively, on the basis of abnormalities in immune cells, ME/CFS is sometimes labelled a neuroimmune condition. Many names have been proposed for the illness. The most commonly used are myalgic encephalomyelitis, chronic fatigue syndrome, and the combined umbrella term myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Reaching consensus on a name has been challenging because the cause and pathology remain unknown. In the WHO's most recent classification, the ICD-11, chronic fatigue syndrome and myalgic encephalomyelitis are named under post-viral fatigue syndrome. The term post-infectious fatigue syndrome was initially proposed as a subset of "chronic fatigue syndrome" with a documented triggering infection, but might also be used as a synonym of ME/CFS or as a broader set of fatigue conditions after infection. At the same time, there are also issues with the use of the previous term, since 1956, myalgic encephalomyelitis (myalgia means 'muscle pain' and encephalomyelitis means 'brain and spinal cord inflammation'), as there is only limited evidence of brain inflammation implied by the name. == Signs and symptoms ==

ME/CFS causes debilitating fatigue, sleep problems, and post-exertional malaise (PEM, overall symptoms getting worse after mild activity). In addition, cognitive issues, orthostatic intolerance (dizziness or nausea when upright) or other physical symptoms may be present (see also ). Symptoms significantly reduce the ability to function and typically last for three to six months before a diagnosis can be confirmed. The fatigue experienced in ME/CFS is of a longer duration and greater severity than in other conditions characterized by fatigue. but can also follow immediately after. PEM can last hours, days, weeks, or months. People with ME/CFS often experience orthostatic intolerance, symptoms that start or worsen with standing or sitting. Symptoms, which include nausea, lightheadedness, and cognitive impairment, often improve again after lying down. Weakness and vision changes may also be triggered by the upright posture. Some have postural orthostatic tachycardia syndrome (POTS), an excessive increase in heart rate after standing up, which can result in fainting. Additionally, individuals may experience orthostatic hypotension, a drop in blood pressure after standing. Other common symptoms Pain and hyperalgesia (an abnormally increased sensitivity to pain) are common in ME/CFS. The pain is not accompanied by swelling or redness. The pain can be present in muscles (myalgia) and joints. Individuals with ME/CFS may have chronic pain behind the eyes and in the neck, as well as neuropathic pain (related to disorders of the nervous system). Headaches and migraines that were not present before the illness can occur as well. However, chronic daily headaches may indicate an alternative diagnosis. Additional common symptoms include irritable bowel syndrome or other problems with digestion, chills and night sweats, shortness of breath or an irregular heartbeat. Some experience sore lymph nodes and a sore throat. People may also develop allergies or become sensitive to foods, lights, noise, smells or chemicals. == Illness severity ==

ME/CFS often leads to serious disability, but the degree varies considerably. ME/CFS is generally classified into four categories of illness severity: • People with mild ME/CFS can usually still work and care for themselves, but they will need their free time to recover from these activities rather than engage in social and leisure activities. • Moderate severity impedes activities of daily living (self-care activities, such as making a meal). People are usually unable to work and require frequent rest. • Those with severe ME/CFS are homebound and can do only limited activities of daily living, for instance brushing their teeth. They may be wheelchair-dependent and spend the majority of their time in bed. • With very severe ME/CFS, people are mostly bed-bound and cannot care for themselves. of individuals with ME/CFS, showing it to be lower than in 20 other chronic conditions|alt=A bar graph showing the average quality of life score of those with ME/CFS. Roughly a quarter of those living with ME/CFS fall into the mild category, and half fall into the moderate or moderate-to-severe categories. The final quarter falls into the severe or very severe category. Functional impairment in ME/CFS can be greater than multiple sclerosis, heart disease, or lung cancer. Fewer than half of people with ME/CFS are employed, and roughly one in five have a full-time job. == Causes ==

The cause of ME/CFS is not yet known. ME/CFS can also begin with multiple minor triggering events, followed by a final trigger that leads to a clear onset of symptoms. but ME/CFS is probably at least as prevalent among African Americans and Hispanics. It used to be thought that ME/CFS was more common among those with higher incomes. Instead, people in minority groups or lower-income groups may have increased risks due to poorer nutrition, lower healthcare access, and increased work stress. How viral infections cause ME/CFS is unclear; it could be via viral persistence or via a "hit and run" mechanism, in which infections dysregulate the immune system or cause autoimmunity. Different types of viral infection have been implicated in ME/CFS, including airway infections, bronchitis, gastroenteritis, or an acute "flu-like illness". Reactivation of latent viruses, in particular EBV and human herpesvirus 6, has also been hypothesised to drive symptoms. EBV is present in about 90% of people, usually in a latent state. The levels of antibody to EBV are commonly higher in those with ME/CFS, indicating possible viral reactivation. == Pathophysiology ==

ME/CFS is associated with changes in several areas, including the nervous and immune systems, as well as disturbances in energy metabolism. Observed changes in the immune system include decreased natural killer cell function and, in some cases, autoimmunity. ME/CFS affects sleep. Individuals experience decreased sleep efficiency, take longer to fall asleep, and take longer to achieve REM sleep, a phase of sleep characterised by rapid eye movement. Changes to non-REM sleep have also been found, together suggesting a role of the autonomic nervous system. Individuals often have a blunted heart rate response to exercise, but a higher heart rate during a tilt table test when the body is rotated from lying flat to an upright position. This again suggests dysfunction in the autonomic nervous system. Immunological People with ME/CFS often have immune system abnormalities. A consistent finding in studies is a decreased function of natural killer cells, a type of immune cell that targets virus-infected and tumour cells. They are also more likely to have active viral infections, correlating with cognitive issues and fatigue. T cells show less metabolic activity. This may reflect they have reached an exhausted state and cannot respond effectively against pathogens. Energy (ICF).|alt=A scatterplot with fifty datapoints. They show that people with ME/CFS score worse in work rate at ventilatory threshold than those with unexplained chronic fatigue on the second day of a 2-day exercise test. Objective signs of PEM have been found with the 2-day cardiopulmonary exercise test. People with ME/CFS have lower performance compared to healthy controls on the first test. On the second test, healthy people's scores stay roughly the same or increase slightly, while those with ME/CFS have a clinically significant decrease in work rate at the anaerobic threshold. Potential causes include mitochondrial dysfunction, and issues with the transport and use of oxygen. Some of the usual recovery processes following exercise may be lacking, providing an alternative explanation for PEM. ATP, the primary energy carrier in cells, is likely more frequently produced from lipids and amino acids than from carbohydrates. Other proposed abnormalities are reduced blood flow to the brain under orthostatic stress (as found in a tilt table test), small-fibre neuropathy, and an increase in the amount of gut microbes entering the blood. The diversity of gut microbes is reduced compared to healthy controls. Female individuals with ME/CFS are more likely to experience endometriosis, early menopause, and other menstrual irregularities than those without the condition. == Diagnosis ==

Diagnosis of ME/CFS is based on symptoms Blood and urine tests are used to rule out other conditions that could be responsible for the symptoms. People with ME/CFS often face significant delays in obtaining a diagnosis, and diagnoses may be missed altogether. As there are no verified biomarkers for ME/CFS, it is not possible to determine which set of criteria is the most accurate. A trade-off must be made between overdiagnosis and missing more diagnoses. The broad Fukuda criteria have a higher risk of overdiagnosis, whereas the strict ICC criteria have a higher risk of missing people. The IOM and NICE criteria fall in the middle. Possible differential diagnoses span a large set of specialties and depend on the medical history. Finally, sleep disorders, coeliac disease, and side effects of medications may also explain symptoms. and the two are often co-diagnosed. Another common condition that often co-occurs with ME/CFS is hypermobile Ehlers–Danlos syndrome (EDS). Unlike ME/CFS, EDS is present from birth. People with ME/CFS are more often hypermobile compared to the general population. Sleep apnea may also co-occur with ME/CFS. However, many diagnostic criteria require ruling out sleep disorders before confirming a diagnosis of ME/CFS. Like with other chronic illnesses, depression and anxiety co-occur frequently with ME/CFS. Depression may be differentially diagnosed by the presence of feelings of worthlessness, the inability to feel pleasure, loss of interest, and/or guilt, and the absence of ME/CFS bodily symptoms such as autonomic dysfunction, pain, migraines, and PEM. People with chronic fatigue, which is not due to ME/CFS or other chronic illnesses, may be diagnosed with idiopathic (unexplained) chronic fatigue. == Management ==

There is no approved drug treatment or cure for ME/CFS, although some symptoms can be treated or managed. Care for ME/CFS involves multidisciplinary healthcare professionals. Usually, the primary care clinician plays an important role in coordinating health care, social care and educational support for those still in school. This coordinator can help provide access to community resources such as occupational therapy and district nursing. Management may start with treating the most disabling symptom first, and tackle symptoms one by one in further health care visits. Pacing and energy management Pacing, or activity management, involves balancing periods of rest with periods of activity. The technique was developed for ME/CFS in the 1980s. Pacing can involve breaking up large tasks into smaller ones and taking extra breaks, or creating easier ways to do activities. For example, this might include sitting down while doing the laundry. The decision to stop an activity (and rest or change an activity) is determined by self-awareness of a worsening of symptoms. Use of a heart rate monitor may help some individuals with pacing. However, these studies have often had a low number of participants and have rarely included methods to check if study participants implemented pacing well. or no evidence of effectiveness. GET can have serious adverse effects. Symptoms of severe ME/CFS may be misunderstood as neglect or abuse during well-being evaluations, and NICE recommends that professionals with experience in ME/CFS should be involved in any type of assessment for safeguarding. == Prognosis ==

Information on the prognosis of ME/CFS is limited. Complete recovery, partial improvement, and worsening are all possible, == Epidemiology ==

Reported prevalence rates vary widely depending on how ME/CFS is defined and diagnosed. Overall, around one in 150 people has ME/CFS. Based on the 1994 CDC diagnostic criteria, the global prevalence rate for CFS is 0.89%. In comparison, estimates using the stricter 1988 CDC criteria or the 2003 Canadian Consensus Criteria for ME/CFS produced a prevalence rate of only 0.17%. Women are diagnosed with ME/CFS about 1.5 to four times more often than men. The incidence rate (the onset of ME/CFS) has two peaks, one at 10–19 and another at 30–39 years, and the prevalence is highest in middle age. == History ==

From 1934 onwards, there were multiple outbreaks globally of an unfamiliar illness, initially mistaken for polio. A 1950s outbreak at London's Royal Free Hospital led to the term "benign myalgic encephalomyelitis" (ME). Those affected displayed symptoms such as malaise, sore throat, pain, and signs of nervous system inflammation. While its infectious nature was suspected, the exact cause remained elusive. In 1970, two UK psychiatrists proposed that these ME outbreaks were psychosocial phenomena, suggesting mass hysteria or altered medical perception as potential causes. This theory, though challenged, sparked controversy and cast doubt on ME's legitimacy in the medical community. An initial case definition of CFS was outlined in 1988; In the 2010s, ME/CFS began to gain more recognition from health professionals and the public. Two reports proved key in this shift. In 2015, the US Institute of Medicine produced a report with new diagnostic criteria that described ME/CFS as a "serious, chronic, complex systemic disease". Following this, the US National Institutes of Health published their Pathways to Prevention report, which gave recommendations on research priorities. == Society and culture ==

relating to ME support in South East Wales|alt=a group of people offering a petition. The group includes a person on a camp bed holding up a placard that says she is in bed 23 hours a day. Controversy ME/CFS is a contested illness, with debates mainly revolving around the cause of the illness and treatments. While ME/CFS is now generally believed to be a multisystem neuroimmune condition, The possible role of chronic viral infection in ME/CFS has been a subject of disagreement. One study caused considerable controversy by establishing a causal relationship between ME/CFS and a retrovirus called XMRV. Some with the illness began taking antiretroviral drugs targeted specifically for HIV/AIDS, another retrovirus, and national blood supplies were suspected to be tainted with the retrovirus. After several years of study, the XMRV findings were determined to be the result of contamination of the testing materials. Treatments based on behavioural and psychological models of the illness have also been the subject of much contention. The largest clinical trial on behavioural interventions, the 2011 PACE trial, concluded that graded exercise therapy and CBT are moderately effective. The trial drew heavy criticism. The study authors weakened their definition of recovery during the trial: some participants now met a key criterion for recovery before the trial started. A reanalysis under the original clinical trial protocol showed no significant difference in recovery rate between treatment groups and the controls receiving standard care. Doctor–patient relations People with ME/CFS often face stigma in healthcare settings, They may also feel forced to prove that they are legitimately ill. Some may be given outdated treatments that provoke symptoms or assume their illness is due to unhelpful thoughts and deconditioning. Economic and social impact ME/CFS negatively impacts people's social lives and relationships. Stress can be compounded by disbelief in the illness from the support network, who can be sceptical due to the subjective nature of diagnosis. Many people with the illness feel socially isolated, and thoughts of suicide are high, especially in those without a supportive care network. Caring for somebody with ME/CFS can be a full-time role, and the stress of caregiving is made worse by the lack of effective treatments. Economic costs due to ME/CFS are significant. In the United States, estimates range from $36 to $51 billion per year, considering both lost wages and healthcare costs. A 2017 estimate for the annual economic burden in the United Kingdom was £3.3 billion. The goal of the day is to raise awareness among the public and health care workers about the diagnosis and treatment of ME/CFS. The date was chosen because it is the birthday of Florence Nightingale, who had an unidentified illness similar to ME/CFS. == Research ==

Research into ME/CFS seeks to find a better understanding of the disease's causes, biomarkers to aid in diagnosis, and treatments to relieve symptoms. In a 2015 report, the US National Academy of Sciences said that "remarkably little research funding" had been dedicated to causes, mechanisms, and treatment. In addition, drug companies have invested very little in the disease. The US National Institutes of Health (NIH) is the largest biomedical funder worldwide. Using rough estimates of disease burden, a study found NIH funding for ME/CFS was only 3% to 7% of the average disease per healthy life year lost between 2015 and 2019. Worldwide, multiple sclerosis, which affects fewer people and results in disability no worse than ME/CFS, received 20 times as much funding between 2007 and 2015. Multiple reasons have been proposed for the low funding levels. Diseases for which society "blames the victim" are frequently underfunded. This may explain why COPD, a severe lung disease often caused by smoking, receives low funding per healthy life year lost. Similarly, for ME/CFS, the historical belief that it is caused by psychological factors may have contributed to lower funding. Gender bias may also play a role; the NIH spends less on diseases that predominantly affect women in relation to disease burden. Less well-funded research areas may also struggle to compete with more mature areas of medicine for the same grants. Various drug treatments for ME/CFS are being explored. Drugs under investigation often target the nervous system, the immune system, autoimmunity, or pain directly. More recently, there has been a growing interest in drugs targeting energy metabolism. Rituximab, a drug that depletes B cells, was studied and found to be ineffective. Another option targeting autoimmunity is immune adsorption, which removes a large set of (auto)antibodies from the blood. Challenges Symptoms and their severity can widely differ among people with ME/CFS. This poses a challenge for research into the cause and progression of the disease. Dividing people into subtypes may help manage this heterogeneity. The existence of multiple diagnostic criteria and variations in how scientists apply them complicate comparisons between studies. Definitions also vary in which co-occurring conditions preclude a diagnosis of ME/CFS. ==See also==