Mapping cerebral blood flow in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance: insights from a systematic review.
Christopoulos, Elena M, Tantanis, Darcy, Huang, Katherine et al. · Journal of translational medicine · 2025 · DOI
Quick Summary
This review examined 118 research studies to understand how blood flow to the brain changes in ME/CFS patients, particularly those who also experience orthostatic intolerance (difficulty maintaining blood pressure when standing). Researchers found that blood flow to the brain is often reduced in both conditions, and when patients have both ME/CFS and orthostatic intolerance together, the reduction in brain blood flow appears to be even more pronounced. This finding suggests that measuring brain blood flow might help doctors track how severe the disease is.
Why It Matters
This systematic review provides comprehensive evidence that cerebral blood flow abnormalities are a measurable biological feature of ME/CFS, potentially useful for disease monitoring and severity assessment. The finding that comorbid orthostatic intolerance amplifies CBF reductions highlights the importance of screening and addressing OI in ME/CFS patients, and calls attention to a commonly overlooked confounding factor in prior ME/CFS research.
Observed Findings
Cerebral blood flow was significantly reduced in 12 of 26 ME/CFS-focused studies compared to healthy controls
Cerebral blood flow was significantly reduced in 56 of 81 orthostatic intolerance-focused studies compared to healthy controls
In 4 of 11 studies examining both conditions together, CBF was further reduced in participants with comorbid ME/CFS and orthostatic intolerance versus ME/CFS alone
73.8% of included study participants were female with a mean age of 39.1 years across 9,185 total participants
Orthostatic intolerance may be a confounding factor in a large proportion of existing ME/CFS cerebral blood flow studies
Inferred Conclusions
Cerebral blood flow reduction is a common finding in ME/CFS, suggesting it represents a measurable biological abnormality relevant to the condition
Cerebral blood flow monitoring may be useful for assessing disease severity in ME/CFS patients
OI is an important confounding variable that has been insufficiently controlled for in previous ME/CFS research
Remaining Questions
What causes the cerebral blood flow reductions in ME/CFS and orthostatic intolerance, and what is the mechanistic link between reduced CBF and patient symptoms?
What This Study Does Not Prove
This review does not establish that reduced cerebral blood flow causes ME/CFS symptoms or that normalizing CBF will cure the disease. It cannot determine causation from the identified associations, and the heterogeneity of measurement methods across studies means findings should be interpreted cautiously. It also does not prove that CBF measurement alone is sufficient for diagnosis or prognosis in individual 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 →
Do cerebral blood flow changes correlate with symptom severity or patient outcomes, and can CBF measurements predict treatment response?
Why has there been so little research specifically examining ME/CFS and orthostatic intolerance together despite their frequent co-occurrence in clinical populations?
Which standardized CBF measurement methods are most reliable and reproducible for monitoring ME/CFS disease progression?