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Behavioral nudges in Facebook ads reached nearly 15 million people across six diverse countries and, consequently, many thousands took the step of navigating to governments' vaccine signup sites. However, none of the treatment ads caused significantly more vaccine signup intent than placebo uniformly across all countries. Critically, reporting the descriptive norm that 87% of people worldwide had either been vaccinated or planned vaccination-social proof-did not meaningfully increase vaccine signup intent in any country and significantly backfired in Taiwan. This result contradicts prominent prior findings. A charge to "protect lives in your family" significantly outperformed placebo in Taiwan and Turkey but saw null effects elsewhere. A message noting that vaccination significantly reduces hospitalization risk decreased signup intent in Brazil and had no significant effects in any other country. Such heterogeneity was the hallmark of the study: some messages saw significant treatment effects in some countries but failed in others. No nudge outperformed the placebo in Russia, a location of high vaccine skepticism. In all, widely touted behavioral nudges often failed to promote vaccine signup intent and appear to be moderated by cultural context., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

While machine coding of data has dramatically advanced in recent years, the literature raises significant concerns about validation of LLM classification showing, for example, that reliability varies greatly by prompt and temperature tuning, across subject areas and tasks-especially in "zero-shot" applications. This paper contributes to the discussion of validation in several different ways. To test the relative performance of supervised and semi-supervised algorithms when coding political data, we compare three models' performances to each other over multiple iterations for each model and to trained expert coding of data. We also examine changes in performance resulting from prompt engineering and pre-processing of source data. To ameliorate concerns regarding LLM's pre-training on test data, we assess performance by updating an existing dataset beyond what is publicly available. Overall, we find that only GPT-4 approaches trained expert coders when coding contexts familiar to human coders and codes more consistently across contexts. We conclude by discussing some benefits and drawbacks of machine coding moving forward., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Perceptions of social norms can have downstream consequences for attitudes and behaviors, especially when it comes to the acceptance of marginalized groups. While interventions focusing on social norms may boost tolerance, few studies test whether variations in norm communication affect individuals' perceptions. Thus, in this paper, we test the effectiveness of three communicative aspects-valence framing (Experiments 1-3), point of view (Experiment 1), and group centrism (Experiment 3)-in shifting perceptions of social norms. Specifically, we investigate whether manipulating these aspects affects perceptions of tolerance of lesbian and gay individuals in Slovakia, where LGBTQ+ acceptance is among the lowest in Europe. We found that while positively valenced messages shifted perceptions toward tolerance, manipulating point of view and group-centrism did not. We believe that these findings can inform interventions intended to shift perceptions of social norms in hostile contexts, an important first step in changing prejudiced attitudes and behaviors.

Objectives: Increasing PaO2 can increase brain tissue PO2 (PbtO2). Nevertheless, the small increase in arterial O2 content induced by hyperoxia does not increase O2 delivery much, especially when cerebral blood flow (CBF) is low, and the effectiveness of hyperoxia as a therapeutic intervention remains controversial. The purpose of this study was to examine the role of regional (r)CBF at the site of the PO2 probe in determining the response of PbtO2 to induced hyperoxia., Methods: The authors measured PaO2 and PbtO2 at baseline normoxic conditions and after increasing inspired O2 concentration to 100% on 111 occasions in 83 patients with severe traumatic brain injury in whom a stable xenon-enhanced computed tomography measurement of CBF was available. The O2 reactivity was calculated as the change in PbtO2 x 100/change in PaO2., Results: The O2 reactivity was significantly different (p < 0.001) at the 5 levels of rCBF (<10, 11-15, 16-20, 21-40, and > 40 ml/100 g/min). When rCBF was < 20 ml/100 g/min, the increase in PbtO2 induced by hyperoxia was very small compared with the increase that occurred when rCBF was > 20 ml/100 g/min., Conclusions: Although the level of CBF is probably only one of the factors that determines the PbtO2 response to hyperoxia, it is apparent from these results that the areas of the brain that would most likely benefit from improved oxygenation are the areas that are the least likely to have increased PbtO2.

Objective: Acute traumatic subdural hematoma complicated by brain parenchymal injury is associated with a 60 to 90% mortality rate. Early surgical evacuation of the mass lesion is essential for a favorable outcome, but the severity of the underlying brain injury determines the outcome, even when surgery has been prompt. The purpose of this study was to analyze tissue biochemical patterns in the brain underlying an evacuated acute subdural hematoma to identify a characteristic pattern of changes that might indicate evolving brain injury., Methods: Prospectively collected data from 33 patients after surgical evacuation of acute subdural hematoma were analyzed. Both a brain tissue oxygen tension probe and an intracerebral microdialysis probe were placed in brain tissue exposed at surgery. On the basis of the postoperative clinical course, the patients were divided into three groups: patients with early intractable intracranial hypertension, patients with evolution of delayed traumatic injury (DTI), and patients with an uncomplicated course (the no-DTI group)., Results: The overall mortality rate was 46%, with 100% mortality in the intracranial hypertension group (five patients). Mortality in the DTI group was 53% compared with only 9% in the no-DTI group (P = 0.002). There were no significant differences in the initial computed tomographic scan characteristics, such as thickness of the subdural hematoma or amount of midline shift, among the three groups. Physiological variables, as well as the microdialysate measures of brain biochemistry, were markedly different in the intracranial hypertension group compared with the other groups. Differences between the other two groups were more subtle but were significant. Significantly lower values of brain tissue oxygen tension (14 +/- 8 mm Hg versus 27 +/- 14 mm Hg) and higher dialysate values of lactate and pyruvate were documented in patients who developed a delayed injury compared with patients with uncomplicated courses (4.1 +/- 2.3 mmol/L versus 1.7 +/- 0.7 mmol/L for lactate, and 104 +/- 47 micromol/L versus 73 +/- 54 micromol/L for pyruvate at 24 h after injury)., Conclusion: Evolution of DTI in the area of brain underlying an evacuated subdural hematoma is associated with a significant increase in mortality. Postoperatively decreasing brain tissue oxygen tension and increasing dialysate concentrations of lactate and pyruvate in this area may warn of evolving brain injury and evoke further diagnostic and therapeutic activity.

The authors report the use of percutaneous transpedicular vertebroplasty performed using polymethylmethacrylate (PMMA) in two patients. These men (53 and 57 years old) had previously undergone open surgery and posterior instrumentation to treat myelomatous compression fractures. Both patients presented with acute back pain that manifested after minor activities. Kyphotic wedge fractures were diagnosed at T-1 in one case and at L-1 in the other. Both patients were treated at other hospitals with laminectomy and instrumented fusion; multiple myeloma was diagnosed after surgery. The patients experienced severe, recalcitrant, and progressive pain; on referral, they were found to have persistent kyphosis. Multiple myelomatous lesions of the spine were seen in one case and in the other the L-1 fracture represented the only site of disease. Percutaneous vertebroplasty was performed by injecting PMMA into the anterior third of the compressed vertebral body. Both patients experienced a 50% reduction in pain immediately after treatment; 3 months later both were walking and reported minimal back pain while undergoing treatment for multiple myeloma. Three years after surgery one patient reported no back pain and no progressive instability of the spine. Four years after surgery the other patient remains pain free, ambulatory, and with overall disease remission. Percutaneous vertebroplasty provided effective analgesia in these two patients with progressive back pain despite posterior stabilization. In both cases, the anterior column was effectively stabilized. A much larger operative intervention with its attendant risks of morbidity was avoided. In addition, subsequent aggressive medical treatment was well tolerated.

This review focuses on recent advances in the treatment of traumatic brain injury (TBI) during 2004 and 2005. Injured brain is a very heterogeneous structure, significantly evolving over time. Implementation of multimodal neuromonitoring will certainly provide more insights into pathophysiology of TBI. More studies are needed to determine how to best incorporate these new parameters into effective management protocols. Based on current literature, corticosteroids should not be indicated for the treatment of TBI. Avoidance or immediate treatment of secondary insults remains a mainstream of clinical care for patients with TBI. It seems that the therapy should focus on control of intracranial hypertension, and values of cerebral perfusion pressure around 60 mm Hg appear to correlate with favorable outcome in most patients. Hypertonic saline may become a preferred osmotherapeutic agent in severely head-injured patients, especially those with refractory intracranial hypertension. Benefit and indications for performing a decompressive craniectomy remain to be determined. Overall, individualized treatment respecting actual status of a patient's intra- and extracranial homeostasis should be the key principle of our current therapeutic approach toward severely head-injured patients.

Introduction: Dynamic testing of cerebral pressure autoregulation is more practical than static testing for critically ill patients. The process of cuff deflation is innocuous in the normal subject, but the systemic and cerebral effects of cuff deflation in severely head-injured patients have not been studied. The purposes of this study were to examine the physiological effects of cuff deflation and to study their impact on the calculation of autoregulatory index (ARI)., Method: In 24 severely head-injured patients, 388 thigh cuff deflations were analyzed. The physiological parameters were recorded before, during, and after a transient decrease in blood pressure. Autoregulation was graded by generating an ARI value from 0 to 9., Results: Mean arterial blood pressure (MAP) dropped rapidly during the first 2-3 seconds, but the nadir MAP was not reached until 8 +/- 7 seconds after the cuff deflation. MAP decreased by an average value of 19 +/- 5 mmHg. Initially the tracings for MAP and cerebral perfusion pressure (CPP) were nearly identical, but after 30 seconds, variable increases in intracranial pressure caused some differences between the MAP and CPP curves. The difference between the ARI values calculated twice using MAP as well as CPP was zero for 70% of left-sided studies and 73% for right-sided studies and less than or equal to 1 for 93% of left- and 95% of right-sided cuff deflations., Conclusion: Transient and relatively minor perturbations were detected in systemic physiology induced by dynamic testing of cerebral pressure autoregulation. Furthermore, this study confirms that the early changes in MAP and CPP after cuff deflation are nearly identical. MAP can substitute for CPP in the calculation of ARI even in the severely brain-injured patient.

Objective: Induced hypertension is commonly used to improve cerebral perfusion, but this treatment may have the deleterious side effect of raising intracranial pressure (ICP). We tested the hypothesis that dynamic pressure autoregulation testing could identify patients who might develop increased ICP during induced hypertension., Methods: Twenty-two studies were performed in 21 patients. Baseline dynamic testing of autoregulation by cuff deflation and carotid compression techniques was performed. After phenylephrine was infused to increase mean arterial pressure by 20 to 30 mm Hg, cuff deflation tests were repeated., Results: The average increase in mean arterial pressure was 32.2 +/- 16.1 mm Hg. This increase was accompanied by increased flow velocity (P < 0.001), brain tissue PO2 (P = 0.011), and regional cerebral blood flow (P = 0.008). Also, dynamic pressure autoregulation consistently improved (P = 0.015). Induced hypertension caused increased ICP (iICP) in 12 patients and a decrease in ICP (dICP) in 9. Baseline jugular venous oxygen saturation in the iICP group was 82 +/- 10% compared with 70 +/- 10% in dICP patients (P = 0.02). Baseline dynamic autoregulatory index for the cuff deflation tests (1.8 +/- 1.4) and baseline transient hyperemic response ratio for the carotid compression tests (1.11 +/- 0.07) were significantly lower in iICP patients (dICP group: autoregulatory index 3.2 +/- 1.7, P = 0.06; transient hyperemic response ratio 1.26 +/- 0.11, P = 0.009). Flow velocity increased more with the increase in blood pressure in the iICP group than in the dICP group: 19.0 +/- 6.8 cm/s versus 10.2 +/- 6.3 cm/s (P = 0.007)., Conclusion: The patients who had an increase in ICP with induced hypertension had a greater degree of impairment of autoregulation and induced hypertension resulted in a greater increase in flow velocity.

Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% to 60% of glioblastoma multiforme tumors, and the most common EGFR mutant, EGFRvIII, is expressed in 24% to 67% of cases. We sought to determine whether glioblastoma multiforme expression of either overexpressed wild-type EGFR or the mutant EGFRvIII is an independent predictor of overall patient survival., Experimental Design: Glioblastoma multiforme patients (n = 196) underwent a > or =95% volumetric tumor resection followed by conformal radiation. Their EGFR and EGFRvIII status was determined by immunohistochemistry and survival analyses were done., Results: In our study of glioblastoma multiforme patients, 46% (n = 91) failed to express EGFR, 54% (n = 105) had overexpression of the wild-type EGFR, and 31% (n = 61) also expressed the EGFRvIII. Patients within groups expressing the EGFR, EGFRvIII, or lacking EGFR expression did not differ in age, sex, Karnofsky performance scale score, extent of tumor resection, or radiation. The median overall survival times for patients with tumors having EGFR expression absent, overexpressed only, or mutant (EGFRvIII) were 0.96, 0.98, and 1.07 years, respectively. However, for patients surviving > or =1 year, these values were 2.03, 2.02, and 1.21 years (P < 0.0001; log-rank test comparing EGFRvIII with all others). This effect remained significant in the multivariate analysis after adjustment for all other cofactors including age and Karnofsky performance scale score (rate ratio 4.34; 95% confidence interval, 2.21-8.51)., Conclusions: Neither the overexpressed wild-type EGFR nor EGFRvIII was an independent predictor of median overall survival in this selected cohort of patients who underwent extensive tumor resection. However, in patients surviving > or =1 year, the expression of EGFRvIII was an independent negative prognostic indicator.

Objective and Importance: Delineation of cerebral white matter tracts using MR tractography adds essential information for planning intracranial surgery. Integrating tractography with intraoperative neuronavigation may reduce the likelihood of new neurological deficits after surgery done to remove tumors adjacent to the projection fibers of eloquent cortex. We report the utility of such integration for the resection of deep (paraventricular) tumors., Clinical Presentation: A 67-year-old male with malignant melanoma underwent stereotactic radiosurgery for a single metastasis within the paraventricular white matter of the right frontal lobe near the corticospinal tract. The lesion doubled in size within 12 months of radiotherapy. Surgical extirpation was performed aided by intraoperative neuronavigation., Technique: MR images of the brain including MR tractography and post-contrast T1-weighted sequences were acquired and imported into a neuronavigational workstation. Asymmetric fusion of contrast-enhanced images and tractography was employed to assist in preservation of the integrity of critical white matter tracts during the surgical procedure., Conclusion: Inclusion of tractography in standard imaging protocols for neuronavigational systems may increase the safety of neurosurgical intervention near white matter tracts, including deep areas adjacent to the ventricles., (2005 S. Karger AG, Basel.)

Objective: Acute traumatic subdural hematoma complicated by brain parenchymal injury is associated with a 60 to 90% mortality rate. Early surgical evacuation of the mass lesion is essential for a favorable outcome, but the severity of the underlying brain injury determines the outcome, even when surgery has been prompt. The purpose of this study was to analyze tissue biochemical patterns in the brain underlying an evacuated acute subdural hematoma to identify a characteristic pattern of changes that might indicate evolving brain injury., Methods: Prospectively collected data from 33 patients after surgical evacuation of acute subdural hematoma were analyzed. Both a brain tissue oxygen tension probe and an intracerebral microdialysis probe were placed in brain tissue exposed at surgery. On the basis of the postoperative clinical course, the patients were divided into three groups: patients with early intractable intracranial hypertension, patients with evolution of delayed traumatic injury (DTI), and patients with an uncomplicated course (the no-DTI group)., Results: The overall mortality rate was 46%, with 100% mortality in the intracranial hypertension group (five patients). Mortality in the DTI group was 53% compared with only 9% in the no-DTI group (P = 0.002). There were no significant differences in the initial computed tomographic scan characteristics, such as thickness of the subdural hematoma or amount of midline shift, among the three groups. Physiological variables, as well as the microdialysate measures of brain biochemistry, were markedly different in the intracranial hypertension group compared with the other groups. Differences between the other two groups were more subtle but were significant. Significantly lower values of brain tissue oxygen tension (14 +/- 8 mm Hg versus 27 +/- 14 mm Hg) and higher dialysate values of lactate and pyruvate were documented in patients who developed a delayed injury compared with patients with uncomplicated courses (4.1 +/- 2.3 mmol/L versus 1.7 +/- 0.7 mmol/L for lactate, and 104 +/- 47 micromol/L versus 73 +/- 54 micromol/L for pyruvate at 24 h after injury)., Conclusion: Evolution of DTI in the area of brain underlying an evacuated subdural hematoma is associated with a significant increase in mortality. Postoperatively decreasing brain tissue oxygen tension and increasing dialysate concentrations of lactate and pyruvate in this area may warn of evolving brain injury and evoke further diagnostic and therapeutic activity.

Background: Carcinoid tumors rarely metastasize to the brain. The objectives of the current study were to assess the frequency of brain metastasis from carcinoid tumors, determine correlates of survival, and describe treatment modalities and their outcomes., Methods: Between January 1977 and December 2003, 1633 patients with a carcinoid tumor were registered at The University of Texas M. D. Anderson Cancer Center. Of those, 24 patients (1.5%) had a diagnosis of brain metastasis. The authors collected demographic and clinical data and performed a statistical analysis., Results: The median age at the time patients were diagnosed with brain metastasis was 60 years. The metastases were treated with whole-brain radiotherapy (WBRT) alone in 7 patients (29%), and 12 patients (50%) underwent surgical resection, 7 of whom (29%) also received WBRT. The median survival time for the entire cohort after diagnosis of the primary tumor was 2.3 years (95% confidence interval [CI], 0.5-4.1 years), and the median survival time after the diagnosis of brain metastasis was 10.0 months (95% CI, 4.0-16.0 months). The longest median survival observed after the diagnosis of brain metastasis (3.2 years) occurred in patients who underwent resection and received WBRT. In the multivariate analysis, the adjusted rate ratio for comparison of all treatments versus combination of neurosurgical intervention and WBRT was 5.7 (95% CI, 1.3-26.1; P = 0.024). A positive effect of surgery followed by WBRT on the duration of survival was detected in patients with a single metastasis (P = 0.084) as well as in those with multiple metastases (P = 0.018)., Conclusions: Prolonged survival was observed in patients < 65 years old as well as in those who underwent surgery and received WBRT in comparison with other treatments. Whenever feasible, neurosurgical resection followed by WBRT seems to be the indicated treatment in patients with brain metastases from carcinoid tumors., ((c) 2004 American Cancer Society)

The purpose of this study was to compare the effects of L-arginine and tetrahydrobiopterin administration on post-traumatic cerebral blood flow (CBF) and tissue levels of NO in injured brain tissue. Rats were anesthetized with isoflurane. Mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations were measured prior to, and for 2 h after a controlled cortical impact injury. L-arginine, 300 mg/kg, tetrahydrobiopterin, 10 mg/kg, or equal volume of saline was given at 5 min after injury. In the saline-treated animals, LDF decreased to 34 +/- 4% of baseline values after injury. NO concentration also decreased by approximately 20 pmol/ml from baseline values. L-arginine and tetrahydrobiopterin administration both resulted in a significant preservation of tissue NO concentrations and an improvement in LDF, compared to control animals given saline. These studies demonstrate that tetrahydrobiopterin administration has a beneficial effect on cerebral blood flow that is similar to L-arginine administration, and may suggest that depletion of tetrahydrobiopterin plays a role in the post-traumatic hypoperfusion of the brain.

The purpose of this study was to examine the patterns of change in microdialysate concentrations of glucose, lactate, pyruvate, and glutamate in the brain during periods of hypoxia/ischemia identified by monitoring brain tissue pO2 (PbtO2). Of particular interest was a better understanding of what additional information could be obtained by the microdialysis parameters that was not available from the PbtO2. Fifty-seven patients admitted with severe traumatic brain injury who had placement of both a brain tissue pO2 (PbtO2) and microdialysis probe were studied. The microdialysis probe was perfused with Ringer's solution at 0.3 microL/min and dialysate was collected at 1-h intervals. The concentration of glucose, pyruvate, lactate, and glutamate were measured in each dialysate sample. Changes in the microdialysis parameters were examined during episodes where the PbtO2 decreased to below 10 mm Hg. Ten episodes of tissue hypoxia/ischemia identified by a decrease in PbtO2 below 10 mm Hg were observed during the period of monitoring. The concentration of the dialysate glucose closely followed the PbtO2. The dialysate pyruvate concentration was more variable and in some patients transiently increased as the PbtO2 dropped below 10 mm Hg. The dialysate concentration of lactate was significantly increased as the PbtO2 decreased to less than 10 mm Hg. Dialysate glutamate was significantly elevated only when PbtO2 decreased to very low levels. Although changes in the PbtO2 provided the earliest sign of hypoxia/ischemia, the microdialysis assays provided additional information about the consequences that the reduced tissue pO2 has on brain metabolism, which may be helpful in managing these critically ill patients.

Nitric oxide (NO) is a gaseous chemical messenger which has functions in the brain in a variety of broad physiological processes, including control of cerebral blood flow, interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, and release of neurotransmitters. As might be expected from the numerous and complex roles that NO normally has, it can have both beneficial and detrimental effects in disease states, including traumatic brain injury. There are two periods of time after injury when NO accumulates in the brain, immediately after injury and then again several hours-days later. The initial immediate peak in NO after injury is probably due to the activity of endothelial NOS and neuronal NOS. Pre-injury treatment with 7-nitroindazole, which probably inhibits this immediate increase in NO by neuronal NOS, is effective in improving neurological outcome in some models of traumatic brain injury (TBI). After the initial peak in NO, there can be a period of relative deficiency in NO. This period of low NO levels is associated with a low cerebral blood flow (CBF). Administration of L-arginine at this early time improves CBF, and outcome in many models. The late peak in NO after traumatic injury is probably due primarily to the activity of inducible NOS. Inhibition of inducible NOS has neuroprotective effects in most models.

Background: It is controversial whether a low cerebral blood flow (CBF) simply reflects the severity of injury or whether ischemia contributes to the brain's injury. It is also not clear whether posttraumatic cerebral hypoperfusion results from intracranial hypertension or from pathologic changes of the cerebral vasculature. The answers to these questions have important implications for whether and how to treat a low CBF., Methods: We performed a retrospective analysis of 77 patients with severe traumatic brain injury who had measurement of CBF within 12 hours of injury. CBF was measured using xenon-enhanced computed tomography (XeCT). Global CBF, physiological parameters at the time of XeCT, and outcome measures were analyzed., Results: Average global CBF for the 77 patients was 36+/-16 mL/100 g/minutes. Nine patients had an average global CBF<18 (average 12+/-5). The remaining 68 patients had a global CBF of 39+/-15. The initial ICP was >20 mmHg in 90% and >30 mmHg in 80% of patients in the group with CBF<18, compared to 33% and 16%, respectively, in the patients with CBF>or=18. Mortality was 90% at 6 months postinjury in patients with CBF<18. Mortality in the patients with CBF>18 was 19% at 6 months after injury., Conclusion: In patients with CBF<18 mL/100 g/minutes, intracranial hypertension plays a major causative role in the reduction in CBF. Treatment would most likely be directed at controlling intracranial pressure, but the early, severe intracranial hypertension also probably indicates a severe brain injury. For levels of CBF between 18 and 40 mL/100 g/minutes, the presence of regional hypoperfusion was a more important factor in reducing the average CBF.

Traumatic brain injury causes a reduction in cerebral blood flow, which may cause additional damage to the brain. The purpose of this study was to examine the role of nitric oxide produced by endothelial nitric oxide synthase (eNOS) in these vascular effects of trauma. To accomplish this, cerebral hemodynamics were monitored in mice deficient in eNOS and wild-type control mice that underwent lateral controlled cortical impact injury followed by administration of either L-arginine, 300 mg/kg, or saline at 5 min after the impact injury. The eNOS deficient mice had a greater reduction in laser Doppler flow (LDF) in the contused brain tissue at the impact site after injury, despite maintaining a higher blood pressure. L-Arginine administration increased LDF post-injury only in the wild-type mice. L-Arginine administration also resulted in a reduction in contusion volume, from 2.4 +/- 1.5 to 1.1 +/- 1.2 mm(3) in wild-type mice. Contusion volume in the eNOS deficient mice was not significantly altered by L-arginine administration. These differences in cerebral hemodynamics between the eNOS-deficient and the wild-type mice suggest an important role for nitric oxide produced by eNOS in the preservation of cerebral blood flow in contused brain following traumatic injury, and in the improvement in cerebral blood flow with L-arginine administration.

Nitric oxide (NO) has important regulatory functions within the central nervous system. NO is oxidized in vivo to nitrate and nitrite (NO(x)). Measurement of these products gives an index of NO production. The purpose of this study was to examine the relation between the brain extracellular concentration of NO metabolites and cerebral blood flow (CBF) after severe traumatic brain injury. Using a chemiluminescence method, NO(x) concentrations were measured in 6,701 microdialysate samples obtained from 60 patients during the first 5 d after severe head injury. Regional and global values of CBF obtained by xenon-enhanced computed tomography were used for analyses. Dialysate NO(x) values were the highest within the first 24 h after brain trauma and gradually decreased over the 5 postinjury d (time effect, P < 0.001). Mean dialysate concentration of NO(x) was 15.5 +/- 17.6 micromol/L (minimum 0.3, maximum 461 micromol/L) and 65% of samples were between 5 and 20 micromol/L. There was a significant relation between regional CBF and dialysate NO(x) levels (r2 = 0.316, P < 0.001). Dialysate NO(x) levels (9.5 +/- 2.2 micromol/L) in patients with critical reduction of regional CBF (<18 mL. 100 g-1. min-1) were significantly lower than in patients with normal CBF (18.6 +/- 8.1 micromol/L; P < 0.001). This relation between the dialysate concentration of NO(x) and regional CBF suggests some role for NO in the abnormalities of CBF that occur after traumatic brain injury.

Arterial hypotension and intracranial hypertension are detrimental to the injured brain. Although artificial elevation of cerebral perfusion pressure (CPP) has been advocated as a means to maintain an adequate cerebral blood flow (CBF), the optimal CPP for the treatment of severe traumatic brain injury (TBI) remains unclear. In addition, CBF evolves significantly over time after TBI, and CBF may vary considerably in patient to patient. For these reasons, a more useful approach may be to consider the optimal CPP in an individual patient at any given time, rather than having an arbitrary goal applied uniformly to all patients. Important information for optimizing CBF is provided by monitoring intracranial pressure in combination with assessment of the adequacy of CBF by using global indicators (for example, jugular oximetry), supplemented when appropriate by local data, such as brain tissue oxygen tension.

Objective: Hypodense lesions identified on computed tomographic (CT) scans are often assumed to indicate ischemia. The purpose of this study was to investigate regional cerebral blood flow (rCBF) in hypodense areas of the brain after severe traumatic brain injury., Methods: CBF was measured by stable xenon-enhanced CT scans. Hypodense areas were identified, and rCBF values as well as CT density were averaged for the region., Results: Thirty (60%) of the 50 patients had a total of 45 hypodense regions, which were associated with either contusion (n = 30) or areas of infarction (n = 15). rCBF in the hypodense regions was variable, ranging from a low of 3.3 to a high of 72.5 ml/100 g/min. The cause of the lesion was the major factor associated with the level of rCBF. Although the average decrease in CT density was similar for the two types of lesions, the average rCBF was significantly lower and the difference in rCBF between the lesion and the contralateral side was greater when the hypodense lesion was associated with a contusion. A critical reduction in rCBF (<20 ml/100 g/min) was found in 19 (63%) of the hypodense regions associated with contusions but in only 4 (27%) of those from areas of infarction., Conclusion: Hypodensity on plain CT scans does not always indicate reduction in CBF. This association was found more commonly when the low-density area was associated with a contusion. In hypodense areas associated with infarction, rCBF was variable and not commonly in the ischemic range at the time the CBF measurement was obtained.

Object: The purpose of this study was to evaluate the extent and timing of impairment of cerebral pressure autoregulation after severe head injury., Methods: In a prospective study of 122 patients with severe head trauma (median Glasgow Coma Scale Score 6), dynamic tests of pressure autoregulation were performed every 12 hours during the first 5 days postinjury and daily during the next 5 days. The autoregulatory index ([ARI] normal value 5 +/- 1.1) was calculated for each test. The changes in the ARI over time were examined and compared with other physiological variables. The ARI averaged 2.8 +/- 1.9 during the first 12 hours postinjury, and continued to decrease to a nadir of 1.7 +/- 1.1 at 36 to 48 hours postinjury. At this nadir, in 87% of the patients the value was less than 2.8. This continued deterioration in the ARI during the first 36 to 48 hours postinjury occurred despite an increase in cerebral blood flow ([CBF], p < 0.05) and in middle cerebral artery blood flow velocity ([BFV], p < 0.001), and could not be explained by changes in cerebral perfusion pressure, end-tidal CO2, or cerebral metabolic rate of O2. A marked decrease in cerebrovascular resistance ([CVR], p < 0.001) accompanied this deterioration in the ARI. Patients with a relatively higher BFV on Day 1 had a lower CVR (p < 0.05) and more impaired pressure autoregulation than those with a lower BFV., Conclusions: The inability of cerebral vessels to regulate CBF normally may play a role in the vulnerability of the injured brain to secondary ischemic insults. These studies indicate that this vulnerability continues and even increases beyond the first 24 hours postinjury. Local factors affecting cerebrovascular tone may be responsible for these findings.

Purpose of Review: This review describes recent advances in multimodal neuromonitoring of patients following severe head injury during the period from 2001 to 2002., Recent Findings: Monitoring intracranial pressure is considered a standard part of therapy despite a lack of randomized studies comparing patients with and without intracranial pressure monitoring. Jugular oximetry and brain tissue oxygen pressure monitoring are being used more frequently as part of a treatment protocol. Intracerebral microdialysis, despite the widespread use as a research tool, still cannot be considered a standard in clinical monitoring. These new monitoring devices may provide useful insight into the evolution of brain injury., Summary: Technology is rapidly changing the nature of neuromonitoring. New devices are becoming available which make the monitoring truly multimodal. Studies are needed to determine how to best incorporate these new parameters into effective management protocols.

The management of cerebral perfusion pressure is among the most controversial treatment issues. Cerebral perfusion pressure (CPP) is normally expressed as the difference between mean arterial blood pressure and intracranial pressure and has two important physiological roles in the patient with severe head injury. First, CPP represents the pressure gradient acting across the cerebrovascular bed and hence is an important factor in the regulation of cerebral blood flow. Second, CPP contributes to the hydrostatic pressure within the intracerebral vessels, and therefore is one of the factors that determines edema formation in the injured brain. The border between adequate and inadequate CPP should be assessed individually and continuously, as it may fluctuate in time. The treatment plan that includes rapid identification of intracranial hemorrhage, rapid evacuation of extra-axial blood, treatment of intracranial hypertension, and promotion of cerebral and systemic perfusion is likely to provide the best outcome for all patients.

The disturbance of normal mechanisms of oxygen delivery and metabolism is a hallmark of severe traumatic brain injury (TBI). In the past, investigations into the status of cerebral oxygen metabolism depended on changes in the differences in oxygen content between arterial and jugular venous blood. The development of jugular venous oximetry permitted continuous monitoring of jugular venous oxygen saturation, thereby overcoming earlier limitations caused by intermittent sampling. Neuromonitoring techniques that utilize only jugular vein sampling provide information only about global cerebral metabolism, but direct measurement of brain tissue oxygen tension via intraparenchymal probes makes possible the assessment of regional cerebral oxygen metabolism. Regional and global neuromonitoring techniques are not competitive or mutually exclusive. Rather, they are best regarded as complementary, with each providing valuable information that has a direct bearing on patient outcomes. The authors review the currently available techniques used in the monitoring of cerebral oxidative metabolism in patients who have sustained severe TBI.