Cerebrovascular Pressure Reactivity Has a Strong and Independent Association With Outcome in Children With Severe Traumatic Brain Injury.

OBJECTIVES: To examine cerebrovascular pressure reactivity index (PRx) in a large cohort of children with severe traumatic brain injury (sTBI) in association with physiologic variables and outcome. DESIGN: Retrospective observational cohort study. SETTING: Red Cross War Memorial Children's Hospital in Cape Town, South Africa. PATIENTS: Pediatric (≤ 14 yr old) sTBI patients with intracranial pressure (ICP) monitoring (postresuscitation Glasgow Coma Score [Glasgow Coma Scale (GCS)] of ≤ 8). MEASUREMENTS AND MAIN RESULTS: Data were analyzed from ICM+ files sampled at 100Hz. PRx (a mathematical indicator of pressure reactivity) was calculated as a moving correlation coefficient between ICP and mean arterial pressure (MAP) as previously described. Associations between PRx, age, GCS, ICP, MAP, and cerebral perfusion pressure (CPP) were examined with summary measures and correlation analysis using high-frequency data. Associations between PRx and mortality/outcome were examined with multivariable logistic regression analysis and the prognostic ability of PRx with receiver operating characteristic (ROCs) curves. The dataset included over 1.7 million minutes (28,634 hr) of MAP and ICP data in 196 children. The series mortality was 10.7% (21/196), and unfavorable outcome 29.6% (58/196). PRx had a moderate positive correlation with ICP ( r = 0.44; p < 0.001), a moderate negative correlation with CPP ( r = -0.43; p < 0.001), and a weak negative correlation with MAP ( r = -0.21; p = 0.004). PRx was consistently higher in patients with poor outcome and had a strong, independent association with mortality (ROC area under the curve = 0.91). A PRx threshold of 0.25 showed the best predictive ability for mortality. CONCLUSIONS: This is the largest cohort of children with PRx analysis of cerebrovascular reactivity to date. PRx had a strong association with outcome that was independent of ICP, CPP, GCS, and age. The data suggest that impaired autoregulation is an independent factor associated with poor outcome and may be useful in directing clinical care.

Brain interstitial glycerol correlates with evolving brain injury in paediatric traumatic brain injury.

PURPOSE: A better understanding of the complex pathophysiology of traumatic brain injury (TBI) is needed to improve our current therapies. Cerebral microdialysis (CMD) is an advanced method to monitor the brain, but little is known about its parameters in children. Brain glycerol, one of the CMD variables, is an essential component of the phospholipid bilayer cell membrane and is considered a useful marker of tissue hypoxia in adults. This study examined the time course of glycerol and its associations in paediatric TBI. METHODS: In this retrospective cohort study, we collected data on children (< 13years) with severe TBI who underwent CMD monitoring. The relationship of glycerol was examined with respect to physiological, radiological variables, and clinical outcome. RESULTS: Twenty-eight children underwent CMD monitoring and had evaluable data. Lesion progression on head computed tomography (CT) demonstrated a strong relationship with glycerol (median glycerol, maximum and initial-to-maximum) when lesion size increased by > 30% (p=0.01, p=0.04 and p=0.004). Absolute glycerol values had a weak but statistically significant association with intracranial pressure and brain oxygenation. We did not find an association with clinical outcome. CONCLUSION: This is the first study to provide data on brain interstitial glycerol in children. CMD glycerol, particularly an increase from baseline, is associated with other markers of injury and with a significant increase in lesion size on repeat head CT. As such, it may represent a useful monitorable marker for evolving injury in paediatric TBI.

Biomarkers of Cerebral Injury and Inflammation in Pediatric Tuberculous Meningitis.

Background: Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neurospecific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods: Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analyzed for the neuromarkers S100B, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), in addition to multiple inflammatory markers. Results were compared with 2 control groups: patients with (1) a fatty filum (abnormal filum terminale of the spinal cord); and (2) pulmonary tuberculosis (PTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results: Data were collected from 44 patients with TBM (cases; median age, 3.3 [min-max 0.3-13.1] years), 11 fatty filum controls (median age, 2.8 [min-max 0.8-8] years) and 9 PTB controls (median age, 3.7 [min-max 1.3-11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE, and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated interleukin (IL) 12p40, interferon-inducible protein 10, and monocyte chemoattractant protein 1 concentrations, whereas infarcts were associated with elevated tumor necrosis factor α, macrophage inflammatory protein 1α, IL-6, and IL-8. Conclusions: CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.

Targeted treatment in severe traumatic brain injury in the age of precision medicine.

In recent years, much progress has been made in our understanding of traumatic brain injury (TBI). Clinical outcomes have progressively improved, but evidence-based guidelines for how we manage patients remain surprisingly weak. The problem is that the many interventions and strategies that have been investigated in randomized controlled trials have all disappointed. These include many concepts that had become standard care in TBI. And that is just for adult TBI; in children, the situation is even worse. Not only is pediatric care more difficult than adult care because physiological norms change with age, but also there is less evidence for clinical practice. In this article, we discuss the heterogeneity inherent in TBI and why so many clinical trials have failed. We submit that a key goal for the future is to appreciate important clinical differences between patients in their pathophysiology and their responses to treatment. The challenge that faces us is how to rationally apply therapies based on the specific needs of an individual patient. In doing so, we may be able to apply the principles of precision medicine approaches to the patients we treat.

Clinical characteristics and neurodevelopmental outcomes of children with tuberculous meningitis and hydrocephalus.

AIM: Tuberculous meningitis (TBM) is a lethal and commonly occurring form of extra-pulmonary tuberculosis in children, often complicated by hydrocephalus which worsens outcome. Despite high mortality and morbidity, little data on the impact on neurodevelopment exists. We examined the clinical characteristics, and clinical and neurodevelopmental outcomes of TBM and hydrocephalus. METHOD: Demographic and clinical data (laboratory and radiological findings) were prospectively collected on children treated for probable and definite TBM with hydrocephalus. At 6 months, clinical outcome was assessed using the Paediatric Cerebral Performance Category Scale and neurodevelopmental outcome was assessed with the Griffiths Mental Development Scale - Extended Version. RESULTS: Forty-four patients (median age 3y 3mo, range 3mo-13y 1mo, [SD 3y 5mo]) were enrolled. The mortality rate was 16%, three patients (6.8%) were in a persistent vegetative state, two were severely disabled (4.5%), and 11 (25%) suffered mild-moderate disability. All cases demonstrated neurodevelopmental deficits relative to controls. Multiple or large infarcts were prognostic of poor outcome. INTERPRETATION: Neurological and neurodevelopmental deficits are common after paediatric TBM with hydrocephalus, and appear to be related to ongoing cerebral ischaemia and consequent infarction. The impact of TBM on these children is multidimensional and presents short- and long-term challenges.

Change in optic nerve sheath diameter as a radiological marker of outcome from endoscopic third ventriculostomy in children.

PURPOSE: The purpose of this study was to investigate the value of the change in optic nerve sheath diameter (ONSD) as a radiological marker of endoscopic third ventriculostomy (ETV) outcome in children. METHODS: Magnetic resonance imaging (MRI) scans of patients on whom ETVs were performed between the periods of January 2009 and June 2013 were reviewed. ONSD measurements on pre- and post-operative images were performed by two blinded observers, and the relationship between the change in these measurements and outcome from ETV were investigated. These findings were then also compared to conventional imaging features associated with ETV outcome. RESULTS: MRI scans of 24 patients were adequate to measure the ONSD pre- and post-operatively. In patients with successful ETV (n = 19), the mean change in ONSD was 0.73 mm and in patients with a failed ETV (n = 5), the mean change in ONSD was 0.18 mm (p = 0.0007). A change in ONSD of 7.5 % of the initial measurement demonstrated a sensitivity of 92.9 % and a sensitivity of 85.7 % for ETV outcome (area under the receiver operating characteristic curve (AUROC) = 0.96). CONCLUSION: Change in ONSD is a useful radiological marker of ETV outcome and may be used in combination with conventional radiological parameters to aid decision-making in this difficult group of patients.

Biomarkers of brain injury in cerebral infections.

BACKGROUND: Central nervous system (CNS) infections present a major burden of disease worldwide and are associated with high rates of mortality and morbidity. Swift diagnosis and initiation of appropriate treatment are vital to minimize the risk of poor outcome; however, tools are lacking to accurately diagnose infection, assess injury severity, and predict outcome. Biomarkers of structural neurological injury could provide valuable information in addressing some of these challenges. CONTENT: In this review, we summarize experimental and clinical research on biomarkers of neurological injury in a range of CNS infectious diseases. Data suggest that in both adults and children, the biomarkers S100B and neuron-specific enlose (NSE), among others, can provide insight into the pathophysiology of CNS infection and injury severity, evolution, and response to treatment. Research into the added utility of combining a panel of biomarkers and in assessing biomarker association with clinical and radiological outcomes warrants further work. Various factors, including age, the establishment of normative values, and comparison of biomarker concentrations across different testing platforms still present challenges in biomarker application. SUMMARY: Research regarding the value of biomarkers in CNS infections is still in its infancy. However, early evidence supports their utility in diagnosis and prognosis, and potentially as effective surrogate end points in the assessment of novel interventions.

Metabolite transport across central nervous system barriers.

Metabolomic analysis of cerebrospinal fluid (CSF) is used to improve diagnostics and pathophysiological understanding of neurological diseases. Alterations in CSF metabolite levels can partly be attributed to changes in brain metabolism, but relevant transport processes influencing CSF metabolite concentrations should be considered. The entry of molecules including metabolites into the central nervous system (CNS), is tightly controlled by the blood-brain, blood-CSF, and blood-spinal cord barriers, where aquaporins and membrane-bound carrier proteins regulate influx and efflux via passive and active transport processes. This report therefore provides reference for future CSF metabolomic work, by providing a detailed summary of the current knowledge on the location and function of the involved transporters and routing of metabolites from blood to CSF and from CSF to blood.

Building consensus for the medical management of children with moderate and severe acute spinal cord injury: a modified Delphi study.

OBJECTIVE: The focus of this modified Delphi study was to investigate and build consensus regarding the medical management of children with moderate and severe acute spinal cord injury (SCI) during their initial inpatient hospitalization. This impetus for the study was based on the AANS/CNS guidelines for pediatric SCI published in 2013, which indicated that there was no consensus provided in the literature describing the medical management of pediatric patients with SCIs. METHODS: An international, multidisciplinary group of 19 physicians, including pediatric neurosurgeons, orthopedic surgeons, and intensivists, were asked to participate. The authors chose to include both complete and incomplete injuries with traumatic as well as iatrogenic etiologies (e.g., spinal deformity surgery, spinal traction, intradural spinal surgery, etc.) due to the overall low incidence of pediatric SCI, potentially similar pathophysiology, and scarce literature exploring whether different etiologies of SCI should be managed differently. An initial survey of current practices was administered, and based on the responses, a follow-up survey of potential consensus statements was distributed. Consensus was defined as ≥ 80% of participants reaching agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). A final meeting was held virtually to generate final consensus statements. RESULTS: Following the final Delphi round, 35 statements reached consensus after modification and consolidation of previous statements. Statements were categorized into the following eight sections: inpatient care unit, spinal immobilization, pharmacological management, cardiopulmonary management, venous thromboembolism prophylaxis, genitourinary management, gastrointestinal/nutritional management, and pressure ulcer prophylaxis. All participants stated that they would be willing or somewhat willing to change their practices based on consensus guidelines. CONCLUSIONS: General management strategies were similar for both iatrogenic (e.g., spinal deformity, traction, etc.) and traumatic SCIs. Steroids were recommended only for injury after intradural surgery, not after acute traumatic or iatrogenic extradural surgery. Consensus was reached that mean arterial pressure ranges are preferred for blood pressure targets following SCI, with goals between 80 and 90 mm Hg for children at least 6 years of age. Further multicenter study of steroid use following acute neuromonitoring changes was recommended.

The frequency of cerebral ischemia/hypoxia in pediatric severe traumatic brain injury.

INTRODUCTION: The frequency of adverse events, such as cerebral ischemia, following traumatic brain injury (TBI) is often debated. Point-in-time monitoring modalities provide important information, but have limited temporal resolution. PURPOSE: This study examines the frequency of an adverse event as a point prevalence at 24 and 72 h post-injury, compared with the cumulative burden measured as a frequency of the event over the full duration of monitoring. METHODS: Reduced brain tissue oxygenation (PbtO(2) < 10 mmHg) was the adverse event chosen for examination. Data from 100 consecutive children with severe TBI who received PbtO(2) monitoring were retrospectively examined, with data from 87 children found suitable for analysis. Hourly recordings were used to identify episodes of PbtO(2) less than 10 mmHg, at 24 and 72 h post-injury, and for the full duration of monitoring. RESULTS: Reduced PbtO(2) was more common early than late after injury. The point prevalence of reduced PbtO(2) at the selected time points was relatively low (10 % of patients at 24 h and no patients at the 72-h mark post-injury). The cumulative burden of these events over the full duration of monitoring was relatively high: 50 % of patients had episodes of PbtO(2) less than 10 mmHg and 88 % had PbtO(2) less than 20 mmHg. CONCLUSION: Point-in-time monitoring in a dynamic condition like TBI may underestimate the overall frequency of adverse events, like reduced PbtO(2), particularly when compared with continuous monitoring, which also has limitations, but provides a dynamic assessment over a longer time period.

The relationship between basal cisterns on CT and time-linked intracranial pressure in paediatric head injury.

PURPOSE: Although intracranial pressure (ICP) monitoring is a cornerstone of care for severe traumatic brain injury (TBI), the indications for ICP monitoring in children are unclear. Often, decisions are based on head computed tomography (CT) scan characteristics. Arguably, the patency of the basal cisterns is the most commonly used of these signs. Although raised ICP is more likely with obliterated basal cisterns, the implications of open cisterns are less clear. We examined the association between the status of perimesencephalic cisterns and time-linked ICP values in paediatric severe TBI. METHODS: ICP data linked to individual head CT scans were reviewed. Basal cisterns were classified as open or closed by blinded reviewers. For the initial CT scan, we examined ICP values for the first 6 h after monitor insertion. For follow-up scans, we examined ICP values 3 h before and after scanning. Mean ICP and any episode of ICP ≥ 20 mmHg during this period were recorded. RESULTS: Data from 104 patients were examined. Basal cisterns were patent in 51.72% of scans, effaced in 34.48% and obliterated in 13.79%. Even when cisterns were open, more than 40% of scans had at least one episode of ICP ≥ 20 mmHg, and 14% of scans had a mean ICP ≥ 20 mmHg. The specificity of open cisterns in predicting ICP < 20 mmHg was poor (57.9%). Age-related data were worse. CONCLUSION: Children with severe TBI frequently may have open basal cisterns on head CT despite increased ICP. Open cisterns should not discourage ICP monitoring.

The effect of blood transfusion on brain oxygenation in children with severe traumatic brain injury.

OBJECTIVE: The indications for blood transfusion in traumatic brain injury are controversial. In particular, little is known about the effect of blood transfusion in childhood traumatic brain injury. This study aimed to examine the influence of blood transfusion on brain tissue oxygen tension in children with severe traumatic brain injury. DESIGN: A retrospective analysis of a prospective observational database of children with severe traumatic brain injury who received brain tissue oxygen tension monitoring and a blood transfusion. SETTING: University-affiliated pediatric hospital. PATIENTS: Children with severe traumatic brain injury and blood transfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Brain tissue oxygen tension was measured in normal-appearing white matter with a commercially available polarographic Clarke-type electrode. Brain tissue oxygen tension values after blood transfusion were compared with pre-transfusion values in hemodynamically stable patients. Limited interventions were allowed during the studied period. Brain tissue oxygen tension values were examined for early (1-4 hrs) and late (24 hrs) changes after blood transfusion, controlling for multiple clinical and physiologic variables with regression techniques. Further comparison was made with matched non-transfused controls to examine the influence of time after injury. Nineteen blood transfusions in 17 patients were evaluated. Brain tissue oxygen tension increased significantly in the early period after blood transfusion (p = .0018; 79% increased, 21% decreased) in comparison with baseline values and matched controls, but the overall changes were small and, in part, influenced by accompanying cerebral perfusion pressure changes. Also, this effect was limited to the early period after blood transfusion and was not significant after 24 hrs. In general, the brain tissue oxygen tension increase was larger in patients with higher baseline brain tissue oxygen tension and lower initial hemoglobin; however, no factors associated with the magnitude of the brain tissue oxygen tension change were significant in multivariate analysis. Increased age of blood did not appear to impair brain tissue oxygen tension changes, but most blood transfusion were <14 days old. CONCLUSIONS: Brain tissue oxygen tension increased transiently in 79% of blood transfusion in pediatric traumatic brain injury patients, and decreased transiently in 21%. Brain tissue oxygen tension returned to baseline within 24 hrs. Reliable predictors of this brain tissue oxygen tension response to blood transfusion, however, remain elusive.

Practical aspects of bedside cerebral hemodynamics monitoring in pediatric TBI.

INTRODUCTION: Disturbances in cerebral hemodynamics may have a profound influence on secondary injury after traumatic brain injury (TBI), and many therapies in the neurocritical care unit may adversely affect cerebral blood flow. However, the clinician is often unaware of this when it occurs because practical methods for monitoring cerebral hemodynamics by the bedside have been lacking. Current imaging studies only provide a snapshot of the brain at one point in time, giving limited information about a dynamic condition. DISCUSSION: This review will focus on key pathophysiological concepts required to understand changes in cerebral hemodynamics after TBI and the principles, potential benefits, and limitations of currently available bedside monitoring techniques, including transcranial Doppler, autoregulation, and local/regional cerebral blood flow.

Methods of monitoring brain oxygenation.

INTRODUCTION: Posttraumatic brain ischemia or hypoxia is a major potential cause of secondary injury that may lead to poor outcome. Avoidance, or amelioration, of this secondary injury depends on early diagnosis and intervention before permanent injury occurs. However, tools to monitor brain oxygenation continuously in the neuro-intensive care unit have been lacking. DISCUSSION: In recent times, methods of monitoring aspects of brain oxygenation continuously by the bedside have been evaluated in several experimental and clinical series and are potentially changing the way we manage head-injured patients. These monitors have the potential to alert the clinician to possible secondary injury and enable intervention, help interpret pathophysiological changes (e.g., hyperemia causing raised intracranial pressure), monitor interventions (e.g., hyperventilation for increased intracranial pressure), and prognosticate. This review focuses on jugular venous saturation, brain tissue oxygen tension, and near-infrared spectroscopy as practical methods that may have an important role in managing patients with brain injury, with a particular focus on the available evidence in children. However, to use these monitors effectively and to understand the studies in which these monitors are employed, it is important for the clinician to appreciate the technical characteristics of each monitor, as well as respective strengths and limitations of each. It is equally important that the clinician understands relevant aspects of brain oxygen physiology and head trauma pathophysiology to enable correct interpretation of the monitored data and therefore to direct an appropriate therapeutic response that is likely to benefit, not harm, the patient.

Intracranial pressure monitoring for traumatic brain injury in the modern era.

INTRODUCTION: Intracranial pressure (ICP) has become a cornerstone of care in adult and pediatric patients with traumatic brain injury (TBI). DISCUSSION: Despite the fact that continuous monitoring of ICP in TBI was described almost 60 years ago, there are no randomized trials confirming the benefit of ICP monitoring and treatment in TBI. There is, however, a large body of clinical evidence showing that ICP monitoring influences treatment and leads to better outcomes if part of protocol-driven therapy. However, treatment of ICP has adverse effects, and there are several questions about ICP management that have yet to be definitively answered, particularly in pediatric TBI. This review examines the history and evolution of ICP monitoring, pathophysiological concepts that influence ICP interpretation, ongoing controversies, and the place of ICP monitoring in modern neurocritical care.

Clinical applications of biomarkers in pediatric traumatic brain injury.

INTRODUCTION: The diagnosis, treatment, and prediction of outcome in pediatric traumatic brain injury (TBI) present significant challenges to the treating clinician. Clinical and radiological tools for assessing injury severity and predicting outcome, in particular, lack sensitivity and specificity. In patients with mild TBI, often there is uncertainty about which patients should undergo radiological imaging and who is at risk for long term neurological sequelae. In severe TBI, often there is uncertainty about which patients will experience secondary insults and what the outcome for individual patients will be. In several other clinical specialties, biomarkers are used to diagnose disease, direct treatment, and prognosticate. However, an ideal biomarker for brain injury has not been found. METHODS: In this review, we examine the various factors that must be taken into account in the search for a reliable biomarker in brain injury. We review the important studies that have investigated common biomarkers of structural brain injury, in particular S100B, neuron-specific enolase, myelin basic protein, and glial fibrillary acid protein. DISCUSSION: The potential uses and limitations of these biomarkers in the context of TBI are discussed.

Brain tissue oxygenation in children diagnosed with brain death.

BACKGROUND: Diagnosing brain death in children is challenging. Guidelines recommend using confirmatory testing to provide ancillary information to support the diagnosis. Brain tissue oxygenation (PbtO(2)) is being increasingly used in the adult neurocritical care for continuous monitoring of the adequacy of brain oxygenation; however, data in pediatrics is limited. Evidence from adult studies suggests that persistent PbtO(2) of 0 mmHg is associated with brain death, but this relationship has not yet been demonstrated in children; therefore, we examined our experience with PbtO(2) monitoring and brain death in children with acute neurological pathology. METHODS: We retrospectively reviewed patient records from a prospectively maintained database of 85 children who were ventilated for coma due to acute neurological injury and who received intracerebral monitoring. RESULTS: We identified five children who had suffered brain death while being monitored. PbtO(2) had decreased to 0 mmHg in all five children at the time of brain death diagnosis. In contrast, PbtO(2) in patients, who did not develop brain death, never decreased to 0 mmHg. We review the benefits and drawbacks of using brain tissue oxygenation as ancillary information in diagnosing brain death in children. CONCLUSIONS: Preliminary data from this study suggest that PbtO(2) decreases to 0 mmHg when brain death occurs in children. Further study is needed to determine the limitations, and the sensitivity and specificity of this finding in a larger group of children.

The effect of increased inspired fraction of oxygen on brain tissue oxygen tension in children with severe traumatic brain injury.

BACKGROUND: This study examines the effect of an increase in the inspired fraction of oxygen (FiO2) on brain tissue oxygen (PbO2) in children with severe traumatic brain injury (TBI). METHODS: A prospective observational study of patients who underwent PbO2 monitoring and an oxygen challenge test (temporary increase of FiO2 for 15 min) was undertaken. Pre- and post-test values for arterial partial pressure of oxygen (PaO2), PbO2, and arterial oxygen content (CaO2) were examined while controlling for any changes in arterial carbon dioxide tension and cerebral perfusion pressure during the test. Baseline transcranial Doppler studies were done. Outcome was assessed at 6 months. RESULTS: A total of 43 tests were performed in 28 patients. In 35 tests in 24 patients, the PbO2 monitor was in normal-appearing white matter and in eight tests in four patients, the monitor was in a pericontusional location. When catheters were pericontusional or in normal white matter the baseline PbO2/PaO2 ratio was similar. PaO2 (P < 0.0001) and PbO2 (P < 0.0001) significantly increased when FiO2 was increased. The magnitude of the PbO2 response (PbO2) was correlated with PaO2 (P < 0.0001, R(2) = 0.37) and CaO2 (P = 0.001, R(2) = 0.23). The PbO2/PaO2 ratio (oxygen reactivity) varied between patients, was related to the baseline PbO2 (P = 0.001, r = 0.54) and was inversely related to outcome (P = 0.02, confidence interval 0.03-0.78). CONCLUSION: Normobaric hyperoxia increases PbO2 in children with severe TBI, but the response is variable. The magnitude of this response is related to the change in PaO2 and the baseline PbO2. A greater response appears to be associated with worse outcome.

Elevated Matrix Metalloproteinase Concentrations Offer Novel Insight Into Their Role in Pediatric Tuberculous Meningitis.

We collected lumbar and ventricular cerebrospinal fluid and serum from 40 children treated for tuberculous meningitis and measured the concentrations of gelatinases and their inhibitors. The concentrations of matrix metalloproteinase 9 (MMP-9), MMP-2, tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2 were significantly elevated in the lumbar CSF samples, and we found interesting dynamics for MMP-9 that offer novel insight into its role in pediatric patients with tuberculous meningitis.