ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

441–460 of 746 studies

E2 ModerateCohortPEM not requiredCase-Control

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome.

MacDonald, K L, Osterholm, M T, LeDell, K H et al.·The American journal of medicine·1996

This study compared 47 people with ME/CFS to 47 matched healthy controls to identify what might trigger or contribute to the illness. Researchers found that people with ME/CFS were more likely to have exercised regularly before getting sick, and women with ME/CFS were more likely to have never had children. Depression was more common after ME/CFS developed, though it wasn't more common before illness onset.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

An examination of the working case definition of chronic fatigue syndrome.

Komaroff, A L, Fagioli, L R, Geiger, A M et al.·The American journal of medicine·1996

Researchers studied 281 patients with severe, long-lasting fatigue to see how well the official definition of ME/CFS worked. They compared these patients to healthy people and people with similar conditions like multiple sclerosis and depression. The study found that certain symptoms—like muscle pain, post-exertion exhaustion, headaches, and flu-like symptoms—were very common in ME/CFS patients but rare in the other groups.

Post-Exertional Malaise

E2 ModerateBehavioralPEM not requiredCase-Control

Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting.

Wessely, S, Chalder, T, Hirsch, S et al.·The American journal of psychiatry·1996

This study followed over 1,900 people in primary care and found that most individuals with ME/CFS also had a current mental health condition like depression or anxiety. The researchers discovered that people with chronic fatigue were much more likely to have psychiatric disorders (60-78%) compared to those without fatigue (19-31%). While the study suggests a strong link between psychiatric conditions and ME/CFS, it does not explain whether one causes the other.

Post-Exertional Malaise

E2 ModerateBehavioralPEM not requiredCross-Sectional

The impact of catastrophic beliefs on functioning in chronic fatigue syndrome.

Petrie, K, Moss-Morris, R, Weinman, J·Journal of psychosomatic research·1995

This study looked at whether how people think about ME/CFS affects how disabled they become. Researchers asked 282 people with ME/CFS what they thought would happen if they pushed themselves too hard, and sorted their answers into catastrophic (very negative) or non-catastrophic thinking. People who had catastrophic thoughts about pushing themselves were significantly more fatigued and more disabled in work, household tasks, sleep, socializing, and hobbies—even though they had been sick for similar lengths of time as others.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

Repetitively negative changing T waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome. Left ventricular dysfunction in a cohort.

Lerner, A M, Lawrie, C, Dworkin, H S·Chest·1993

This study looked at heart activity recorded over 24 hours in ME/CFS patients compared to others. All 24 ME/CFS patients showed unusual patterns on their heart monitors (abnormal T waves), compared to only 22% of people without ME/CFS. Further testing found that 8 out of 60 ME/CFS patients had mild heart pumping problems that only showed up during exercise, even though their resting heart function appeared normal. The researchers suggest ME/CFS fatigue might be related to the heart not working well during normal daily activities.

Post-Exertional Malaise

E2 ModerateReviewPEM unclearReview-Narrative

Symptoms and signs of chronic fatigue syndrome.

Komaroff, A L, Buchwald, D·Reviews of infectious diseases·1991

This review summarizes what doctors have learned about chronic fatigue syndrome (ME/CFS) by studying approximately 510 patients. The hallmark features include a sudden illness-like onset, long-lasting exhaustion that severely limits daily activities, and a unique symptom called postexertional malaise—where patients feel much worse after physical or mental activity. Many patients also experience fever, sore throat, swollen lymph nodes, muscle pain, sleep problems, and difficulty concentrating.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Aerobic work capacity in patients with chronic fatigue syndrome.

Riley, M S, O'Brien, C J, McCluskey, D R et al.·BMJ (Clinical research ed.)·1990

This study tested how much physical activity patients with ME/CFS could manage on a treadmill and compared them to healthy people and those with irritable bowel syndrome. Researchers found that ME/CFS patients got tired much faster, had higher heart rates during exercise, and felt like they were working much harder than the other groups—even though they weren't doing as much activity.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

Cardiac function at rest and with exercise in the chronic fatigue syndrome.

Montague, T J, Marrie, T J, Klassen, G A et al.·Chest·1989

This study looked at heart function in 41 ME/CFS patients compared to healthy volunteers. While the hearts looked normal at rest, patients became exhausted during exercise much sooner than healthy people—their heart rates climbed more slowly and didn't reach the expected levels, even though their resting heart rhythms and structure were completely normal.

Post-Exertional Malaise

E3 PreliminaryGuidelinePEM requiredGuideline

[Transdisciplinary Expert Statement: care guide for people severely affected by ME/CFS in home-based care].

Hermisson, Joachim, Schreiner, Claudia, Weichselbaumer, Stefanie et al.·Wiener medizinische Wochenschrift (1946)·2026

This guide describes practical home-care approaches for people severely affected by ME/CFS, developed by combining advice from patients and family caregivers with input from nursing, physiotherapy, and medical professionals. The guide addresses how to adjust daily care activities—such as nutrition, hygiene, and communication—to avoid overexertion and post-exertional malaise (PEM). However, because this is a compiled expert consensus rather than a systematic trial, the strength of evidence for each recommendation remains unclear.

Severe MEInterventionsPost-Exertional Malaise

E3 PreliminaryReviewPEM requiredReview-Narrative

Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.

Nunes, Massimo, Kell, Loren, Slaghekke, Anouk et al.·Cell death & disease·2026

This study proposes that ME/CFS and long COVID may be caused by damage to the blood vessels (endothelial cells) that occurs after a viral infection. When these cells become damaged and 'senescent' (aged), they release harmful substances that cause inflammation, blood clots, and reduced blood flow to the brain and other organs. The study suggests that a faulty immune system keeps these damaged blood vessels from healing, which is why symptoms persist for months or years after the initial infection.

Immune SystemPost-Exertional Malaise

E3 PreliminaryGuidelinePEM requiredGuideline

Guidance on Home-Based Care for People with Severe ME/CFS: A Transdisciplinary Expert Statement.

Hermisson, Joachim, Schreiner, Claudia, Weichselbaumer, Stefanie et al.·Wiener medizinische Wochenschrift (1946)·2026

This is a clinical guidance document developed by experts across nursing, physical therapy, medicine, and public health to help healthcare professionals and family caregivers provide home-based care for people with severe ME/CFS. The guide describes practical adjustments to everyday care tasks—such as nutrition, personal hygiene, communication, and emotional support—designed to respect the exertion thresholds associated with post-exertional malaise (PEM), the hallmark symptom of ME/CFS. The recommendations are based on strategies reported as helpful by patients and family caregivers, though the strength of evidence for each measure has not been formally graded in this summary.

Severe MEInterventionsPost-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Physiotherapy management of long COVID in adults.

Nygren-Bonnier, Malin, Holland, Anne E·Journal of physiotherapy·2026

This study examines how physical therapy and rehabilitation approaches can help adults with long COVID manage their symptoms and improve function. The review looks at different physiotherapy strategies that healthcare providers use to treat long COVID patients. Understanding which approaches work best can help patients and doctors make better decisions about treatment options.

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale.

Friedberg, Fred, LeBaron, Tyler W·Frontiers in medicine·2026

This review examines whether hydrogen-rich water might help ME/CFS patients. Hydrogen is a simple molecule that may reduce inflammation and improve energy production in cells—two problems linked to ME/CFS. Early studies show it may help reduce fatigue and improve daily functioning with few side effects, though the research is still very limited.

Post-Exertional Malaise

E3 PreliminaryCohortPEM unclearObservational

Treatment of post-COVID symptoms with auricular vagus nerve stimulation.

Gebetsroither, Patrick, Ettenauer, Thomas, Likar, Rudolf·Wiener medizinische Wochenschrift (1946)·2026

Researchers tested a treatment called auricular vagus nerve stimulation (mild electrical stimulation applied to the ear) in 9 patients with long COVID symptoms. After 4 weeks of treatment, patients reported improvement in 28 out of 35 symptoms they were tracked for, with particular benefits for pain, fatigue, exhaustion after activity, sleep problems, and heart/blood pressure irregularities. Many of these improvements lasted when patients were checked again 12 weeks later.

Post-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Significant aggravation of pre-existing myalgic encephalomyelitis/chronic fatigue syndrome following proton beam therapy for sphenoid wing meningioma: case report.

Fischer, Christian, Seidlitz, Annekatrin, Krause, Mechthild·Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]·2026

This is a single case report of a 46-year-old woman with ME/CFS whose condition severely worsened after receiving proton beam radiation therapy for a brain tumor. Over months following treatment, she went from being ambulatory to completely bedridden, with worsening fatigue, pain, dizziness, and cognitive problems. The report suggests that radiation may have triggered this deterioration, but it remains unclear whether this outcome would occur in other ME/CFS patients undergoing similar treatment.

Pain and SensitizationSevere MEEnergy MetabolismCognitive Impairment

E3 PreliminaryCommentaryPEM requiredEditorial

Expert perspectives on Myalgic encephalomyelitis/chronic fatigue syndrome - Insights from the 3rd International Conference of the Charité Fatigue Center.

Fehrer, Annick, Windzio, Lara, Schoening, Simon et al.·Autoimmunity reviews·2026

Nearly 4,000 ME/CFS researchers and experts gathered at an international conference in May 2025 to share the latest discoveries about this serious illness. They discussed how ME/CFS develops, better ways to diagnose it, and new treatments being tested. The conference highlighted that while COVID-19 has brought more attention and funding to ME/CFS research, the disease is still not well understood and needs much more study.

Energy MetabolismImmune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM requiredReview-Narrative

Lactate, Capnia, and Fat Oxidation as Therapeutic Axes for SARS-CoV-2 Spike Protein-Induced Sequelae.

Gracidas, Carlos, Levy, Rakeem, Varon, Joseph et al.·Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme·2026

This review suggests that ME/CFS and long COVID symptoms—including exhaustion, brain fog, and crashing after activity—may be caused by problems with how the body's energy-producing structures (mitochondria) work. The authors propose that treatments targeting three areas could help: improving the body's ability to handle lactate (a byproduct of exertion), increasing oxygen delivery to tissues, and helping the body burn fat for energy more efficiently, similar to how endurance athletes train.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM required

From fatigue to physiology: Submaximal 2-day cardiopulmonary exercise test and emerging standards in long COVID.

Risbano, Michael G·Experimental physiology·2026

This study examines how a special two-day exercise test can help doctors understand the physical changes that happen in long COVID and ME/CFS patients. Instead of pushing patients to their maximum effort, researchers used a gentler approach to measure heart and lung function, which may be safer and more revealing for people with these conditions. The study aims to create new standard ways of testing that better capture what's happening in patients' bodies.

Post-Exertional Malaise

E3 PreliminaryCommentaryPEM not requiredEditorial

An Overview of Severe Myalgic Encephalomyelitis.

Vink, Mark, Vink-Niese, Alexandra·Journal of clinical medicine·2026

This article reviews what we know about severe ME/CFS, a serious illness that can leave people completely bedbound and dependent on caregivers. Currently, there is no blood test or scan that can diagnose ME/CFS, though a special two-day exercise test can help document the problem. The authors emphasize that severe ME/CFS is a major medical condition that has received very little research funding, and there are currently no proven treatments available.

Severe MEPost-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Resolution of Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome symptoms following kanshoho, a low-pressure muscle relaxation technique: A case report.

Amitani, Haruka, Sakato, Takashi, Asakawa, Akihiro·Explore (New York, N.Y.)·2026

A woman with Long COVID and ME/CFS who had severe fatigue, pain, brain fog, and sleep problems tried a gentle hands-on relaxation technique called kanshoho along with activity pacing advice. After 10 treatment sessions over 2.5 months, her symptoms completely resolved, and she was able to stop her antidepressant medication without symptom worsening. While this is just one person's experience, it suggests this low-pressure approach might help some ME/CFS patients who cannot tolerate exercise-based treatments.

Post-Exertional Malaise

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A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome.

An examination of the working case definition of chronic fatigue syndrome.

Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting.

The impact of catastrophic beliefs on functioning in chronic fatigue syndrome.

Repetitively negative changing T waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome. Left ventricular dysfunction in a cohort.

Symptoms and signs of chronic fatigue syndrome.

Aerobic work capacity in patients with chronic fatigue syndrome.

Cardiac function at rest and with exercise in the chronic fatigue syndrome.

[Transdisciplinary Expert Statement: care guide for people severely affected by ME/CFS in home-based care].

Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.

Guidance on Home-Based Care for People with Severe ME/CFS: A Transdisciplinary Expert Statement.

Physiotherapy management of long COVID in adults.

Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale.

Treatment of post-COVID symptoms with auricular vagus nerve stimulation.

Significant aggravation of pre-existing myalgic encephalomyelitis/chronic fatigue syndrome following proton beam therapy for sphenoid wing meningioma: case report.

Expert perspectives on Myalgic encephalomyelitis/chronic fatigue syndrome - Insights from the 3rd International Conference of the Charité Fatigue Center.

Lactate, Capnia, and Fat Oxidation as Therapeutic Axes for SARS-CoV-2 Spike Protein-Induced Sequelae.

From fatigue to physiology: Submaximal 2-day cardiopulmonary exercise test and emerging standards in long COVID.

An Overview of Severe Myalgic Encephalomyelitis.

Resolution of Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome symptoms following kanshoho, a low-pressure muscle relaxation technique: A case report.

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Neuroinflammation Evidence

Metabolism & Mitochondria

Biomarkers

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