Ursula K. Rohlwink

Methods of monitoring brain oxygenation

IntroductionPosttraumatic 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.DiscussionIn 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.

The relationship between intracranial pressure and brain oxygenation in children with severe traumatic brain injury.

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 Childrens 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.

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.

Standardized Methods for Enhanced Quality and Comparability of Tuberculous Meningitis Studies

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.

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

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.

Biomarkers of cerebral injury and inflammation in pediatric tuberculous meningitis.

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.

Imaging Features of the Brain, Cerebral Vessels and Spine in Pediatric Tuberculous Meningitis With Associated Hydrocephalus.

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.

Local and global challenges in pediatric traumatic brain injury outcome and rehabilitation assessment

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.

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.

Hydrocephalus Surgery in Childhood Tuberculous Meningitis with Hydrocephalus

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.