Ghali, Alaa, Lacout, Carole, Ghali, Maria et al. · Journal of clinical medicine · 2021 · DOI
This study looked at whether certain new or unusual symptoms might warn ME/CFS patients that a post-exertional malaise (PEM) flare is coming. Researchers reviewed medical records from 197 ME/CFS patients and found that about 14% experienced mood changes or other new symptoms before their baseline symptoms got worse. Interestingly, these patients had less intense PEM flares than those without warning symptoms, suggesting these early signals might help patients prepare or prevent more severe crashes.
Identifying prodromal or warning symptoms could enable ME/CFS patients to modify activity proactively, potentially reducing PEM severity and improving quality of life. This study is among the first to systematically examine whether early symptom changes predict and correlate with PEM intensity, opening a new avenue for patient-centered symptom monitoring and prevention strategies.
This study does not prove that early symptoms cause PEM or that they reliably predict PEM in all patients; only 13.7% of the cohort exhibited them. The retrospective design cannot establish whether identifying these signals allows patients to successfully prevent or modify PEM, nor does it clarify the biological mechanism linking prodromal symptoms to reduced PEM intensity. Causality and the generalizability to diverse ME/CFS populations remain unconfirmed.
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
Ghali, Alaa, Lacout, Carole, Ghali, Maria, Gury, Aline, Delattre, Estelle, Lavigne, Christian, et al. (2021). Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Retrospective Analysis of 197 Patients.. Journal of clinical medicine. https://doi.org/10.3390/jcm10112517
BibTeX
@article{mecfsatlas-ghali-2021-warning-signals,
author = {Ghali, Alaa and Lacout, Carole and Ghali, Maria and Gury, Aline and Delattre, Estelle and Lavigne, Christian and Urbanski, Geoffrey},
title = {Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Retrospective Analysis of 197 Patients.},
journal = {Journal of clinical medicine},
year = {2021},
doi = {10.3390/jcm10112517},
note = {PubMed: 34200126},
url = {https://www.mecfsatlas.com/evidence/ghali-2021-warning-signals},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/ghali-2021-warning-signals
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