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

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 O Rossetti; Pascal Stammet; Susann Ullén; Henrik Zetterberg; Erik Westhall; Marion Moseby-Knappe

doi:10.1212/WNL.0000000000200335

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

Neurology. 2022 Jun 14;98(24):e2487-e2498. doi: 10.1212/WNL.0000000000200335. Epub 2022 Apr 25.

Authors

Linnéa Grindegård¹, Tobias Cronberg², Sofia Backman², Kaj Blennow², Josef Dankiewicz², Hans Friberg², Christian Hassager², Janneke Horn², Troels W Kjaer², Jesper Kjaergaard², Michael Kuiper², Niklas Mattsson-Carlgren², Niklas Nielsen², Anne-Fleur van Rootselaar², Andrea O Rossetti², Pascal Stammet², Susann Ullén², Henrik Zetterberg², Erik Westhall², Marion Moseby-Knappe²

Affiliations

¹ From Neurology (L.G., T.C., N.M.-C., M.M.-K.), Clinical Neurophysiology (S.B., E.W.), Cardiology (J.D.), and Anaesthesia and Intensive Care (H.F.), Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Malmö; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Cardiology (C.H.), Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Denmark; Departments of Intensive Care (J.H.) and Neurology/Clinical Neurophysiology (A.-F-V.R.), Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center, University of Amsterdam, the Netherlands; Departments of Clinical Neurophysiology (T.W.K.) and Cardiology (J.K.), Rigshospitalet University Hospital, Copenhagen, Denmark; Department of Intensive Care (M.K.), Medical Center Leeuwarden, the Netherlands; Clinical Memory Research Unit, Faculty of Medicine (N.M.-C.), and Wallenberg Centre for Molecular Medicine (N.M.-C.), Lund University; Anaesthesia and Intensive Care, Department of Clinical Sciences Lund (N.N.), Lund University, Helsingborg Hospital, Sweden; Department of Neurology (A.O.R.), CHUV and University of Lausanne, Switzerland; Department of Anesthesia and Intensive Care (P.S.), Centre Hospitalier de Luxembourg; Department of Life Sciences and Medicine (P.S.), Faculty of Science, Technology and Medicine, University of Luxembourg; Clinical Studies Sweden (S.U.), Skåne University Hospital, Lund; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China. linnea.grindegard@med.lu.se.
² From Neurology (L.G., T.C., N.M.-C., M.M.-K.), Clinical Neurophysiology (S.B., E.W.), Cardiology (J.D.), and Anaesthesia and Intensive Care (H.F.), Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Malmö; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Cardiology (C.H.), Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Denmark; Departments of Intensive Care (J.H.) and Neurology/Clinical Neurophysiology (A.-F-V.R.), Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center, University of Amsterdam, the Netherlands; Departments of Clinical Neurophysiology (T.W.K.) and Cardiology (J.K.), Rigshospitalet University Hospital, Copenhagen, Denmark; Department of Intensive Care (M.K.), Medical Center Leeuwarden, the Netherlands; Clinical Memory Research Unit, Faculty of Medicine (N.M.-C.), and Wallenberg Centre for Molecular Medicine (N.M.-C.), Lund University; Anaesthesia and Intensive Care, Department of Clinical Sciences Lund (N.N.), Lund University, Helsingborg Hospital, Sweden; Department of Neurology (A.O.R.), CHUV and University of Lausanne, Switzerland; Department of Anesthesia and Intensive Care (P.S.), Centre Hospitalier de Luxembourg; Department of Life Sciences and Medicine (P.S.), Faculty of Science, Technology and Medicine, University of Luxembourg; Clinical Studies Sweden (S.U.), Skåne University Hospital, Lund; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; and Hong Kong Center for Neurodegenerative Diseases (H.Z.), China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Brain Injuries* / blood
Brain Injuries* / physiopathology
Electroencephalography
Humans
Intermediate Filaments
Neurofilament Proteins / blood*
Out-of-Hospital Cardiac Arrest* / blood
Out-of-Hospital Cardiac Arrest* / physiopathology

Substances

Biomarkers
Neurofilament Proteins

Associated data

ClinicalTrials.gov/NCT01020916