An Unpredictable Brain Is a Conscious, Responsive Brain.

Severe traumatic brain injuries typically result in loss of consciousness or coma. In deeply comatose patients with traumatic brain injury, cortical dynamics become simple, repetitive, and predictable. We review evidence that this low-complexity, high-predictability state results from a passive cortical state, represented by a stable repetitive attractor, that hinders the flexible formation of neuronal ensembles necessary for conscious experience. Our data and those from other groups support the hypothesis that this cortical passive state is because of the loss of thalamocortical input. We identify the unpredictability and complexity of cortical dynamics captured by local field potential as a sign of recovery from this passive coma attractor. In this Perspective article, we discuss how these electrophysiological biomarkers of the recovery of consciousness could inform the design of closed-loop stimulation paradigms to treat disorders of consciousness.

Thoracic Intervertebral Disc Herniation Associated With Chronic Anabolic Androgenic Steroid Use: A Case Report.

Anabolic androgenic steroids (AAS) are relatively cheap and accessible medications, commonly used by athletes and bodybuilders for performance enhancement and muscle growth stimulation. AAS usage has been associated with musculoskeletal injuries, such as tendon and ligament ruptures, and numerous other detrimental health effects. Despite these risks, individuals continue to self-administer these drugs in supraphysiologic doses. Here, we present a case of a male bodybuilder with chronic AAS use who developed a spinal thoracic intervertebral disc herniation requiring decompression and fusion. We use this case to highlight a severe potential risk associated with chronic AAS abuse and review the current literature on the biochemical, physical, and physiologic mechanisms linking chronic AAS use, weight-bearing exercise, and the risk of musculoskeletal injuries such as intervertebral disc herniations.

The Impact of Perilesional Heatsink Structures on Ablation Volumes in Laser Interstitial Thermal Therapy for Brain Metastases.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has demonstrated promise in surgical neuro-oncology because of its effectiveness in delivering precise thermal energy to lesions. The extent of ablation (EOA) is a prognostic factor in improving patient outcomes but is often affected by perilesional heatsink structures, which can lead to asymmetric ablations. The purpose of this study was to quantitatively evaluate the impact of various perilesional heatsink structures on the EOA in LITT for brain metastases. METHODS: Twenty-seven procedures for 22 unique patients with brain metastases fit the inclusion criteria. Intracranial heatsink structures were identified: sulci, meninges, cerebrospinal fluid (CSF) spaces, and vasculature. Asymmetric ablation was determined by measuring 3 pairs of orthogonal distances from the proximal, midpoint, and distal locations along the laser catheter to the farthest edge of the ablation zone bilaterally. Distances from the same points on the laser catheter to the nearest heatsink were also recorded. The Heatsink Effect Index was created to serve as a proxy for asymmetric ablation. Pearson correlations, t -tests, and analysis of variance were the statistical analyses performed. RESULTS: From the midpoint of the catheter, the 27 heatsinks were meninges (40.7%), sulci (22.2%), vasculature (22.2%), and CSF spaces (14.8%). Across all points along the catheter track, there was a significant generalized heatsink effect on asymmetric ablations ( P < .0001). There was a negative correlation observed between asymmetric ablations and EOA from the midpoint of the laser catheter (r = -0.445, P = .020). Compared with sulci, CSF spaces trended toward a greater effect on asymmetric ablation volumes ( P = .069). CONCLUSION: This novel quantitative analysis shows that perilesional heatsinks contribute to asymmetric ablations. CSF spaces trended toward higher degrees of asymmetric ablations. Importantly, neurosurgeons may anticipate asymmetric ablations preoperatively if heatsinks are located within 13.3 mm of the laser probe midpoint. These preliminary results may guide surgical decision-making in LITT for metastatic brain lesions.

Brain Circuitry of Consciousness: A Review of Current Models and a Novel Synergistic Model With Clinical Application.

How consciousness arises in the brain has important implications for clinical decision-making. We summarize recent findings in consciousness studies to provide a toolkit for clinicians to assess deficits in consciousness and predict outcomes after brain injury. Commonly encountered disorders of consciousness are highlighted, followed by the clinical scales currently used to diagnose them. We review recent evidence describing the roles of the thalamocortical system and brainstem arousal nuclei in supporting awareness and arousal and discuss the utility of various neuroimaging studies in evaluating disorders of consciousness. We explore recent theoretical progress in mechanistic models of consciousness, focusing on 2 major models, the global neuronal workspace and integrated information theory, and review areas of controversy. Finally, we consider the potential implications of recent research for the day-to-day decision-making of clinical neurosurgeons and propose a simple "three-strikes" model to infer the integrity of the thalamocortical system, which can guide prognosticating return to consciousness.

In-Hospital Amantadine Does Not Improve Outcomes After Severe Traumatic Brain Injury: An 11-Year Propensity-Matched Retrospective Analysis.

BACKGROUND: Disruption of dopamine neurotransmission is associated with functional impairment after severe traumatic brain injury (sTBI). This has prompted the study of dopamine agonists, such as amantadine, to assist recovery of consciousness. Randomized trials have mostly addressed the posthospital setting, with inconsistent findings. Therefore, we evaluated the efficacy of early amantadine administration on recovery of consciousness after sTBI. METHODS: We searched the medical records of all patients with sTBI admitted to our hospital between 2010 and 2021 who survived 10 days postinjury. We identified all patients receiving amantadine and compared them with all patients not receiving amantadine and a propensity score-matched nonamantadine group. Primary outcome measures included discharge Glasgow Coma Scale, Glasgow Outcome Scale-Extended score, length of stay, mortality, recovery of command-following (CF), and days to CF. RESULTS: In our study population, 60 patients received amantadine and 344 did not. Compared with the propensity score-matched nonamantadine group, the amantadine group had no difference in mortality (86.67% vs. 88.33%, P = 0.783), rates of CF (73.33% vs. 76.67%, P = 0.673), or percentage of patients with severe (3-8) discharge Glasgow Coma Scale scores (11.11% vs. 12.28%, P = 0.434). In addition, the amantadine group was less likely to have a favorable recovery (discharge Glasgow Outcome Scale-Extended score 5-8) (14.53% vs. 16.67%, P < 0.001), had a longer length of stay (40.5 vs. 21.0 days, P < 0.001), and had a longer time to CF (11.5 vs. 6.0 days, P = 0.011). No difference in adverse events existed between groups. CONCLUSIONS: Our findings do not support the early administration of amantadine for sTBI. Larger inpatient randomized trials are necessary to further investigate amantadine treatment for sTBI.

Predicting traumatic brain injury outcomes using a posterior dominant rhythm.

OBJECTIVE: Predicting severe traumatic brain injury (sTBI) outcomes is challenging, and existing models have limited applicability to individual patients. This study aimed to identify metrics that could predict recovery following sTBI. The researchers strived to demonstrate that a posterior dominant rhythm on electroencephalography is strongly associated with positive outcomes and to develop a novel machine learning-based model that accurately forecasts the return of consciousness. METHODS: In this retrospective study, the authors assessed all intubated adults admitted with sTBI (Glasgow Coma Scale [GCS] score ≤ 8) from 2010 to 2021, who underwent EEG recording < 30 days from sTBI (n = 195). Seventy-three clinical, radiographic, and EEG variables were collected. Based on the presence of a PDR within 30 days of injury, two cohorts were created-those with a PDR (PDR[+] cohort, n = 51) and those without (PDR[-] cohort, n = 144)-to assess differences in presentation and four outcomes: in-hospital survival, recovery of command following, Glasgow Outcome Scale-Extended (GOS-E) score at discharge, and GOS-E score at 6 months post discharge. AutoScore, a machine learning-based clinical score generator that selects and assigns weights to important predictive variables, was used to create a prognostic model that predicts in-hospital survival and recovery of command following. Lastly, the MRC-CRASH and IMPACT traumatic brain injury predictive models were used to compare expected patient outcomes with true outcomes. RESULTS: At presentation, the PDR(-) cohort had a lower mean GCS motor subscore (1.97 vs 2.45, p = 0.048). Despite no difference in predicted outcomes (via MRC-CRASH and IMPACT), the PDR(+) cohort had superior rates of in-hospital survival (84.3% vs 63.9%, p = 0.007), recovery of command following (76.5% vs 53.5%, p = 0.004), and mean discharge GOS-E score (3.00 vs 2.39, p = 0.006). There was no difference in the 6-month GOS-E score. AutoScore was then used to identify the 7 following variables that were highly predictive of in-hospital survival and recovery of command: age, body mass index, systolic blood pressure, pupil reactivity, blood glucose, and hemoglobin (all at presentation), and a PDR on EEG. This model had excellent discrimination for predicting in-hospital survival (area under the curve [AUC] 0.815) and recovery of command following (AUC 0.700). CONCLUSIONS: A PDR on EEG in sTBI patients predicts favorable outcomes. The authors' prognostic model has strong accuracy in predicting these outcomes, and performed better than previously reported models. The authors' model can be valuable in clinical decision-making as well as counseling families following these types of injuries.

Low-molecular-weight heparin compared with unfractionated heparin in critically ill COVID-19 patients.

BACKGROUND: Thrombosis in COVID-19 worsens mortality. In our study, we sought to investigate how the dose and type of anticoagulation (AC) can influence patient outcomes. METHODS: This is a single-center retrospective analysis of critically ill intubated patients with COVID-19, comparing low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) at therapeutic and prophylactic doses. Of 218 patients, 135 received LMWH (70 prophylactic, 65 therapeutic) and 83 UFH (11 prophylactic, 72 therapeutic). The primary outcome was mortality. Secondary outcomes were thromboembolic complications confirmed on imaging and major bleeding complications. Cox proportional-hazards regression models were used to determine whether the type and dose of AC were independent predictors of survival. We performed Kaplan-Meier survival analysis to compare the cumulative survivals. RESULTS: Overall, therapeutic AC, with either LMWH (65% vs 79%, P = .09) or UFH (32% vs 46%, P = .73), conveyed no survival benefit over prophylactic AC. UFH was associated with a higher mortality rate than LMWH (66% vs 28%, P = .001), which was also evident in the multivariable analysis (LMWH vs UFH mortality, hazard ratio: 0.47, P = .001) and in the Kaplan-Meier survival analysis. Thrombotic and bleeding complications did not depend on the AC type (prophylactic LMWH vs UFH: thrombosis P = .49, bleeding P = .075; therapeutic LMWH vs UFH: thrombosis P = .5, bleeding P = .17). When comparing prophylactic with therapeutic AC, the rate of both thrombotic and bleeding complications was higher with the use of LMWH compared with UFH. In addition, transfusion requirements were significantly higher with both therapeutic LMWH and UFH. CONCLUSIONS: Among intubated critically ill COVID-19 intensive care unit patients, therapeutic AC, with either LMWH or UFH, conveyed no survival benefit over prophylactic AC. AC with LMWH was associated with higher cumulative survival compared with AC with UFH.

Acute Gastrointestinal Injury and Feeding Intolerance as Prognostic Factors in Critically Ill COVID-19 Patients.

BACKGROUND: Although acute gastrointestinal injury (AGI) and feeding intolerance (FI) are known independent determinants of worse outcomes and high mortality in intensive care unit (ICU) patients, the incidence of AGI and FI in critically ill COVID-19 patients and their prognostic importance have not been thoroughly studied. METHODS: We reviewed 218 intubated patients at Stony Brook University Hospital and stratified them into three groups based on AGI severity, according to data collected in the first 10 days of ICU course. We used chi-square test to compare categorical variables such as age and sex and two-sample t-test or Mann-Whitney U-tests for continuous variables, including important laboratory values. Cox proportional hazards regression models were utilized to determine whether AGI score was an independent predictor of survival, and multivariable analysis was performed to compare risk factors that were deemed significant in the univariable analysis. We performed Kaplan-Meier survival analysis based on the AGI score and the presence of FI. RESULTS: The overall incidence of AGI was 95% (45% AGI I/II, 50% AGI III/IV), and FI incidence was 63%. Patients with AGI III/IV were more likely to have prolonged mechanical ventilation (22 days vs 16 days, P-value <0.002) and higher mortality rate (58% vs 28%, P-value <0.001) compared to patients with AGI 0/I/II. This was confirmed with multivariable analysis which showed that AGI score III/IV was an independent predictor of higher mortality (AGI III/IV vs AGI 0/I/II hazard ratio (HR), 2.68; 95% confidence interval (CI), 1.69-4.25; P-value <0.0001). Kaplan-Meier survival analysis showed that both AGI III/IV and FI (P-value <0.001) were associated with worse outcomes. Patients with AGI III/IV had higher daily and mean D-dimer and CRP levels compared to AGI 0/I/II (P-value <0.0001). CONCLUSIONS: The prevalence of AGI and FI among critically ill COVID-19 patients was high. AGI grades III/IV were associated with higher risk for prolonged mechanical ventilation and mortality compared to AGI 0/I/II, while it also correlated with higher D-dimer and C-reactive protein (CRP) levels. FI was independently associated with higher mortality. The development of high-grade AGI and FI during the first days of ICU stay can serve as prognostic tools to predict outcomes in critically ill COVID-19 patients.

Aggressive Anticoagulation May Decrease Mortality in Obese Critically Ill COVID-19 Patients.

BACKGROUND: Obesity is a widely accepted risk factor for the development of severe COVID-19. We sought to determine the survival benefit of early initiation of aggressive anticoagulation in obese critically ill COVID-19 patients. METHODS: We retrospectively reviewed 237 intubated patients at a single academic accredited bariatric center and stratified them based on their BMI into 2 groups, obese (BMI > 30) and non-obese (BMI ≤ 30). We used chi-square tests to compare categorical variables such as age and sex, and two-sample t-tests or Mann Whitney U-tests for continuous variables, including important laboratory values. Cox proportional-hazards regression models were utilized to determine whether obesity was an independent predictor of survival and multivariable analysis was performed to compare risk factors that were deemed significant in the univariable analysis. Survival with respect to BMI and its association with level of anticoagulation in the obese cohort was evaluated using Kaplan-Meier models. RESULTS: The overall mortality in the obese and non-obese groups was similar at 47% and 44%, respectively (p = 0.65). Further analysis based on the level of AC showed that obese patients placed on early aggressive AC protocol had improved survival compared to obese patients who did not receive protocol based aggressive AC (ON-aggressive AC protocol 26% versus OFF-aggressive AC protocol 61%, p = 0.0004). CONCLUSIONS: The implementation of early aggressive anticoagulation may balance the negative effects of obesity on the overall mortality in critically ill COVID-19 patients.

D-Dimer-Driven Anticoagulation Reduces Mortality in Intubated COVID-19 Patients: A Cohort Study With a Propensity-Matched Analysis.

Objective: Examine the possible beneficial effects of early, D-dimer driven anticoagulation in preventing thrombotic complications and improving the overall outcomes of COVID-19 intubated patients. Methods: To address COVID-19 hypercoagulability, we developed a clinical protocol to escalate anticoagulation based on serum D-dimer levels. We retrospectively reviewed all our first 240 intubated patients with COVID-19. Of the 240, 195 were stratified into patients treated based on this protocol (ON-protocol, n = 91) and the control group, patients who received standard thromboprophylaxis (OFF-protocol, n = 104). All patients were admitted to the Stony Brook University Hospital intensive care units (ICUs) between February 7th, 2020 and May 17, 2020 and were otherwise treated in the same manner for all aspects of COVID-19 disease. Results: We found that the overall mortality was significantly lower ON-protocol compared to OFF-protocol (27.47 vs. 58.66%, P < 0.001). Average maximum D-dimer levels were significantly lower in the ON-protocol group (7,553 vs. 12,343 ng/mL), as was serum creatinine (2.2 vs. 2.8 mg/dL). Patients with poorly controlled D-dimer levels had higher rates of kidney dysfunction and mortality. Transfusion requirements and serious bleeding events were similar between groups. To address any possible between-group differences, we performed a propensity-matched analysis of 124 of the subjects (62 matched pairs, ON-protocol and OFF-protocol), which showed similar findings (31 vs. 57% overall mortality in the ON-protocol and OFF-protocol group, respectively). Conclusions: D-dimer-driven anticoagulation appears to be safe in patients with COVID-19 infection and is associated with improved survival. What This Paper Adds: It has been shown that hypercoagulability in patients with severe COVID-19 infection leads to thromboembolic complications and organ dysfunction. Anticoagulation has been variably administered to these patients, but it is unknown whether routine or escalated thromboprophylaxis provides a survival benefit. Our data shows that escalated D-dimer driven anticoagulation is associated with improved organ function and overall survival in intubated COVID-19 ICU patients at our institution. Importantly, we found that timely escalation of this anticoagulation is critical in preventing organ dysfunction and mortality in patients with severe COVID-19 infection.