Continuous monitoring methods of cerebral compliance and compensatory reserve: a scoping review of human literature.

Objective.Continuous monitoring of cerebrospinal compliance (CC)/cerebrospinal compensatory reserve (CCR) is crucial for timely interventions and preventing more substantial deterioration in the context of acute neural injury, as it enables the early detection of abnormalities in intracranial pressure (ICP). However, to date, the literature on continuous CC/CCR monitoring is scattered and occasionally challenging to consolidate.Approach.We subsequently conducted a systematic scoping review of the human literature to highlight the available continuous CC/CCR monitoring methods.Main results.This systematic review incorporated a total number of 76 studies, covering diverse patient types and focusing on three primary continuous CC or CCR monitoring metrics and methods-Moving Pearson's correlation between ICP pulse amplitude waveform and ICP, referred to as RAP, the Spiegelberg Compliance Monitor, changes in cerebral blood flow velocity with respect to the alternation of ICP measured through transcranial doppler (TCD), changes in centroid metric, high frequency centroid (HFC) or higher harmonics centroid (HHC), and the P2/P1 ratio which are the distinct peaks of ICP pulse wave. The majority of the studies in this review encompassed RAP metric analysis (n= 43), followed by Spiegelberg Compliance Monitor (n= 11), TCD studies (n= 9), studies on the HFC/HHC (n= 5), and studies on the P2/P1 ratio studies (n= 6). These studies predominantly involved acute traumatic neural injury (i.e. Traumatic Brain Injury) patients and those with hydrocephalus. RAP is the most extensively studied of the five focused methods and exhibits diverse applications. However, most papers lack clarification on its clinical applicability, a circumstance that is similarly observed for the other methods.Significance.Future directions involve exploring RAP patterns and identifying characteristics and artifacts, investigating neuroimaging correlations with continuous CC/CCR and integrating machine learning, holding promise for simplifying CC/CCR determination. These approaches should aim to enhance the precision and accuracy of the metric, making it applicable in clinical practice.

Near-Infrared Spectroscopy Regional Oxygen Saturation Based Cerebrovascular Reactivity Assessments in Chronic Traumatic Neural Injury versus in Health: A Prospective Cohort Study.

Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2)-based cerebrovascular reactivity (CVR) monitoring has enabled entirely non-invasive, continuous monitoring during both acute and long-term phases of care. To date, long-term post-injury CVR has not been properly characterized after acute traumatic neural injury, also known as traumatic brain injury (TBI). This study aims to compare CVR in those recovering from moderate-to-severe TBI with a healthy control group. A total of 101 heathy subjects were recruited for this study, along with 29 TBI patients. In the healthy cohort, the arterial blood pressure variant of the cerebral oxygen index (COx_a) was not statistically different between males and females or in the dominant and non-dominant hemispheres. In the TBI cohort, COx_a was not statistically different between the first and last available follow-up or by the side of cranial surgery. Surprisingly, CVR, as measured by COx_a, was statistically better in those recovering from TBI than those in the healthy cohort. In this prospective cohort study, CVR, as measured by NIRS-based methods, was found to be more active in those recovering from TBI than in the healthy cohort. This study may indicate that in individuals that survive TBI, CVR may be enhanced as a neuroprotective measure.

Time-Series Modeling and Forecasting of Cerebral Pressure-Flow Physiology: A Scoping Systematic Review of the Human and Animal Literature.

The modeling and forecasting of cerebral pressure-flow dynamics in the time-frequency domain have promising implications for veterinary and human life sciences research, enhancing clinical care by predicting cerebral blood flow (CBF)/perfusion, nutrient delivery, and intracranial pressure (ICP)/compliance behavior in advance. Despite its potential, the literature lacks coherence regarding the optimal model type, structure, data streams, and performance. This systematic scoping review comprehensively examines the current landscape of cerebral physiological time-series modeling and forecasting. It focuses on temporally resolved cerebral pressure-flow and oxygen delivery data streams obtained from invasive/non-invasive cerebral sensors. A thorough search of databases identified 88 studies for evaluation, covering diverse cerebral physiologic signals from healthy volunteers, patients with various conditions, and animal subjects. Methodologies range from traditional statistical time-series analysis to innovative machine learning algorithms. A total of 30 studies in healthy cohorts and 23 studies in patient cohorts with traumatic brain injury (TBI) concentrated on modeling CBFv and predicting ICP, respectively. Animal studies exclusively analyzed CBF/CBFv. Of the 88 studies, 65 predominantly used traditional statistical time-series analysis, with transfer function analysis (TFA), wavelet analysis, and autoregressive (AR) models being prominent. Among machine learning algorithms, support vector machine (SVM) was widely utilized, and decision trees showed promise, especially in ICP prediction. Nonlinear models and multi-input models were prevalent, emphasizing the significance of multivariate modeling and forecasting. This review clarifies knowledge gaps and sets the stage for future research to advance cerebral physiologic signal analysis, benefiting neurocritical care applications.

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.

BACKGROUND: Optimal 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. METHODS: CPPopt 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. RESULTS: This 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. CONCLUSIONS: Our 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 Monitoring and Treatment Thresholds in Acute Neural Injury: A Narrative Review of the Historical Achievements, Current State, and Future Perspectives.

Since its introduction in the 1960s, intracranial pressure (ICP) monitoring has become an indispensable tool in neurocritical care practice and a key component of the management of moderate/severe traumatic brain injury (TBI). The primary utility of ICP monitoring is to guide therapeutic interventions aimed at maintaining physiological ICP and preventing intracranial hypertension. The rationale for such ICP maintenance is to prevent secondary brain injury arising from brain herniation and inadequate cerebral blood flow. There exists a large body of evidence indicating that elevated ICP is associated with mortality and that aggressive ICP control protocols improve outcomes in severe TBI patients. Therefore, current management guidelines recommend a cerebral perfusion pressure (CPP) target range of 60-70 mm Hg and an ICP threshold of >20 or >22 mm Hg, beyond which therapeutic intervention should be initiated. Though our ability to achieve these thresholds has drastically improved over the past decades, there has been little to no change in the mortality and morbidity associated with moderate-severe TBI. This is a result of the "one treatment fits all" dogma of current guideline-based care that fails to take individual phenotype into account. The way forward in moderate-severe TBI care is through the development of continuously derived individualized ICP thresholds. This narrative review covers the topic of ICP monitoring in TBI care, including historical context/achievements, current monitoring technologies and indications, treatment methods, associations with patient outcome and multi-modal cerebral physiology, present controversies surrounding treatment thresholds, and future perspectives on personalized approaches to ICP-directed therapy.

Evaluation of Morlet Wavelet Analysis for Artifact Detection in Low-Frequency Commercial Near-Infrared Spectroscopy Systems.

Regional cerebral oxygen saturation (rSO2), a method of cerebral tissue oxygenation measurement, is recorded using non-invasive near-infrared Spectroscopy (NIRS) devices. A major limitation is that recorded signals often contain artifacts. Manually removing these artifacts is both resource and time consuming. The objective was to evaluate the applicability of using wavelet analysis as an automated method for simple signal loss artifact clearance of rSO2 signals obtained from commercially available devices. A retrospective observational study using existing populations (healthy control (HC), elective spinal surgery patients (SP), and traumatic brain injury patients (TBI)) was conducted. Arterial blood pressure (ABP) and rSO2 data were collected in all patients. Wavelet analysis was determined to be successful in removing simple signal loss artifacts using wavelet coefficients and coherence to detect signal loss artifacts in rSO2 signals. The removal success rates in HC, SP, and TBI populations were 100%, 99.8%, and 99.7%, respectively (though it had limited precision in determining the exact point in time). Thus, wavelet analysis may prove to be useful in a layered approach NIRS signal artifact tool utilizing higher-frequency data; however, future work is needed.

Break-induced replication promotes formation of lethal joint molecules dissolved by Srs2.

Break-induced replication (BIR) is a DNA double-strand break repair pathway that leads to genomic instabilities similar to those observed in cancer. BIR proceeds by a migrating bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains unknown how this ssDNA is prevented from unscheduled pairing with the template, which can lead to genomic instability. Here, we propose that uncontrolled Rad51 binding to this ssDNA promotes formation of toxic joint molecules that are counteracted by Srs2. First, Srs2 dislodges Rad51 from ssDNA preventing promiscuous strand invasions. Second, it dismantles toxic intermediates that have already formed. Rare survivors in the absence of Srs2 rely on structure-specific endonucleases, Mus81 and Yen1, that resolve toxic joint-molecules. Overall, we uncover a new feature of BIR and propose that tight control of ssDNA accumulated during this process is essential to prevent its channeling into toxic structures threatening cell viability.