Lange, G, DeLuca, J, Maldjian, J A et al. · Journal of the neurological sciences · 1999 · DOI
Researchers used brain MRI scans to look for abnormalities in people with ME/CFS and compared them to healthy controls. They found that some ME/CFS patients—specifically those without a separate psychiatric diagnosis—had small spots of unusual tissue in the white matter of their brains, mostly in the frontal lobes (the front part of the brain). These brain changes were not found in healthy people or in ME/CFS patients who also had psychiatric diagnoses.
This study provides objective neuroimaging evidence that some ME/CFS patients have detectable brain abnormalities, potentially validating cognitive complaints and suggesting a biological basis for the illness. By stratifying patients by psychiatric status, it highlights that ME/CFS is heterogeneous and that relevant pathology may be obscured when groups are combined—an important insight for future research design and patient characterization.
This study does not prove that white matter hyperintensities cause cognitive impairment, only that they are associated with it. It cannot establish whether these brain changes precede illness onset, develop during illness, or are specific to ME/CFS rather than other conditions. The cross-sectional design prevents causal inference, and findings in one subset (CFS-No Psych) do not necessarily apply to all ME/CFS patients.
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
Lange, G, DeLuca, J, Maldjian, J A, Lee, H, Tiersky, L A, & Natelson, B H (1999). Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome.. Journal of the neurological sciences. https://doi.org/10.1016/s0022-510x(99)00243-9
BibTeX
@article{mecfsatlas-lange-1999-brain-mri,
author = {Lange, G and DeLuca, J and Maldjian, J A and Lee, H and Tiersky, L A and Natelson, B H},
title = {Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome.},
journal = {Journal of the neurological sciences},
year = {1999},
doi = {10.1016/s0022-510x(99)00243-9},
note = {PubMed: 10567042},
url = {https://www.mecfsatlas.com/evidence/lange-1999-brain-mri},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/lange-1999-brain-mri
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