Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024.

Endovascular therapy of isolated posterior cerebral artery occlusion stroke with and without general anesthesia.

BACKGROUND: The optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA). METHODS: Patients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality. RESULTS: Among 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups. CONCLUSION: In patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar.

Endovascular Thrombectomy Versus Intravenous Thrombolysis of Posterior Cerebral Artery Occlusion Stroke.

BACKGROUND AND PURPOSE: Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. METHODS: From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0-1) and independent outcome (mRS 0-2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. RESULTS: Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3-P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79-1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05-2.12), sICH (aOR 2.87, 95% CI 1.23-6.72), and mortality (aOR 1.77, 95% CI 1.07-2.95). CONCLUSION: Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability.

BACKGROUND AND PURPOSE: We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. METHODS: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1). RESULTS: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). CONCLUSION: A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Distal Medium Vessel Occlusion Strokes: Understanding the Present and Paving the Way for a Better Future.

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.

Endovascular Versus Medical Therapy in Posterior Cerebral Artery Stroke: Role of Baseline NIHSS Score and Occlusion Site.

BACKGROUND: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site. METHODS: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality. RESULTS: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (Pinteraction=0.312) but did with functional independence (Pinteraction=0.010), with a similar trend on excellent outcome (Pinteraction=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score (Pinteraction=0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 (Pinteraction=0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM. CONCLUSIONS: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. METHODS: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. RESULTS: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). DISCUSSION: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT04096248. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus.

BACKGROUND: Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. METHODS: Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. RESULTS: During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results. CONCLUSION: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke.

INTRODUCTION: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. PATIENTS AND METHODS: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. RESULTS: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). CONCLUSION: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; Unique identifier: NCT04096248.

What is the influence of biomechanical variables on the Y balance test performance in recreational runners?

BACKGROUND: Asymmetries and poor Y balance test (YBT) performance are associated with an increased risk of injuries in athletes. The aim of this study was to investigate the association between YBT performance with biomechanical variables in runners. METHODS: The runners underwent the YBT, followed by the assessment of center of pressure, plank position, muscle strength (MS) of hip flexors, extensors, abductors, and external rotators, knee extensors, ankle dorsiflexion range of motion (ROM), Q angle, forefoot alignment, and passive hip internal rotation. Associations between variables were examined using multiple linear regression models with the Bayesian Information Criterion. RESULTS: 122 cases were analyzed. The R2 values were 0.38; 0.05; 0.06; and 0.15 for the anterior, posteromedial, posterolateral and composite directions models, respectively. The anterior reach in the YBT was associated with ankle dorsiflexion ROM [Sß 95%IC: 0.43 (0.32-0.55)], passive hip internal rotation [Sß 95%IC: 0.35 (0.24-0.47)], MS of the hip extensors [Sß 95%IC: 0.19 (0.07-0.31)] and forefoot alignment [Sß 95%IC: 0.14 (-0.25-0.02)]. The posteromedial and posterolateral reach were associated with MS of the hip flexors [Sß 95%IC: 0.23 (0.09-0.37) and 0.24 (0.11-0.38)], respectively. The composite score was associated with MS of the hip flexors [Sß 95%IC: 0.31 (0.18-0.45)], ankle dorsiflexion ROM [Sß 95%IC: 0.24 (0.10-0.37)] and Q angle [Sß 95%IC: 0.18 (0.04-0.31)]. CONCLUSION: YBT performance in different directions demonstrated specific associations with key biomechanical factors.

Comparative Analysis of Transposable Elements Dynamics in Fish with Different Sex Chromosome Systems.

Transposable elements (TEs) are widespread genomic components with substantial roles in genome evolution and sex chromosome differentiation. In this study, we compared the TE composition of three closely related fish with different sex chromosome systems: Megaleporinus elongatus (Z1Z1Z2Z2/Z1W1Z2W2), Megaleporinus macrocephalus (ZZ/ZW) (both with highly differentiated W sex chromosomes), and Leporinus friderici (without heteromorphic sex chromosomes). We created custom TE libraries for each species using clustering methods and manual annotation and prediction, and we predicted TE temporal dynamics through divergence-based analysis. The TE abundance ranged from 16 to 21% in the three mobilomes, with L. friderici having the lowest overall. Despite the recent amplification of TEs in all three species, we observed differing expansion activities, particularly between the two genera. Both Megaleporinus recently experienced high retrotransposon activity, with a reduction in DNA TEs, which could have implications in sex chromosome composition. In contrast, L. friderici showed the opposite pattern. Therefore, despite having similar TE compositions, Megaleporinus and Leporinus exhibit distinct TE histories that likely evolved after their separation, highlighting a rapid TE expansion over short evolutionary periods.

Chromosomal and genomic analysis suggests single origin and high molecular differentiation of the B chromosome of Abracris flavolineata.

Supernumerary chromosomes (B chromosomes) have been an intriguing subject of study. Our understanding of the molecular differentiation of B chromosomes from an interpopulation perspective remains limited, with most analyses involving chromosome banding and mapping of a few sequences. To gain insights into the molecular composition, origin, and evolution of B chromosomes, we conducted cytogenetic and next-generation sequencing analysis of the repeatome in the grasshopper Abracris flavolineata across various populations. Our results unveiled the presence of B chromosomes in two newly investigated populations and described new satellite DNA sequences. While we observed some degree of genetic connection among A. flavolineata populations, our comparative analysis of genomes with and without B chromosomes provided evidence of two new B chromosome variants. These variants exhibited distinct compositions of various repeat classes, including transposable elements and satellite DNAs. Based on shared repeats, their chromosomal location, and the C-positive heterochromatin content on the B chromosome, these variants likely share a common origin but have undergone distinct molecular differentiation processes, resulting in varying degrees of heterochromatinization. Our data serves as a detailed example of the dynamic and differentiated nature of B chromosome molecular content at the interpopulation level, even when they share a common origin.

Rescue Therapy for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Pooled Analysis of the Society of Vascular and Interventional Neurology Registry.

OBJECTIVE: We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT). METHODS: This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32-2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21-3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28-0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42-0.89, p = 0.009). INTERPRETATION: Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024.

Anesthesia modality in endovascular treatment for distal medium vessel occlusion stroke: intention-to-treat propensity score-matched analysis.

BACKGROUND: The optimal anesthesia modality during endovascular treatment (EVT) for distal medium vessel occlusion (DMVO) stroke is uncertain. We aimed to evaluate the association of the anesthesia modality with procedural and clinical outcomes following EVT for DMVO stroke. METHODS: This is a multicenter retrospective analysis of a prospectively collected database. Patients were included if they had DMVO involving the middle cerebral artery-M3/4, anterior cerebral artery-A2/3, or posterior cerebral artery-P1/P2-3, and underwent EVT. The cohort was divided into two groups, general anesthesia (GA) and non-general anesthesia (non-GA), and compared based on the intention-to-treat principle as primary analysis. We used propensity scores to balance the two groups. The primary outcome was the shift in the degree of disability as measured by the 90-day modified Rankin Scale (mRS). Secondary outcomes included successful reperfusion, as well as excellent (mRS 0-1) and good (mRS 0-2) clinical outcomes at 90 days. Safety measures included procedural complications, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: Among 366 DMVO thrombectomies, 61 matched pairs were eligible for analysis. Median age and National Institutes of Health Stroke Scale score as well as other baseline demographic and clinical characteristics were balanced between both groups. The GA group had no difference in the overall degree of disability (common OR 1.19, 95% CI 0.52 to 2.86, P=0.67) compared with the non-GA arm. Likewise, the GA group had comparable rates of successful reperfusion (OR 2.38, 95% CI 0.80 to 7.07, P=0.12), good/excellent clinical outcomes (OR 1.14, 95% CI 0.44 to 2.96, P=0.79/(OR 0.65, 95% CI 0.24 to 1.81, P=0.41), procedural complications (OR 1.00, 95% CI 0.19 to 5.16, P>0.99), sICH (OR 3.24, 95% CI 0.83 to 12.68, P=0.09), and 90-day mortality (OR 1.43, 95% CI 0.48 to 4.27, P=0.52) compared with the non-GA group. CONCLUSIONS: In patients with DMVO, our study showed that GA and non-GA groups had similar procedural and clinical outcomes, as well as safety measures. Further larger controlled studies are warranted.

Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD).

BACKGROUND: Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs). METHODS: Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010-22 (development cohort) and 2018-22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls. RESULTS: Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis ß coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84-0.91) and 0.82 (0.73-0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI -0.5 to -0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity. CONCLUSION: The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data.

Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study.

BACKGROUND: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. METHODS: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. CONCLUSIONS: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

Subjects with carotid webs demonstrate pro-thrombotic hemodynamics compared to subjects with carotid atherosclerosis.

Carotid artery webs (CaW) are non-atherosclerotic projections into the vascular lumen and have been linked to up to one-third of cryptogenic strokes in younger patients. Determining how CaW affects local hemodynamics is essential for understanding clot formation and stroke risk. Computational fluid dynamics simulations were used to investigate patient-specific hemodynamics in carotid artery bifurcations with CaW, bifurcations with atherosclerotic lesions having a similar degree of lumen narrowing, and with healthy carotid bifurcations. Simulations were conducted using segmented computed tomography angiography geometries with inlet boundary conditions extracted from 2D phase contrast MRI scans. The study included carotid bifurcations with CaW (n = 13), mild atherosclerosis (n = 7), and healthy bifurcation geometries (n = 6). Hemodynamic parameters associated with vascular dysfunction and clot formation, including shear rate, oscillatory shear index (OSI), low velocity, and flow stasis were calculated and compared between the subject groups. Patients with CaW had significantly larger regions containing low shear rate, high OSI, low velocity, and flow stasis in comparison to subjects with mild atherosclerosis or normal bifurcations. These abnormal hemodynamic metrics in patients with CaW are associated with clot formation and vascular dysfunction and suggest that hemodynamic assessment may be a tool to assess stroke risk in these patients.

Heterochromatin Is Not the Only Place for satDNAs: The High Diversity of satDNAs in the Euchromatin of the Beetle Chrysolina americana (Coleoptera, Chrysomelidae).

The satellitome of the beetle Chrysolina americana Linneo, 1758 has been characterized through chromosomal analysis, genomic sequencing, and bioinformatics tools. C-banding reveals the presence of constitutive heterochromatin blocks enriched in A+T content, primarily located in pericentromeric regions. Furthermore, a comprehensive satellitome analysis unveils the extensive diversity of satellite DNA families within the genome of C. americana. Using fluorescence in situ hybridization techniques and the innovative CHRISMAPP approach, we precisely map the localization of satDNA families on assembled chromosomes, providing insights into their organization and distribution patterns. Among the 165 identified satDNA families, only three of them exhibit a remarkable amplification and accumulation, forming large blocks predominantly in pericentromeric regions. In contrast, the remaining, less abundant satDNA families are dispersed throughout euchromatic regions, challenging the traditional association of satDNA with heterochromatin. Overall, our findings underscore the complexity of repetitive DNA elements in the genome of C. americana and emphasize the need for further exploration to elucidate their functional significance and evolutionary implications.

Voltage-based magnetization switching and reading in magnetoelectric spin-orbit nanodevices.

As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies.