Brain tissue changes, network dysfunction, and cerebral hemodynamic deficits in postural orthostatic tachycardia syndrome

Tachycardia upon standing implicates cardiovascular dysreflexia, potentially resulting from impaired autonomic regulation. However, the pathophysiology of POTS remains unclear. Here, we evaluated the central nervous system in postural orthostatic syndrome (POTS). The purpose of this study was to evaluate brain tissue changes, functional networks (the central autonomic network), and cerebral hemodynamic status in patients with POTS using magnetic resonance imaging (MRI) and autonomic reflex challenges. Individuals with POTS and age- and sex-matched healthy controls were enrolled. Brain MRI data were collected with a 3.0-T scanner at rest and during functional MRI using 3 autonomic reflex challenges: passive leg raise, mental arithmetic, and isometric handgrip reflex. 38 participants were enrolled (18 patients with POTS and 20 controls). No significant differences emerged in age, sex, or body mass index between patients with POTS and controls (P > .05). Patients with POTS had higher anxiety and depression symptoms. Although global screening indicators of cognitive function were preserved (Montreal Cognitive Assessment test: POTS vs controls, 28 ± 1 vs 29 ± 1; P = .2), executive function was slowed in POTS (Trail Making Test Part B: POTS vs controls, 44 ± 12 vs 67 ± 34; P = .008). Brain tissue structural changes (P < .005) and reduced cerebral blood flow appeared in patients with POTS compared with controls (P < .005). Furthermore, impaired neural responses were seen in patients with POTS during passive leg raise, mental arithmetic, and isometric handgrip reflex challenges (P < .005), despite preserved peripheral reflex function (P > .05). Patients with POTS show evidence of brain tissue structural changes, impaired central neural responses, and reduced cerebral blood flow in autonomic regulatory sites during cardiovascular reflex testing. These findings indicate that central autonomic control deficits may help explain cardiovascular dysreflexia in POTS.