Novel brain SPECT imaging unravels abnormal cerebral perfusion in patients with POTS and cognitive dysfunction, 2025, Marie-Claire Seeley et al

Abstract
Cognitive dysfunction is frequently reported in individuals with postural orthostatic tachycardia syndrome (POTS), possibly resulting from reduced cerebral blood flow (CBF).

We used brain SPECT, an accessible imaging modality that has not been systematically evaluated in this patient group. Retrospective review of participants from our registry was undertaken to identify those who had a brain SPECT performed for investigation of cognitive dysfunction. Abnormal CBF was taken as z-score > 2 standard deviations of healthy control reference values. Patient reported outcome measures (PROMs) such as autonomic, gastric and quality of life symptom scores were analyzed.

From a total of 56 participants (mean 34.8 ± 10.7 years, 88% females), PROMs indicate: moderate to severe autonomic dysfunction in 75%; at least mild to moderate gastroparesis in 23%; low global health rating and utility scores. Abnormal CBF was seen in 61% but did not differ by POTS triggers. The regions with the lowest mean z-scores were the lateral prefrontal and sensorimotor cortices. Hierarchal regression analyses found number of brain regions with abnormal CBF, autonomic and gastric symptoms to account for 51% of variances in health utility.

Cerebral hypoperfusion is prevalent in those with POTS and cognitive dysfunction even whilst supine, contributing to reduced quality of life.
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I wonder. Do we know if all these “reduced blood flow to the head” findings might not just be a result of decondition/laying flat more often?

 

I don't know what the study is, but in the NIH research roadmap webinar, Peter Rowe said van Campen et al found no association between VO2 and cerebral blood flow reduction upon standing.

Might be interesting to look at how CBF relates to length of illness (proxy for how deconditioned a person is) when controlling for severity.

 

Here it is:

Comparison of the Degree of Deconditioning in ME/CFS Patients with and without Orthostatic Intolerance, 2022, van Campen & Visser

 

Is the reduced cerebral blood flow secondary to the brain being less metabolically active?

 

61% of POTS patients having a CBF value in the bottom 5% of the control reference values is an interesting result. I don't know much about SPECT but given others have had similar findings it seems like a plausible abnormality.

 

I don't think we know yet. We know there are metabolic problems in ME, and vascular problems, but where does it start or end. Let me quote Isaac Asimov - a circle has no end. I strongly suspect that in complex systemic issues with mutual feedback and feedforward loops that the dynamics of what is happening is more important than strictly direction.

 

POTS is not the only form of OI, but its a start.

 

21% of the cohort were in full-time employment.