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Seizures and Cognitive Outcome After Traumatic Brain Injury: A Post Hoc Analysis

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Abstract

Introduction

Seizures and abnormal periodic or rhythmic patterns are observed on continuous electroencephalography monitoring (cEEG) in up to half of patients hospitalized with moderate to severe traumatic brain injury (TBI). We aimed to determine the impact of seizures and abnormal periodic or rhythmic patterns on cognitive outcome 3 months following moderate to severe TBI.

Methods

This was a post hoc analysis of the multicenter randomized controlled phase 2 INTREPID2566 clinical trial conducted from 2010 to 2016 across 20 United States Level I trauma centers. Patients with nonpenetrating TBI and postresuscitation Glasgow Coma Scale scores 4–12 were included. Bedside cEEG was initiated per protocol on admission to intensive care, and the burden of ictal-interictal continuum (IIC) patterns, including seizures, was quantified. A summary global cognition score at 3 months following injury was used as the primary outcome.

Results

142 patients (age mean + / − standard deviation 32 + / − 13 years; 131 [92%] men) survived with a mean global cognition score of 81 + / − 15; nearly one third were considered to have poor functional outcome. 89 of 142 (63%) patients underwent cEEG, of whom 13 of 89 (15%) had severe IIC patterns. The quantitative burden of IIC patterns correlated inversely with the global cognition score (r =  − 0.57; p = 0.04). In multiple variable analysis, the log-transformed burden of severe IIC patterns was independently associated with the global cognition score after controlling for demographics, premorbid estimated intelligence, injury severity, sedatives, and antiepileptic drugs (odds ratio 0.73, 95% confidence interval 0.60–0.88; p = 0.002).

Conclusions

The burden of seizures and abnormal periodic or rhythmic patterns was independently associated with worse cognition at 3 months following TBI. Their impact on longer-term cognitive endpoints and the potential benefits of seizure detection and treatment in this population warrant prospective study.

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Fig. 1

Modified from study protocols (Neu-2566-TBI-001 and Neu-2566-TBI-002). cEEG, continuous electroencephalography, EFIC, exception from informed consent, ED, emergency department, LAR, legally authorized representative

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Funding

The INTREPID2566 trial was supported in part by grants from the U.S. Army Medical Research and Materiel Command (FT) and by Neuren Pharmaceuticals Limited. A preliminary version of this work was completed in partial fulfillment of the Master of Science degree in Clinical and Translational Research in the Division of Epidemiology, University of Cincinnati College of Medicine made possible through an Institutional Clinical and Translational Science Award (NIH/NCATS 1UL1TR001425). Author BF is supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health (K23NS101123). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Defense or the National Institutes of Health.

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Authors and Affiliations

  1. Department of Neurology & Rehabilitation Medicine, University of Cincinnati Gardner Neuroscience Institute, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0517, USA

    Brandon Foreman, Hyunjo Lee, Moshe A. Mizrahi, Laura B. Ngwenya & Michael Privitera

  2. Collaborative for Research on Acute Neurological Injuries, University of Cincinnati,, Cincinnati, OH, USA

    Brandon Foreman, Hyunjo Lee, Jed A. Hartings & Laura B. Ngwenya

  3. Department of Neurosurgery, University of Cincinnati Gardner Neuroscience Institute, University of Cincinnati, Cincinnati, OH, USA

    Brandon Foreman, Jed A. Hartings & Laura B. Ngwenya

  4. Walter Reed Army Institute of Research, Brain Trauma, Neuroprotection and Neurorestoration Branch, Silver Springs, MD, USA

    Frank C. Tortella

  5. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Nanhua Zhang

  6. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Nanhua Zhang

  7. San Francisco Memory and Aging Center, University of California, San Francisco,, CA, USA

    Joel H. Kramer

Authors
  1. Brandon Foreman
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  2. Hyunjo Lee
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  8. Nanhua Zhang
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Contributions

BF: conceived and designed the analysis, performed the analysis, wrote the paper, HL: contributed data and/or analysis tools, performed the analysis, critical revisions to the paper, MAM: contributed data and/or analysis tools, JAH: collected the data, critical revisions to the paper, LBN: critical revisions to the paper and relevant content expertise, MP: collected the data, contributed data or analysis tools, FCT: conceived and designed the initial study, collected the data, NZ: performed the analysis, JHK: contributed to performance of the analysis and relevant content expertise. Authorship requirements have been met, and the final manuscript was approved by all authors.

Corresponding author

Correspondence to Brandon Foreman.

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Conflicts of interest

The INTREPID2566 trial was supported in part by grants from the U.S. Army Medical Research and Materiel Command (FT) and by Neuren Pharmaceuticals Limited. B. Foreman received research support through the NIH/NINDS. He also receives research funding through the DOD and NSF and speaking fees from UCH Pharma, Inc. M. Privitera received research funds through Neuren Pharmaceuticals Ltd for directing the Core EEG as part of the INTREPID2566 trial. He also receives grant support from GW/Greenwich and YK, performs EEG interpretation for Sage, Inc. and serves on the DSMB for Astrellas. F.C. Tortella served as principal investigator for the INTREPID2566 trial and received funding through the DOD and Neuren Pharmaceuticals Limited. The remaining authors report no relevant conflicts of interest.

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Foreman, B., Lee, H., Mizrahi, M.A. et al. Seizures and Cognitive Outcome After Traumatic Brain Injury: A Post Hoc Analysis. Neurocrit Care 36, 130–138 (2022). https://doi.org/10.1007/s12028-021-01267-4

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  • DOI: https://doi.org/10.1007/s12028-021-01267-4

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