Risultati per: Stroke

Stroke, Ahead of Print. Brain arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms are major causes of hemorrhagic stroke, yet noninvasive therapies to prevent growth or rupture are lacking. Understanding the genetic basis of these malformations is critical for uncovering underlying mechanisms, developing targeted prevention strategies, and identifying novel therapeutic targets. This review highlights the causal genes and signaling pathways in AVMs, CCMs, and intracranial aneurysms, noting both their commonalities and differences. For AVMs, somatic mutations in the Ras/MAPK (mitogen-activated protein kinase) and MAPK/ERK (extracellular signal–regulated kinase) pathway are key, particularly in sporadic cases, whereas hereditary conditions like hereditary hemorrhagic telangiectasia and capillary malformation–AVM involve the TGF-β (transforming growth factor β), Ephrin receptor, and angiopoietin-VEGF (vascular endothelial growth factor) signaling pathways. In CCMs, pathways affecting endothelial junctions and vascular stability, such as the ROCK (RhoA/Rho–associated coiled-coil containing kinases) pathway, play a central role. Although the genetic drivers of intracranial aneurysms are more diverse and less clearly linked to specific pathways, there is some overlap with genes in the TGF-β and endothelial function pathways seen in AVMs and CCMs. Emerging therapies for AVMs and CCMs include MAPK/ERK inhibitors, anti-VEGF treatments, and RhoA/ROCK inhibitors, showing potential in preclinical models. Due to the genetic overlap, these advancements may also offer future therapeutic strategies for intracranial aneurysms. As personalized medicine progresses, the development of reliable biomarkers, such as the candidate biomarker VEGF for AVMs and CCMs, will be crucial for guiding treatment decisions. In conclusion, ongoing research into genetic pathways holds promise for novel therapeutic targets that could transform the management of vascular malformations and reduce the risk of hemorrhagic stroke.

Objectives
This systematic review examines prehospital and in-hospital delays in acute stroke care in Indonesia.

Design
Systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources
We conducted a thorough search across 11 databases, ClinicalTrials.gov registries and three preprint repositories up until October 2024.

Eligibility criteria
Studies that examined risk variables associated with hospital delays in the treatment of acute stroke in Indonesian individuals were included.

Data extraction and synthesis
Two reviewers each carried out the data extraction and risk-of-bias evaluation separately. The quality of the study was evaluated using the Risk of Bias in Non-randomised Studies of Exposures tool. The ‘combining p values’ approach and albatross plots were used to synthesise the findings.

Results
A total of 27 studies with 3610 patients were included. Key factors contributing to prehospital delays included low educational level (p=0.014, 6 studies), low socioeconomic status (p=0.003, 5 studies), cultural beliefs affecting decision-making (p

Stroke, Ahead of Print.

Stroke, Ahead of Print. BACKGROUND:As the impact of stroke remains, primary healthcare will continue to be a critical platform managing the poststroke journey. We aimed to identify stroke survivors assisted by community health worker in Brazil and how they relate to the location of rehabilitation facilities locations.METHODS:We developed a cross-sectional study using deidentified data from a real-world database generated by a free data collection app used by community health workers from May 2015 to January 2021 in Brazil to identify stroke survivors and to assess demographics and clinical characteristics. We used data from a public database, Cadastro Nacional de Estabelecimentos de Saúde, for identifying rehabilitation facilities. Locations were obtained by a geocoding application programming interface (Google Maps Platform), distances were measured in kilometers, and travel time in minutes.RESULTS:Among 2 397 764 individuals assisted by community health workers, 21 785 were stroke survivors, representing a 0.9% prevalence. Among this subgroup, the majority were in the Northeast region (n=10 951; 50.3%) and 16 922 (77.7%) in urban areas. Most individuals (n=11 504; n=142; 52.8%) were women, the mean age was 66.5 (SD, 14.7), and 4313 reported physical disability. In total, 348 rehabilitation facilities were identified, mostly located in the Southeast region (40.8%). The mean distance from stroke survivor to facility was 79.13 km (SD, 97.73; median [1Q, 3Q], 47.64 km [12.19, 107.80 km]), and mean travel time was 81.18 minutes (SD, 85.85). The Southern region recorded the largest mean and median distance (mean 175.58 km; SD, 163.18; median [1Q, 3Q] 88.47 [59.38, 425.38]) to rehabilitation center and the longest mean travel time (144.48 minutes; SD, 112.57; median [1Q, 3Q] 92.34 [60.59, 305.12]).CONCLUSIONS:Despite the availability of rehabilitation centers in Brazil, geographic access as represented by the distances and travel times observed access is still suboptimal. As a means of improving the clinical pathway and resource allocation, the use of large real-world databases and adequate analysis may become a key component for real needs assessments.

Stroke, Ahead of Print. BACKGROUND:It is unclear how poststroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic and hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, and cryptogenic/other determined causes), and poststroke cognitive decline.METHODS:We pooled participants from 4 US cohort studies (1971–2019). Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1 SD difference in cognition. The median follow-up for the primary outcome was 6.0 (interquartile range, 3.2–9.2) years. Linear mixed-effects models estimated changes in cognition after stroke.RESULTS:We identified 1143 dementia-free individuals with acute stroke during follow-up: 1061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, and 30.8% Black. The median age at stroke was 74.1 (interquartile range, 68.6–79.3) years. On average, ischemic stroke survivors showed declines in global cognition (−0.35 [95% CI, −0.43 to −0.27] points/y;P

Stroke, Ahead of Print. The 2024 Guidelines for the Primary Prevention of Stroke, recently updated by the American Heart Association and the American Stroke Association, serve as an essential resource for clinicians aiming to reduce the growing impact of cerebrovascular disease. These guidelines emphasize modifiable risk factors and population-specific considerations, covering a range of cardiovascular conditions, including hypertension, diabetes, atherosclerotic disease, and genetic predispositions to stroke. However, a notable omission in these guidelines is the absence of specific recommendations for patients with thrombotic thrombocytopenic purpura. Indeed, these patients are particularly susceptible to stroke, which can be the sole manifestation of the disease. Given the established association between thrombotic thrombocytopenic purpura and ischemic stroke and the effectiveness of preventive interventions, future guidelines should include specific recommendations for patients with thrombotic thrombocytopenic purpura to avert thrombotic events, including stroke. In that regard, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) activity measurement should be considered in the workup of cryptogenic stroke.

Stroke, Ahead of Print.

Stroke, Ahead of Print. BACKGROUND:Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is recommended for secondary prevention in patients with a minor stroke or transient ischemic attack. However, the effectiveness of DAPT can be significantly influenced by genetic variations. This study aimed to estimate the impact of multiple single-nucleotide polymorphisms across various genes on DAPT efficacy using polygenic risk score (PRS).METHODS:In this post hoc analysis, we included 2905 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), which enrolled a total of 5170 patients in China between October 2009 and July 2012. The primary outcome was new stroke within 90 days. Sixteen single-nucleotide polymorphisms across 7 genes involved in clopidogrel metabolism were selected for PRS development. PRS were calculated by summing single-nucleotide polymorphisms from each individual. The Cox proportional-hazards regression model was utilized to estimate the hazard ratio (HR) and 95% CIs of PRS. The predictive value of PRS was estimated by C statistic and compared with a previously validated model.RESULTS:The elevated PRSs were associated with an increased risk of new stroke within 90 days (Ptrend=0.01). The efficacy of DAPT versus aspirin alone in preventing 1-year composite vascular events was significantly different between patients with low (adjusted HR, 0.47 [95% CI, 0.31–0.71]) and high PRSs (adjusted HR, 0.84 [95% CI, 0.60–1.18];Pinteraction=0.03). In patients receiving DAPT, higher PRSs were associated with increased risk of new stroke and composite vascular events at 90 days (adjusted HR per SD increase was 1.51 [95% CI, 1.15–1.99]) and at 1 year (adjusted HR per SD increase was 1.34 [95% CI, 1.08–1.67]). The C statistic for predicting 90-day new stroke using the PRS developed in this study was 0.57 (95% CI, 0.52–0.62), compared with 0.52 (95% CI, 0.48–0.55) for the ABCD-GENE score.CONCLUSIONS:Using PRS integrating multiple genes may enhance the precision of secondary prevention strategies for patients with minor stroke or transient ischemic attack in the short and long term.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT00979589.

Stroke, Ahead of Print.

Stroke, Ahead of Print. BACKGROUND:More than half of patients with ischemic stroke experience futile reperfusion, increasing the risk of death and disabilities despite a successful recanalization. The reason behind this is debated, and we aim to investigate cerebrovascular changes toward a broader understanding of these conditions. We hypothesize that ischemic stroke reperfusion modifies the expression profile in the microvasculature in a spatial manner toward peri-infarct brain edema and circulatory failure.METHODS:We investigated the early (24-hour) changes in spatial gene expression in the brain parenchymal endothelial cells and mural cells following ischemia stroke reperfusion in 13- to 14-week-old C57BL/6JRj male mice (n=5). Ischemia was induced by occlusion of the middle cerebral artery for 60 minutes, and Nissl staining was used to validate infarct size. Spatial transcriptomics complemented by bulk proteomics was conducted in the peri-infarct cortex region and validated with immunohistochemical semiquantification of proteins of interest. To avoid individual biological variations, changes in the peri-infarct cortex region were expressed relatively to the matching contralateral hemisphere region.RESULTS:Ischemic stroke reperfusion impaired the blood-brain barrier integrity through junctionalCldn5(claudin-5) downregulation, changes of the actin cytoskeleton adhesion, and high expression of the proinflammatoryIl-6(interleukin-6). Molecules important for extracellular Ca2+influx and intracellular Ca2+release,Cacna1e(R-type Ca2+channels),Orai2,Ryr3,Itpr1, andItpka(inositol-trisphosphate 3-kinase A), were markedly reduced. Furthermore, reducedGrm5(glutamate receptor 5) associated with upregulatedNfatc3andStat3implicates suppression of the contractile phenotype, suggesting reduced poststroke vascular resistance due to loss of mural cell tone. The complete spatial transcriptomics map over the ipsilateral and contralateral hemispheres is available online as a Web tool.CONCLUSIONS:Emphasizing the spatial molecular pattern behind blood-brain barrier disruption and loss of the vascular tone in the acute phase following ischemic stroke reperfusion suggests the gene expression contribution for a therapeutic target in ischemia-reperfusion abnormalities.

Stroke, Ahead of Print. BACKGROUND:The benefits and safety of mechanical thrombectomy (MT) in patients with prestroke disability, classified as modified Rankin Scale (mRS) score of 3 to 4, and anterior circulation stroke remain uncertain. This study aims to evaluate these factors using data from the Italian Registry of Endovascular Treatment in Acute Stroke.METHODS:We analyzed data collected between 2015 and 2021, comparing functional outcomes (mRS), symptomatic intracerebral hemorrhage, and recanalization rates (Thrombolysis in Cerebral Infarction) at 90 days post-MT in patients with prestroke mRS score of 3 to 4 versus 0 to 2. A good outcome was defined as no change in the mRS score from baseline. Subgroup analysis was stratified by age.RESULTS:A total of 11.411 (96%) patients with prestroke mRS score of 0 to 2 and 477 (4%) patients with prestroke mRS score of 3 to 4 were included. Compared with patients with a baseline mRS score 0 to 2, those with mRS score 3 to 4 were older (82 versus 75 years;P

Stroke, Ahead of Print. BACKGROUND:Various measures of abnormal left atrial (LA) structure or function (LA myopathy) are associated with a higher risk of ischemic stroke and dementia, independent of atrial fibrillation. However, limited data exist on their prognostic usefulness. Therefore, we aimed to assess the ability of markers of LA myopathy to improve the prediction of ischemic stroke and dementia.METHODS:The ARIC study (Atherosclerosis Risk in Communities) is a prospective community-based cohort study. For this analysis, we included participants who attended visit 5 (2011–2013) without a history of stroke or atrial fibrillation and had a 12-lead ECG and a transthoracic echocardiogram. Markers of LA myopathy included P wave abnormalities from 12-lead ECG, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and LA volume and strain parameters from the echocardiogram. The primary composite outcome comprised ischemic stroke and dementia, which were ascertained through hospital surveillance, cohort follow-up, and death registries. To determine improvement in risk prediction of the composite outcome, each marker was individually added to a model that included CHA2DS2-VASc variables, and Akaike information criterion, C statistic, and its change were computed. Cox proportional hazards models were used to assess the independent association of LA myopathy markers with the outcome.RESULTS:Among 4712 participants (59% female; mean age, 74 years), 193 ischemic strokes and 769 dementia cases were ascertained over a median follow-up of 8.3 years. Of LA myopathy markers, only LA reservoir strain and NT-proBNP significantly improved C statistic when added to the CHA2DS2-VASc model (base C statistic, 0.677) for the prediction of the composite outcome. Adding the LA reservoir yielded the highest increase in C statistic (0.010 [95% CI, 0.003–0.017]), and the model including the LA reservoir showed the lowest Akaike information criterion. In multivariable regression models, LA volume index, NT-proBNP, and LA strain parameters were significantly associated with the composite outcome.CONCLUSIONS:Of various LA myopathy markers, LA reservoir yields the greatest improvement in the prediction of ischemic stroke and dementia, supporting its use to identify people at high risk of cerebrovascular events and dementia.

Introduction
Stroke presents a considerable burden not only to patients but also to their families and society at large. In many instances, stroke patients opt for home rehabilitation, relying on family caregivers for daily assistance. This dynamic significantly influences the physiological, psychological and social well-being of these caregivers. Despite its importance, the phenomenon of self-regulatory fatigue (SRF) among family caregivers has received insufficient attention in the literature. Therefore, the objective of this study is to investigate the levels of SRF, the characteristics of associated symptoms and the trajectories of symptom change experienced by family caregivers of stroke patients.

Methods and analysis
This research employs a mixed-methods approach, combining a cross-sectional study with a prospective longitudinal quantitative and qualitative design. The Chinese version of the SRF Scale and the Chinese version of Patient-Reported Outcomes Measurement Information System profile-29 are used to assess SRF, psychological and physiological symptoms, and related functional outcomes among family caregivers of stroke patients. Latent class growth analysis will be employed to model the heterogeneous developmental trajectories of SRF-related symptoms among family caregivers of stroke patients. Reflexive thematic analysis will be employed to analyse, organise and summarise qualitative data, to identify the experiences and management needs related to SRF among family caregivers during home care. Through this comprehensive mixed-methods approach, the study aims to: investigate the levels of SRF experienced by family caregivers of stroke patients, identify patterns and trajectories of related symptoms. The integration of cross-sectional and longitudinal data allows for a thorough examination of both immediate and long-term aspects of caregiver experiences, providing valuable insights into the complex dynamics of SRF in this population.

Ethics and dissemination
The study protocol was approved by the Medical Ethics Committee of the University of South China (approval number 2023-NHHL-051). Data collection was authorised by the ethics committees of the First Affiliated Hospital, Second Affiliated Hospital and Nanhua Affiliated Hospital of the University of South China. The results of this study will be disseminated through publication in pertinent peer-reviewed journals, presentation at local and international conferences, and communication with all relevant stakeholders.

Trial registration number
ChiCTR2400082717.

Background
Electroacupuncture (EA) is commonly used in clinical settings as a significant method for treating a variety of pain and cerebrovascular disorders. Despite its widespread use, there is limited information on the impact of perioperative EA on postoperative stroke. This study aimed to investigate whether preoperative EA therapy could reduce the occurrence of acute stroke in patients undergoing interventional surgery for intracranial aneurysms.

Methods/design
This single-centre, double-blind, placebo-controlled, randomised clinical trial aims to recruit 280 patients undergoing embolisation of intracranial aneurysms under general anaesthesia. Participants will be randomly assigned to either the EA group or sham electroacupuncture (SEA) group. The EA group will receive treatment half an hour before surgery, while the SEA group will receive sham acupuncture. The primary outcome will be the occurrence of acute stroke within 7 days post surgery. Secondary outcomes include the incidence of symptomatic and occult stroke within the same timeframe, the occurrence of cerebral vasospasm during the operation and the number of intraoperative cerebrovascular dissections.

Ethics and dissemination
This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2023-SR-538.A1). The study started on 17 May 2024, and it is expected to end on 31 March 2025. The results of our study will be published in peer-reviewed journals.

Trial registration number
ChiCTR2300076960.

Introduction
Combining repetitive transcranial magnetic stimulation (rTMS) with robotic training could result in more significant improvements in motor function than either treatment alone. The efficacy of this combination may depend on the sequencing of the interventions. However, few studies have explored the possibility of interleaving or alternating between the two treatment modalities within a single session or over a shorter time frame. The objective of this study is to evaluate the efficacy of alternating rTMS and soft-hand rehabilitation robot therapy to enhance upper limb and hand function in patients with ischaemic stroke.

Methods and analysis
This multicentre study will be conducted as a single-blind, controlled, randomised trial, enrolling 132 post-stroke patients with a disease duration ranging from 1 week to 3 months. The study participants will be randomly assigned to group A (n=44), group B (n=44) and group C (n=44). All participants will undergo a 4-week neurological rehabilitation programme, which includes standardised physical and occupational therapy administered by experienced therapists. Group A will receive 10 Hz high-frequency rTMS (HF-rTMS) over the ipsilesional primary motor cortex (iM1) for 20 min, followed by 20 min of soft-hand rehabilitation robot training. Group B will receive 5 min of 10 Hz HF-rTMS over the iM1 followed by 5 min of soft-hand rehabilitation robot training, repeated four times. Group C will receive sham rTMS with other parameters identical to those of group A. The above treatments will be administered once daily, 5 days a week, for 4 weeks. The primary outcome measurement is the Fugl-Meyer assessment of upper extremity (FMA-UE). The secondary outcome measurements include the Hong Kong edition of Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK), the Modified Ashworth Scale (MAS), and the International Classification of Functioning, Disability and Health upper extremity entries (ICF-Upper Extremity Entries). Assessments will be conducted at baseline and after 4 weeks of treatment.

Ethics and dissemination
This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2024-SR-515). The findings of this study will be spread through networks of scientists, professionals and the general public, as well as peer-reviewed scientific papers and presentations at pertinent conferences.

Trial registration number
ChiCTR2400089583.

Stroke, Ahead of Print. BACKGROUND:Decades of experimental and clinical data revealed that spreading depolarizations (SDs) play a central causal role in the development of cortical lesions after acute brain injury. However, clinical documentation of events at the onset of focal ischemic stroke and during the initial phase of cortical injury development is lacking because electroencephalography monitoring of SD typically starts hours or days later. Here, we used nonhuman primates to map electrophysiological pathology through focal ischemic stroke’s onset and acute stage.METHODS:Craniotomies were performed over both hemispheres on 4 male and 1 female nemestrina and rhesus macaques aged 23 years to 32 years. Subdural electrode arrays were placed bilaterally over the middle cerebral artery territory, recording from 24 electrodes 1 cm apart on the left cortex and 7 on the right. After 30 minutes of baseline monitoring, the left middle cerebral artery and, in some cases, also the left internal carotid or anterior cerebral arteries were permanently occluded with aneurysmal clips.RESULTS:Repetitive SDs occurred during the next 3 hours, followed by terminal SD during euthanasia. No epileptiform activity was observed in any of the 5 animals. Nonspreading electrical silence developed in the ischemic core within seconds of ischemic onset, followed by terminal SD and SD-initiated negative ultraslow potential after several minutes. These events defined the ischemic core and led to histologically confirmed cell damage. Initial and subsequent transient SDs caused spreading depression of spontaneous activity in the normally perfused surrounding cortex without any signs of histological damage. Cardiocirculatory arrest at the end of experiments first induced nonspreading depression of activity followed by SD and, eventually, the SD-initiated negative ultraslow potential, which indicated brain death.CONCLUSIONS:Results in gyrencephalic nonhuman primates hold significant implications for understanding the role of SD in acute brain injury development and for the clinical translation and diagnosis of pathologies manifested in the SD continuum.