McComas, A J, Miller, R G, Gandevia, S C · Advances in experimental medicine and biology · 1995 · DOI
This review examines why people with nervous system disorders experience extreme tiredness and weakness. The authors looked at several conditions—including post-polio syndrome, multiple sclerosis, spinal cord injury, ALS, and ME/CFS—and found that damage to nerves can make muscles tire much more easily than normal. Lack of physical activity can make this problem worse over time.
This study helps explain why ME/CFS patients experience disproportionate fatigue by examining overlapping neurological mechanisms seen across similar conditions. Understanding these shared pathways—including impaired muscle recruitment and neuromuscular dysfunction—provides a framework for investigating the biological basis of fatigue in ME/CFS rather than attributing it solely to deconditioning or psychological factors.
This review does not establish specific mechanisms unique to ME/CFS or prove that any particular cellular component causes fatigue in this population. The inclusion of diverse neurological disorders does not demonstrate that ME/CFS shares identical pathophysiology with these conditions, and the review design cannot establish causation or quantify the relative contribution of different mechanisms to fatigue severity.
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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