Egg, R, Högl, B, Glatzl, S et al. · Multiple sclerosis (Houndmills, Basingstoke, England) · 2002 · DOI
This study looked at whether problems with the nervous system's ability to regulate automatic body functions (like pupil responses) might explain fatigue in multiple sclerosis patients. Researchers measured pupil movements in MS patients and healthy volunteers, then compared these measurements to fatigue severity scores. Surprisingly, they found the opposite of what they expected: people with more pupil instability actually reported less fatigue, not more.
This study is relevant to ME/CFS research because sympathovagal imbalance has been similarly hypothesized as a mechanism for fatigue in chronic fatigue syndrome. The unexpected negative finding challenges a widely-held assumption about autonomic dysfunction and fatigue, suggesting researchers should look beyond simple ANS dysregulation to explain persistent fatigue in neurological conditions.
This study does not prove that autonomic dysfunction plays no role in fatigue—it only shows that pupillary unrest specifically does not correlate with fatigue severity in this MS cohort. The inverse correlation finding is counterintuitive and may reflect measurement artifacts, confounding variables, or population-specific factors that were not explored. Cross-sectional design prevents any causal conclusions about ANS function and fatigue mechanisms.
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
Egg, R, Högl, B, Glatzl, S, Beer, R, & Berger, T (2002). Autonomic instability, as measured by pupillary unrest, is not associated with multiple sclerosis fatigue severity.. Multiple sclerosis (Houndmills, Basingstoke, England). https://doi.org/10.1191/1352458502ms793oa
BibTeX
@article{mecfsatlas-egg-2002-autonomic-instability,
author = {Egg, R and Högl, B and Glatzl, S and Beer, R and Berger, T},
title = {Autonomic instability, as measured by pupillary unrest, is not associated with multiple sclerosis fatigue severity.},
journal = {Multiple sclerosis (Houndmills, Basingstoke, England)},
year = {2002},
doi = {10.1191/1352458502ms793oa},
note = {PubMed: 12120699},
url = {https://www.mecfsatlas.com/evidence/egg-2002-autonomic-instability},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/egg-2002-autonomic-instability
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