Kallmes, David F.

Background Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with extensive baseline ischemic injury (AIS-EBI). We conducted a systematic review and meta-analysis of RCTs reporting EVT for AIS-EBI. Methods Using the Nested Knowledge AutoLit software, we conducted a systematic literature review from inception to 12 February 2023 within Web of Science, Embase, Scopus, and PubMed databases. Results of the TESLA trial were included on 10 June 2023. We included RCTs that compared EVT to MEDT for AIS with large ischemic core volume. The primary outcome of interest was a modified Rankin Score (mRS) 0-2. Secondary outcomes of interest included early neurological improvement (ENI), mRS 0-3, thrombolysis in cerebral infarction (TICI) 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. A random-effects model was used to calculate risk ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results We included four RCTs with 1310 patients, 661 of whom underwent EVT and 649 of whom were treated with MEDT. EVT was associated with greater rates of mRS 0-2 (RR = 2.33, 95% CI = 1.75–3.09; P -value < 0.001), mRS 0-3 (RR = 1.68, 95% CI = 1.33–2.12; P -value < 0.001), and ENI (RR = 2.24, 95% CI = 1.55–3.24; P -value < 0.001). Rates of sICH (RR = 1.99, 95% CI = 1.07–3.69; P -value = 0.03) were greater in the EVT group. Mortality (RR = 0.98, 95% CI = 0.83–1.15; P -value = 0.79) was comparable between the EVT and MEDT groups. The rate of successful reperfusion in the EVT group was 79.9% (95% CI = 75.6–83.6). Conclusions Although the rate of sICH was greater in the EVT group, EVT conferred a greater clinical benefit to MEDT for AIS-EBI based on available RCTs.

Background The Woven EndoBridge (WEB) has been specifically developed to manage wide neck bifurcation intracranial aneurysms. A wide range of aneurysm occlusion rates and device-related complications are reported in different papers, and a lack of collective evidence in this regard. Objective To clarify the long-term efficacy and safety outcomes of intracranial aneurysm treatment with WEB devices. Methods A systematic literature search was performed on PubMed, Scopus, Web of Science, and Embase databases on April 25, 2023. Considering the eligibility criteria, all the studies reporting the outcomes of the intracranial aneurysm treatment with WEB device at 1 and/or more than 1 year were included. Data elements of interest were extracted and analyzed using R software version 4.2.1. Results Twenty-seven articles were included. Complete occlusion rate was 56.85%, 67.10%, and 56.34% at one year, beyond one year, and at/beyond two years of follow-up, respectively. Adequate occlusion rate was 87.11% at one year, 91.16% beyond one year, and 88.87% at/beyond two years of follow-up. WEB compression and aneurysm recurrence rates increased from 17.62% and 0.58% at one year to 42.59% and 18.99% beyond one year of follow-up, respectively. An increase in retreatment rate from 3.45% at one year to 7.15% beyond one year of follow-up was found. Conclusion The current study supports the long-term efficacy of WEB devices for the treatment of intracranial aneurysms. However, an increase in WEB compression, aneurysm recurrence, and retreatment rates beyond one year reveals the importance of follow-ups after the first year of WEB placement.

Background Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT’s specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. Methods In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). Results Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0–2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0–2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. Conclusions Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.

Background Intra-procedural characterization of stroke thromboemboli might guide mechanical thrombectomy (MT) device choice to improve recanalization rates. Electrochemical impedance spectroscopy (EIS) has been used to characterize various biological tissues in real time but has not been used in thrombus. Objective To perform a feasibility study of EIS analysis of thrombi retrieved by MT to evaluate: (1) the ability of EIS and machine learning to predict red blood cell (RBC) percentage content of thrombi and (2) to classify the thrombi as “RBC-rich” or “RBC-poor” based on a range of cutoff values of RBC. Methods ClotbasePilot was a multicentric, international, prospective feasibility study. Retrieved thrombi underwent histological analysis to identify proportions of RBC and other components. EIS results were analyzed with machine learning. Linear regression was used to evaluate the correlation between the histology and EIS. Sensitivity and specificity of the model to classify the thrombus as RBC-rich or RBC-poor were also evaluated. Results Among 514 MT,179 thrombi were included for EIS and histological analysis. The mean composition in RBC of the thrombi was 36% ± 24. Good correlation between the impedance-based prediction and histology was achieved (slope of 0.9, R 2 = 0.53, Pearson coefficient = 0.72). Depending on the chosen cutoff, ranging from 20 to 60% of RBC, the calculated sensitivity for classification of thrombi ranged from 77 to 85% and the specificity from 72 to 88%. Conclusion Combination of EIS and machine learning can reliably predict the RBC composition of retrieved ex vivo AIS thrombi and then classify them into groups according to their RBC composition with good sensitivity and specificity.

ImportancePrevious randomized clinical trials (RCTs) have supported the use of endovascular therapy (EVT) in late-window acute ischemic stroke (AIS; 6-24 hours). However, little is known about the use of EVT in very late-window AIS (&amp;gt;24 hours).ObjectiveTo examine outcomes following EVT for very late-window AIS.Data SourcesA systematic review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed to search for articles published from database inception until December 13, 2022.Study SelectionThis systematic review and meta-analysis included published studies regarding very late-window AIS treated with EVT. Multiple reviewers screened studies, and an extensive manual search of the references of included articles was performed to identify any missed articles. Of the 1754 initially retrieved studies, 7 published between 2018 and 2023 were ultimately included.Data Extraction and SynthesisData were extracted independently by multiple authors and evaluated for consensus. Data were pooled using a random-effects model. This study is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline, and the protocol was prospectively registered with PROSPERO.Main Outcomes and MeasuresThe primary outcome of interest was functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2). Secondary outcomes included thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), 90-day mortality, early neurological improvement (ENI), and early neurological deterioration (END). Frequencies and means were pooled with the corresponding 95% CIs.ResultsThis review included 7 studies involving a total of 569 patients. The mean baseline National Institutes of Health Stroke Scale score was 13.6 (95% CI, 11.9-15.5), and the mean Alberta Stroke Program Early CT Score was 7.9 (95% CI, 7.2-8.7). The mean time from last known well and/or onset to puncture was 46.2 hours (95% CI, 32.4-65.9 hours). Frequencies for the primary and secondary outcomes were 32.0% (95% CI, 24.7%-40.2%) for functional independence (90-day mRS scores of 0-2) and 81.9% (95% CI, 78.5%-84.9%) for TICI scores of 2b to 3, 45.3% (95% CI, 36.6%-54.4%) for TICI scores of 3, 6.8% (95% CI, 4.3%-10.7%) for sICH, and 27.2% (95% CI, 22.9%-31.9%) for 90-day mortality. In addition, frequencies were 36.9% (95% CI, 26.4%-48.9%) for ENI and 14.3% (95% CI, 7.1%-26.7%) for END.Conclusions and RelevanceIn this review, EVT for very late-window AIS was associated with favorable frequencies of 90-day mRS scores of 0 to 2 and TICI scores of 2b to 3 and with low frequencies of 90-day mortality and sICH. These results suggest that EVT may be safe and associated with improved outcomes for very late-window AIS, although RCTs and prospective, comparative studies are needed to determine which patients may benefit from very late intervention.

Background Endovascular thrombectomy (EVT) is a treatment option for acute ischemic stroke due to large vessel occlusion. The use of a balloon-guided catheter (BGC) for EVT via transradial access (TRA) has emerged as a treatment approach, but its efficacy and safety compared to existing practices are uncertain. Methods A systematic literature review was performed using Embase, PubMed, Scopus, Web of Science databases, and manual search. Studies reporting safety and efficacy metrics for TRA BGC EVT were included. Data regarding recanalization time, thrombolysis in cerebral infarction (TICI), modified Rankin scale (mRS), symptomatic intracranial hemorrhage (sICH), first pass effect (FPE), and additional complications was pooled using a random-effects model to calculate event rates and 95% confidence intervals (CI). Results The search yielded five studies (n = 117). The mean time from puncture to final recanalization was 34.5 (95% CI = 30.5 to 39.14, I 2 = 0%, P-value = 0.37) min. Successful recanalization (TICI 2b-3) and complete recanalization (TICI 3) occurred in 96.6% (95% CI = 91.24 to 98.71, I 2 = 0%, P-value = 0.99) and 55.2% (95% CI = 42.14 to 67.54, I 2 = 0%, P-value = 0.39) of cases, respectively. FPE occurred in 67.5% (95% CI = 51.73 to 80.10, I 2 = 0%, P-value = 0.56) of patients. mRS 0-2 was achieved in 41.2% (95% CI = 27.34 to 56.65, I 2 = 70%, P-value = 0.07) of patients. sICH occurred in 5.0% (95% CI = 1.25 to 17.91, I 2 = 0%, P-value = 1.00) of patients. Local complications of radial hematoma and radial vasospasm occurred in 5.0% (95% CI = 0.49 to 12.36, I 2 = 29%, P-value = 0.24) and 2.1% (95% CI = 1.25 to 17.91, I 2 = 71%, P-value = 0.03) of cases, respectively. Switch to femoral access was necessary in 3.7% (95% CI = 0.00 to 14.07, I 2 = 68%, P-value = 0.02) of procedures. The average number of passes per procedure was 1.6 (95% CI = 1.15 to 2.11, I 2 = 88%, P-value < 0.001). Conclusion TRA BGC EVT has potential as a safe and efficacious treatment option compared to existing methods. However, additional, prospective studies are necessary to inform clinical decision making.

Introduction Various clinical trials addressing large core acute ischemic stroke (AIS) are ongoing from multiple international groups. Future development of clinical guidelines depends on meta‐analyses of these trials calling for a degree of homogeneity of elements across the different studies. The aim of this common data element study was to provide an overview of the key features of pertinent large core infarct trials. Methods PubMed and ClinicalTrials.gov databases were screened for published and ongoing clinical trials assessing mechanical thrombectomy in patients with AIS with large core infarct. Nested Knowledge AutoLit living review platform was utilized to categorize primary and secondary outcomes as well as inclusion and exclusion criteria for patient selection in the clinical trials. Results The most reported data element was ASPECTS score, but with varied definitions of what compromises large core. Non‐utility‐weighted modified Rankin Score (mRS) was reported in 6/7 studies as the primary outcome, while the utility‐weighted mRS was the outcome of interest in the TESLA trial, all of them at the 3‐months mark, with only LASTE looking for mRS shift at the 6‐months mark. Secondary outcomes had more variations. Mortality is reported separately only in 4/7 trials, all at the 3‐month mark. Additionally, the TENSION trial reports the frequency of serious adverse events, including mortality, at the 1‐week and 12‐month mark. Conclusions In the published and the ongoing large core trials, there is a large degree of variability in the collected data elements. Differences in definition and timepoints renders reaching a unified standard difficult, which hinders high quality meta‐analyses and cohesive evidence‐driven synthesis.

Background Dual antiplatelet therapy (DAPT) is frequently used in treating cerebral aneurysms with flow diverters (FDs), whereas single antiplatelet therapy (SAPT) is used mostly with coated FDs and in ruptured aneurysms. We conducted a systematic review and meta-analysis to explore the safety profile of SAPT in FDs. Methods PubMed, Web of Science, OVID Embase, OVID Medline, and Scopus were searched to 1st November 2022. Outcomes of interest included ischemic and hemorrhagic complications, conversion to DAPTs, and in-stent stenosis rates under long-term SAPT. SAPT is divided into aspirin (ASA) vs. non-ASA group (ticagrelor or prasugrel). Subgroup analysis was performed for ruptured vs. non-ruptured aneurysms and coated vs. non-coated FDs. All data were analyzed using R software version 4.2.2. Results Twelve studies with 240 total patients (43 patients in the ASA group and 197 patients in the non-ASA group) were included in our meta-analysis. The pooled ischemic occlusion rate was 9.8% (95% CI = 4.87−18.95: p-value = 0.09) for SAPTs. The ASA group had significantly higher ischemic complication rates compared to the non-ASA group (20.8% vs. 6.3%, respectively, p-value = 0.02). The pooled hemorrhagic complication rate was 3.5% (95% CI = 1.38−8.81: p-value > 0.99). The hemorrhagic rates of ASA group were 9.3%% (95% CI = 3.54−22.30) over the non-ASA group 2.1% (95% CI = 0.58−7.54) ( p-value > 0.99). The overall in-stent stenosis rate was 2.3% (95% CI = 1.06−5.14: p-value > 0.99). The ischemic complication rates were comparable between coated vs non-coated FDs (10.7% vs. 5.5% p-value = 0.39). In stent stenosis rate were 1.9% (95% CI = 0.72−4.96) in coated FDs over 4.4% (95% CI = 1.11−16.11) ( p-value = 0.32). The ruptured and non-ruptured groups also showed comparable results in terms of ischemic (17.6% vs. 7.1% respectively, p-value = 0.24) and hemorrhagic complications (9.8% vs. 1.1%, respectively, p-value = 0.08). Conclusions Flow diverter treatment under ASA monotherapy resulted in relatively high ischemic complication rates. However, SAPT with prasugrel or ticagrelor monotherapy is promising for coated FDs and ruptured aneurysm treatments. Given the overall small sample size and also the likely presence of known and unknown biases regarding choice of antiplatelet therapy between groups, larger cohort studies are needed to evaluate SAPT treatment outcomes.

Symptomatic non-stenotic carotid plaques (SyNC) are an under-researched and under-recognized source of stroke. Various imaging markers of non-stenotic carotid plaques that are associated with stroke risk have been identified, but these causal relationships need to be confirmed in additional prospective studies. Currently, there exists neither a standardized SyNC definition nor a dedicated set of imaging protocols, although researchers have started to address these shortcomings. Moreover, many neuroradiologists are still unaware of the condition, and hence do not comment on high-risk plaque features other than stenosis in their reports. Regarding SyNC treatment, scant data exist as to whether and to what extent medical, interventional and surgical treatments could influence the course of the disease; the relative lack of data on the ‘natural’ history of untreated SyNC makes treatment comparisons difficult. In our opinion, endovascular SyNC treatment represents the most promising treatment option for SyNC, since it allows for targeted elimination of the embolic source, with few systemic side effects and without the need for general anesthesia. However, currently available carotid devices are designed to treat stenotic lesions, and thus are not optimally designed for SyNC. Developing a device specifically tailored to SyNC could be an important step towards establishing endovascular SyNC treatment in clinical practice. In this review, we provide an overview of the current state of evidence with regard to epidemiological, clinical and imaging features of SyNC, propose a SyNC definition based on imaging and clinical features, and outline a possible pathway towards evidence-based SyNC therapies, with a special focus on endovascular SyNC treatment.

Background Federal research funding is highly sought after but may be challenging to attain. A clear understanding of funding for specific diseases, such as cerebrovascular disorders, might help researchers regarding which National Institutes of Health (NIH) institutes fund research into specific disorders and grant types. Objective To examine the current scope of NIH grant funding for cerebrovascular conditions. Methods The NIH-developed RePORTER was used to extract active NIH-funded studies related to cerebrovascular diseases through January 2023. Duplicate studies were removed, and projects were manually screened and labeled in subcategories as clinical and basic science and as research subcategories. Extracted data included total funding, grant types, institutions that received funding, and diseases studied. Python (version 3.9) and SciPy library were used for statistical analyses. Results We identified 1232 cerebrovascular projects across seven diseases with US$699 952 926 in total funding. The cerebrovascular diseases with the greatest number of grants were ischemic stroke (705, or 57.2% of all funded projects), carotid disease (193, or 15.7%), and hemorrhagic stroke (163, or 13.2%). R01 grants were the most common mechanism of funding (632 grants, or 51.3%). The National Institute of Neurological Disorders and Stroke (NINDS) funded the most projects (504 projects; US$325 536 405), followed by the National Heart, Lung, and Blood Institute (NHLBI) (376 projects; US$216 784 546). Conclusion Cerebrovascular disease receives roughly US$700 million in NIH funding. Ischemic stroke accounts for the majority of NIH-funded cerebrovascular projects, and R01 grants are the most common funding mechanism. Notably, NHLBI provides a large proportion of funding, in addition to NINDS.