International Journal of Stroke最新文献

Background: Recombinant prourokinase (rhPro-UK) is a specific plasmin activator, which has been approved to treat acute myocardial infarction in China.

Aim: This phase 3 trial aimed to further demonstrate the efficacy and safety of rhPro-UK in patients with acute ischemic stroke (AIS) within 4.5 h of symptom onset.

Methods and design: RhPro-UK in AIS within 4.5 h of stroke onset trial-2 (PROST-2) is a multicenter, prospective randomized, open-label, blinded end-point, non-inferiority, recombinant tissue plasmin activator (rt-PA)-controlled, phase 3 trial. A total of 1552 patients who are eligible for intravenous thrombolytic therapy from 72 clinical sites will be randomly assigned to receive either rhPro-UK 35 mg (15 mg bolus + 20 mg infusion/30 min) or rt-PA 0.9 mg/kg (10% bolus + 90% infusion/1 h).

Study outcomes: The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary efficacy outcomes include the proportion of patients with mRS score of 0-2, the distribution of mRS, self-care ability in daily life on the Barthel Index at 90 days, the proportion of subjects with ⩾ 4 points decrease in National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score ⩽ 1 from baseline at 24 h and 7 days after treatment. Safety outcomes are symptomatic intracranial hemorrhage (sICH) and major systematic bleeding within 7 days as well as death from all causes within 90 days.

Discussion: The results from the PROST-2 trial will comprehensively elucidate the efficacy and safety profile of rhPro-UK as a potential alternative agent for stroke thrombolysis.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591.

Background: Insulin resistance (IR) is of growing concern yet its association with white matter integrity remains controversial. We aimed to investigate the association between IR and white matter integrity in nondiabetic adults.

Methods: This cross-sectional analysis was conducted based on the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study. A total of 1709 nondiabetic community-dwelling adults with available diffusion-weighted imaging based on brain magnetic resonance imaging and completed oral glucose tolerance test were included. IR was measured noninvasively by insulin sensitivity indices (ISI), including ISIcomposite and ISI_0,120, as well as homeostasis model assessment of insulin resistance (HOMA-IR). White matter microstructure abnormalities were identified by diffusion-weighted imaging along with tract-based spatial statistical analysis to compare diffusion metrics between groups. The multivariable linear regression models were applied to measure the association between white matter microstructure abnormalities and IR.

Results: A total of 1709 nondiabetic individuals with a mean age of 60.8 ± 6.4 years and 54.1% female were included. We found that IR was associated with a significant increase in mean diffusivity, axial diffusivity, and radial diffusivity extensively in cerebral white matter in regions such as the anterior corona radiata, superior corona radiata, anterior limb of internal capsule, external capsule, and body of corpus callosum. The pattern of associations was more marked for ISIcomposite and ISI_0,120. However, the effect of IR on white matter integrity was attenuated after, in addition, adjustment for history of hypertension and cardiovascular disease and antihypertensive medication use.

Conclusion: Our findings indicate a significant association between IR and white matter microstructural abnormalities in nondiabetic middle-aged community residents, while these associations were greatly influenced by the history of hypertension and cardiovascular disease, and antihypertensive medication use. Further investigation is needed to clarify the role of IR in white matter integrity, whereas prophylactic strategies of maintaining a low IR status may ameliorate disturbances in white matter integrity.

Data accessibility statement: The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Background: Hyperglycemia is associated with worse stroke outcomes, but it is uncertain whether tight glycemic control during the acute stroke period is associated with a better outcome. We conducted a meta-analysis to compare the effect of tight glycemic control versus loose glycemic control in the acute phase of stroke patients.

Methods: A literature search was performed to identify randomized controlled trials comparing the safety and efficacy of tight glycemic control with a relatively loose control of blood glucose of acute stroke (ischemic or hemorrhagic) patients within 24 h after stroke onset. We required that the blood glucose level of the patients should not be lower than 6.11 mmol/L at the time of enrollment, and for the intensive blood glucose control range, we defined the blood glucose level as lower than that of the control group. The primary efficacy outcome measure was deaths from any cause at 90 days. Secondary efficacy outcomes comprised the number of participants with modified Rankin score (mRS). We define mRS scores 0-2 as favorable scores, recurrent stroke, and the National Institute of Health Stroke Scale or the European Stroke Scale scores. We defined the number of participants with hypoglycemia as our primary safety outcome. Subgroup analysis was performed according to age, the variety of interventions, maintained glucose level, and status of hypoglycemia on National Institute of Health Stroke Scale (NIHSS) scores or European Stroke Scale (ESS) scores.

Results: Fifteen randomized controlled trials (RCTs) with 2957 participants meeting the including criteria were identified and included in this meta-analysis, although not all included data on every outcome measure. Data on the primary efficacy endpoint, mortality at 90 days, was available in 11 RCTs, a total of 2575 participants. There was no significant difference between the intervention and control groups (odds ratio (OR): 1.00; 95% confidence interval (CI): 0.81-1.23; P = 0.99). For secondary endpoints, there was no difference between intervention and control groups for a mRS from 0 to 2 (OR: 0.96; 95% CI: 0.80-1.15; P = 0.69; data from 9 RCTs available), or recurrent stroke (OR: 1.34; 95% CI: 0.92-1.96; P = 0.13; data from 3 RCTs available). For NIHSS scores or ESS scores, there was a small difference in favor of intensive controls (standardized mean difference: -0.29; 95% CI: -0.54 to -0.04; P = 0.02). There was a marked increase in hypoglycemia with tight control: (OR of 9.46 (95% CI: 4.59-19.50; P < 0.00001; data from 9 RCTs available).

Conclusion: There was no difference between tight and loose glycemic control on mortality, independence, or recurrent stroke outcome in acute stroke, but an increase in hypoglycemia. There was a small effect improvement on neurological scales, but the relevance of this needs to be confirmed in future adequately powered studies.

Background: Following transient ischemic attack (TIA) and minor stroke, the risk of recurrent stroke can be significantly reduced with short-duration dual antiplatelet therapy (DAPT). We wish to investigate whether 10 days of DAPT is as effective as 21 days' treatment.

Study design: This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA + clopidogrel) is non-inferior to 21 days of DAPT in patients with acute ischemic stroke (AIS) or high-risk TIA. In both groups, DAPT is started within 24 hours of symptom onset. This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size is 1932.

Outcomes: Non-inferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intra-cranial and systemic hemorrhage.

Study period: Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025.

Discussion: The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes.

Background: Recent randomized trials have shown the benefit of mechanical thrombectomy (MT) also in patients with an established large ischemic core.

Aims: The purpose of this study was to define baseline predictors of clinical outcome in patients with large vessel occlusion (LVO) in the anterior circulation and an Alberta Stroke Program Early CT score (ASPECTS) ⩽ 5, undergoing MT.

Material and methods: The databases of 16 comprehensive stroke centers were retrospectively screened for patients with LVO and ASPECTS ⩽5 that received MT. Baseline clinical and neuroradiological features, including the differential contribution of all ASPECTS regions to the composite score, were collected. Primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. Statistical analysis used a logistic regression model and random forest algorithm.

Results: A total of 408 patients were available for analysis. In multivariate model, among baseline features, lower age (odd ratio (OR) = 0.962, 95% confidence interval (CI) = 0.943-0.982) and lower National Institute of Health Stroke Scale (NIHSS) score (OR = 0.911, 95% CI = 0.862-0.963) were associated with the mRS score 0-2. Involvement of the M2 (OR = 0.398, 95% CI = 0.206-0.770) or M4 (OR = 0.496, 95% CI = 0.260-0.945) ASPECTS regions was associated with an unfavorable outcome. Random forest analysis confirmed that age and baseline NIHSS score are the most important variables influencing clinical outcome, whereas involvement of cortical regions M5, M4, M2, and M1 can have a negative impact.

Conclusion: Our retrospective analysis shows that, along with age and baseline clinical impairment, presence of early ischemic changes involving cortical areas has a role in clinical outcome in patients with large ischemic core undergoing MT.

Data access statement: The data that support the findings of this study are available upon reasonable request.

Background: Endovascular thrombectomy (EVT) has been proven as the standard treatment for acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO). However, the ideal anesthetic strategy during EVT still remains unclear. Therefore, this systematic review and meta-analysis aimed to determine the optimal anesthetic modality for patients with AIS undergoing EVT based on current randomized controlled trials (RCTs).

Methods: The databases Medline (via PubMed), EMBASE, Web of Science, and the Cochrane Library were searched for RCTs comparing general anesthesia (GA) and conscious sedation (CS) in AIS patients undergoing EVT. The primary outcome was a favorable functional outcome at 90 days postintervention. Data analysis was conducted using the Review Manager software (RevMan V.5.3).

Results: Eight RCTs involving 1199 patients were included. There was no significant difference between GA and CS group in the rate of functional independence (risk ratio (RR) = 1.10, 95% confidence interval (CI) = 0.96 to 1.25; p = 0.17; I² = 30%). Compared with the CS group, the GA group attained a higher successful recanalization rate (RR = 1.14, 95% CI = 1.08 to 1.20; p < 0.00001; I² = 17%). In addition, patients in the GA were associated with a higher rate of hypotension (RR = 1.87, 95% CI = 1.44 to 2.41; p < 0.00001; I² = 66%) and a higher incidence of pneumonia (RR = 1.38, 95% CI = 1.05 to 1.8; p = 0.02; I² = 37%).

Conclusion: For AIS patients receiving EVT, the choice of anesthetic modality did not influence the 3-month neurological outcome while GA is superior to CS in terms of successful reperfusion rate. Moreover, the patients in the GA group were at a higher risk of developing hypotension and pneumonia. Further studies are required to provide more sufficient evidence.

Background: Global access to acute stroke treatment is variable worldwide, with notable gaps in low and middle-income countries (LMIC), especially in rural areas. Ensuring a standardized method for pinpointing the existing regional coverage and proposing potential sites for new stroke centers is essential to change this scenario.

Aims: To create and apply computational strategies (CSs) to determine optimal locations for new acute stroke centers (ASCs), with a pilot application in nine Latin American regions/countries.

Methods: Hospitals treating acute ischemic stroke (AIS) with intravenous thrombolysis (IVT) and meeting the minimum infrastructure requirements per structured protocols were categorized as ASCs. Hospitals with emergency departments, noncontrast computed tomography (NCCT) scanners, and 24/7 laboratories were identified as potential acute stroke centers (PASCs). Hospital geolocation data were collected and mapped using the OpenStreetMap data set. A 45-min drive radius was considered the ideal coverage area for each hospital based on the drive speeds from the OpenRouteService database. Population data, including demographic density, were obtained from the Kontur Population data sets. The proposed CS assessed the population covered by ASCs and proposed new ASCs or artificial points (APs) settled in densely populated areas to achieve a target population coverage (TPC) of 95%.

Results: The observed coverage in the region presented significant disparities, ranging from 0% in the Bahamas to 73.92% in Trinidad and Tobago. No country/region reached the 95% TPC using only its current ASCs or PASCs, leading to the proposal of APs. For example, in Rio Grande do Sul, Brazil, the introduction of 132 new centers was suggested. Furthermore, it was observed that most ASCs were in major urban hubs or university hospitals, leaving rural areas largely underserved.

Conclusions: The MAPSTROKE project has the potential to provide a systematic approach to identify areas with limited access to stroke centers and propose solutions for increasing access to AIS treatment.

Data access statement: Data used for this publication are available from the authors upon reasonable request.

Background: Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data.

Methods: Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined.

Findings: The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results.

Interpretation: Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.

Background: Patent foramen ovale (PFO) is a congenital anatomical variant which is associated with strokes in young adults. Contrary to vascular risk factors and atherosclerosis, a PFO is present from birth. However, it is completely unknown how an anatomical structure that is already present at birth in a large proportion of the population can convert into a PFO that causes stroke in a few. Recent studies reported a significant association between certain trigger factors and ischemic stroke in young adults. This study aims to investigate these triggers in PFO-associated stroke.

Methods: The ODYSSEY study, a multicenter prospective cohort study between 2013 and 2021, included patients aged 18-49 years experiencing their first-ever ischemic event. Participants completed a questionnaire about exposure to potential trigger factors. A case-crossover design was used to assess the relative risks (RR) with 95% confidence intervals (95% CI). The primary outcome was the RR of potential trigger factors for PFO-associated stroke.

Results: Overall, 1043 patients completed the questionnaire and had an ischemic stroke, of which 124 patients had a PFO-associated stroke (median age 42.1 years, 45.2% men). For patients with PFO-associated stroke, the RR was 26.0 (95% CI 8.0-128.2) for fever, 24.2 (95% CI 8.5-68.7) for flu-like disease, and 3.31 (95% CI 2.2-5.1) for vigorous exercise.

Conclusion: In conclusion, flu-like disease, fever, and vigorous exercise may convert an asymptomatic PFO into a stroke-causing PFO in young adults.

Data access statement: The raw and anonymized data used in this study can be made available to other researchers on request. Written proposals can be addressed to the corresponding author and will be assessed by the ODYSSEY investigators for appropriateness of use, and a data sharing agreement in accordance with Dutch regulations will be put in place before data are shared.