TY - JOUR
T1 - Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla
AU - Wagoner, Ashley L.
AU - Olson, John D.
AU - Westwood, Brian M.
AU - Fortunato, John E.
AU - Diz, Debra I.
AU - Shaltout, Hossam A.
N1 - Funding Information:
This study was supported by Centers for Integrative Medicine and Hypertension & Vascular Research at Wake Forest Baptist Health, American Heart Association Grant AHA12CRP9420029 (to J. E. Fortunato, principal investigator), and the Farley Hudson Foundation.
Funding Information:
We thank Anya Brown and the MRI Center at Wake Forest Baptist Health. GRANTS This study was supported by Centers for Integrative Medicine and Hypertension & Vascular Research at Wake Forest Baptist Health, American Heart Association Grant AHA12CRP9420029 (to J. E. Fortunato, principal investi-gator), and the Farley Hudson Foundation.
Publisher Copyright:
© 2019 the American Physiological Society.
PY - 2019/8
Y1 - 2019/8
N2 - Children with orthostatic intoler-ance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Accompanying brain transmitter and metabolite profiles are unknown. In this study, we used proton (1H) magnetic resonance spectroscopy (1H-MRS) to quantify markers of neuronal and glial integrity in a pilot study of children with OI compared with asymptomatic controls. Eighteen participants ages 10 –18 yr were evaluated for blood pressure, heart rate (HR), and calculated indexes of autonomic function in supine and upright positions and, within an average of 2 wk, underwent1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. As a result, of the 18 participants, 11 tested positive for OI and 7 did not. OI subjects exhibited higher HR and lower HRV and high-frequency α-index (HFα), an index of parasympathetic vagal tone, during standing compared with non-OI. HRV, sequence all (Seq All), high-and low-frequency (HFα and LFα) estimates of the spontaneous BRS decreased significantly, while BP variabilty increased significantly during standing only in subjects with OI. OI subjects had higher myoinositol (mIns) and total choline (tCho), markers of glial inflammation. Upright HFα and Seq All inversely correlated to supine tCho and mIns, respectively, independent of age and sex. In conclusions, in this pilot study, children with OI exhibit higher mIns and tCho in the dorsal medulla while supine that may reflect the well-established impairment in regulation of the autonomic nervous system upon standing. Neuroinflammation as an underlying cause or consequence of autonomic dysfunction is an intriguing possibility requiring further study. NEW & NOTEWORTHY (1H) magnetic resonance spectroscopy detected elevated markers of neuroinflammation in the dorsal medulla in children with impaired autonomic responses to head upright tilt. This first report of altered brain metabolites in this population provides a basis for future clinical studies using this methodology to aide in understanding complex autonomic disease states.
AB - Children with orthostatic intoler-ance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Accompanying brain transmitter and metabolite profiles are unknown. In this study, we used proton (1H) magnetic resonance spectroscopy (1H-MRS) to quantify markers of neuronal and glial integrity in a pilot study of children with OI compared with asymptomatic controls. Eighteen participants ages 10 –18 yr were evaluated for blood pressure, heart rate (HR), and calculated indexes of autonomic function in supine and upright positions and, within an average of 2 wk, underwent1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. As a result, of the 18 participants, 11 tested positive for OI and 7 did not. OI subjects exhibited higher HR and lower HRV and high-frequency α-index (HFα), an index of parasympathetic vagal tone, during standing compared with non-OI. HRV, sequence all (Seq All), high-and low-frequency (HFα and LFα) estimates of the spontaneous BRS decreased significantly, while BP variabilty increased significantly during standing only in subjects with OI. OI subjects had higher myoinositol (mIns) and total choline (tCho), markers of glial inflammation. Upright HFα and Seq All inversely correlated to supine tCho and mIns, respectively, independent of age and sex. In conclusions, in this pilot study, children with OI exhibit higher mIns and tCho in the dorsal medulla while supine that may reflect the well-established impairment in regulation of the autonomic nervous system upon standing. Neuroinflammation as an underlying cause or consequence of autonomic dysfunction is an intriguing possibility requiring further study. NEW & NOTEWORTHY (1H) magnetic resonance spectroscopy detected elevated markers of neuroinflammation in the dorsal medulla in children with impaired autonomic responses to head upright tilt. This first report of altered brain metabolites in this population provides a basis for future clinical studies using this methodology to aide in understanding complex autonomic disease states.
KW - Inflammation
KW - Magnetic resonance spectroscopy
KW - Myoinositol
KW - Orthostatic intolerance
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U2 - 10.1152/ajpheart.00680.2018
DO - 10.1152/ajpheart.00680.2018
M3 - Article
C2 - 31225987
AN - SCOPUS:85070788985
SN - 0363-6135
VL - 317
SP - H323-H329
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 2
ER -