Christopoulos et al. (2025)
- Authors: Elena M. Christopoulos, Darcy Tantanis, Katherine Huang, Elena K. Schneider-Futschik, Paul R. Gooley, Kegan J. Moneghetti, Christopher W. Armstrong.
- Institutes: Department of Biochemistry and Pharmacology, Bio21 Institute, The University of Melbourne, Parkville, VIC, Australia; Cardiometabolic Health and Exercise Physiology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
- Publisher: Journal of Translational Medicine.
- Link: DOI
Summary
This large-scale review of 118 studies consolidates the evidence that reduced blood flow to the brain is a common feature in both ME/CFS and orthostatic intolerance. The key finding for patients is that having both ME/CFS and OI (like POTS) appears to worsen this blood flow problem significantly. This provides a strong physiological basis for symptoms like brain fog, light-headedness, and post-exertional malaise, especially those triggered by being upright. By establishing reduced CBF as a consistent and measurable abnormality, this work strengthens the case for its use as a potential biomarker for disease severity and points towards future treatments aimed at improving cerebral circulation.
What was researched?
This systematic review assessed existing research to determine if cerebral blood flow (CBF) is reduced in patients with ME/CFS and/or orthostatic intolerance (OI). The researchers specifically investigated whether having both ME/CFS and OI at the same time leads to an even greater reduction in blood flow to the brain.
Why was it researched?
A large proportion of people with ME/CFS experience symptoms of orthostatic intolerance, which are thought to be caused by decreased cerebral blood flow. This reduction in CBF may be a major contributing factor to the cognitive impairment known as ‘brain fog’. This review aimed to synthesize the evidence from numerous studies to clarify the relationship between these conditions and CBF, potentially aiding future diagnosis and treatment.
How was it researched?
This was a systematic literature review that followed PRISMA guidelines. Researchers searched four major scientific databases for studies published up to February 14th, 2025, that measured CBF in ME/CFS, OI, or both. From an initial pool of 14,928 articles, 118 studies met the inclusion criteria. These studies were grouped into those focusing on ME/CFS alone (26 studies), OI alone (81 studies), or both conditions combined (11 studies), encompassing a total of 9,185 participants.
What has been found?
The review found that CBF was significantly reduced in a substantial portion of studies focusing on ME/CFS alone (12 out of 26) and in a majority of studies on OI alone (56 out of 81) when compared to healthy controls. More importantly, a majority of the articles that directly compared ME/CFS patients with and without OI (4 out of 7) found that having both conditions resulted in a significantly larger decrease in CBF than having ME/CFS alone.
Discussion
The authors noted several limitations, including the high variability in methods used to measure CBF across studies (e.g., MRI, TCD, SPECT), which made a direct meta-analysis impossible. They also highlighted that many ME/CFS studies did not screen for OI, which may have acted as a confounding factor. Furthermore, severely ill patients are often unable to participate in studies involving orthostatic challenges like tilt table tests, meaning the most affected segment of the patient population is likely underrepresented.
Conclusion & Future Work
The authors conclude that cerebral blood flow is reduced in both ME/CFS and OI, and having both conditions comorbidly amplifies this reduction. They suggest that monitoring CBF could be a valuable tool for assessing disease severity in ME/CFS patients. The researchers emphasize that understanding how ME/CFS and OI interact to affect CBF is crucial for improving diagnosis and developing targeted therapies.