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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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345 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

321–340 of 345 studies

E3 PreliminaryCommentaryPEM unclearEditorial

Chiari I malformation as a cause of orthostatic intolerance symptoms: a media myth?

Garland, E M, Robertson, D·The American journal of medicine·2001

Some people with ME/CFS and fibromyalgia have heard that a brain condition called Chiari I malformation might be causing their symptoms, especially dizziness and fainting when standing up. This editorial reviews whether that claim is actually supported by scientific research and concludes that there is very little reliable evidence backing up this connection, despite media coverage and patient discussions online.

Autonomic Nervous System

E3 PreliminaryReviewPEM unclearReview-Narrative

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Buskila, D·Current opinion in rheumatology·2001

This review examined fibromyalgia (FM), chronic fatigue syndrome (CFS), and related pain conditions across different countries. Researchers found that pain sensitivity involves brain chemistry (including a system called NMDA), hormone imbalances, and nervous system problems. CFS was found in about 0.4% of a large community sample, with many children recovering well, though the study notes that no major new treatments were tested during this period.

Pain and SensitizationAutonomic Nervous System

E3 PreliminaryReviewPEM unclearReview-Narrative

Neuroendocrine mechanisms in fibromyalgia-chronic fatigue.

Buskila, D, Press, J·Best practice & research. Clinical rheumatology·2001

This review examines why fibromyalgia and ME/CFS cause such similar symptoms like fatigue, pain, and problems with the nervous system. Researchers found that both conditions involve problems with hormones, how the body processes pain, and how the autonomic nervous system (which controls automatic body functions) works. The study suggests these conditions may share the same underlying cause: dysfunction in the central nervous system.

Autonomic Nervous System

E3 PreliminaryCommentaryPEM unclearEditorial

Potential mechanisms in chemical intolerance and related conditions.

Clauw, D J·Annals of the New York Academy of Sciences·2001

Many people with ME/CFS, fibromyalgia, and related conditions experience chemical intolerance alongside other symptoms like pain and fatigue. This study reviews research suggesting that these conditions share common biological problems, particularly in how the nervous system processes sensory information—making everyday smells, sounds, or lights feel unusually unpleasant or overwhelming. While stress and worry can sometimes make symptoms worse, the evidence shows that physical changes in the body's sensory processing are doing much of the heavy lifting in causing symptoms.

Autonomic Nervous System

E3 PreliminaryMechanismPEM not requiredMechanistic

Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension.

Torpy, D J, Bachmann, A W, Grice, J E et al.·The Journal of clinical endocrinology and metabolism·2001

This study examined a family with a genetic mutation affecting a protein called corticosteroid-binding globulin (CBG), which helps transport the stress hormone cortisol in the blood. People with this mutation had unusually low blood pressure and chronic fatigue—in fact, 86% of affected adults met criteria for chronic fatigue syndrome. The findings suggest that problems with how the body handles cortisol may contribute to fatigue disorders.

Autonomic Nervous System

E3 PreliminaryMechanismPEM not requiredObservational

Role of impaired lower-limb venous innervation in the pathogenesis of the chronic fatigue syndrome.

Streeten, D H·The American journal of the medical sciences·2001

This study found that people with ME/CFS have problems with how blood vessels in their feet respond to stress. When standing up, their blood pressure drops abnormally after a delay, and their foot veins don't tighten properly in response to a hormone (norepinephrine) that normally helps maintain blood pressure. This suggests that the nerves controlling blood vessels in the legs may not be working correctly in ME/CFS.

Autonomic Nervous System

E3 PreliminaryCohortPEM not requiredCase-Control

Does severe nutcracker phenomenon cause pediatric chronic fatigue?

Takahashi, Y, Ohta, S, Sano, A et al.·Clinical nephrology·2000

Researchers found that 9 children with chronic fatigue all had a rare blood vessel condition called nutcracker phenomenon, where a vein gets compressed and restricts blood flow. These children also had symptoms of autonomic dysfunction (problems with automatic body functions like heart rate and blood pressure) and were originally thought to have psychological problems. The study suggests that this vascular compression might be connected to their fatigue and other symptoms.

Autonomic Nervous System

E3 PreliminaryReviewPEM not requiredReview-Narrative

Ruscus aculeatus (butcher's broom) as a potential treatment for orthostatic hypotension, with a case report.

Redman, D A·Journal of alternative and complementary medicine (New York, N.Y.)·2000

Many people with ME/CFS experience orthostatic hypotension—a sudden drop in blood pressure when standing up—which can be severely disabling. This paper reviews why existing medications for this condition often don't work well and proposes that Ruscus aculeatus (butcher's broom), a plant-based supplement used in Europe, might help by improving blood vessel function and preventing blood from pooling in the legs.

Autonomic Nervous System

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Autonomic nervous system dysfunction in adolescents with postural orthostatic tachycardia syndrome and chronic fatigue syndrome is characterized by attenuated vagal baroreflex and potentiated sympathetic vasomotion.

Stewart, J M·Pediatric research·2000

This study looked at how the nervous system controls heart rate and blood pressure in adolescents with ME/CFS and POTS when they stand up or tilt their head upward. Researchers found that both groups had similar problems: their bodies couldn't properly regulate heart rate through the vagus nerve (which normally helps calm the heart), and their blood vessels were overly tense. This mismatch may explain why these patients experience dizziness, rapid heartbeat, and fatigue when standing.

Autonomic Nervous System

E3 PreliminaryReviewPEM unclearReview-Narrative

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Buskila, D·Current opinion in rheumatology·2000

This review article examines the connections between fibromyalgia, chronic fatigue syndrome (ME/CFS), and myofascial pain syndrome. Researchers found that people with these conditions often have tender points in their muscles, hormonal imbalances affecting stress response, and possible immune system involvement. The study suggests that talking therapies like cognitive behavioral therapy may help manage chronic pain in these conditions, and that children and adolescents with these illnesses often improve over time.

Pain and SensitizationAutonomic Nervous System

E3 PreliminaryMechanismPEM not requiredObservational

The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome.

Streeten, D H, Thomas, D, Bell, D S·The American journal of the medical sciences·2000

This study found that many ME/CFS patients experience a sudden drop in blood pressure and abnormal heart rate acceleration when standing up, along with symptoms like dizziness. The researchers discovered that low red blood cell volume was present in most patients tested, and that wearing inflatable compression pants could quickly reverse these standing problems. This suggests that problems with blood pooling in the legs when upright may contribute to ME/CFS symptoms.

Autonomic Nervous System

E3 PreliminaryReviewPEM unclearReview-Narrative

Sympathetic nervous system function in fibromyalgia.

Petzke, F, Clauw, D J·Current rheumatology reports·2000

This review examines how the sympathetic nervous system—the part that controls your 'fight or flight' stress response—works differently in fibromyalgia patients. Researchers looked at various ways to measure sympathetic function, including heart rate changes, stress hormone levels, and physical responses to stress. The authors also compared findings in fibromyalgia to similar conditions like ME/CFS, irritable bowel syndrome, and migraine to identify common patterns.

Autonomic Nervous System

E3 PreliminaryCohortPEM not requiredCase-Control

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

Rowe, P C, Barron, D F, Calkins, H et al.·The Journal of pediatrics·1999

This study looked at 12 teenagers who had both ME/CFS and a connective tissue condition called Ehlers-Danlos syndrome (EDS). All of them also experienced problems with blood pressure and heart rate when standing up (orthostatic intolerance). The researchers found that abnormal connective tissue in blood vessels may cause blood to pool in the legs when standing, which could explain why these conditions often occur together.

Autonomic Nervous System

E3 PreliminaryReviewPEM unclearReview-Narrative

The importance of orthostatic intolerance in the chronic fatigue syndrome.

Schondorf, R, Freeman, R·The American journal of the medical sciences·1999

This review examines how problems with standing up (orthostatic intolerance) are connected to ME/CFS. Many people with ME/CFS experience symptoms like dizziness, fatigue, trouble concentrating, shaking, and nausea when standing or sitting upright. The authors review what we know about this connection, including how to diagnose it, what tests can help, what might cause it, and how it might be treated.

Autonomic Nervous SystemDiagnostics

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: a hypothesis focusing on the autonomic nervous system.

Pagani, M, Lucini, D·Clinical science (London, England : 1979)·1999

This study looked at whether ME/CFS might be caused by problems with the autonomic nervous system—the part of your nervous system that controls automatic functions like heart rate and blood pressure. The researchers measured how the heart's electrical activity varied in ME/CFS patients and found signs suggesting their nervous systems were stuck in a 'revved up' state at rest but didn't respond normally to challenges.

Autonomic Nervous System

E3 PreliminaryReviewPEM not requiredReview-Narrative

[No strong evidence of disturbed regulation of blood pressure in chronic fatigue syndrome].

Smit, A A, Bolweg, N M, Lenders, J W et al.·Nederlands tijdschrift voor geneeskunde·1998

Some ME/CFS patients experience dizziness or fainting when standing up, and researchers wondered if this was due to problems controlling blood pressure. This review looked at four studies that tested this by having patients lie flat and then tilt them upright to see how their bodies responded. While some patients did show heart rate increases or fainting, many of these patients already had these symptoms before testing, making it unclear whether the problem is truly a core feature of ME/CFS or something else.

Autonomic Nervous System

E3 PreliminaryReviewPEM not requiredReview-Narrative

Autonomic neuropathies.

Low, P A·Current opinion in neurology·1998

This review explores how problems with the autonomic nervous system—the part of your nervous system that controls automatic functions like heart rate and temperature regulation—may play a role in several conditions, including ME/CFS. The author discusses how antibodies (immune proteins) targeting autonomic structures are found in some diseases, and notes that some autonomic problems can be treated with medications like midodrine or erythropoietin.

Autonomic Nervous System

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome.

Stewart, J, Weldon, A, Arlievsky, N et al.·Clinical autonomic research : official journal of the Clinical Autonomic Research Society·1998

This study looked at how the nervous system controls heart rate in children with ME/CFS during a tilt test (where patients lie flat then are gradually tilted upright). Researchers found that children with ME/CFS had much lower heart rate variability—a measure of how well the nervous system adjusts the heart—compared to children who faint from other causes and healthy controls. When tilted, children with ME/CFS did not show the normal nervous system adjustments that other groups showed, suggesting their autonomic nervous system (which controls involuntary functions) may not be working properly.

Autonomic Nervous System

E3 PreliminaryReviewPEM unclearReview-Narrative

The connection between chronic fatigue syndrome and neurally mediated hypotension.

Wilke, W S, Fouad-Tarazi, F M, Cash, J M et al.·Cleveland Clinic journal of medicine·1998

Some ME/CFS patients experience a problem where their blood pressure drops abnormally when they stand up, a condition called neurally mediated hypotension. This review examines research showing that this blood pressure response may be linked to ME/CFS symptoms. Understanding this connection could help explain why some patients feel worse with certain activities and may guide treatment options.

Autonomic Nervous System

E3 PreliminaryReviewPEM not requiredReview-Narrative

Neurotic, neuromuscular and autonomic nervous form of magnesium imbalance.

Durlach, J, Bac, P, Durlach, V et al.·Magnesium research·1997

This review discusses how low magnesium levels in the body can affect the nervous system and cause symptoms like fatigue, muscle twitching, heart palpitations, and breathing problems. The authors describe how magnesium deficiency can mimic or contribute to chronic fatigue syndrome and similar conditions, and they explain tests (like EMG and blood tests) that can help diagnose this problem. They also suggest that taking magnesium supplements by mouth at appropriate doses may help relieve these symptoms.

Autonomic Nervous System

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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.