Acute biomarkers of consciousness are associated with recovery after severe traumatic brain injury.

Objective: Determine whether acute behavioral, electroencephalography (EEG), and functional MRI (fMRI) biomarkers of consciousness are associated with outcome after severe traumatic brain injury (TBI). Methods: Patients with acute severe TBI admitted consecutively to the intensive care unit (ICU) participated in a multimodal battery assessing behavioral level of consciousness (Coma Recovery Scale-Revised [CRS-R]), cognitive motor dissociation (CMD; task-based EEG and fMRI), covert cortical processing (CCP; stimulus-based EEG and fMRI), and default mode network connectivity (DMN; resting-state fMRI). The primary outcome was 6-month Disability Rating Scale (DRS) total scores. Results: We enrolled 55 patients with acute severe TBI. Six-month outcome was available in 45 (45.2±20.7 years old, 70% male), of whom 10 died, all due to withdrawal of life-sustaining treatment (WLST). Behavioral level of consciousness and presence of command-following in the ICU were each associated with lower (i.e., better) DRS scores (p=0.003, p=0.011). EEG and fMRI biomarkers did not strengthen this relationship, but higher DMN connectivity was associated with better recovery on multiple secondary outcome measures. In a subsample of participants without command-following on the CRS-R, CMD (EEG:18%; fMRI:33%) and CCP (EEG:91%; fMRI:79%) were not associated with outcome, an unexpected result that may reflect the high rate of WLST. However, higher DMN connectivity was associated with lower DRS scores (ρ[95%CI]=-0.41[-0.707, -0.027]; p=0.046) in this group. Interpretation: Standardized behavioral assessment in the ICU may improve prediction of recovery from severe TBI. Further research is required to determine whether integrating behavioral, EEG, and fMRI biomarkers of consciousness is more predictive than behavioral assessment alone.