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.
Seeley et al 2025
Extracts
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.
Results
A total of 62 patients with POTS were identified to have previously undergone brain SPECT imaging from 440 patients enrolled in the registry over the study period. Six patients were excluded due to incomplete data leaving 56 participants eligible for inclusion in this analysis (Table 1 & Supplementary Fig. 2). The mean age was 34.8 ± 10.7 years with an average body mass index of 26.5 ± 6.4 kg/m2 and there was a Caucasian (95%) and female sex (88%) preponderance. Most of the participants were tertiary educated (71%), however, only 21% were in fulltime employment. The onset of POTS symptoms was reported at a median age of 28 years (IQR 16–37) after a diagnostic delay of 4.9 ± 6.1 years.
A discernible trigger with temporal proximity to POTS symptom onset was found in 71% of the cohort. SARS-CoV-2 infection was the most common of these (29%) followed by infections other than COVID-19 (20%), and trauma/concussion (13%). A further 10% had a mixture of other associated onset triggers such as vaccination, pregnancy and surgery. Of the 16 patients with COVID-19 related POTS, 87% had at least two SARS-CoV-2 vaccinations prior to their infection. All had laboratory confirmed mild COVID-19 infection that did not require hospitalization or oxygen therapy. The most common co-morbid conditions were migraine (54%), hEDS (45%) and myalgic encephalomyelitis (36%).
Conclusion
There is a high prevalence of reduced cerebral perfusion in those with POTS, which is detectable with supine brain SPECT imaging and is associated with diminished quality of life. The most frequently affected areas are prefrontal lateral and sensorimotor cortices. Reduced cerebral perfusion appears to be more prevalent in those with comorbid joint hypermobility syndrome and independent of POTS triggers. These results highlight the need for further research to delineate the etiology and mechanistic pathways underlying neurovascular dysfunction in post-viral and autonomic syndromes including long-COVID. Future prospective studies may explore the role of therapies such as exercise, vasoconstrictors and fluid management on cerebral perfusion.
MEA Comment
While this research is looking at blood flow to the brain (cerebral blood flow) and problems with short term memory and concentration (cognitive dysfunction) in people who have postural orthostatic tachycardia syndrome (PoTS) the findings are also relevant to ME/CFS.
This is because a significant proportion of people with ME/CFS, especially those in younger age groups, also have PoTS and cognitive dysfunction is a key diagnostic feature of ME/CFS.
It is also worth noting that decreased cerebral blood flow has been reported in ME/CFS using the same type of neuroimaging technique (SPECT scans) that was used in this study.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
