Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome.

  title={Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome.},
  author={Anthony L. Komaroff},
When does an illness become a disease? When the underlying biological abnormalities that cause the symptoms and signs of the illness are clarified. The illness now called myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) was first described in the mid-1980s. At that time, nothing was known about its underlying biology. Indeed, because many standard laboratory test results were normal, some clinicians explained to patients that “there is nothing wrong.” There was, of course, an… 

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review

A pathophysiological approach to understanding the essential concepts of ME/CFS is presented, with an emphasis on the population, clinical, and genetic concepts associated with ME/ CFS.

How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS

We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management.

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

The frequent observation of additional brain area recruitment and consistent observation of sluggish fMRI signal response suggest abnormal neurovascular coupling in ME/CFS.

Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

This paper summarizes and expands on the previous publications about the relevance of findings from critical illness for ME/CFS and describes interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses.

Documenting disability in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

The range of methods used in successful US disability claims are summarized, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment.

Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

This study comprehensively described the journey of the development of case definitions and compared the symptom criteria and provides broader insights and explanations to understand the complexity of ME/CFS for clinicians and researchers.

A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome

It is suggested that elevated energy strain may result from exertion-triggered tissue hypoxia and lead to systemic metabolic adaptation and compensation and through various mechanisms, such metabolic dysfunction represents a likely mediator of key symptoms in ME/CFS and possibly a target for supportive intervention.

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance

The results of a randomized, placebo-controlled trial using intranasal mechanical stimulation targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ∼30% reduction in overall symptom scores after eight weeks of treatment are reported.



Role of infection and neurologic dysfunction in chronic fatigue syndrome.

The evidence is consistent with the hypothesis that CFS, in some cases, can be triggered and perpetuated by several chronic infections that directly or indirectly affect the nervous system, and that symptoms are a reflection of the immune response to the infection.

Metabolic features of chronic fatigue syndrome

Targeted, broad-spectrum metabolomics of plasma showed that chronic fatigue syndrome is a highly concerted hypometabolic response to environmental stress that traces to mitochondria and was similar to the classically studied developmental state of dauer, opening a fresh path for the rational development of new therapeutics.

Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

The decrease in WR at VT of 6.3–9.8% on the 2nd day of consecutive-day CPET may represent an objective biomarker that can be used to assist with the diagnosis of ME/CFS.

Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results

Comparing blood volumes based on the presence or absence of orthostatic symptoms suggests that accounting for symptoms of OI could enhance the detection of the subset with reduced blood volume, as well as a significantly lower blood volume compared to the expected value.

Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Evidence to date indicates that ME/CFS patients are uniquely unable to reproduce CPET measures during a second test, despite giving maximal effort during both tests, due to the effects of PEM on energy production.

Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy

The extended MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain may indicate that ME/ CFS involves neuroinflammation.

A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

A nanoelectronics assay designed as an ultrasensitive assay capable of directly measuring biomolecular interactions in real time, at low cost, and in a multiplex format and a classifier for ME/CFS patients capable of identifying new patients, required for a robust diagnostic tool are developed.

Moving toward answers in ME/CFS

  • NIH Director’s Blog. March 21,
  • 2017