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Ethically Translating Advanced Neurotechnologies for Disorders of Consciousness: A Survey of Clinicians' Perspectives.

Although evaluation of disorders of consciousness (DoC) following brain injury has traditionally relied on bedside behavioral examination, advances in neurotechnology have elucidated novel approaches to detecting and predicting recovery of consciousness. Professional society guidelines now recommend that clinicians integrate these neurotechnologies into clinical practice as part of multimodal evaluations for some patients with DoC but have not crafted concrete protocols for this translation. Little is known about the experiences and ethical perspectives held by key stakeholder groups around the clinical implementation of advanced neurotechnologies to detect and predict recovery of consciousness. Recognizing this knowledge gap, the Data-Driven Neuroethics for Consciousness Detection (DECODE)survey examined clinicians' perspectives on advanced neurotechnologies for DoC care, including access to and rates of adoption, perceived utility, facilitators and barriers to adoption in clinical settings, ethical considerations surrounding clinical implementation, and challenges encountered in ensuring care for patients with acute and prolonged DoC. Mixed-methods analysis including qualitative analysis, grounded theory methodology, and ethical analysis was employed to assess responses and key themes. Ninety-two clinicians consented to the survey. More than 70% believed that standard bedside behavioral examination is insufficient, and nearly 60% viewed advanced neurotechnologies as integral in optimal DoC evaluation. Training gaps and limited institutional infrastructure were identified as salient barriers to clinical implementation. Thematic analysis revealed concerns about the interpretation of results, impact on surrogates, and validity of test results. Ethical themes of prognostic uncertainty, nihilism, and access also permeated multiple domains. Considerations surrounding access, knowledge base, results interpretation, and communication with surrogates are cross-cutting ethical threads shaping the clinical translation of advanced neurotechnologies for DoC. These components represent opportunities for implementation science work focused on democratizing access to neurotechnologies, educating clinicians on the use of novel techniques and interpretation of results, conducting multisite validation studies, and standardizing approaches to communicating test results.

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Cisternal Blood Clearance Attenuates Systemic Inflammatory Response After Subarachnoid Hemorrhage

Abstract Background Aneurysmal subarachnoid hemorrhage (SAH) frequently triggers systemic inflammatory response syndrome (SIRS). SIRS has been associated with inferior outcomes and, specifically, delayed cerebral infarction after aneurysmal SAH. Here, we assess the impact of intracranial blood clearance through stereotactic catheter ventriculocisternostomy on SIRS in patients with aneurysmal SAH. Methods We assessed daily SIRS criteria (heart rate > 90 beats/min, respiratory rate > 20 breaths/min or abnormal respiratory coefficient, temperature > 38 °C or < 36 °C, white blood cell count < 4000 or > 12,000 cells/mm3) between admission and day 21 in 80 consecutive patients who underwent cisternal lavage through stereotactic catheter ventriculocisternostomy from 2015 to 2022. These patients were compared with 80 matched controls who received treatment at our institution between 2010 and 2015. We conducted a mixed effects model analysis using restricted maximum likelihood estimation to assess the effects of treatment groups on the SIRS rate while accounting for repeated measures. Additionally, Bonferroni’s correction was employed to examine specific differences between groups at different time points. Results The mean percentages of patients meeting SIRS criteria during the first 21 days after aneurysmal SAH were 23% in the matched cohort group and 14% in patients who underwent cisternal lavage (p < 0.001). Additionally, significant differences were observed in the mean leukocyte count (p = 0.047), mean heart rate (p = 0.019), and mean respiratory rate (p = 0.0018) between the two groups. However, there was no significant difference in mean body temperature (p = 0.36). Conclusions Intracranial blood clearance and cisternal lavage after aneurysmal SAH is associated with a decline in SIRS prevalence and severity.

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Heart Rate Variability and Cerebral Autoregulation in Patients with Traumatic Brain Injury with Paroxysmal Sympathetic Hyperactivity Syndrome.

Severe traumatic brain injury (TBI) can lead to transient changes in autonomic nervous system (ANS) functioning and development of paroxysmal sympathetic hyperactivity (PSH) syndrome. Clinical manifestation of ANS disorders may be obscured by therapeutic interventions in TBI. This study aims to analyze ANS metrics and cerebral autoregulation in patients with PSH syndrome to determine their significance in early prognostication. This single-center retrospective study investigated the relationship between changes in ANS metrics, cerebral autoregulation, and PSH syndrome. Arterial blood pressure and intracranial pressure signals were monitored for 5 days post TBI. ANS metrics included time and frequency domain heart rate variability (HRV) metrics. Cerebral autoregulation was assessed using the pressure reactivity index. Sixty-six patients with severe TBI (median age 33 [interquartile range 26-50] years) were analyzed, and PSH was confirmed in nine cases. Impairment of cerebral autoregulation was observed in 67% of patients with PSH and 72% without the syndrome. Patients with PSH had higher HRV in the low-frequency range (LF; 253 ± 178 vs. 176 ± 227 ms2; p = 0.035) and lower heart rates (HRs; 70 ± 7 vs. 78 ± 19 bpm; p = 0.027) compared to those without PSH. A receiver operating characteristic curve analysis indicated that HR (area under the curve(AUC) = 0.73, p = 0.006) and HRV in the LF (AUC = 0.70, p = 0.009) are moderate predictors of PSH. In the multiple logistic regression model for PSH, diffuse axonal trauma (odds ratio(OR) = 10.82, 95% confidence interval(CI) = 1.70-68.98, p = 0.012) and HR (OR =0.91, 95% CI 0.84-0.98, p = 0.021) were significant factors. Elevated HRV in the LF and decreased HR may serve as early predictors of PSH syndrome development, particularly in patients with diffuse axonal trauma. Further research is needed to investigate the utility of the cerebral autoregulation-ANS relationship in PSH prognostication.

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Continuous Blood Pressure Indices During the First 72 Hours and Functional Outcome in Patients with Spontaneous Intracerebral Hemorrhage.

Management of intracerebral hemorrhage (ICH) is challenged by limited therapeutic options and a complex relationship between blood pressure (BP) dynamics, especially BP variability (BPV) and ICH outcome. In an exploratory analysis of prospectively collected data on consecutive patients with nontraumatic ICH between 2015 and 2020, continuous BP accessed via an arterial line extracted from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) was analyzed over the first 72 h post admission. Arterial lines were used as part of standard clinical practice in the intensive care, ensuring high fidelity and real-time data essential for acute care settings. BPV was assessed through successive variation (SV), standard deviation (SD), and coefficient of variation using all available BP measurements. Multivariate regression models were applied to evaluate the association between BPV indices and functional outcome at 3 months. Among 261 patients (mean age 69.6 ± 15.2 years, 47.9% female, median National Institutes of Health Stroke Scale [NIHSS] score 6 [interquartile range 2-12]) analyzed, lower systolic BP upon admission (< 140 mm Hg) and lower systolic BPV were significantly associated with favorable outcome, whereas higher diastolic BPV correlated with improved outcomes. In the multivariate analysis, diastolic BPV (SD, SV) within the first 72 h post admission emerged as an independent predictor of good functional outcome (modified Rankin Scale score < 3; odds ratio 1.123, 95% confidence interval CI 1.008-1.184, p = 0.035), whereas systolic BPV (SD) showed a negative association. Patients with better outcomes also exhibited distinct clinical characteristics, including younger age, lower median NIHSS scores, and less prevalence of anticoagulation therapy upon admission. This study shows the prognostic value of BPV in the acute phase of ICH. Lower systolic BPV (SD) and higher diastolic BPV (SD, SV) were associated with better functional outcomes, challenging traditional BP management strategies. These findings might help to tailor a personalized BP management in ICH.

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Iodine-Based Dual-Energy Computed Tomography After Mechanical Thrombectomy Predicts Secondary Neurologic Decline from Cerebral Edema After Severe Stroke.

Patients with severe stroke are at high risk of secondary neurologic decline (ND) from the development of malignant cerebral edema (MCE). However, early infarcts are hard to diagnose on conventional head computed tomography (CT). We hypothesize that high-energy (190keV) virtual monochromatic imaging (VMI) from dual-energy CT (DECT) imaging enables earlier detection of ND from MCE. Consecutive patients with severe stroke with National Institute of Health Stroke Scale (NIHSS) scores > 15 and DECT within 10h of mechanical thrombectomy from May 2020 to March 2022 were included. We excluded patients with parenchymal hematoma type 2 transformation. Retrospective analysis of clinical and novel variables included the VMI Alberta Stroke Program Early CT Score (ASPECTS), total iodine content, and VMI infarct volume. The primary outcome was secondary ND, defined using a composite outcome variable of clinical worsening (increase in NIHSS score ≥ 4 or decrease in Glasgow Coma Scale score > 2) or malignant radiographical edema (midline shift ≥ 5mm at the level of the septum pellucidum). Fisher's exact test and Wilcoxon's test were used for univariate analysis. Logistic regression was used to develop prediction models for categorical outcomes. Eighty-four patients with severe stroke with a median age of 67.5 (interquartile range [IQR] 57-78) years and an NIHSS score of 22 (IQR 18-25) were included. Twenty-nine patients had ND. The VMI ASPECTS, total iodine content, and VMI infarct volume were associated with ND. The VMI ASPECTS, VMI infarct volume, and total iodine content were predictors of ND after adjusting for age, sex, initial NIHSS score, and tissue plasminogen activator administration, with areas under the receiver operating characteristic curve (AUROC) of 0.691 (95% confidence interval [CI] 0.572-0.810), 0.877 (95% CI 0.800-0.954), and 0.845 (95% CI 0.750-0.940). By including all three predictors, the model achieved an AUROC of 0.903 (95% CI 0.84-0.97) and was cross-validated by the leave one out method, with an AUROC of 0.827. The VMI ASPECTS and VMI infarct volume from DECT are superior to the conventional CT ASPECTS and are novel predictors for secondary ND due to MCE after severe stroke. Clinical trial registration ClinicalTrials.gov identifier: NCT04189471.

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Acute Traumatic Coma Awakening Induced by Median Nerve Electrical Stimulation: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) is widely recognized as a major cause of death and disability. Optimizing recovery from coma is a priority for improving patient prognosis. Recently, an increasing number of studies have demonstrated that median nerve electrical stimulation (MNES) may be a potential approach for comatose patients awakening with TBI, although the results of these studies are not consistent. The aim of this study was to evaluate the effects of the MNES on recovery from coma in patients with TBI based on data from randomized controlled trials. The PubMed, Embase, Ovid MEDLINE, Cochrane Library, and China National Knowledge Infrastructure electronic databases were systematically searched from their inception to July 2023 using specific keywords. The χ2 test and I2 test were used to evaluate the heterogeneity across these studies. The mean differences with 95% confidence intervals (CIs) and relative risk (RR) with 95% CIs were adopted to analyze the continuous outcomes and binary outcomes, respectively. A total of 1831 patients from 18 studies were included in this meta-analysis. There were significant differences in the proportions of patients who regained consciousness between the MNES group and the control group after treatment (RR 1.36, 95% CI 1.18-1.56; P < 0.001) and at 6 months after injury (RR 1.31, 95% CI 1.16-1.47; P < 0.001). MNES significantly improved the Glasgow Coma Scale score (mean difference 2.38, 95% CI 1.78-2.98; P < 0.001). Furthermore, no significant differences in complications between the two groups of patients were observed, including pneumonitis (RR 0.86, 95% CI 0.72-1.03; P = 0.107), seizures (RR 1.24, 95% CI 0.49-3.10; P = 0.651), or gastric hemorrhage (RR 1.08, 95% CI 0.60-1.93; P = 0.795).The results of the present study indicate that patients with TBI in the MNES group recovered from coma more rapidly after treatment and at 6months after injury. These results suggest that MNES is an effective approach for coma awakening after TBI.

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A Survey of Surrogates and Health Care Professionals Indicates Support of Cognitive Motor Dissociation-Assisted Prognostication.

Prognostication of patients with acute disorders of consciousness is imprecise but more accurate technology-supported predictions, such as cognitive motor dissociation (CMD), are emerging. CMD refers to the detection of willful brain activation following motor commands using functional magnetic resonance imaging or machine learning-supported analysis of the electroencephalogram in clinically unresponsive patients. CMD is associated with long-term recovery, but acceptance by surrogates and health care professionals is uncertain. The objective of this study was to determine receptiveness for CMD to inform goals of care (GoC) decisions and research participation among health care professionals and surrogates of behaviorally unresponsive patients. This was a two-center study of surrogates of and health care professionals caring for unconscious patients with severe neurological injury who were enrolled in two prospective US-based studies. Participants completed a 13-item survey to assess demographics, religiosity, minimal acceptable level of recovery, enthusiasm for research participation, and receptiveness for CMD to support GoC decisions. Completed surveys were obtained from 196 participants (133 health care professionals and 63 surrogates). Across all respondents, 93% indicated that they would want their loved one or the patient they cared for to participate in a research study that supports recovery of consciousness if CMD were detected, compared to 58% if CMD were not detected. Health care professionals were more likely than surrogates to change GoC with a positive (78% vs. 59%, p = 0.005) or negative (83% vs. 59%, p = 0.0002) CMD result. Participants who reported religion was the most important part of their life were least likely to change GoC with or without CMD. Participants who identified as Black (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.04-0.36) or Hispanic/Latino (OR 0.39, 95% CI 0.2-0.75) and those for whom religion was the most important part of their life (OR 0.18, 95% CI 0.05-0.64) were more likely to accept a lower minimum level of recovery. Technology-supported prognostication and enthusiasm for clinical trial participation was supported across a diverse spectrum of health care professionals and surrogate decision-makers. Education for surrogates and health care professionals should accompany integration of technology-supported prognostication.

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Caring for Coma after Severe Brain Injury: Clinical Practices and Challenges to Improve Outcomes: An Initiative by the Curing Coma Campaign.

Severe brain injury can result in disorders of consciousness (DoC), including coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. Improved emergency and trauma medicine response, in addition to expanding efforts to prevent premature withdrawal of life-sustaining treatment, has led to an increased number of patients with prolonged DoC. High-quality bedside care of patients with DoC is key to improving long-term functional outcomes. However, there is a paucity of DoC-specific evidence guiding clinicians on efficacious bedside care that can promote medical stability and recovery of consciousness. This Viewpoint describes the state of current DoC bedside care and identifies knowledge and practice gaps related to patient care with DoC collated by the Care of the Patient in Coma scientific workgroup as part of the Neurocritical Care Society's Curing Coma Campaign. The gap analysis identified and organized domains of bedside care that could affect patient outcomes: clinical expertise, assessment and monitoring, timing of intervention, technology, family engagement, cultural considerations, systems of care, and transition to the post-acute continuum. Finally, this Viewpoint recommends future research and education initiatives to address and improve the care of patients with DoC.

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