Dynamics of critical closing pressure explain cerebral autoregulation impairment in acute cerebrovascular disease.

INTRODUCTION: Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP). METHODS: Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (>50 years), and AIS patients. RESULTS: Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 second) peak in CrCP dynamic response, that was not influenced by age. CONCLUSION: These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature. .

Physiological Variability during Prehospital Stroke Care: Which Monitoring and Interventions Are Used?

Prehospital care is a fundamental component of stroke care that predominantly focuses on shortening the time between diagnosis and reaching definitive stroke management. With growing evidence of the physiological parameters affecting long-term patient outcomes, prehospital clinicians need to consider the balance between rapid transfer and increased physiological-parameter monitoring and intervention. This systematic review explores the existing literature on prehospital physiological monitoring and intervention to modify these parameters in stroke patients. The systematic review was registered on PROSPERO (CRD42022308991) and conducted across four databases with citation cascading. Based on the identified inclusion and exclusion criteria, 19 studies were retained for this review. The studies were classified into two themes: physiological-monitoring intervention and pharmacological-therapy intervention. A total of 14 included studies explored prehospital physiological monitoring. Elevated blood pressure was associated with increased hematoma volume in intracerebral hemorrhage and, in some reports, with increased rates of early neurological deterioration and prehospital neurological deterioration. A reduction in prehospital heart rate variability was associated with unfavorable clinical outcomes. Further, five of the included records investigated the delivery of pharmacological therapy in the prehospital environment for patients presenting with acute stroke. BP-lowering interventions were successfully demonstrated through three trials; however, evidence of their benefit to clinical outcomes is limited. Two studies investigating the use of oxygen and magnesium sulfate as neuroprotective agents did not demonstrate an improvement in patient's outcomes. This systematic review highlights the absence of continuous physiological parameter monitoring, investigates fundamental physiological parameters, and provides recommendations for future work, with the aim of improving stroke patient outcomes.

Patient experience of bladder cancer: A data linkage study.

Introduction: Bladder cancer is one of the most common cancers worldwide and can be managed with a range of approaches, including conservative, medical and surgical therapies. Treatment may be associated with considerable morbidity, but despite this, little data exist to reflect patients' subsequent experience. This study aims to evaluate patients' experiences of bladder cancer care by linking data from a national cancer experience survey with data routinely collected from National Health Service (NHS) sources. This study considers patient perspectives and makes recommendations to improve the patient experience of bladder cancer care. Methods: Anonymised data from the National Cancer Patient Experience Survey (NCPES) for patients who had received care for bladder cancer were collated and linked with demographic and treatment data. Questions from the NCPES were then categorised into different themes based on their content. This study focused on themes relating to lifestyle, activities of daily living (ADL), symptoms, psychological impact and body perception. Statistical analyses were used to investigate the relationship between patient reported experience, demographics and type of care received. Results: NCPES data from 673 patients (487 male, 29 undisclosed) with at least T1 bladder cancer were analysed. Statistically significant differences were identified across the five investigated patient experience themes. No significant difference was seen in patient reported experience between bladder cancer drug treatments (such as intravesical BCG vs. intravesical chemotherapy vs. systemic chemotherapy) and radiotherapy types (curative vs. palliative). Patients treated with cystectomy had significantly worse experiences relating to body image and ADL but not when compared with patients treated with radical radiotherapy. Patients with long-term health conditions reported worse experiences for all five themes compared with those without. Conclusion: The literature surrounding the experience of patients with bladder cancer is limited. This data linkage study demonstrates the impact of bladder cancer care on five patient experience themes, including the effect of different treatment types and the presence of long-term health conditions. While limited by sample size and data comprehensiveness, this study aims to inform clinicians and service providers of factors affecting patient experience of bladder cancer care, to stimulate service review and development.

Effects of Blood Pressure on Brain Tissue Pulsation Amplitude in a Phantom Model.

OBJECTIVE: The precise mechanism and determinants of brain tissue pulsations (BTPs) are poorly understood, and the impact of blood pressure (BP) on BTPs is relatively unexplored. This study aimed to explore the relationship between BP parameters (mean arterial pressure [MAP] and pulse pressure [PP]) and BTP amplitude, using a transcranial tissue Doppler prototype. METHODS: A phantom brain model generating arterial-induced BTPs was developed to observe BP changes in the absence of confounding variables and cerebral autoregulation feedback processes. A regression model was developed to investigate the relationship between bulk BTP amplitude and BP. The separate effects of PP and MAP were evaluated and quantified. RESULTS: The regression model (R2 = 0.978) revealed that bulk BTP amplitude measured from 27 gates significantly increased with PP but not with MAP. Every 1 mm Hg increase in PP resulted in a bulk BTP amplitude increase of 0.29 µm. CONCLUSION: Increments in BP were significantly associated with increments in bulk BTP amplitude. Further work should aim to confirm the relationship between BP and BTPs in the presence of cerebral autoregulation and explore further physiological factors having an impact on BTP measurements, such as cerebral blood flow volume, tissue distensibility and intracranial pressure.

Point/counterpoint: Cerebrovascular resistance is a flawed concept.

The relationship between cerebral blood flow and blood pressure is a critical part of investigation of cerebral autoregulation. Conventionally, cerebrovascular resistance (CVR) has been used to describe this relationship, but the underlying principles used for this method is flawed in real-world application for several reasons. Despite this, the use of CVR remains entrenched within current literature. This 'Point/Counterpoint' review provides a summary of the flaws in using CVR and explains the benefits of calculating the more accurate critical closing pressure (CrCP) and resistance-area product (RAP) parameters, with support of real-world data.

Magnetic resonance imaging of the pulsing brain: a systematic review.

OBJECTIVE: To perform a systematic review of the literature exploring magnetic resonance imaging (MRI) methods for measuring natural brain tissue pulsations (BTPs) in humans. METHODS: A prospective systematic search of MEDLINE, SCOPUS and OpenGrey databases was conducted by two independent reviewers using a pre-determined strategy. The search focused on identifying reported measurements of naturally occurring BTP motion in humans. Studies involving non-human participants, MRI in combination with other modalities, MRI during invasive procedures and MRI studies involving externally applied tests were excluded. Data from the retrieved records were combined to create Forest plots comparing brain tissue displacement between Chiari-malformation type 1 (CM-I) patients and healthy controls using an independent samples t-test. RESULTS: The search retrieved 22 eligible articles. Articles described 5 main MRI techniques for visualisation or quantification of intrinsic brain motion. MRI techniques generally agreed that the amplitude of BTPs varies regionally from 0.04 mm to ~ 0.80 mm, with larger tissue displacements occurring closer to the centre and base of the brain compared to peripheral regions. Studies of brain pathology using MRI BTP measurements are currently limited to tumour characterisation, idiopathic intracranial hypertension (IIH), and CM-I. A pooled analysis confirmed that displacement of tissue in the cerebellar tonsillar region of CM-I patients was + 0.31 mm [95% CI 0.23, 0.38, p < 0.0001] higher than in healthy controls. DISCUSSION: MRI techniques used for measurements of brain motion are at an early stage of development with high heterogeneity across the methods used. Further work is required to provide normative data to support systematic BTPs characterisation in health and disease.

Brain tissue motion in acute hemorrhagic stroke using amplified MRI (aMRI).

Brain tissue pulsates with each cardiac cycle, however the effect of disease on this natural motion is still unclear. Current literature mainly focuses on healthy brain tissue, with only limited studies looking at disease states such as Chiari malformation and acute ischemic stroke. This case report advances on recent literature by describing the case of a patient with an acute intracerebral hemorrhage and demonstrating an amplified MRI cine of the brain's motion. A clearer understanding of the effects of disease on brain motion may guide clinical application of pulsation measurement.

Cerebrovascular tone and resistance measures differ between healthy control and patients with acute intracerebral haemorrhage: exploratory analyses from the BREATHE-ICH study.

Objective.Cerebral autoregulation impairment in acute neurovascular disease is well described. The recent BREATHE-ICH study demonstrated improvements in dynamic cerebral autoregulation, by hypocapnia generated by hyperventilation, in the acute period following intracranial haemorrhage (ICH). This exploratory analysis of the BREATHE-ICH dataset aims to examine the differences in hypocapnic responses between healthy controls and patients with ICH, and determine whether haemodynamic indices differ between baseline and hypocapnic states.Approach.Acute ICH patients were recruited within 48 h of onset and healthy volunteers were recruited from a university setting. Transcranial Doppler measurements of the middle cerebral artery were obtained at baseline and then a hyperventilation intervention was used to induce hypocapnia. Patients with ICH were then followed up at 10-14 D post-event for repeated measurements.Main results.Data from 43 healthy controls and 12 patients with acute ICH met the criteria for statistical analysis. In both normocapnic and hypocapnic conditions, significantly higher critical closing pressure and resistance area product were observed in patients with ICH. Furthermore, critical closing pressure changes were observed to be sustained at 10-14 D follow up. During both the normocapnic and hypocapnic states, reduced autoregulation index was observed bilaterally in patients with ICH, compared to healthy controls.Significance.Whilst this exploratory analysis was limited by a small, non-age matched sample, significant differences between ICH patients and healthy controls were observed in factors associated with cerebrovascular tone and resistance. These differences suggest underlying cerebral autoregulation changes in ICH, which may play a pivotal role in the morbidity and mortality associated with ICH.

Emerging Detection Techniques for Large Vessel Occlusion Stroke: A Scoping Review.

Background: Large vessel occlusion (LVO) is the obstruction of large, proximal cerebral arteries and can account for up to 46% of acute ischaemic stroke (AIS) when both the A2 and P2 segments are included (from the anterior and posterior cerebral arteries). It is of paramount importance that LVO is promptly recognised to provide timely and effective acute stroke management. This review aims to scope recent literature to identify new emerging detection techniques for LVO. As a good comparator throughout this review, the commonly used National Institutes of Health Stroke Scale (NIHSS), at a cut-off of ≥11, has been reported to have a sensitivity of 86% and a specificity of 60% for LVO. Methods: Four electronic databases (Medline via OVID, CINAHL, Scopus, and Web of Science), and grey literature using OpenGrey, were systematically searched for published literature investigating developments in detection methods for LVO, reported from 2015 to 2021. The protocol for the search was published with the Open Science Framework (10.17605/OSF.IO/A98KN). Two independent researchers screened the titles, abstracts, and full texts of the articles, assessing their eligibility for inclusion. Results: The search identified 5,082 articles, in which 2,265 articles were screened to assess their eligibility. Sixty-two studies remained following full-text screening. LVO detection techniques were categorised into 5 groups: stroke scales (n = 30), imaging and physiological methods (n = 15), algorithmic and machine learning approaches (n = 9), physical symptoms (n = 5), and biomarkers (n = 3). Conclusions: This scoping review has explored literature on novel and advancements in pre-existing detection methods for LVO. The results of this review highlight LVO detection techniques, such as stroke scales and biomarkers, with good sensitivity and specificity performance, whilst also showing advancements to support existing LVO confirmatory methods, such as neuroimaging.

Acute ischemic stroke diagnosis using brain tissue pulsations.

Healthy brain tissue pulsates with the cardiac cycle, but whether brain tissue pulsations (BTPs) are impaired by tissue ischemia due to ischemic stroke is currently unclear. This study is the first to explore the clinical potential of measuring BTPs using ultrasound in acute ischemic stroke patients. BTPs were measured in 24 healthy volunteers (aged 52-82 years) and 14 acute ischemic stroke patients (aged 51-86 years) using a novel Transcranial Tissue Doppler (TCTD) method. Measurements were quick to perform and were well tolerated by all subjects. A mixed-methods approach was used for blinded analysis of recordings. This identified qualitative disruption of BTPs in acute stroke patients, which were used to create an analysis checklist. Blinded BTP analysis by novices using the checklist resulted in high sensitivity but low specificity for stroke detection. Quantitative analysis also identified differences between stroke and healthy participants, including weaker BTPs in stroke patients. This first study reporting BTP characteristics in acute ischemic stroke revealed weaker brain tissue pulsations and waveform disruption in acute stroke patients. However, further clinical evaluation using a larger sample size is required to confirm these findings and to explore whether TCTD monitoring might be beneficial for clinical neuromonitoring.

The Effects of Hypocapnia on Brain Tissue Pulsations.

Hypocapnia is known to affect patients with acute stroke and plays a key role in governing cerebral autoregulation. However, the impact of hypocapnia on brain tissue pulsations (BTPs) is relatively unexplored. As BTPs are hypothesised to result from cerebrovascular resistance to the inflow of pulsatile arterial blood, it has also been hypothesised that cerebral autoregulation changes mediated by hypocapnia will alter BTP amplitude. This healthy volunteer study reports measurements of BTPs obtained using transcranial tissue Doppler (TCTD). Thirty participants underwent hyperventilation to induce mild hypocapnia. BTP amplitude, EtCO2, blood pressure, and heart rate were then analysed to explore the impact of hypocapnia on BTP amplitude. Significant changes in BTP amplitude were noted during recovery from hypocapnia, but not during the hyperventilation manoeuvre itself. However, a significant increase in heart rate and pulse pressure and decrease in mean arterial pressure were also observed to accompany hypocapnia, which may have confounded our findings. Whilst further investigation is required, the results of this study provide a starting point for better understanding of the effects of carbon dioxide levels on BTPs. Further research in this area is needed to identify the major physiological drivers of BTPs and quantify their interactions with other aspects of cerebral haemodynamics.

Brain Tissue Pulsation in Healthy Volunteers.

It is well known that the brain pulses with each cardiac cycle, but interest in measuring cardiac-induced brain tissue pulsations (BTPs) is relatively recent. This study was aimed at generating BTP reference data from healthy patients for future clinical comparisons and modelling. BTPs were measured through the forehead and temporal positions as a function of age, sex, heart rate, mean arterial pressure and pulse pressure. A multivariate regression model was developed based on transcranial tissue Doppler BTP measurements from 107 healthy adults (56 male) aged from 20-81 y. A subset of 5 participants (aged 20-49 y) underwent a brain magnetic resonance imaging scan to relate the position of the ultrasound beam to anatomy. BTP amplitudes were found to vary widely between patients (from ∼4 to ∼150 µm) and were strongly associated with pulse pressure. Comparison with magnetic resonance images confirmed regional variations in BTP with depth and probe position.

Ultrasound measurement of brain tissue movement in humans: A systematic review.

INTRODUCTION: It has long been suggested that ultrasound could be used to measure brain tissue pulsations in humans, but potential clinical applications are relatively unexplored. The aim of this systematic review was to explore and synthesise available literature on ultrasound measurement of brain tissue motion in humans. METHODS: Our systematic review was designed to include predefined study selection criteria, quality evaluation, and a data extraction pro-forma, registered prospectively on PROSPERO (CRD42018114117). The systematic review was conducted by two independent reviewers. RESULTS: Ten studies were eligible for the evidence synthesis and qualitative evaluation. All eligible studies confirmed that brain tissue motion over the cardiac cycle could be measured using ultrasound; however, data acquisition, analysis, and outcomes varied. The majority of studies used tissue pulsatility imaging, with the right temporal window as the acquisition point. Currently available literature is largely exploratory, with measurements of brain tissue displacement over a narrow range of health conditions and ages. Explored health conditions include orthostatic hypotension and depression. CONCLUSION: Further studies are needed to assess variability in brain tissue motion estimates across larger cohorts of healthy subjects and in patients with various medical conditions. This would be important for informing sample size estimates to ensure future studies are appropriately powered. Future research would also benefit from a consistent framework for data analysis and reporting, to facilitate comparative research and meta-analysis. Following standardisation and further healthy participant studies, future work should focus on assessing the clinical utility of brain tissue pulsation measurements in cerebrovascular disease states.