Abstract P069: 1H-Magnetic Resonance Spectroscopy Reveals Elevation of MyoInositol and Other Markers of Inflammation in the Dorsal Medulla of Children with Orthostatic Intolerance

Abstract

Children with orthostatic intolerance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Inflammation is proposed as a possible factor contributing to impaired HRV in cardiometabolic disorders; whether systemic or brain inflammation better predicts impaired HRV is arguable. We used 1H magnetic resonance spectroscopy (MRS) to quantify markers of neuronal and glial integrity in children with OI compared with asymptomatic controls. Fifteen subjects ages 10-18 years were evaluated for blood pressure, HR, and autonomic function in supine and upright positions and 7 tested positive for OI. An average of 2 weeks following OI testing all subjects underwent 1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. OI subjects had higher myoinositol (mIns) as a marker of glial inflammation than asymptomatic controls (7.8 ± 0.4 vs 5.6 ± 0.9 mmol/L, p = 0.03). Trends were observed for higher glycerophosphocholine (higher GPC, reduced myelination and axonal integrity) (2.3 ± 0.2 vs 1.8 ± 0.2 mmol/L, p = 0.08) and lower N-acetyl aspartate (lower NAA, reduced neuronal integrity) (2.8 ± 0.3 vs. 3.7 ± 0.4 mmol/L, p = 0.1) in OI subjects vs controls (mean ± SEM). mIns concentrations did not correlate with indices of autonomic function measured in the supine position. However, supine measures of mIns correlated with autonomic measures taken in the upright position: negatively correlated with spontaneous BRS (R = -0.64, p = 0.01), parasympathetic tone measured by high frequency alpha index (HFα, R= -0.547, p=0.04) and HRV measured by root of mean square of successive differences (rMSSD, R = -0.45, p = 0.09); there was a positive correlation with HR (R = 0.53, p < 0.05). In summary, children with OI have higher mIns in dorsal medulla while supine that is predictive of impairment in BRS, HRV and parasympathetic tone upon upright posture. This first report that OI in children is associated with elevated mIns, a marker of glial inflammation in a variety of neuropathies, raises the intriguing possibility that brain inflammation plays a role in the autonomic dysfunction observed while standing in these subjects. Support: Centers for Integrative Medicine and Hypertension & Vascular Research; AHA12CRP9420029