Komaroff, Anthony L, Takahashi, Ryosuke, Yamamura, Takashi et al. · Brain and nerve = Shinkei kenkyu no shinpo · 2018 · DOI
This review examines objective, measurable evidence that ME/CFS is a real physical illness, not just a psychological condition. Researchers looked at studies showing that ME/CFS involves problems with the brain, immune system, and how the body uses energy. They found that immune activation—where the body's defense system becomes overactive—may be a key driver of ME/CFS symptoms.
This review provides evidence that ME/CFS has measurable biological markers rather than being primarily psychological, which can help validate patient experiences and support clinical recognition. Understanding immune activation as a potential trigger offers a mechanistic framework that may guide future treatment development and biomarker-based diagnostic approaches.
This review does not prove that any single cause definitively explains all ME/CFS cases, as the evidence reviewed suggests multiple overlapping biological abnormalities. It also does not establish the causal direction between immune activation and symptoms—immune markers could be secondary responses rather than primary triggers. The review summarizes existing studies but does not establish new treatment efficacy or provide definitive diagnostic criteria.
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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