Stroke (Hoboken, N.J.)最新文献

Background: With the increasing use of tenecteplase for acute ischemic stroke, it is important to determine its safety in young adults. We aimed to characterize the clinical characteristics and imaging findings of young adults (≤45 years) in the AcT trial (Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada) and to compare their safety and efficacy outcomes.

Methods: This is a secondary analysis of the AcT trial, a phase 3 pragmatic multicenter registry-linked randomized controlled trial. We describe clinical and imaging characteristics of young adults with acute ischemic stroke. Logistic regression adjusted for sex and stroke severity was performed to assess safety and efficacy outcomes between the tenecteplase and alteplase arms.

Results: Of the 1577 enrolled patients, 68 (4.31%) were ≤45 years. Of 53 patients with available comorbidity data, 33 (62.26%) had no comorbidities. Hypertension was the most common comorbidity (n=8, 15%), whereas cardiac pathologies were observed in a smaller proportion (n=4, 7.5%). Intracranial atherosclerosis was identified in 7 patients (10%) and carotid or vertebral artery dissection in 6 patients (9%). Safety outcomes, including mortality, intracranial hemorrhage, and serious adverse events, were similar between the tenecteplase and alteplase arms. Excellent functional outcome (modified Rankin Scale score 0-1) at 90 days was better in the tenecteplase arm (84.72% versus 45%; adjusted odds ratio, 6.55 [95% CI, 1.89-22.71]).

Conclusions: The majority of young adults presenting with acute ischemic stroke did not have any traditional risk factors for stroke at presentation. Safety outcomes were similar between the tenecteplase and alteplase arms. Although functional outcomes were observed to be better in the tenecteplase arm, these findings are exploratory and should be interpreted cautiously, given the study's limited sample size and lack of adjustment for key confounders.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Background: The RESCUE-ICAS study (Registry of Emergent Large-Vessel Occlusion due to Intracranial Stenosis) demonstrated that patients undergoing acute stenting of intracranial atherosclerosis with large-vessel occlusion after mechanical thrombectomy had better outcomes than those undergoing mechanical thrombectomy alone. We present 2 secondary analyses of RESCUE-ICAS to evaluate intracranial stenting among patients who achieved successful reperfusion.

Methods: From a prospective observational cohort of 25 stroke centers (2022-2023), patients with acute intracranial occlusion, National Institutes of Health Stroke Scale score ≥6, and 50% to 99% residual stenosis or occlusion after endovascular thrombectomy were included. In the first analysis, we compared patients with stenting versus those without stenting from among those patients with a final modified Thrombolysis in Cerebral Infarction score of 2B-3. In the second analysis, we compared patients who underwent stenting with those who did not from among the patients with a Thrombolysis in Cerebral Infarction (TICI) score of 2B-3 before stenting. The odds of a favorable 90-day mRS (0-2) and 24-hour MRI infarct volume <30 mL were assessed using multivariable logistic regression. We also examined the rates of symptomatic ICH and death at 90 days in these cohorts.

Results: Overall, 351 (84.2%) patients had successful reperfusion, with 181 (51.7%) undergoing stenting. More patients who underwent acute stenting achieved an mRS score of 0 to 2 at 90 days (adjusted odds ratio, 1.88; P=0.024). Patients who underwent stent placement were more likely to have 24-hour MRI infarct volume <30 mL (70.1% versus 54.8%, P=0.022). Our second analysis demonstrated that 89 patients who underwent acute intracranial stenting after successful perfusion (postmechanical thrombectomy) experienced higher odds of mRS scores of 0 to 2 at 90 days (adjusted odds ratio, 2.19 [95% CI, 1.01-4.74]) and 24-hour MRI infarct volume <30 mL (adjusted odds ratio, 3.27 [95% CI, 1.05-10.19]) than the 170 without stenting after successful reperfusion. There was no significant difference in rates of symptomatic ICH (7.2% versus 5.3%; P=0.466) or death at 90 days (22.7% versus 25.9%; P=0.480).

Conclusions: Among both the cohort with final successful reperfusion and the cohort with initial successful reperfusion after mechanical thrombectomy alone, intracranial stenting was associated with better long-term clinical and radiographic outcomes, without higher morbidity and mortality.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05403593.

Background: Portable, low-field magnetic resonance imaging (MRI) has the potential to expand access to neuroimaging in environments where conventional MRI is limited. However, diffusion-weighted imaging at low magnetic field is challenged by a low signal-to-noise ratio and gradient strength, which may limit diagnostic confidence in acute ischemic stroke evaluation, particularly for very small strokes. In this study, we evaluated a combination of novel pulse sequences and low-field MRI hardware to enhance lesion detection.

Methods: Patients with a suspected diagnosis of acute ischemic stroke were prospectively enrolled at 3 centers. Diffusion-weighted imaging was performed using a single-direction (SD) or a custom multi-direction (MD) sequence comprising 3 orthogonal directions. Imaging was acquired on 2 0.064 T hardware versions: a first-generation C-arm system (Swoop v1) and a next-generation H-arm system featuring optimized gradient amplifiers, form factor, and cooling system (Swoop v2). Diagnostic accuracy and the lower limit of lesion detection were calculated for both SD and MD images on each system compared with ground-truth MRI (1.5-3 T).

Results: A total of 95 patients (n=62 confirmed acute ischemic stroke; n=33 stroke mimics) were included. On SD images, agreement between assessors regarding lesion detection was κ=0.72, and κ=0.84 on MD images. The positive predictive value for differentiating acute ischemic stroke from stroke mimics was 78.2% on SD and 95% on MD images. For SD images, a lesion volume cut point of 0.6 mL yielded a sensitivity of 89% and specificity of 88%. For MD images, the lesion volume cut point was 0.4 mL, with a corresponding sensitivity of 86% and specificity of 83%. MD imaging on the next-generation v2 system improved image uniformity (P<0.05), reduced scan time by ≈30%, and enabled the detection of lesions as small as 0.15 mL (2.8 mm maximum diameter).

Conclusions: Implementation of diffusion-weighted imaging optimization strategies on low-field MRI improves detection of very small strokes in a clinically feasible time frame.

Background: The effectiveness of platelet reactivity unit (PRU)-guided individualized antiplatelet therapy for intracranial aneurysm treatment remains uncertain.

Methods: This retrospective study evaluated 1705 patients with 1883 unruptured intracranial aneurysms who received endovascular treatments at a tertiary center between March 2018 and December 2020. Patients were divided into 2 groups: a standard group (aspirin and clopidogrel without PRU) and an individualized group where antiplatelet therapy was adjusted or switched to low-dose prasugrel based on preprocedural PRU values by VerifyNow. In the individualized group, hyporesponsiveness was defined as PRU>238 or inhibition <26%, prompting transition to low-dose prasugrel, whereas hyperresponsiveness was defined as PRU<86 or inhibition >74%, leading to dose withholding. The primary outcome was thromboembolic and hemorrhagic complications within 1 month. Thromboembolic complications included intraprocedural thrombosis, transient ischemic attack, and ischemic stroke confirmed on diffusion-weighted imaging; microembolism was defined as acute diffusion-weighted imaging lesions <1 cm. Hemorrhagic complications encompassed intracranial bleeding and extracranial access site hematomas (retroperitoneal hematoma, puncture-site pseudoaneurysm). Functional outcomes were assessed using the modified Rankin Scale. Subgroup analyses were performed for complex procedures, defined as stent-assisted coiling and flow diversion.

Results: Average patient age was 58.0±10.8 years; 72.4% were female. The cohort included 1020 patients in the standard group and 685 in the individualized group. No significant difference in overall thromboembolic complications was observed between the standard (2.4%) and individualized groups (1.3%; P=0.127). However, individualized therapy significantly reduced thromboembolic events in complex procedures, including stent-assisted embolization and flow diversion (3.3% versus 1.0%; P=0.017; P for interaction=0.049). In the flow diverter subgroup, the incidence of microembolism was significantly lower in the individualized group (47.8% versus 26.8%; P=0.049). Hemorrhagic complication rates were similar between groups.

Conclusions: Individualized antiplatelet therapy based on PRU measurements did not impact overall outcomes but reduced ischemic complications in complex endovascular treatments without increasing bleeding risks. Further validation is necessary.

Background: Recent randomized clinical trials have demonstrated that endovascular thrombectomy (EVT) improves outcomes in patients with large ischemic cores. Despite these findings, hyperacute decision-making in large-core acute ischemic stroke remains challenging, as patients continue to face high rates of disability and mortality. Clear communication of risks and benefits is essential, and visual aids may improve comprehension in emergency settings.

Methods: Ninety-day modified Rankin Scale score distributions were pooled from 6 large-core thrombectomy trials: RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial), SELECT-2 (Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke), ANGEL-ASPECT (Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core), TENSION (Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window), TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke), and LASTE (Large Stroke Therapy Evaluation). Outcomes included functional independence (modified Rankin Scale score, 0-2), acceptable outcome (modified Rankin Scale score, 0-3), symptomatic intracranial hemorrhage, and decompressive hemicraniectomy. Benefit per hundred and harm per hundred were calculated by comparing EVT with medical management. Net benefit was defined as benefit per hundred minus harm per hundred. Visual decision aids, including a Single Personograph Choice Consequence Matrix, were developed to illustrate the pooled results.

Results: Across 1872 patients, EVT increased rates of functional independence (19.5% versus 7.5%) and acceptable outcomes (36.5% versus 20.0%) compared with medical management. EVT also reduced severe disability (12.2% versus 20.6%) and mortality (31.0% versus 37.2%). Rates of symptomatic intracranial hemorrhage were 5.5% in the EVT arm and 3.2% in the medical management arm, while hemicraniectomy occurred in 12.1% and 10.4%, respectively, corresponding to an excess harm of 3.9%. The calculated benefit per hundred ranged from 16.5% (modified Rankin Scale score, 0-2) to 55.6% (ordinal shift), with an average of 36.1%. The visual aid illustrated that when scaled to a cohort of 100 patients receiving EVT, 40 would be expected to benefit, 4 to experience harm, 31 to die, and 29 to show no difference compared with medical management.

Conclusions: EVT for large-core acute ischemic stroke provides substantial benefit despite increased risks of hemorrhage and surgical rescue. Visual decision aids based on pooled trial data offer an objective method for presenting outcomes, supporting informed and timely decision-making in acute stroke care.

Background: The clinical relevance of glymphatic dysfunction in patients with subarachnoid hemorrhage (SAH) remains unclear. This study aimed to evaluate glymphatic system function in patients with aneurysmal SAH using the diffusion tensor imaging-based analysis along the perivascular space (ALPS) index and to investigate its association with the development of hydrocephalus and clinical outcomes. In particular, we explored whether hydrocephalus could act as a potential mediator of the relationship between glymphatic dysfunction and poor functional outcome.

Methods: We retrospectively analyzed 60 patients with aneurysmal SAH who underwent magnetic resonance imaging, including diffusion tensor imaging, at a median of 18 days after onset. The ALPS index was calculated from directional diffusivity values in the deep white matter, and its relationship with 3-month functional outcomes (modified Rankin Scale) and shunt-dependent hydrocephalus was examined. A logistic regression-based causal mediation analysis was performed to assess whether hydrocephalus statistically mediated the association between a low ALPS index (<1) and poor outcome (modified Rankin Scale score ≥3).

Results: The ALPS index was significantly lower in patients with poor outcomes (median [interquartile range], 1.09 [0.91-1.17]) than in those with favorable outcomes (1.29 [1.16-1.44]; P=0.0002). Shunt-dependent hydrocephalus occurred more frequently in the poor outcome group and was associated with a markedly reduced ALPS index (median, 0.99). Mediation analysis with covariates including age and World Federation of Neurosurgical Societies grade revealed that the total effect of a low ALPS index on poor outcome was significant (odds ratio, 7.98 [95% CI, 1.12-56.79]), and this effect was largely mediated by hydrocephalus development (indirect effect odds ratio, 3.11 [95% CI, 1.23-7.89]; proportion mediated=0.78).

Conclusions: Reduced ALPS index, which may reflect impaired glymphatic transport, was associated with poor functional outcomes in patients with aneurysmal SAH. This relationship appeared to be largely mediated by the presence of shunt-dependent hydrocephalus. Although causality cannot be established in this observational study, these findings suggest that glymphatic dysfunction may play a clinically relevant role in the pathophysiology of SAH-related hydrocephalus and outcome.

Background: Process-of-care time measures provide important information about hyperacute stroke interventions and performance of systems of care. These measures are often highly skewed, and mean-based summary statistics may be misleading. Percentile-based statistics (eg, median) conveniently and unbiasedly summarize the proportion of patients treated within a given timeframe. Despite this, mean-based synthesis methods are primarily recommended by the Cochrane Handbook for Systematic Reviews of Interventions for meta-analyses. We aim to investigate the reporting and statistical comparison of process-of-care time measures in published hyperacute stroke trials and systematic reviews of trials and provide methodological foundation for meta-analysis in future studies.

Methods: A systematic scoping review of studies reporting or comparing time measures between events in the delivery of hyperacute stroke care was undertaken (Protocol DOI: 10.11124/JBIES-23-00136). Of 2321 studies identified through the database search, 146 studies were included. We analyzed the statistical agreement of transformation-based methods using process-of-care time data from hyperacute stroke clinical trials. We graphically and statistically compared mean- and percentile-based meta-analysis techniques for process-of-care time measures.

Results: Overall, 49 of 146 (34%) studies reported a process-of-care time measure using only the mean/SD. Under the normal distribution assumption, impossible (negative) time values would have been observed in 40 of 49 (82%) of those studies. Transformation-based imputation methods showed moderate agreement with the true SD (Lin Concordance Correlation Coefficient=0.88). Mean-based and median-based meta-analysis provided comparable results when analyzing summary measures of between-arm treatment effects and differed substantially when analyzing individual-arm summary measures.

Conclusions: We recommend that stroke researchers: (1) summarize a sufficient set of process-of-care time measures using the median/interquartile range and use consistent rank-based analysis methods; (2) exercise caution in utilizing transformation-based methods to impute the mean/SD of process-of-care time measures; and (3) use median-based meta-analytical techniques for the synthesis of process-of-care time measures.

Background: This study compares microsurgical clipping, endovascular coiling, and conservative management strategies for unruptured intracranial aneurysms using network meta-analysis to generate a treatment hierarchy that supports evidence-based decision-making.

Methods: The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Network Meta-Analyses guidelines. Eligible studies included randomized controlled trials and comparative observational cohorts of adults with unruptured intracranial aneurysms treated by clipping, coiling, or conservative observation. Primary outcomes were all-cause mortality and poor functional outcome (modified Rankin Scale score >2). Secondary outcomes included morbidity, complete aneurysm occlusion, and retreatment. A comprehensive search of PubMed, Embase, and the Cochrane Library through May 2025 identified 7 eligible studies, of which 4 provided sufficient data for network analysis.

Results: The 4 included studies, 1 randomized trial and 3 observational cohorts, encompassed >500 patients. All compared clipping and coiling, and 2 also evaluated conservative management. Endovascular coiling ranked most favorable for reducing mortality and poor functional outcomes, though estimates were imprecise. Clipping was associated with higher morbidity than coiling but demonstrated trends toward superior anatomic durability, including higher occlusion rates and fewer retreatments. Conservative management was linked to worse survival and functional outcomes, with limited data on anatomic end points. Subgroup analyses of anterior and posterior circulation aneurysms yielded similar patterns.

Conclusions: Endovascular coiling appears to offer the best short- to intermediate-term outcomes, whereas microsurgical clipping provides more durable long-term protection despite greater procedural risks. Conservative observation remains the least favorable strategy and may be reserved for highly selected low-risk patients. Further large-scale trials are needed, particularly in posterior circulation aneurysms and for patient-centered outcomes such as quality of life and cognition.