Novel Prediction of Recovery of Consciousness in Acute Traumatic Brain Injury

/ABSTRACT Traumatic brain injury (TBI) is a major cause of death and disability in the U.S. and beyond. More than half of TBI deaths occur in the context of acute withdrawal of life-sustaining treatment (WLST). The decision to continue towards neurorehabilitation versus transition to WLST hinges on predictions of recovery. Predicting recovery, however, is challenging. Recovery predictions drive care decisions, but even seasoned clinicians cannot make reliable predictions. The stakes are high: surrogates overwhelmingly view a persistent vegetative state after severe TBI as worse than death. Yet, late recovery and functional independence may be possible for many. Among those who die after WLST, up to one third may have recovered to functional independence. Correctly identifying those patients in the intensive care unit could equate to up to 10,000 lives saved annually with good functional recovery by preventing premature WLST. We must move beyond prognostic uncertainty. A potential diagnostic tool is available: the injured brain’s response to anesthesia reveals its likelihood to recover, and this response is measurable with electroencephalography (EEG). Anesthesia can induce distinctive patterns of brain network reconfiguration. In patients with disorders of consciousness, detection of these brain network reconfigurations in response to propofol anesthesia may allow us to correctly identify patients with the capacity to recover consciousness. In our preliminary work, we quantified the reconfiguration of high-density EEG network hubs and directed functional connectivity before, during, and after propofol anesthesia to obtain an index of propofol-induced network reconfiguration. This index discriminated with high accuracy between patients who did or did not later regain consciousness. This work was limited to 10 patients with disorders of consciousness after acquired brain injury, of which 2 had acute TBI. This tool has the potential to apply to acute TBI patients. To address this evidence gap, this R21 proposes to enroll 30 unresponsive acute TBI patients from our intensive care unit, both isolated and polytrauma TBI, in a prospective study with two Specific Aims: (1) to develop a novel propofol-induced index to predict recovery of consciousness after acute TBI in the intensive care unit; and (2) to quantify the added value of this novel index for TBI prognostication. We will use high-density and clinical-grade EEG to measure the brain’s response to the neurophysiological perturbation of propofol anesthesia and then calculate the accuracy of this novel index to predict recovery of consciousness 6 months later. This project leverages our high-volume, high-acuity trauma center with a large pool of severe TBI patients. This interdisciplinary team science collaboration leverages the diverse skillsets of four female investigators: a trauma surgeon intensivist, a neurologist specializing in critical care EEG, a neuroscientist focused on recovery of consciousness, and an engineer focused on consciousness and neuroprognosis. Eventually, this pragmatic, bedside prognosticator for unresponsive, acute TBI patients may provide hope of recovery and prevent early inappropriate WLST. Project Number: 1R21NS142653-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Amelia Maiga | Institution: VANDERBILT UNIVERSITY MEDICAL CENTER, NASHVILLE, TN | Award Amount: $262,500 | Activity Code: R21 | Study Section: Surgery, Anesthesiology and Trauma Study Section[SAT] View on NIH RePORTER: https://reporter.nih.gov/project-details/11303832