Glossary
ME/CFS research glossary
Definitions of key terms used in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) research and across the atlas — including diagnostic criteria, biomedical mechanisms, case definition terminology, and evidence classification.
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Autonomic dysfunction
Impaired regulation of the autonomic nervous system — the network governing heart rate, blood pressure, digestion, and other automatic body functions. In ME/CFS, autonomic dysfunction commonly presents as orthostatic intolerance, POTS, and reduced heart rate variability.
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Biomarker
A measurable biological indicator — such as a protein level, gene expression pattern, metabolite concentration, or imaging finding — that correlates with a disease state or process. Identifying reliable biomarkers for ME/CFS is a major research priority.
Browse related research →Brain fog
A colloquial term for cognitive impairment in ME/CFS, characterised by difficulties with attention, working memory, information processing speed, and word retrieval. Research has documented objective cognitive abnormalities in ME/CFS patients in addition to subjective complaints.
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Canadian Consensus Criteria (CCC)
A 2003 diagnostic framework for ME/CFS requiring post-exertional malaise as a mandatory criterion, along with fatigue, sleep dysfunction, pain, neurological/cognitive manifestations, and at least one autonomic, neuroendocrine, or immune symptom. Widely considered the most clinically specific of the major case definitions.
Browse related research →Case definition quality
In the atlas, case definition quality (Strict / Adequate / Weak / Unclear) reflects whether a study used a diagnostic framework requiring post-exertional malaise and other core ME/CFS features. Studies with strict case definitions identify a more homogeneous patient population.
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Dysautonomia
A broad term for conditions involving dysfunction of the autonomic nervous system, including postural orthostatic tachycardia syndrome (POTS), orthostatic intolerance, and heart rate variability impairment. Dysautonomia is common in ME/CFS and Long COVID.
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Endothelial dysfunction
Impaired function of the endothelium — the inner lining of blood vessels — affecting vascular tone, blood flow regulation, and clotting. Increasingly studied in ME/CFS and Long COVID as a potential contributor to circulatory symptoms and post-exertional impairment.
Evidence level (E0–E3)
The atlas classifies studies by evidence level based on study design and replication status. E0: systematic reviews and meta-analyses. E1: replicated human evidence from multiple independent studies. E2: single-study or moderate-quality observational evidence. E3: preliminary, preprint, or mechanistic findings. Higher levels indicate stronger and more generalisable findings.
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Fukuda criteria
The 1994 CDC case definition for chronic fatigue syndrome, requiring six or more months of unexplained fatigue plus four of eight additional symptoms. Does not require post-exertional malaise. Captures a broader and more heterogeneous population than CCC or ICC, which affects the generalisability of findings to core ME/CFS.
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HPA axis (hypothalamic-pituitary-adrenal axis)
The neuroendocrine system regulating cortisol production and the body’s stress response. ME/CFS research has documented consistent patterns of HPA axis dysregulation, including mild hypocortisolism, attenuated diurnal cortisol variation, and blunted stress responsiveness.
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International Consensus Criteria (ICC)
A 2011 case definition for ME/CFS that requires post-exertional malaise as a primary criterion and explicitly uses the term “myalgic encephalomyelitis.” Generally considered to identify a more severely ill and homogeneous patient population than Fukuda criteria.
Browse related research →IOM / SEID criteria
The 2015 Institute of Medicine criteria, proposing the name “systemic exertion intolerance disease” (SEID). Requires post-exertional malaise, impaired function, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance alongside profound fatigue. Widely influential in clinical and research settings.
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Metabolomics
The large-scale study of small molecules (metabolites) in biological samples such as blood, urine, or cerebrospinal fluid. Metabolomics analyses in ME/CFS have identified altered energy metabolism profiles consistent with mitochondrial dysfunction and cellular energy stress.
Browse related research →Mitochondrial dysfunction
Impairment in the function of mitochondria — the cellular organelles responsible for energy production (ATP synthesis). Documented in ME/CFS research and proposed as a mechanism underlying cellular energy limitations, fatigue, and post-exertional malaise.
Browse related research →Multi-omics
The combined analysis of multiple biological data types — such as genomics, transcriptomics, proteomics, and metabolomics — to identify patterns associated with disease. Multi-omics approaches are increasingly used in ME/CFS research to identify patient subgroups and biomarker candidates.
Browse related research →Myalgic encephalomyelitis (ME)
The medical name for ME/CFS, reflecting neurological and immunological involvement. “Myalgic” refers to muscle pain; “encephalomyelitis” refers to inflammation involving the brain and spinal cord. The name is used in the International Consensus Criteria (2011) and reflects the biomedical character of the illness.
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Neuroinflammation
Inflammation in the central nervous system, involving activation of microglia — the brain’s resident immune cells. PET imaging studies have documented evidence of neuroinflammation in ME/CFS patients, with implications for cognitive impairment, sensory sensitivity, and neurological symptoms.
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Oxford criteria
A 1991 case definition for CFS requiring only unexplained fatigue as its primary criterion, with no requirement for post-exertional malaise or other ME/CFS-specific features. Associated with high rates of diagnostic heterogeneity and considered the weakest of the major case definitions for identifying core ME/CFS.
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PASC (post-acute sequelae of SARS-CoV-2)
The clinical term for Long COVID — persistent symptoms lasting four weeks or more after the acute phase of COVID-19 infection. A significant proportion of PASC patients meet diagnostic criteria for ME/CFS, and research into PASC has directly informed understanding of ME/CFS mechanisms.
Browse related research →PEM (post-exertional malaise)
The worsening of ME/CFS symptoms following physical, cognitive, or emotional exertion, typically delayed by hours to days. PEM is the defining diagnostic criterion of ME/CFS under the Canadian Consensus Criteria, International Consensus Criteria, and IOM 2015 guidelines, and distinguishes ME/CFS from most other fatiguing conditions.
Browse related research →Post-infectious illness
A category of conditions that develop following infection and persist beyond the acute phase. ME/CFS is recognised as a post-infectious illness in many cases. Long COVID is the most recent and widely studied example, sharing mechanisms with ME/CFS including immune dysregulation, autonomic dysfunction, and post-exertional symptom worsening.
Browse related research →POTS (postural orthostatic tachycardia syndrome)
A form of autonomic dysfunction characterised by a significant increase in heart rate upon standing — typically defined as an increase of at least 30 beats per minute — often accompanied by dizziness, lightheadedness, and cognitive symptoms. Frequently observed in ME/CFS and Long COVID patients.
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Two-day CPET (cardiopulmonary exercise testing)
A research protocol in which patients undergo maximal exercise testing on two consecutive days. In ME/CFS, aerobic capacity and anaerobic threshold typically decline significantly on day two — a pattern not seen in healthy controls, deconditioning, or most other fatiguing conditions — providing objective, reproducible evidence of post-exertional impairment.
Browse related research →Explore the atlas