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Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury

Lee, Hyunjo MD1; Mizrahi, Moshe A. MD1; Hartings, Jed A. PhD2,3; Sharma, Sameer MD1; Pahren, Laura MS4; Ngwenya, Laura B. MD PhD2,3,5; Moseley, Brian D. MD5; Privitera, Michael MD5; Tortella, Frank C. PhD6; Foreman, Brandon MD, FACNS1

doi: 10.1097/CCM.0000000000003639
Neurologic Critical Care

Objectives: After traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome.

Design: Post hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID2566 study ( NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as “ictal-interictal continuum”; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures.

Setting: Twenty U.S. level I trauma centers.

Patients: Patients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4–12 were included.

Interventions: None.

Measurements and Main Results: Among 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30–9.09), absence of N2 sleep transients (3.69; 1.69–8.20), predominant delta activity (2.82; 1.32–6.10), and discontinuous background (5.33; 2.28–12.96) within the first 72 hours of monitoring.

Conclusions: Severe ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.

1Division of Neurocritical Care, Department of Neurology & Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH.

2Department of Neurosurgery, University of Cincinnati, Cincinnati, OH.

3Neurotrauma Center at University of Cincinnati Gardner Neuroscience Institute, Cincinnati, OH.

4College of Engineering and Applied Science, Cincinnati, OH.

5Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH.

6Brain Trauma, Neuroprotection and Neurorestoration Branch, Walter Reed Army Institute of Research, Silver Spring, MD.

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.

Dr. Lee contributed to electroencephalography (EEG) analysis, data analysis and interpretation, article draft and revisions, figure creation. Dr. Mizrahi contributed to study design, EEG review and oversight, article draft, and critical revisions. Dr. Hartings contributed to study design, article draft, and critical revisions. Dr. Sharma contributed to article draft and critical revisions. Dr. Pahren contributed to EEG review, study design, article review. Dr. Ngwenya contributed to study design, article draft, and critical revisions. Dr. Moseley contributed to EEG review, article review. Dr. Privitera contributed to study concept, study design, EEG review and oversight, article draft and critical revisions. Dr. Tortella contributed to randomized controlled trial design and data acquisition. Dr. Foreman contributed to study design, study concept, EEG review and oversight, data analysis and interpretation, article draft and critical revisions.

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The INTREPID2566 trial was supported, in part, by grants from the U.S. Army Medical Research and Materiel Command (to Dr. Tortella) and by Neuren Pharmaceuticals Limited. Supported, in part, by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number K23NS101123 (to Dr. Foreman). Research funding for the parent randomized controlled trial was obtained in part through the DOD by one of the study authors (to Dr. Tortella), who served as principal investigator for the parent randomized controlled trial.

Dr. Moseley’s institution received funding from Neuren Pharmaceuticals (for the INTREPID trial in traumatic brain injury, during which this electroencephalography data were obtained), LivaNova, Sunovion, GW Pharma, and Nonin Medical Inc., NYU, and he received funding from LivaNova, Eisai, UCB, and Validus Pharmaceuticals. Dr. Privitera received funding from Sage. Dr. Foreman’s institution received funding from the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke; and he received funding from UCB Inc. Speakers Bureau. Dr. Privitera received research funds through Neuren Pharmaceuticals Limited for participation in parent randomized controlled trial. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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