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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 6,113 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by review quality. 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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381 studies

E0 — Consensus629E1 — Replicated320E2 — Moderate2,745E3 — Preliminary2,419

ME/CFS4,003Long COVID206Post-infectious189Overlapping1,031

Required for diagnosis410Not specified / unclear2,176Not required3,527

Post-Exertional Malaise1,039Cognitive Dysfunction1,709Pain1,606Unrefreshing Sleep785Orthostatic Intolerance468

Cytokines812Gene Expression566Metabolomics468Neuroimaging463Autoantibodies454

Infection-Triggered1,155Long COVID Overlap562Pediatric491Severe226

Strong Phenotyping427Sex-Stratified325Severe ME Included114

Systematic Review258Meta-Analysis59RCT300

Higher42Moderate2,570Preliminary3,224Weak277

Peer-reviewed6,056Preprint3Unclear54

21–40 of 381 studies

E0 ConsensusPEM not requiredPreliminarySystematic-ReviewEditor reviewed

A Review Study on the Beneficial Effects of Baduanjin.

Zou, Liye, Pan, Zhujun, Yeung, Albert et al.·Journal of alternative and complementary medicine (New York, N.Y.)·2018

This review looked at 22 studies about Baduanjin, a gentle Chinese exercise that combines movement with mental focus. The studies suggest that Baduanjin may help improve thinking abilities, mood, sleep, and physical symptoms in people with various conditions, including those with chronic fatigue-like illness. However, the authors note that better-quality, longer-lasting studies are needed before we can be confident about these benefits.

Cognitive Impairment

E0 ConsensusPEM requiredModerate confidenceReview-NarrativeEditor reviewed

[Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review].

Komaroff, Anthony L, Takahashi, Ryosuke, Yamamura, Takashi et al.·Brain and nerve = Shinkei kenkyu no shinpo·2018

This review examines objective, measurable evidence that ME/CFS is a real physical illness, not just a psychological condition. Researchers looked at studies showing that ME/CFS involves problems with the brain, immune system, and how the body uses energy. They found that immune activation—where the body's defense system becomes overactive—may be a key driver of ME/CFS symptoms.

Immune SystemCognitive ImpairmentPost-Exertional Malaise

E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review.

Teodoro, Tiago, Edwards, Mark J, Isaacs, Jeremy D·Journal of neurology, neurosurgery, and psychiatry·2018

Many people with ME/CFS report cognitive problems like brain fog, forgetfulness, and difficulty concentrating. This review of 95 studies found that while patients consistently describe these symptoms, standard memory and thinking tests often show normal or only mild problems. The authors suggest that pain, fatigue, and the body's excessive self-monitoring may force the brain to work harder on everyday tasks, making thinking feel more exhausting even when test results look relatively normal.

Cognitive Impairment

E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Attentional and interpretive bias towards illness-related information in chronic fatigue syndrome: A systematic review.

Hughes, Alicia, Hirsch, Colette, Chalder, Trudie et al.·British journal of health psychology·2016

This review looked at research studies examining how people with ME/CFS pay attention to and interpret information about illness and symptoms. The studies found that some people with ME/CFS tend to notice health-related threats more quickly and interpret their body sensations as signs of illness more readily than healthy people do. These thinking patterns may help keep the fatigue and illness beliefs going, even when other factors aren't actively causing symptoms.

Cognitive Impairment

E0 ConsensusPEM unclearModerate confidenceReview-NarrativeEditor reviewed

Dysfunctional syndromes and fibromyalgia: a 2012 critical digest.

Sarzi-Puttini, Piercarlo, Atzeni, Fabiola, Di Franco, Manuela et al.·Clinical and experimental rheumatology·2012

This review looked at several long-lasting conditions that cause widespread pain, tiredness, sleep problems, and difficulty concentrating—conditions that don't always show up clearly on standard medical tests. The researchers examined fibromyalgia, ME/CFS, and irritable bowel syndrome to understand how they're connected and what causes symptoms to keep happening. They found that these conditions share similar patterns in how the nervous system processes pain and fatigue.

Pain and SensitizationCognitive Impairment

E0 ConsensusPEM not requiredHigher confidenceMeta-AnalysisEditor reviewed

Behavior problems in children and adolescents with chronic physical illness: a meta-analysis.

Pinquart, Martin, Shen, Yuhui·Journal of pediatric psychology·2011

This large review of 569 studies found that children and teenagers with chronic physical illnesses—including ME/CFS—experience higher rates of emotional and behavioral problems compared to healthy peers. Children with ME/CFS showed particularly high levels of emotional problems like anxiety and depression. The review emphasizes that doctors should routinely screen young patients with chronic illnesses for psychological distress and refer them to mental health services when needed.

Cognitive Impairment

E0 ConsensusPEM not requiredHigher confidenceMeta-AnalysisEditor reviewed

Cognitive functioning in chronic fatigue syndrome: a meta-analysis.

Cockshell, S J, Mathias, J L·Psychological medicine·2010

This study combined results from 50 research papers to understand how ME/CFS affects thinking and memory. Researchers found that people with ME/CFS have real, measurable problems with attention, memory, and processing speed—essentially, the brain takes longer to handle and organize information. However, other thinking skills like vocabulary, reasoning, and basic motor skills were not affected.

Cognitive Impairment

E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity.

Panossian, Alexander, Wikman, Georg·Current clinical pharmacology·2009

This review examined whether herbal supplements called adaptogens can help with fatigue and ME/CFS. Researchers found that some adaptogens—particularly Rhodiola rosea—showed promise in clinical studies for improving attention, thinking, and mental energy in people with fatigue and chronic fatigue syndrome. The review suggests these herbs may work by helping the body manage stress through changes in specific stress-response proteins and hormones.

Cognitive Impairment

E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

Approved and investigational uses of modafinil : an evidence-based review.

Kumar, Raminder·Drugs·2008

This review looked at studies testing modafinil, a medication that promotes wakefulness, in different conditions including sleep disorders and fatigue-related illnesses. The authors found that modafinil works well for approved conditions like narcolepsy and sleep apnea, but studies testing it for chronic fatigue syndrome were very small and gave unclear results. The medication can cause side effects like insomnia, headaches, and appetite loss, and may interact with other drugs.

SleepCognitive Impairment

E0 ConsensusPEM not requiredModerate confidenceEditorialEditor reviewed

Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment.

Gur, Ali, Oktayoglu, Pelin·Current pharmaceutical design·2008

This review examines how ME/CFS and fibromyalgia may both involve problems in the nervous system—specifically in how the brain processes pain, manages stress hormones, and controls automatic body functions. The authors discuss why current treatments are limited and explore new medication approaches that target brain chemicals involved in pain and fatigue.

SleepAutonomic Nervous SystemCognitive Impairment

E0 ConsensusPEM not requiredModerate confidenceMeta-AnalysisEditor reviewed

Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms.

Cairns, Victoria, Godwin, Jon·International journal of epidemiology·2005

This study looked at patients who had Lyme disease and found that many experienced long-lasting fatigue, muscle and joint pain, and thinking difficulties even after antibiotic treatment. Researchers combined results from five previous studies comparing Lyme disease patients to healthy controls and found these symptoms were significantly more common in the Lyme disease group. The symptom pattern was notably different from other conditions like fibromyalgia or depression.

Pain and SensitizationCognitive Impairment

E0 ConsensusPEM not requiredPreliminaryEditorialEditor reviewed

Medically unexplained symptoms and neuropsychological assessment.

Binder, Laurence M, Campbell, Keith A·Journal of clinical and experimental neuropsychology·2004

This review examines several long-term illnesses—including ME/CFS—where patients experience real symptoms but standard medical tests don't show an obvious cause. The authors found that some patients do have measurable thinking and memory problems, but these may result from a combination of stress, past trauma, and how the body responds to illness rather than from traditional brain disease alone.

Cognitive Impairment

E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Psychological treatment of patients with chronic toxic encephalopathy: lessons from studies of chronic fatigue and whiplash.

van Hout, Moniek S E, Wekking, Ellie M, Berg, Ina J et al.·Psychotherapy and psychosomatics·2003

This review looked at studies on psychological treatments for chronic toxic encephalopathy (a condition from long-term solvent exposure) and compared them with research on chronic fatigue syndrome and whiplash injuries. The reviewers found that cognitive-behavioral therapy (CBT)—a type of talk therapy that helps change unhelpful thinking patterns—and gradually increasing activity levels showed promise in helping people with fatigue and thinking problems. They suggest these same approaches might help people with toxic encephalopathy, though more research is needed.

Cognitive Impairment

E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Neuropsychological functioning in chronic fatigue syndrome: a review.

Michiels, V, Cluydts, R·Acta psychiatrica Scandinavica·2001

This review looked at studies examining thinking and memory problems in ME/CFS patients. Researchers found that people with ME/CFS commonly experience slower thinking speed, difficulty holding information in working memory, and trouble learning new information. The study noted that brain scans haven't shown a consistent pattern that uniquely identifies ME/CFS patients, and that fatigue severity doesn't fully explain the cognitive problems.

Cognitive Impairment

E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Neuropsychology of chronic fatigue syndrome: a critical review.

Tiersky, L A, Johnson, S K, Lange, G et al.·Journal of clinical and experimental neuropsychology·1997

This review examined research on thinking and memory problems in ME/CFS patients. The clearest finding was that people with ME/CFS struggle with processing information quickly and efficiently, similar to when your brain feels sluggish. However, overall intelligence and complex thinking skills remain normal. Emotional factors like anxiety or depression can make cognitive problems feel worse, though it's unclear if they directly affect actual thinking performance.

Cognitive Impairment

E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Neurocognitive functioning in chronic fatigue syndrome.

DiPino, R K, Kane, R L·Neuropsychology review·1996

This review examined research on thinking and memory problems reported by people with ME/CFS. While patients consistently describe difficulties concentrating and remembering things, scientific tests of these abilities have shown mixed and unclear results. The authors suggest that researchers need to improve how they design studies and what tests they use to better understand these cognitive challenges.

Cognitive Impairment

E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

War syndromes and their evaluation: from the U.S. Civil War to the Persian Gulf War.

Hyams, K C, Wignall, F S, Roswell, R·Annals of internal medicine·1996

Researchers reviewed historical records of illnesses that appeared in soldiers after wars, dating back to the U.S. Civil War through the Persian Gulf War. They found that across different wars and time periods, veterans reported similar symptoms like exhaustion, breathing problems, headaches, and difficulty concentrating. However, the researchers concluded that these symptoms don't appear to be one single disease, and that lack of proper comparison groups and research methods made it hard to determine what actually caused these illnesses.

Cognitive Impairment

E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Chronic fatigue syndrome and depression: cause, effect, or covariate.

Abbey, S E, Garfinkel, P E·Reviews of infectious diseases·1991

Many people with ME/CFS experience depression, but it's unclear why. This review examines four possible explanations: depression might be the main illness with fatigue as a symptom, depression might develop because of having ME/CFS, both conditions might occur together separately, or depression might be incorrectly diagnosed. The authors discuss how depression can affect medical tests used to study ME/CFS, which is important to understand when interpreting research results.

Cognitive Impairment

E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Cognitive and mood-state changes in patients with chronic fatigue syndrome.

Grafman, J, Johnson, R, Scheffers, M·Reviews of infectious diseases·1991

This review examined whether ME/CFS causes problems with memory, thinking, and mood. The researchers found that while some people with acute mono or EBV infection may have thinking difficulties, they couldn't confirm this happens in ME/CFS patients using objective tests. However, they did notice that people with ME/CFS often have depression or anxiety either before or alongside their illness.

Cognitive Impairment

E1 ReplicatedPEM unclearModerate confidenceRCTEditor reviewed

Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome.

Vernon, Suzanne D, Rond, Candace, Sun, Yifei et al.·Frontiers in neurology·2025

This study tested whether a compound called oxaloacetate (OAA) could help people with ME/CFS feel less fatigued and think more clearly. Over 90 days, people taking OAA showed better cognitive improvement and slightly more ability to stay upright compared to those taking a placebo. The results suggest that fatigue and thinking problems are closely linked in ME/CFS, and treating one may help improve the other.

Cognitive Impairment

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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.