The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
Glassford, Julian A G · Frontiers in physiology · 2017 · DOI
Quick Summary
This article reviews research suggesting that ME/CFS may result from problems in how the nervous system and immune system interact. The author discusses how physical strain on the spine and nerves, combined with prolonged infections and immune activation, may trigger a chain reaction of inflammation in the brain and throughout the body. This inflammation can affect energy production, hormone balance, and how the body processes pain.
Why It Matters
This review provides patients and clinicians with a comprehensive framework for understanding how multiple biological systems may interact to produce ME/CFS symptoms. By integrating disparate research findings into a coherent disease model, it helps legitimize ME/CFS as a neurological condition and may guide future research priorities and therapeutic targets.
Observed Findings
Glial activation is associated with oxidative and nitrosative stress in the central nervous system
Neuroinflammation can trigger distortions in noxious sensory signaling leading to central sensitization
Chronic immune activation from persistent infection may drive sustained neurological dysfunction
Multiple body systems (endocrine, immune, mitochondrial) show dysfunction patterns in ME/CFS
Postural and biomechanical factors may contribute to chronic pain signaling in ME/CFS patients
Inferred Conclusions
ME/CFS results from a combination of neuroinflammatory mechanisms rather than a single cause
Sustained glial activation and central sensitization represent key pathophysiological processes perpetuating symptoms
Multiple triggering factors (biomechanical, infectious, immune) likely interact synergistically to produce the multi-systemic disease presentation
Neuroinflammation and gliopathy are central features warranting therapeutic investigation
Remaining Questions
Which ME/CFS patients fit each proposed etiological pathway, and are there patient subgroups with distinct primary mechanisms?
What This Study Does Not Prove
This review does not prove causation—it synthesizes existing research without presenting new experimental evidence. It cannot determine which proposed mechanism is primary or whether all three factors are necessary for disease development. The relative importance of postural/biomechanical versus infectious triggers remains unresolved.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →