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March 22, 2022; 98 (12) Research Article

Magnetic Resonance Spectroscopy of Hypoxic-Ischemic Encephalopathy After Cardiac Arrest

View ORCID ProfileJong Woo Lee, Lasya P. Sreepada, Matthew B. Bevers, Karen Li, Benjamin M. Scirica, Danuzia Santana da Silva, Galen V. Henderson, Camden Bay, View ORCID ProfileAlexander P. Lin
First published January 11, 2022, DOI: https://doi.org/10.1212/WNL.0000000000013297
Jong Woo Lee
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Lasya P. Sreepada
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Matthew B. Bevers
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Karen Li
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Benjamin M. Scirica
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Danuzia Santana da Silva
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Galen V. Henderson
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Camden Bay
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Alexander P. Lin
From the Department of Neurology (J.W.L., M.B., K.L., G.V.H.), Department of Radiology (L.S., C.B., A.P.L.), and Department of Medicine, Division of Cardiology (B.S., D.S.d.S.), Brigham and Women's Hospital, Boston, MA.
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Magnetic Resonance Spectroscopy of Hypoxic-Ischemic Encephalopathy After Cardiac Arrest
Jong Woo Lee, Lasya P. Sreepada, Matthew B. Bevers, Karen Li, Benjamin M. Scirica, Danuzia Santana da Silva, Galen V. Henderson, Camden Bay, Alexander P. Lin
Neurology Mar 2022, 98 (12) e1226-e1237; DOI: 10.1212/WNL.0000000000013297

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Abstract

Background and Objectives To correlate brain metabolites with clinical outcome using magnetic resonance spectroscopy (MRS) in patients undergoing targeted temperature management (TTM) after cardiac arrest and assess their relationships to MRI and EEG variables.

Methods A prospective cohort of 50 patients was studied. The primary outcome was coma recovery to follow commands. Comparison of MRS measures in the posterior cingulate gyrus, parietal white matter, basal ganglia, and brainstem were also made to 25 normative controls.

Results Fourteen of 50 patients achieved coma recovery before hospital discharge. There was a significant decrease in total N-acetylaspartate (NAA/Cr) and an increase in lactate/creatine (Lac/Cr) in patients who did not recover, with changes most prominent in the posterior cingulate gyrus. Patients who recovered had decrease in NAA/Cr as compared to controls. NAA/Cr had a strong monotonic relationship with MRI cortical apparent diffusion coefficient (ADC); Lac level exponentially increased with decreasing ADC. EEG suppression/burst suppression was strongly associated with Lac elevation.

Discussion NAA and Lac changes are associated with clinical/MRI/EEG changes consistent with hypoxic-ischemic encephalopathy (HIE) and are most prominent in the posterior cingulate gyrus. NAA/Cr decrease observed in patients with good outcomes suggests mild HIE in patients asymptomatic at hospital discharge. The appearance of cortical Lac represents a deterioration of aerobic energy metabolism and is associated with EEG background suppression, synaptic transmission failure, and severe, potentially irreversible HIE.

Classification of Evidence This study provides Class IV evidence that in patients undergoing TTM after cardiac arrest, brain MRS–determined decrease in total NAA/Cr and an increase in Lac/Cr are associated with an increased risk of not recovering.

Glossary

ADC=
apparent diffusion coefficient;
BG=
basal ganglia;
cEEG=
continuous video EEG;
Cho=
choline;
Cr=
creatine;
CPC=
cerebral performance category;
CRLB=
Cramer-Rao lower bounds;
Gln=
glutamine;
Glu=
glutamate;
Glx=
glutamate + glutamine;
GS=
glutamine synthetase;
HIE=
hypoxic-ischemic encephalopathy;
Lac=
lactate;
mI=
myoinositol;
MNI=
Montreal Neurologic Institute;
MRS=
magnetic resonance spectroscopy;
NAA=
N-acetylaspartate;
PAG=
phosphate-activated glutaminase;
PCG=
posterior cingulate gyrus;
PWM=
parietal white matter;
ROSC=
return of spontaneous circulation;
SVD=
singular value decomposition;
TTM=
targeted temperature management;
WLST=
withdrawal of life-sustaining treatment

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • This article was prepublished in medRxiv (doi: 10.1101/2021.05.13.21257029).

  • Class of Evidence: NPub.org/coe

  • CME Course: NPub.org/cmelist

  • Received March 2, 2021.
  • Accepted in final form December 27, 2021.
  • © 2022 American Academy of Neurology
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