Pagani, M, Lucini, D, Mela, G S et al. · Clinical science (London, England : 1979) · 1994 · DOI
This study examined how the nervous system controls heart rate in people with unexplained fatigue compared to healthy people. Using heart rate recordings, researchers found that fatigue patients showed an imbalance in their autonomic nervous system—specifically, the part that triggers the "fight or flight" response was overactive while the calming part was underactive, even at rest.
This study provides objective, non-invasive physiological evidence that ME/CFS involves quantifiable autonomic nervous system dysfunction rather than just subjective symptoms. These findings support the biological basis of unexplained chronic fatigue and suggest that autonomic testing could help identify and understand the condition, potentially improving diagnosis and treatment strategies.
This study demonstrates association between fatigue and autonomic imbalance but does not establish causation—it is unclear whether sympathetic overactivity causes fatigue or results from it. As a cross-sectional study, it cannot determine whether this autonomic pattern is present before fatigue develops or how it changes over time. The findings are also specific to heart rate control and do not necessarily explain all mechanisms underlying ME/CFS symptoms.
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Pagani, M, Lucini, D, Mela, G S, Langewitz, W, & Malliani, A (1994). Sympathetic overactivity in subjects complaining of unexplained fatigue.. Clinical science (London, England : 1979). https://doi.org/10.1042/cs0870655
BibTeX
@article{mecfsatlas-pagani-1994-sympathetic-overactivity,
author = {Pagani, M and Lucini, D and Mela, G S and Langewitz, W and Malliani, A},
title = {Sympathetic overactivity in subjects complaining of unexplained fatigue.},
journal = {Clinical science (London, England : 1979)},
year = {1994},
doi = {10.1042/cs0870655},
note = {PubMed: 7874856},
url = {https://www.mecfsatlas.com/evidence/pagani-1994-sympathetic-overactivity},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/pagani-1994-sympathetic-overactivity
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