Evidence browser

E2 ModerateCohortPEM unclearObservational

Free-water-corrected diffusion and adrenergic/muscarinic antibodies in myalgic encephalomyelitis/chronic fatigue syndrome.

Kimura, Yukio, Sato, Wakiro, Maikusa, Norihide et al.·Journal of neuroimaging : official journal of the American Society of Neuroimaging·2023

Researchers used a specialized brain imaging technique to look for signs of inflammation in the brains of ME/CFS patients and compared these findings to levels of harmful antibodies (immune proteins) in their blood. They found that certain antibodies were linked to visible changes in a specific brain region called the right frontal operculum, and that longer disease duration was associated with more brain changes. These findings suggest that ME/CFS may involve both immune system dysfunction and measurable changes in brain structure.

Neuroinflammation

Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome.

Friedberg, Fred, Adamowicz, Jenna L, Bruckenthal, Patricia et al.·Scientific reports·2023

This study looked at how men and women with ME/CFS respond differently to a simple exercise test (a six-minute walk). Researchers tracked fatigue levels and heart function for 15 days in 37 ME/CFS patients and 14 healthy people. Women with ME/CFS felt more tired after the first walk test, while men reported fewer work limitations in the days after exercise. Surprisingly, the study did not find the expected differences between men and women in how long it took to recover.

E2 ModerateDiagnosticPEM requiredCross-Sectional

Evaluating case diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): toward an empirical case definition.

Conroy, Karl E, Islam, Mohammed F, Jason, Leonard A·Disability and rehabilitation·2023

This study looked at how doctors diagnose ME/CFS by analyzing symptoms reported by over 2,300 patients from around the world. Researchers used statistical methods to identify which symptoms tend to occur together, then compared their findings to three existing diagnostic guidelines. They found that the symptoms cluster into seven main groups, with post-exertional malaise (worsening after activity), cognitive problems, and sleep issues being particularly important.

SleepPost-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID.

Yamamoto, Yukichika, Otsuka, Yuki, Tokumasu, Kazuki et al.·Journal of clinical medicine·2023

This study looked at 234 people with long COVID to understand why some developed ME/CFS (a severe fatigue condition) while others didn't. Researchers found that people who developed ME/CFS had significantly higher levels of ferritin, a protein that stores iron, in their blood compared to those with long COVID fatigue alone or no fatigue. The finding was especially strong in women, suggesting that a simple blood test measuring ferritin might help predict who is at risk of developing ME/CFS after COVID-19.

Biomarkers

Do diagnostic criteria for ME matter to patient experience with services and interventions? Key results from an online RDS survey targeting fatigue patients in Norway.

Kielland, Anne, Liu, Jing, Jason, Leonard A·Journal of health psychology·2023

This study surveyed 660 people with ME/CFS in Norway to understand how different diagnostic criteria and symptoms affect their experiences with treatments and healthcare services. Most patients reported that available interventions had little benefit or made them feel worse. The researchers found that post-exertional malaise (a hallmark symptom where activity makes fatigue and other symptoms worse) was strongly linked to how patients tolerated different treatments, suggesting this symptom should be a key consideration when recommending interventions.

Experiences of carers of youth, adult children and spouses with ME/CFS.

Baken, Don M, Ross, Kirsty J, Hodges, Lynette D et al.·Chronic illness·2023

This study looked at how caring for someone with ME/CFS affects family members and close caregivers across different life stages—parents of young people with ME/CFS, adult children caring for parents, and spouses. Researchers surveyed 36 carers about their experiences and found two major challenges: lack of knowledge about the condition and its wide-ranging impact on their lives. While many experiences were shared across all groups, carers of young people faced particular struggles with providing care without clear guidance, while carers of adults and spouses worried most about what the future would hold.

E2 ModerateCohortPEM not requiredCross-Sectional

Health system support among patients with ME/CFS in Switzerland.

Tschopp, Rea, König, Rahel S, Rejmer, Protazy et al.·Journal of Taibah University Medical Sciences·2023

This Swiss study surveyed 169 ME/CFS patients to understand their experiences with the healthcare system. Patients faced long delays in getting diagnosed (averaging 6.7 years), saw many doctors before getting correct answers (11.1 appointments on average), and were frequently told their symptoms were psychological rather than physical. The study found that doctors in Switzerland lack knowledge about ME/CFS, leading to frustration, inappropriate treatments, and some patients traveling abroad for proper diagnosis.

Diagnostics

Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa.

Hannestad, Ulf, Apostolou, Eirini, Sjögren, Per et al.·Frontiers in medicine·2023

This study found that people with ME/CFS who caught COVID-19 showed signs of a dormant virus (adenovirus) waking up in their mouth and throat. The researchers compared saliva samples from ME/CFS patients and healthy people, and only the ME/CFS patients showed this reactivation after COVID-19 infection. This suggests that ME/CFS patients may have a weakened immune system that cannot keep these latent viruses under control when faced with a new infection like COVID-19.

Immune System

E2 ModerateCohortPEM not requiredObservational

A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression.

Kendler, Kenneth S, Rosmalen, Judith G M, Ohlsson, Henrik et al.·Psychological medicine·2023

This study looked at the family histories of over 5 million Swedish people to understand whether ME/CFS, fibromyalgia, and irritable bowel syndrome share common genetic roots. Researchers found that people with these conditions have a distinctive pattern of genetic risk that affects multiple body systems—including pain, mood, immune function, and sleep—rather than being limited to one specific area like depression or rheumatoid arthritis. This suggests these functional somatic disorders may arise from a complex genetic vulnerability affecting several interconnected systems rather than a single cause.

E2 ModerateBehavioralPEM not requiredCross-Sectional

End-Tidal CO2 in Patients with Panic Disorder, Stress-Related or Functional Syndromes, Versus Healthy Controls.

Ramakers, Indra, Van Den Houte, Maaike, Van Oudenhove, Lukas et al.·Applied psychophysiology and biofeedback·2023

This study looked at how people with ME/CFS, fibromyalgia, burnout, and panic disorder breathe differently compared to healthy people. Researchers measured carbon dioxide levels in participants' breath while they rested and during a breathing challenge. They found that people with chronic conditions like ME/CFS showed less active stress responses in their breathing, while those with acute stress conditions showed overactive breathing patterns.

Autonomic Nervous System

E2 ModerateCohortPEM requiredCase-Control

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and COVID-19: is there a connection?

AlMuhaissen, Suha, Abu Libdeh, Amal, ElKhatib, Yara et al.·Current medical research and opinion·2023

This study looked at whether people who had COVID-19 might develop ME/CFS afterward. Researchers asked 437 people who had COVID-19 questions based on the official diagnostic criteria for ME/CFS. They found that about 8% of COVID-19 patients met the criteria for ME/CFS, suggesting there may be a connection between the two illnesses.

Diagnostics

Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Retornaz, Frédérique, Stavris, Chloé, Jammes, Yves·Clinical biomechanics (Bristol, Avon)·2023

This study looked at whether problems with how muscle cells communicate during and after exercise might explain why people with ME/CFS have weak muscles. Researchers compared two groups of ME/CFS patients—those whose muscles showed electrical signal problems after exercise and those who didn't. They found that patients with these electrical problems had weaker grip strength both before and after exercise, and their symptoms got worse after physical activity.

E2 ModerateCohortPEM unclearObservational

Post-Acute Sequelae of COVID-19 (PASC) in Pediatrics: Factors That Impact Symptom Severity and Referral to Treatment.

Soprano, Catherine M, Ngo, Ryan, Konys, Casey A et al.·Children (Basel, Switzerland)·2023

This study looked at how long COVID (called PASC) affects children and teenagers, comparing their experiences to adults. The researchers reviewed medical records to understand what symptoms young people had and whether they were referred to specialized treatment programs. The main finding was that young people with long COVID tend to have less severe symptoms than adults, though many young patients were not referred for treatment even when they needed it.

Long COVID Overlap

Focus on post-exertional malaise when approaching ME/CFS in specialist healthcare improves satisfaction and reduces deterioration.

Wormgoor, Marjon E A, Rodenburg, Sanne C·Frontiers in neurology·2023

This study looked at whether ME/CFS specialists in Norway were paying attention to post-exertional malaise (PEM)—the worsening of symptoms after physical or mental effort, which is a key feature of ME/CFS. They surveyed nearly 900 patients about their experiences in specialist clinics and hospitals. The results showed that when doctors focused on PEM and helped patients avoid overexertion, patients felt better, were more satisfied with their care, and were less likely to get worse after treatment.

E2 ModerateCohortPEM not requiredCross-Sectional

In Schizophrenia, Chronic Fatigue Syndrome- and Fibromyalgia-Like Symptoms are Driven by Breakdown of the Paracellular Pathway with Increased Zonulin and Immune Activation-Associated Neurotoxicity.

Maes, Michael, Andrés-Rodríguez, Laura, Vojdani, Aristo et al.·CNS & neurological disorders drug targets·2023

This study looked at people with schizophrenia who also experience fatigue and pain symptoms similar to ME/CFS and fibromyalgia. Researchers found that these symptoms may be caused by a breakdown in the intestinal barrier (the paracellular pathway), which allows harmful substances into the bloodstream and triggers immune system activation. This immune activation then produces neurotoxic byproducts that may cause the fatigue and pain symptoms.

NeuroinflammationImmune System

E2 ModerateCohortPEM not required

Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): impact of self-reported fatigue and illness duration.

Byrne, Hollie, Josev, Elisha K, Knight, Sarah J et al.·Brain structure & function·2023

This study looked at the size of the hypothalamus (a small part of the brain that controls many body functions) in teenagers with ME/CFS compared to healthy teenagers. While the overall brain structure sizes were similar between the two groups, researchers found that in ME/CFS patients, certain areas of the hypothalamus were slightly larger when fatigue was more severe, and other areas grew larger with longer illness duration. This suggests the hypothalamus may play a role in ME/CFS, though more research is needed to understand what this means.

Adults with ME/CFS report surprisingly high rates of youth symptoms: A qualitative analysis of patient blog commentary.

Johnson, Madeline, Torres, Chelsea, Watts-Rich, Halli et al.·Work (Reading, Mass.)·2023

This study asked adults with ME/CFS about whether they experienced symptoms during childhood. Researchers analyzed comments from patients on a popular blog forum and found that about 43% of adults reported having ME/CFS before age 18. The study identified common themes in patients' stories, including mental health struggles, family history of illness, feeling misunderstood by others, and difficulties at school.

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression.

Berkis, Uldis, Svirskis, Simons, Krumina, Angelika et al.·Frontiers in immunology·2023

This study looked for blood markers that could help doctors understand how severe ME/CFS is and track disease progression. Researchers measured inflammation-related proteins, immune system components, and antibodies against nerve receptors in blood samples from healthy people and patients with mild, moderate, and severe ME/CFS. They found that certain markers—especially antibodies against beta2-adrenergic and M4 receptors, along with specific immune proteins—showed promise for distinguishing disease severity, with over 90% accuracy in identifying who has ME/CFS versus who is healthy.

BiomarkersImmune System