Miller, Robert G · American journal of physical medicine & rehabilitation · 2002 · DOI
Fatigue in people with muscle and nerve diseases works differently than tiredness in healthy people, and scientists are now developing better tools to measure it. This paper reviews what we know about two types of fatigue: one that comes from the brain and nervous system (central fatigue) and one that comes from the muscles themselves (peripheral fatigue). The authors explain how these different types of fatigue affect people with conditions like ME/CFS, post-polio syndrome, and other neuromuscular diseases.
Understanding whether ME/CFS fatigue arises from central nervous system dysfunction, muscle-level problems, or both is crucial for developing targeted treatments and explaining why standard exercise recommendations may not work for all patients. This review's comparison of ME/CFS fatigue mechanisms with other well-characterized neuromuscular diseases provides a framework for investigating what distinguishes ME/CFS pathophysiology. Clarifying these mechanisms could help validate ME/CFS as a distinct medical condition and guide rehabilitation approaches.
As a review paper, this study does not present new original research data and cannot prove causation between any specific fatigue mechanism and symptom severity in ME/CFS. The abstract does not clarify whether findings from other neuromuscular diseases directly apply to ME/CFS or whether ME/CFS has unique fatigue mechanisms not seen in the other conditions reviewed. This work provides a conceptual framework rather than definitive evidence about which fatigue mechanisms are primary drivers of disability in ME/CFS.
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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Primary citation
Miller, Robert G (2002). Role of fatigue in limiting physical activities in humans with neuromuscular diseases.. American journal of physical medicine & rehabilitation. https://doi.org/10.1097/00002060-200211001-00011
BibTeX
@article{mecfsatlas-miller-2002-role-fatigue,
author = {Miller, Robert G},
title = {Role of fatigue in limiting physical activities in humans with neuromuscular diseases.},
journal = {American journal of physical medicine & rehabilitation},
year = {2002},
doi = {10.1097/00002060-200211001-00011},
note = {PubMed: 12409815},
url = {https://www.mecfsatlas.com/evidence/miller-2002-role-fatigue},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/miller-2002-role-fatigue
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