158 - Seizures induce significant changes in cerebral oxidative metabolism following neonatal encephalopathy

Friday, April 28, 2023

5:15 PM – 7:15 PM ET

Poster Number: 158
Publication Number: 158.135

Alan Bainbridge, UCLH NHS Foundation Trust, London, England, United Kingdom; Giles S. kendall, University College London, London, England, United Kingdom; Magdalena Sokolska, University College London Hospitals, London, England, United Kingdom; Kelly Pegoretti Baruteau, University College London, London, England, United Kingdom; Francisco Torrealdea, UCLH, London, England, United Kingdom; Sean Mathieson, University College Cork, Rosscarbery, Cork, Ireland; Nicola J. Robertson, University College London and University of Edinburgh, Bicester, England, United Kingdom; Geraldine B. Boylan, University College Cork, Cork, Cork, Ireland; Subhabrata Mitra, University College London, London, England, United Kingdom

Presenting Author(s)

SM

Subhabrata Mitra, PhD (he/him/his)

Associate Professor and Honorary Consultant Neonatologist
University College London
London, England, United Kingdom

Background: Neonatal seizures cause further brain injury and are common following neonatal encephalopathy (NE). Proton magnetic resonance spectroscopy (MRS) is an important tool for the assessment of injury and prognostication following NE.

Objective:

The purpose of this study is to identify-a) the impact of neonatal seizures on brain metabolism following NE and, b) identify changes in individual metabolites.

Design/Methods:

Data were collected from 58 term neonates with NE (corrected gestational age of 36-44 weeks) undergoing hypothermia (18 severe & 40 moderate NE) and were scanned in a 3T MR scanner between 5-14 days of age. Infants were continuously monitored with video-EEG and all electrographic seizures were annotated. Conventional MR imaging was obtained along with MRS using a single voxel positioned in the thalamus-basal ganglia region. MRS data were analysed using Tarquin. Metabolite ratios were calculated from the fitted data. The data were further analysed using a combined reference method to assess the impact on individual metabolites: metabolite signals were weighted inversely to the standard deviation of each metabolite within the cohort and then summed to generate a reference value (CRef) against which the metabolites of interest can be ratioed. Metabolites with normal distributions within the cohort (Aspartate, Creatine(Cr), Choline(Cho), NAA (N-acetyl aspartate), Taurine and Glutamate+glutamine(Glx)) were included in CRef. Threonine(Thr) was included in the Tarquin basis set to better fit the region around 1.3ppm–the sum of Lactate and threonine was analysed rather than the fitted lactate alone.

Results:

25 (43%) neonates developed seizures (10 moderate & 15 severe NE). Total electrographic seizure burden ranged from 1.92-614.95 mins (mean=162.91mins; SD=147.48mins). Severe NE had 3.33 times increased chance of developing seizures compared to moderate NE. Significant differences between seizure and non-seizure groups were noted (after adjusting for degree of NE), both for metabolite ratios (Lac/NAA, Lac/Cho, Lac/Cr), and individual metabolites ratioed to CRef (Lac, Cho, Cr, Glx), using two-way ANOVA and post hoc comparisons (table 1).

Conclusion(s):

Neonatal seizures themselves induced significant changes in cerebral energy metabolism. The combined reference method can better elucidate the impact on individual metabolites. Seizure-induced metabolite changes were primarily driven by increased Lac (increased anaerobic state), reduced Cho in neonates with seizures (deranged phospholipid metabolism) and increased Glx (disturbance of excitatory mediator turnover) in this study.