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Background: Traumatic spinal cord injury (tSCI) impacts patients and their families acutely and often for the long term. The ability of clinicians to share prognostic information about mortality and functional outcomes allows patients and their surrogates to engage in decision-making and plan for the future. These guidelines provide recommendations on the reliability of acute-phase clinical predictors to inform neuroprognostication and guide clinicians in counseling adult patients with tSCI or their surrogates., Methods: A narrative systematic review was completed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of an appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Timing/Setting question was framed as "When counseling patients or surrogates of critically ill patients with traumatic spinal cord injury, should < predictor, with time of assessment if appropriate > be considered a reliable predictor of < outcome, with time frame of assessment >?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four Grading of Recommendations Assessment, Development, and Evaluation criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. Good practice recommendations addressed essential principles of neuroprognostication that could not be framed in the Population/Intervention/Comparator/Outcome/Timing/Setting format. Throughout the guideline development process, an individual living with tSCI provided perspective on patient-centered priorities., Results: Six candidate clinical variables and one prediction model were selected. Out of 11,132 articles screened, 369 met inclusion criteria for full-text review and 35 articles met eligibility criteria to guide recommendations. We recommend pathologic findings on magnetic resonance imaging, neurological level of injury, and severity of injury as moderately reliable predictors of American Spinal Cord Injury Impairment Scale improvement and the Dutch Clinical Prediction Rule as a moderately reliable prediction model of independent ambulation at 1 year after injury. No other reliable or moderately reliable predictors of mortality or functional outcome were identified. Good practice recommendations include considering the complete clinical condition as opposed to a single variable and communicating the challenges of likely functional deficits as well as potential for improvement and for long-term quality of life with SCI-related deficits to patients and surrogates., Conclusions: These guidelines provide recommendations about the reliability of acute-phase predictors of mortality, functional outcome, American Spinal Injury Association Impairment Scale grade conversion, and recovery of independent ambulation for consideration when counseling patients with tSCI or their surrogates and suggest broad principles of neuroprognostication in this context., (© 2023. The Author(s).)

Background: Family caregivers of patients with severe acute brain injury (SABI) admitted to intensive care units (ICUs) with coma experience heightened emotional distress stemming from simultaneous stressors. Stress and coping frameworks can inform psychosocial intervention development by elucidating common challenges and ways of navigating such experiences but have yet to be employed with this population. The present study therefore sought to use a stress and coping framework to characterize the stressors and coping behaviors of family caregivers of patients with SABI hospitalized in ICUs and recovering after coma., Methods: Our qualitative study recruited a convenience sample from 14 US neuroscience ICUs. Participants were family caregivers of patients who were admitted with ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, or hypoxic-ischemic encephalopathy; had experienced a comatose state for > 24 h; and completed or were scheduled for tracheostomy and/or gastrostomy tube placement. Participants were recruited < 7 days after transfer out of the neuroscience ICU. We conducted live online video interviews from May 2021 to January 2022. One semistructured interview per participant was recorded and subsequently transcribed. Recruitment was stopped when thematic saturation was reached. We deductively derived two domains using a stress and coping framework to guide thematic analysis. Within each domain, we inductively derived themes to comprehensively characterize caregivers' experiences., Results: We interviewed 30 caregivers. We identified 18 themes within the two theory-driven domains, including ten themes describing practical, social, and emotional stressors experienced by caregivers and eight themes describing the psychological and behavioral coping strategies that caregivers attempted to enact. Nearly all caregivers described using avoidance or distraction as an initial coping strategy to manage overwhelming emotions. Caregivers also expressed awareness of more adaptive strategies (e.g., cultivation of positive emotions, acceptance, self-education, and soliciting social and medical support) but had challenges employing them because of their heightened emotional distress., Conclusions: In response to substantial stressors, family caregivers of patients with SABI attempted to enact various psychological and behavioral coping strategies. They described avoidance and distraction as less helpful than other coping strategies but had difficulty engaging in alternative strategies because of their emotional distress. These findings can directly inform the development of additional resources to mitigate the long-term impact of acute psychological distress among this caregiver population., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: The objective of this document is to provide recommendations on the formal reliability of major clinical predictors often associated with intracerebral hemorrhage (ICH) neuroprognostication., Methods: A narrative systematic review was completed using the Grading of Recommendations Assessment, Development, and Evaluation methodology and the Population, Intervention, Comparator, Outcome, Timing, Setting questions. Predictors, which included both individual clinical variables and prediction models, were selected based on clinical relevance and attention in the literature. Following construction of the evidence profile and summary of findings, recommendations were based on Grading of Recommendations Assessment, Development, and Evaluation criteria. Good practice statements addressed essential principles of neuroprognostication that could not be framed in the Population, Intervention, Comparator, Outcome, Timing, Setting format., Results: Six candidate clinical variables and two clinical grading scales (the original ICH score and maximally treated ICH score) were selected for recommendation creation. A total of 347 articles out of 10,751 articles screened met our eligibility criteria. Consensus statements of good practice included deferring neuroprognostication-aside from the most clinically devastated patients-for at least the first 48-72 h of intensive care unit admission; understanding what outcomes would have been most valued by the patient; and counseling of patients and surrogates whose ultimate neurological recovery may occur over a variable period of time. Although many clinical variables and grading scales are associated with ICH poor outcome, no clinical variable alone or sole clinical grading scale was suggested by the panel as currently being reliable by itself for use in counseling patients with ICH and their surrogates, regarding functional outcome at 3 months and beyond or 30-day mortality., Conclusions: These guidelines provide recommendations on the formal reliability of predictors of poor outcome in the context of counseling patients with ICH and surrogates and suggest broad principles of neuroprognostication. Clinicians formulating their judgments of prognosis for patients with ICH should avoid anchoring bias based solely on any one clinical variable or published clinical grading scale., (© 2023. The Author(s).)

Background: Moderate-severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers., Methods: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted., Results: After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining "poor" functional outcomes. For consistency, we treated "poor" as "unfavorable". Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using "moderately reliable" predictors or prediction models, the clinician must acknowledge "substantial" uncertainty in the prognosis., Conclusions: These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication., (© 2024. The Author(s).)

Background: To facilitate comparative research, it is essential for the fields of neurocritical care and rehabilitation to establish common data elements (CDEs) for disorders of consciousness (DoC). Our objective was to identify CDEs related to goals-of-care decisions and family/surrogate decision-making for patients with DoC., Methods: To achieve this, we formed nine CDE working groups as part of the Neurocritical Care Society's Curing Coma Campaign. Our working group focused on goals-of-care decisions and family/surrogate decision-makers created five subgroups: (1) clinical variables of surrogates, (2) psychological distress of surrogates, (3) decision-making quality, (4) quality of communication, and (5) quality of end-of-life care. Each subgroup searched for existing relevant CDEs in the National Institutes of Health/CDE catalog and conducted an extensive literature search for additional relevant study instruments to be recommended. We classified each CDE according to the standard definitions of "core", "basic", "exploratory", or "supplemental", as well as their use for studying the acute or chronic phase of DoC, or both., Results: We identified 32 relevant preexisting National Institutes of Health CDEs across all subgroups. A total of 34 new instruments were added across all subgroups. Only one CDE was recommended as disease core, the "mode of death" of the patient from the clinical variables subgroup., Conclusions: Our findings provide valuable CDEs specific to goals-of-care decisions and family/surrogate decision-making for patients with DoC that can be used to standardize studies to generate high-quality and reproducible research in this area., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors., Methods: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: "When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?" Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format., Results: Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors., Conclusions: These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence., (© 2023. The Author(s).)

Background: Guillain-Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10-30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates., Methods: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: "When counseling patients or surrogates of critically ill patients with Guillain-Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format., Results: Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication., Conclusions: These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed., (© 2023. The Author(s).)

Background: There is a critical need to improve support for families making difficult shared decisions about patient care with clinicians in the neuroscience ICU (neuro-ICU). The aim of this study is to identify patient- and family-related factors associated with dissatisfaction with shared decision-making support among families of neuro-critically ill patients., Methods: We conducted a retrospective observational cohort study using survey data that had been collected from a consecutive sample of family members of patients in the neuro-ICU (one family member per patient) at two US academic centers. Satisfaction with shared decision-making support on ICU discharge had been measured among family members using one specific Likert scale item on the Family Satisfaction in the ICU 24 survey, a validated survey instrument for families of patients in the ICU. We dichotomized top-box responses for this particular item as an outcome variable and identified available patient- and family-related covariates associated with dissatisfaction (i.e., less than complete satisfaction) via univariate and multivariate analyses., Results: Among 355 surveys, 180 (49.5%) of the surveys indicated dissatisfaction with support during decision-making. In a multivariate model, no preexisting characteristics of families or patients ascertainable on ICU admission were predictive of dissatisfaction. However, among family factors determined during the ICU course, experiencing three or fewer formal family meetings (odds ratio 1.93 [confidence interval 1.13-3.31]; p = 0.01) was significantly predictive of dissatisfaction with decisional support in this cohort with an average patient length of stay of 8.6 days (SD 8.4). There was also a trend toward a family's decision to keep a patient as full code, without treatment limitations, being predictive of dissatisfaction (odds ratio 1.80 [confidence interval 0.93-3.51]; p = 0.08)., Conclusions: Family dissatisfaction with neuro-ICU shared decision-making support is not necessarily predicted by any preexisting family or patient variables but appears to correlate with participating in fewer formal family meetings during ICU admission. Future studies to improve family satisfaction with neurocritical care decision-making support should have broad inclusion criteria for participants and should consider promoting frequency of family meetings as a core strategy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Coma trajectories are characterized by quick awakening or protracted awakening. Outcome is bookended by restored functionality or permanent cognitively and physically debilitated states. Given the stakes, prognostication cannot be easily questioned as a judgment call, and a scientific underpinning is elemental. Conventional wisdom in determining coma-outcome trajectories posits that (1) predictive models are better than personal experiences, (2) self-fulfilling prophesy is unchecked and driven by nihilism, with little regard for prior probability outcomes, and (3) recovery is impacted by patients' prior wishes and preexisting medical conditions-but also by what families are told about the patient's state and anticipated clinical course. Moreover, a predicted good outcome can be offset by a major subsequent complication, or a predicted poor outcome can be offset by aggressive care. This article examines some of these concepts, including how we decide on aggressiveness of care, how we judge quality of life, and the impact on outcome. Most patients who awaken quickly do well and can resume their pretrauma injury lives. In worse off, slow-to-awaken patients, outcomes are a mixed bag of limited innate resilience, depleted cognitive and physical reserves, and adjusted quality of life. Bias and noise are factors not easily measured in outcome prediction, but their influence on recovery trajectories raises some troubling issues., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Patients with a severe acute brain injury admitted to the intensive care unit often have a poor neurological prognosis. In these situations, a clinician is responsible for conducting a goals-of-care conversation with the patient's surrogate decision makers. The diversity in thought and background of surrogate decision makers can present challenges during these conversations. For this reason, our study aimed to identify predictive characteristics of US surrogate decision makers' favoring life-sustaining treatment (LST) over comfort measures only for patients with severe acute brain injury., Methods: We analyzed data from a cross-sectional survey study that had recruited 1588 subjects from an online probability-based US population sample. Seven hundred and ninety-two subjects had randomly received a hypothetical scenario regarding a relative intubated with severe acute brain injury with a prognosis of severe disability but with the potential to regain some consciousness. Seven hundred and ninety-six subjects had been randomized to a similar scenario in which the relative was projected to remain vegetative. For each scenario, we conducted univariate analyses and binary logistic regressions to determine predictors of LST selection among available respondent characteristics., Results: 15.0% of subjects selected LST for the severe disability scenario compared to 11.4% for the vegetative state scenario (p = 0.07), with those selecting LST in both groups expressing less decisional certainty. For the severe disability scenario, independent predictors of LST included having less than a high school education (adjusted OR = 2.87, 95% CI = 1.23-6.76), concern regarding prognostic accuracy (7.64, 3.61-16.15), and concern regarding the cost of care (4.07, 1.80-9.18). For the vegetative scenario, predictors included the youngest age group (30-44 years, 3.33, 1.02-10.86), male gender (3.26, 1.75-6.06), English as a second language (2.94, 1.09-7.89), Evangelical Protestant (3.72, 1.28-10.84) and Catholic (4.01, 1.72-9.36) affiliations, and low income (< $25 K)., Conclusion: Several demographic and decisional characteristics of US surrogate decision makers predict LST selection for patients with severe brain injury with varying degrees of poor prognosis. Surrogates concerned about the cost of medical care may nevertheless be inclined to select LST, albeit with high levels of decisional uncertainty, for patients projected to have severe disabilities., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background/objective: Prognostication is a routine part of the delivery of neurocritical care for most patients with acute neurocritical illnesses. Numerous prognostic models exist for many different conditions. However, there are concerns about significant gaps in knowledge regarding optimal methods of prognostication., Methods: As part of the Arbeitstagung NeuroIntensivMedizin meeting in February 2018 in Würzburg, Germany, a joint session on prognostication was held between the German NeuroIntensive Care Society and the Neurocritical Care Society. The purpose of this session was to provide presentations and open discussion regarding existing prognostic models for eight common neurocritical care conditions (aneurysmal subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, traumatic brain injury, traumatic spinal cord injury, status epilepticus, Guillain-Barré Syndrome, and global cerebral ischemia from cardiac arrest). The goal was to develop a qualitative gap analysis regarding prognostication that could help inform a future framework for clinical studies and guidelines., Results: Prognostic models exist for all of the conditions presented. However, there are significant gaps in prognostication in each condition. Furthermore, several themes emerged that crossed across several or all diseases presented. Specifically, the self-fulfilling prophecy, lack of accounting for medical comorbidities, and absence of integration of in-hospital care parameters were identified as major gaps in most prognostic models., Conclusions: Prognostication in neurocritical care is important, and current prognostic models are limited. This gap analysis provides a summary assessment of issues that could be addressed in future studies and evidence-based guidelines in order to improve the process of prognostication.

Background: Prior studies of patients in the intensive care unit have suggested racial/ethnic variation in end-of-life decision making. We sought to evaluate whether race/ethnicity modifies the implementation of comfort measures only status (CMOs) in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH)., Methods: We analyzed data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a prospective cohort study specifically designed to enroll equal numbers of white, black, and Hispanic subjects. ICH patients aged ≥ 18 years were enrolled in ERICH at 42 hospitals in the USA from 2010 to 2015. Univariate and multivariate logistic regression analyses were implemented to evaluate the association between race/ethnicity and CMOs after adjustment for potential confounders., Results: A total of 2705 ICH cases (912 black, 893 Hispanic, 900 white) were included in this study (mean age 62 [SD 14], female sex 1119 [41%]). CMOs patients comprised 276 (10%) of the entire cohort; of these, 64 (7%) were black, 79 (9%) Hispanic, and 133 (15%) white (univariate p < 0.001). In multivariate analysis, compared to whites, blacks were half as likely to be made CMOs (OR 0.50, 95% CI 0.34-0.75; p = 0.001), and no statistically significant difference was observed for Hispanics. All three racial/ethnic groups had similar mortality rates at discharge (whites 12%, blacks 9%, and Hispanics 10%; p = 0.108). Other factors independently associated with CMOs included age (p < 0.001), premorbid modified Rankin Scale (p < 0.001), dementia (p = 0.008), admission Glasgow Coma Scale (p = 0.009), hematoma volume (p < 0.001), intraventricular hematoma volume (p < 0.001), lobar (p = 0.032) and brainstem (p < 0.001) location and endotracheal intubation (p < 0.001)., Conclusions: In ICH, black patients are less likely than white patients to have CMOs. However, in-hospital mortality is similar across all racial/ethnic groups. Further investigation is warranted to better understand the causes and implications of racial disparities in CMO decisions.

Severe traumatic brain injury (sTBI) is a major contributor to long-term disability and a leading cause of death worldwide. Medical management of the sTBI patient, beginning with prehospital triage, is aimed at preventing secondary brain injury. This review discusses prehospital and emergency department management of sTBI, as well as aspects of TBI management in the intensive care unit where advances have been made in the past decade. Areas of emphasis include intracranial pressure management, neuromonitoring, management of paroxysmal sympathetic hyperactivity, neuroprotective strategies, prognostication, and communication with families about goals of care. Where appropriate, differences between the third and fourth editions of the Brain Trauma Foundation guidelines for the management of severe traumatic brain injury are highlighted.

Background: The early subjective clinical judgment of clinicians outperforms formal prognostic scales for accurate determination of outcome after intracerebral hemorrhage (ICH), with the judgment of physicians and nurses having equivalent accuracy. This study assessed specific decisional factors that physicians and nurses incorporate into early predictions of functional outcome., Methods: This prospective observational study enrolled 121 ICH patients at five US centers. Within 24 h of each patient's admission, one physician and one nurse on the clinical team were each surveyed to predict the patient's modified Rankin Scale (mRS) at 3 months and to list up to 10 subjective factors used in prognostication. Factors were coded and compared between (1) physician and nurse and (2) accurate and inaccurate surveys, with accuracy defined as an exact prediction of mRS., Results: Aside from factors that are components of the ICH or FUNC scores, surveys reported pre-existing comorbidities (40.0%), other clinical or radiographic factors not in clinical scales (43.0%), and non-clinical/radiographic factors (21.9%) as important. Compared to physicians, nurses more frequently listed neurologic examination components (Glasgow Coma Scale motor, 27.3 vs. 5.8%, p < 0.0001; GCS verbal, 12.4 vs. 0.0%, p < 0.0001) and non-clinical/radiographic factors (31.4 vs. 12.4%, p = 0.0005). Physicians more frequently listed neuroimaging factors (ICH location, 33.9 vs. 7.4%, p < 0.0001; intraventricular hemorrhage, 13.2 vs. 2.5%, p = 0.003). There was no difference in listed factors between accurate versus inaccurate surveys., Conclusions: Clinicians frequently utilize factors outside of the components of clinical scales for prognostication, with physician and nurses focusing on different factors despite having similar accuracy.

Background and Purpose: As survival rates have increased for intracerebral hemorrhage (ICH) patients, there is limited information regarding recovery beyond 3-6 months. This study was conducted to examine recovery curves using the modified Rankin Scale (mRS) and Barthel Index (BI) up to 12 months post-injury., Methods: We prospectively enrolled 173 patients admitted with ICH who were subsequently evaluated using the mRS and BI at discharge as well as 3, 6, and 12 months. Repeated measures nonparametric testing was conducted to assess functional trajectories across time., Results: The mRS scores showed significant improvement between discharge (median 4) and 3 (median 4), 6 (median 4), and 12 months (median 3) (p values <0.001). However, the mRS scores did not differ between follow-up time-points (i.e., 3-6, 6-12 months). There was significant improvement in scores using the BI (p values <0.001), showing improvement between discharge (mean 43.0) and 3 (mean 73.0), 6 (mean 78.2), and 12 months (mean 83.4). Additionally, there were differences in the BI between 3 and 12 months (p = 0.013), as well as between 6 and 12 months (p = 0.025)., Conclusions: The BI may be a more sensitive measure of long-term recovery post-injury than the mRS, which shows minimal improvement for some survivors after 3 months. BI scores indicate survivors continually improve till 12 months post-injury. These results may have implications for the prognostication of ICH and design of clinical trial outcome measures.

Background and Purpose: Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of mortality, less is known regarding the relationship between more specific ICH locations and functional outcome. This review summarizes current work studying how ICH location affects outcome, with an emphasis on how studies designate regions of interest., Methods: A systematic search of the OVID database for relevant studies was conducted during August 2015. Studies containing an analysis of functional outcome by ICH location or laterality were included. As permitted, the effect size of individual studies was standardized within a meta-analysis., Results: Thirty-seven studies met the inclusion criteria, the majority of which followed outcome at 3 months. Most studies found better outcomes on the Modified Rankin Scale (mRS) or Glasgow Outcome Score (GOS) with lobar compared to deep ICHs. While most aggregated deep structures for analysis, some studies found poorer outcomes for thalamic ICH in particular. Over half of the studies did not have specific methodological considerations for location designations, including blinding or validation., Conclusions: Multiple studies have examined motor-centric outcomes, with few studies examining quality of life (QoL) or cognition. Better functional outcomes have been suggested for lobar versus non-lobar ICH; few studies attempted finer topographic comparisons. This study highlights the need for improved reporting in ICH outcomes research, including a detailed description of hemorrhage location, reporting of the full range of functional outcome scales, and inclusion of cognitive and QoL outcomes.

Estrogen has been known to reduce the development of Alzheimer's disease (AD). However, exact mechanisms are not clear. We investigated whether estrogen can increase amyloid-beta (Aβ) degradation and affects Aβ-induced memory impairment in an estrogen deficiency model. Estrogen receptor alpha (ERα) knockout mice and wild-type mice were intracerebroventricular (ICV) infused with Aβ (300 pmol) for 2 weeks. Cognitive function was then assessed by the Morris water maze test and passive avoidance test. In addition, Western blot analysis, immunostaining, immunofluorescence staining, ELISA, and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of ERα knockout mice. In our present study, Aβ was accumulated more in the ERα knockout mice brain and greatly worsened memory impairment and glial activation as well as neurogenic inflammation. These results suggest that estrogen may protect memory impairment by stimulating the degradation of Aβ and down-regulate neurogenic inflammation as well as amyloidogenesis.

In the neuroscience intensive care unit (NICU), most patients lack the capacity to make their own preferences known. This fact leads to situations where surrogate decision makers must fill the role of the patient in terms of making preference-based treatment decisions, oftentimes in challenging situations where prognosis is uncertain. The neurointensivist has a large responsibility and role to play in this shared decision-making process. This review covers how NICU patient preferences are determined through existing advance care documentation or surrogate decision makers and how the optimum roles of the physician and surrogate decision maker are addressed. We outline the process of reaching a shared decision between family and care team and describe a practice for conducting optimum family meetings based on studies of ICU families in crisis. We review challenges in the decision-making process between surrogate decision makers and medical teams in neurocritical care settings, as well as methods to ameliorate conflicts. Ultimately, the goal of shared decision making is to increase knowledge amongst surrogates and care providers, decrease decisional conflict, promote realistic expectations and preference-centered treatment strategies, and lift the emotional burden on families of neurocritical care patients.

The objectives of this study was to improve poly-γ-glutamic acid (γ-PGA) production by Bacillus subtilis D7 isolated from a Korean traditional fermented food and to assess its antioxidant activity for applications in the cosmetics and pharmaceutical industries. Strain D7 produced γ-PGA in the absence of L-glutamic acid, indicating L-glutamic acid-independent production. However, the addition of L-glutamic acid increased γ-PGA production. Several tricarboxylic acid cycle intermediates and amino acids could serve as the metabolic precursors for γ-PGA production, and the addition of pyruvic acid and D-glutamic acid to culture medium improved the yield of γ-PGA markedly. The maximum yield of γ-PGA obtained was 24.93 ± 0.64 g/l in improved medium, which was about 5.4-fold higher than the yield obtained in basal medium. γ-PGA was found to have 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (46.8 ± 1.5 %), hydroxyl radical scavenging activity (52.0 ± 1.8 %), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS) radical scavenging activity (42.1 ± 1.8 %), nitric oxide scavenging activity (35.1 ± 1.3 %), reducing power (0.304 ± 0.008), and metal chelating activity (91.3 ± 3.5 %). These results indicate that γ-PGA has a potential use in the food, cosmetics, and biomedical industries for the development of novel products with radical scavenging activity. As far as we are aware, this is the first report to describe the antioxidant activityof γ-PGA produced by bacteria.

Nicastrin (NCT) is a component of the presenilin protein complex, which is involved in the cleavage of β-amyloid precursor protein (βAPP) and Notch. The aim of this study was to determine the manner in which overexpression of wild-type human nicastrin (hNCTw) or mutant human nicastrin (hNCTm, D336A/Y337A) regulates brain functions and amyloid precusor protein (APP) processing. For this, we created transgenic (Tg) mice expressing neuron-specific enolase (NSE)-controlled hNCTw or hNCTm and measured their phenotypes as time passed. The NSE/hNCTw and NSE/hNCTm Tg groups exhibited greater behavioral dysfunction from 10 months of age than the non-Tg group, although their severities differed. Further, activity and component levels of the γ-secretase complex were significantly elevated in NSE/hNCTw Tg mice, expect for PEN-2. These alterations induced stimulation of APP processing, resulting in overproduction of Aβ-42 peptide in the NSE/hNCTw Tg group, whereas the NSE/hNCTm Tg group showed a comparatively weaker effect. Furthermore, the highest expression levels of β-secretase and NICD were observed in the NSE/hNCTw Tg group, similar to other phenotypes. Especially, a significances interference on the interaction between NCT and γ-secretase substrates was detected in NSE/hNCTm Tg groups compare with NSE/hNCTw Tg group. These results indicate that hNCTw overexpression in Tg mice promoted active assembly of the γ-secretase complex through modulation of APP processing and behavior, whereas the lesser effect in NSE/hNCTm Tg mice was due to reduced expression of hNCTm. These Tg mice could be useful for the development and application of therapeutic drugs in an animal model of Alzheimer's disease.

A combination of selenium (Se) with other trace element is associated with partially modulate fatty acid distribution as well as reduction of the body weight and feed efficiency. To investigate whether or not Se treatment has an impact on lipid metabolism, we examined the levels of lipid metabolism-related factors, including abdominal fat, adiponectin, cholesterol, very long chain dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) in 20-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats following sodium selenite treatment for 2 weeks. Herein, we observed that (a) Se treatment induced insulin-like effects by lowering the serum glucose level in rats; (b) Se-treated rats showed significance values decreases in abdominal fat mass, adipocyte size, and adiponectin, which are associated with lipid metabolism; (c) Se treatment led to reduced levels of cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol; (d) fat tissue in Se-treated rats displayed significantly lower expression of adipocyte marker genes along with increased expression of VLCAD and MCAD; and (e) fatty liver formation and β-oxidation gene expression were both significantly reduced in liver tissue of Se-treated rats. Therefore, our results suggest that Se may induce inhibition of adipocyte hypertrophy and abdominal fat accumulation along with suppression of fatty liver formation by the differential regulation of the gene expression for fatty acid β-oxidation in the OLETF model.

Nonregulatable promoters have been mainly used to produce transgenic mice that express the human genes for Alzheimer's disease (AD). The aim of this study was to produce doubly transgenic mice expressing the regulatable tet promoter-controlled transactivator (tTA) and human mutant presenilin 2 (N141I, hPS2m) genes in order to examine the AD-related phenotypes at the basal and inducible levels. To achieve this, the first lineage of the transgenic line, expressing Tet/tTA and the second lineage of transgenic mice, expressing Tet/hPS2m, were created, and the doubly transgenic mice were produced by crossing the Tet/tTA-transgenic mice with the Tet/hPS2m-transgenic mice. The doubly transgenic mice and nontransgenic littermates were then treated with or without doxycycline. The results showed that removing doxycycline from the transgenic mice resulted in the induction of the transgene, a Wnt signaling defect, behavioral impairment, elevated amyloid-beta-42 and gamma-secretase activity compared with in the group given doxycyline. Moreover, the expression levels of the hPS2m transgene decreased gradually in the transgenic males, with clear changes becoming apparent between 2 and 4 wk of age. Castrating these males resulted in an increased expression level of the hPS2m gene. This was restored to the normal levels by treatment with testosterone. Therefore, tetregulated transgenic mice can be used to examine the effect of the basal or inducible expression levels of hPS2m on the pathology of AD at the "on/off" states at any stage of development.