Cerebrovascular Reactivity Index Research Articles

P.104 Prognostic value of NIRS regional oxygen saturation based cerebrovascular reactivity in TBI: a Canadian high resolution traumatic brain injury (CAHR-TBI) cohort study

Background: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR). This study aimed to identify threshold values of rSO2 and rSO2 based CVR at which outcomes worsened following traumatic brain injury (TBI). Methods: A retrospective multi-institutional cohort study was performed. The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. 2x2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated to identify the most discriminative significant threshold. Results: In the cohort of 129 patients rSO2 did not have any statistically significant threshold value. For COx and COx_a, an optimal threshold value of 0.2 was identified for both survival and favorable outcomes with values above this associated with worse outcomes. Conclusions: In this study, raw rSO2was found to contain no significant prognostic information. However, rSO2 based indices of CVR, were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

P.119 NIRS regional oxygen saturation based cerebrovascular reactivity in the recovery from moderate/severe TBI

Background: Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) based cerebrovascular reactivity (CVR) indicies have enable the entirely non-invasive continuous monitoring. This study aims to compare CVR in those recovering from moderate/severe TBI to a health control group. Methods: In this prospective cohort study the cerebral oxygen CVR index, COx_a (using rSO2 and arterial blood pressure), was measured in subjects with moderate/severe TBI at follow-up. COx_a was also measured in a group of healthy controls. CVR was compared within and between these groups using conventional statistics. Results: A total of 101 heathy subject were recruited for this study along with 29 TBI patients. In the health cohort COx_a was not statistically different between males and females or in the dominate and non-dominate hemisphere. The TBI cohort, COx_a was not statistically different between first and last available follow up. Surprisingly, CVR as measured by COx_a was statistically better in those recovering from TBI than in the healthy cohort. Conclusions: In the prospective cohort study, CVR as measured by NIRS based methods, was found to be more active in those recovering from TBI than in a healthy cohort. This study may indicate that, in those that survive TBI, CVR may be enhanced as a neuroprotective measure.

120 Outcome Related Thresholds of Near Infrared Spectroscopy Based Cerebrovascular Reactivity Metrics in Moderate Severe TBI: A Canadian High Resolution-TBI (CAHR-TBI) Cohort Study

INTRODUCTION: Dysfunctional cerebrovascular reactivity (CVR)/autoregulation contributes to secondary injury following traumatic brain injury (TBI). Currently, monitoring of CVR relies on intracranial pressure (ICP) monitoring and has known thresholds at which outcomes worsen. Interest has shifted to less invasive near infrared spectroscopic (NIRS) regional cerebral oxygen saturation (rSO2) based measures of CVR. However, threshold levels at which outcomes worsen have not yet been determined for these indices. METHODS: A retrospective multi-institutional cohort study utilizing the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative database was performed. The cohort included TBI patients with ICP, arterial blood pressure (ABP), and rSO2 monitoring treated in adult intensive care units (ICU). COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and ABP) were calculated for each subject as the rSO2 based indices of CVR. 2 x 2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated and the threshold producing the highest value was identified as providing the best discriminative value. RESULTS: A total of 129 patients were included. For both COx and COx_a an optimal threshold value of 0.2 was identified for both survival (χ2 = 9.57, p = 0.0020; χ2 = 13.04, p = 0.0003 respectively) and favorable outcomes (χ2 = 5.98, p = 0.0145; χ2 = 8.94, p = 0.0028 respectively) with values above this associated with worse outcomes. Notably, there was no identifiable threshold for raw rSO2 values at which outcomes were identified to worsen. CONCLUSIONS: In this multi-institutional cohort study, COx and COx_a were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Prognostic value of near-infrared spectroscopy regional oxygen saturation and cerebrovascular reactivity index in acute traumatic neural injury: a CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Cohort Study

BackgroundNear-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR) due to its noninvasive nature and high spatial resolution. However, the prognostic utility of these parameters has not yet been determined. This study aimed to identify threshold values of rSO2 and rSO2-based CVR at which outcomes worsened following traumatic brain injury (TBI).MethodsA retrospective multi-institutional cohort study was performed. The cohort included TBI patients treated in four adult intensive care units (ICU). The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. Grand mean thresholds along with exposure-based thresholds were determined utilizing sequential chi-squared analysis and univariate logistic regression, respectively.ResultsIn the cohort of 129 patients, there was no identifiable threshold for raw rSO2 at which outcomes were found to worsen. For both COx and COx_a, an optimal grand mean threshold value of 0.2 was identified for both survival and favorable outcomes, while percent time above − 0.05 was uniformly found to have the best discriminative value.ConclusionsIn this multi-institutional cohort study, raw rSO2was found to contain no significant prognostic information. However, rSO2-based indices of CVR, COx and COx_a, were found to have a uniform grand mean threshold of 0.2 and exposure-based threshold of − 0.05, above which clinical outcomes markedly worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Non-Invasive Estimation of Intracranial Pressure-Derived Cerebrovascular Reactivity Using Near-Infrared Spectroscopy Sensor Technology in Acute Neural Injury: A Time-Series Analysis.

The contemporary monitoring of cerebrovascular reactivity (CVR) relies on invasive intracranial pressure (ICP) monitoring which limits its application. Interest is shifting towards near-infrared spectroscopic regional cerebral oxygen saturation (rSO2)-based indices of CVR which are less invasive and have improved spatial resolution. This study aims to examine and model the relationship between ICP and rSO2-based indices of CVR. Through a retrospective cohort study of prospectively collected physiologic data in moderate to severe traumatic brain injury (TBI) patients, linear mixed effects modeling techniques, augmented with time-series analysis, were utilized to evaluate the ability of rSO2-based indices of CVR to model ICP-based indices. It was found that rSO2-based indices of CVR had a statistically significant linear relationship with ICP-based indices, even when the hierarchical and autocorrelative nature of the data was accounted for. This strengthens the body of literature indicating the validity of rSO2-based indices of CVR and potential greatly expands the scope of CVR monitoring.

Time spent above optimal cerebral perfusion pressure is not associated with failure to improve in outcome in traumatic brain injury

BackgroundOptimal cerebral perfusion pressure (CPPopt) has emerged as a promising personalized medicine approach to the management of moderate-to-severe traumatic brain injury (TBI). Though literature demonstrating its association with poor outcomes exists, there is yet to be work done on its association with outcome transition due to a lack of serial outcome data analysis. In this study we investigate the association between various metrics of CPPopt and failure to improve in outcome over time.MethodsCPPopt was derived using three different cerebrovascular reactivity indices; the pressure reactivity index (PRx), the pulse amplitude index (PAx), and the RAC index. For each index, % times spent with cerebral perfusion pressure (CPP) above and below its CPPopt and upper and lower limits of reactivity were calculated. Patients were dichotomized based on improvement in Glasgow Outcome Scale-Extended (GOSE) scores into Improved vs. Not Improved between 1 and 3 months, 3 and 6 months, and 1- and 6-month post-TBI. Logistic regression analyses were then conducted, adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables.ResultsThis study included a total of 103 patients from the Winnipeg Acute TBI Database. Through Mann–Whitney U testing and logistic regression analysis, it was found that % time spent with CPP below CPPopt was associated with failure to improve in outcome, while % time spent with CPP above CPPopt was generally associated with improvement in outcome.ConclusionsOur study supports the existing narrative that time spent with CPP below CPPopt results in poorer outcomes. However, it also suggests that time spent above CPPopt may not be associated with worse outcomes and is possibly even associated with improvement in outcome.

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices and Their Critical Thresholds: A Canadian High Resolution-Traumatic Brain Injury Validation Study.

Current neurointensive care guidelines recommend intracranial pressure (ICP) and cerebral perfusion pressure (CPP) centered management for moderate-severe traumatic brain injury (TBI) because of their demonstrated associations with patient outcome. Cerebrovascular reactivity metrics, such as the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC index, have also demonstrated significant prognostic capabilities with regard to outcome. However, critical thresholds for cerebrovascular reactivity indices have only been identified in two studies conducted at the same center. In this study, we aim to determine the critical thresholds of these metrics by leveraging a unique multi-center database. The study included a total of 354 patients from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative. Based on 6-month Glasgow Outcome Scores, patients were dichotomized into alive versus dead and favorable versus unfavorable. Chi-square values were then computed for incrementally increasing values of each physiological parameter of interest against outcome. The values that generated the greatest chi-squares for each parameter were considered to be the thresholds with the greatest outcome discriminatory capacity. To confirm that the identified thresholds provide prognostic utility, univariate and multivariable logistical regression analyses were performed adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Through the chi-square analysis, a lower limit CPP threshold of 60 mm Hg and ICP thresholds of 18 mm Hg and 22 mm Hg were identified for both survival and favorable outcome predictions. For the cerebrovascular reactivity metrics, different thresholds were identified for the two outcome dichotomizations. For survival prediction, thresholds of 0.35, 0.25, and 0 were identified for PRx, PAx, and RAC, respectively. For favorable outcome prediction, thresholds of 0.325, 0.20, and 0.05 were found. Univariate logistical regression analysis demonstrated that the time spent above/below thresholds were associated with outcome. Further, multivariable logistical regression analysis found that percent time above/below the identified thresholds added additional variance to the IMPACT core model for predicting both survival and favorable outcome. In this study, we were able to validate the results of the previous two works as well as to reaffirm the ICP and CPP guidelines from the Brain Trauma Foundation (BTF) and the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Statistical properties of cerebral near infrared and intracranial pressure-based cerebrovascular reactivity metrics in moderate and severe neural injury: a machine learning and time-series analysis

BackgroundCerebrovascular reactivity has been identified as a key contributor to secondary injury following traumatic brain injury (TBI). Prevalent intracranial pressure (ICP) based indices of cerebrovascular reactivity are limited by their invasive nature and poor spatial resolution. Fortunately, interest has been building around near infrared spectroscopy (NIRS) based measures of cerebrovascular reactivity that utilize regional cerebral oxygen saturation (rSO2) as a surrogate for pulsatile cerebral blood volume (CBV). In this study, the relationship between ICP- and rSO2-based indices of cerebrovascular reactivity, in a cohort of critically ill TBI patients, is explored using classical machine learning clustering techniques and multivariate time-series analysis.MethodsHigh-resolution physiologic data were collected in a cohort of adult moderate to severe TBI patients at a single quaternary care site. From this data both ICP- and rSO2-based indices of cerebrovascular reactivity were derived. Utilizing agglomerative hierarchical clustering and principal component analysis, the relationship between these indices in higher dimensional physiologic space was examined. Additionally, using vector autoregressive modeling, the response of change in ICP and rSO2 (ΔICP and ΔrSO2, respectively) to an impulse in change in arterial blood pressure (ΔABP) was also examined for similarities.ResultsA total of 83 patients with 428,775 min of unique and complete physiologic data were obtained. Through agglomerative hierarchical clustering and principal component analysis, there was higher order clustering between rSO2- and ICP-based indices, separate from other physiologic parameters. Additionally, modeled responses of ΔICP and ΔrSO2 to impulses in ΔABP were similar, indicating that ΔrSO2 may be a valid surrogate for pulsatile CBV.ConclusionsrSO2- and ICP-based indices of cerebrovascular reactivity relate to one another in higher dimensional physiologic space. ΔICP and ΔrSO2 behave similar in modeled responses to impulses in ΔABP. This work strengthens the body of evidence supporting the similarities between ICP-based and rSO2-based indices of cerebrovascular reactivity and opens the door to cerebrovascular reactivity monitoring in settings where invasive ICP monitoring is not feasible.

Understanding recovery of language after stroke: insights from neurovascular MRI studies.

Stroke causes a disruption in blood flow to the brain that can lead to profound language impairments. Understanding the mechanisms of language recovery after stroke is crucial for the prognosis and effective rehabilitation of people with aphasia. While the role of injured brain structures and disruptions in functional connectivity have been extensively explored, the relationship between neurovascular measures and language recovery in both early and later stages has not received sufficient attention in the field. Fully functioning healthy brain tissue requires oxygen and nutrients to be delivered promptly via its blood supply. Persistent decreases in blood flow after a stroke to the remaining non-lesioned tissue have been shown to contribute to poor language recovery. The goal of the current paper is to critically examine stroke studies looking at the relationship between different neurovascular measures and language deficits and mechanisms of language recovery via changes in neurovascular metrics. Measures of perfusion or cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide complementary approaches to understanding neurovascular mechanisms post stroke by capturing both cerebral metabolic demands and mechanical vascular properties. While CBF measures indicate the amount of blood delivered to a certain region and serve as a proxy for metabolic demands of that area, CVR indices reflect the ability of the vasculature to recruit blood flow in response to a shortage of oxygen, such as when one is holding their breath. Increases in CBF during recovery beyond the site of the lesion have been shown to promote language gains. Similarly, CVR changes, when collateral vessels are recruited to help reorganize the flow of blood in hypoperfused regions, have been related to functional recovery post stroke. In the current review, we highlight the main findings in the literature investigating neurovascular changes in stroke recovery with a particular emphasis on how language abilities can be affected by changes in CBF and CVR. We conclude by summarizing existing methodological challenges and knowledge gaps that need to be addressed in future work in this area, outlining a promising avenue of research.

P.118 Near infrared spectroscopy based indices of cerebrovascular reactivity cluster with intracranial pressure based indices in moderate to severe TBI patients

Background: Cerebrovascular reactivity has been identified as an important contributor to secondary injury following moderate to severe traumatic brain injury (TBI). “Gold-standard” intracranial pressure (ICP) based indies of cerebrovascular reactivity are limited by their invasive nature poor spatial resolution. Near infrared spectroscopy (NIRS) based indices of cerebrovascular reactivity are minimally invasive and have improved spatial resolution. In this study, classical machine-learning algorithms are leveraged to better characterize the relationship between these indices. Methods: High-resolution physiologic data was collected in a cohort of adult moderate to severe TBI patients. From this data both ICP and NIRS based indices of cerebrovascular reactivity were derived. Utilizing Agglomerative Hierarchical Clustering (AHC) and Principal Component Analysis, the relationship between these indices in higher dimensional physiologic space was examined. Results: A total of 83 patients with 314,395 minutes of unique and complete physiologic data was obtained. Through AHC and PCA there was higher order clustering between NIRS and ICP based indices, separate from other physiologic parameters. Conclusions: NIRS and ICP based indices of cerebrovascular reactivity relate to one another in higher dimensional physiologic space. NIRS based indices of cerebrovascular reactivity may be a viable alternative to ICP based indices.

P.119 Quantification of the relationship between near infrared spectroscopy based and intracranial pressure based indices of cerebrovascular reactivity in moderate to severe TBI

Background: Cerebrovascular reactivity is an important contributor to secondary injury following traumatic brain injury (TBI). The poor spatial resolution and invasive nature of “Gold-standard” intracranial pressure (ICP) based indies of cerebrovascular reactivity limit their use. Near infrared spectroscopy (NIRS) based indices of cerebrovascular reactivity are minimally invasive and have improved spatial resolution. The precise relationship between NIRS and ICP based indices is quantified utilizing times series analysis and advanced statistical techniques. Methods: High-resolution physiologic data was collected in a cohort of adult moderate to severe TBI patients at a single quaternary care site. From this data both ICP and NIRS based indices of cerebrovascular reactivity were derived. The times series structure of these indices was determined and used to correct for autocorrelation in a linear mixed effects model of ICP based indices from NIRS based indices of cerebrovascular reactivity. Results: A total of 83 patients were included in this study. Times series analysis coupled with mixed effects modeling was utilized to examine the relationship between ICP and NIRS based indices of cerebrovascular reactivity. Conclusions: Times series analysis coupled with mixed effects modeling allows for a more complete understanding of the relationship between ICP and NIRS based indices of cerebrovascular reactivity in the setting TBI.

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

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. Retrospective observational cohort study. Red Cross War Memorial Children's Hospital in Cape Town, South Africa. Pediatric (≤ 14 yr old) sTBI patients with intracranial pressure (ICP) monitoring (postresuscitation Glasgow Coma Score [Glasgow Coma Scale (GCS)] of ≤ 8). 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. 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.

Cerebrovascular Pressure Reactivity According to Long-Pressure Reactivity Index During Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage

BackgroundSpreading depolarization (SD) has been linked to the impairment of neurovascular coupling. However, the association between SD occurrence and cerebrovascular pressure reactivity as a surrogate of cerebral autoregulation (CA) remains unclear. Therefore, we analyzed CA using the long-pressure reactivity index (L-PRx) during SDs in patients with aneurysmal subarachnoid hemorrhage (aSAH).MethodsA retrospective study of patients with aSAH who were recruited at two centers, Heidelberg (HD) and Berlin (BE), was performed. Continuous monitoring of mean arterial pressure (MAP) and intracranial pressure (ICP) was recorded. ICP was measured using an intraparenchymal probe in HD patients and was measure in BE patients through external ventricular drainage. Electrocorticographic (ECoG) activity was continuously recorded between 3 and 13 days after hemorrhage. Autoregulation according to L-PRx was calculated as a moving linear Pearson’s correlation of 20-min averages of MAP and ICP. For every identified SD, 60-min intervals of L-PRx were averaged, plotted, and analyzed depending on SD occurrence. Random L-PRx recording periods without SDs served as the control.ResultsA total of 19 patients (HD n = 14, BE n = 5, mean age 50.4 years, 9 female patients) were monitored for a mean duration of 230.4 h (range 96–360, STD ± 69.6 h), during which ECoG recordings revealed a total number of 277 SDs. Of these, 184 represented a single SD, and 93 SDs presented in clusters. In HD patients, mean L-PRx values were 0.12 (95% confidence interval [CI] 0.11–0.13) during SDs and 0.07 (95% CI 0.06–0.08) during control periods (p < 0.001). Similarly, in BE patients, a higher L-PRx value of 0.11 (95% CI 0.11–0.12) was detected during SDs than that during control periods (0.08, 95% CI 0.07–0.09; p < 0.001). In a more detailed analysis, CA changes registered through an intraparenchymal probe (HD patients) revealed that clustered SD periods were characterized by signs of more severely impaired CA (L-PRx during SD in clusters: 0.23 [95% CI 0.20–0.25]; single SD: 0.09 [95% CI 0.08–0.10]; control periods: 0.07 [95% CI 0.06–0.08]; p < 0.001). This group also showed significant increases in ICP during SDs in clusters compared with single SD and control periods.ConclusionsNeuromonitoring for simultaneous assessment of cerebrovascular pressure reactivity using 20-min averages of MAP and ICP measured by L-PRx during SD events is feasible. SD occurrence was associated with significant increases in L-PRx values indicative of CA disturbances. An impaired CA was found during SD in clusters when using an intraparenchymal probe. This preliminary study validates the use of cerebrovascular reactivity indices to evaluate CA disturbances during SDs. Our results warrant further investigation in larger prospective patient cohorts.

The relationship of vascular complications with cerebrovascular reactivity and endothelial dysfunction in patients with obstructive sleep apnea

To assess the relationship of vascular complications with cerebrovascular reactivity (CVR) and endothelial dysfunction in patients with obstructive sleep apnea (OSA). One hundred and twelve patients were examined. The patients were stratified into the main group with moderate and severe OSA and the control group without apnea. All patients underwent anthropometry, polysomnography, transcranial dopplerography and duplex scanning of the brachial artery. Patients with OSA showed a more frequent decrease in post-occlusive vascular dilatation. The CVR indices in the hypercapnic test in the main group were in the range of 0.91-0.97 and significantly lower after 1 minute on the left, after 5 minutes on both sides and after 10 minutes on the left. A positive correlation during a hypercapnic test between the CVR on the left after 10 minutes and the desaturation index (r=0.287, p=0.021), between the CVR on the left after 5 and 10 minutes and acute cerebrovascular accident (r=0.248, p=0.048 and r=0.285, p=0.022, respectively), as well as a negative correlation between the indicators of the middle cerebral artery and chronic cerebral ischemia were established in patients with apnea. Timely assessment of pathological changes in central and peripheral hemodynamics in patients with OSA will allow diagnosing early signs of vascular complications, which will further improve the personalized strategy for the prevention of stroke and chronic cerebral ischemia.

Impact of Chronological Age and Biological Sex on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Study.

Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP)-based indices: 1) pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP); 2) pulse amplitude index (PAx)-correlation between pulse amplitude of ICP (AMP) and MAP; and 3) RAC-correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60), and decades of age (< 30, 30-39, 40-49, 50-59, 60-69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC, and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect impairment in TBI patients with advancing age. Further investigation into the utility of PAx and RAC is required, as they may prove useful for certain subgroups of patients.

Initial neurocritical care of severe traumatic brain injury: New paradigms and old challenges.

Early neurocritical care aims to ameliorate secondary traumatic brain injury (TBI) and improve neural salvage. Increased engagement of neurosurgeons in neurocritical care is warranted as daily briefings between the intensivist and the neurosurgeon are considered a quality indicator for TBI care. Hence, neurosurgeons should be aware of the latest evidence in the neurocritical care of severe TBI (sTBI). We conducted a narrative literature review of bibliographic databases (PubMed and Scopus) to examine recent research of sTBI. This review has several take-away messages. The concept of critical neuroworsening and its possible causes is discussed. Static thresholds of intracranial pressure (ICP) and cerebral perfusion pressure may not be optimal for all patients. The use of dynamic cerebrovascular reactivity indices such as the pressure reactivity index can facilitate individualized treatment decisions. The use of ICP monitoring to tailor treatment of intracranial hypertension (IHT) is not routinely feasible. Different guidelines have been formulated for different scenarios. Accordingly, we propose an integrated algorithm for ICP management in sTBI patients in different resource settings. Although hyperosmolar therapy and decompressive craniectomy are standard treatments for IHT, there is a lack high-quality evidence on how to use them. A discussion of the advantages and disadvantages of invasive ICP monitoring is included in the study. Addition of beta-blocker, anti-seizure, and anticoagulant medications to standardized management protocols (SMPs) should be considered with careful patient selection. Despite consolidated research efforts in the refinement of SMPs, there are still many unanswered questions and novel research opportunities for sTBI care.

Acute physiologic prediction of pediatric post-traumatic epilepsy

ObjectivePost-traumatic epilepsy (PTE) is a known complication of traumatic brain injury (TBI). Limited physiologic biomarkers have been investigated in relation to pediatric PTE. Our aim is to identify clinical, physiologic and neuroimaging biomarkers predictive of pediatric PTE arising during the acute care phase after injury. MethodsWe performed a retrospective analysis from a prospectively collected clinical database of pediatric patients who underwent multimodality neurologic monitoring that included continuous electroencephalography and intracranial pressure (ICP) monitoring. Biomarkers included hemodynamic vital signs, model-based indices of cerebrovascular pressure reactivity (CVPR) and autonomic function (AF), electroencephalographic abnormalities, and neuroimaging abnormalities on the initial CT scan on day of imaging. Our primary outcome, PTE, was classified as the presence of unprovoked seizures 2 months post-injury or the continued need for antiseizure medications at 12-month post-injury. We utilized univariate logistic regression to identify biomarkers associated with PTE. Results61 surviving patients were included in this study, among which 10 (16.4%) developed PTE. We identified that PTE was associated with increased ICP (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.02–1.52), increased pressure reactivity indices (92.53, 2.84->999.99), increased wavelet pressure reactivity indices (121.76, 2.84->999.99), increased CT Marshall scores (1.76, 1.13–2.74), decreased HRsd (0.54, 0.33–0.87) and the presence of epileptiform discharges (8.06, 1.85–35.17), and abnormal sleep spindles (4.88, 1.18–20.00). Whereas early post-traumatic seizures within the first 7 days post-injury were associated with PTE development (7.58, 1.81–39.68), this association was significant for such seizures occurring between 24 and 168 h post-injury (21.47, 4.18–110.38), and not for seizures occurring within 24 h post-injury. Among patients experiencing early post-traumatic seizures, increased time with seizures on surface electroencephalography was associated with PTE development (7.28, 2.05–73.14). We also identified that development of PTE was associated with worsened functional outcomes identified by increased Glasgow Outcome Scale – Extended Pediatric (GOSE-PEDs) scores (3.18, 1.68–8.01). ConclusionPediatric PTE development is associated with increased ICP, impaired CVPR, low heart rate variability, worsened neuroimaging findings, and electroencephalographic abnormalities identified during intensive care. Further studies are needed to investigate strategies to mitigate pediatric PTE development.

Near Infrared Spectroscopy for Poor Grade Aneurysmal Subarachnoid Hemorrhage-A Concise Review.

Delayed cerebral ischemia (DCI) disproportionately affects poor grade aneurysmal subarachnoid hemorrhage (aSAH) patients. An unreliable neurological exam and the lack of appropriate monitoring leads to unrecognized DCI, which in turn is associated with severe long-term deficits and higher mortality. Near Infrared Spectroscopy (NIRS) offers simple, continuous, real time, non-invasive cerebral monitoring. It provides regional cerebral oxygen saturation (c-rSO2), which reflects the balance between cerebral oxygen consumption and supply. Reports have demonstrated a good correlation with other cerebral oxygen and blood flow monitoring, and credible cerebrovascular reactivity indices were also derived from NIRS signals. Multiple critical c-rSO2 values have been reported in aSAH patients, based on various thresholds, duration, variation from baseline or cerebrovascular reactivity indices. Some were associated with vasospasm, some with DCI and others with clinical outcomes. However, the poor grade aSAH population has not been specifically studied and no randomized clinical trial has been published. The available literature does not support a specific NIRS-based intervention threshold to guide diagnostic or treatment in aSAH patients. We review herein the fundamental basic concepts behind NIRS technology, relationship of c-rSO2 to other brain monitoring values and their potential clinical interpretation. We follow with a critical evaluation of the use of NIRS in the aSAH population, more specifically its ability to diagnose vasospasm, to predict DCI and its association to outcome. In summary, NIRS might offer significant potential for poor grade aSAH in the future. However, current evidence does not support its use in clinical decision-making, and proper technology evaluation is required.

Practical Considerations for Continuous Time-Domain Cerebrovascular Reactivity Indices in Traumatic Brain Injury: Do Scaling Errors in Parent Signals Matter?

Literature pertaining to traumatic brain injury care involves the mediation and control of secondary brain injury mechanisms, chief among these is cerebral autoregulation. Cerebral autoregulation is frequently assessed through surrogate measures of cerebrovascular reactivity. An important aspect to acknowledge when calculating cerebrovascular reactivity indices is the linearity within two-parent bio-signals or variables. We highlighted the concept of linearity in raw parent bio-signals used for the calculation of the cerebrovascular reactivity index and what potential implications linearity carries for index derivation. Key of which is that the initial differencing or location of the pressure probes does not influence linear methods of cerebral reactivity calculations so long as the slow-wave vasogenic changes are being recorded.

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices, Chronological Age, and Biological Sex in Traumatic Brain Injury: A Scoping Review.

To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p < 0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p < 0.05) in the limited available literature. However, no literature exists comparing PAx or RAC with biological sex. Findings showed that aging was associated with impaired CVR. We observed a trend between female sex and worse PRx values, but the literature was limited and statistical significance was borderline. The identified studies were few in number, carried significant population heterogeneity, and utilized grand averaging of large epochs of physiology during statistical comparisons with age and biological sex. Because of the heterogeneous nature of TBI populations and limited focus on the effects of age and sex on outcomes in TBI, it is challenging to highlight the differences between the indices and patient age groups and sex. The largest study showing an association between PRx and age was done by Zeiler and colleagues, where 165 patients were studied noting that patients with a mean PRx value above zero had a mean age above 51.4 years versus a mean age of 41.4 years for those with a mean PRx value below zero (p = 0.0007). The largest study showing an association between PRx and sex was done by Czosnyka and colleagues, where 469 patients were studied noting that for patients <50 years of age, PRx was worse in females (0.11 ± 0.047) compared to males (0.044 ± 0.031), p < 0.05. The findings from these 10 studies provide preliminary data, but are insufficient to definitively characterize the impact of age and sex on CVR in moderate/severe TBI. Future work in the field should focus on the impact of age and sex on multi-modal cerebral physiological monitoring.