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Randomized Controlled Trial
. 2024 May 1;41(4):344-350.
doi: 10.1097/WNP.0000000000001011. Epub 2023 Apr 12.

Macroperiodic Oscillations: A Potential Novel Biomarker of Outcome in Neonatal Encephalopathy

Jennifer C Keene  1 , Maren E Loe  2   3 , Talie Fulton  4 , Maire Keene  1   2   3   4   5   6 , Amit Mathur  5 , Michael J Morrissey  1 , Stuart R Tomko  1 , Zachary A Vesoulis  6 , John M Zempel  1 , ShiNung Ching  2 , Réjean M Guerriero  1
Affiliations
Randomized Controlled Trial

Macroperiodic Oscillations: A Potential Novel Biomarker of Outcome in Neonatal Encephalopathy

Jennifer C Keene et al. J Clin Neurophysiol. .

Abstract

Purpose: Neonatal encephalopathy (NE) is a common cause of neurodevelopmental morbidity. Tools to accurately predict outcomes after therapeutic hypothermia remain limited. We evaluated a novel EEG biomarker, macroperiodic oscillations (MOs), to predict neurodevelopmental outcomes.

Methods: We conducted a secondary analysis of a randomized controlled trial of neonates with moderate-to-severe NE who underwent standardized clinical examination, magnetic resonance (MR) scoring, video EEG, and neurodevelopmental assessment with Bayley III evaluation at 18 to 24 months. A non-NE cohort of neonates was also assessed for the presence of MOs. The relationship between clinical examination, MR score, MOs, and neurodevelopmental assessment was analyzed.

Results: The study included 37 neonates with 24 of whom survived and underwent neurodevelopmental assessment (70%). The strength of MOs correlated with severity of clinical encephalopathy. MO strength and spread significantly correlated with Bayley III cognitive percentile ( P = 0.017 and 0.046). MO strength outperformed MR score in predicting a combined adverse outcome of death or disability ( P = 0.019, sensitivity 100%, specificity 77% vs. P = 0.079, sensitivity 100%, specificity 59%).

Conclusions: MOs are an EEG-derived, quantitative biomarker of neurodevelopmental outcome that outperformed a comprehensive validated MRI injury score and a detailed systematic discharge examination in this small cohort. Future work is needed to validate MOs in a larger cohort and elucidate the underlying pathophysiology of MOs.

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Conflict of interest statement

This research was supported in part by the Thrasher Foundation (A. Mathur and J. M. Zempel), the Washington University Institute of Clinical and Translational Sciences (UL1TR002345—R. M. Guerriero and S. Ching), and NIH grant K23NS111086 (Z. A. Vesoulis). Funding agencies had no role in the design or analysis of this study. None of the authors have potential conflicts of interest to be disclosed.

Figures

Figure 1.
Figure 1.
Macroperiodic oscillations (MOs) observed in a 2 day old infant with neonatal encephalopathy. MOs are visualized in a 2.5 hour epoch of a 12 hour display(top panel) and a 10 minute epoch of a 1 hour display (bottom panel) on color density spectral array (CDSA) of all EEG channels.
Figure 2:
Figure 2:. Relationship between MOs and the severity of encephalopathy.
A scatterplot of the strength of MOs (Qmax) vs spread of MOs (Qsp) with color and shape indicating degree of encephalopathy by Sarnat criteria at the time of EEG initiation as moderate encephalopathy, severe encephalopathy, or non-encephalopathy comparison (characterization of event cohort). A trend toward stronger, more focal MOs is seen with an increasing degree of clinical encephalopathy.
Figure 3 A-B:
Figure 3 A-B:. MOs strength and MOs spread in neonates who did and did not experience seizures.
MOs strength (A) and MOs spread (B) was compared for the group of neonates who had seizure detected on EEG (n = 14) and those who did not (n = 23) with no significant differences found
Figure 3 A-B:
Figure 3 A-B:. MOs strength and MOs spread in neonates who did and did not experience seizures.
MOs strength (A) and MOs spread (B) was compared for the group of neonates who had seizure detected on EEG (n = 14) and those who did not (n = 23) with no significant differences found
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