Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla

Ashley L. Wagoner, John D. Olson, Brian M. Westwood, John Edward Fortunato, Debra I. Diz, Hossam A. Shaltout*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)H323-H329
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume317
Issue number2
DOIs
StatePublished - Aug 1 2019

Fingerprint

Orthostatic Intolerance
Heart Rate
Inflammation
Choline
Baroreflex
Neuroglia
Autonomic Nervous System Diseases
Magnets
Supine Position
Autonomic Nervous System
Brain
Inositol
Magnetic Resonance Spectroscopy
Head
Blood Pressure
Population

Keywords

  • Inflammation
  • Magnetic resonance spectroscopy
  • Myoinositol
  • Orthostatic intolerance

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Wagoner, Ashley L. ; Olson, John D. ; Westwood, Brian M. ; Fortunato, John Edward ; Diz, Debra I. ; Shaltout, Hossam A. / Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla. In: American Journal of Physiology - Heart and Circulatory Physiology. 2019 ; Vol. 317, No. 2. pp. H323-H329.
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Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla. / Wagoner, Ashley L.; Olson, John D.; Westwood, Brian M.; Fortunato, John Edward; Diz, Debra I.; Shaltout, Hossam A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 317, No. 2, 01.08.2019, p. H323-H329.

Research output: Contribution to journalArticle

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 Edward

AU - Diz, Debra I.

AU - Shaltout, Hossam A.

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KW - Magnetic resonance spectroscopy

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