ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

61–80 of 184 studies

E2 ModerateMechanismPEM unclearMechanistic

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Yasuhito Nakatomi, Kei Mizuno, Akira Ishii et al.·Brain, Behavior, and Immunity·2014·n=9

Japanese researchers used PET imaging with a neuroinflammation tracer (PK11195) in 9 ME/CFS patients and healthy controls. They found significantly elevated neuroinflammation signals across multiple brain regions in ME/CFS patients, particularly in the cingulate cortex, thalamus, and brainstem — areas regulating fatigue and cognition.

Neuroinflammation

E2 ModerateReviewPEM unclearReview-Narrative

The neuroinflammatory hypothesis of chronic fatigue syndrome/myalgic encephalomyelitis: an update

Jarred W. Younger, Linda Yan, Sean Mackey·Journal of Neuroinflammation·2014·n=18

Using thermography and brain temperature imaging at Stanford, this study found evidence consistent with neuroinflammation — specifically elevated brain temperature — in ME/CFS patients compared to healthy controls. Brain regions associated with pain and fatigue showed the strongest signal.

Neuroinflammation

E2 ModerateCohortPEM unclearCase-Control

In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

Maes, Michael, Ringel, Karl, Kubera, Marta et al.·Journal of affective disorders·2013

This study found that people with ME/CFS often develop antibodies (immune proteins) against serotonin, a chemical messenger in the brain. These antibodies were linked to higher levels of inflammation, signs of bacteria leaking from the gut, and worse symptoms including pain, fatigue, brain fog, and mood changes. The findings suggest ME/CFS involves immune system problems that may contribute to the condition's core symptoms.

NeuroinflammationImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome.

Schutzer, Steven E, Angel, Thomas E, Liu, Tao et al.·PloS one·2011

This study examined spinal fluid from people with post-treatment Lyme disease and ME/CFS to see if these two conditions are different. Using advanced laboratory techniques, researchers found that each condition has a unique pattern of proteins in the spinal fluid, meaning they appear to be distinct diseases rather than the same illness. This discovery could eventually help doctors tell these conditions apart and develop better treatments for each.

Neuroinflammation

E2 ModerateCohortPEM not requiredCross-Sectional

Spinal fluid abnormalities in patients with chronic fatigue syndrome.

Natelson, Benjamin H, Weaver, Shelley A, Tseng, Chin-Lin et al.·Clinical and diagnostic laboratory immunology·2005

Researchers performed spinal taps on 44 ME/CFS patients and 13 healthy people to look for signs of brain inflammation. They found that 30% of ME/CFS patients had abnormal levels of white blood cells or proteins in their spinal fluid, compared to none in the healthy group. They also found that certain immune molecules were different in ME/CFS patients, particularly in those with sudden flu-like symptom onset. These results suggest that ME/CFS may involve real physical changes in the nervous system, not just psychological factors.

NeuroinflammationImmune System

E3 PreliminaryMechanismPEM unclearCross-Sectional

Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME/CFS.

Bragée, Björn, Li, Peng, Meadows, Danielle et al.·Scientific reports·2026

Researchers analyzed fluid from the spinal cords of 31 ME/CFS patients to study 902 different proteins and understand what might be happening in their bodies. They found that patients with certain heart-related symptoms (POTS) had different protein patterns, and those with more severe ME/CFS had changes in immune system and blood clotting proteins. These protein patterns suggest several biological processes may be involved in ME/CFS, providing clues for future research.

NeuroinflammationImmune System

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Post-COVID neurological sequelae, proposed mechanisms and therapeutic approaches].

Slama Schwok, Anny·Medecine sciences : M/S·2026

This review examines the long-term neurological effects that some people experience after COVID-19 infection, affecting about 5% of patients. The symptoms include brain fog, chronic fatigue, anxiety, depression, and nerve inflammation, which significantly impact daily life. The authors examine the underlying biological mechanisms—such as brain inflammation, disrupted brain chemistry, immune dysfunction, and blood vessel problems—that may cause these symptoms to help guide future treatments.

Neuroinflammation

E3 PreliminaryReviewPEM unclearReview-Narrative

Immunosenescence-Driven Hemodynamic Dysregulation and Cognitive Impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Integrative Perspective.

Xu, Huimin, Luo, Yingzhe, Wu, Xi·Comprehensive Physiology·2026

This review examines how ME/CFS may involve aging of the immune system that affects blood flow to the brain, causing cognitive problems like 'brain fog.' The researchers propose that this immune aging triggers chronic inflammation, reduces oxygen delivery to brain cells, and damages the protective barrier around the brain, leading to memory and thinking difficulties. The authors suggest that treatments targeting inflammation, improving blood vessel function, and modulating immune responses could help improve cognition in ME/CFS patients.

Neuroinflammation

E3 PreliminaryCommentaryPEM unclearEditorial

Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.

Blitshteyn, Svetlana, Doherty, Taylor A, Steinman, Lawrence·ImmunoTargets and therapy·2026

This editorial argues that three related conditions—POTS, ME/CFS, and Long COVID—should be understood and studied together as disorders affecting both the nervous system and immune system. The authors identify several common problems in these conditions, including heart rate abnormalities when standing, immune system dysfunction, and reduced blood flow to the brain. They believe treating these as a single category of disease could improve how doctors train, research, and care for patients with these serious illnesses.

NeuroinflammationImmune System

E3 PreliminaryMechanismPEM not requiredMechanistic

Chronic fatigue syndrome induced by environmental toxic exposure: Effects of polyhexamethyleneguanidine phosphate exposure on mitochondrial function and neural health.

Yang, Hyo-Seon, Lee, Jin-Seok, Kang, Mi-Hyun et al.·Environmental research·2026

This study found that exposure to humidifier disinfectants—cleaning chemicals used in humidifiers—may trigger ME/CFS by damaging the energy-producing structures (mitochondria) inside our cells and disrupting communication in the brain. Researchers compared patients with ME/CFS who had been exposed to these chemicals to laboratory mice exposed to the same chemicals, and both showed similar problems with mitochondrial function and brain health. The findings suggest that environmental toxins could be a trigger for ME/CFS in some people.

Neuroinflammation

E3 PreliminaryMechanismPEM not requiredMechanistic

Immunomodulatory and locomotor regulations via Diosgenin treatment in lipopolysaccharide-induced chronic fatigue syndrome (CFS)/ depressive despair symptom: an in vivo assessment.

Shirole, Rahul Lotan, Khalane, Mohan Rajendra, Nage, Vijayeta Pralhad et al.·Naunyn-Schmiedeberg's archives of pharmacology·2026

This study tested a natural compound called diosgenin (found in fenugreek) to see if it could help with fatigue and depression-like symptoms in mice given a substance that triggered an immune response similar to what happens in ME/CFS. Mice treated with diosgenin showed improvements in activity levels, reduced fatigue-like behavior, and their brains had less inflammation and stress. The results suggest diosgenin might be worth investigating further as a potential treatment.

NeuroinflammationImmune System

E3 PreliminaryReviewPEM requiredReview-Narrative

Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.

Gupta, Gautam, Buonsenso, Danilo, Wood, John et al.·Comprehensive Physiology·2025

This review examines how Long Covid causes persistent symptoms affecting multiple body systems. The research suggests that SARS-CoV-2 virus may hide in body tissues, trigger ongoing immune problems, and damage how cells produce energy, which could explain fatigue and post-exertion crashes. These mechanisms appear similar to ME/CFS, suggesting the two conditions may share common biological pathways.

NeuroinflammationImmune SystemPost-Exertional Malaise

E3 PreliminaryCommentaryPEM not requiredEditorial

Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.

Livieratos, Achilleas, Lockley, Steven W, Tsiodras, Sotirios·EClinicalMedicine·2025

This article discusses how infections like COVID-19 can disrupt the body's internal 24-hour clock, leading to persistent fatigue and sleep problems. The authors explain that viral infections may damage the genes and cellular machinery that control our daily rhythms, trigger inflammation in the brain, and harm energy-producing structures in our cells. Understanding these mechanisms could help doctors develop better treatments for Long COVID and chronic fatigue syndrome.

Neuroinflammation

E3 PreliminaryMechanismPEM not requiredMechanistic

PKM2 accelerated the progression of chronic fatigue syndrome via promoting the H4K12la/ NF-κB induced neuroinflammation and mitochondrial damage.

Sun, Meng, Zhang, Xinwen, Feng, Xinli et al.·Scientific reports·2025

This study in mice explored how a protein called PKM2 may contribute to ME/CFS by increasing inflammation in the brain and damaging energy-producing structures inside cells (mitochondria). Researchers found that when PKM2 levels increased, cognitive problems worsened and brain cells showed more damage, while reducing PKM2 improved these outcomes. The mechanism involves lactate buildup and activation of inflammatory pathways in the brain.

Neuroinflammation

E3 PreliminaryReviewPEM unclearReview-Narrative

The Gut-Brain-Immune Axis in Environmental Sensitivity Illnesses: Microbiome-Centered Narrative Review of Fibromyalgia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Multiple Chemical Sensitivity.

Watai, Kentaro, Taniguchi, Masami, Azuma, Kenichi·International journal of molecular sciences·2025

This review examines how changes in gut bacteria may contribute to ME/CFS, fibromyalgia, and multiple chemical sensitivity—three conditions that share similar symptoms like fatigue, pain, and sensitivity to environmental triggers. The researchers found that people with these conditions tend to have fewer helpful bacteria and more harmful bacteria in their gut, which may affect how their immune system and brain work. The review suggests that treatments targeting the microbiome—such as probiotics or other interventions—might help, though more research is needed to confirm this.

NeuroinflammationEnergy MetabolismImmune System

E3 PreliminaryMechanismPEM unclearCross-Sectional

Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients.

Shahbaz, Shima, Rezaeifar, Maryam, Syed, Hussein et al.·Brain, behavior, and immunity·2025

Researchers studied blood samples from Long COVID patients with ME/CFS-like symptoms and compared them to healthy controls. They found that certain genes related to immune function and brain health were turned on in the patients, while others were turned off. The study also discovered unusual activation of smell-related genes and changes in immune cell types, suggesting the body remains in a state of ongoing inflammation and stress.

NeuroinflammationBiomarkersImmune System

E3 PreliminaryReviewPEM unclearReview-Narrative

Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.

Fronticelli Baldelli, Giovanni, Buonsenso, Danilo·Children (Basel, Switzerland)·2025

This review proposes that a protein called mTOR may be the key link between infections and the long-lasting symptoms seen in ME/CFS and similar post-infection illnesses. The authors suggest that when mTOR stays overactive after an infection, it can damage the barrier that protects the brain, allow immune cells to enter brain tissue, and cause ongoing inflammation that affects how the brain works. They outline a step-by-step pathway explaining how this might happen and suggest that targeting mTOR could be a new treatment approach.

NeuroinflammationImmune System

E3 PreliminaryReviewPEM not requiredReview-Narrative

Management of Fibromyalgia: Novel Nutraceutical Therapies Beyond Traditional Pharmaceuticals.

Antonelli, Antonella, Bianchi, Marzia, Fear, Elizabeth Jane et al.·Nutrients·2025

This review examines how natural plant-based compounds, particularly polyphenols, might help manage fibromyalgia pain without the side effects of traditional medications. Fibromyalgia and ME/CFS are related conditions that involve abnormal pain signaling in the nervous system, persistent fatigue, and sleep problems. The authors suggest that natural products could be safer alternatives to current drugs like antidepressants and anticonvulsants, which can cause dependence and tolerance over time.

Neuroinflammation

E3 PreliminaryReviewPEM not requiredReview-Narrative

From Fork to Brain: The Role of AGE-RAGE Signaling and the Western Diet in Neurodegenerative Disease.

Pomroy, Haylie J, Mote, Arjun, Mathew, Simeon et al.·NeuroSci·2025

This review examines how certain compounds called AGEs (advanced glycation end products) form in food and in our bodies, and how they may contribute to brain damage and disease. AGEs are created when food is cooked at high temperatures or processed, and when they build up in the body, they can trigger inflammation and harm cells. The authors suggest that limiting AGEs in the diet might help prevent or slow down brain diseases, though more research is needed to confirm this.

Neuroinflammation

E3 PreliminaryMechanismPEM requiredMechanistic

Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.

Drosen, Molly E, Bulbule, Sarojini, Gottschalk, Gunnar et al.·Immunologic research·2025

Researchers gave mice a drug that overactivates a protein called mTOR and found it triggered muscle weakness, nerve damage, and worsening fatigue after exercise—similar to post-exertional malaise (PEM) in ME/CFS. The drug blocked a cellular cleanup system called autophagy, which led to inflammation and damage to the nerves controlling muscles. Mice engineered to have impaired autophagy showed similar problems, suggesting that broken autophagy may be involved in ME/CFS fatigue and exercise intolerance.

NeuroinflammationPost-Exertional Malaise

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Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

The neuroinflammatory hypothesis of chronic fatigue syndrome/myalgic encephalomyelitis: an update

In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome.

Spinal fluid abnormalities in patients with chronic fatigue syndrome.

Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME/CFS.

[Post-COVID neurological sequelae, proposed mechanisms and therapeutic approaches].

Immunosenescence-Driven Hemodynamic Dysregulation and Cognitive Impairment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Integrative Perspective.

Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.

Chronic fatigue syndrome induced by environmental toxic exposure: Effects of polyhexamethyleneguanidine phosphate exposure on mitochondrial function and neural health.

Immunomodulatory and locomotor regulations via Diosgenin treatment in lipopolysaccharide-induced chronic fatigue syndrome (CFS)/ depressive despair symptom: an in vivo assessment.

Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.

Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.

PKM2 accelerated the progression of chronic fatigue syndrome via promoting the H4K12la/ NF-κB induced neuroinflammation and mitochondrial damage.

The Gut-Brain-Immune Axis in Environmental Sensitivity Illnesses: Microbiome-Centered Narrative Review of Fibromyalgia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Multiple Chemical Sensitivity.

Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients.

Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.

Management of Fibromyalgia: Novel Nutraceutical Therapies Beyond Traditional Pharmaceuticals.

From Fork to Brain: The Role of AGE-RAGE Signaling and the Western Diet in Neurodegenerative Disease.

Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.

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