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

Grindegård, Linnéa LU orcid ; Cronberg, Tobias LU ; Backman, Sofia LU ; Blennow, Kaj ; Dankiewicz, Josef LU orcid ; Friberg, Hans LU ; Hassager, Christian ; Horn, Janneke ; Kjaer, Troels W. and Kjaergaard, Jesper , et al. (2022) In Neurology 98(24). p.2487-2498
Abstract

Background and ObjectivesEEG 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.MethodsWe 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... (More)

Background and ObjectivesEEG 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.MethodsWe 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.ResultsA 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.DiscussionBenign, 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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
98
issue
24
pages
2487 - 2498
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85131903308
  • pmid:35470143
ISSN
0028-3878
DOI
10.1212/WNL.0000000000200335
language
English
LU publication?
yes
id
eeea7637-e88d-4abd-a289-f2dca9734b5a
date added to LUP
2022-10-10 11:03:40
date last changed
2023-11-21 04:48:44
@article{eeea7637-e88d-4abd-a289-f2dca9734b5a,
  abstract     = {{<p>Background and ObjectivesEEG 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.MethodsWe 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.ResultsA 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 &lt; 0.001). Both background and the amount of discharges were independently strongly associated with NfL levels (p &lt; 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 &lt; 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.DiscussionBenign, 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. </p>}},
  author       = {{Grindegård, Linnéa and Cronberg, Tobias and Backman, Sofia and Blennow, Kaj and Dankiewicz, Josef and Friberg, Hans and Hassager, Christian and Horn, Janneke and Kjaer, Troels W. and Kjaergaard, Jesper and Kuiper, Michael and Mattsson-Carlgren, Niklas and Nielsen, Niklas and Van Rootselaar, Anne Fleur and Rossetti, Andrea O. and Stammet, Pascal and Ullén, Susann and Zetterberg, Henrik and Westhall, Erik and Moseby-Knappe, Marion}},
  issn         = {{0028-3878}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{24}},
  pages        = {{2487--2498}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Neurology}},
  title        = {{Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest : A Post Hoc Analysis of the TTM Trial}},
  url          = {{http://dx.doi.org/10.1212/WNL.0000000000200335}},
  doi          = {{10.1212/WNL.0000000000200335}},
  volume       = {{98}},
  year         = {{2022}},
}