ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

21–40 of 179 studies

E0 ConsensusReviewPEM unclearReview-Narrative

The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

Moghimi, Narges, Di Napoli, Mario, Biller, José et al.·Current neurology and neuroscience reports·2021

This review examined what we know about how COVID-19 can affect the nervous system in people who experience long-term symptoms after infection (called PASC or long COVID). The researchers looked at published studies to understand how common these neurological problems are, who is most at risk, why they happen, and how they might be treated. They found that long COVID can range from mild to severely disabling symptoms that last weeks or longer, and that multiple factors—including lingering inflammation, immune system problems, and possible viral effects on the brain—may play a role.

NeuroinflammationImmune System

E0 ConsensusReviewPEM unclearSystematic-Review

Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings.

Nelson, Todd, Zhang, Lan-Xin, Guo, Hui et al.·Frontiers in neurology·2021

This review examined brain imaging studies to understand how ME/CFS affects the brainstem, which is the part of the brain that controls vital functions like heart rate, breathing, and sleep. Researchers found that people with ME/CFS often show changes in the brain's structure and how different brain regions communicate with each other. These findings suggest that problems in the brainstem might explain many ME/CFS symptoms, though more research is needed to fully understand the connections.

Neuroinflammation

E0 ConsensusReviewPEM requiredReview-Narrative

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.

Paul, Bindu D, Lemle, Marian D, Komaroff, Anthony L et al.·Proceedings of the National Academy of Sciences of the United States of America·2021

This review examines how COVID-19 and ME/CFS may share similar biological problems, particularly an imbalance in how the body handles harmful molecules called free radicals. Both conditions appear to involve problems with inflammation, energy production in cells, and a slowed metabolism. While this research shows these biological abnormalities exist in both illnesses, more studies are needed to understand exactly how they work together and how to treat them.

NeuroinflammationPost-Exertional Malaise

E0 ConsensusReviewPEM not requiredReview-Narrative

Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities.

Chaves-Filho, Adriano José Maia, Macedo, Danielle S, de Lucena, David Freitas et al.·Behavioural brain research·2019

This review examined how depression and ME/CFS might share common causes in the brain, specifically through immune cells called microglia. Researchers found that when these brain immune cells become overactive, they may trigger both depression and the fatigue characteristic of ME/CFS. The study suggests that reducing this immune activation could potentially help treat both conditions.

NeuroinflammationImmune System

E0 ConsensusReviewPEM unclearReview-Narrative

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease.

Lombardi, Vincent C, De Meirleir, Kenny L, Subramanian, Krishnamurthy et al.·The Journal of nutritional biochemistry·2018

Your gut bacteria and brain communicate constantly with each other in ways that affect your immune system and inflammation levels. This review looks at how diet and nutrition can change your gut bacteria in ways that might help prevent or treat brain-related diseases that involve immune problems. The authors suggest that maintaining healthy gut bacteria through food choices could be an important treatment strategy.

NeuroinflammationImmune System

E0 ConsensusReviewPEM not requiredReview-Narrative

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome.

Dell'Osso, Liliana, Bazzichi, Laura, Baroni, Stefano et al.·Clinical and experimental rheumatology·2015

This review examined whether ME/CFS, fibromyalgia, and mood disorders like depression might share similar root causes involving inflammation and immune system dysfunction. Researchers looked at scientific papers from 2000-2014 and found striking similarities in how these conditions affect the brain, nervous system, and immune system. The findings suggest these seemingly different conditions may be connected through common biological mechanisms rather than being completely separate diseases.

NeuroinflammationImmune System

E0 ConsensusReviewPEM unclearReview-Narrative

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

Maes, Michael·Progress in neuro-psychopharmacology & biological psychiatry·2011

Depression and ME/CFS often occur together, and this study suggests they share common biological root causes involving inflammation and oxidative stress (damage to cells). While depression and ME/CFS look different clinically, they appear to involve similar underlying problems with the immune system, energy production, and antioxidant defenses. The authors argue these should be considered connected disorders rather than two separate conditions that happen to co-occur.

NeuroinflammationImmune System

E0 ConsensusReviewPEM not requiredMeta-Analysis

Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data.

Pihur, Vasyl, Datta, Somnath, Datta, Susmita·Bioinformation·2011

Researchers combined multiple types of biological data from ME/CFS patients and healthy controls to identify genes that may contribute to ME/CFS and its severity. They found 11 genes of potential importance, with one gene called WASF3 standing out as possibly influencing fatigue through a specific cellular pathway in the brain.

NeuroinflammationImmune System

E0 ConsensusReviewPEM not requiredReview-Narrative

Autoantibodies associated with psychiatric disorders.

Margutti, Paola, Delunardo, Federica, Ortona, Elena·Current neurovascular research·2006

This review examines evidence that the immune system can sometimes produce antibodies that attack the brain and blood vessels, potentially causing psychiatric symptoms like depression, anxiety, and psychosis. The authors discuss how this autoimmune mechanism may occur in several conditions, including chronic fatigue syndrome, and review what we know about antibodies in psychiatric disorders including schizophrenia and autism.

Neuroinflammation

E1 ReplicatedTrialPEM not requiredRCT

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Natelson, Benjamin H, Vu, Diana, Mao, Xiangling et al.·The journal of pain·2015

This study tested whether a medication called milnacipran could reduce brain inflammation and pain in fibromyalgia patients. Researchers measured a chemical called lactate in the brain using a special MRI scan and found that fibromyalgia patients had higher levels than healthy people. After 8 weeks of treatment, patients taking milnacipran showed lower lactate levels and less pain compared to those taking placebo, suggesting the medication may work by reducing brain inflammation.

NeuroinflammationBiomarkers

E2 ModerateCohortPEM unclearCross-Sectional

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Inderyas, Maira et al.·Frontiers in neuroscience·2026

Researchers used a brain imaging technique called DTI-ALPS to measure how well the brain clears waste during sleep in 31 ME/CFS patients and 27 healthy controls. They observed that ME/CFS patients had lower measurements than controls, and these measurements were associated with worse sleep disturbance and concentration problems. However, this is a preliminary study in a small group, and it remains unclear whether reduced glymphatic function actually causes ME/CFS symptoms or is simply correlated with them.

NeuroinflammationBiomarkersSleepCognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome.

Chinnappan, Baskaran, Kempuraj, Duraisamy, Aenlle, Kristina K et al.·Frontiers in immunology·2026

Researchers measured two immune proteins (IL-11 and MMP-9) in the blood of 40 ME/CFS patients and compared them to healthy controls, finding higher levels in the ME/CFS group. In the laboratory, they also showed that immune cells called mast cells release MMP-9 when exposed to a protein from Epstein-Barr virus. These are preliminary observations in one study that suggest these proteins may be associated with ME/CFS, but this does not yet establish their role in the disease.

NeuroinflammationBiomarkersImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion-Based Neuroinflammation Imaging Study.

Yu, Qiang, Kothe, Kiana, Kwiatek, Richard A et al.·Human brain mapping·2026

This study used advanced brain imaging to look for signs of inflammation in the white matter (the brain's communication cables) of ME/CFS patients compared to healthy people. Researchers found several differences in how water moves through brain tissue in ME/CFS patients, suggesting there may be swelling, immune cell activity, and changes to nerve fibers. These imaging markers could potentially help doctors identify and track ME/CFS in the future.

Neuroinflammation

E2 ModerateCohortPEM unclearObservational

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.

Kim, Laura, Cammà, Guido, Peters, Claudia Kedor et al.·Journal of translational medicine·2026

This observational study of 30 ME/CFS patients reported improvements in physical functioning, fatigue, and pain after 40 sessions of hyperbaric oxygen therapy (HBOT), with associated changes in brain connectivity patterns. However, this is a single-group study without a control arm receiving a sham or alternative treatment, so we cannot yet determine whether observed improvements were due to HBOT itself or other factors such as expectancy or natural variation.

NeuroinflammationInterventionsAutonomic Nervous SystemCognitive Impairment

E2 ModerateCohortPEM not requiredCross-Sectional

Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.

Omdal, Roald, Lenning, Ole Bernt, Jonsson, Grete et al.·Brain, behavior, & immunity - health·2026

A study of 48 people with long-COVID and 48 recovered controls found that fatigue was much more severe in the long-COVID group, but common blood markers of inflammation and cellular stress did not differ between the groups. This suggests that the fatigue in long-COVID may not be driven by the types of inflammation typically measured in blood tests, though the researchers note their findings are preliminary and limited to the biomarkers they tested.

NeuroinflammationBiomarkersImmune SystemLong COVID Overlap

E2 ModerateCohortPEM unclearObservational

Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.

Gile, Brooke, Bulbule, Sarojini, Toriola, Mubaraq A et al.·Journal of translational medicine·2026

A pilot study observed that people with ME/CFS who received low-dose rapamycin reported improvements in fatigue symptoms over 90 days, and blood tests showed changes in purine metabolism and mitochondrial energy markers. However, this was a small observational study without a placebo control group, so it does not yet establish whether rapamycin actually causes these improvements or whether the observed biochemical changes are responsible for symptom relief.

NeuroinflammationBiomarkersEnergy MetabolismInterventions

E2 ModerateCohortPEM requiredCase-Control

Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling.

Hunter, Ewan, Alshaker, Heba, Bundock, Oliver et al.·Journal of translational medicine·2025

Researchers developed a new blood test called EpiSwitch®CFS that may help diagnose ME/CFS by detecting specific patterns in how DNA is organized in blood cells. When tested on stored blood samples from 47 ME/CFS patients and 61 healthy people, the test correctly identified 92% of ME/CFS patients and correctly ruled out 98% of healthy controls. This could potentially help doctors diagnose ME/CFS more reliably, since there is currently no standard blood test for the condition.

NeuroinflammationBiomarkersImmune System

E2 ModerateCohortPEM not requiredCase-Control

Affective and chronic fatigue symptoms are associated with serum neuronal damage markers in Parkinson's disease.

Al-Hakeim, Hussein Kadhem, Khudhair, Hayder Naji, Ranaei-Siadat, Sayed-Omid et al.·Scientific reports·2025

This study looked at people with Parkinson's disease who also experienced depression and extreme fatigue, similar to ME/CFS. Researchers found that certain proteins in the blood that signal brain cell damage were elevated in these patients, and these proteins were connected to inflammation, blood sugar problems, and the mood and fatigue symptoms they experienced.

NeuroinflammationImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al.·The American journal of medicine·2025

Researchers used advanced brain imaging to measure chemical imbalances in ME/CFS and long COVID patients compared to healthy people. They found that two important brain chemicals—glutamate and N-acetyl-aspartate—were significantly higher in patients with both conditions. These chemical imbalances were connected to how severe patients' symptoms were, suggesting that abnormal brain chemistry may play a role in the exhaustion and other symptoms these patients experience.

Neuroinflammation

E2 ModerateCohortPEM unclearCross-Sectional

Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.

Almulla, Abbas F, Maes, Michael, Zhou, Bo et al.·Journal of advanced research·2025

This study found that people with Long COVID have unusual immune responses targeting the brain and nerve cells. Researchers measured antibodies (immune proteins) in people with Long COVID and healthy controls, discovering that Long COVID patients have significantly higher levels of antibodies attacking several brain proteins. These brain-targeted immune responses were strongly linked to fatigue severity and mood symptoms like depression and anxiety.

Neuroinflammation

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The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

Brainstem Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings.

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.

Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities.

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease.

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome.

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data.

Autoantibodies associated with psychiatric disorders.

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Disrupted glymphatic function and its relationship with sleep and cognitive impairment in ME/CFS assessed via DTI-ALPS.

Elevated serum levels of interleukin-11 and matrix metalloproteinase-9 in myalgic encephalomyelitis/chronic fatigue syndrome.

Evidence of White Matter Neuroinflammation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Diffusion-Based Neuroinflammation Imaging Study.

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.

Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.

Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.

Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling.

Affective and chronic fatigue symptoms are associated with serum neuronal damage markers in Parkinson's disease.

Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.

Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.

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