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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 6,171 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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1198 studies

E0 — Consensus644E1 — Replicated320E2 — Moderate2,785E3 — Preliminary2,422

ME/CFS4,028Long COVID217Post-infectious189Overlapping1,051

Required for diagnosis415Not specified / unclear2,222Not required3,534

Post-Exertional Malaise1,067Cognitive Dysfunction1,737Pain1,621Unrefreshing Sleep800Orthostatic Intolerance479

Cytokines819Gene Expression568Metabolomics475Neuroimaging468Autoantibodies458

Infection-Triggered1,175Long COVID Overlap589Pediatric494Severe231

Strong Phenotyping439Sex-Stratified327Severe ME Included118

Systematic Review266Meta-Analysis60RCT300

Peer-reviewed6,114Preprint3Unclear54

1161–1180 of 1,198 studies

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Infection by human herpesvirus type 6: epidemiology, immunopathology and clinical implications].

Lozano de León, F, Gutiérrez Fernández, J, Martín Mazuelos, E et al.·Revista clinica espanola·1992

This review summarizes what scientists know about human herpesvirus type 6 (HHV-6), a common virus that most people carry their whole lives. The virus can cause rash illnesses in children and mono-like symptoms in adults, and some research suggests it might play a role in chronic fatigue syndrome and other long-term illnesses.

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Chronic fatigue immune dysfunction syndrome].

Uchida, A·Nihon rinsho. Japanese journal of clinical medicine·1992

ME/CFS causes extreme tiredness that lasts longer than six months and may be linked to a viral infection that doesn't go away normally. Researchers found that people with ME/CFS have problems with immune cells, especially natural killer (NK) cells, which normally help fight off viruses and control the immune system. When NK cell function improved in some patients, their ME/CFS symptoms got better, suggesting that fixing these immune cells might be key to recovery.

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Therapy of chronic fatigue syndrome].

Uchida, A·Nihon rinsho. Japanese journal of clinical medicine·1992

This review examined different treatment options for ME/CFS by looking at past clinical studies. Researchers found that while most treatments tested didn't work well, a few showed promise—including intravenous immunoglobulin therapy, magnesium supplements, and treatments designed to boost natural killer cells (immune cells that help fight infection). The authors suggest that immune system problems may play a role in ME/CFS, and fixing these problems might help patients feel better.

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Viral infection and its causative role for chronic fatigue syndrome].

Okano, M·Nihon rinsho. Japanese journal of clinical medicine·1992

This review examines whether viral infections, particularly Epstein-Barr virus (EBV), cause ME/CFS. The author notes that ME/CFS shares symptoms with chronic EBV infection—including fatigue, swollen lymph nodes, and fever—but the connection remains unclear. The review also discusses a more severe condition called severe chronic active EBV infection and highlights that the true cause and best treatment for ME/CFS are still unknown.

E3 PreliminaryCohortPEM not requiredCase-Control

[Chronic fatigue syndrome, a case of high anti-HHV-6 antibody titer and one associated with primary hyperaldosteronism].

Kato, Y, Kamijima, S, Kashiwagi, A et al.·Nihon rinsho. Japanese journal of clinical medicine·1992

This study describes two women with ME/CFS who had unusual medical findings. One woman had very high levels of antibodies to HHV-6, a virus that may reactivate in ME/CFS patients. The second woman's ME/CFS symptoms improved when she had high blood pressure and a hormone imbalance, but her symptoms returned after surgery to remove an adrenal gland. These cases suggest that viruses and hormones might play a role in ME/CFS, though more research is needed to understand how.

E3 PreliminaryMechanismPEM not requiredMechanistic

Immunologically mediated fatigue: a murine model.

Chao, C C, DeLaHunt, M, Hu, S et al.·Clinical immunology and immunopathology·1992

Researchers infected mice with agents that trigger immune system activation and found that the mice became fatigued—they ran much less on their exercise wheels and took longer to groom themselves after swimming. The infected mice also showed elevated levels of a immune signaling molecule called TGF-beta, which is also found at high levels in ME/CFS patients. This study suggests that an overly active immune response may be directly responsible for the fatigue experienced in ME/CFS.

E3 PreliminaryReviewPEM unclearReview-Narrative

Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome.

Ur, E, White, P D, Grossman, A·European archives of psychiatry and clinical neuroscience·1992

This paper proposes that certain immune signals in the brain called cytokines (particularly IL-1 and IL-6) may become overactive in ME/CFS and depression, triggering a chain reaction in the body's stress system that produces fatigue and other symptoms. The authors suggest that viral infections might trigger this cytokine activation. While this is a theoretical proposal rather than a study with patient data, it offered an important new way of thinking about what causes chronic fatigue and depression.

E3 PreliminaryCohortPEM not requiredCase-Control

[A case of chronic fatigue syndrome who showed a beneficial effect by intravenous administration of magnesium sulphate].

Takahashi, H, Imai, K, Katanuma, A et al.·Arerugi = [Allergy]·1992

This case study describes a 29-year-old woman with ME/CFS who had severe fatigue, fever, swollen lymph nodes, and muscle pain that didn't improve with standard treatments. When doctors gave her intravenous magnesium sulphate once a week for about 6 weeks, her extreme tiredness improved and she was able to do more daily activities, eventually leaving the hospital.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome.

Winters, E G, Quinet, R J·The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society·1992

ME/CFS is a complex illness characterized by severe, debilitating fatigue that often starts suddenly with flu-like symptoms. While researchers have investigated viruses and immune system changes in ME/CFS patients, no single cause has been definitively identified. Currently, there is no specific cure, though cognitive behavioral therapy and certain medications may help some patients manage their condition.

E3 PreliminaryMechanismPEM not requiredMechanistic

Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus.

Berneman, Z N, Ablashi, D V, Li, G et al.·Proceedings of the National Academy of Sciences of the United States of America·1992

Researchers isolated a virus called HHV-7 from a patient with ME/CFS and studied how it infects cells. They found that HHV-7 is related to another herpesvirus (HHV-6) but is genetically different enough to be classified as its own distinct virus. However, the study found no clear link between HHV-7 and ME/CFS in the general population.

E3 PreliminaryCohortPEM not requiredObservational

Chronic fatigue syndrome: studies on skeletal muscle.

Grau, J M, Casademont, J, Pedrol, E et al.·Clinical neuropathology·1992

This study looked at muscle tissue samples from 20 ME/CFS patients to understand why muscles feel so tired and weak. The researchers found that most patients had either normal muscle tissue or only minor changes, and they did not find the patterns of inflammation typically seen in viral muscle diseases. The study also tested whether L-carnitine supplements could help patients improve over three months, but found no clinical benefit.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome.

Calabrese, L, Danao, T, Camara, E et al.·American family physician·1992

ME/CFS is a condition where people experience severe, disabling tiredness that starts suddenly and lasts at least six months, often getting worse with physical activity. Patients often have fever, sore throat, and tender lymph nodes, along with sleep problems and muscle pain. Treatment focuses on education, support, gentle exercise, and managing individual symptoms like sleep issues and pain.

E3 PreliminaryPEM not required

Epstein-Barr virus-related persistent erythema multiforme in chronic fatigue syndrome.

Drago, F, Romagnoli, M, Loi, A et al.·Archives of dermatology·1992

This case study describes a single patient with ME/CFS who developed an unusual, long-lasting skin rash called erythema multiforme that didn't respond to standard steroid treatment. Researchers found evidence of Epstein-Barr virus (EBV)—the virus that causes infectious mononucleosis—in the skin lesions and other body tissues. The rash improved when the patient was treated with an antiviral medication (acyclovir), but returned when the medication was stopped.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Human herpesvirus-6 (HHV-6) (short review).

Ablashi, D V, Salahuddin, S Z, Josephs, S F et al.·In vivo (Athens, Greece)·1991

This review examines Human Herpesvirus-6 (HHV-6), a common virus that most people carry. The virus can reactivate in people with certain illnesses, including ME/CFS. The study found that people with ME/CFS sometimes have higher levels of antibodies to HHV-6, suggesting the virus may be active in their bodies.

E3 PreliminaryMechanismPEM unclear

Immunodysregulation and chronic fatigue syndrome.

Kundu, S K, Ahronheim, G A, Menezes, J·Canada diseases weekly report = Rapport hebdomadaire des maladies au Canada·1991

This study examined whether ME/CFS involves problems with the immune system that aren't working properly. The researchers looked at immune system dysfunction in patients with chronic fatigue syndrome to understand if an imbalance in immune responses might explain the illness. This early research helped establish that immune abnormalities could be involved in ME/CFS.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Molecular approaches to epidemiologic evaluation of viruses as risk factors for patients who have chronic fatigue syndrome.

Miller, G·Reviews of infectious diseases·1991

This paper proposes that studying how viral infections like flu, hepatitis, and mono can trigger long-term fatigue might help us understand ME/CFS. The researchers suggest examining not just whether someone had a virus, but how much virus was present, which type of virus it was, where it spread in the body, and whether the virus was active or dormant. They also recommend looking carefully at how individual patients' immune systems respond to specific parts of viruses.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Detection of Epstein-Barr virus with molecular hybridization techniques.

Pagano, J S·Reviews of infectious diseases·1991

This paper reviews different laboratory techniques for detecting Epstein-Barr virus (EBV), a common virus that some researchers suspect might play a role in ME/CFS. The authors explain that newer methods like genetic testing and blood analysis are much faster and more accurate than older traditional tests, and could help scientists understand whether EBV actually causes chronic fatigue syndrome.

E3 PreliminaryMechanismPEM not requiredMechanistic

Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera.

Balachandran, N, Tirawatnapong, S, Pfeiffer, B et al.·The Journal of infectious diseases·1991

This study examined how the immune system responds to human herpesvirus 6 (HHV-6), a virus that researchers have investigated in ME/CFS patients. Scientists took blood samples from healthy people and patients with various conditions including ME/CFS, and looked at which HHV-6 proteins the immune system recognized. They found that people with detectable antibodies (immune proteins) against HHV-6 recognized multiple viral proteins, with stronger responses corresponding to higher antibody levels.

E3 PreliminaryCohortPEM not requiredObservational

Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany.

Hilgers, A, Krueger, G R, Lembke, U et al.·In vivo (Athens, Greece)·1991

This study followed 35 ME/CFS patients in Germany for up to eight years and found that most experienced severe fatigue, joint and muscle pain, sore throats, and various other symptoms. Researchers found evidence of herpesvirus reactivation in about 73% of patients and Epstein-Barr virus in about 34%, suggesting ongoing viral activity may play a role in the condition. While treatments were tried including immune therapy and antiviral drugs, none consistently worked well, though immune globulin therapy showed the most promise.

E3 PreliminaryMechanismPEM unclearObservational

Anti-neuronal antibody levels in chronic fatigue syndrome patients with neurologic abnormalities.

Buchwald, D, Wener, M H, Komaroff, A L·Arthritis and rheumatism·1991

This study looked at whether people with ME/CFS who have neurological symptoms (like problems with thinking or nerve function) have unusual antibodies in their blood that attack nerve cells. Researchers tested blood samples from ME/CFS patients and compared antibody levels between those with and without neurological problems. The goal was to understand whether immune system misdirection might be causing some of the neurological symptoms patients experience.

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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.