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Background: Many randomized controlled trials (RCT) have assessed new treatments in subarachnoid hemorrhage (SAH), yet most show no treatment efficacy. One explanation is the statistical analysis of the primary endpoint was not as efficient as possible. We reanalyzed SAH RCTs with various statistical tests to determine whether the statistical method affects RCT primary outcome.Methods: Individual patient data for the primary outcome (Glasgow outcome scale [GOS]) of two SAH RCTs were analyzed using 15 statistical methods. For tests requiring outcome dichotomization, multiple cut-points in the 5-level GOS were assessed. Next, a synthetic dataset generated using random sampling with replacement from ten SAH RCTs was assessed using the same statistical tests. A Friedman test (two-way non-parametric analysis of variance) determined which tests produced the highest average absolute Z-values. The number of times each test reported significance of pResults: Bootstrapping with replacement produced the best-ranking results, followed by three χ2-tests: one differentiating excellent (GOS=5) from good (GOS=4), poor (GOS=2-3), or dead (GOS=1) outcomes; one differentiating favorable (GOS=4-5) from poor or dead outcomes; and one differentiating favorable (GOS=4-5) from unfavorable outcomes. Each of these reported statistical significance for both RCTs, as did the following ranked tests, respectively: Wilcoxon median test, Student’s t-test, ordinal logistic regression, median test, and a chi-square dichotomizing excellent (GOS≥4) and inferior outcomes. Statistical significance for one or neither RCT was reported by two Cochrane-Armitage tests and two logistic regressions with alternate versions of bucketing, the Kolmogorov-Smirnov test and chi-square test differentiating surviving from dead patients. The synthetic dataset returned similar results, with the same nine most and six least efficient tests.Conclusions: Bootstrapping produced the most efficient results but is time-and resource-intensive. Chi-square tests grouping outcomes into dichotomous or multiple buckets are also efficient, and their ease of use and popularity make them appropriate candidates for statistical analysis in future SAH RCTs.

Author(s): Vitt, Jeffrey R; Sun, Chung-Huan; Le Roux, Peter D; Hemphill, J Claude | Abstract: Purpose of reviewSpontaneous intracerebral hemorrhage (ICH) is common, associated with a high degree of mortality and long-term functional impairment, and remains without effective proven treatments. Surgical hematoma evacuation can reduce mass effect and decrease cytotoxic effects from blood product breakdown. However, results from large clinical trials that have examined the role of open craniotomy have not demonstrated a significant outcome benefit over medical management. We review the data on minimally invasive surgery (MIS) that is emerging as a treatment modality for spontaneous ICH.Recent findingsThe use of MIS for supratentorial ICH has increased significantly in recent years and appears to be associated with decreased mortality and improved functional outcome compared with medical management. The role of MIS for posterior fossa ICH is ill-defined. Currently available MIS devices allow for stereotactic aspiration and thrombolysis, endoport-mediated evacuation, and endoscopic aspiration. Clinical series demonstrate that MIS can facilitate significant hematoma volume reduction and may be associated with less morbidity than conventional open surgical approaches.SummaryMIS is an appealing treatment modality for supratentorial ICH and with careful patient selection and technologic advances has the potential to improve neurologic outcomes and reduce mortality. Early and extensive hematoma evacuation are important therapeutic targets and current studies are underway that have the potential to change the management for ICH patients.

OBJECTIVES: To estimate the impact of goal-directed therapy on outcome after traumatic brain injury, our team applied goal-directed therapy to standardize care in patients with moderate to severe traumatic brain injury, who were enrolled in a large multicenter clinical trial. DESIGN: Planned secondary analysis of data from Progesterone for the Treatment of Traumatic Brain Injury III, a large, prospective, multicenter clinical trial. SETTING: Forty-two trauma centers within the Neurologic Emergencies Treatment Trials network. PATIENTS: Eight-hundred eighty-two patients were enrolled within 4 hours of injury after nonpenetrating traumatic brain injury characterized by Glasgow Coma Scale score of 4–12. MEASUREMENTS AND MAIN RESULTS: Physiologic goals were defined a priori in order to standardize care across 42 sites participating in Progesterone for the Treatment of Traumatic Brain Injury III. Physiologic data collection occurred hourly; laboratory data were collected according to local ICU protocols and at a minimum of once per day. Physiologic transgressions were predefined as substantial deviations from the normal range of goal-directed therapy. Each hour where goal-directed therapy was not achieved was classified as a “transgression.” Data were adjudicated electronically and via expert review. Six-month outcomes included mortality and the stratified dichotomy of the Glasgow Outcome Scale-Extended. For each variable, the association between outcome and either: 1) the occurrence of a transgression or 2) the proportion of time spent in transgression was estimated via logistic regression model. RESULTS: For the 882 patients enrolled in Progesterone for the Treatment of Traumatic Brain Injury III, mortality was 12.5%. Prolonged time spent in transgression was associated with increased mortality in the full cohort for hemoglobin less than 8 gm/dL (p = 0.0006), international normalized ratio greater than 1.4 (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0003), and systolic blood pressure less than 90 mm Hg (p < 0.0001). In the patient subgroup with intracranial pressure monitoring, prolonged time spent in transgression was associated with increased mortality for intracranial pressure greater than or equal to 20 mm Hg (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0293), hemoglobin less than 8 gm/dL (p = 0.0220), or systolic blood pressure less than 90 mm Hg (p = 0.0114). Covariates inversely related to mortality included: a single occurrence of mean arterial pressure less than 65 mm Hg (p = 0.0051) or systolic blood pressure greater than 180 mm Hg (p = 0.0002). CONCLUSIONS: The Progesterone for the Treatment of Traumatic Brain Injury III clinical trial rigorously monitored compliance with goal-directed therapy after traumatic brain injury. Multiple significant associations between physiologic transgressions, morbidity, and mortality were observed. These data suggest that effective goal-directed therapy in traumatic brain injury may provide an opportunity to improve patient outcomes.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to examine its impact on outcome.This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO(2) was monitored. The relationship between Hgb-categorized into four quartiles (≤9; 9-10; 10.1-11;11 g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with compromised PbtO(2) was defined as episodes of Hgb ≤ 9 g/dl with simultaneous PbtO(2)20 mmHg. Outcome was assessed at 30 days using the Glasgow outcome score (GOS), dichotomized as favorable (GOS 4-5) vs. unfavorable (GOS 1-3).We analyzed 474 simultaneous Hgb and PbtO(2) samples from 80 patients (mean age 44 ± 20 years, median GCS 4 (3-7)). Using Hgb11 g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO(2), PaCO(2)), Hgb ≤ 9 g/dl was the only Hgb level that was associated with lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p0.001). Anemia with simultaneous PbtO(2)20 mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score.In this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no greater than 9 g/dl was associated with compromised PbtO(2). Anemia with simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.

Traumatic axonal injury (TAI) is the most common and important pathology of traumatic brain injury (TBI). However, little is known about potential indirect effects of TAI on dendrites. In this study, we used a well-established in vitro model of axonal stretch injury to investigate TAI-induced changes in dendrite morphology. Axons bridging two separated rat cortical neuron populations plated on a deformable substrate were used to create a zone of isolated stretch injury to axons. Following injury, we observed the formation of dendritic alterations or beading along the dendrite shaft. Dendritic beading formed within minutes after stretch then subsided over time. Pharmacological experiments revealed a sodium-dependent mechanism, while removing extracellular calcium exacerbated TAI's effect on dendrites. In addition, blocking ionotropic glutamate receptors with the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 prevented dendritic beading. These results demonstrate that axon mechanical injury directly affects dendrite morphology, highlighting an important bystander effect of TAI. The data also imply that TAI may alter dendrite structure and plasticity in vivo. An understanding of TAI's effect on dendrites is important since proper dendrite function is crucial for normal brain function and recovery after injury.

Objective - To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH).Design - Cohort study with logistic regression analysis to combine predictors and treatment modality.Setting - Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries.Participants - Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models.Main outcome measure - Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale.Results - Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a "neuroimaging model," with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort.Conclusion - The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.

Objectives: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disorder that still requires much clinical study. However, the decision to participate in a randomized clinical trial, particularly a neuroemergency trial, is a complex one. The purposes of this survey were to determine who would participate in a randomized clinical trial that intended to examine transfusion practices after SAH, to identify who could serve as potential proxy decision-makers, and to find which patient characteristics were associated with the decision to participate. Methods: This was a cross-sectional study using a self-administered questionnaire, composed of a brief description of the proposed trial followed by questions about participation using a 5-point Likert scale. Information sought included potential decision-maker, demographic data, setting and reason for current health care access, and personal or family history of neurologic injury. Results: Nine-hundred five subjects were enrolled during emergency department (ED) visits, office visits, hospital admissions, or online, during a 1-month period: 63% were women and 46% were white. Nonneurologic problems were the leading reason (90%) for health care access, but 45% had a personal or family history of neurologic injury. Overall, 54% (95% confidence interval [CI] = 51% to 57%) of subjects stated they would definitely or probably consent to participate. No subject characteristics were associated with this decision: age (p = 0.28), sex (p = 0.16), race/ethnicity (p = 0.07), education (p = 0.44), religion (p = 0.42), clinical setting (p = 0.14), reason for visit (p = 0.58), and/or history of neurologic injury (p = 0.33). The vast majority (88%) identified a family member as the proxy decision-maker, again without differences among groups. Conclusions: Greater than half of respondents stated they would participate in a proposed emergency treatment trial for SAH. Our survey suggests that the decision to participate is highly individualized, because no demographic, pathologic, historical, or access-related predictors of choice were found. Educational materials designed for this type of trial would need to be broad-based. Family members should be considered as proxy decision-makers where permitted by federal and local regulations.

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research., SCOPUS: re.j, info:eu-repo/semantics/published

Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research the Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.

Osteogenic protein-1 (OP-1), a member of the transforming growth factor-beta (TGF-β) superfamily, has been demonstrated to stimulate dendrite growth from sympathetic neurons in culture. However, it is not known whether OP-1 affects dendrite growth from central nervous system neurons. Therefore we quantified axon and primary, secondary, and total dendritic growth from embryonic mouse cortical neurons (E 18) grown in vitro in a chemically defined medium. Morphology and double immunolabeling (MAP2, NF-H) were used to identify cortical dendrites and axons after 3 days in vitro. Cell morphology, neuron survival, and axon length were similar under all experimental conditions. The number of primary dendrites also was similar; however, the length of primary dendrites and the length and number of secondary dendrites were significantly increased by the addition of OP-1 to the culture medium. This increase in dendrite growth was dose-dependent; maximal dendritic growth was observed after the addition of 30–100 ng/ml of OP-1 to the culture medium. Specific support of dendrite growth was not observed when neurons were exposed to other members of the TGF-β superfamily. These findings demonstrate that OP-1 selectively increases dendrite growth from cerebral cortical neurons in vitro.

Future clinical or scientific innovations may bring about improvements in the management of intracranial aneurysms and subarachnoid hemorrhage. However, there are several potential avenues for improvement in the care of, and present management of, patients with cerebral aneurysms. These opportunities for improvement exist in areas of prevention, systems approach and organization of cerebrovascular centers, physician and patient education, screening and treatment of unruptured aneurysms, and advances in surgical and endovascular therapy. All such advances, however, will depend on rigorous academic evaluation.

Reactive astrocytes are thought to be impediments to axon regrowth following injury to the mammalian central nervous system. Axon and dendrite growth, however, appear to be differently controlled by normal astrocytes in vitro. To determine whether reactive astrocytes differ in their ability to support axons or dendrites, embryonic (E18) mouse cortical neurons were cocultured with P4 and P12 rat astroglial cells derived from normal or lesioned cortex. After 5 days in vitro, axon and dendrite outgrowth from isolated neurons was quantified with double-labeling immunohistochemical techniques. Reactive astrocytes were able to maintain primary dendrite growth, principally primary dendrite number. Axon elongation, however, was significantly reduced on both neonatal and more mature reactive astrocytes. These results indicate that reactive astrocytes may exhibit separate mechanisms to control dendrite and axon growth.

BACKGROUND Increased intracranial pressure (ICP) can cause brain ischemia and compromised brain oxygen (PbtO2 < or = 20 mm Hg) after severe traumatic brain injury (TBI). OBJECTIVE We examined whether decompressive craniectomy (DC) to treat elevated ICP reduces the cumulative ischemic burden (CIB) of the brain and therapeutic intensity level (TIL). METHODS Ten severe TBI patients (mean age, 31.4 +/- 14.2 years) who had continuous PbtO2 monitoring before and after delayed DC were retrospectively identified. Patients were managed according to the guidelines for the management of severe TBI. The CIB was measured as the total time spent between a PbtO2 of 15 to 20, 10 to 15, and 0 to 10 mm Hg. The TIL was calculated every 12 hours. Mixed-effects models were used to estimate changes associated with DC. RESULTS DC was performed on average 2.8 days after admission. DC was found to immediately reduce ICP (mean [SEM] decrease was 7.86 mm Hg [2.4 mm Hg]; P = .005). TIL, which was positively correlated with ICP (r = 0.46, P < or = .001), was reduced within 12 hours after surgery and continued to improve within the postsurgical monitoring period (P

Adverse neurological outcome is a major cause of long-term morbidity in ex-preterm children. To investigate the effect of parturition and inflammation on the fetal brain, we utilized two in vivo mouse models of preterm birth. To mimic the most common human scenario of preterm birth, we used a mouse model of intrauterine inflammation by intrauterine infusion of lipopolysaccharide (LPS). To investigate the effect of parturition on the immature fetal brain, in the absence of inflammation, we used a non-infectious model of preterm birth by administering RU486. Pro-inflammatory cytokines (IL-10, IL-1beta, IL-6 and TNF-alpha) in amniotic fluid and inflammatory biomarkers in maternal serum and amniotic fluid were compared between the two models using ELISA. Pro-inflammatory cytokine expression was evaluated in the whole fetal brains from the two models. Primary neuronal cultures from the fetal cortex were established from the different models and controls in order to compare the neuronal morphology. Only the intrauterine inflammation model resulted in an elevation of inflammatory biomarkers in the maternal serum and amniotic fluid. Exposure to inflammation-induced preterm birth, but not non-infectious preterm birth, also resulted in an increase in cytokine mRNA in whole fetal brain and in disrupted fetal neuronal morphology. In particular, Microtubule-associated protein 2 (MAP2) staining was decreased and the number of dendrites was reduced (P < 0.001, ANOVA between groups). These results suggest that inflammation-induced preterm birth and not the process of preterm birth may result in neuroinflammation and alter fetal neuronal morphology.

OBJECTIVE: Red blood cell transfusion (RBCT) is associated with medical complications in general medical and surgical patients. We examined the hypothesis that RBCT during intensive care unit (ICU) care is associated with medical complications after subarachnoid hemorrhage (SAH). METHODS: We retrospectively analyzed a prospective observational database containing 421 patients with SAH (mean age, 51.5 years; standard deviation, 14.6 years). Logistic regression models were used to adjust for age, admission hemoglobin (Hgb), clinical grade, average ICU Hgb, and symptomatic vasospasm. RESULTS:Two hundred fourteen patients received an RBCT during their ICU stay. Medical complications were identified in 156 patients and were more common in those who received blood (46%) than in those who did not (29.8%) (P < .001). Major medical complications (cardiac, pulmonary, renal, or hepatic) occurred in 111 patients, and minor complications (eg, skin rash, deep vein thrombosis) occurred in 45 patients. Any non-central nervous system infection (n =183 ; P < .001), including pneumonia (n = 103; P < .001) or septicemia (n = 36; P=.02), was more common with RBCT. Central nervous system infections (meningitis, cranial wound, n = 15) also were associated with RBCT (P = .03). Mechanically ventilated patients (n = 259) were more likely to have received an RBCT than those who did not (P < .001). When logistic regression was used to control for age, admission clinical grade and Hgb, average ICU Hgb, symptomatic vasospasm, and other admission variables associated with outcome, the following factors (odds ratio; 95% confidence interval) were associated with RBCT: any medical complication (1.8; 1.1-3.0), major medical complications (2.1; 1.2-3.7), any infection (2.8; 1.7-4.5), pneumonia (2.6; 1.5-4.7), septicemia (2.9; 1.2-6.8), and need for mechanical ventilation (2.8; 1.5-5.1). CONCLUSION: These data suggest that RBCTs are associated with medical complications after SAH. However, the data do not infer causation, and further study is necessary to better define the indications for transfusion after SAH.

Background and Purpose— The optimal hemoglobin (Hgb) target after aneurysmal subarachnoid hemorrhage is not precisely known. We sought to examine the threshold of Hgb concentration associated with an increased risk of cerebral metabolic dysfunction in patients with poor-grade subarachnoid hemorrhage. Methods— Twenty consecutive patients with poor-grade subarachnoid hemorrhage who underwent multimodality neuromonitoring (intracranial pressure, brain tissue oxygen tension, cerebral microdialysis) were studied prospectively. Brain tissue oxygen tension and extracellular lactate/pyruvate ratio were used as markers of cerebral metabolic dysfunction and the relationship between Hgb concentrations and the incidence of brain hypoxia (defined by a brain tissue oxygen tension 40) was analyzed. Results— Compared with higher Hgb concentrations, a Hgb concentration P =0.02), higher lactate/pyruvate ratio (29 [interquartile range, 25 to 38] versus 36 [interquartile range, 26 to 59], P =0.16), and an increased incidence of brain hypoxia (21% versus 52%, P P =0.03). On multivariable analysis, a Hgb concentration P P =0.02) after adjusting for cerebral perfusion pressure, central venous pressure, PaO 2 /FIO 2 ratio, and symptomatic vasospasm. Conclusions— A Hgb concentration

Background and Purpose— The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). Methods— Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature ≥38.3°C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). Results— Compared to fever, induced normothermia resulted in lower LPR (40±24 versus 32±9, P P P P Conclusions— Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required., JOURNAL ARTICLE, SCOPUS: re.j, info:eu-repo/semantics/published

Objective The purpose of this study was to elucidate possible mechanisms of fetal neuronal injury in inflammation-induced preterm birth. Study Design With the use of a mouse model of preterm birth, the following primary cultures were prepared from fetal brains: (1) control neurons (CNs), (2) lipopolysaccharide-exposed neurons (LNs), (3) control coculture (CCC) that consisted of neurons and glia, and (4) lipopolysaccharide-exposed coculture (LCC) that consisted of lipopolysaccharide-exposed neurons and glia. CNs and LNs were treated with culture media from CN, LN, CCC, and LCC after 24 hours in vitro. Immunocytochemistry was performed for culture characterization and neuronal morphologic evidence. Quantitative polymerase chain reaction was performed for neuronal differentiation marker, microtubule-associated protein 2, and for cell death mediators, caspases 1, 3, and 9. Results Lipopolysaccharide exposure in vivo did not influence neuronal or glial content in cocultures but decreased the expression of microtubule-associated protein 2 in LNs. Media from LNs and LCCs induced morphologic changes in control neurons that were comparable with LNs. The neuronal damage caused by in vivo exposure (LNs) could not be reversed by media from control groups. Conclusion Lipopolysaccharide-induced preterm birth may be responsible for irreversible neuronal injury.

Jugular bulb oxygen monitoring can be used to estimate the adequacy of cerebral blood flow to support cerebral metabolism after severe head injury. In the present study, the authors studied the cerebral arteriovenous oxygen difference (AVDO2) before and after treatment in 32 head-injured patients (Glasgow Coma Scale scores ¾ 8) to examine the relationships among AVDO2 and cerebral perfusion pressure (CPP), delayed cerebral infarction, and outcome. Fifteen patients (Group A) underwent craniotomy for hematoma evacuation and 17 (Group B) received mannitol for sustained intracranial hypertension (intracranial pressure > 20 mm Hg, > 10 minutes). Radiographic evidence of delayed cerebral infarction was observed in 14 patients. Overall, 17 patients died or were severely disabled. Cerebral AVDO2 was elevated before craniotomy or mannitol administration; the mean AVDO2 for all patients before treatment was 8.6 ± 1.8 vol%. Following craniotomy or mannitol administration, the AVDO2 decreased in 27 patients and increased in five patients (mean AVDO2 6.2 ± 2.1 vol% in all patients; 6 ± 1.9 vol% in Group A; and 6.4 ± 2.4 vol% in Group B). The mean CPP was 75 ± 9.8 mm Hg and no relationship with AVDO2 was demonstrated. Before treatment, the AVDO2 was not associated with delayed cerebral infarction or outcome. By contrast, a limited improvement in elevated AVDO2 after craniotomy or mannitol administration was significantly associated with delayed cerebral infarction (Group A: p < 0.001; Group B: p < 0.01). Similarly, a limited improvement in elevated AVDO2 after treatment was significantly associated with an unfavorable outcome (Group A: p < 0.01; Group B: p < 0.001). In conclusion, these findings strongly indicate that, despite adequate cerebral perfusion, limited improvement in elevated cerebral AVDO2 after treatment consisting of either craniotomy or mannitol administration may be used to help predict delayed cerebral infarction and poor outcome after traumatic brain injury.