Stroke (Hoboken, N.J.)最新文献

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 Current challenges include insufficient stakeholder engagement, opaque decision-making, outdated trial methodologies, and rigid regulatory paradigms that fail to incorporate real-world evidence and emerging technologies.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 Additionally, existing safety assessment frameworks require modernization, as outdated adverse event thresholds fail to capture long-term risks and nuanced safety concerns in neurovascular interventions.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 Moving forward, regulatory decision-making must be grounded in robust, transparent data rather than outdated paradigms, ensuring that approvals are based on verifiable, patient-centered outcomes rather than arbitrary historical precedents.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.

Background: For acute ischemic stroke due to intracranial large-vessel occlusion in the anterior circulation, guidelines recommend treatment with intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator and endovascular thrombectomy (EVT). We investigated whether plasma fibrinolysis biomarkers were associated with the treatment effect of EVT, with or without IVT with recombinant tissue plasminogen activator, and their potential implications for clinical and radiological outcomes.

Methods: In this post hoc analysis of MR CLEAN-NO IV, we measured fibrinolytic biomarkers (tissue plasminogen activator, global clot lysis time, and D-dimer) before and 24 hours post reperfusion and assessed their associations with patients' clinical and radiological outcomes based on National Institutes of Health Stroke Scale score, modified Rankin Scale (mRS) score, post-EVT extended thrombolysis in cerebral infarction score, and final infarct size. To quantify these associations, we used linear and logistic regression.

Results: Blood was collected from 214 of 536 included patients, who received IVT+EVT (N = 108) or EVT alone (N = 106). In the IVT+EVT group, D-dimer levels 24 hours after treatment were higher and clot lysis time lower than in the EVT group, indicating more fibrinolysis. Pearson correlation showed that high D-dimer levels before and 24 hours after EVT were correlated with unfavorable long-term functional outcomes (mRS at 90 days), and D-dimer levels 24 hours after EVT linked to large infarct size. High tissue plasminogen activator levels after IVT+EVT were correlated with successful reperfusion. However, regression analysis adjusted for confounders showed no associations between fibrinolytic biomarkers and clinical or radiological outcomes.

Conclusion: None of the fibrinolysis biomarkers were independently associated with outcomes in adjusted regression analysis, failing to support their use as predictors for treatment decisions or therapeutic effectiveness. However, exploratory analyses suggested that higher tissue plasminogen activator levels after IVT+EVT correlated with successful reperfusion, whereas elevated D-dimer levels were linked to unfavorable outcomes and larger infarct size post-EVT. Larger studies are needed to clarify their role in stroke treatment with IVT and/or EVT.

Clinical trial registration: This study is a substudy of the MR CLEAN-NO IV trial, which is registered at the ISRCTN registry (ISRCTN80619088, https://www.isrctn.com/ISRCTN80619088).

Background: The optimal therapeutic approach for acute ischaemic stroke due to distal medium vessel occlusion remains uncertain. The use of endovascular therapy in this context is restricted by challenges in navigating distal vessels with available devices. This study aimed to assess the safety and effectiveness of the Red43 aspiration catheter (Penumbra, Alameda, CA) in patients experiencing stroke due to distal medium vessel occlusion.

Methods: A retrospective analysis was conducted on consecutive patients who underwent mechanical thrombectomy for acute ischemic stroke at a single high-volume comprehensive stroke center from April 2023 to March 2024. Patients were included if they had an acute ischemic stroke with distal medium vessel occlusion and were treated using the Red43 aspiration catheter.

Results: The Red43 aspiration catheter successfully reached the occlusion site in 94% of cases. modified treatment in cerebral ischemia 2b-3 reperfusion was achieved in 77% of patients following initial use of the Red43 catheter, whereas modified treatment in cerebral ischemia 2c-3 reperfusion was observed in 66%. No cases of symptomatic intracranial hemorrhage, vessel perforation, or dissection occurred during the procedure.

Conclusion: The Red43 aspiration catheter demonstrated a high rate of successful reperfusion with a favorable safety profile in the treatment of distal medium vessel occlusion stroke.

Background: Recanalization sometimes fails during endovascular thrombectomy due to target vessel access failure. Two-dimensional/3-dimensional fusion imaging in the Siemens ARTIS Icono biplane platform may facilitate access by fusing the preoperative computed tomography angiography with procedural imaging. This observational study aimed to evaluate vascular access, success rates, and procedure times in endovascular thrombectomies with fusion imaging compared to standard treatment.

Methods: Patients treated with endovascular thrombectomy for ischemic stroke at Skåne University Hospital in Lund, Sweden, were consecutively included. Baseline and procedural characteristics were gathered from radiological patient records. Procedural success rate and lead times such as groin-to-recanalization times were evaluated. Associations between fusion imaging and first-pass recanalization and groin to first pass <30 minutes were also assessed.

Results: Of 347 patients, fusion imaging was used in 68 cases. Failure to reach the occlusion occurred in 6 (2%) of the nonfusion cases compared with none in the fusion group. Successful recanalization (modified Treatment in Cerebral Infarction score ≥2b) was obtained in all fusion cases, compared with 86% in the nonfusion group (P = 0.001). First-pass recanalization occurred in 72% and 49% of the fusion and nonfusion groups respectively (P<0.001). The groin-to-recanalization time was significantly shorter in fusion cases compared with nonfusion (33 versus 43 min, P = 0.04). When adjusting for age and sex, fusion was significantly associated with first-pass recanalization (odds ratio, 2.70; [95% CI, 1.51-4.86]; P<0.001).

Conclusion: Fusion imaging use in the Siemens ARTIS Icono biplane platform in endovascular thrombectomy is not associated with worsened procedural results and appears to decrease failed target artery access risk and increase procedural success rate as well as first-pass success rate, without procedure prolongation. These initial observational findings need to be further evaluated in prospective randomized studies.

Background: Augmented Reality (AR) enables visualization of and interaction with both physical and virtual environments. Holograms can allow 3D image transmission to distant sites, allowing patients to interact with providers as if in the same space. Our prior publication resulted in high satisfaction/immersion for patients interacting with Holo-Stroke providers. Our aim here was to determine if providers assessing CTAs for large vessel occlusion (LVO) would result in reliability and satisfaction.

Methods: Thirty-six head CTAs were de-identified and scored by Stroke Faculty, Fellows, and Nurse Practitioners for LVO using DICOM viewer. CTAs were presented 2 months later via Holo-Stroke. Holograms were positioned in 3D-space, viewable through the Hololens-2, and scored by the same providers. Kappa Reliability was assessed comparing scores to gold-standard (radiology report). Satisfaction was assessed via Likert scale.

Results: Thirteen providers scored the CTAs. Overall Kappa reliability, compared to gold standard, was 0.78(81%)DICOMvs.0.94(94%)Holo-Stroke-CTA(p<0.0001). Overall %correct was 81%vs.94%(p<0.001). Holo-Stroke-CTA's reliability improved for most examiners: Overall (κ=0.78(81%)vs.0.94(94%)), Faculty (κ=0.85(87%)vs.0.92(93%)), NPs (κ=0.81(83%)vs.0.90(92%)), and Fellows (κ=0.68(72%)vs.0.97(97%)). Overall MCA (κ=0.76(86%)vs.0.93(96%)), ICA (κ=0.8(88%)vs.0.9(94%)), and Basilar (κ=0.73(95%)vs. 0.82(96%)) scored high, with marked improvement for ACA (κ=0.3(39%)vs. 0.91(94%)), and PCA (κ=0.55(70%)vs.0.95(98%)). Likert satisfaction "Overall" was (18DICOM,48Holo-Stroke-CTA;p=0.002) with %increasing from 39% to 96%. "Immersion" scores were (0,10;p=0.001), "Ease of Use" (5,9;p=0.002), "Accuracy" (7,9;p=0.002), "Technology Advancement" (4,10;p=0.001), and "Interest" (3,10;p=0.002).

Conclusions: Holo-Stroke-CTA resulted in higher reliability and satisfaction vs. standard DICOM tele-stroke tele-radiology. Providers noted the ability to see 3D vessels in virtual space, vs. scrolling through axial/sagittal/coronal images, resulted in higher accuracy. Even for trainees and difficult to assess vessels, providers were more able to identify LVOs using Holo-Stroke-CTA. Providers were enthusiastic for the immersive radiology assessment, with the ability to immersively resize, rotate, and investigate hologram in 3D virtual space. Though further assessments are needed, Holo-Stroke-CTA can help providers more easily, and at-a-glance, evaluate CTA for LVO.

Background: Predicting and managing spontaneous Cervical Artery Dissections (CeAD) is challenging due to the absence of tools for early identification of high-risk individuals. This study seeks to gather evidence on the predictive value of high-intensity transient signals (HITS) detected by Transcranial Doppler for recurrent ischemic events (IEs) following CeAD.

Methods: We performed a systematic review and meta-analysis of published studies along with the data from our cohort. Following PRISMA guidelines, we searched Pubmed, Embase and Scopus to identify studies that evaluated HITS in patients with CeAD with the aim of predicting IEs. Data were pooled using a random effects model, with odds ratio (OR) and its 95% confidence interval (CI) as the effect size. Heterogeneity was assessed with the Q statistic and I² test, while subgroup analysis evaluated the impact of dissected artery (carotid vs vertebral) on the relationship between HITS and ischemic events. Our retrospective study included consecutive patients diagnosed with CeAD, followed for 90 days to record IEs. Univariable and multivariable analyses were performed to identify factors associated with recurrent TIAs or strokes within 90 days post-CeAD.

Results: Our systematic review included five prior studies, which, combined with our center's sample size, provided data for a total of 306 patients. The meta-analysis indicated that HITS is a significant predictor of IEs (OR: 13.25, 95% CI [2.97-59.13], p<0.01) with low heterogeneity (I2 = 42%, p = 0.13). However, subgroup analysis indicated that HITS are a significant predictor only for carotid artery dissections (p<0.01), and not for vertebral artery dissections (p=0.11). The cohort consisted of 34 patients (mean age: 46.8 years, 55.9% male). The incidence of IEs was 20% in our cohort and all of them (100%) had HITSs in TCD. In multivariable analysis, the presence of HITS (p=0.006) and intra-luminal thrombosis (p=0.02) were significant predictors of IEs.

Conclusions: The presence of HITS detected by TCD is a strong predictor of IEs in patients with Carotid artery dissections. This highlights the clinical value of TCD in identifying high-risk patients and emphasizes the need for proactive management strategies to reduce the risk of future IEs in this subgroup.