E2 ModeratePreliminaryPEM unclearMechanisticPeer-reviewedReviewed
Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Yasuhito Nakatomi, Kei Mizuno, Akira Ishii et al. · Brain, Behavior, and Immunity · 2014 · DOI
Quick Summary
Japanese researchers used PET imaging with a neuroinflammation tracer (PK11195) in 9 ME/CFS patients and healthy controls. They found significantly elevated neuroinflammation signals across multiple brain regions in ME/CFS patients, particularly in the cingulate cortex, thalamus, and brainstem — areas regulating fatigue and cognition.
Why It Matters
This study independently corroborated neuroinflammation findings from other groups using direct PET imaging. It identified specific brain regions showing elevated glial activation in ME/CFS, providing anatomical detail to the neuroinflammation hypothesis.
Observed Findings
- Significantly elevated neuroinflammation signals detected via PK11195 PET imaging in ME/CFS patients (n=9) compared to healthy controls
- Elevated neuroinflammation localized to cingulate cortex, thalamus, and brainstem regions
- These affected brain regions are known to regulate fatigue perception and cognitive function
Inferred Conclusions
- Neuroinflammation, particularly microglial/macrophage activation, may be a pathological feature of ME/CFS
- Central nervous system inflammation in fatigue-regulating brain areas could mechanistically contribute to cardinal ME/CFS symptoms
Remaining Questions
- Does elevated neuroinflammation represent a primary pathogenic mechanism or secondary consequence of ME/CFS?
- How do neuroinflammation levels correlate with symptom severity, disease duration, or clinical outcomes in larger cohorts?
- Do newer, more specific microglial tracers (e.g., PBR06, F-DPA714) confirm these findings and better distinguish microglial from macrophage involvement?
What This Study Does Not Prove
With only 9 ME/CFS patients, this is an underpowered study. The PK11195 tracer has relatively low specificity for microglia vs. macrophages. Replication with larger samples and newer tracers is needed.
Tags
Method Flag:PEM_UNCLEARSmall SampleEXPLORATORYBIOLOGICALLY_RELEVANTPEM Not DefinedWeak Case Definition
Symptom:Fatigue
Biomarker:CytokinesNeuroimagingBlood Biomarker
Metadata
- DOI
- 10.1016/j.bbi.2014.04.001
- Sample size
- 9 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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