Risultati per: Stroke

Stroke, Ahead of Print. BACKGROUND:Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), aStachybotrys microsporatriprenyl phenol family member, may extend this therapeutic window.METHODS:In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence).RESULTS:Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42–87) and 8 (6–21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34–85) and 8 (6–22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0–12.1) and 10.0 (3.7–12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0–5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1–13.8]) for placebo (P=0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score

Stroke, Ahead of Print. In recent years, stroke incidence in older adults has declined strikingly, but stroke in younger women has become more common. Abnormalities of menstruation, the shedding of the uterine lining at the beginning of each menstrual cycle, may offer clues about stroke risk in young and midlife women. Endometrial and structural uterine abnormalities are associated with anemia and may be associated with hypercoagulability, possibly increasing stroke risk. Patient factors that influence both menstruation and stroke risk include coagulopathies, polycystic ovarian syndrome, endometriosis, migraine, and other systemic disorders, in addition to menopause. Environmental and iatrogenic factors that influence both menstruation and stroke risk include hormonal contraceptives, nicotine, xenoestrogens, phytoestrogens, oophorectomy, and hysterectomy. Importantly, secondary stroke prevention can affect menstruation. Our current review presents literature supporting the idea that abnormal menstruation may indicate elevated stroke risk in premenopausal women.

Stroke, Ahead of Print. BACKGROUND:Patients with premorbid dementia have been generally excluded from trials of stroke therapies, and their dementia diagnosis may affect the care received. There are few data on the quality of stroke care and outcomes in these patients.METHODS:We compared the quality of care and outcomes for acute ischemic stroke patients with versus without premorbid dementia using national data from the Get With The Guidelines-Stroke registry between July 1, 2020, and December 31, 2021. Process outcomes included receiving intravenous thrombolysis, endovascular thrombectomy, and additional national quality measures. Clinical outcomes included ambulatory status at discharge, discharge destination, and mortality. The analyses were adjusted for patient and hospital characteristics.RESULTS:Among 609 350 patients with acute ischemic stroke, 29 751 of 546 407 (5.4%) had documented prestroke dementia (median age, 84 [interquartile range, 78–89]; 62.8% female). Patients with versus without premorbid dementia were more likely to arrive via emergency medical services (70.5% versus 46.8%) and had more severe strokes (median National Institutes of Health Stroke Scale score, 7 [interquartile range, 3–15] versus 3 [interquartile range, 1–8]). They were less likely to be admitted to a comprehensive stroke center (17.9% versus 22.7%;P

Stroke, Ahead of Print.

Introduction
Successful reperfusion does not always lead to good neurological outcomes and impaired microcirculation can be one of the underlying causes. Intra-arterial alteplase after mechanical thrombectomy (MT) may improve microcirculation contributing to neurological recovery, but prospective randomised studies are still needed to validate its efficacy and safety. We aim to assess the efficacy and safety of intra-arterial alteplase after MT for acute ischaemic stroke (AIS) with large-vessel occlusion (LVO).

Methods and analysis
The Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy (PEARL) study is a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. We consecutively screen AIS patients with anterior circulation LVO and National Institute of Health Stroke Scale of 6–25, who reach stable expanded Thrombolysis in Cerebral Infarction scores of 2b50-3 on angiography after MT. Eligible participants are 1:1 randomly assigned to the experimental group and the control group. Participants in the experimental group will receive intra-arterial alteplase (0.225 mg/kg and a maximum dose of 20 mg) after MT and standard medical treatment, while those in the control group will receive standard medical treatment alone after the procedure. The primary outcome is the proportion of patients with a 90-day modified Rankin scale of 0–1. A total of 324 participants are required to test the superiority hypothesis with 80% power at a two-tailed significance level of 0.05.

Ethics and dissemination
This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY-2023-390-02) and will be conducted following the Declaration of Helsinki. Ethical approvals have been obtained separately for all centres participating in the study. Study results will be published in peer-reviewed academic journals.

Trial registration number
NCT05856851.

Stroke, Ahead of Print. BACKGROUND:An increasing number of monogenic conditions underlying stroke are being identified. We explored the possibilities of increasing the diagnostic yield of monogenic stroke in a population under 56 years of age.METHODS:Fifty probands ≤55 years at their first stroke episode were characterized clinically and investigated by whole genome sequencing. Probands had one or more of: (1) one or more first to second degree relatives with stroke under 60 years or same stroke-causing condition/disease; (2) no hypertension, hypercholesterolemia, diabetes, heart disease, or smoking; or (3) either multiple stroke episodes or multiple arterial dissections. Variants with minor allele frequency under 0.01, identified by using our stroke gene panels, were assessed. The stroke subtypes, including large artery atherosclerotic, large artery nonatherosclerotic (tortuosity, dolichoectasia, aneurysm, nonatherosclerotic dissection, or occlusion), cerebral small vessel disease, cardioembolic (arrhythmia, heart defect, or cardiomyopathy), coagulation dysfunctions (venous thrombosis, arterial thrombosis, or bleeding tendency), intracerebral hemorrhage, vascular malformations (cavernoma or arteriovenous malformations), metabolic disorders, or cryptogenic embolic, were used for genotype-phenotype correlation. In a final step, we combined genetic and clinical information to determine if the genetic variant likely was the cause of stroke in the patients.RESULTS:Whole genome sequencing of younger patients with stroke identified 17 clinically matching genetic variants in 15 of 50 (30%) patients, while a stronger clinical correlation with stroke was established in only 6 (12%) of them. Stroke-related genetic variants were identified in 4 of 5 (80%) patients with cardioembolic stroke subtype, 3 of 4 (75%) with intracerebral hemorrhage, 7 of 18 (39%) with cryptogenic embolic stroke, 1 of 6 (17%) with small vessel disease, and 3 of 15 (20%) of patients with nonatherosclerotic large artery stroke, including 1 of 11 (9%) with cervical dissection stroke.CONCLUSIONS:Careful clinical interpretation of whole genome data using stroke gene panels can detect monogenic causes of early stroke, allowing individualized follow-up and opening new possibilities for potential treatment.

Annals of Internal Medicine, Ahead of Print.

This noninferiority randomized clinical trial investigates whether tenecteplase is noninferior to alteplase for the treatment of Chinese patients with acute ischemic stroke eligible for intravenous thrombolysis within 4.5 hours after symptom onset.

Introduction
Respiratory dysfunction is a notable complication in stroke patients, in which the diaphragm, as the primary respiratory muscle, directly influences lung function. Repetitive peripheral magnetic stimulation (rPMS) is a new, non-invasive approach that is used to treat brain and nerve problems. Few studies have examined the effect of magnetic stimulation on the phrenic nerve, breathing and diaphragm in stroke patients. This study aims to assess the effect of magnetic phrenic nerve stimulation on respiratory muscle function and lung function in adults with stroke. The results of this study may provide a promising approach to managing respiratory dysfunction in stroke patients.

Methods and analysis
This randomised controlled trial is designed to compare the effectiveness of bilateral magnetic phrenic nerve stimulation (rPMS) and conventional rehabilitation training in enhancing respiratory muscle strength, lung function indicators, diaphragmatic excursion and diaphragm thickness in patients with respiratory muscle weakness. Thirty patients admitted to the First Hospital of Fujian Medical University will be included in this study. Participants in the intervention group will undergo daily bilateral magnetic phrenic nerve stimulation for 2 weeks. Stimulation will be administered at a frequency of 25 Hz, with a pulse duration of 1.1 s and an inter-pulse interval of 5.9 s, for 5 days each week. Primary outcome measures will be assessed at baseline and after 2 weeks (end of the intervention) to evaluate the efficacy of rPMS compared with conventional rehabilitation techniques.

Ethics and dissemination
Before commencing the study, all participants will receive a comprehensive explanation of the study procedures, including the assessments. They will also be provided informed consent forms for review, completion and signing. This study was approved by the Ethics Committee for Research at the First Affiliated Hospital of Fujian Medical University (No.: MRCTA, ECFAH of FMU [2021]641, dated 10 November 2023) (Appendix & ). The trial protocol will strictly adhere to the Uniform Standards for Reporting of Trials (CONSORT) statement. The trial has been registered with the Chinese Clinical Trial Registry.
Dissemination of individual findings for each participant will be available at the end of the study. The findings will be disseminated to different interest groups, participants or other patients with respiratory dysfunction through journal papers and/or conference presentations. The results of the primary trial will be submitted for publication in a peer-reviewed journal.

Registration
ChiCTR2300075669, registered on 12 September 2023.

A meta-analysis finds a potential signal favoring anticoagulation for patent foramen ovale and mixed results for left atrial enlargement.

Stroke, Ahead of Print. BACKGROUND:Sex critically determines stroke pathophysiology and recovery. To reveal potential gaps in stroke care, we analyzed sex-specific differences in the stroke patient hospital admission and treatment process.METHODS:In this single-center retrospective analysis, we screened all patients referred to our stroke center between 2014 and 2020 with suspicion of stroke (n=7112). Patients with different cerebrovascular events and stroke mimics were included. We collected demographic hospitalization and 90-day follow-up data and stratified results according to sex. In a logistic regression analysis for 90-day functional outcome, we estimated the effect of sex corrected for the clinically most relevant confounders.RESULTS:Of 7102 patients, 56.7% were male and 43.3% female. Women were older (median, 76.3 years; interquartile range (IQR), 64–84, versus 70.7; IQR, 59–79;P

Stroke, Ahead of Print.

Stroke, Ahead of Print. BACKGROUND:Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials. Optimal timing of hsCRP/IL-6 measurement poststroke is unknown, as early blood levels may be confounded by the inflammatory response to brain infarction.METHODS:Using individual-participant data from a systematic review, we performed a time-course analysis to investigate the association between hsCRP/IL-6 and recurrent events stratified by timing of sampling. The prespecified coprimary end points after sample measurement were: (1) recurrent major adverse cardiovascular events (first major coronary event, recurrent stroke, or vascular death) and (2) recurrent stroke (ischemic, hemorrhagic, or unspecified). The poststroke dynamics of IL-6/hsCRP were analyzed by plotting their median (interquartile interval) concentrations within each tenth of the sampling timeframe. Acute/postacute phases were defined for each biomarker according to the shape of this relationship.RESULTS:There were data for 9798 patients from 11 studies (19 891 person-years follow-up, 10 observational cohorts, and 1 randomized trial). Each marker was measured once. IL-6 was markedly elevated

Stroke, Ahead of Print.

Stroke, Ahead of Print.

Stroke, Ahead of Print. Ischemic stroke is one of the leading causes of disability and mortality worldwide. Thrombosis is the main pathological process of stroke and is therefore an important therapeutic target in stroke prevention. In recent years, with the development of endovascular treatment and therefore retrieving the thrombus for further investigation, evidence is accumulating that immune cells are inextricably linked to stroke pathogenesis. Circulating immune cells have been found to induce immunothrombosis, and they actively participate in the formation of the thrombus by promoting platelet recruitment and thrombin activation. Additionally, the formation of thromboinflammation leads to increased instability of atherosclerotic plaques. We review the concepts of stroke immunothrombosis and thromboinflammation and the effect of immune cells on vessel recanalization and patient outcome. In addition, we elaborate on the possible mechanism of immune cells being activated and participating in thrombosis in ischemic stroke.