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Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial

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  • Linnéa Grindegård
  • Tobias Cronberg
  • Sofia Backman
  • Kaj Blennow
  • Josef Dankiewicz
  • Hans Friberg
  • Christian Hassager
  • Janneke Horn
  • Troels W Kjaer
  • Jesper Kjaergaard
  • Michael Kuiper
  • Niklas Mattsson-Carlgren
  • Niklas Nielsen
  • Anne-Fleur van Rootselaar
  • Andrea Rossetti
  • Pascal Stammet
  • Susann Ullén
  • Henrik Zetterberg
  • Erik Westhall
  • Marion Moseby-Knappe
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BACKGROUND AND OBJECTIVES: EEG is widely used for prediction of neurologic outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explored the association between EEG and neurofilament light (NfL) as a marker of neuroaxonal injury, evaluated whether highly malignant EEG patterns are reflected by high NfL levels, and explored the association of EEG backgrounds and EEG discharges with NfL.

METHODS: We performed a post hoc analysis of the Target Temperature Management After Out-of-Hospital Cardiac Arrest trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours postarrest. Patients who awoke or died prior to 36 hours postarrest were excluded. EEG experts blinded to clinical information classified EEG background, amount of discharges, and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NfL after trial completion. The highest available concentration at 48 or 72 hours postarrest was used.

RESULTS: A total of 262/939 patients with EEG and NfL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NfL levels than patients with malignant patterns and NfL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI 1.4-6.1 and 6.5-26.2, respectively; effect size 0.47; p < 0.001). Both background and the amount of discharges were independently strongly associated with NfL levels (p < 0.001). The EEG background had a stronger association with NfL levels than EEG discharges (R2 = 0.30 and R2 = 0.10, respectively). NfL levels in patients with a continuous background were lower than for any other background (95% CI for discontinuous, burst-suppression, and suppression, respectively: 2.26-18.06, 3.91-41.71, and 5.74-41.74; effect size 0.30; p < 0.001 for all). NfL levels did not differ between suppression and burst suppression. Superimposed discharges were only associated with higher NfL levels if the EEG background was continuous.

DISCUSSION: Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NfL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NfL may be useful to better identify patients misclassified by single methods.

TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT01020916.

Original languageEnglish
JournalNeurology
Volume98
Issue number24
Pages (from-to)e2487-e2498
ISSN0028-3878
DOIs
Publication statusPublished - 14 Jun 2022

Bibliographical note

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

    Research areas

  • Biomarkers, Brain Injuries, Electroencephalography, Humans, Intermediate Filaments, Neurofilament Proteins, Out-of-Hospital Cardiac Arrest

ID: 77893921