Recent Submissions

  • Effects of blood pressure on brain tissue pulsation amplitude in a phantom model

    Ince, Jonathan; Pallett, Edward; Chung, Emma; Nicholls, Jennifer K (2023-09)
    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.
  • The role of the autonomic nervous system in cerebral blood flow regulation in stroke: A review

    Robinson, Thompson; Minhas, Jatinder S (2023-02-27)
    Stroke is a pathophysiological condition which results in alterations in cerebral blood flow (CBF). The mechanism by which the brain maintains adequate CBF in presence of fluctuating cerebral perfusion pressure (CPP) is known as cerebral autoregulation (CA). Disturbances in CA may be influenced by a number of physiological pathways including the autonomic nervous system (ANS). The cerebrovascular system is innervated by adrenergic and cholinergic nerve fibers. The role of the ANS in regulating CBF is widely disputed owing to several factors including the complexity of the ANS and cerebrovascular interactions, limitations to measurements, variation in methods to assess the ANS in relation to CBF as well as experimental approaches that can or cannot provide insight into the sympathetic control of CBF. CA is known to be impaired in stroke however the number of studies investigating the mechanisms by which this occurs are limited. This literature review will focus on highlighting the assessment of the ANS and CBF via indices derived from the analyses of heart rate variability (HRV), and baroreflex sensitivity (BRS), and providing a summary of both clinical and animal model studies investigating the role of the ANS in influencing CA in stroke. Understanding the mechanisms by which the ANS influences CBF in stroke patients may provide the foundation for novel therapeutic approaches to improve functional outcomes in stroke patients.
  • Three-dimensional simulations of embolic stroke and an equation for sizing emboli from imaging

    Swienton, David; Chung, Emma (2023-02-21)
    Stroke simulations are needed to run in-silico trials, develop hypotheses for clinical studies and to interpret ultrasound monitoring and radiological imaging. We describe proof-of-concept three-dimensional stroke simulations, carrying out in silico trials to relate lesion volume to embolus diameter and calculate probabilistic lesion overlap maps, building on our previous Monte Carlo method. Simulated emboli were released into an in silico vasculature to simulate 1000 s of strokes. Infarct volume distributions and probabilistic lesion overlap maps were determined. Computer-generated lesions were assessed by clinicians and compared with radiological images. The key result of this study is development of a three-dimensional simulation for embolic stroke and its application to an in silico clinical trial. Probabilistic lesion overlap maps showed that the lesions from small emboli are homogeneously distributed throughout the cerebral vasculature. Mid-sized emboli were preferentially found in posterior cerebral artery (PCA) and posterior region of the middle cerebral artery (MCA) territories. For large emboli, MCA, PCA and anterior cerebral artery (ACA) lesions were comparable to clinical observations, with MCA, PCA then ACA territories identified as the most to least probable regions for lesions to occur. A power law relationship between lesion volume and embolus diameter was found. In conclusion, this article showed proof-of-concept for large in silico trials of embolic stroke including 3D information, identifying that embolus diameter could be determined from infarct volume and that embolus size is critically important to the resting place of emboli. We anticipate this work will form the basis of clinical applications including intraoperative monitoring, determining stroke origins, and in silico trials for complex situations such as multiple embolisation.
  • Antiplatelet treatment for acute secondary prevention of non-cardioembolic minor stroke / transient ischaemic attack: an update for the acute physician

    Minhas, Jatinder S; Robinson, Thompson; Eveson, David; Mistri, Amit (2022-09)
    Acute stroke is the leading cause of disability in the UK and a leading cause of mortality worldwide. The majority of patients with ischaemic stroke present with minor deficits or transient ischaemic attack (TIA), and are often first seen by patient-facing clinicians. Urgent evaluation and treatment are important as many patients are at high risk of major vascular events and death within hours to days after the index event. This narrative review summarises the evidence on four antiplatelet treatments for non-cardioembolic stroke prevention: aspirin, clopidogrel, dipyridamole and ticagrelor. Each of these drugs has a unique mechanism and has been tested as a single agent or in combination. Aspirin, when given early is beneficial and short-term treatment with aspirin and clopidogrel has been shown to be more effective in high-risk TIA / minor stroke. This review concludes by highlighting gaps in evidence, including scope for future trials that could potentially change clinical practice.
  • Directional sensitivity of dynamic cerebral autoregulation during spontaneous fluctuations in arterial blood pressure at rest

    Robinson, Thompson
    Directional sensitivity, the more efficient response of cerebral autoregulation to increases, compared to decreases, in mean arterial pressure (MAP), has been demonstrated with repeated squat-stand maneuvers (SSM). In 43 healthy subjects (26 male, 23.1 ± 4.2 years old), five min. recordings of cerebral blood velocity (bilateral Doppler ultrasound), MAP (Finometer), end-tidal CO2 (capnograph), and heart rate (ECG) were obtained during sitting (SIT), standing (STA) and SSM. A new analytical procedure, based on autoregressive-moving average models, allowed distinct estimates of the autoregulation index (ARI) by separating the MAP signal into its positive (MAP+D) and negative (MAP-D) derivatives. ARI+D was higher than ARI-D (p < 0.0001), SIT: 5.61 ± 1.58 vs 4.31 ± 2.16; STA: 5.70 ± 1.24 vs 4.63 ± 1.92; SSM: 4.70 ± 1.11 vs 3.31 ± 1.53, but the difference ARI+D-ARI-D was not influenced by the condition. A bootstrap procedure determined the critical number of subjects needed to identify a significant difference between ARI+D and ARI-D, corresponding to 24, 37 and 38 subjects, respectively, for SSM, STA and SIT. Further investigations are needed on the influences of sex, aging and other phenotypical characteristics on the phenomenon of directional sensitivity of dynamic autoregulation.
  • The scalability of common paradigms for assessment of cognitive function: A functional transcranial Doppler study

    Robinson, Thompson (2022-03-28)
    Cognitive paradigms induce changes in cerebral blood flow (CBF) associated with increased metabolic demand, namely neurovascular coupling (NVC). We tested the hypothesis that the effect of complexity and duration of cognitive paradigms will either enhance or inhibit the NVC response. Bilateral CBF velocity (CBFV) in the middle cerebral arteries (MCAs) via transcranial Doppler ultrasound (TCD), blood pressure (BP), electrocardiogram (ECG) and end-tidal CO2 (EtCO2) of 16 healthy participants (aged 21-71 years) were simultaneously recorded at rest and during randomized paradigms of different complexities (naming words beginning with P-,R-,V- words and serial subtractions of 100-2,100-7,1000-17), and durations (5s, 30s and 60s). CBFV responses were population mean normalized from a 30-s baseline period prior to task initiation. A significant increase in bilateral CBFV response was observed at the start of all paradigms and provided a similar pattern in most responses, irrespective of complexity or duration. Although significant inter-hemispherical differences were found during performance of R-word and all serial subtraction paradigms, no lateralisation was observed in more complex naming word tasks. Also, the effect of duration was manifested at late stages of 100-7, but not for other paradigms. CBFV responses could not distinguish different levels of complexity or duration with a single presentation of the cognitive paradigm. Further studies of the ordinal scalability of the NVC response are needed with more advanced modelling techniques, or different types of neural stimulation.
  • Magnetic resonance imaging of the pulsing brain: a systematic review

    Chowdhury, Alimul; Chung, Emma (2022-10-15)
    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.
  • Mortality in a multiethnic population attending a one-stop TIA clinic

    Minhas, Jatinder S; Hussain, Shazia; Robinson, Thompson; Eveson, David; Mistri, Amit (2022-09-1)
    Introduction: Studies indicate a 13-27% mortality rate following a transient ischaemic attack (TIA). However, outcomes following TIA/minor stroke since the introduction of rapid-access TIA clinics and prompt vascular risk factor intervention are not known. Specifically, there is paucity of data comparing outcomes between people who are diagnosed with an "acute cerebrovascular" (CV) event or an alternative non-cardiovascular diagnosis (non-CV) in a rapid-access TIA clinic. We aimed to assess the mortality in such a setting. Methods: A retrospective observational study was undertaken at the Leicester rapid-access secondary care TIA clinic. Data included information collected at the first clinic visit (including comorbidities, and primary diagnosis, categorized as CV and non-CV) and the date of death for people dying during follow-up. Results: 11,524 subjects were included with 33,164 years of follow-up data; 4,746 (41.2%) received a CV diagnosis. The median follow-up time was 2.75 years (interquartile range 1.36-4.32). The crude mortality rate was 37.3 (95% CI: 35.3-39.5) per 1,000 person-years (PTPY). The mortality rate was higher following a CV diagnosis (50.8 [47.2-54.7] PTPY) compared to a non-CV diagnosis (27.9 [25.7-30.4] PTPY), and for males, older people, those of white ethnicity, and people with orthostatic hypotension (OH). Discussion: This study identified possible risk factors associated with a higher mortality in TIA clinic attendees, who may benefit from specific intervention. Future research should explore the underlying causes and the effect of specific targeted management strategies.
  • High non-adherence rates to secondary prevention by chemical adherence testing in patients with TIA

    Lane, Dan; Robinson, Thompson; Eveson, David; Mistri, Amit; Patel, Prashanth; Gupta, Pankaj (2022-07-25)
    Introduction: Transient ischaemic attack (TIA) clinics are important for secondary prevention of fatal or disabling stroke. Non-adherence to prescribed medications is an important reason for treatment failure but difficult to diagnose. This study ascertained the utility of a novel biochemical tool in the objective biochemical diagnosis of non-adherence. Methods: One-hundred consecutive urine samples collected from patients attending the TIA clinic, at a tertiary centre, were analysed for presence or absence of prescribed cardiovascular medications using liquid chromatography-mass spectrometry (LC-MS/MS). Patients were classified as adherent or non-adherent, respectively. Demographic and clinical characteristics were compared between the two cohorts. Univariate regression analyses were performed for individual variables and model fitting was undertaken for significant variables. Results: The mean duration of follow-up from the index event was 31 days [standard deviation (SD): 18.9]. The overall rate of non-adherence for at least one medication was 24%. In univariate analysis, the number of comorbidities [3.4 (SD: 1.9) vs. 2.5 (1.9), P = 0.032] and total number of all prescribed medications [6.0 (3.3) vs 4.4 (2.1), P = 0.032] were higher in the non-adherent group. On multivariate analysis, the total number of medications prescribed correlated with increased non-adherence (odds ratio: 1.27, 95% Confidence Intervals: 1.1-1.5, P = 0.01). Conclusions: LC-MS/MS is a clinically useful tool for the diagnosis of non-adherence. Nearly a quarter of TIA patients were non-adherent to their cardiovascular medications Addressing non-adherence early may reduce the risk of future disabling cardiovascular events.
  • Dynamics of the cerebral autoregulatory response to paced hyperventilation assessed using subcomponent and time-varying analyses

    Minhas, Jatinder S; Robinson, Thompson (2022-08-03)
    Cerebral blood flow (CBF) can be altered by a change in partial pressure of arterial CO2 (Pco2), being reduced during hyperventilation (HPV). Critical closing pressure (CrCP) and resistance area product (RAP) are parameters that can be studied to understand this change, but their dynamic response has not been investigated during paced HPV (PHPV). Seventy-five participants had recordings at rest and during PHPV. Blood pressure (BP) (Finometer), bilateral CBF velocity (CBFV) (transcranial Doppler), end-tidal CO2 (capnography), and heart rate (HR) were recorded continuously. Subcomponent analysis (SCA) and time-varying CrCP, RAP, and dynamic cerebral autoregulation (autoregulation index, ARI) were estimated by comparing PHPV with poikilocapnia. PHPV caused a change in CBFV (P < 0.01), EtCO2, (P < 0.01), HR (P < 0.001), and RAP (P < 0.01). SCA demonstrated RAP was the main parameter explaining the changes in CBFV due to PHPV. The time-varying step responses for CBFV and RAP during PHPV demonstrated considerable nonstationarity compared with poikilocapnia (P < 0.00001). Although time-varying ARI was temporarily depressed, after 60 s of PHPV it was significantly higher (6.81 ± 1.88) (P < 0.0001) than in poikilocapnia (5.08 ± 1.86). The mean plateau of the RAP step response was -98.3 ± 58.8% 60 s after the onset of PHPV but -71.7 ± 45.0% for poikilocapnia (P = 0.0026), with no corresponding changes in CrCP (P = 0.6). Further work is needed to assess the role of sex and aging in our findings, and the potential for using RAP and CrCP to improve the sensitivity and specificity of CO2 reactivity studies in cerebrovascular conditions.NEW & NOTEWORTHY The dynamic response of critical closing pressure (CrCP) and resistance-area product (RAP) of the cerebral circulation to a step change in mean arterial pressure can shed light on the nonstationary changes induced by paced hyperventilation and the effects of hypocapnia on the autoregulation of cerebral blood flow. Contrary to hypercapnia, where the response is dominated by CrCP, hypocapnia shows an initial depression of cerebral autoregulation, followed by improvements controlled by changes in RAP.
  • Adapted cardiac rehabilitation for people with sub-acute, mild-to-moderate stroke: a mixed methods feasibility study

    Robinson, Thompson; Drewry, S; Singh, Sally (2021-11-29)
    Objective: To determine the recruitment strategy, acceptability, adherence, outcome measures, and adverse events for a definitive study that will explore adapted cardiac rehabilitation (CR) for people post-stroke with mild-to-moderate severity stroke in the sub-acute stage of recovery. Design: Mixed methods feasibility study. Setting: Acute hospital setting, neurology outpatients and community hospitals. Participants: 32 participants with stroke (mean age: 64.4 years) of median National Institutes of Health Stroke Scale (NIHSS) score 2 (range: 0 to 6) within six months of stroke. Intervention: All participants attended six weeks, adapted CR within one to six months after a stroke. A combined class with people post cardiac event. Main outcome measures: Incremental shuttle walk test (ISWT), blood pressure, heart rate, weight, body mass index, quality of life, fatigue, anxiety and depression, tone, falls, stroke attitude and knowledge, physical activity (accelerometry) and functional ability. Qualitative: Interviews with participants, non-participants and people post-cardiac event. Focus groups with Stroke and CR teams. Results: 32 participants were recruited. The programme was acceptable to people with mild stroke (NIHSS<3) and people post cardiac events; 80% of classes attended, a mean of 9.6 classes, with six drop-outs. The ISWT was an acceptable outcome measure (for NIHSS<3) and most measures showed positive changes. There was one adverse event. Conclusion: A definitive study to determine the effect of six weeks of adapted CR on cardiorespiratory fitness (CRf) in people who have had a mild severity stroke (NIHSS<3) in the sub-acute phase of recovery, is feasible. Teams need specialist education and support. A more specialist service may be needed for people with a stroke severity defined by NIHSS>2. Clinical trial registration number: ISRCTN14861846.
  • Effect of tranexamic acid administration on remote cerebral ischemic lesions in acute spontaneous intracerebral hemorrhage: A substudy of a randomized clinical trial

    Gallagher, Rebecca; Swienton, David (2022-03-21)
    Importance: Hyperintense foci on diffusion-weighted imaging (DWI) that are spatially remote from the acute hematoma occur in 20% of people with acute spontaneous intracerebral hemorrhage (ICH). Tranexamic acid, a hemostatic agent that is under investigation for treating acute ICH, might increase DWI hyperintense lesions (DWIHLs). Objective: To establish whether tranexamic acid compared with placebo increased the prevalence or number of remote cerebral DWIHLs within 2 weeks of ICH onset. Design, setting, and participants: This prospective nested magnetic resonance imaging (MRI) substudy of a randomized clinical trial (RCT) recruited participants from the multicenter, double-blind, placebo-controlled, phase 3 RCT (Tranexamic Acid for Hyperacute Primary Intracerebral Hemorrhage [TICH-2]) from July 1, 2015, to September 30, 2017, and conducted follow-up to 90 days after participants were randomized to either the tranexamic acid or placebo group. Participants had acute spontaneous ICH and included TICH-2 participants who provided consent to undergo additional MRI scans for the MRI substudy and those who had clinical MRI data that were compatible with the brain MRI protocol of the substudy. Data analyses were performed on an intention-to-treat basis on January 20, 2020. Interventions: The tranexamic acid group received 1 g in 100-mL intravenous bolus loading dose, followed by 1 g in 250-mL infusion within 8 hours of ICH onset. The placebo group received 0.9% saline within 8 hours of ICH onset. Brain MRI scans, including DWI, were performed within 2 weeks. Main outcomes and measures: Prevalence and number of remote DWIHLs were compared between the treatment groups using binary logistic regression adjusted for baseline covariates. Results: A total of 219 participants (mean [SD] age, 65.1 [13.8] years; 126 men [57.5%]) who had brain MRI data were included. Of these participants, 96 (43.8%) were randomized to receive tranexamic acid and 123 (56.2%) were randomized to receive placebo. No baseline differences in demographic characteristics and clinical or imaging features were found between the groups. There was no increase for the tranexamic acid group compared with the placebo group in DWIHL prevalence (20 of 96 [20.8%] vs 28 of 123 [22.8%]; odds ratio [OR], 0.71; 95% CI, 0.33-1.53; P = .39) or mean (SD) number of DWIHLs (1.75 [1.45] vs 1.81 [1.71]; mean difference [MD], -0.08; 95% CI, -0.36 to 0.20; P = .59). In an exploratory analysis, participants who were randomized within 3 hours of ICH onset or those with chronic infarcts appeared less likely to have DWIHLs if they received tranexamic acid. Participants with probable cerebral amyloid angiopathy appeared more likely to have DWIHLs if they received tranexamic acid. Conclusions and relevance: This substudy of an RCT found no evidence of increased prevalence or number of remote DWIHLs after tranexamic acid treatment in acute ICH. These findings provide reassurance for ongoing and future trials that tranexamic acid for acute ICH is unlikely to induce cerebral ischemic events. Trial registration: Identifier: ISRCTN93732214.
  • The development of a self-management intervention for stroke survivors - My Life After Stroke (MLAS)

    Johnson, Vicki; Davies, Melanie (2022-02-03)
    Purpose: Long-term needs of stroke survivors (especially psychosocial needs and stroke prevention) are not adequately addressed. Self-management programmes exist but the optimal content and delivery approach is unclear. We aim to describe the process undertook to develop a structured self-management programme to address these unmet needs. Materials and methods: Based on the Medical Research Council framework for complex interventions, the development involved three phases: "Exploring the idea": Evidence synthesis and patient and public involvement (PPI) with stroke survivors, carers and healthcare professionals. "The iterative phase": Development and iterative refinement of the format, content, underpinning theories and philosophy of the self-management programme My Life After Stroke (MLAS), with PPI. MLAS consists of two individual appointments and four group sessions over nine weeks, delivered interactively by two trained facilitators. It aims to build independence, confidence and hope and focusses on stroke prevention, maximising physical potential, social support and managing emotional responses. MLAS is grounded in the narrative approach and social learning theory. "Ready for research": The refinement of a facilitator curriculum and participant resources to support programme delivery. Results: Through a systematic process, we developed an evidence- and theory-based self-management programme for stroke survivors. Conclusions: MLAS warrants evaluation in a feasibility study.Implications for rehabilitationMy Life After Stroke(MLAS) has been developed using a systematic process, to address the unmet needs of stroke survivors.This systematic process, involved utilising evidence, theories, patient and public involvement, expertise and guidelines from other long-term conditions. This may further help the development of similar self-management programme within the field of stroke.MLAS warrants further evaluation within a feasibility study.
  • Neurological complications in high-risk patients undergoing coronary artery bypass surgery

    Mariscalco, Giovanni (2021-05-31)
    Background: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass and minimal or no aortic manipulation may be associated with a lower risk of neurological complications. We investigated this issue in patients with a high risk of perioperative stroke. Methods: Data on 7352 patients who underwent isolated CABG from January 2015 to May 2017 were included in the multicenter study E-CABG (European Coronary Artery Bypass Grafting) registry. Of these, 684 patients had an increased risk of neurological complications, ie, previous stroke or transient ischemic attack, severe carotid artery stenosis or occlusion, or previous carotid artery intervention. In this subgroup, we analyzed the rates of the combined primary endpoint comprising any postoperative stroke or transient ischemic attack. A comparative analysis between CABG with and without aortic cross-clamping was performed. Results: The primary endpoint was more often reached when aortic cross-clamping was used (propensity score matching, without vs with aortic cross-clamp: 0.9% vs 7.2%; P = .016). In comparison with all other revascularization techniques, off-pump CABG with avoidance of aortic manipulation was associated with the lowest rate of neurological complications (0.7%). Conclusions: In patients with increased risk of perioperative stroke, aortic manipulation including the use of cardiopulmonary bypass or partial clamping for central anastomoses is associated with higher rates of postoperative neurological complications. These patients may benefit from off-pump surgery without aortic manipulation if complete revascularization can be ensured.
  • Brain tissue motion in acute hemorrhagic stroke using amplified MRI (aMRI)

    Ince, Jonathan; Wormleighton, Joanne; Chung, Emma; Minhas, Jatinder S (2022-02)
    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.
  • Emerging detection techniques for large vessel occlusion stroke: A scoping review

    Nicholls, Jennifer; Chung, Emma (2022-01-06)
    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.
  • Review of studies on dynamic cerebral autoregulation in the acute phase of stroke and the relationship with clinical outcome

    Minhas, Jatinder S (2021-09-13)
    Acute stroke is associated with high morbidity and mortality. In the last decades, new therapies have been investigated with the aim of improving clinical outcomes in the acute phase post stroke onset. However, despite such advances, a large number of patients do not demonstrate improvement, furthermore, some unfortunately deteriorate. Thus, there is a need for additional treatments targeted to the individual patient. A potential therapeutic target is interventions to optimize cerebral perfusion guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). This narrative led to the development of the INFOMATAS (Identifying New targets FOr Management And Therapy in Acute Stroke) project, designed to foster interventions directed towards understanding and improving hemodynamic aspects of the cerebral circulation in acute cerebrovascular disease states. This comprehensive review aims to summarize relevant studies on assessing dCA in patients suffering acute ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage. The review will provide to the reader the most consistent findings, the inconsistent findings which still need to be explored further and discuss the main limitations of these studies. This will allow for the creation of a research agenda for the use of bedside dCA information for prognostication and targeted perfusion interventions.
  • Bi-atrial thrombus straddling a patent foramen ovale with bilateral embolization: A therapeutic challenge

    Dattani, Abhishek; Safwan, Kassem; Ansari, Mohammedimran; Somani, Riyaz (2022-01)
    Stroke is a leading cause of morbidity and mortality across the world and a significant portion of ischemic strokes have a cardiac source. We report a case of a 55-year-old male who presented with an ischemic stroke and bilateral pulmonary emboli secondary to an intra-cardiac thrombus straddling a patent foramen ovale, which was clearly seen using transesophageal echocardiography. We discuss the management dilemma associated with this clinical picture given the risk of hemorrhagic transformation in the acute phase of an ischemic stroke. Our case demonstrates the need for a multidisciplinary approach in an area of medicine that lacks clear guidelines.
  • Predictors and outcomes of neurological deterioration in intracerebral hemorrhage: Results from the TICH-2 randomized controlled trial

    Mistri, Amit
    Neurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexamic acid in IntraCerebral Hemorrhage-2 (TICH-2) randomized controlled trial were analyzed. Neurological deterioration was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 or a decline in Glasgow Coma Scale of ≥ 2. Neurological deterioration was considered to be early if it started ≤ 48 h and late if commenced between 48 h and 7 days after onset. Logistic regression was used to identify predictors and effects of neurological deterioration and the effect of tranexamic acid on neurological deterioration. Of 2325 patients, 735 (31.7%) had neurological deterioration: 590 (80.3%) occurred early and 145 (19.7%) late. Predictors of early neurological deterioration included recruitment from the UK, previous ICH, higher admission systolic blood pressure, higher NIHSS, shorter onset-to-CT time, larger baseline hematoma, intraventricular hemorrhage, subarachnoid extension and antiplatelet therapy. Older age, male sex, higher NIHSS, previous ICH and larger baseline hematoma predicted late neurological deterioration. Neurological deterioration was independently associated with a modified Rankin Scale of > 3 (aOR 4.98, 3.70-6.70; p < 0.001). Tranexamic acid reduced the risk of early (aOR 0.79, 0.63-0.99; p = 0.041) but not late neurological deterioration (aOR 0.76, 0.52-1.11; p = 0.15). Larger hematoma size, intraventricular and subarachnoid extension increased the risk of neurological deterioration. Neurological deterioration increased the risk of death and dependency at day 90. Tranexamic acid reduced the risk of early neurological deterioration and warrants further investigation in ICH.
  • Investigating the association between depression and cerebral haemodynamics-A systematic review and meta-analysis

    Chithiramohan, Tamara; Parekh, Jvalant; Minhas, Jatinder S; Robinson, Thompson; Divall, Pip; Beishon, Lucy
    Background: Vascular mechanisms may play a role in depression. The aim of this review is to summarise the evidence on alterations in cerebral haemodynamics in depression. Methods: MEDLINE (1946- present), Embase (1947-present), Web of Science (1970-present), PsycINFO (1984-present), CINAHL (1976-present) and CENTRAL were searched using a predefined search strategy. A meta-analysis was conducted in four groups: 1) global cerebral blood flow (CBF) in ml/min/100 g, 2) CBF velocity (CBFv) in cm/s (maximum flow of left middle cerebral artery, 3) combined CBF and CBFv, 4) Ratio of uptake of Tc 99 m HMPAO (region of interest compared to whole brain). Data are presented as mean difference or standardised mean difference and 95% confidence interval (95% CI). A narrative synthesis of the remaining studies was performed. Results: 87 studies were included. CBF was significantly reduced in depressed patients compared to HC [15 studies, 538 patients, 416 HC, MD: -2.24 (95% CI -4.12, -0.36), p = 0.02, I2 = 64%]. There were no statistically significant differences in other parameters. The narrative synthesis revealed variable changes in CBF in depressed patients, particularly affecting the anterior cingulate and prefrontal cortices. Limitations: There were various sources of heterogeneity including the severity of depression, use of antidepressant medication, imaging modality used and reporting of outcomes. All of these factors made direct comparisons between studies difficult. Conclusions: The reduction in CBF in depressed patients compared to HCs may indicate a role for assessment and CBF altering interventions in high-risk groups. However, results were inconsistent across studies, warranting further work to investigate specific subgroups.

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