E2 ModerateModerate confidencePEM requiredObservationalPeer-reviewedReviewed
Worsening Symptoms Is Associated with Larger Cerebral Blood Flow Abnormalities during Tilt-Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
van Campen, C Linda M C, Rowe, Peter C, Visser, Frans C · Medicina (Kaunas, Lithuania) · 2023 · DOI
Quick Summary
This study found that ME/CFS patients with worsening symptoms had larger problems with blood flow to their brain during a standing-up test (tilt test). When researchers compared patients at two visits, those who got sicker showed a bigger drop in brain blood flow (from 19% to 31%), while patients who stayed stable showed no change in blood flow reduction. The more severe a patient's ME/CFS became, the greater the reduction in blood flow to the brain.
Why It Matters
This research provides objective physiological evidence linking ME/CFS disease severity to measurable brain blood flow abnormalities, potentially validating patient-reported symptom worsening with biological markers. Understanding this relationship may help clinicians assess disease progression and could inform future therapeutic targets aimed at improving cerebral perfusion in ME/CFS.
Observed Findings
- Patients with worsening symptoms showed %CBF reduction increase from 19% to 31% between visits (p<0.0001)
- Disease severity distribution shifted dramatically in symptomatic worsening group from 51/45/4% (mild/moderate/severe) to 1/72/27% (p<0.0001)
- Stable disease group (n=39) showed no significant change in %CBF reduction (both 24%, p=ns) or severity distribution
- Combined analysis across 219 patients showed stepwise correlation: mild disease 25% CBF reduction, moderate 29%, severe 33% (p<0.0001)
Inferred Conclusions
- Disease severity and cerebral blood flow reduction during tilt testing are highly associated in ME/CFS patients
- A larger percentage reduction in cerebral blood flow is related to more severe disease presentation
- The relationship suggests a possible causal mechanism where impaired cerebral perfusion during orthostatic stress may drive symptom worsening
Remaining Questions
- Does cerebral blood flow reduction cause symptoms, or do underlying disease mechanisms cause both CBF abnormalities and symptom worsening?
- What physiological mechanisms drive the progressive increase in CBF reduction as disease severity worsens?
- Can interventions that improve cerebral blood flow during tilt testing reduce symptom severity or prevent disease progression?
What This Study Does Not Prove
While the study suggests a possible causal relationship between CBF reduction and symptom worsening, it cannot definitively prove causation—the direction of causality remains uncertain, and both may be consequences of underlying disease mechanisms. The study also does not establish whether CBF reduction is the primary cause of symptoms or a secondary manifestation of ME/CFS pathology.
Tags
Symptom:Orthostatic IntoleranceFatigue
Biomarker:Neuroimaging
Phenotype:Severe
Method Flag:Strong PhenotypingSevere ME Included
Metadata
- DOI
- 10.3390/medicina59122153
- PMID
- 38138257
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- 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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