E1 ReplicatedModerate confidencePEM requiredObservationalPeer-reviewedReviewed
Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia
C. M. C. van Campen, F. C. Visser, P. C. Rowe · Journal of Internal Medicine · 2020 · DOI
Quick Summary
In the largest study of its kind, 429 ME/CFS patients underwent head-up tilt testing with simultaneous cerebral blood flow monitoring. Nearly all ME/CFS patients showed significantly reduced cerebral blood flow when upright, even when blood pressure and heart rate were normal. The reduction correlated with symptom severity.
Why It Matters
This large study demonstrates that reduced brain blood flow in upright posture is nearly universal in ME/CFS — even without classic POTS criteria being met. It explains the cognitive symptoms and post-exertional worsening that many patients experience and suggests that hemodynamic support may be a treatment avenue.
Observed Findings
- Reduced cerebral blood flow during upright posture in nearly all 429 ME/CFS patients
- Reduced cerebral blood flow occurred independent of hypotension or tachycardia
- Cerebal blood flow reduction correlated with symptom severity
- Findings detected via simultaneous head-up tilt testing and cerebral blood flow monitoring
Inferred Conclusions
- Cerebrovascular dysfunction may be a characteristic physiological marker of ME/CFS
- Normal hemodynamic responses (blood pressure and heart rate) do not preclude significant cerebral perfusion abnormalities in ME/CFS
Remaining Questions
- Is reduced cerebral blood flow a primary causative mechanism, a secondary consequence, or an epiphenomenon of ME/CFS?
- Do treatments targeting cerebral blood flow improve ME/CFS symptoms and functional outcomes?
What This Study Does Not Prove
This study cannot determine whether reduced cerebral blood flow is a cause of ME/CFS, a consequence, or simply a feature. Treatment implications require separate trial evidence.
Tags
Method Flag:PEM_DEFINEDIOM_CRITERIABIOLOGICALLY_RELEVANTCLINICAL_ENDPOINTWeak Case Definition
Symptom:Orthostatic IntoleranceFatigue
Biomarker:Neuroimaging
Metadata
- DOI
- 10.1111/joim.13042
- Case definition
- IOM/SEID Criteria
- Sample size
- 429 patients
- Control group
- Yes
- Review status
- Editor reviewed
- Evidence level
- Replicated human evidence from multiple independent studies
- Last updated
- 12 April 2026
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 →
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