Risultati per: Stroke

Background and objective
In a drive-the-doctor (DD) paradigm, an interventionalist travels from a comprehensive stroke centre (CSC) to primary stroke centres (PSCs) to perform endovascular thrombectomy (EVT) for acute ischaemic stroke due to large vessel occlusion (LVO). The DD paradigm may reduce time delays from onset to recanalisation. This study aimed to analyse the cost-effectiveness of the DD paradigm versus a drip-and-ship (DS) paradigm, where LVO patients are transferred from PSCs to a CSC for EVT in the northern Netherlands.

Design
Economic evaluation was performed using a simulation model combined with a decision tree and a Markov model.

Setting
Stroke centres in the northern Netherlands.

Participants
A hypothetical cohort of 100 000 LVO patients with an average age of 70 years.

Interventions
Two strategies were tested, including the DD paradigm with one upgraded PSC and the DD paradigm with two upgraded PSCs.

Main outcome measures
Total costs and quality-adjusted life years (QALYs) were measured over a 15-year time horizon from a Dutch healthcare provider perspective. An incremental cost-effectiveness ratio (ICER) of 50 000 was used as a willingness-to-pay threshold. One-way sensitivity, probabilistic sensitivity and scenario analyses (interventionalist transportation by car, ambulance and helicopter) were conducted to examine parameter uncertainty.

Results
The DD paradigm using car as a transport modality and two PSCs was the optimal strategy, resulting in the lowest ICER. This strategy provided an additional 0.13 QALYs at incremental costs of 2367, yielding an ICER of 18 306 compared with current practice. The DD paradigm with two PSCs reduced ICERs compared with the scenario with one PSC when varying transportation modalities (car, ambulance and helicopter). Probabilistic sensitivity analyses showed that the DD paradigm with two PSCs using car was preferred in 72% of 10 000 Monte Carlo simulations.

Conclusions
The DD paradigm appeared cost-effective for LVO patients and may be considered a promising evolution for a regional stroke network.

Stroke, Ahead of Print. BACKGROUND:We aimed to determine whether extensive severe computed tomography (CT) hypodensity, representing blood-brain barrier injury, would be associated with a reduced benefit of endovascular therapy (EVT) in patients presenting with large core stroke.METHODS:This study is an exploratory analysis of SELECT2 (Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke), a randomized controlled trial of EVT versus medical management in patients with large ischemic core who presented to 31 comprehensive stroke centers across the United States, Canada, Europe, Australia, and New Zealand. Visible CT hypodensity was outlined, and a threshold of severe CT hypodensity was defined as the lower 99% CI of contralateral thalamic gray matter in Hounsfield units (HU). The association between the volume of severe CT hypodensity and modified Rankin Scale (mRS) score of 0 to 3 was evaluated using logistic regression models, with adjustment for age, National Institutes of Health Stroke Scale, total noncontrast CT core volume, and a volume-by-treatment interaction. The relationship between severe CT hypodensity volume and the probability of an mRS score of 0 to 3 was used to select clinically relevant volume cut points for further evaluation. The treatment effect of EVT versus medical management on independent ambulation and hemicraniectomy was assessed in 2 subgroups based on these volume cut points.RESULTS:In 322 patients, the median CT density was 31 HU (interquartile range, 28–34). The selected threshold of severe CT hypodensity was 26 HU. The volume of ischemic core ≤26 HU (per 1 mL increase) was associated with lower odds of mRS score of 0 to 3 after EVT (adjusted odds ratio [aOR], 0.96 [95% CI, 0.94–0.99]), but not medical management (aOR, 1.01 [95% CI, 0.98–1.03];Pinteraction

Stroke, Ahead of Print. BACKGROUND:Fluid-attenuated inversion recovery vascular hyperintensities (FVH) are high signal intensities on magnetic resonance imaging resulting from sluggish or stagnant flow through vessels. This investigation describes the prevalence, risk factors, and outcomes associated with FVH in pediatric arterial ischemic stroke (AIS).METHODS:Retrospective review of children aged 29 days to 18 years in a single institution stroke registry from 2006 to 2022 with AIS. Magnetic resonance imaging were assessed for large vessel occlusion (LVO), FVH score, modified Alberta Stroke Program Early Computed Tomography Score, and AIS volume. The association between demographic and imaging factors with the presence of and high FVH burden was assessed using Fisher exact, Pearson χ2, or Kruskal-Wallis tests. Wilcoxon rank-sum test evaluated the association of FVH score with the presence of LVO and poor outcome. The relationship between FVH score and age, time to magnetic resonance imaging, stroke volume, modified Alberta Stroke Program Early Computed Tomography Score, Pediatric National Institutes of Health Stroke Scale, and Pediatric Stroke Outcome Measure score were assessed using Spearman correlation. A multivariable logistic regression was used to evaluate predictors of FVH.RESULTS:In total, 273 patients with AIS were screened, and 83 met the inclusion criteria. Patients were a median age of 11.6 years (range, 1 month–18 years) and 37% were female. FVH were present in 53% of the cohort. Median FVH score was 0 (interquartile range, 0–2) in those without LVO and 5.5 (interquartile range, 3–7) in those with LVO (P

Stroke, Ahead of Print. BACKGROUND:Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals.METHODS:This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression.RESULTS:In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13];P=0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91];P=0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58];P

Stroke, Ahead of Print. Stroke remains a predominant cause of death and long-term disability among adults worldwide. Emerging evidence suggests that proteinopathies, characterized by the aggregation and accumulation of misfolded proteins, may play a significant role in the aftermath of stroke and the progression of neurodegenerative disorders. In this review, we explore preclinical and clinical research on key proteinopathies associated with stroke, including tau, Aβ (amyloid-β), TDP-43 (TAR DNA-binding protein 43), α-synuclein, and UCH-L1 (ubiquitin C-terminal hydrolase-L1). We focus on their potential as biomarkers for recovery management and as novel treatment targets that may enhance neuronal repair and mitigate secondary neurodegeneration. The involvement of these proteinopathies in various aspects of stroke, including neuroinflammation, oxidative stress, neuronal damage, and vascular dysfunction, underscores their potential. However, further investigations are essential to validate the clinical utility of these biomarkers, elucidate the mechanisms connecting proteinopathies to poststroke neurodegeneration, and develop targeted interventions. Identifying specific protein signatures associated with stroke outcomes could facilitate the advancement of precision medicine tailored to individual patient needs, significantly enhancing the quality of life for stroke survivors.

Introduction
Arm weakness after stroke is one of the leading causes of adult-onset disability. Invasive vagus nerve stimulation (VNS) paired with rehabilitation has been shown to improve arm recovery in chronic stroke. Small studies of non-invasive or transcutaneous VNS (tVNS) suggest it is safe and tolerable. However, it is not known whether tVNS paired with rehabilitation is effective in promoting arm recovery in chronic stroke and what the mechanisms of action are.

Methods and analysis
TRICEPS is a UK multicentre, double-blinded, superiority, parallel-group, three-arm two-stage with an option to select promising arm(s) at 50% accrual, individually randomised, sham-controlled trial. Up to 243 participants will be randomised (1:1:1) using minimisation via a restricted, web-based centralised system. tVNS will be delivered by a movement-activated tVNS system (TVNS Technologies), which delivers stimulation during repetitive task practice. Rehabilitation will consist of repetitive task training for 1 hour a day, 5 days per week for 12 weeks. Participants will be adults with anterior circulation ischaemic stroke between 6 months and 10 years prior with moderate-severe arm weakness. The primary outcome measure will be the change in Upper Limb Fugl-Meyer total motor score at 91 days after the start of treatment. Secondary outcome measures include the Wolf Motor Function Test, the Modified Ashworth Scale to assess spasticity in the affected arm and the Stroke-Specific Quality of Life Scale. A mechanistic substudy including 40 participants will explore the mechanisms of active versus sham tVNS using multimodal MRI and serum inflammatory cytokine levels. Participant recruitment started on 30 November 2023.

Ethics and dissemination
The study has received ethical approval from the Cambridge Central Research Ethics Committee (REC reference: 22/NI/0134). Dissemination of results will be via publications in scientific journals, meetings, written reports and articles in stakeholder publications.

Trial registration number
ISRCTN20221867.

Stroke, Ahead of Print. BACKGROUND:Recently, various polygenic risk score (PRS)–based methods were developed to improve stroke prediction. However, current PRSs (including cross-ancestry PRS) poorly predict recurrent stroke. Here, we aimed to determine whether the best PRS for Japanese individuals can also predict stroke recurrence in this population by extensively comparing the methods and maximizing the predictive performance for stroke onset.METHODS:We used data from the disease-oriented BBJ1 (BioBank Japan first cohort; recruited between 2003 and 2007, n=179 938) to derive and optimize the PRSs using a 10-fold cross-validation. We integrated the optimized PRSs for multiple traits, such as vascular risk factors and stroke subtypes to generate a single PRS using the meta-scoring approach (metaGRS). We used an independent BBJ2 (BBJ second cohort; recruited between 2012 and 2017, n=41 929) as a test sample to evaluate the association of the metaGRS with stroke and recurrent stroke. In addition, we analyzed its association stratified by risk factors. We administered 3 distinct tests to consider the potential index event bias.RESULTS:We analyzed recurrent stroke cases (n=174) and nonrecurrent stroke controls (n=1153) among subjects within the BBJ2. After adjusting for known risk factors, metaGRS was associated with stroke recurrence (adjusted odds ratio per SD, 1.18 [95% CI, 1.00–1.39];P=0.044), although no significant correlation was observed with the published PRSs. The outcomes derived from these examinations did not provide any significant indication of the influence of index event bias. The high metaGRS group without a history of hypertension had a higher risk of stroke recurrence than that of the low metaGRS group (adjusted odds ratio, 2.24 [95% CI, 1.07–4.66];P=0.032). There was no association at all in the hypertension group (adjusted odds ratio, 1.21 [95% CI, 0.69–2.13];P=0.50).CONCLUSIONS:The metaGRS developed in a Japanese cohort predicted stroke recurrence in an independent cohort of patients. In particular, it predicted an increased risk of recurrence among stroke patients without hypertension. These findings provide clues for additional genetic risk stratification and help in developing personalized strategies for stroke recurrence prevention.

Stroke, Ahead of Print. BACKGROUND:Thalamic stroke (TS) often presents with complex clinical manifestations, including sleep-wake disturbances, cognitive deficits, and autonomic dysregulation, yet the interaction between these functional alterations remains poorly understood. We aimed to investigate these interactions in a case-control lesion study.METHODS:Patients with acute TS and no-stroke controls were included prospectively in this study. The data were collected from June 2020 to September 2022 at the stroke unit or sleep laboratory of the Inselspital (Bern). Sleep-wake variables (questionnaires, actigraphy, polysomnography including electroencephalography-based sleep macroarchitecture and microarchitecture, and analysis of electroencephalography spectral power), nocturnal heart rate variability, and cognition (5 tests: processing speed, attention, working memory, visual memory, and verbal memory) were assessed at study inclusion (within 5 days poststroke for patients with stroke).RESULTS:Data from 16 patients with TS and 32 control volunteers were analyzed. All patients with stroke had lesions of the ventral nuclei, while 9 of 16 patients with stroke also had lesions in the mediodorsal nucleus (1 bilateral). TS was characterized by long sleep duration and high nocturnal heart rate variability with parasympathetic dominance. The alterations in sleep electroencephalography included a decrease in cyclic alternating pattern index, slow spindle density, the quantity of isolated sawtooth wave segments, and electroencephalography spectral power predominantly affecting the alpha band. The mediodorsal lesions were associated with a decrease in sleep spindle amplitude and slow wave amplitude and with an increase in phasic rapid eye movement sleep. Furthermore, patients with TS had deficits in processing speed, working memory, and verbal memory, mostly pronounced in patients with mediodorsal lesions. In a combined data set, multiple correlations were observed between sleep-wake, autonomic, and cognitive parameters, many of which depended on the presence of a TS.CONCLUSIONS:These findings emphasize the role of the thalamus in the regulation of sleep-wake, autonomic, and cognitive functions and their interactions and provide the theoretical basis for the therapies targeting the thalamus.

Stroke, Ahead of Print. BACKGROUND:The optimal anesthetic approach for patients with acute ischemic stroke with large vessel occlusion but low National Institutes of Health Stroke Scale receiving mechanical thrombectomy remains unclear. We aimed to evaluate the association of anesthetic strategies with procedural and clinical outcomes, hypothesizing that conscious sedation/local anesthesia (CS/LA) may offer a more favorable risk-benefit ratio than general anesthesia (GA).METHODS:Multicenter cohort study screening all thrombectomy patients prospectively enrolled in GSR-ET (German Stroke Registry-Endovascular Treatment) across 25 centers between 2015 and 2021. Patients with an admission National Institutes of Health Stroke Scale score of

Yang X, He X, Pan D, et al. Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. BMJ Open 2024;14:e091059. doi: 10.1136/bmjopen-2024091059
This article was previously published with an error.
Figure 1 has been updated. During the trial, some participating centres underwent official name changes. The figure now reflects the revised names while maintaining the original study site distribution. These changes neither affect the centres themselves or the conduct of the trial nor the study’s data and conclusions.

Objectives
Changes in poststroke heart rate variability (HRV) might be helpful for early identification of patients with neurological impairment and poor prognosis, which could allow for early intervention to reduce adverse outcomes. The aim of this study is to perform a scoping review to identify the influence of poststroke HRV on the neurological impairment severity and the prognosis among patients with ischaemic stroke (IS).

Design
The study design allows us to examine existing research, identify the research gaps and target the important areas for future research. In the search and report process, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines and checklist were used.

Data sources
Three databases (PubMed, Web of Science and Ovid MEDLINE (Ovid)) were searched before December 2023.

Eligibility criteria for selecting studies
The literature related to the topic of this study was mainly included, and the articles were excluded if they only focused on cerebral haemorrhage or were reviews, guidelines, books, etc.

Data extraction and synthesis
Descriptive analysis was used to display the distribution of the included studies and then the summary method was adopted for further analysing.

Results
3251 articles that may be related to the scoping review topic were screened. After title and abstract screening and full-text reading, 21 records were finally included. Whether at discharge (n=6) or after follow-up (n=11), it was found that when the SD of all normal-to-normal intervals (SDNN) or the SD of the averages of normal-to-normal intervals decreased, the neurological impairment severity would be increased, including dysarthria, aphasia and hemiplegia. The root mean square of successive differences, the ratio of low frequency to high frequency and the high frequency were valuable predictors for the occurrence of adverse cardiocerebrovascular events. And the poor prognosis among patients with IS might be influenced by SDNN.

Conclusion
This scoping review confirmed that post-IS HRV indicators can predict neurological impairment and prognosis of patients with stroke, highlighting a potential direction for early intervention. Large independent cohorts should be used to evaluate the predictive performance, reliability and potential limitations of these indicators in the future, and it will be important to explore interventions that make HRV change.

Stroke, Volume 56, Issue 4, Page 807-807, April 1, 2025.

Stroke, Volume 56, Issue 4, Page 1026-1035, April 1, 2025. BACKGROUND:In ischemic stroke due to large vessel occlusion, cerebral blood flow is impaired by thromboemboli, which can originate from various sources in the body. A better understanding of thromboembolus composition can improve our understanding of the underlying pathophysiology and potentially guide improvement of prevention strategies. The aim of this study therefore was to perform a large-sample multi-parameter quantitative histological analysis of retrieved thromboemboli from stroke patients.METHODS:Thromboemboli (n=501) were collected from thrombectomy-treated ischemic stroke patients at AZ Groeninge Hospital (Kortrijk, Belgium) and CHU Lille (Lille, France). Stroke etiology was determined by the treating stroke specialist using the TOAST classification system (Trial of ORG 10172 in Acute Stroke Treatment). Extensive histological analysis, blinded to stroke etiology, was performed for key thrombus constituents including red blood cells (RBCs), platelets, fibrin, von Willebrand Factor, leukocytes, citrullinated histone H3 (as a marker for neutrophil extracellular traps), and extracellular (ex)DNA. Quantitative histology results were linked to etiology.RESULTS:Compared with large-artery atherosclerotic thromboemboli, cardioembolic thromboemboli contained significantly fewer RBCs and significantly more platelets, fibrin, leukocytes, and exDNA. Interestingly, cryptogenic thromboemboli contained relatively low amounts of RBCs and high amounts of platelets, similar to cardioembolic thromboemboli. A multivariable logistic regression model indicated that it is difficult to predict stroke etiology based on the individual thrombus composition.CONCLUSIONS:Based on a large sample cohort of stroke thromboemboli, we found that cardiac thromboemboli contained fewer RBCs and more platelets than atherosclerotic thromboemboli and that cryptogenic thromboemboli have a similar composition to cardiac thromboemboli in terms of RBCs and platelets.

Stroke, Volume 56, Issue 4, Page 948-956, April 1, 2025. BACKGROUND:Evidence of the cost implications and health outcomes associated with the use of mobile stroke units (MSU) is required to support their utilization. We aimed to evaluate the causal effect of the use of an MSU compared with a standard ambulance on hospitalization costs and 90- to 180-day health outcomes.METHODS:Causal effect estimation was performed using patient-level data from a cohort of patients with stroke in 2018 identified from the Australian Stroke Clinical Registry (Victoria) and Melbourne MSU. These data were linked to Ambulance Victoria and government-held administrative data sets. In total, linked data from 8657 patients were available. Propensity score matching was used to define comparator groups within a target trial framework. Costs included emergency department and hospital admission costs in the first 180 days after stroke. Multivariable regression analyses of the matched data were used to compare costs and outcomes (mortality and modified Rankin Scale) between MSU and standard ambulance groups.RESULTS:The target trial sample included 96 patients transported by the MSU (intervention) and 198 patients transported by standard ambulance services (control). Of these, the mean age was 76 years and 157 (53%) were men. A greater proportion of patients received mechanical thrombectomy in the intervention group than the control group (40% versus 23%;P

Stroke, Volume 56, Issue 4, Page 915-925, April 1, 2025. BACKGROUND:Diffusion-weighted magnetic resonance imaging is essential for diagnosing ischemic stroke and identifying targets for emergency revascularization. Apparent diffusion coefficient (ADC) maps derived from diffusion-weighted magnetic resonance imaging are commonly used to locate the infarct core, but they are not strictly quantitative and can vary across platforms and sites due to technical factors. This retrospective study was conducted to examine how differences in ADC map generation, resulting from varied protocols across platforms and sites, affect the determination of infarct core size, location, and related clinical outcomes in acute stroke.METHODS:In this retrospective study, 726 patients with acute anterior circulation stroke from a cohort of 1210 unique visits to the Lausanne University Hospital between May 2018 and January 2021 were selected, excluding patients with poor quality imaging or no magnetic resonance imaging or clinical information available. Diffusion-weighted magnetic resonance imaging data were used to generate ADC maps as they would appear from different protocols: 2 simulated with low- and medium-angular resolution (4 and 12 diffusion gradient directions) and 1 with high-angular resolution (20 directions). Using DEFUSE criteria and image postprocessing, ischemic cores were localized; core volume, location, and associations to the National Institutes of Health Stroke Scale and modified Rankin Scale scores were compared between the 2 imaging sequences.RESULTS:Significant differences were observed in the ADC distribution within white matter, particularly in the kurtosis and skewness, with the segmented infarct core volume being higher in protocols with reduced angular resolution compared with the 20-directions data (7.63 mL versus 3.78 mL). The volumetric differences persisted after correcting for age, sex, and type of intervention. Infarcted voxel’s locations varied significantly between the 2 protocols. This variability affected associations between infarct core volume and clinical scores, with lower associations observed for 4-direction data compared with 20-direction data for the National Institutes of Health Stroke Scale at admission and after 24 hours, and modified Rankin Scale after 3 months, further confirmed by multivariate regression.CONCLUSIONS:Imaging protocol heterogeneity leads to significant changes in the ADC distribution, ischemic core location, size, and association with clinical scores. Work is needed in standardizing imaging protocols to improve the reliability of ADC as an imaging biomarker in stroke management protocols to improve the reliability of ADC as an imaging biomarker in stroke management.

Città della salute e della scienza: “Emergenza senza precedenti”