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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 6,145 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 →

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510 studies

E0 — Consensus637E1 — Replicated320E2 — Moderate2,768E3 — Preliminary2,420

ME/CFS4,014Long COVID212Post-infectious189Overlapping1,045

Required for diagnosis412Not specified / unclear2,201Not required3,532

Post-Exertional Malaise1,055Cognitive Dysfunction1,723Pain1,612Unrefreshing Sleep793Orthostatic Intolerance474

Cytokines816Gene Expression567Metabolomics469Neuroimaging466Autoantibodies457

Infection-Triggered1,170Long COVID Overlap580Pediatric492Severe228

Strong Phenotyping435Sex-Stratified326Severe ME Included116

Systematic Review263Meta-Analysis60RCT300

Peer-reviewed6,088Preprint3Unclear54

481–500 of 510 studies

E3 PreliminaryReviewPEM not requiredReview-Narrative

Definition and measurement of fatigue.

Barofsky, I, Legro, M W·Reviews of infectious diseases·1991

This paper examines how fatigue is defined and measured in ME/CFS, highlighting that these definitions have not been well-developed in medical research. The authors reviewed different tools available to measure fatigue—ranging from simple single-item questions to more complex multi-part assessments—and discussed how fatigue in ME/CFS differs from fatigue studied in healthy people in laboratory settings. They emphasize the need to study fatigue as it actually occurs in patients with ME/CFS and to use consistent measurement methods across research.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

A supplemental interview for forms of "affective spectrum disorder".

Pope, H G, Hudson, J I·International journal of psychiatry in medicine·1991

Researchers created a standardized interview tool to help diagnose seven different conditions—including chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, migraines, narcolepsy, Tourette's disorder, and kleptomania—based on the idea that these disorders may be related to each other. They developed questions following a recognized medical interview format and tested the tool with over 100 patients. The authors suggest these conditions may share common underlying features related to mood and emotion regulation.

E3 PreliminaryCommentaryPEM not requiredEditorial

Chronic fatigue syndrome: is it real?

Kroenke, K·Postgraduate medicine·1991

This 1991 editorial discusses what doctors understood about ME/CFS at that time. The author suggests that ME/CFS is likely connected to depression, mild immune system problems, or a combination of both, rather than being caused by Epstein-Barr virus alone. The article recommends that doctors use careful patient interviews, physical exams, and basic blood tests to diagnose the condition, and that supportive, hopeful care is important for treatment.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Issues and problems in the conduct of epidemiologic research on chronic fatigue syndrome.

Grufferman, S·Reviews of infectious diseases·1991

This paper discusses how scientists should study ME/CFS using epidemiology—a research method that looks at how diseases spread through populations. The authors outline the main problems researchers face when studying ME/CFS, such as unclear diagnostic criteria and limited understanding of the condition, and suggest practical solutions. They emphasize that case-control studies (comparing people who have ME/CFS with similar people who don't) should be a priority for understanding what causes the illness.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Evaluation and management of patients with chronic fatigue.

Matthews, D A, Manu, P, Lane, T J·The American journal of the medical sciences·1991

This review article examines how doctors diagnose and treat patients who experience chronic fatigue in everyday medical practice. The authors note that chronic fatigue has many possible causes, including medical illnesses, psychiatric conditions like depression and anxiety, lifestyle factors, and medications. They emphasize that building trust with patients and using a combination of psychiatric evaluation, functional assessment, and both medication and behavioral therapy approaches are important for effective care.

E3 PreliminaryCohortPEM unclearObservational

Clinical observations of chronic fatigue syndrome.

Mildon, C A·Canada diseases weekly report = Rapport hebdomadaire des maladies au Canada·1991

This 1991 study documents clinical observations of people with ME/CFS, describing what doctors noticed when examining patients with this condition. The report provides early descriptive information about how the illness presented in patients during that time period. While limited in scope, it contributes to the historical medical record of ME/CFS recognition.

E3 PreliminaryReviewPEM unclearReview-Narrative

Post-viral fatigue syndrome. Epidemiology: lessons from the past.

Jenkins, R·British medical bulletin·1991

This review examines the history of post-viral fatigue syndrome (PVFS), including early outbreaks of what we now call ME/CFS, and how doctors have understood and tracked this illness over time. The author notes that cases are not officially recorded by health authorities, making it hard to spot when the condition becomes more common in communities. The review explores important questions about how the illness is defined, why some people develop it after infections, and how psychological factors relate to the physical symptoms.

E3 PreliminaryCommentaryPEM unclearEditorial

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Goldenberg, D L·Current opinion in rheumatology·1991

This review examines three related conditions—fibromyalgia, chronic fatigue syndrome, and myofascial pain—that often occur together and cause pain, tiredness, and sleep problems. Researchers are discovering that these conditions may share common biological causes involving how the body senses pain, hormone imbalances, and problems with muscle function. Unfortunately, the new treatments being tested at that time were not particularly effective.

Pain and SensitizationSleepDiagnostics

E3 PreliminaryCommentaryPEM not requiredEditorial

Neuro-ocular Lyme borreliosis.

Smith, J L·Neurologic clinics·1991

This study suggests that some patients diagnosed with chronic fatigue syndrome (CFS) might actually have Lyme disease, a tick-borne infection that can affect the brain and eyes. The authors recommend doctors ask CFS patients detailed questions about tick exposure and check for specific eye and neurological problems, then use blood and urine tests to look for evidence of Lyme infection.

E3 PreliminaryReviewPEM unclearReview-Narrative

[Chronic fatigue syndrome, fibromyalgia and depression].

Martin-Du-Pan, R·Revue medicale de la Suisse romande·1990

This 1990 review article examines the relationships between chronic fatigue syndrome (ME/CFS), fibromyalgia, and depression. The author discusses how these three conditions sometimes occur together and explores whether they share common features or causes. The paper helps clarify how ME/CFS and fibromyalgia are distinct from depression, even though all three can cause fatigue and other overlapping symptoms.

E3 PreliminaryReviewPEM unclearReview-Narrative

The chronic fatigue syndrome: a return to common sense.

Denman, A M·Postgraduate medical journal·1990

This 1990 opinion piece argues that ME/CFS should be understood through practical, straightforward clinical observation rather than overly complex theories. The author advocates for a 'common sense' approach to recognizing and managing the condition based on what doctors actually observe in patients.

E3 PreliminaryCommentaryPEM not requiredEditorial

[Chronic fatigue syndrome--a new disease picture?].

Nix, W A·Der Nervenarzt·1990

This editorial from 1990 discusses that ME/CFS was becoming more commonly diagnosed at that time, but doctors weren't sure if it was one distinct disease or simply a label given to many different conditions. The author notes that we still need to understand whether ME/CFS has a physical cause, a psychological cause, or both, and that each patient may need individual evaluation.

E3 PreliminaryCommentaryPEM not requiredEditorial

Neurasthenia in the 1980s: chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders.

Greenberg, D B·Psychosomatics·1990

In the 1980s, doctors thought chronic fatigue syndrome might be caused by a virus called Epstein-Barr virus (the virus that causes mononucleosis). This editorial explains that while this seemed like a logical explanation, the virus is not actually the cause of chronic fatigue syndrome. The author points out that many people with chronic fatigue also have depression or anxiety, and notes that these mental health conditions should be carefully evaluated and treated rather than overlooked.

E3 PreliminaryCommentaryPEM not requiredEditorial

Is chronic fatigue syndrome synonymous with effort syndrome?

Rosen, S D, King, J C, Wilkinson, J B et al.·Journal of the Royal Society of Medicine·1990

This 1990 study examined whether chronic fatigue syndrome (CFS) might actually be caused by a breathing pattern problem called chronic hyperventilation. The researchers found that 93 out of 100 patients diagnosed with CFS showed signs of this breathing issue instead. They suggest doctors should check patients for hyperventilation problems before diagnosing them with ME or CFS.

E3 PreliminaryCommentaryPEM not requiredEditorial

[Chronic fatigue syndrome].

Ewig, S, Dengler, H J·Klinische Wochenschrift·1990

This paper discusses chronic fatigue syndrome (CFS) as a condition that can develop after viral infections like Epstein-Barr virus or Coxsackie-B virus. Researchers noted that CFS may actually be several different diseases with different causes rather than one single condition. The authors emphasize that diagnosis requires ruling out other medical conditions first, and that at this time, we don't have enough knowledge to recommend specific treatments.

E3 PreliminaryReviewPEM unclearReview-Narrative

Old wine in new bottles: neurasthenia and 'ME'.

Wessely, S·Psychological medicine·1990

This paper compares ME/CFS with an older condition called neurasthenia that was common in the late 1800s and early 1900s. Both illnesses share similar symptoms of extreme fatigue and were popular diagnoses when people believed they were caused by physical (not mental) problems and affected successful, hardworking people. The author argues that understanding ME/CFS requires looking at both brain biology and social factors, not just one or the other.

E3 PreliminaryReviewPEM unclearReview-Narrative

Confounding features of the fibromyalgia syndrome: a current perspective of differential diagnosis.

Bennett, R M·The Journal of rheumatology. Supplement·1989

This article discusses how fibromyalgia syndrome can be confused with many other conditions, including chronic fatigue syndrome, because they share similar symptoms like pain and tiredness. When doctors misdiagnose fibromyalgia or take too long to identify it, patients may receive wrong treatments and become frustrated with their care. Understanding the differences between these conditions is important so patients get the correct diagnosis and appropriate help.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome. A critical appraisal of the role of Epstein-Barr virus.

Koo, D·The Western journal of medicine·1989

Early research suggested that a virus called Epstein-Barr virus (EBV) might cause ME/CFS, leading to the disease sometimes being called "chronic EBV syndrome." However, this review shows that the antibody levels used to detect EBV exposure are similar in people with ME/CFS, healthy people, and people with other illnesses, making it impossible to prove EBV actually causes the condition. Since most people have been exposed to EBV at some point, we cannot easily tell whether the virus causes ME/CFS or if people with ME/CFS simply show different antibody patterns because they are already sick.

E3 PreliminaryReviewPEM unclearReview-Narrative

Myalgic encephalomyelitis.

Gordon, N·Developmental medicine and child neurology·1988

This is a review article about myalgic encephalomyelitis (ME), a serious condition that causes extreme tiredness, muscle pain, and cognitive difficulties. The author examines what was known about ME in 1988, including how it affects the brain and nervous system, and discusses different theories about what might cause it.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Chronic fatigue syndrome: a working case definition.

Holmes, G P, Kaplan, J E, Gantz, N M et al.·Annals of internal medicine·1988

This landmark 1988 paper proposed a new name and formal definition for what was previously called 'chronic Epstein-Barr virus syndrome.' The authors recognized that the condition was poorly understood and inconsistently diagnosed, so they renamed it 'chronic fatigue syndrome' (ME/CFS) and created a working definition to help doctors identify and study it more consistently. This definition focused on severe, ongoing fatigue along with other symptoms like sore throat, headaches, and muscle pain.

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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.