E3 PreliminaryPreliminaryPEM not requiredReview-NarrativePeer-reviewedReviewed
Standard · 3 min
Pathophysiological mechanisms of fatigue and multidisciplinary management strategies (Review).
Zhou, Hong, Yu, Wenwen, Lei, Jiaming et al. · Experimental and therapeutic medicine · 2026 · DOI
Quick Summary
This review examines why people feel extreme fatigue and how doctors can better manage it. The authors explain that fatigue involves problems with how the body makes energy, stress chemicals in the body, and the immune system. They discuss how new technologies and teamwork between different medical specialists—plus telemedicine—can help patients with chronic fatigue syndrome and other conditions feel better.
Why It Matters
This review is relevant to ME/CFS patients and researchers because it synthesizes current understanding of fatigue mechanisms—particularly mitochondrial dysfunction, energy metabolism abnormalities, and immune system dysregulation—conditions that characterize ME/CFS pathophysiology. The emphasis on multidisciplinary, individualized management and telemedicine accessibility addresses real barriers to care that ME/CFS patients face. The call for improved fatigue assessment models and biomarker-driven interventions aligns with the field's need for objective diagnostic criteria.
Observed Findings
Abnormal energy metabolism, oxidative stress, and mitochondrial dysfunction appear central to fatigue pathogenesis across multiple conditions.
Disorders in the neuro-endocrine-immune network contribute to fatigue through multilevel regulatory mechanisms.
Microbiome-gut-brain axis dysfunction represents a key systemic integration mechanism in fatigue.
Telemedicine applications improve patient compliance and accessibility to fatigue management.
Fatigue manifests across diverse conditions including chronic fatigue syndrome, endocrine, neurological, and autoimmune diseases.
Inferred Conclusions
Fatigue is a multisystem disorder requiring understanding of integrated energy, immune, and neuroendocrine dysfunction rather than single-system approaches.
Individualized, multidisciplinary collaborative management represents the current standard for fatigue care.
Future progress depends on translating molecular mechanisms into novel intervention targets and developing objective fatigue assessment models.
Telemedicine technology can enhance accessibility and adherence in fatigue management strategies.
Remaining Questions
How can molecular mechanisms of fatigue be effectively translated into targeted clinical interventions with proven efficacy?
What This Study Does Not Prove
This review does not establish causation or test specific hypotheses through original research; it synthesizes existing knowledge without presenting new primary data. It does not validate any particular diagnostic test, biomarker, or treatment intervention for ME/CFS specifically. The broad scope across multiple fatigue-causing conditions means conclusions cannot be assumed to apply equally to ME/CFS without disease-specific evidence.
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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