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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.

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. In this retrospective cohort study, we collected data on children ( 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. 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.

Tuberculous meningitis (TBM) is the most severe form of TB with high rates of mortality and morbidity. Here we conduct RNA-sequencing on whole blood as well as on ventricular and lumbar cerebrospinal fluid (CSF) of pediatric patients treated for TBM. Differential transcript expression of TBM cases are compared with healthy controls in whole blood and with non-TB cerebral infection controls in CSF. Whole blood RNA-Seq analysis demonstrates a distinct immune response pattern in TBM, with significant increase in both canonical and non-canonical inflammasome activation and decrease in T-cell activation. In ventricular CSF, a significant enrichment associated with neuronal excitotoxicity and cerebral damage is detected in TBM. Finally, compartmental comparison in TBM indicates that the ventricular profile represents brain injury whereas the lumbar profile represents protein translation and cytokine signaling. Together, transcriptomic analysis shows that disease processes differ between the periphery and the central nervous system, and within brain compartments., Tuberculosis meningitis (TBM) is a severe form of TB with limited treatment options. Here, the authors perform RNA sequencing on whole blood and on ventricular and lumbar cerebrospinal fluid (CSF) samples from pediatric patients treated for TBM to characterize the immune response and tissue damage.

Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury. Here we review the steps from primary infection to cerebral disease, factors that contribute to the virulence of the organism and the vulnerability of the host and discuss the immune response and the clinical manifestations arising. Priorities for future research directions are suggested. Review on how morbidity and mortality caused by tuberculous meningitis is mediated by a dysregulated immune response.

Evidence-based analgosedation in severe pediatric traumatic brain injury (pTBI) management is lacking, and improved pharmacological understanding is needed. This starts with increased knowledge of factors controlling the pharmacokinetics (PK) of unbound drug at the target site (brain) and related drug effect(s). This prospective, descriptive study tested a pediatric physiology-based pharmacokinetic software model by comparing actual plasma and brain extracellular fluid (brainECF) morphine concentrations with predicted concentration-time profiles in severe pTBI patients (Glasgow Coma Scale [GCS], ≤8). Plasma and brainECF samples were obtained after legal guardian written consent and were collected from 8 pTBI patients (75% male; median age, 96 months [34.0–155.5]; median weight, 24 kg [14.5–55.0]) with a need for intracranial pressure monitoring (GCS, ≤8) and receiving continuous morphine infusion (10–40 μg/kg/h). BrainECF samples were obtained by microdialysis. BrainECF samples were taken from “injured” and “uninjured” regions as determined by microdialysis catheter location on computed head tomography. A previously developed physiology-based software model to predict morphine concentrations in the brain was adapted to children using pediatric physiological properties. The model predicted plasma morphine concentrations well for individual patients (97% of data points within the 90% prediction interval). In addition, predicted brainECF concentration-time profiles fell within a 90% prediction interval of microdialysis brainECF drug concentrations when sampled from an uninjured area. Prediction was less accurate in injured areas. This approach of translational physiology-based PK modeling allows prediction of morphine concentration-time profiles in uninjured brain of individual patients and opens promising avenues towards evidence-based pharmacotherapies in pTBI.

Tuberculous meningitis (TBM) is the most fatal form of tuberculosis and frequently occurs in children. The inflammatory process initiates secondary brain injury processes that lead to death and disability. Much remains unknown about this cerebral inflammatory process, largely because of the difficulty in studying the brain. To date, studies have typically examined samples from sites distal to the site of disease, such as spinal cerebrospinal fluid (CSF) and blood. In this pilot study, we examined the feasibility of using direct brain microdialysis (MD) to detect inflammatory mediators in brain extracellular fluid (ECF) in TBM. MD was used to help guide neurocritical care in 7 comatose children with TBM by monitoring brain chemistry for up to 4 days. Remnant ECF fluid was stored for offline analysis. Samples of ventricular CSF, lumbar CSF and blood were collected at clinically indicated procedures for comparison. Inflammatory mediators were quantified using multiplex technology. All inflammatory markers, with the exception of interleukin (IL)-10 and IL-12p40, were detected in the ECF. Cytokine concentrations were generally lower in ECF than ventricular CSF in time-linked specimens. Individual cases showed ECF cytokine increases coinciding with marked increases in ECF glycerol or decreases in ECF glucose. Cytokine levels and glycerol were generally higher in patients with more severe disease. This is the first report of inflammatory marker analysis from samples derived directly from the brain and in high temporal resolution, demonstrating feasibility of cerebral MD to explore disease progression and possibly therapy response in TBM.

Background Tuberculous meningitis (TBM) is a medical emergency, yet there are no standardized treatment guidelines for the medical or neurosurgical management of these patients and little data on neurocritical care. We conducted an international survey to understand current medical and neurosurgical TBM management and resource availability to provide baseline data needed for future multicenter trials addressing unanswered clinical research questions and the establishment of standardized guidelines. Methods An online survey of 77 questions covering medical and neurosurgical TBM management aimed at clinicians/nurses treating TBM was distributed as an anonymous link through email invitation, international organizations’ membership distribution, and direct links on organizational webpages or social media. The survey remained open for 5 months. Data were summarized with frequencies and percentages. Results The survey had 222 responses from 43 countries representing 6 continents. Most respondents were from tertiary care facilities, with broad access to medical and neurosurgical resources. There was significant heterogeneity in general supportive care, and TBM-specific management demonstrated considerable divergence from current standard-of-care practices. The lack of standardized guidelines was identified as a major challenge in TBM management. General and neurocritical care were largely absent. Resources for bedside supportive care and noninvasive monitoring were broadly accessible. Conclusions These findings suggest that current TBM management could be improved by the establishment of internationally accepted treatment guidelines based on available evidence, and that numerous centers have resources available to participate in future multicenter trials, even for basic interventions, that may further improve patient outcomes globally., Tuberculous meningitis is a medical emergency, yet no standardized treatment guidelines exist. We surveyed treatment and resource availability from 43 countries, which demonstrated heterogeneity and divergence from standard of care. Resources for bedside supportive care and monitoring were broadly accessible.

Tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, has poorly understood immunopathology and high mortality and morbidity despite antituberculous therapy. This calls for accelerated clinical and basic science research in this field. As TBM disproportionally affects poorer communities, studies are often performed in resource-limited environments, creating challenges for data collection and harmonisation. Comparison of TBM studies has been hampered by variation in sampling strategies, study design and choice of study endpoints. Based on literature review and expert consensus, this paper provides firstly, practical recommendations to enable thorough diagnostic, pathophysiological and pharmacokinetic studies using clinical samples, and facilitates better data aggregation and comparisons across populations and settings. Secondly, we discuss clinically relevant study endpoints, including neuroimaging, functional outcome, and cause of death, with suggestions of how these could be applied in different designs for future TBM studies.

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.

Analgosedation is a fundamental part of traumatic brain injury (TBI) treatment guidelines, encompassing both first and second tier supportive strategies. Worldwide analgosedation practices continue to be heterogeneous due to the low level of evidence in treatment guidelines (level III) and the choice of analgosedative drugs is made by the treating clinician. Current practice is thus empirical and may result in unfavourable (often hemodynamic) side effects. This article presents an overview of current analgosedation practices in the paediatric intensive care unit (PICU) and addresses pitfalls both in the short and long term. We discuss innovative (pre-)clinical research that can provide the framework for initiatives to improve our pharmacological understanding of analgesic and sedative drugs used in paediatric severe TBI and ultimately facilitate steps towards evidence-based and precision pharmacotherapy in this vulnerable patient group.

Summary This viewpoint defines a tuberculous meningitis core dataset, including demographic and clinical information, key patient management and monitoring data, and standardized reporting of patient outcomes. Wide adoption of standardized methods will provide a robust evidence base to improve patient outcomes., Tuberculous meningitis (TBM) remains a major cause of death and disability in tuberculosis-endemic areas, especially in young children and immunocompromised adults. Research aimed at improving outcomes is hampered by poor standardization, which limits study comparison and the generalizability of results. We propose standardized methods for the conduct of TBM clinical research that were drafted at an international tuberculous meningitis research meeting organized by the Oxford University Clinical Research Unit in Vietnam. We propose a core dataset including demographic and clinical information to be collected at study enrollment, important aspects related to patient management and monitoring, and standardized reporting of patient outcomes. The criteria proposed for the conduct of observational and intervention TBM studies should improve the quality of future research outputs, can facilitate multicenter studies and meta-analyses of pooled data, and could provide the foundation for a global TBM data repository.

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.

Tuberculosis (TB) remains the single biggest infectious cause of death globally, claiming almost two million lives and causing disease in over 10 million individuals annually. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with various physiological roles implicated as key factors contributing to the spread of TB. They are involved in the breakdown of lung extracellular matrix and the consequent release of Mycobacterium tuberculosis bacilli into the airways. Evidence demonstrates that MMPs also play a role in central nervous system (CNS) tuberculosis, as they contribute to the breakdown of the blood brain barrier and are associated with poor outcome in adults with tuberculous meningitis (TBM). However, in pediatric TBM, data indicate that MMPs may play a role in both pathology and recovery of the developing brain. MMPs also have a significant role in HIV-TB-associated immune reconstitution inflammatory syndrome in the lungs and the brain, and their modulation offers potential novel therapeutic avenues. This is a review of recent research on MMPs in pulmonary and CNS TB in adults and children and in the context of co-infection with HIV. We summarize different methods of MMP investigation and discuss the translational implications of MMP inhibition to reduce immunopathology.

Tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, has poorly understood immunopathology and high mortality and morbidity despite antituberculous therapy. This calls for accelerated clinical and basic science research in this field. As TBM disproportionally affects poorer communities, studies are often performed in resource-limited environments, creating challenges for data collection and harmonisation. Comparison of TBM studies has been hampered by variation in sampling strategies, study design and choice of study endpoints. Based on literature review and expert consensus, this paper provides firstly, practical recommendations to enable thorough diagnostic, pathophysiological and pharmacokinetic studies using clinical samples, and facilitates better data aggregation and comparisons across populations and settings. Secondly, we discuss clinically relevant study endpoints, including neuroimaging, functional outcome, and cause of death, with suggestions of how these could be applied in different designs for future TBM studies.

Tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, has poorly understood immunopathology and high mortality and morbidity despite antituberculous therapy. This calls for accelerated clinical and basic science research in this field. As TBM disproportionally affects poorer communities, studies are often performed in resource-limited environments, creating challenges for data collection and harmonisation. Comparison of TBM studies has been hampered by variation in sampling strategies, study design and choice of study endpoints. Based on literature review and expert consensus, this paper provides firstly, practical recommendations to enable thorough diagnostic, pathophysiological and pharmacokinetic studies using clinical samples, and facilitates better data aggregation and comparisons across populations and settings. Secondly, we discuss clinically relevant study endpoints, including neuroimaging, functional outcome, and cause of death, with suggestions of how these could be applied in different designs for future TBM studies.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. Preventing secondary injury by controlling physiological parameters (e.g. intracranial pressure [ICP], cerebral perfusion pressure [CPP] and brain tissue oxygen [PbtO2]) has a potential to improve outcome. Low PbtO2 is independently associated with poor clinical outcomes in both adults and children. However, no studies have investigated associations between low PbtO2 and neuropsychological and behavioural outcomes following severe pediatric TBI (pTBI). We used a quasi-experimental case-control design to investigate these relationships. A sample of 11 TBI patients with a Glasgow Coma Scale score ≤8 who had PbtO2 and ICP monitoring at the Red Cross War Memorial Children’s Hospital underwent neuropsychological evaluation ≥1 year post-injury. Their performance was compared to that of 11 demographically matched healthy controls. We then assigned each TBI participant into one of two subgroups, (1) children who had experienced at least one episode of PbtO2 ≤ 10 mmHg or (2) children for whom PbtO2 > 10 mmHg throughout the monitoring period, and compared their results on neuropsychological evaluation. TBI participants performed significantly more poorly than controls in several cognitive domains (IQ, attention, visual memory, executive functions and expressive language) and behavioural (e.g. externalizing behaviour) domains. The PbtO2 ≤ 10 mmHg group performed significantly worse than the PbtO2 > 10 mmHg group in several cognitive domains (IQ, attention, verbal memory, executive functions and expressive language), but not on behavioural measures. Results demonstrate that low PbtO2 may be prognostic of not only mortality but also neuropsychological outcomes.

Traumatic brain injury (TBI) is a major public health problem associated with high morbidity and mortality rates in children in both high- and low- and middle-income countries. Predicting outcome after pediatric TBI is challenging given the wide range of injury and non-injury-related factors which may have an impact. Some of these factors are relevant globally (like heterogeneity in patient and injury-related factors and research methodology) and others are more specific to local contexts (like sociodemographic and cultural factors). The assessment of rehabilitation outcomes post-TBI are similarly challenging given the various methodological limitations, disparities in access to rehabilitation, and limited awareness of deficits, which are encountered globally, as well as the lack of services in the local settings. In this article, we discuss these global and local challenges to outcome and rehabilitation assessment following pediatric TBI.

Summary Neurospecific biomarkers were elevated in pediatric tuberculous meningitis and showed an increasing temporal profile in patients who died, whereas markers of inflammation decreased in all patients regardless of outcome. Secondary injury mechanisms initiated by inflammation likely cause ongoing brain damage., 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.

Tuberculous (TB) hydrocephalus is in many ways unique among the various causes of hydrocephalus. It is an ancient infection that has plagued patients and their clinicians for millennia. Yet in the twenty-first century, mortality still remains high, survivors are often left with significant disabilities, and the management of TB hydrocephalus remains nonstandardized across the world. Each center has its own preference for interventions that range from medical treatment, temporary ventricular drainage, endoscopy, shunt surgery, and various combinations of each. Similarly, the patient selection criteria for each of these interventions are variably applied. In this chapter we discuss the key pathophysiological aspects of the disease and how these may influence the way we select the best way to treat our patients from the various protocols described.

Background Pediatric tuberculous meningitis (TBM) leads to high rates of mortality and morbidity. Prompt diagnosis and initiation of treatment are challenging; imaging findings play a key role in establishing the presumptive diagnosis. General brain imaging findings are well reported; however, specific data on cerebral vascular and spinal involvement in children are sparse. Methods This prospective cohort study examined admission and followed up computed tomography brain scans and magnetic resonance imaging scans of the brain, cerebral vessels (magnetic resonance angiogram) and spine at 3 weeks in children treated for TBM with hydrocephalus (HCP; inclusion criteria). Exclusion criteria were no HCP on admission, treatment of HCP or commencement of antituberculosis treatment before study enrollment. Imaging findings were examined in association with outcome at 6 months. Results Forty-four patients (median age 3.3 [0.3-13.1] years) with definite (54%) or probable TBM were enrolled. Good clinical outcome was reported in 72%; the mortality rate was 16%. Infarcts were reported in 66% of patients and were predictive of poor outcome. Magnetic resonance angiogram abnormalities were reported in 55% of patients. Delayed tuberculomas developed in 11% of patients (after starting treatment). Spinal pathology was more common than expected, occurring in 76% of patients. Exudate in the spinal canal increased the difficulty of lumbar puncture and correlated with high cerebrospinal fluid protein content. Conclusion TBM involves extensive pathology in the central nervous system. Severe infarction was predictive of poor outcome although this was not the case for angiographic abnormalities. Spinal disease occurs commonly and has important implications for diagnosis and treatment. Comprehensive imaging of the brain, spine and cerebral vessels adds insight into disease pathophysiology.

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.

Background. Paediatric traumatic brain injury (PTBI) is a major public health problem. However, recent epidemiological data for PTBI in South Africa (SA) are lacking. Objectives. To establish a demographic profile of severe PTBI admissions to the Red Cross War Memorial Children's Hospital (RCWMCH) over a 5-year period, by investigating trends in annual admissions, age, sex, language, time and day of injury, and aetiology. Methods. This retrospective, descriptive, quantitative study included children admitted to the RCWMCH with severe traumatic brain injury (TBI) between June 2006 and April 2011, who required intracranial monitoring. We used the Division of Paediatric Neurosurgery's TBI database to identify cases for inclusion in the study and to gather demographic and injury information. Results. Descriptive statistics suggested that: (i) the number of annual admissions did not vary substantially across the study period; (ii) the peak admission age was 6 years; (iii) more boys than girls were admitted; (iv) the major mechanism of injury was pedestrian road traffic accidents; and (v) most injuries occurred on weekends. These results are discussed against the backdrop of international research on PTBI and reflect the extent to which epidemiological findings on TBI in high-income countries compare with those from low- and middle-income countries such as SA. Conclusion. The identification of aetiological factors and the description of demographic profiles of children sustaining TBI constitutes a basis for preventative policy administration and intervention strategies in SA. Language: en

Background Intracranial pressure (ICP) monitoring is a cornerstone of care for severe traumatic brain injury (TBI). Management of ICP can help ensure adequate cerebral blood flow and oxygenation. However, studies indicate that brain hypoxia may occur despite normal ICP and the relationship between ICP and brain oxygenation is poorly defined. This is particularly important for children in whom less is known about intracranial dynamics. Objective To examine the relationship between ICP and partial pressure of brain tissue oxygen (PbtO2) in children with severe TBI (Glasgow Coma Scale score ≤ 8) admitted to Red Cross War Memorial Children's Hospital, Cape Town. Methods The relationship between time-linked hourly and high-frequency ICP and PbtO2 data was examined using correlation, regression, and generalized estimating equations. Thresholds for ICP were examined against reduced PbtO2 using age bands and receiver-operating characteristic curves. Results Analysis using more than 8300 hourly (n = 75) and 1 million high-frequency data points (n = 30) demonstrated a weak relationship between ICP and PbtO2 (r = 0.05 and r = 0.04, respectively). No critical ICP threshold for low PbtO2 was identified. Individual patients revealed a strong relationship between ICP and PbtO2 at specific times, but different relationships were evident over longer periods. Conclusion The relationship between ICP and PbtO2 appears complex, and several factors likely influence both variables separately and in combination. Although very high ICP is associated with reduced PbtO2, in general, absolute ICP has a poor relationship with PbtO2. Because reduced PbtO2 is independently associated with poor outcome, a better understanding of ICP and PbtO2 management in pediatric TBI seems to be needed.

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. 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. 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

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.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.