EMEA News Q3 2026

Introduction – Myalgic Encephalomyelitis (ME)

Myalgic encephalomyelitis (ME) is a complex, multisystem disorder with debilitating symptoms. Although sometimes referred to as ME/CFS, the term ME is more appropriate as it avoids the trivialising connotations of "chronic fatigue syndrome" (CFS), now considered outdated and failing to capture the condition's severity and complexity.

The term "myalgic encephalomyelitis" reflects muscle pain (myalgia) and the historical view of potential inflammation of the brain and spinal cord (encephalomyelitis), highlighting the condition's neurological and muscular aspects. The pathophysiology of ME is not yet fully understood, and the condition may involve subtypes and various underlying mechanisms.

ME is marked by profound fatigue that is not alleviated by rest, post-exertional malaise (PEM), cognitive impairment, sleep disturbances, and pain. It affects individuals of all ages, genders, and backgrounds, with a higher prevalence among women.

The onset of ME is most often sudden over weeks, but may be gradual over months typically following an infectious illness.

ME can significantly affect an individual's ability to work, engage in social activities, and maintain personal relationships, leading to substantial reduction in functional capacity and quality of life. The economic burden is also considerable, with costs associated with healthcare, lost productivity, and informal care.

Historically, research into ME has been critically under-resourced, leading to widespread ignorance about the disease that then allows misinformation and scepticism amongst healthcare professionals to question legitimacy. Consequently, patients face stigmatisation and a lack of recognition, exacerbating their challenges. Recent research advances have begun to unravel ME's biological underpinnings, providing validation for patients and hope for improved diagnosis and treatment.

The prevalence of ME is estimated to be from 0.2% up to 0.85% of the population, although underdiagnosis, misdiagnosis, and lack of recognition may lead to underestimation. The precise prevalence is unknown due to lack of standardisation of recording systems. The World Health Organization (WHO) has recognised ME as a neurological condition since 1969, classified under "diseases of the nervous system" with ICD code G93.3 (ICD-10) and, with the most recent revision, with 8E49 (ICD-11).

With the COVID-19 pandemic, many patients who developed post-acute sequelae of COVID-19 meet the criteria for ME, possibly significantly increasing the prevalence of ME.

Historical Outbreaks

While ME is not typically classified as an epidemic disease, several historical outbreaks have similarities to ME:

Royal Free Hospital Outbreak (1955): One of the earliest documented outbreaks occurred at the Royal Free Hospital in London, affecting numerous hospital staff and leading to the initial recognition of ME as a distinct syndrome.

Inclusive District Nursing Division Outbreak (1934): A documented outbreak in Los Angeles among nurses and doctors was characterised by symptoms similar to ME, including fatigue, muscle pain, and neurological symptoms.

Akureyri Disease (1948-1949): An outbreak in Akureyri, Iceland, affected many residents with symptoms resembling ME.

Dalston, London Outbreak (1950s): Another notable outbreak occurred in Dalston, London, where a cluster of cases exhibited symptoms consistent with ME.

Other Historical Outbreaks: Several other documented outbreaks with symptoms resembling ME have occurred, including those in Switzerland, South Africa, and the United States.

These outbreaks often occurred in institutional settings, such as hospitals and schools, and contributed to the recognition of ME as a distinct clinical entity by highlighting the post-infectious nature of ME. However, it is important to note that the classification and diagnosis of ME have evolved over time, and historical outbreaks may not all meet current diagnostic criteria.

Aetiology, Pathophysiology, Symptoms, and Clinical Presentation

ME is characterised by a diverse array of symptoms that significantly impair quality of life, reflecting underlying pathophysiological processes involving multiple biological systems.

Aetiology. While the exact cause remains unknown, research points to involvement of several biological systems, including circulatory, immune, metabolic, and neurological dysfunctions. Several factors may contribute to the development of ME:

Infectious Triggers: Many patients report the onset of ME following an infectious illness, such as Epstein-Barr virus or other viral infections. These infections may trigger an abnormal immune response that persists long after the initial infection has resolved.

Genetic Predisposition: Certain genetic variants may increase susceptibility to ME, particularly in response to environmental triggers such as infections.

Environmental Factors: Exposure to environmental toxins or stressors may also play a role in the development of ME, although the precise mechanisms are not yet fully understood.

Core Symptoms and Pathophysiology. The core symptoms of ME are diverse and significantly impair quality of life, reflecting underlying pathophysiological processes. Profound fatigue in ME is debilitating and unrelenting, distinct from ordinary tiredness in its severity and persistence. It is not alleviated by rest and is often accompanied by weakness and lack of energy. This fatigue may be linked to metabolic abnormalities, including impaired energy production and mitochondrial dysfunction, leading to a chronic state of energy depletion. Abnormalities in blood circulation may also be central to the disease.

Post-exertional malaise (PEM) is a mandatory feature of ME, where even minimal physical or cognitive effort above one's capacity can lead to a significant delayed onset of exacerbation of symptoms, lasting for days or weeks. PEM manifests as extreme fatigue, muscle pain, cognitive difficulties, and flu-like symptoms. It may arise from a combination of immune dysregulation and metabolic abnormalities, with abnormal immune system responses to exertion potentially triggering inflammation and oxidative stress, exacerbating symptoms.

Cognitive impairment, often referred to as "brain fog," includes difficulties with concentration, memory, and information processing. Patients struggle with tasks that require sustained mental effort, such as continuous conversations. Word-finding difficulties and reduced memory are common.

Despite feeling constantly fatigued, individuals with ME often experience insomnia and unrefreshing sleep. They may also suffer from disrupted sleep patterns and other sleep disorders. Sleep disturbances in ME may be related to dysregulation of the autonomic nervous system and abnormalities in neurotransmitter function, which can disrupt sleep architecture and quality.

Muscle and joint pain are common, as are headaches. Some patients also experience neuropathic pain, which can be particularly challenging to manage. Symptoms such as orthostatic intolerance, where patients experience dizziness or light-headedness upon standing, are frequently reported. This may be due to abnormalities in blood flow regulation to the brain. Autonomic dysfunction in ME may be related to immune and metabolic abnormalities.

Patients with ME often report flu-like symptoms, including sore throat, swollen lymph nodes, and increased susceptibility to infections. Abnormalities in both the innate and adaptive immune systems have been observed in ME patients, including altered cytokine profiles and evidence of chronic, low-grade inflammation.

Clinician Perspectives – Diagnostic and Management Challenges

The diagnosis of ME is primarily clinical, as currently there are no specific biomarkers or diagnostic tests. The lack of objective measures makes diagnosis challenging, and the lack of recognition in many countries leads to delayed or missed diagnoses. Differential diagnosis is crucial to rule out other conditions with similar symptoms, such as depression, fibromyalgia, and autoimmune disorders.

Several diagnostic criteria and guidelines for ME have evolved over time:

Canadian Consensus Criteria (2003): These criteria emphasise post-exertional malaise, fatigue, sleep dysfunction, pain, and neurological/cognitive manifestations as core symptoms. They also include autonomic, neuroendocrine, and immune manifestations.

Jason criteria for children (2006): Similar to the Canadian Consensus Criteria but adapted for children, these criteria emphasise the core symptoms of ME, including post-exertional malaise, fatigue, sleep dysfunction, pain, and neurological/cognitive manifestations.

International Consensus Criteria (2011): Developed by an international panel, these criteria build upon the Canadian Consensus Criteria and emphasise post-exertional neuroimmune exhaustion as a hallmark feature. They also include guidelines for assessing the severity and impact of symptoms on daily functioning.

Institute of Medicine (IOM) Criteria (2015): The IOM (now the National Academy of Medicine) established diagnostic criteria requiring three core symptoms: substantial reduction in pre-illness activity levels, post-exertional malaise, and unrefreshing sleep. Patients must also exhibit cognitive impairment or orthostatic intolerance, with symptoms being moderate to severe and present more than 50% of the time.

NICE Guidelines (2021): The National Institute for Health and Care Excellence (NICE) in the UK published revised guidelines for ME/CFS that focus on recognising the condition and providing individualised management plans. These guidelines emphasise early diagnosis, personalised care, and avoiding treatments that may cause harm, such as graded exercise therapy (GET). These guidelines also highlight the need for shared decision-making between healthcare providers and patients.

Criteria that do not require PEM as mandatory, such as the Fukuda Criteria (1994), are outdated.

Criteria and guidelines provide a framework for diagnosing ME, but the diagnostic process is often challenging and drawn out. Clinicians face several obstacles, including:

Complexity of Diagnosis: Diagnosing ME is challenging due to the lack of specific biomarkers and the heterogeneity of symptoms. The process requires thorough ME symptom knowledge, medical history, physical examination, and the exclusion of other conditions with similar symptoms. A central diagnostic criterion is severely reduced functional capacity, which can be identified using the FUNCAP questionnaire to recognise PEM. Clinicians must rely on their clinical acumen and modern diagnostic criteria due to the absence of definitive diagnostic tests.

Limited Treatment Options: The management of ME focuses on symptom relief and improving quality of life, as there is currently no cure or evidence-based effective treatment. Clinicians must navigate limited treatment options and tailor management strategies to each patient's unique needs.

Patient-Centred Care: Effective ME management requires a patient-centred approach, involving active listening, shared decision-making, and a deep understanding of the patient's experiences and priorities. Clinicians must be empathetic, validate the patient's symptoms, and recognise the significant impact ME has on daily life. Listening to carers is also valuable. However, hospital specialists often see patients only for diagnosis, leaving follow-up to primary care. Those who see patients regularly, often even before disease onset, may have much better understanding of the clinical hallmarks of ME.

Stigma and Scepticism: Historically, ME has faced stigma and scepticism, with some healthcare professionals questioning its legitimacy due to years of neglect. This has contributed to underdiagnosis and inadequate support for patients. Clinicians who recognise ME can advocate for patients and challenge misconceptions. ME has inherent clinical features that may foster disbelief in its severity or existence. Patients may seem healthy during social interactions but experience post-exertional malaise (PEM) afterwards or manage their energy by reducing other activities. They may also deliberately or necessarily exceed their capacity limits, going unnoticed by others, and experience PEM later. This energy management often involves reducing activities before and after social interactions, remaining unnoticed by others.

Education and Awareness: Many clinicians lack adequate education and training on ME due to insufficient research funding and misinformation. Increasing awareness and providing comprehensive education on ME is essential for improving clinical practice and patient outcomes. Clinicians must stay updated with the latest research and guidelines, and health ministries need to provide up-to-date education based on current research.

Clinicians face significant challenges in diagnosing and managing ME, but their dedication, empathy, involvement in research, and support of advocacy efforts can be crucial for improving patient outcomes and advancing our understanding of this complex condition and shaping the future of ME research.

Impact on Patients

ME has a profound impact on patients' lives, affecting their ability to work, engage in social activities, and maintain personal relationships. The physical and psychological burden can be immense, leading to significant reductions in quality of life:

Reduced Functional Capacity: Profound fatigue and post-exertional malaise (PEM) severely limit patients' ability to perform daily tasks. Even simple activities can trigger PEM, leading to a cycle of exertion and recovery that significantly reduces functional capacity. Patients must manage their energy levels carefully, using pacing techniques to avoid exacerbating symptoms.

Social Isolation: The unpredictable nature of ME symptoms can lead to social isolation. Patients may cancel plans due to fluctuating symptoms or PEM, leading to a decline in social interactions and support networks. The invisibility of many ME symptoms can make it difficult for others to understand the extent of the illness, further exacerbating feelings of isolation.

Cognitive Challenges: Cognitive impairment, often referred to as "brain fog," can affect memory, concentration, and information processing. These cognitive difficulties can affect work performance, educational pursuits, and daily decision-making, leading to frustration and reduced self-confidence.

Emotional and Psychological Burden: Living with a chronic, debilitating condition such as ME can take a significant emotional toll, on patients and carers. Patients may experience feelings of helplessness due to the unpredictable nature of the illness and the lack of effective treatments. The struggle to maintain a sense of identity and purpose can be profound.

Economic Impact: ME can have a substantial economic impact, with many patients unable to work or maintain full-time employment. The loss of income, combined with the costs of medical care and battles to obtain disability support, can lead to additional stress and financial strain. The economic impact can also extend to carers and family members who may need to reduce their working hours or give up employment to provide care.

Research Landscape

The research landscape for Myalgic Encephalomyelitis (ME) is evolving gradually, with efforts focused on understanding the underlying mechanisms, identifying biomarkers, improving diagnosis, and developing effective treatments. Patient and Public Involvement (PPI) is now a standard requirement to ensure studies adequately address patient needs.

Despite these efforts, ME research remains severely underfunded, with few clinical trials conducted. Current studies explore immune, metabolic, and neurological dysfunctions, including chronic inflammation, mitochondrial dysfunction, and neuroinflammation, as these may contribute to the development and progression of ME. Understanding these mechanisms is critical for identifying potential therapeutic targets.

Biomarker research aims to improve early diagnosis, track disease progression, and assess treatment responses. Investigations focus on cytokine profiles, metabolic intermediates, and neuroimaging findings. Genetic predispositions and epigenetic changes are also being studied to understand how environmental triggers, such as infections, may increase susceptibility to ME.

There is an urgent need for clinical trials to evaluate both repurposed drugs and novel therapies targeting specific pathways involved in ME. Longitudinal studies and patient registries are essential for tracking the natural history of the disease, identifying subtypes, and assessing long-term intervention outcomes. These efforts provide valuable data for developing personalised treatment approaches.

Collaboration between researchers, clinicians, and patient groups plays a crucial role in advancing ME research. Initiatives such as the European ME Research Group (EMERG) and Young EMERG aim to build capacity and encourage early-career researchers to consider making a career of research into ME.

The overlap between ME and post-infectious syndromes, such as Long COVID, highlights the importance of studying infectious triggers. Research into the similarities and differences between these conditions may inform improved diagnostic methods and treatment strategies.

Adequate funding and a coordinated long-term strategy are essential for meaningful progress. Conversely, piecemeal funding and the absence of such a strategy risk losing another generation to this debilitating disease.

Conclusion

Myalgic encephalomyelitis is a complex, multisystem disorder that presents significant challenges for patients, clinicians, and researchers.

The profound impact of ME on patients' lives underscores the urgent need for improved diagnostic tools and effective treatments.

Current research focuses on understanding pathophysiological mechanisms, identifying biomarkers, and developing targeted therapies. However, the research landscape for ME remains chronically underfunded.

The economic burden on society due to ME is immense and should, in itself, warrant increased and sustained investment in research, awareness, and education, as well as a commitment to patient-centred care.

About Young EMERG

The European ME Research Group (EMERG) is a network of European ME researchers that was created to collaborate and share knowledge in research into ME. Young EMERG, the European ME Research Group for young and early-career researchers, was established to build capacity and encourage early-career researchers to build a career of research into ME.