E2 ModeratePreliminaryPEM unclearReview-NarrativePeer-reviewedReviewed
The neuroinflammatory hypothesis of chronic fatigue syndrome/myalgic encephalomyelitis: an update
Jarred W. Younger, Linda Yan, Sean Mackey · Journal of Neuroinflammation · 2014 · DOI
Quick Summary
Using thermography and brain temperature imaging at Stanford, this study found evidence consistent with neuroinflammation — specifically elevated brain temperature — in ME/CFS patients compared to healthy controls. Brain regions associated with pain and fatigue showed the strongest signal.
Why It Matters
This study provided early evidence for neuroinflammation as a biological feature of ME/CFS, independent of psychiatric explanations. It supported PET imaging studies finding similar signals in brain regions linked to fatigue.
Observed Findings
- Elevated brain temperature in ME/CFS patients compared to healthy controls
- Strongest thermal signals in brain regions associated with pain processing
- Strongest thermal signals in brain regions associated with fatigue
- Thermography and brain temperature imaging detected measurable differences between groups
Inferred Conclusions
- Neuroinflammation may be present in ME/CFS patients
- Pain and fatigue symptoms may correlate with regional brain temperature elevation
- Brain temperature imaging is a potentially useful investigative tool for ME/CFS
Remaining Questions
- Does elevated brain temperature directly indicate neuroinflammation or could other physiological mechanisms explain the findings?
- What is the clinical significance of observed brain temperature differences—do they correlate with symptom severity or disease progression?
- Can these findings be reproduced in larger, more diverse patient populations?
What This Study Does Not Prove
Brain temperature is an indirect measure of neuroinflammation. This small study cannot confirm the presence, extent, or clinical significance of brain inflammation in ME/CFS.
Tags
Method Flag:PEM_UNCLEARSmall SampleEXPLORATORYBIOLOGICALLY_RELEVANTWeak Case DefinitionExploratory Only
Symptom:Post-Exertional MalaiseCognitive DysfunctionFatigue
Biomarker:CytokinesBlood Biomarker
Metadata
- DOI
- 10.1186/s12974-014-0111-6
- Sample size
- 18 patients
- Control group
- Yes
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 7 April 2026
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 →
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