Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury

Abstract

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 INTREPID study (ClinicalTrials.gov: 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.

Figure 1.

Representative continuous electroencephalography (cEEG) epoch demonstrating background classification. High-frequency filter=70 Hz, notch filter=60 Hz, and time constant=0.12 s. (A) I Normal: 9-Hz posterior dominant (alpha) rhythm during a period of relative wakefulness. (B) I Normal: N2 sleep with a prominent sleep spindle (bold line) and K-complex (box). (C) I Mild: predominant theta background activity. (D) I Mild: rudimentary N2 sleep transients (K-complex, box). (E) II Moderate: continuous, irregular 1 to 3-Hz delta activity without N2 sleep transients. (F) III Severe: bursts (>500ms and >3phases) of generalized activity on a suppressed (<10 μV) background, or burst-suppression pattern.

Figure 2.

Representative continuous electroencephalography (cEEG) epochs demonstrating ictal-interictal continuum (IIC) classification. High-frequency filter=70 Hz, notch filter=60 Hz, and time constant=0.12 s. (A) IIC II Mild: generalized rhythmic delta activity (GRDA) that is frontally predominant with a frequency of approximately 1-Hz. (B) III Moderate: slow-frequency (0.25-Hz) generalized periodic discharges (GPDs). (C) III Moderate: lateralized rhythmic delta activity (LRDA) with a frequency of approximately 1-Hz (box), most prominent in the right temporal region. (D) IV Severe: LRDA between 1.5 to 2-Hz (box), predominantly in the left temporal region. (E) IV Severe: irregular (in morphology and repetition rate) 0.5-Hz lateralized periodic discharges (LPDs) in the left hemisphere. (F) IV Severe: electrographic seizure (ESz) that evolves in morphology and frequency from 2-Hz to 5-Hz rhythmic discharges in the left temporal region.

Figure 3.

Forest plot and receiver operator characteristic curves (ROC) of continuous electroencephalography (cEEG) variables associated with an increased risk of unfavorable outcome. (A) Common odds ratios are adjusted for International Mission for Prognosis and Analysis of Clinical Trials in traumatic brain injury (IMPACT) score (age, Glasgow Coma Scale motor score, pupillary reactivity), Injury Severity Score (ISS), intraventricular hemorrhage (IVH), GABAergic sedatives and infusion of study drug and are displayed on a logarithmic scale. (B) ROC showing accuracy for prediction of dichotomized unfavorable outcome by linear predictor (LP) from IMPACT core model and LP combined with cEEG variables. The area-under-the-curve (AUC) values were 0.649 for the LP, 0.768 after adding 24-hr cEEG variables to the LP, 0.764 after adding 72-hr cEEG variables to LP, 0.689 after adding discontinuous background to LP and 0.712 after adding moderate-to-severe background to LP. CI, confidence interval; PDR, posterior dominant rhythm.