Recovery Potential in Patients Who Died After Withdrawal of Life-Sustaining Treatment: A TRACK-TBI Propensity Score Analysis.

Among patients with severe traumatic brain injury (TBI), there is high prognostic uncertainty but growing evidence that recovery of independence is possible. Nevertheless, families are often asked to make decisions about withdrawal of life-sustaining treatment (WLST) within days of injury. The range of potential outcomes for patients who died after WLST (WLST+) is unknown, posing a challenge for prognostic modeling and clinical counseling. We investigated the potential for survival and recovery of independence after acute TBI in patients who died after WLST. We used Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data and propensity score matching to pair participants with WLST+ to those with a similar probability of WLST (based on demographic and clinical characteristics), but for whom life-sustaining treatment was not withdrawn (WLST-). To optimize matching, we divided the WLST- cohort into tiers (Tier 1 = 0-11%, Tier 2 = 11-27%, Tier 3 = 27-70% WLST propensity). We estimated the level of recovery that could be expected in WLST+ participants by evaluating 3-, 6-, and 12-month Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale outcomes in matched WLST- participants. Of 90 WLST+ participants (80% male, mean [standard deviation; SD] age = 59.2 [17.9] years, median [IQR] days to WLST = 5.4 [2.2, 11.7]), 80 could be matched to WLST- participants. Of 56 WLST- participants who were followed at 6 months, 31 (55%) died. Among survivors in the overall sample and survivors in Tiers 1 and 2, more than 30% recovered at least partial independence (GOSE ≥4). In Tier 3, recovery to GOSE ≥4 occurred at 12 months, but not 6 months, post-injury. These results suggest a substantial proportion of patients with TBI and WLST may have survived and achieved at least partial independence. However, death or severe disability is a common outcome when the probability of WLST is high. While further validation is needed, our findings support a more cautious clinical approach to WLST and more complete reporting on WLST in TBI studies.

Correcting cardiorespiratory noise in resting-state functional MRI data acquired in critically ill patients.

Resting-state functional MRI is being used to develop diagnostic, prognostic and therapeutic biomarkers for critically ill patients with severe brain injuries. In studies of healthy volunteers and non-critically ill patients, prospective cardiorespiratory data are routinely collected to remove non-neuronal fluctuations in the resting-state functional MRI signal during analysis. However, the feasibility and utility of collecting cardiorespiratory data in critically ill patients on a clinical MRI scanner are unknown. We concurrently acquired resting-state functional MRI (repetition time = 1250 ms) and cardiac and respiratory data in 23 critically ill patients with acute severe traumatic brain injury and in 12 healthy control subjects. We compared the functional connectivity results from two approaches that are commonly used to correct cardiorespiratory noise: (i) denoising with cardiorespiratory data (i.e. image-based method for retrospective correction of physiological motion effects in functional MRI) and (ii) standard bandpass filtering. Resting-state functional MRI data in 7 patients could not be analysed due to imaging artefacts. In 6 of the remaining 16 patients (37.5%), cardiorespiratory data were either incomplete or corrupted. In patients (n = 10) and control subjects (n = 10), the functional connectivity results corrected with the image-based method for retrospective correction of physiological motion effects in functional MRI did not significantly differ from those corrected with bandpass filtering of 0.008-0.125 Hz. Collectively, these findings suggest that, in critically ill patients with severe traumatic brain injury, there is limited feasibility and utility to denoising the resting-state functional MRI signal with prospectively acquired cardiorespiratory data.

Return to Work Within Four Months of Grade 3 Diffuse Axonal Injury.

Neuroprognostication following diffuse axonal injury (DAI) has historically relied on neuroimaging techniques with lower spatial resolution and contrast than techniques currently available in clinical practice. Since the initial studies of DAI classification and prognosis in the 1980s and 1990s, advances in neuroimaging have improved detection of brainstem microbleeds, a hallmark feature of Grade 3 DAI that has traditionally been associated with poor neurologic outcome. Here, we report clinical and radiologic data from two patients with severe traumatic brain injury and grade 3 DAI who recovered functional independence and returned to work within 4 months of injury. Importantly, both patients were scanned using 3 Tesla MRI protocols that included susceptibility-weighted imaging (SWI), a technique that provides enhanced sensitivity for detecting brainstem microbleeds. These observations highlight the importance of developing approaches to DAI classification and prognosis that better align with contemporary neuroimaging capabilities.

Disorders of Consciousness Associated With COVID-19: A Prospective Multimodal Study of Recovery and Brain Connectivity.

BACKGROUND AND OBJECTIVES: In patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile. METHODS: In a prospective longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury and who were planned to undergo a brain MRI. We performed resting-state fMRI and diffusion MRI to evaluate functional and structural connectivity compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge and 3 and 6 months after discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC. RESULTS: After screening 1,105 patients with COVID-19, we enrolled 12 with COVID-DoC. The median age was 63.5 years (interquartile range 55-76.3 years). After the exclusion of 1 patient who died shortly after enrollment, all of the remaining 11 patients recovered consciousness 0 to 25 days (median 7 [5-14.5] days) after the cessation of continuous IV sedation. At discharge, all surviving patients remained dependent: median GOSE score 3 (1-3) and median DRS score 23 (16-30). Ultimately, however, except for 2 patients with severe polyneuropathy, all returned home with normal cognition and minimal disability: at 3 months, median GOSE score 3 (3-3) and median DRS score 7 (5-13); at 6 months, median GOSE score 4 (4-5), median DRS score 3 (3-5). Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in those with COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to that in patients with severe TBI. DISCUSSION: Patients who survived invariably recovered consciousness after COVID-DoC. Although disability was common after hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT04476589.