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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,205 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

Sort

250 studies

E0 — Consensus654E1 — Replicated321E2 — Moderate2,807E3 — Preliminary2,423

ME/CFS4,040Long COVID224Post-infectious190Overlapping1,064

Required for diagnosis417Not specified / unclear2,251Not required3,537

Post-Exertional Malaise1,082Cognitive Dysfunction1,749Pain1,628Unrefreshing Sleep805Orthostatic Intolerance484

Cytokines821Gene Expression573Metabolomics477Neuroimaging472Autoantibodies460

Infection-Triggered1,182Long COVID Overlap604Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review272Meta-Analysis61RCT301

Peer-reviewed6,148Preprint3Unclear54

121–140 of 250 studies

E2 ModerateCohortPEM unclearCross-Sectional

Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies.

Ravindran, Murugan K, Zheng, Yin, Timbol, Christian et al.·BMC neurology·2011

This study found that headaches—especially migraines—are much more common in people with ME/CFS than in healthy people. Researchers studied two groups and found that 84% of people with ME/CFS experienced migraines, compared to only 5% of healthy controls. People with ME/CFS who had migraines with visual symptoms (aura) showed more severe dizziness, memory problems, and heart-related symptoms than those without aura.

Pain and Sensitization

E2 ModerateBehavioralPEM not requiredCross-Sectional

Clinical characteristics of patients with medically unexplained chronic widespread pain: a primary care center study.

Lee, Kye Hwa, Kim, Cheol Hwan, Shin, Ho Cheol et al.·Korean journal of family medicine·2011

This study examined 109 patients with chronic widespread pain to understand what makes medically unexplained pain different from pain caused by known medical or psychological conditions. Researchers found that patients with unexplained pain had more tender points on their body, greater fatigue, and more functional impairment than those with pain linked to known medical causes, but were very similar to those with pain linked to psychological factors.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCase-Control

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study.

Moldofsky, Harvey, Patcai, John·BMC neurology·2011

This study looked at people who had severe SARS infection and were unable to return to work for over a year afterward. These patients experienced long-lasting fatigue, widespread muscle pain, weakness, depression, and poor sleep quality. Researchers found that their sleep patterns and symptoms were very similar to those seen in fibromyalgia and chronic fatigue syndrome.

Pain and SensitizationSleep

E2 ModerateCohortPEM not requiredCross-Sectional

Co-occurrence and associations of pain and fatigue in a community sample of Dutch adults.

Creavin, Samuel T, Dunn, Kate M, Mallen, Christian D et al.·European journal of pain (London, England)·2010

This study looked at how often pain and fatigue occur together in everyday people. Researchers found that when someone has chronic widespread pain, they are much more likely to also experience persistent fatigue, and vice versa. People who had both symptoms were more likely to also experience anxiety or depression, and certain factors like being overweight, having other chronic diseases, or low activity levels made having both symptoms more common.

Pain and Sensitization

E2 ModerateBehavioralPEM not requiredCross-Sectional

Latent class analysis of functional somatic symptoms in a population-based sample of twins.

Kato, Kenji, Sullivan, Patrick F, Pedersen, Nancy L·Journal of psychosomatic research·2010

This study looked at how people with chronic fatigue and multiple physical symptoms cluster into different groups. Researchers studied over 28,000 twins and found five distinct groups: those with no symptoms, those mainly tired, those with stomach problems, those with pain, and those with many symptoms across all areas. The study suggests that while genes play a small role, environmental factors (like stress, infections, or lifestyle) are much more important in determining who develops these symptoms.

Pain and Sensitization

E2 ModerateBehavioralPEM not requiredCross-Sectional

Childhood maltreatment and migraine (part III). Association with comorbid pain conditions.

Tietjen, Gretchen E, Brandes, Jan L, Peterlin, B Lee et al.·Headache·2010

This study looked at people with migraine who came to headache clinics and asked whether childhood trauma (abuse or neglect) was connected to having multiple pain conditions at the same time, including chronic fatigue syndrome. They found that people who experienced emotional abuse or physical neglect as children were more likely to have multiple pain conditions as adults, even after accounting for depression and anxiety.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCross-Sectional

Phenotypes of chronic fatigue syndrome in children and young people.

May, Margaret, Emond, Alan, Crawley, Esther·Archives of disease in childhood·2010

Researchers studied 333 children and young people with ME/CFS to see if the illness presents differently in different people. They found three main patterns: one involving muscle and joint pain, another involving migraine-like symptoms with sensitivity to light and sound, and a third involving sore throat and swollen lymph nodes. These different patterns were linked to varying levels of severity, suggesting that ME/CFS affects children in different ways.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCase-Control

Adolescent offspring of mothers with chronic fatigue syndrome.

Smith, Mark S, Buchwald, Dedra S, Bogart, Andy et al.·The Journal of adolescent health : official publication of the Society for Adolescent Medicine·2010

This study looked at whether teenagers whose mothers have ME/CFS are more likely to develop ME/CFS themselves or experience fatigue and other related symptoms. Researchers compared 26 teenagers with mothers who had ME/CFS to 45 teenagers whose mothers were healthy. While teenagers with affected mothers showed higher rates of prolonged fatigue and ME/CFS diagnosis, the differences were small and not statistically proven.

Pain and SensitizationSleep

E2 ModerateBehavioralPEM not requiredCross-Sectional

Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis.

van Hoogmoed, Dewy, Fransen, Jaap, Bleijenberg, Gijs et al.·Rheumatology (Oxford, England)·2010

This study looked at severe fatigue in people with rheumatoid arthritis (RA), a condition that causes joint inflammation. Researchers found that 42% of RA patients experienced severe fatigue that felt frustrating and exhausting. Importantly, this severe fatigue was more closely linked to pain, mood, sleep quality, and how patients thought about their fatigue—rather than to inflammation markers alone.

Pain and SensitizationSleep

E2 ModerateCohortPEM not requiredCross-Sectional

Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome.

Nickel, J Curtis, Tripp, Dean A, Pontari, Michel et al.·The Journal of urology·2010

This study looked at how often bladder pain syndrome occurs alongside other conditions like irritable bowel syndrome, fibromyalgia, and ME/CFS. Researchers found that people with bladder pain syndrome were much more likely to have these other conditions compared to healthy controls. Importantly, people who had multiple overlapping conditions experienced worse pain, sleep problems, depression, and lower quality of life than those with just one condition.

Pain and SensitizationSleep

E2 ModerateCohortPEM unclearCase-Control

Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study.

Meeus, Mira, Nijs, Jo, Huybrechts, Sven et al.·Clinical rheumatology·2010

This study tested whether people with ME/CFS feel pain more intensely than healthy people, even in areas where they don't typically experience pain. Researchers measured how much pressure patients and healthy volunteers could tolerate before feeling pain. They found that ME/CFS patients with chronic pain had significantly lower pain thresholds everywhere on their body, suggesting their nervous system may be in a heightened state of sensitivity.

Pain and Sensitization

E2 ModerateBehavioralPEM not requiredCross-Sectional

"Functional" or "psychosomatic" symptoms, e.g. a flu-like malaise, aches and pain and fatigue, are major features of major and in particular of melancholic depression.

Maes, Michael·Neuro endocrinology letters·2009

This study looked at whether depression and ME/CFS share similar physical symptoms like fatigue, muscle pain, and feeling like you have an infection. Researchers found that people with severe depression often experience these "body-centered" symptoms as a major part of their illness. The findings suggest that doctors should pay more attention to these physical symptoms when diagnosing and treating depression.

Pain and SensitizationCognitive Impairment

E2 ModerateCohortPEM not requiredCross-Sectional

Allodynia in migraine: association with comorbid pain conditions.

Tietjen, Gretchen E, Brandes, Jan L, Peterlin, B Lee et al.·Headache·2009

This study looked at how often migraine patients experience allodynia—pain or discomfort from things that normally wouldn't hurt, like light touch on the skin. The researchers found that 60% of migraine patients had at least one allodynic symptom, and those with allodynia were much more likely to also have other chronic pain conditions like fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome, as well as depression and anxiety.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCross-Sectional

Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy.

Crawley, E, Sterne, J A C·Archives of disease in childhood·2009

This study looked at how often children with ME/CFS attended school and how their physical abilities changed over time. Researchers found that 62% of children attended school 40% of the time or less, and those with better physical function were more likely to go to school. The study suggests that improving school attendance should focus on treatments that reduce fatigue and pain, not treatments for anxiety.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCross-Sectional

The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome.

Torres-Harding, Susan, Sorenson, Matthew, Jason, Leonard et al.·Journal of applied biobehavioral research·2008

This study looked at cortisol, a stress hormone, in 108 people with ME/CFS to see if abnormal cortisol levels were connected to symptoms like fatigue and pain. The researchers found that people with unusual cortisol patterns—especially those who didn't show the normal daily rise and fall—reported higher levels of fatigue. While abnormal cortisol appears linked to some ME/CFS symptoms, scientists still aren't sure whether this hormonal change causes the illness or results from it.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCase-Control

Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study.

Meeus, Mira, Nijs, Jo, Van de Wauwer, Naomi et al.·Pain·2008

This study tested how quickly the body's natural pain-blocking system kicks in when ME/CFS patients experience heat pain compared to healthy people. Researchers immersed participants' arms in warm water and tracked pain levels over time. They found that people with ME/CFS have stronger pain sensations overall, and their bodies take longer to activate the natural pain-suppression mechanism that normally reduces pain during ongoing stimulation.

Pain and Sensitization

E2 ModerateBehavioralPEM not requiredCross-Sectional

Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing.

Nijs, Jo, Van de Putte, Karen, Louckx, Fred et al.·Pain medicine (Malden, Mass.)·2008

This study looked at 36 women with ME/CFS who experience widespread pain to understand how their thoughts about pain (called 'pain catastrophizing'—expecting the worst and feeling helpless) relate to their actual pain levels, ability to exercise, and daily functioning. Researchers found that negative thinking patterns about pain were strongly connected to how much bodily pain patients reported and how much their condition limited their activities. The study suggests that addressing these thought patterns might be an important part of managing ME/CFS with pain.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCross-Sectional

Chronic fatigue syndrome in children aged 11 years old and younger.

Davies, S, Crawley, E·Archives of disease in childhood·2008

This study looked at young children under age 12 with ME/CFS at a specialist clinic in Bath, UK. The researchers found that even very young children (including one as young as 2 years old) can have ME/CFS and experience severe disability, with symptoms almost identical to those seen in teenagers. Children in this age group attended school only about 40% of the time on average and reported high levels of fatigue and pain.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCase-Control

Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome.

Ullrich, Philip M, Afari, Niloofar, Jacobsen, Clemma et al.·Pain medicine (Malden, Mass.)·2007

This study compared identical twins where one had ME/CFS and one did not to understand pain sensitivity. Researchers tested how twins responded to cold pain and found that while people with ME/CFS reported significantly higher levels of pain and fatigue during the test, their actual physical pain thresholds were not substantially different from their unaffected twins. This suggests that the pain experience in ME/CFS may be more about how the brain perceives and processes pain rather than a difference in the body's basic pain detection system.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCross-Sectional

Endometriosis is associated with prevalence of comorbid conditions in migraine.

Tietjen, Gretchen E, Bushnell, Cheryl D, Herial, Nabeel A et al.·Headache·2007

This study found that women with migraines who also have endometriosis (a painful condition affecting the uterus) experience more frequent and severe headaches than women with migraines alone. Women with both conditions were also more likely to have other related conditions like chronic fatigue syndrome, anxiety, and bladder pain. The findings suggest these conditions may share common underlying factors, possibly related to hormones.

Pain and Sensitization

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.