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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 →

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360 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

221–240 of 360 studies

E2 ModerateCohortPEM not requiredCross-Sectional

Autonomic instability, as measured by pupillary unrest, is not associated with multiple sclerosis fatigue severity.

Egg, R, Högl, B, Glatzl, S et al.·Multiple sclerosis (Houndmills, Basingstoke, England)·2002

This study looked at whether problems with the nervous system's ability to regulate automatic body functions (like pupil responses) might explain fatigue in multiple sclerosis patients. Researchers measured pupil movements in MS patients and healthy volunteers, then compared these measurements to fatigue severity scores. Surprisingly, they found the opposite of what they expected: people with more pupil instability actually reported less fatigue, not more.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Hemodynamic and neurohumoral responses to head-up tilt in patients with chronic fatigue syndrome.

Timmers, H J L M, Wieling, W, Soetekouw, P M M B et al.·Clinical autonomic research : official journal of the Clinical Autonomic Research Society·2002

This study looked at whether ME/CFS patients have problems with blood pressure and heart rate control when standing up or tilting upright. Researchers tested 36 ME/CFS patients and 36 healthy people by tilting them upright for 40 minutes while measuring heart function and stress hormones. About 28% of ME/CFS patients had abnormal responses (like fainting symptoms or rapid heart rate), compared to 17% of healthy controls, though this difference was not statistically significant.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Cardiovascular response to upright tilt in fibromyalgia differs from that in chronic fatigue syndrome.

Naschitz, J E, Rozenbaum, M, Rosner, I et al.·The Journal of rheumatology·2001

This study compared how the bodies of people with fibromyalgia and ME/CFS respond to standing up from lying down. Researchers measured blood pressure and heart rate while patients lay down and then tilted upright for 30 minutes. They found that fibromyalgia and ME/CFS patients had very different cardiovascular responses to this position change, suggesting these are two distinct conditions rather than the same illness.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCross-Sectional

Hemodynamic instability in chronic fatigue syndrome: indices and diagnostic significance.

Naschitz, J E, Sabo, E, Naschitz, S et al.·Seminars in arthritis and rheumatism·2001

This study tested how the body's blood pressure and heart rate respond when patients stand up from lying down (a tilt test). Researchers found that people with ME/CFS have much more unstable cardiovascular responses compared to healthy people and those with other conditions. A mathematical score called the hemodynamic instability score (HIS) could correctly identify ME/CFS patients 97% of the time, suggesting this test might help doctors diagnose the condition.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCase-Control

Enhanced sensitivity of the peripheral cholinergic vascular response in patients with chronic fatigue syndrome.

Spence, V A, Khan, F, Belch, J J·The American journal of medicine·2000

This study looked at how blood vessels in ME/CFS patients respond to a natural chemical in the body called acetylcholine, which helps control blood vessel widening and narrowing. Researchers compared blood vessel responses in ME/CFS patients versus healthy people and found that ME/CFS patients showed an unusually strong reaction. This finding suggests that the nervous system's control of blood vessels may work differently in ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Results of isoproterenol tilt table testing in monozygotic twins discordant for chronic fatigue syndrome.

Poole, J, Herrell, R, Ashton, S et al.·Archives of internal medicine·2000

This study tested whether a condition called neurally mediated hypotension (a sudden drop in blood pressure) might be causing ME/CFS. Researchers compared identical twins where one had ME/CFS and one was healthy, using a tilt table test to measure blood pressure responses. They found that healthy twins and twins with ME/CFS had similar rates of this blood pressure problem, suggesting it is probably not a main cause of ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

The capnography head-up tilt test for evaluation of chronic fatigue syndrome.

Naschitz, J E, Rosner, I, Rozenbaum, M et al.·Seminars in arthritis and rheumatism·2000

This study tested whether a special tilt table test that measures blood pressure, heart rate, breathing, and carbon dioxide levels could help diagnose ME/CFS. Researchers compared 32 ME/CFS patients to 32 healthy people during this test. ME/CFS patients showed abnormal responses—like drops in blood pressure, increases in heart rate, faster breathing, and lower carbon dioxide levels—while healthy people did not, suggesting this test might help identify ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCross-Sectional

Neurally mediated hypotension in fatigued Gulf War veterans: a preliminary report.

Davis, S D, Kator, S F, Wonnett, J A et al.·The American journal of the medical sciences·2000

This study tested whether fatigued Gulf War veterans have problems with blood pressure control when standing up quickly (a condition called neurally mediated hypotension), similar to what researchers have seen in ME/CFS patients. The researchers tilted 14 fatigued Gulf War veterans on a special table and compared their responses to two groups of unfatigued veterans and non-veterans. They found that fatigued veterans were more likely to experience dangerous drops in blood pressure during the test, suggesting their autonomic nervous system (the part that automatically controls heart rate and blood pressure) may not be working properly.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCase-Control

Dysautonomia in chronic fatigue syndrome vs. fibromyalgia.

Rosner, I, Rozenbaum, M, Naschitz, J E et al.·The Israel Medical Association journal : IMAJ·2000

This study compared how the nervous systems of people with ME/CFS and fibromyalgia function differently, focusing on dysautonomia—problems with the automatic nervous system that controls heart rate, blood pressure, and other body functions. Researchers used a case-control design to examine whether these two conditions show distinct patterns of autonomic dysfunction. The findings help clarify whether ME/CFS and fibromyalgia are separate conditions with different underlying nervous system problems.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Orthostatic intolerance in the chronic fatigue syndrome.

Schondorf, R, Benoit, J, Wein, T et al.·Journal of the autonomic nervous system·1999

This study looked at whether ME/CFS patients experience problems with blood pressure and heart rate when standing up quickly, a condition called orthostatic intolerance. Researchers tested 75 ME/CFS patients and 48 healthy controls using a tilt table test and other physical challenges. They found that 40% of ME/CFS patients had orthostatic intolerance compared to fewer healthy controls, suggesting this may be an important symptom in some patients that could be treated.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Autonomic function in patients with chronic fatigue syndrome.

Soetekouw, P M, Lenders, J W, Bleijenberg, G et al.·Clinical autonomic research : official journal of the Clinical Autonomic Research Society·1999

Researchers tested whether ME/CFS patients have problems with the part of the nervous system that automatically controls heart rate and blood pressure. They compared 37 ME/CFS patients to 38 healthy people using several tests (like standing up quickly, holding their breath, and doing mental math). The study found only minor differences, suggesting that major autonomic problems may not be the primary issue in ME/CFS, though some specific responses to stress were reduced.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue.

Stewart, J M, Gewitz, M H, Weldon, A et al.·The Journal of pediatrics·1999

This study looked at how the hearts and blood pressure of adolescents with ME/CFS and a related condition called orthostatic tachycardia syndrome (OTS) respond when they stand up or are tilted upright. Researchers found that adolescents with ME/CFS had more severe problems with standing (like dizziness and fainting) than those with OTS, but the underlying patterns were quite similar. The study suggests that OTS may be a milder version of the same blood pressure and heart rate problems seen in ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Cardiovascular response during head-up tilt in chronic fatigue syndrome.

LaManca, J J, Peckerman, A, Walker, J et al.·Clinical physiology (Oxford, England)·1999

This study tested how the hearts of ME/CFS patients respond to positional changes using a tilt table test, where participants lie flat then are gradually tilted upward for 45 minutes. While ME/CFS patients showed different baseline heart rates and heart pumping patterns compared to healthy controls, the overall frequency of fainting-like responses was similar between the two groups.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Orthostatic intolerance in adolescent chronic fatigue syndrome.

Stewart, J M, Gewitz, M H, Weldon, A et al.·Pediatrics·1999

This study looked at how the bodies of adolescents with ME/CFS respond when they stand up or tilt upright. Researchers found that nearly all ME/CFS patients showed significant problems with this response, including rapid heart rate, blood pressure drops, and symptoms like dizziness and fainting. These problems were much more common in ME/CFS patients than in healthy teenagers or those with simple fainting disorders.

Autonomic Nervous System

E2 ModerateBehavioralPEM not requiredCross-Sectional

Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: support for a neural sensitization model.

Bell, I R, Baldwin, C M, Russek, L G et al.·Journal of women's health·1998

This study looked at whether women with chemical sensitivity (difficulty tolerating everyday chemicals) had experienced more childhood stress or difficult relationships with their fathers compared to women with depression alone or women without these conditions. The researchers found that women with chemical sensitivity had weaker relationships with their fathers and showed signs of nervous system overactivity. The study suggests that repeated exposure to stress early in life might train the nervous system to react more strongly to chemicals and other triggers.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Autonomic testing in patients with chronic fatigue syndrome.

De Becker, P, Dendale, P, De Meirleir, K et al.·The American journal of medicine·1998

This study tested how the nervous system that controls heart rate and blood pressure works in ME/CFS patients compared to healthy people. Researchers found that ME/CFS patients had higher heart rates and stronger stress responses when standing up, suggesting their bodies may be overactive in certain stress situations. However, these findings did not fully explain why ME/CFS patients experience fatigue and problems with exercise.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredObservational

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.

van de Luit, L, van der Meulen, J, Cleophas, T J et al.·Angiology·1998

This study found that people with ME/CFS have unusually large swings in heart rate and blood pressure throughout the day and night, even though the overall pattern matches healthy controls. Importantly, their nighttime blood pressure drops too low (below 100 mm Hg systolic), which may contribute to fatigue and other symptoms. When treated with a heart-strengthening medication called inopamil, nighttime blood pressure improved, but melatonin actually made it worse.

Autonomic Nervous System

E2 ModerateReviewPEM not requiredReview-Narrative

Relationship Between Chronic Fatigue Syndrome and Neurally Mediated Hypotension.

Calkins, H, Rowe, PC·Cardiology in review·1998

This study explored a possible connection between ME/CFS and a condition called neurally mediated hypotension, where blood pressure drops suddenly due to problems with nerve signals that control blood vessels. Researchers found that when they treated patients for this blood pressure problem, about two-thirds of ME/CFS patients felt better. While these early results were promising, the study notes that larger, more rigorous trials were needed to confirm whether this treatment truly helps.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue.

Streeten, D H, Anderson, G H·Clinical autonomic research : official journal of the Clinical Autonomic Research Society·1998

This study looked at whether problems with blood pressure regulation—specifically a delayed drop in blood pressure when standing up—might explain why some people with chronic fatigue syndrome feel so exhausted. Researchers surveyed 431 patients with various neurological and hormonal disorders and found that fatigue was very common in people with delayed blood pressure drops and low cortisol levels (70-83%), but much less common in people with other conditions like multiple system atrophy (7-33%). This suggests a possible connection between blood pressure regulation problems and severe fatigue.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Long- and short-term blood pressure and RR-interval variability and psychosomatic distress in chronic fatigue syndrome.

Duprez, D A, De Buyzere, M L, Drieghe, B et al.·Clinical science (London, England : 1979)·1998

Researchers compared blood pressure and heart rate patterns in people with ME/CFS to healthy controls. They found that people with ME/CFS had normal blood pressure readings, but their heart rates were consistently higher. When lying down, people with ME/CFS also showed reduced variability in blood pressure patterns compared to healthy controls.

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.