Terminology

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This page is a glossary of key ME/CFS-related terms. (For help editing this page, see Help:Glossary.)

Symbols and non-Latin characters

α: α / Α. Greek letter alpha or alfa (a symbol used in science), equivalent to "a".

β: β / Β. Greek letter beta (a symbol used in science), equivalent to "b".

γ: γ / Γ. Greek letter gamma/gamme (a symbol used in science), third letter of the Greek alphabet. Equivalent to the letter "g".

δ: δ / Δ. Greek letter delta (a symbol used in science). Equivalent to a "d".

ε: ε / Ε. Greek letter epsilon (a symbol used in science). Equivalent to an "e".

θ: θ / Θ. Greek letter theta/theeta (a symbol used in science). Eighth letter of the Greek alphabet, equivalent to "th".

λ: λ / Λ. Greek letter lambda/lamda (a symbol used in science). Equivalent to the letter "L".

μ: μ / Μ - Greek letter mu (a symbol used in science). Equivalent to the letter "m". The symbol μ is often used for units of weight, μg meaning microgram.^[1]

μg: A microgram, a millionth of a gram. Micrograms can be written as mcg or μg. 1000 micrograms (1000mcg) is equivalent to 1 milligram (1mg).^[2]

τ: τ / Τ. Greek letter tau (a symbol used in science). Equivalent to a "t". Tau pathologies or tauopathies are a group of neurological disorders.^[3]

ω: ω / Ω - Greek letter omega (a symbol used in science). Last letter of the Greek alphabet.

A

abzymes: (Abzs) - an antibody with enzymatic activity (antibody + enzyme).^[4]

accuracy: The "closeness of an observation to the true clinical state".^[5] With respect to diagnostic tests, "accuracy" means how specific and sensitive the test is.^[6]

Action for ME: (AfME) - Action for ME is a British non-profit organization that was set up in 1987 as The M.E. Action Campaign. Its founders were Martin Lev, Sue Findlay and Clare Francis. In September 1993 it changed its name and logo to Action for ME and Chronic Fatigue. It then changed its name in 1993 to Action for ME.^[7]

adverse reaction: Any unintended or unwanted response to a treatment, whether in a clinical trial or licensed treatment. May be minor or serious.^[8]

AfME: See Action for ME.

Agency for Healthcare Research and Quality: (AHRQ) - Agency for Healthcare Research and Quality is a United States government agency under the U.S. Department of Health and Human Services. Their mission is "to produce evidence to make health care safer, higher quality, more accessible, equitable, and affordable.^[9] A representative of the Agency for Healthcare Research and Quality sat on the (now disbanded) CFSAC committee as an Ex Officio Member.

agonist: A chemical that binds to the receptor and stimulates it's function, e.g., morphine is an opioid agonist that binds to the opioid receptor, reducing pain. The opposite of an antagonist.^[10]^[11]

AHRQ: See Agency for Healthcare Research and Quality.

All-Party Parliamentary Group on Myalgic Encephalomyelitis: (APPG) - A British group of backbench members of parliament, from all political parties and from Houses of Commons and Lords, who meet to discuss ME.

American Psychiatric Association: (APA) - The main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world.^[12] Not to be confused with the American Psychological Association (also APA).

amygdala: Part of the brain, within the temporal lobe. Related to memory and emotional behavior.^[13]

anaphylaxis: "an often severe and sometimes fatal systemic reaction in a susceptible individual upon exposure to a specific antigen (such as wasp venom or penicillin) after previous sensitization". Typically causes breathing problems, fainting or loss of consciousness, fast heartbeat, itching, and hives.^[14]^[15] (Learn more: www.nhs.uk)

antagonist: A chemical that reduces or helps block the activity of another chemical in the body. For example, most antihistamines are H1 antagonists because they block the H1 histamine receptor, which helps relieve allergy symptoms. The opposite of an agonist.^[16]^[17]

antibodies: Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

anticholinergic: (ACh) - Involving blocking the neurotransmitter acetylcholine. Anticholinergic side effects may include dilated pupils in the eyes, photophobia, dry mouth, decreased mucus in the lungs, respiratory depression, decreased gastrointestinal motility, constipation, decreased then increased blood pressure, rapid heartbeat or heart palpitations, urinary retention, vasodilation, drowsiness, confusion, and agitation, and decreased sweating.^[18]^:45^[19]

antinuclear antibodies: (ANA) - "A circulating group of autoantibodies that are produced by the body when the immune system mistakenly recognizes normal components of its own cell nucleus as foreign."^[20]

antitussive: See expectorant.

ANZMES: See Associated New Zealand ME Society.

APA: See American Psychiatric Association.

apoptosis: a type of cell death in which a cell, in response to a threat, initiates a series of molecular steps that lead to its orderly death. This is one method the body uses to get rid of unneeded or abnormal cells. This form of cell suicide is also called programmed cell death.^[21]

APPG: See All-Party Parliamentary Group on Myalgic Encephalomyelitis.

assay: 1. (verb) analysis (as of an ore or drug) to determine the presence, absence, or quantity of one or more components.^[22] 2. (noun) In biochemistry, any laboratory protocol used to test a sample for one or more qualities.

Associated New Zealand ME Society: (ANZMES) - A New Zealand group for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients and their caregivers.

Association of Young People with ME: (AYME) - AYME was a UK national charity supporting children and young people affected by ME/CFS with members under 25. It's lead medical advisor was Doctor Esther Crawley. In April 2017 the charity merged with Action for ME, forming its Children's Services department run by Mary-Jane Willows.^[23]

atrophy: A decrease in size or wasting away of a body part, e.g. muscle wasting or progressive decline.^[24] (Learn more: me-pedia.org)

autoantibody: An antibody that works against the body's own antigens, a hallmark of autoimmune diseases. Autoantibodies are the opposite of an antibodies.^[25]^[20]^:40

AYME: See Association of Young People with ME.

B

B cell: B lymphocyte, or a type of white blood cell, which is involved in the immune response by secreting antibodies to ward off infections. In mammals, they are mostly matured in the bone marrow.^[26]

bias: Bias in research is "a systematic deviation of an observation from the true clinical state".^[5] (Learn more: me-pedia.org)

biomedical research: basic medical research on organisms, such as humans or other living things, that helps increase medical knowledge.^[27] (Learn more: me-pedia.org)

biopsychosocial model: (BPS) - A school of thought, usually based in psychology, which claims illness and disease to be the result of the intermingling of biological, psychological and social causes. (Learn more: me-pedia.org)

blinded trial: A clinical trial is blinded if either the participants or the researchers don't know which treatment group they are allocated to until after the results are interpreted.^[28]^[29] (Learn more: www.nottingham.ac.uk)

BMJ: The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

bodily distress disorder: See somatic symptom disorder.

BPS: See biopsychosocial model.

bradycardia: A slowness of the heartbeat, so that the pulse rate is less than 60 per minute in an adult.^[30]

brainstem: Region of the midbrain in adults, includes midbrain, pons, and medulla oblongata and develops.^[13]

Broca's area: Region of brain linked to the movement needed for speech. Within the front temporal lobe, In the side of the brain devoted to language (usually the left side).^[13]

C

Canadian Consensus Criteria: (CCC) - A set of diagnostic criteria used to diagnose ME/CFS, developed by a group of practicing ME/CFS clinicians in 2003. The CCC is often considered to be the most complex criteria, but possibly the most accurate, with the lowest number of patients meeting the criteria. Led to the development of the International Consensus Criteria (ICC) in 2011.^[31]

cardiopulmonary exercise test: See two-day cardiopulmonary exercise test.

cartilage: firm, whitish, flexible connective tissue found in various forms in the larynx and respiratory tract, in structures such as the external ear, and in the articulating surfaces of joints^[32]

CBT: See cognitive behavioral therapy.

CCC: See Canadian consensus criteria.

CDC: See Centers for Disease Control and Prevention.

cell membrane: A very thin membrane, composed of lipids and protein, that surrounds the cytoplasm of a cell and controls the passage of substances into and out of the cell.^[33]

Centers for Disease Control and Prevention: (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

central nervous system: (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

cerebellum: A part of the brain at the back of the skull in vertebrates, beneath the occipital lobe of the cerebrum. Its name reflects the fact that it looks like a smaller version of the cerebrum. Its main known functions are the coordination of unconscious muscle movements and the maintenance of body positional equilibrium.^[34]

cerebral: 1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.^[35]}

cerebral blood flow: (CBF) - the amount of blood that goes through the arterial tree in the brain in a given amount of time^[36]

cholinergic: Involving the neurotransmitter acetylcholine. Cholinergic side effects include diarrhea, blurred vision, decreased intraocular pressure, contricted pupil in the eyes, sweating, increased saliva and mucus on the lungs, bronchial constriction, increased gastrointestinal tone, decreased blood pressure, slow heart rate, and contraction of bladder detrusor muscle. muscle spasms/cramps, low blood pressure, slowed heart rate, nausea and vomiting, increased saliva and sweating, shortness of breath, and urinating more often.^[18]^[37]^[38]

CFIDS: See Chronic Fatigue and Immune Dysfunction Syndrome.

CFS: See chronic fatigue syndrome.

CFSAC: See Chronic fatigue syndrome advisory committee.

CFS/ME: See ME/CFS.

CFS/ME Research Collaborative: See UK CFS/ME Research Collaborative.

chronic disease: a disease or condition that usually lasts for 3 months or longer and may get worse over time.^[39] Chronic diseases are long-term (typically incurable and requiring long-term management) but are not necessarily severe.^[40]

chronic fatigue: (CF) - Persistent and abnormal fatigue is a symptom, not an illness. It may be caused by depression, multiple sclerosis, fibromyalgia, chronic fatigue syndrome or many other illnesses. The term "chronic fatigue" should never be confused with the disease chronic fatigue syndrome.^[31]

Chronic Fatigue and Immune Dysfunction Syndrome: (CFIDS) - Chronic Fatigue and Immune Dysfunction Syndrome is another term for Chronic Fatigue Syndrome, but one which emphasizes the immunological aspects of the disease. Popular in the 1990s, this term has apparently fallen into disuse.

chronic fatigue syndrome: (CFS) - A fatigue-based illness. The term CFS was invented invented by the U.S. Centers for Disease Control as an replacement for myalgic encephalomyelitis (ME). Some view CFS as a neurological disease, others use the term for any unexplained long-term fatigue without additional symptoms (idiopathic chronic fatigue). Sometimes used as a the term as a synonym of myalgic encephalomyelitis, despite the different diagnostic criteria.^[41]

Chronic Fatigue Syndrome Advisory Committee: (CFSAC) - (sometimes pronounced SIF-SACK) A US government advisory council that met twice per year, covering current topics related to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Meetings usually lasted for two days and the results were presented to the Secretary of Health and Human Services (HHS). After 15 years, on September 5, 2018, CFSAC's charter was not renewed by the Department of HHS, effectively dissolving the committee without notice or warning.^[42]

chronic illness: any long-term illness, regardless of the severity.^[43] Chronic illnesses are typically incurable, requiring long-term management.^[40]

circadian rhythm: Physical, mental, and behavioral changes that follow a 24-hour cycle, responding mostly to light and dark. Controlled the brain's hypothalamus.^[44] (Learn more: www.nigms.nih.gov)

coenzyme Q10: (CoQ10) - Coenzyme Q10 (also known as ubiquinone) is found in the mitochondria and, as a component of the electron transport chain, plays an important role in aerobic respiration. The chemically-reduced form of CoQ10 is called ubiquinol.

clivus: the smooth sloping surface on the upper posterior part of the body of the sphenoid bone supporting the pons and the basilar artery^[45]

cofactor: A substance that acts with another substance to bring about certain effects.^[46] In biochemistry, a cofactor is a molecule that is necessary for a given biochemical reaction, but is not an enzyme or substrate of the reaction.

cognition: Thought processes, including attention, reasoning, and memory.

collapse: See post-exertional malaise.

cognitive behavioral therapy: (CBT) - A type of psychotherapy geared toward modifying alleged unhealthy thinking, behaviors or illness beliefs. One of the treatment arms used in the controversial PACE trial.

conversion disorder: See somatic symptom disorder.

CoQ10: See coenzyme Q10.

CPET: See two-day cardiopulmonary exercise test.

crash: See post-exertional malaise.

creatine: (CR) - A natural substance that turns into creatine phosphate in the body, which helps make ATP. ATP provides the energy for muscles Often taken as a supplement to improve sports performance.^[47] (Learn more: www.webmd.com)

cytokine: any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system.^[48] (Learn more: me-pedia.org)

cytokine storm: an uncontrolled, sometimes life-threatening, excessive immune response, involving very high levels of proinflammatory cytokines and widespread tissue damage.^[49]^[50]

cytomegalovirus: (CMV) - A common herpesvirus found in humans. Like other herpesviruses, it is a life-long infection that remains in a latent state inside the human body, until it is 'reactivated' by appropriate conditions. CMV infects between 60% to 70% of adults in industrialized countries and close to 100% in emerging countries. Much is unknown about this virus, although it has been found in salivary glands and myeloid blood cells such as monocytes. It has also been linked to the development of certain cancers. Congenital CMV is a leading infectious cause of deafness, learning disabilities, and intellectual disability. A common treatment for CMV is valganciclovir, commonly known as Valcyte.^[51]

D

Diagnostic and Statistical Manual of Mental Disorders: (DSM) - A psychiatric reference book published by the American Psychiatric Association, often referred to as "the psychiatrist's Bible". Although the most recent version (DSM-5) purports to be the authoritative guide to the diagnosis of mental disorders, the editors of both previous versions of the manual have heavily criticized the current version due to the climate of secrecy that shrouded the development of the latest version. 69% of the people who worked on DSM-5 reported having ties to the pharmaceutical industry.^[52] Dr. Allen Frances, who headed the development of the previous version, warned of dangerous unintended consequences such as new false 'epidemics'.^[53] The British Psychological Society criticized DSM-5 diagnoses as "clearly based largely on social norms, with 'symptoms' that all rely on subjective judgements" and expressed a major concern that "clients and the general public are negatively affected by the continued and continuous medicalisation of their natural and normal responses to their experiences". A petition signed by over 13,000 mental health professionals stated that the lowered diagnostic thresholds in DSM-5, combined with entirely subjective criteria based on western social norms, would "lead to inappropriate medical treatment of vulnerable populations".^[54] The director of the US National Institute of Mental Health, Dr. Thomas R. Insel, pointed out that the diagnoses in DSM-5 had no scientific validity whatsoever.^[55] (Learn more: www.scientificamerican.com)

dorsal root ganglion: (DRG) - A group of nerve cells in the spinal cord.^[56] (Learn more: www.ncbi.nlm.nih.gov)

double blinded trial: A clinical trial is double blinded if neither the participants nor the researchers know which treatment group they are allocated to until after the results are interpreted. This reduces bias.^[28]^[29] (Learn more: www.nottingham.ac.uk)

DSM-5: See Diagnostic and Statistical Manual of Mental Disorders.

dysautonomia: disorders of the autonomic nervous system that cause disturbances in all or some autonomic functions, may cause problems regulating autonomic functions, including heart rate, blood pressure, body temperature, and digestion.^[57] Can cause symptoms including lightheadedness, fainting, unstable blood pressure, and orthostatic intolerance.^[58]

E

endogenous: Growing or originating from within an organism.^[59]

Energy Envelope Theory: A self-management tool developed and tested by Dr. Leonard Jason to reduce symptom severity and the frequency of post-exertional malaise or relapses for people with ME/CFS. According to this theory, ME/CFS patients should not expend more energy than they perceive they have, as this results in post-exertional malaise and higher disability. Instead patients are advised to stay within their energy envelope, meaning the physical limits the disease has imposed upon them.^[60] As the energy envelope theory also cautions about the dangers of under-exertion, its principles are almost identical to ‘pacing’, an activity management strategy for ME patients devised by Ellen Goudsmit in the UK.^[61]

enterovirus: A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

enzyme: a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.^[62]

epigenome: all of the chemical compounds that are not part of the DNA sequence, but are on or attached to DNA as a way to regulate gene activity^[63]

etiology: The cause of origin, especially of a disease.^[64]

eukaryote: any cell or organism that possesses a clearly defined nucleus, unlike bacteria.^[65] Eukaryotes include yeast, fungus, plants, and animals.

exosome: See extracellular vesicle.

expectorant: An antitussive is a cough suppressant, an expectorant is a cough suppressant that helps someone discharge or cough up mucus.^[66]^[67]

extracellular vesicle: An extracellular vesicle (sometimes abbreviated EV) is a piece of a cell that has broken off and formed a separate membrane-bound vesicle. A membrane-bound vesicle is like a bubble, or like a mini-cell, in that it has a membrane surrounding some liquid. An extracellular vesicle may also contain some parts of the cell from which the extracellular vesicle arose. There are currently two types of extracellular vesicles: "exosomes" and "microvesicles". An "exosome" is an extracellular vesicle that began inside the cell as an intracellular vesicle known as an "endosome". A "microvesicle" is an extracellular vesicle that begins at the cell surface, and pinches off the cell's own membrane to form a separate vesicle.^[68] (Learn more: journals.physiology.org)

F

flare-up: A symptoms flare in ME/CFS is a temporary increase in symptoms, alternatively known as experiencing post-exertional malaise.^[69]^[70] May be referred to as a "crash" or "collapse".

foramen magnum: the large opening in the skull through which the spinal cord passes to merge with the lower brain^[71]

Fukuda criteria: The most commonly used diagnostic criteria for chronic fatigue syndrome, created by the United States Centers for Disease Control (CDC).^[72]

G

ganglion: A ganglion is a group of neuron cell bodies in the peripheral nervous system. Plural: ganglia / ganglions^[73]

gaslighting: gaslighting is a form of emotional abuse which involves persistently denying or refusing to accept facts, and frequently leads to the other person doubting their own experiences.^[74] Medical gaslighting is when doctors or health health blame a patient's symptoms on psychological factors or deny the patient's illness entirely, for example wrongly telling patients that they are not sick.^[75]

genome: an organism's complete set of DNA, including all of its genes^[76]

GET: See Graded exercise therapy.

glutamate: (Glu) - Glutamate is one of the amino acids used by the body to make proteins. It is a salt or ester of glutamic acid, and the terms glutamate and glutamic acid are often used interchangeably. It also functions as the principal excitatory neurotransmitter in the brain.^[77]^[78]

glutamic acid: See glutamate.

graded exercise therapy: (GET) - A gradual increase in exercise or activity, according to a pre-defined plan. Focuses on overcoming the patient's alleged unhelpful illness beliefs that exertion can exacerbate symptoms, rather than on reversing physical deconditioning. Considered controversial, and possibly harmful, in the treatment or management of ME. One of the treatment arms of the controversial PACE trial.^[79]

gray matter hyperintensity: See T2 hyperintensity.

green, leafy vegetables: A group of vegetables with many health benefits. Includes spinach, kale, arugula (rocket), collard greens, romaine lettuce, bok choy, mustard greens and chard. Too many may reduce the effects of perscription blood thinners.^[80]

H

heart rate: (HR) - the number of times the heart beats within a certain time period, usually a minute^[81]

heart rate monitor: (HRM) - A device that measures your heart rate (pulse rate). Heart rate monitors may come as a chest strap, wrist strap, smartwatch, or even as a mobile phone app. Heart rate monitors are often used by ME/CFS patients to pace their exertion, in order to avoid post-exertional malaise (PEM). For more information, see pacing with a heart rate monitor.

heart rate variability: (HRV) - A measurement of the variability of the heart rate over time. When the heart rate is consistent, there will be a low heart rate variability. When the heart rate is constantly changing, there will be a high heart rate variability. Heart rate variability is often used by ME/CFS patients to monitor their autonomic nervous system, as high heart rate variability is associated with the sympathetic nervous system and low heart rate variability is associated with the parasympathetic nervous system.

hepatic: involving or associated with the liver^[82]

hippocampus: The hippocampus consists of gray matter deep in the temporal lobe of the brain. Very important for forming long-term memories. Plural: hippocampi.^[13]

HLA complex: See human leukocyte antigen complex.

holistic: Treating mind, body and spirit together, with the aim of achieving wellness and good health.^[83] May be within modern medicine or alternative / traditional medicine.

homeopathy: Alternative medicine based on the idea that the lower the dose of medication, the more effective it is. Many homeopathic remedies are so diluted that none of the original substance remains. Others may contain substantial amounts of active ingredients that may cause side effects or drug interactions.^[83] (Learn more: www.nccih.nih.gov)

homeostasis: the maintenance of stable internal biological conditions (e.g. body temperature) in a changable environmen^[84]

HRV: See heart rate variability.

human leukocyte antigen complex: (HLA) - A set of genes responsible for a given person's immune response to potential threats. Specifically, HLA genes encode proteins which help the immune system to distinguish the body's own proteins from proteins which are made by foreign invaders like bacteria and viruses. The HLA complex can vary greatly from person to person, generating unique immune and allergic responses. (Learn more: mecfsresearchreview.me)

hyperintensity: See T2 hyperintensity.

hypoglycemia: abnormal decrease of sugar in the blood^[85]

hypothalamus: Major region of the brain that coordinates autonomic and endocrine control of homeostasis.^[13]

I

iatrogenesis: Accidental harm caused by a doctor, by medical treatment, or by diagnostic procedures.^[86]

ICC: See International Consensus Criteria.

ICD: See International Classification of Diseases.

immunoglobulin: See antibody.

immunologist: A clinical immunologist is medical doctor specializing immune system problems that lead to infections, immunodeficiency disorders, autoimmune diseases, and autoinflammatory diseases including anaphylaxis ans allergies^[87]

immunomodulator: An immunomodulator is a substance that affects the functioning of the immune system^[88]

indole: (IDO) - a signalling molecule produced by bacteria as a result of metabolising tryptophan, found in the intestines^[89]^[90]^[91]

indoleproprionate: (IPA) - a small molecule produced in the gut, has anti-inflammatory and antioxidant properties^[92]^[93]

indoleamine: (IDO) - any derivatives of an indole (e.g., serotonin, tryptophan) that contain an amine group^[94]

Institute of Medicine: See National Academy of Medicine.

Institute of Medicine report: (IOM report) - A report that was commissioned by the U.S. government and was published by the Institute of Medicine on February 10, 2015. The report was titled "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" and proposed the term Systemic Exertion Intolerance Disease (SEID). Among its key findings were that "This disease is characterized by profound fatigue, cognitive dysfunction, sleep abnormalities, autonomic manifestations, pain, and other symptoms that are made worse by exertion of any sort." The report further stated "Between 836,000 and 2.5 million Americans suffer from myalgic encephalomyelitis/chronic fatigue syndrome."

International Classification of Diseases: (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)

International Consensus Criteria: (ICC) - A set of diagnostic criteria, based on the Canadian Consensus Criteria, that argued for the abandonment of the term "chronic fatigue syndrome" and encouraged the sole use of the term "myalgic encephalomyelitis".

invisible illness: A chronic condition or illness, such as ME/CFS, which may not be apparent to others. Sufferers may look healthy, yet be in poor health. Symptoms of the illness may not be visible and can be misunderstood or go unnoticed by others. Also, patients may wind up secluded or homebound due to the illness and become "invisible". (Learn more: me-pedia.org)

IOM: See National Academy of Medicine.

J

K

kinesiophobia: excessive and irrational fear of physical movement due to fear of painful injury or reinjury.^[95]^[96] (Learn more: me-pedia.org)

L

leafy greens: See green, leafy vegetables.

ligament: the tissue that connects two or more bones at a joint^[97]

lightheadedness: the condition of being dizzy or on the verge of fainting^[98]

limbic cortex: Part of the brain (within the cerebral cortex) involved in emotion, memory and behavior. Part of the limbic system.^[73]

limbic system: The limbic system is a group of structures between the forebrain and hindbrain mostly linked to emotions, memories and behavior. Includes the amygdala, limbic cortex, hypothalamus, cingulate gyrus, parahippocampal gyrus, hippocampus and hippocampal formation, dentate gyrus, subicular complex and septal area.^[73]^[99]

M

magnetic levitation device: A device which uses ferrofluid (a liquid which can become magnetized) in a glass capillary tube surrounded by magnets. This creates a density gradient and cells move to their respective densities within the tube. According to Ron Davis, white blood cells in CFS patients may be less dense than those of healthy controls, indicating the possible use of the device as an inexpensive diagnostic test. (Learn more: www.omf.ngo)

mass spectrometer: A device which converts molecules to ions, or charged particles. It then uses magnetic and electric fields to sort the ions according to their mass (similar to weight) and charge, in order to identify the molecules or measure their characteristics.

mastocytosis: A type of mast cell disease in which chronic symptoms are related to overproduction or over-accumulation of mast cells. Not to be confused with Mast Cell Activation Syndrome (MCAS), where there are normal numbers of mast cells, but abnormal activity.^[100]

ME: See myalgic encephalomyelitis.

ME/CFS: An acronym that combines myalgic encephalomyelitis with chronic fatigue syndrome. Sometimes they are combined because people have trouble distinguishing one from the other. Sometimes they are combined because people see them as synonyms of each other.

ME/CFS Severely Ill, Big Data Study: See Severely Ill Patient Study.

medically unexplained physical symptoms: (MUPS) - Technically, this term means that no cause or explanation for the patient's symptoms has yet been found. However, patients diagnosed with "MUPS" are generally lumped into a psychosomatic, or psychologically-caused category by those in the medical profession, without any scientific basis for doing so.

medically unexplained symptoms: See medically unexplained physical symptoms.

membrane: The word "membrane" can have different meanings in different fields of biology. In cell biology, a membrane is a layer of molecules that surround its contents. Examples of cell-biology membranes include the "cell membrane" that surrounds a cell, the "mitochondrial membranes" that form the outer layers of mitochondria, and the "viral envelope" that surrounds enveloped viruses. In anatomy or tissue biology, a membrane is a barrier formed by a layer of cells. Examples of anatomical membranes include the pleural membranes that surrounds the lungs, the pericardium which surrounds the heart, and some of the layers within the blood-brain barrier.

metabolic trap hypothesis: An hypothesis which proposes that the normal metabolic functioning of the cell has become "trapped" in an abnormal state, which may lead to body-wide symptoms.

metabolite: A chemical compound produced by, or involved in, metabolism. The term is often used to refer to the degradation products of drugs in the body.

metabolomics: The analysis of the chemical metabolism within cells, tissues or organisms. The term is often used to refer to the full set of metabolites found in a cell in a given environment.

microbiome: The full collection of microscopic organisms (especially bacteria and fungi) which are present in a particular environment, particularly inside the human body.^[101]

microglia: A type of immune cell, called a macrophage, that lives in the brain. For historical reasons, macrophages have different names based on the part of the body that they normally live in. Macrophages that normally live in the blood are called monocytes. Macrophages that normally live in the skin are called Langerhans cells. Macrophages that normally live in the liver are called Kupffer cells. And macrophages that normally live in the central nervous system are called microglia. Microglia were originally classified as glial cells, under the assumption that the cells had a merely structural function, before it was realized that the cells were in fact immune cells. As the "sentinel cells" of the central nervous system, microglia survey their environment for abnormalities such as infection or tissue damage, and then initiate an immune response to fight the infection or repair the tissue damage.^[102]

migraineur: Someone who experiences migraines^[103] (Learn more: www.merriam-webster.com)

microvesicle: See extracellular vesicle.

Millions Missing: A global campaign, first led by #MEAction in May 2016, which aims to gain awareness, community, education, research, funding and treatment equality for Myalgic Encephalomyelitis. The campaign uses the hashtag #MillionsMissing on Twitter.

mitochondria: Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

mitochondrion: See mitochondria.

morphology: The form and structure of plants and animals. A branch of biology.^[104]

mouse model: The use of special strains of mice to study a human disease or condition, and how to prevent and treat it^[105]

MUPS: See medically unexplained physical symptoms.

MUS: See medically unexplained physical symptoms.

muscle atrophy: See atrophy.

myalgia: Muscle pain^[106]

myalgic encephalomyelitis: (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome.^[70] A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.^[107]

myalgic encephalopathy: An alternate term that is sometimes used for myalgic encephalomyelitis, by people who believe the evidence for inflammation in ME is insufficient. This terminology reflects the belief that the "-itis" suffix implies inflammation.

myocarditis: inflammation of the heart muscle^[108]

mycotoxin: "a poisonous substance produced by a fungus and especially a mold"^[109]

N

NAM: See National Academy of Medicine.

nanoneedle: A device with microscopic dimensions which measures electrical impedance across a blood cell. According to Ron Davis, the nanoneedle measured increased electrical impedance in the blood cells of 10 ME/CFS patients when stressed with salt, but not in healthy controls. Accordingly, this device has been proposed as a potential diagnostic test to distinguish ME/CFS patients from healthy controls. (Learn more: www.omf.ngo)

nanotechnology: Nanotechnology is the science used to make things that are extremely small and can only be seen using a microscope.^[110]

NASA 10-minute lean test: A variation of a test used by NASA researchers to test for orthostatic intolerance. A simple test which is recommended by the Bateman Horne Center for ME and Fibromyalgia patients. (Learn more: batemanhornecenter.org)

National Academy of Medicine: (NAM) - An American non-profit, non-governmental organization which provides expert advice to governmental agencies on issues relating to biomedical science, medicine and health. Formerly known as the Institute of Medicine (IOM).

National Institutes of Health: (NIH) - A set of biomedical research institutes operated by the U.S. government, under the auspices of the Department of Health and Human Services.

naturopath: a practitioner who uses a system of treatment of disease that avoids drugs and surgery and emphasizes the use of natural agents (such as air, water, and herbs) and physical means (such as tissue manipulation and electrotherapy)^[111]

neoplasm: tumor^[112]

neuroendocrine: relating to hormones that influence the nervous system^[113]

NICE guidelines: Clinical guidelines used in the UK.^[114]

NIH: See National Institutes of Health.

nocturia: urination at night especially when excessive^[115]

O

objective outcome: An outcome of a clinical trial that is independent of the judgement of opinion of the assessor/clinician, e.g. distance walked in 6 minutes. Patient-reported outcomes like questionnaires are not objectives.^[116]

orthostatic intolerance: (OI) - The development of symptoms when standing upright, where symptoms are relieved upon reclining. Patients with orthostatic intolerance have trouble remaining upright for more than a few seconds or a few minutes, depending upon severity. In severe orthostatic intolerance, patients may not be able to sit upright in bed. Orthostatic intolerance is often a sign of dysautonomia. There are different types of orthostatic intolerance, including postural orthostatic tachycardia syndrome (POTS).

Oxford criteria: A set of diagnostic criteria for chronic fatigue syndrome. These criteria focus on "fatigue" as the defining symptom.

Oxford University: a prestigious university located in Oxford, England renowned for its teaching and research in health and medicine^[117]

oxidative phosphorylation: (OXPHOS) - The oxidative phosphorylation pathway produces more than 95% of a cell's energy in the form of ATP. This is done by the mitochondria, in a process called chemiosmosis.^[118]^[119]^[120]

P

PACE trial: A controversial study which claimed that CBT and GET were effective in treating "CFS/ME", despite the fact that its own data did not support this conclusion. Its results and methodology were widely disputed by patients, scientists, and the peer-reviewed scientific literature.

pacing: The practice of staying within one's "energy envelope" or personal limit by combining periods of activity with periods of rest or avoiding exerting beyond a certain level. ME/CFS patients use pacing to avoid or reduce post-exertional malaise (PEM). Some patients use a heart rate monitor to help with pacing.

PEM: See post-exertional malaise.

PENE: See post-exertional neuroimmune exhaustion.

perivascular space: See Virchow-Robin space.

pharyngitis: An irritation or swelling of the top part of the throat, at the back of the mouth, usually caused by an infection such as Streptococcus. The hallmark symptom is a sore throat without cough.^[121]^[122]

phase one: A drug trial involving only a small group of humans, often healthy volunteers, to assess drug safety and side effects. Typically 20-80 participants, often using a comparison group.^[123]^[124]^[125]

phase two: A trial involve patients to assess side effects and effectiveness for a particular clinical condition. Typically 100-300 patients.^[123]^[124]^[125]

phase three: Last phase of clinical trials before a drug can be approved for public use. Whereas Phase one assesses basic safety, and Phase two assesses basic efficacy, Phase three uses many trial participants to fully assess both safety and efficacy, and overall benefit/risk.^[123]

phase four: Carried out after a drug is FDA-approved, including postmarket requirements and studies required by the study sponsor. Phase IV trials collect additional information about a drug's safety, efficacy, or optimal use.^[123]

photophobia: Light intolerance, including feeling pain from strong light.^[126] (Learn more: www.merriam-webster.com)

phonophobia: Sound intolerance or hypersensitivity, e.g. during a migraine.^[127] (Learn more: www.merriam-webster.com)

physiological: Concerning living organisms, such as cells or the human body.^[128] Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

physiological stress: The stress placed on living organisms, such as cells or people, e.g. the result of an injury to the body, surgery, walking outside in cold and wet conditions without a coat, or malnutrition.^[129] Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

PI-ME/CFS: Post-Infectious ME/CFS, a term used by NIH for the NIH Post-Infectious ME/CFS Study (Intramural ME/CFS Study) (Learn more: me-pedia.org)

plasma: The liquid part of blood, lymph, or milk after removing any suspended material.^[130] Most of the time, "plasma" simply refers to blood, after all the blood cells have been removed. If you also remove the clotting factors, then the plasma is referred to as "serum".

plasma membrane: See cell membrane.

platelet: (also known as a thrombocyte) A colorless disk-like blood cell that assists in blood clotting by adhering to other platelets and to damaged linings of blood vessels.^[131] Simply put, platelets clump together to form blood clots. (A blood clot is also called a thrombus.) People with low levels of platelets may have trouble with blood clotting, and may bleed easily from minor wounds.

placelet-activating factor: (PAF) - "A cytokine involved in a number of processes, especially platelet aggregation, inflammation, and anaphylaxis, which is released from a variety of cells including basophils and neutrophils."^[132]^[133]

post-exertional malaise: (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

post-exertional neuroimmune exhaustion: (PENE) - An alternative term for post-exertional malaise (PEM), used by people who find that the word 'malaise' fails to capture the serious nature of the condition. Used in the Institute of Medicine (IOM) report.^[134]

postural orthostatic tachycardia syndrome: (POTS) - A form of orthostatic intolerance where the cardinal symptom is excessive tachycardia due to changing position (e.g. from lying down to sitting up).

POTS: See postural orthostatic tachycardia syndrome.

presyncope: The sensation that one is about to faint and lose consciousness. It usually is described as a severe lightheaded feeling, often associated with unsteadiness or falling. The sensation arises because the cerebral cortex is temporarily not receiving adequate oxygen, usually because of diminished blood flow.^[135]

prion: A protein with an unknown function that lives on the surface of brain cells. Abnormal proteins linked to disease are all known as prions.^[136]

projection: 1. In psychology, a defense mechanism involves attribution unpleasant feelings to another person. May be abusive, e.g., a person accusing someone else of something that they themselves are doing or feeling. Often linked to gaslighting.^[137]
2. Estimate or forecast based on trends.
3. Something that extends out from something else.
4. How something is presented.^[138]^[139] (Learn more: www.forbes.com)

prolcatin: (PRL) - Hormone released by the anterior pituitary gland to cause milk production in females.^[140] (Learn more: www.forbes.com)

protozoa: Protozoa are microscopic organisms. They usually exists as a single, independent cell. Examples include the parasites giardia lamblia, toxoplasma gondii and babesia.^[141]^[142]

psychosomatic: See somatic symptom disorder.

PwME: Acronym for a "Person with ME" (myalgic encephalomyelitis).

Q

R

Ramsay definition: A clinical definition of myalgic encephalomyelitis (ME) developed by Melvin Ramsay after 30 years of treating and researching ME patients. Since this definition was in place before the U.S. Centers for Disease Control invented the term "chronic fatigue syndrome", the Ramsay definition is sometimes considered the last clinical definition that may be unbiased by the ensuing diagnostic confusion.

regional cerebral blood flow: (rCBF) - The amount of blood flow to a specific area of the brain in a particular period of time.^[143]

renal: involving, related to or in the area of the kidneys^[144]

randomized controlled trial: (RCT) - A trial in which participants are randomly assigned to two groups, with one group receiving the treatment being studied and a control or comparison group receiving a sham treatment, placebo, or comparison treatment.^[145]

RCT: See randomized controlled trial.

S

seahorse analyzer: An instrument which measures oxygen consumption rate and extracellular acidification rate in live cells, in real time, producing information regarding important cellular functions such as mitochondrial respiration and glycolysis.

SEID: See systemic exertion intolerance disease.

serum: The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)^[146]

Severely Ill Big Data Study: See Severely Ill Patient Study.

Severely Ill Patient Study: (SIPS) - A study funded by the Open Medicine Foundation and led by Ron Davis and Wenzhong Xiao. It includes over 1000 tests per patient, including the patients' genome, gene expression, metabolomics, microbiome, and others. Formerly known as the ME/CFS Severely Ill Big Data Study. (Learn more: www.omf.ngo)

SF-36: See Short Form 36-Item Health Survey.

Short Form 36-Item Health Survey: (SF-36) - A 36-item patient-reported questionnaire, used to determine patient health status and quality of life.

side effect: See adverse reaction.

single nucleotide polymorphism: (SNP) - A single nucleotide polymorphism (SNP, pronounced "snip") is a potential genetic mutation that occurs in a single spot in the human genome; a difference in a single DNA building block.^[147]^[148] SNPs are often represented by an "rs" number, such as "rs53576".^[149]

SNP: See single nucleotide polymorphism.

Social Security Administration: (SSA) - SSA is the United States government department for disability benefits, unemployment, and social security/welfare that handles SSD and SSI disability payments.

social security disability: (SSD) - United States government disability benefits. Used for those who have previously paid tax and is not means tested. (Learn more: me-pedia.org)

somatic: An adjective relating to the physical body or physical symptoms. It is often contrasted with the adjective "psychological", which refers to the human mind or mental symptoms. In biology, "somatic cells" refer to all the cells of the body, except those which form an egg or sperm.

somatic symptoms: Physical or bodily symptoms. May be used to mean bodily symptoms that are not the result of a known physical or biological illness.^[150]^[151]

somatic symptom disorder: A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

Although "Somatic Symptom Disorder" is the term used by DSM-5, the term "Bodily Distress Disorder" has been proposed for ICD-11.^[152]^[153] (Learn more: www.psychologytoday.com)

somatization: See somatic symptom disorder.

somatoform disorder: See somatic symptom disorder.

somnolence: Drowsiness or a state of "near-sleep", a strong desire for sleep, or oversleeping.^[154]

spoon theory: An analogy which equates the amount of ability that someone with chronic illness has to complete daily tasks to a limited number of spoons. People with chronic illnesses who must ration their energy throughout the day are sometimes referred to as "spoonies".^[155] (Learn more: butyoudontlooksick.com)

spoonie: See spoon theory.

sprain: an injury involving a stretched or torn ligament (the tissue that connects two or more bones at a joint is stretched or torn).^[97]

muscle strain: An injury involving a stretched or torn muscle or tendon (tendons are fibrous cords of tissue that connect muscle to bone).^[97]

stress: Stress can by either physical or psychological, or both.^[129] Stress is either 1) a state of emotional or psychological strain or 2) the physical stress (pressure or tension) that a physical object such the human body is placed under, e.g., a stress test is a medical test that monitors the cardiovascular system during strenuous exercise.^[128]^[156]

stress fracture: A tiny crack in a bone caused by repetitive forces such as running or by normal use of a bone that's weakened by a condition such as osteoporosis.^[157]

subcortical hyperintensity: See T2 hyperintensity.

subcutaneous: "being, living, occurring, or administered under the skin"^[158]

subjective outcome: An outcome of a clinical trial that depends on the judgement or opinion of the assessor or patient, e.g. asking if fatigue has increased or decreased "a little" or "a lot", patient questionnaires like the Chalder Fatigue Scale, and other patient-reported outcome measures (PROMs).^[116]

subluxation: partial dislocation (as of one of the bones in a joint), common in Ehlers-Danlos Syndromes^[159]

supine: lying on the back or with the face upward^[160]

supplementary security income: (SSI) - United States government disability benefit for those who have not enough work history to claim SSD, including children. Provides payments to adults and children with a disability. Means tested. (Learn more: me-pedia.org)

syncope: A medical term for fainting. A loss of consciousness resulting from insufficient blood flow to the brain.^[161]

systemic exertion intolerance disease: (SEID) - A term for ME/CFS that aims to avoid the stigma associated with the term "chronic fatigue syndrome", while emphasizing the defining characteristic of post-exertional malaise (PEM). SEID was defined as part of the diagnostic criteria put together by the Institute of Medicine (IOM) report of 10 February 2015.^[162]

T

T cell: A type of white blood cell which is mostly produced or matured in the thymus gland (hence T-cell) and is involved in the adaptive immune response on a cellular level. Also known as a T lymphocyte. (Learn more: www.youtube.com)

T2 hyperintensity: An unusual bright spot on a T2-weighted MRI of the brain. Also known as an Unidentified Bright Object (UBO). T2 hyperintensities are often found in the periventricular region, where they may be referred to as "white matter hyperintensities" or "leukoaraiosis". They may also be found in the basal ganglia or brainstem, where they are sometimes referred to as "gray matter hyperintensities", or "subcortical hyperintensities". T2 hyperintensities can represent different things: lesions, dilated Virchow-Robin spaces, or demyelination. They are commonly found in elderly individuals and in neurological disorders. (Learn more: www.ncbi.nlm.nih.gov)

tachycardia: An unusually rapid heart beat. Can be caused by exercise or illness. A symptom of postural orthostatic tachycardia syndrome (POTS).^[163] (Learn more: www.heart.org)

tendon: a fibrous cord of tissue that connects muscle to bone.^[97]

tilt table test: A diagnostic test to determine orthostatic intolerance or other forms of dysautonomia. The patient is strapped to a table and the table is tilted while the patient is monitored.

two-day cardiopulmonary exercise test: (CPET) - A diagnostic test which involves testing an ME/CFS patient exercising on an exercise machine, while monitoring their respiration, especially oxygen consumption. This test is repeated the following day in order to confirm the patient's inability to replicate the first-day performance. This test is thought to be the most objective way to detect post-exertional malaise.

U

ubiquinol: See coenzyme Q10.

ubiquinone: See coenzyme Q10.

UK CFS/ME Research Collaborative: (CMRC) - A UK group of researchers and ME/CFS patient groups led by Professor Stephen Holgate.^[164] Its launch in 2013 was covered by the Science Media Centre.^[165] Since 2014, the collaborative sponsors the CFS/ME Research Collaborative Conference.

Unidentified Bright Object: See T2 hyperintensity.

V

vertigo: An illusion of movement, typically whirling, spinning or tilting.^[166]

vesicle: In cell biology, a vesicle is any "bubble" of liquid surrounded by a layer of molecules forming an enclosing membrane.

Virchow-Robin space: A space inside the blood-brain barrier that surrounds blood vessels. They are also known as perivascular spaces. Immune cells from the blood often enter the Virchow-Robin space, but are unable to enter the brain. In cases of neuroinflammation, immune cells may accumulate in the Virchow-Robin space, unable to enter the brain. This accumulation of immune cells (called perivascular cuffing) may lead to an enlarged Virchow-Robin space. Enlarged Virchow-Robin spaces may be visible in an MRI image of the brain.^[167]

virome: The human virome is the collection of all viruses that are found in or on humans.^[168]

VO2 Max: (VO2max) - the maximum amount of oxygen the body can utilize during a specified period of usually intense exercise (Volume of O2 Maximal)^[169]

W

white matter hyperintensity: See T2 hyperintensity.

WHO: See World Health Organization.

World Health Organization: (WHO) - "A specialized agency of the United Nations that is concerned with public health. It was established on 7 April 1948, and is headquartered in Geneva, Switzerland. The WHO is a member of the United Nations Development Group. Its predecessor, the Health Organization, was an agency of the League of Nations." The International Statistical Classification of Diseases and Related Health Problems (ICD) is maintained by WHO.^[170]

X

Y

Z

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