Stroke (Hoboken, N.J.)最新文献

Background: Flow diverter stent (FDS) deployment with coil embolization (CE) achieves high aneurysmal occlusion rates. However, no established guidelines exist for the optimal packing density (PD) when treating large or giant aneurysms. This study aimed to investigate the optimal PD in FDS deployment with CE.

Methods: This retrospective multicenter study involved 97 consecutive patients with unruptured large or giant (≥ 10 mm) aneurysms treated with FDS deployment alone or with FDS and CE, between August 2019 and December 2023. We calculated the volume embolization ratio as the coil PD using Angiosuite Neuro Edition ver. 10.03. We defined O'Kelly-Marotta grading scale D as complete obliteration (CO) at 6 months after deployment and analyzed the associations between the PD and aneurysmal CO.

Results: Seventeen patients (means ± SD age, 53.8±9.94 years; 14 [82.4%] female patients) in the FDS with CE group, and 18 patients (63.6±12.4 years; 14 [77.8%] female patients) in the FDS alone group were included for analysis. CO was achieved in 14 (82.3%) patients in the FDS with CE group and 9 (50.0%) in the FDS alone group (P = 0.08). volume embolization ratio (≥ 8.9%) was significantly associated with CO in the univariable analysis (P = 0.01; odds ratio: 14.3 [95% CI: 1.57-129.9]) and the multivariable analysis (P = 0.02; odds ratio, 10.5 [95% CI: 1.09-100.7]).

Conclusion: It may be unnecessary to continue CE after the PD has reached 8.9% volume embolization ratio when treating large or giant intracranial aneurysms with combined FDS and CE.

Background: Mobile stroke unit (MSU) has been demonstrated to significantly reduce time to treatment and increase the chances of early intravenous thrombolysis with positive effect on clinical outcomes. The evidence of its impact on the treatment time metrics and outcomes in endovascular treatment-eligible patients outside of large clinical trials is limited. We sought to investigate the potential workflow benefits of MSU-based care compared with emergency medical services-based care for endovascular treatment-eligible patients.

Methods: This is an observational, cross-sectional study, based on a retrospective review of a single-center, prospectively maintained, mechanical thrombectomy database spanning June 2018 to November 2023. Patients receiving endovascular treatment for large-vessel occlusion strokes were divided in 2 groups: MSU-transported and emergency medical services-transported (mothership) presenting within MSU operating days/hours. Treatment time metrics and clinical outcomes were compared.

Results: A total of 565 patients who fit inclusion criteria were identified: 66 were transported via MSU and 499 were transported via emergency medical services. MSU-transported patients were more likely to be within treatment window for intravenous thrombolysis and to bypass multimodal imaging. The co-primary end points (door to angio, door to puncture, and door to reperfusion times) favored the MSU-transported patients (41 versus 62 minutes, 58 versus 82 minutes, 96 versus 127 minutes; P<0.001). The times from last known well to puncture were significantly shorter in the MSU-transported group (237 versus 389 minutes, P = 0.021). Functional outcomes at 90 days and rates of intracerebral hemorrhage were similar between the 2 groups.

Conclusion: In this single-center analysis, MSU-transported patients demonstrated improved time metrics, with shorter treatment times when compared with emergency medical services-transported patients. Outcomes and safety parameters did not differ between the 2 groups.

Background: Transcranial Doppler (TCD) is widely used to predict cerebral vasospasm in patients with subarachnoid hemorrhage by monitoring mean flow velocity (MFV) in major cerebral arteries. However, its accuracy in identifying specific arteries affected by vasospasm remains unclear. This study investigates the correlation between elevated MFV and the actual location of vasospasm, considering the influence of adjacent artery vasospasms.

Methods: We conducted a retrospective observational study of patients with subarachnoid hemorrhage who underwent transcranial Doppler monitoring and subsequent angiography between March 2017 and December 2020. The primary exposure was the maximum MFV recorded in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and intracranial internal carotid artery (ICA). The primary outcome was the presence and location of vasospasm, confirmed by angiography. The Kruskal-Wallis test compared MFV distributions among vasospasm groups, and logistic regression evaluated associations between MFV values and vasospasm presence in each artery.

Results: Among 367 hemispheres, vasospasm was present in 16%, with 7% involving a single artery and 8% involving multiple arteries. MFV increased not only in arteries directly affected by vasospasm but also in adjacent arteries (P<0.001, Kruskal-Wallis test). MCA vasospasm was associated with increased MCA MFV (odds ratio [OR], 1.036 [95% CI, 1.019-1.053], P<0.001). ICA vasospasm was associated with increased ICA MFV (OR, 1.023 [95% CI, 1.006-1.040], P = 0.007). ACA vasospasm, however, was not associated with ACA MFV (OR, 1.011 [95% CI, 0.996-1.025], P = 0.142) but instead correlated with MCA MFV (OR, 1.040 [95% CI, 1.024-1.056], P<0.001).

Conclusion: MFV elevations occur in both affected and adjacent arteries, suggesting the interconnected response of cerebral arteries to vasospasm. Unlike MCA and ICA, ACA vasospasm does not correlate with ACA MFV but instead with MCA MFV. These findings challenge conventional assumptions about transcranial Doppler interpretation and suggest that MFV increases should be viewed as a general marker of vasospasm rather than an artery-specific indicator.

Background: Tandem lesions pose unique challenges in the endovascular treatment of acute ischemic stroke. We aimed to compare the clinical and procedural outcomes of patients with tandem lesions and extracranial internal carotid artery (ICA) complete occlusion versus those with moderate to severe stenosis.

Methods: This is a subanalysis of a multicenter cohort of patients with acute anterior circulation tandem lesions treated with intracranial mechanical thrombectomy and carotid artery stenting, between January 2015 and December 2020. The patients were categorized into 2 groups: extracranial ICA stenosis >70% to 99% and complete occlusion. Outcomes included successful and excellent recanalization, functional independence, symptomatic intracranial hemorrhage, and puncture-to-recanalization time. Sensitivity analyses were conducted based on varying degrees of stenosis, and we explored interactions with age, Alberta Stroke Program Early CT [Computed Tomography] Score, National Institutes of Health Stroke Scale, procedural antiplatelets, ICA treatment approach, ICA lesion etiology, Intravenous thrombolysis, and use of a balloon-guide catheter.

Results: The study included 323 patients; 166 (51.4%) of whom presented with ICA occlusion and 157 (48.6%) with severe stenosis. Patients with ICA occlusion had significantly higher rates of previous stroke/transient ischemic attack, and antegrade ICA treatment approach. The comparison between both groups in univariable and multivariable analysis revealed no significant differences in the rates of successful and excellent recanalization, functional independence, symptomatic intracranial hemorrhage, and additional outcomes. The median puncture-to-recanalization time was longer in the occlusion group (adjusted coefficient, 1.21 [95% CI 1.01-1.46], P = 0.05). When categorized into 3 groups (occlusion, severe, and moderate stenosis), median puncture-to-recanalization time was significantly higher in patients with occlusion (adjusted coefficient, 1.34 [95% CI, 1.04-1.71], P = 0.022), and a trend toward statistical significance was observed in patients with severe stenosis (adjusted coefficient, 1.29 [95% CI, 0.98-1.71], P = 0.068), compared with patients with moderate stenosis. Interaction analysis did not yield significant differences.

Conclusion: In patients with tandem lesions, those with ICA occlusion presented longer puncture-to-recanalization time than patients with cervical stenosis. This observation might be linked to higher rates of an antegrade approach in patients with ICA occlusion.

Background: The potential role of adjunctive intra-arterial thrombolysis (IAT) in improving outcomes following mechanical thrombectomy (MT) remains unclear. This meta-analysis evaluates the efficacy and safety of IAT after MT compared to MT alone in patients with acute ischemic stroke.

Methods: We searched PubMed, Embase, and the Cochrane Library from inception to January 2025 with no language restrictions. Additionally, grey literature sources were explored. Randomized controlled trials comparing IAT after MT versus MT alone in acute ischemic stroke were included. Odds ratios (ORs) with 95% CIs were pooled using a random-effects model in R. Trial sequential analysis was performed for the primary favorable outcomes assuming a 30% relative risk increase, an alpha level of 5%, and 80% power. The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1 at 90 days); secondary outcomes included good functional outcome (modified Rankin Scale score 0-2), symptomatic and any intracranial hemorrhage, and severe adverse events.

Results: Four randomized controlled trials encompassing 1395 patients (MT and IAT: 701; MT alone: 694) met the inclusion criteria. The pooled analysis demonstrated significantly improved excellent functional outcome (OR, 1.31 [95% CI, 1.06-1.63]) in patients receiving IAT after MT compared with MT alone. No statistically significant difference was observed for good functional outcome (OR, 1.07 [95% CI, 0.86-1.32]), all-cause death (OR, 0.92 [95% CI 0.70-1.21]), symptomatic intracranial hemorrhage (OR, 1.31 [95% CI, 0.74-2.34]), any intracranial hemorrhage (OR, 1.30 [95% CI, 0.96-1.76]), and severe adverse events (OR, 1.05 [95% CI, 0.67-1.66]). Trial sequential analysis revealed sufficient evidence to confirm a 30% relative risk increase for excellent functional outcome. The overall quality of evidence was moderate except for good functional outcome, rated as low.

Conclusion: IAT following MT was associated with increased odds of excellent functional outcomes at 90 days compared with MT alone, with no significant differences observed in intracranial hemorrhage, all-cause mortality, or severe adverse events.

Background: Equitable access to health care is heavily affected by socioeconomic factors. However, the effects of such disparities in accessing life-saving treatments remain incompletely characterized. Here we explore the impact of disparities on access to endovascular treatments for large vessel occlusion acute ischemic stroke.

Methods: From our prospectively maintained multihospital registry, we identified patients with large vessel occlusion acute ischemic stroke from January 2019-June 2020. Patient addresses and zip codes were matched to census-tract level area deprivation index (ADI) scores that were obtained from Neighborhood Atlas. ADI is a validated neighborhood-level measure that uses variables such as income, education, and employment to quantify the level of deprivation in an area. The primary outcome was use of endovascular thrombectomy by ADI tertile, adjusted for age, Alberta Stroke Program Early CT [Computed Tomography] Score, and National Institutes of Health Stroke Scale score, and was determined using multivariable logistic regression and expressed as odds ratio (OR [95% CI]). Secondary outcomes included use of intravenous tissue plasminogen activator, 90-day disability outcomes, last known well to arrival, transfer status, and discharge disposition.

Results: Among 484 patients with large vessel occlusion acute ischemic stroke, the median age was 70, 46.5% were female, 41.5% were non-Hispanic White, 28.1% were non-Hispanic Black, and 15.5% identified as Hispanic. Median national ADI was 57.5 (interquartile range, 33-78). ADI was significantly associated with race, a higher prevalence of stroke risk factors (hypertension, diabetes, hyperlipidemia, prior strokes), and a higher last known well to arrival time. In the univariable analysis and generalized mixed-effects logistic model, patients with acute ischemic stroke large vessel occlusion in greater ADI neighborhoods had lower odds of undergoing endovascular treatments compared with the lowest ADI group (OR = 0.45, P value = 0.014); however, no significant difference was observed in the odds of receiving intravenous tissue plasminogen activator between the different groups.

Conclusion: Patients residing in disadvantaged neighborhoods (greater ADI regions) may have reduced rates of reperfusion therapy, despite comparable acute stroke presentation symptoms. These findings are consistent with prior studies demonstrating poorer health outcomes in these populations.

The regulatory landscape for neurovascular innovation in the United States remains fragmented, delaying the development and approval of novel diagnostics, drugs, and devices critical to addressing the burden of stroke and other neurovascular disorders. Despite the significant public health impact, regulatory progress has been sluggish, with only two drugs approved for acute stroke in the Food and Drug Administration's (FDA) history, highlighting the need for a shift from a reactive to a proactive, productivity-driven regulatory approach. Current challenges include insufficient stakeholder engagement, opaque decision-making, outdated trial methodologies, and rigid regulatory paradigms that fail to incorporate real-world evidence and emerging technologies. The lack of transparency in trial oversight, inconsistent adjudication processes, and ineffective conflict-of-interest management further hinder trust in regulatory decisions. Additionally, existing safety assessment frameworks require modernization, as outdated adverse event thresholds fail to capture long-term risks and nuanced safety concerns in neurovascular interventions. To address these gaps, regulatory pathways must be realigned with the FDA's broader mission by integrating accelerated approval mechanisms, expanding expert input, and fostering continuous engagement with clinicians, researchers, and industry leaders. Enhancing trial methodologies through standardized imaging core lab processes, adaptive trial designs, and comprehensive safety monitoring will improve the reliability and applicability of clinical data. Furthermore, the recalibration of outcome measures-balancing technical imaging end points with meaningful clinical metrics-ensures that new therapies demonstrate not only efficacy but also real-world benefit. The integration of artificial intelligence, real-world data, and telehealth solutions has the potential to revolutionize regulatory oversight, facilitating dynamic trial adaptations and streamlining approval timelines. Moving forward, regulatory decision-making must be grounded in robust, transparent data rather than outdated paradigms, ensuring that approvals are based on verifiable, patient-centered outcomes rather than arbitrary historical precedents. By modernizing its approach, the FDA can enhance innovation while maintaining rigorous safety and efficacy standards, ultimately accelerating the translation of life-saving neurovascular therapies into clinical practice. This reform-driven strategy offers a clear roadmap for addressing long-standing inefficiencies, ensuring that regulatory oversight supports rather than hinders advancements in stroke and neurovascular care.

Background: The optimal treatment of acute large vessel occlusion with concomitant extracranial steno-occlusive disease of the internal carotid artery remains unclear. The PICASSO (Proximal Internal Carotid Artery Acute Stroke Secondary to Tandem or Local Occlusion Thrombectomy Trial) randomized clinical trial is designed to answer the question whether acute carotid stenting is superior to a nonacute stenting approach in the setting of a tandem lesion or tandem occlusion.

Methods: PICASSO is a prospective, randomized, controlled, multicenter, open label, assessor-blinded acute ischemic stroke trial with pragmatic design enrolling up to 404 patients at up to 60 sites. Patients with anterior circulation large vessel occlusion with severe stenosis or complete occlusion (70%-100%) of the extracranial carotid artery who meet the imaging and clinical eligibility criteria will be randomized in a 1:1 ratio to undergo mechanical thrombectomy of the intracranial lesion plus emergent stenting of the extracranial lesion versus mechanical thrombectomy plus no stenting up to 16 hours from last known well.

Results: The primary efficacy outcome is the ordinal shift of 90-day modified Rankin Scale (mRS) score. The primary analysis will be based on the intention-to-treat principle stratified by the Alberta Stroke Program Early CT [Computed Tomography] Score (7-8 versus 9-10), degree of proximal carotid stenosis (70%-90% versus 91%-100%), NIHSS (≤ 10 versus > 10), and use of intravenous thrombolysis. The primary safety outcome is symptomatic intracranial hemorrhage. Secondary outcomes include 1-year mRS (dichotomized and ordinal), successful reperfusion, and vessel patency at follow-up. Subgroup analyses will include comparison of intravenous versus oral antiplatelets in the stenting arm, and treatment of proximal intracranial occlusion first versus a simultaneous approach.

Conclusion: PICASSO is a pragmatic randomized trial, designed to address the safety and efficacy of mechanical thrombectomy with acute carotid stenting versus nonacute stenting with or without delayed revascularization treatment in patients with anterior circulation large vessel occlusion and concomitant extracranial severe stenosis or complete occlusion.

Clinical trial registration: NCT05611242.

Background: In the AcT (Alteplase compared to Tenecteplase) trial, tenecteplase (0.25 mg/kg) was non-inferior to alteplase (0.9 mg/kg) for efficacy, and similar in terms of safety in patients with acute ischemic stroke presenting within 4.5 hours of stroke symptom onset. Additional analyses were required to support regulatory approval.

Methods: Individual patient data from the AcT study were independently re-analyzed to confirm the robustness of the primary results; adhere to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use reporting guidelines; and fulfill regulatory requirements, such as re-analysis to account for known effect modifiers of thrombolytic therapy and investigation of potential bias at randomization. These data were part of the submission to the European Medicines Agency.

Results: The primary endpoint results from AcT were found to be reproducible, robust, not a chance finding, and without bias, confirming that tenecteplase was non-inferior to alteplase and significantly superior to control. The pharmacologic effect of tenecteplase in relation to sex, age, National Institutes of Health Stroke Scale score (disease severity) at baseline, and onset to treatment time was very similar to the pharmacologic effect of alteplase. Similar event rates for symptomatic intracerebral hemorrhage and death were observed for both groups. In January 2024, tenecteplase was approved for the treatment of acute ischemic stroke in Europe.

Conclusion: Regulatory agencies require specific analyses in order to assess potential bias. Successful customization and extended re-analysis of data from AcT to meet regulatory requirements and adhere to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use reporting guidelines demonstrate that it is possible to bridge the gap between academia and regulatory approval.