Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group.

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches

Enhanced physical health screening for people with severe mental illness in Hong Kong: results from a one-year prospective case series study

Background People with severe mental illness have significantly poorer physical health compared to the general population; previous health screening studies conducted outside Asian countries have demonstrated the potential in addressing this issue. This case series aimed to explore the effects and utility of integrating an enhanced physical health screening programme for community dwelling patients with severe mental illness into routine clinical practice in Hong Kong. Method This study utilises a consecutive prospective case series design. The serious mental illness Health Improvement Profile (HIP) was used as a screening tool at baseline and repeated at 12 months follow-up. Results A total of 148 community-based patients with severe mental illness completed the study. At one year follow-up analysis showed a significant improvement in self-reported levels of exercise and a reduction in the numbers of patients prescribed medications for diabetes However, mean waist circumference increased at follow-up. In addition to the statistically significant results some general trends were observed, including: a lack of deterioration in most areas of cardiovascular risk; a reduction in medicines prescribed for physical health problems; and general improvements in health behaviours over the 12 month period. Conclusions The findings demonstrate that using the HIP is feasible and acceptable in Hong Kong. The results of the enhanced physical health-screening programme are promising, but require further testing using a randomised controlled trial design in order to more confidently attribute the improvements in well-being and health behaviours to the HIP. Trial registration Clinical trial registration number: ISRCTN1258247

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage

Enhanced physical health screening for people with severe mental illness in Hong Kong: results from a one-year prospective case series study

Background People with severe mental illness have significantly poorer physical health compared to the general population; previous health screening studies conducted outside Asian countries have demonstrated the potential in addressing this issue. This case series aimed to explore the effects and utility of integrating an enhanced physical health screening programme for community dwelling patients with severe mental illness into routine clinical practice in Hong Kong. Method This study utilises a consecutive prospective case series design. The serious mental illness Health Improvement Profile (HIP) was used as a screening tool at baseline and repeated at 12 months follow-up. Results A total of 148 community-based patients with severe mental illness completed the study. At one year follow-up analysis showed a significant improvement in self-reported levels of exercise and a reduction in the numbers of patients prescribed medications for diabetes However, mean waist circumference increased at follow-up. In addition to the statistically significant results some general trends were observed, including: a lack of deterioration in most areas of cardiovascular risk; a reduction in medicines prescribed for physical health problems; and general improvements in health behaviours over the 12 month period. Conclusions The findings demonstrate that using the HIP is feasible and acceptable in Hong Kong. The results of the enhanced physical health-screening programme are promising, but require further testing using a randomised controlled trial design in order to more confidently attribute the improvements in well-being and health behaviours to the HIP. Trial registration Clinical trial registration number: ISRCTN1258247

Development and application of bivariate 2D-EMD for the analysis of instantaneous flow structures and cycle-to-cycle variations of in-cylinder flow

International audienceThe bivariate two dimensional empirical mode decomposition (Bivariate 2D-EMD) is extended to estimate the turbulent fluctuations and to identify cycle-to-cycle variations (CCV) of in-cylinder flow. The Bivariate 2D-EMD is an adaptive approach that is not restricted by statistical convergence criterion, hence it can be used for analyzing the nonlinear and non-stationary phenomena. The methodology is applied to a high-speed PIV dataset that measures the velocity field within the tumble symmetry plane of an optically accessible engine. The instantaneous velocity field is decomposed into a finite number of 2D spatial modes. Based on energy considerations, the in-cylinder flow large-scale organized motion is separated from turbulent fluctuations. This study is focused on the second half of the compression stroke. For most of the cycles, the maximum of turbulent fluctuations is located between 50 and 30 crank angle degrees before top dead center (TDC). In regards to the phase-averaged velocity field, the contribution of CCV to the fluctuating kinetic energy is approximately 55% near TDC

Compensatory-reserve-weighted intracranial pressure versus intracranial pressure for outcome association in adult traumatic brain injury: a CENTER-TBI validation study

Background: Compensatory-reserve-weighted intracranial pressure (wICP) has recently been suggested as a supplementary measure of intracranial pressure (ICP) in adult traumatic brain injury (TBI), with a single-center study suggesting an association with mortality at 6 months. No multi-center studies exist to validate this relationship. The goal was to compare wICP to ICP for association with outcome in a multi-center TBI cohort. Methods: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived ICP and wICP (calculated as wICP = (1 12 RAP) 7 ICP; where RAP is the compensatory reserve index derived from the moving correlation between pulse amplitude of ICP and ICP). Various univariate logistic regression models were created comparing ICP and wICP to dichotomized outcome at 6 to 12 months, based on Glasgow Outcome Score\u2014Extended (GOSE) (alive/dead\u2014GOSE 65 2/GOSE = 1; favorable/unfavorable\u2014GOSE 5 to 8/GOSE 1 to 4, respectively). Models were compared using area under the receiver operating curves (AUC) and p values. Results: wICP displayed higher AUC compared to ICP on univariate regression for alive/dead outcome compared to mean ICP (AUC 0.712, 95% CI 0.615\u20130.810, p = 0.0002, and AUC 0.642, 95% CI 0.538\u2013746, p < 0.0001, respectively; no significant difference on Delong\u2019s test), and for favorable/unfavorable outcome (AUC 0.627, 95% CI 0.548\u20130.705, p = 0.015, and AUC 0.495, 95% CI 0.413\u20130.577, p = 0.059; significantly different using Delong\u2019s test p = 0.002), with lower wICP values associated with improved outcomes (p < 0.05 for both). These relationships on univariate analysis held true even when comparing the wICP models with those containing both ICP and RAP integrated area under the curve over time (p < 0.05 for all via Delong\u2019s test). Conclusions: Compensatory-reserve-weighted ICP displays superior outcome association for both alive/dead and favorable/unfavorable dichotomized outcomes in adult TBI, through univariate analysis. Lower wICP is associated with better global outcomes. The results of this study provide multi-center validation of those seen in a previous single-center study

Univariate comparison of performance of different cerebrovascular reactivity indices for outcome association in adult TBI: a CENTER-TBI study

Background: Monitoring cerebrovascular reactivity in adult traumatic brain injury (TBI) has been linked to global patient outcome. Three intra-cranial pressure (ICP)-derived indices have been described. It is unknown which index is superior for outcome association in TBI outside previous single-center evaluations. The goal of this study is to evaluate indices for 6- to 12-month outcome association using uniform data harvested in multiple centers. Methods: Using the prospectively collected data from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, the following indices of cerebrovascular reactivity were derived: PRx (correlation between ICP and mean arterial pressure (MAP)), PAx (correlation between pulse amplitude of ICP (AMP) and MAP), and RAC (correlation between AMP and cerebral perfusion pressure (CPP)). Univariate logistic regression models were created to assess the association between vascular reactivity indices with global dichotomized outcome at 6 to 12 months, as assessed by Glasgow Outcome Score\u2013Extended (GOSE). Models were compared via area under the receiver operating curve (AUC) and Delong\u2019s test. Results: Two separate patient groups from this cohort were assessed: the total population with available data (n = 204) and only those without decompressive craniectomy (n = 159), with identical results. PRx, PAx, and RAC perform similar in outcome association for both dichotomized outcomes, alive/dead and favorable/unfavorable, with RAC trending towards higher AUC values. There were statistically higher mean values for the index, % time above threshold, and hourly dose above threshold for each of PRx, PAx, and RAC in those patients with poor outcomes. Conclusions: PRx, PAx, and RAC appear similar in their associations with 6- to 12-month outcome in moderate/severe adult TBI, with RAC showing tendency to achieve stronger associations. Further work is required to determine the role for each of these cerebrovascular indices in monitoring of TBI patients

Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study

Background: After traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome. Methods: Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test). Results: Twenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes. Conclusions: Patients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP