Roberto Llorens Salvador, Presenter: Nothing to Disclose

Stefan Bluml PhD, Abstract Co-Author: Nothing to Disclose

Jessica Lee Wisnowski PhD, Abstract Co-Author: Nothing to Disclose

Tai-Wei Wu, Abstract Co-Author: Nothing to Disclose

Aaron Jordan Reitman DO, Abstract Co-Author: Nothing to Disclose

Robert Giesler RN, Abstract Co-Author: Nothing to Disclose

Claire McLean, Abstract Co-Author: Nothing to Disclose

Phillip Friedlich, Abstract Co-Author: Nothing to Disclose

Eugenia Ho MD, Abstract Co-Author: Nothing to Disclose

Ashok Panigrahy MD, Abstract Co-Author: Nothing to Disclose

Marvin Dale Nelson MD, Abstract Co-Author: Nothing to Disclose

Istvan Seri MD, PhD, Abstract Co-Author: Grant, Covidien AG

Therapeutic hypothermia (TH) aims to mitigate the effects of hypoxic-ischemic injury (HIE) in neonates by exerting favorable effects on multiple pathways contributing to brain injury such as energy metabolism and excitatory amino acid metabolism. Here we explored (a) the feasibility of quantifying excitatory and inhibitory neurotransmitters in patients undergoing TH in vivo and (b) the impact of TH on neurotransmitter concentrations.

15 newborns (mean gestational age = 38.9±1.9) with moderate (m)-HIE (n=12) and severe (s)-HIE (n=3), based on Sarnat staging, were examined by MR spectroscopy (MRS) during and after TH. The study during TH typically occurred between 24-48 h into 72 hours of hypothermia treatment at 33.5 °C. Hypothermia was maintained using a Blanketrol system (CSZ Medical; modified with extension tubing) and continuously monitored with a rectal temperature probe. Post-HT studies were carried out 3-5 days after rewarming. MR spectra were obtained using a single voxel PRESS sequence (echo time =35ms, repetition time =2000ms) with regions of interest localized to the basal ganglia, thalamus and medial parietal grey matter. Absolute concentrations were quantitated using LCModel (V6.3-1C, Stephen Provencher Inc.). All studies were performed on a Philips 3.0T Achieva scanner using a neonatal SENSE coil. Paired t-tests were used to compare concentrations during and after TH while non-parametric tests (Mann-Whitney U) were used to compare neonates with s-HIE and m-HIE (SPSS v.21, IBM Corporation).

Spectra of high quality during and after TH were obtained for all patients. Glutamate, aspartate and GABA concentrations were reduced by 20%, 11% and 24%, respectively during TH compared to afterwards (all p 0.5). However, aspartate was reduced by 17% among neonates with s-HIE (p < 0.02). Glutamine was elevated to 178% during TH among neonates with s-HIE (p < 0.02).

Therapeutic hypothermia, now widely implemented for neuroprotection in neonatal HIE, is associated with reduced concentrations of excitatory and inhibitory neurotransmitters. However, glutamine concentrations remain elevated among neonates with s-HIE, indicating ongoing excitotoxicity and glutamate detoxification by conversion to glutamine.

Early MRI/S may aid in the management of neonatal HIE and suggests an adjuvant role for glutamate receptor anatagonists in neonates with s-HIE.

Llorens Salvador, R, Bluml, S, Wisnowski, J, Wu, T, Reitman, A, Giesler, R, McLean, C, Friedlich, P, Ho, E, Panigrahy, A, Nelson, M, Seri, I, Glutamate, Aspartate and GABA are Reduced during Therapeutic Hypothermia in Neonates with Hypoxic-ischemic Encephalopathy.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14014328.html