Second-dose intravenous thrombolysis with tenecteplase in alteplase-resistant medium-vessel-occlusion strokes: A retrospective and comparative study.

INTRODUCTION: In intracranial medium-vessel occlusions (MeVOs), intravenous thrombolysis (IVT) shows inconsistent effectiveness and endovascular interventions remains unproven. We evaluated a new therapeutic strategy based on a second IVT using tenecteplase for MeVOs without early recanalization post-alteplase. PATIENTS AND METHODS: This retrospective, comparative study included consecutively low bleeding risk MeVO patients treated with alteplase 0.9 mg/kg at two stroke centers. One center used a conventional single-IVT approach; the other applied a dual-IVT strategy, incorporating a 1-h post-alteplase MRI and additional tenecteplase, 0.25 mg/kg, if occlusion persisted. Primary outcomes were 24-h successful recanalization for efficacy and symptomatic intracranial hemorrhage (sICH) for safety. Secondary outcomes included 3-month excellent outcomes (modified Rankin Scale score of 0-1). Comparisons were conducted in the overall cohort and a propensity score-matched subgroup. RESULTS: Among 146 patients in the dual-IVT group, 103 failed to achieve recanalization at 1 h and of these 96 met all eligible criteria and received additional tenecteplase. Successful recanalization at 24 h was higher in the 146 dual-IVT cohort patients than in the 148 single-IVT cohort patients (84% vs 61%, p < 0.0001), with similar sICH rate (3 vs 2, p = 0.68). Dual-IVT strategy was an independent predictor of 24-h successful recanalization (OR, 2.7 [95% CI, 1.52-4.88]; p < 0.001). Dual-IVT cohort patients achieved higher rates of excellent outcome (69% vs 44%, p < 0.0001). Propensity score matching analyses supported all these associations. CONCLUSION: In this retrospective study, a dual-IVT strategy in selected MeVO patients was associated with higher odds of 24-h recanalization, with no safety concerns. However, potential center-level confounding and biases seriously limit these findings' interpretation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05809921.

Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: "INSIST" study.

BACKGROUND: People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France. METHODS: We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs. RESULTS: Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47-7.15] versus 1.38 [1.24-1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7-159.0] versus 126.4 [117.2-136.4]; stroke recurrence: 86.7 [66.4-113.4] versus 66.5 [59.2-74.6]; mortality 291.5 [259.1-327.9] versus 144.1 [134.3-154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66-2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378). CONCLUSIONS: The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.

Incidence and predictors of intracranial hemorrhage after intravenous thrombolysis with tenecteplase.

BACKGROUND: Despite its increasing use, there are limited data on the risk of intracranial hemorrhage (ICH) after intravenous thrombolysis with tenecteplase in the setting of acute ischemic stroke. Our aim was to investigate the incidence and predictors of ICH after tenecteplase administration. METHODS: We reviewed data from the prospective ongoing multicenter TETRIS (Tenecteplase Treatment in Ischemic Stroke) registry. Patients with available day-1 imaging were included in this study. Clinical, imaging and biological variables were collected. Follow-up imaging performed 24 h after IVT was locally reviewed by senior neuroradiologists and neurologists. The incidence of parenchymal hematoma (PH) and any ICH were investigated. Potential predictors of PH and any ICH were assessed in multivariable logistic regressions. Subgroup analyses focusing on patients intended for endovascular treatment were performed. RESULTS: PH and any ICH occurred in 126/1321 (incidence rate: 9.5%, 95% CI 8.1-11.2) and 521/1321 (39.4%, 95% CI 36.8-42.1) patients, respectively. Symptomatic ICH was observed in 77/1321 (5.8%; 95% CI 4.7-7.2). PH occurrence was significantly associated with poorer functional outcomes (p < 0.0001) and death (p < 0.0001) after 3 months. Older age (aOR = 1.03; 95% CI 1.01-1.05), male gender (aOR = 2.07; 95% CI 1.28-3.36), a history of hypertension (aOR = 2.08; 95% CI 1.19-3.62), a higher baseline NIHSS (aOR = 1.07; 95% CI 1.03-1.10) and higher admission blood glucose level (aOR = 1.12; 95% CI 1.05-1.19) were independently associated with PH occurrence. Similar associations were observed in the subgroup of patients intended for endovascular treatment. CONCLUSION: We quantified the incidence of ICH after IVT with tenecteplase in a real-life prospective registry and determined independent predictors of ICH. These findings allow to identify patients at high risk of ICH.

Dynamic Evolution of Infarct Volumes at MRI in Ischemic Stroke Due to Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: The typical infarct volume trajectories in stroke patients, categorized as slow or fast progressors, remain largely unknown. This study aimed to reveal the characteristic spatiotemporal evolutions of infarct volumes caused by large vessel occlusion (LVO) and show that such growth charts help anticipate clinical outcomes. METHODS: We conducted a secondary analysis from prospectively collected databases (FRAME, 2017-2019; ETIS, 2015-2022). We selected acute MRI data from anterior LVO stroke patients with witnessed onset, which were divided into training and independent validation datasets. In the training dataset, using Gaussian mixture analysis, we classified the patients into 3 growth groups based on their rate of infarct growth (diffusion volume/time-to-imaging). Subsequently, we extrapolated pseudo-longitudinal models of infarct growth for each group and generated sequential frequency maps to highlight the spatial distribution of infarct growth. We used these charts to attribute a growth group to the independent patients from the validation dataset. We compared their 3-month modified Rankin scale (mRS) with the predicted values based on a multivariable regression model from the training dataset that used growth group as an independent variable. RESULTS: We included 804 patients (median age 73.0 years [interquartile range 61.2-82.0 years]; 409 men). The training dataset revealed nonsupervised clustering into 11% (74/703) slow, 62% (437/703) intermediate, and 27% (192/703) fast progressors. Infarct volume evolutions were best fitted with a linear (r = 0.809; p < 0.001), cubic (r = 0.471; p < 0.001), and power (r = 0.63; p < 0.001) function for the slow, intermediate, and fast progressors, respectively. Notably, the deep nuclei and insular cortex were rapidly affected in the intermediate and fast groups with further cortical involvement in the fast group. The variable growth group significantly predicted the 3-month mRS (multivariate odds ratio 0.51; 95% CI 0.37-0.72, p < 0.0001) in the training dataset, yielding a mean area under the receiver operating characteristic curve of 0.78 (95% CI 0.66-0.88) in the independent validation dataset. DISCUSSION: We revealed spatiotemporal archetype dynamic evolutions following LVO stroke according to 3 growth phenotypes called slow, intermediate, and fast progressors, providing insight into anticipating clinical outcome. We expect this could help in designing neuroprotective trials aiming at modulating infarct growth before EVT.

Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study.

BACKGROUND: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients. METHODS: We conducted an international retrospective study of MeVO cases. A propensity score matching algorithm was used to mitigate potential differences across patients undergoing GA and conscious sedation (CS). Comparisons in clinical and safety outcomes were performed between the two study groups GA and CS. The favourable outcome was defined as a modified Rankin Scale (mRS) 0-2 at 90 days. Safety outcomes were 90-days mortality and symptomatic intracranial hemorrhage (sICH). Predictors of a favourable outcome and sICH were evaluated with backward logistic regression. RESULTS: After propensity score matching 668 patients were included in the CS and 264 patients in the GA group. In the matched cohort, either strategy CS or GA resulted in similar rates of good functional outcomes (50.1% vs. 48.4%), and successful recanalization (89.4% vs. 90.2%). The GA group had higher rates of 90-day mortality (22.6% vs. 16.5%, p < 0.041) and sICH (4.2% vs. 0.9%, p = 0.001) compared to the CS group. Backward logistic regression did not identify GA vs CS as a predictor of good functional outcome (OR for GA vs CS = 0.95 (0.67-1.35)), but GA remained a significant predictor of sICH (OR = 5.32, 95% CI 1.92-14.72). CONCLUSION: Anaesthetic strategy in MeVOs does not influence favorable outcomes or final successful recanalization rates, however, GA may be associated with an increased risk of sICH and mortality.

Comparison of rescue intracranial stenting versus best medical treatment alone in acute refractory large vessel occlusion: study protocol for the PISTAR multicenter randomized trial.

BACKGROUND: Mechanical thrombectomy (MT) has become a standard treatment for acute ischemic strokes (AIS). However, MT failure occurs in approximately 10-30% of cases, leading to severe repercussions (with mortality rates up to 40% according to observational data). Among the available rescue techniques, rescue intracranial stenting (RIS) appears as a promising option. OBJECTIVE: This trial is poised to demonstrate the superiority of RIS in addition to the best medical treatment (BMT) in comparison with BMT alone, in improving the functional outcomes at 3 months for patients experiencing an AIS due to a large vessel occlusion refractory to MT (rLVO). METHODS: Permanent Intracranial STenting for Acute Refractory large vessel occlusions (PISTAR) is a multicenter prospective randomized open, blinded endpoint trial conducted across 11 French University hospitals. Adult patients (≥18 years) with an acute intracranial occlusion refractory to standard MT techniques will be randomized 1:1 during the procedure to receive either RIS+BMT (intervention arm) or BMT alone (control arm). RESULTS: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin Scale score ≤2 and evaluated by an independent assessor blinded to the randomization arm. Secondary outcomes include hemorrhagic complications, all adverse events, and death. The number of patients to be included is 346. Two interim analyses are planned with predefined stopping rules. CONCLUSION: The PISTAR trial is the first randomized controlled trial focusing on the benefit of RIS in rLVOs. If positive, this study will open new insights into the management of AIS. TRIAL REGISTRATION NUMBER: NCT06071091.

Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study.

BACKGROUND: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. METHODS: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. RESULTS: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). CONCLUSION: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

Use of the pRESET LITE thrombectomy device in combined approach for medium vessel occlusions: A multicenter evaluation.

PURPOSE: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO. METHODS: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes. RESULTS: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2). CONCLUSION: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.

Impact of Day 1 carotid patency on outcome in dissection-related tandem occlusions treated with mechanical thrombectomy.

BACKGROUND: The clinical benefit of mechanical thrombectomy(MT) for stroke patients with tandem occlusion is similar to that of isolated intracranial occlusions. However, the management of cervical internal carotid artery(ICA) occlusion during the MT, particularly in the setting of carotid dissection, remains controversial. We aimed to investigate the clinical impact of cervical ICA patency at day 1 on 3-month functional outcome. METHODS: We collected data from the Endovascular Treatment in Ischemic Stroke, a prospective national registry in 30 French centers performing MT between January 2015 and January 2022. Inclusion criteria were consecutive tandem occlusions related to cervical ICA dissection treated with MT. Tandem occlusions of other etiology, isolated cervical ICA occlusions without intracranial thrombus and patients without day-1 ICA imaging were excluded. Primary endpoint was the 3-month functional outcome. Secondary endpoints included intracranial hemorrhage(ICH), excellent outcome, mortality and early neurological improvement. A sensitivity analysis was performed in patients with intracranial favorable recanalization after MT. RESULTS: During the study period, 137 patients were included of which 89(65%) presented ICA patency at day 1. The odds of favorable outcome did not significantly differ between patients with patent and occluded ICA at day 1(68.7 vs 59.1%;aOR=1.30;95%CI 0.56-3.00,p=0.54). Excellent outcome, early neurological improvement, mortality and ICH were also comparable between groups. Sensitivity analysis showed similar results. CONCLUSION: ICA patency at day 1 in patients with tandem occlusions related to dissection did not seem to influence functional outcome. Endovascular recanalization of the cervical ICA including stenting might not be systematically required in this setting.

Endovascular therapy of acute vertebrobasilar occlusions: influence of first-line strategy in the Endovascular Treatment in Ischemic Stroke (ETIS) Registry.

BACKGROUND: The choice of the first-line technique in vertebrobasilar occlusions (VBOs) remains challenging. We aimed to report outcomes in a large cohort of patients and to compare the efficacy and safety of contact aspiration (CA) and combined technique (CoT) as a first-line endovascular technique in patients with acute VBOs. METHODS: We retrospectively analyzed clinical and neuroradiological data of patients with VBOs from the prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France between January 2015 and August 2023. The primary outcome was the first pass effect (FPE) rate, whereas modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3 and 2c-3, number of passes, need for rescue strategy, modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage (sICH) were secondary outcomes. We performed univariate and multivariate analyses to investigate differences between the two groups. RESULTS: Among the 583 included patients (mean age 66.2 years, median National Institutes of Health Stroke Scale (NIHSS) 13, median posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) 8), 393 were treated with CA alone and 190 with CoT. Procedures performed with CA were shorter compared with CoT (28 vs 47 min, P<0.0001); however, no differences were observed in terms of FPE (CA 43.3% vs CoT 38.4%, P=0.99), and successful final recanalization (mTICI 2b-3, CA 92.4% vs CoT 91.8%, P=0.74) did not differ between the two groups. Functional independence and sICH rates were also similar, whereas mortality was significantly lower in the CA group (34.5% vs 42.9%; OR 1.79, 95% CI 1.03 to 3.11). CONCLUSIONS: We observed no differences in FPE, mTICI 2b-3, sICH, and functional independence between the two study groups. First-line CA was associated with shorter procedures and lower mortality rates than CoT.

Social and clinical vulnerability in stroke and STEMI management during the COVID-19 pandemic: a registry-based study.

OBJECTIVE: This study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment elevation myocardial infarction (STEMI) patients. DESIGN: Two cohorts of STEMI and stroke patients in the Aquitaine neurocardiovascular registry. SETTING: Six emergency medical services, 30 emergency units, 14 hospitalisation units and 11 catheterisation laboratories in the Aquitaine region in France. PARTICIPANTS: This study involved 9218 patients (6436 stroke and 2782 STEMI patients) in the neurocardiovascular registry from January 2019 to August 2020. PRIMARY OUTCOME MEASURES: Care management times in both cohorts: first medical contact-to-procedure time for the STEMI cohort and emergency unit admission-to-imaging time for the stroke cohort. Associations between social (deprivation index) and clinical (age >65 years, neurocardiovascular history) vulnerabilities and care management times were analysed using multivariate linear mixed models, with an interaction on the time period (pre-wave, per-wave and post-first COVID-19 wave). RESULTS: The first medical contact procedure time was longer for elderly (p<0.001) and 'very socially disadvantaged' (p=0.003) STEMI patients, with no interaction regarding the COVID-19 period (age, p=0.54; neurocardiovascular history, p=0.70; deprivation, p=0.64). We found no significant association between vulnerabilities and the admission imaging time for stroke patients, and no interaction with respect to the COVID-19 period (age, p=0.81; neurocardiovascular history, p=0.34; deprivation, p=0.95). CONCLUSIONS: This study revealed pre-existing inequalities in care management times for vulnerable STEMI and stroke patients; however, these inequalities were neither accentuated nor reduced during the first COVID-19 wave. Measures implemented during the crisis did not alter the structured emergency pathway for these patients. TRIAL REGISTRATION NUMBER: NCT04979208.

Evaluation of acute mechanical revascularization in large stroke (ASPECTS ⩽5) and large vessel occlusion within 7 h of last-seen-well: The LASTE multicenter, randomized, clinical trial protocol.

RATIONALE: Mechanical thrombectomy (MT), the standard of care for acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO), is generally not offered to patients with large baseline infarct (core). Recent studies demonstrated MT benefit in patients with anterior circulation stroke and large core (i.e. Alberta Stroke Program Early Computed Tomography Score, ASPECTS 3-5). However, its benefit in patients with the largest core (ASPECTS 0-2) remains unproven. AIM: To compare the efficacy and safety of MT plus best medical treatment (BMT) and of BMT alone in patients with ASPECTS 0-5 (baseline computed tomography (CT) or magnetic resonance imaging (MRI)) and anterior circulation LVO within 7 h of last-seen-well. SAMPLE SIZE ESTIMATE: To detect with a two-sided test at 5% significance level (80% power) a common odds ratio of 1.65 for 1-point reduction in the 90-day modified Rankin Scale (mRS) score in the MT + BMT arm versus BMT arm and to anticipate 10% of patients with missing primary endpoint, 450 patients are planned to be included by 36 centers in France, Spain, and the United States. METHODS AND DESIGN: LArge Stroke Therapy Evaluation (LASTE) is an international, multicenter, Prospectively Randomized into two parallel (1:1) arms, Open-label, with Blinded Endpoint (PROBE design) trial. Eligibility criteria are diagnosis of AIS within 6.5 h of last-seen-well (or negative fluid-attenuated inversion recovery (FLAIR) if unknown stroke onset time), ASPECTS 0-5 (ASPECTS 4-5 for ⩾80-year-old patients), and LVO in the anterior circulation (intracranial internal carotid artery (ICA) and M1 or M1-M2 segment of the middle cerebral artery (MCA)). STUDY OUTCOMES: The primary endpoint is the day-90 mRS score distribution (shift analysis) with mRS categories 5 and 6 coalesced into one category. Secondary endpoints include day-180 mRS score, rates of 90-day and 180-day mRS score = 0-2 and 0-3, rate of decompressive craniectomy, the National Institutes of Health Stroke Scale (NIHSS) score change, revascularization and infarct volume growth at 24 h, and quality of life at day 90 and 180. Safety outcomes (90-day all-cause mortality, procedural complications, symptomatic intracerebral hemorrhage, and early NIHSS score worsening) are recorded. A dynamic balanced randomization (1:1) is used to distribute eligible patients into the experimental arm and control arm, by incorporating the center and these pre-specified factors: baseline ASPECTS (0-3 vs 4-5), age (⩽70 vs >70 years), baseline NIHSS (<20 vs ⩾20), intravenous thrombolysis (no vs yes), admission mode (Drip-and-Ship vs Mothership), occlusion site (intracranial ICA vs MCA-M1 or M1-M2), intravenous fibrinolysis (no vs yes), and last-seen-well to randomization time (0-4.5 vs >4.5-6.5 h). DISCUSSION: The LASTE trial will determine MT efficacy and safety in patients with ASPECTS 0-5 and LVO in the anterior circulation. TRIAL REGISTRATION: LASTE Trial NCT03811769.

First pass effect as an independent predictor of functional outcomes in medium vessel occlusions: An analysis of an international multicenter study.

INTRODUCTION: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce. PATIENTS AND METHODS: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months. RESULTS: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively. CONCLUSION: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Indications for surgical evacuation of cerebellar intracerebral hemorrhage: consensus guidelines from the French Society of Neurosurgery (SFNC) and the French Society of Vascular Neurology (SFNV).

BACKGROUND: Cerebellar intracerebral hemorrhage (ICH) is associated with poor functional prognosis and high mortality. Surgical evacuation has been proposed to improve outcome. The purpose of this review was to determine the benefit of surgical evacuation of cerebellar ICH and to establish guidelines for when it should be performed. METHOD: The writing committee comprised 9 members of the SFNV and the SFNC. Recommendations were established based on a literature review using the PICO questions. The American Heart Association (AHA) classification was used to define recommendation level. In case of insufficient evidence, expert opinions were provided. RESULTS: Levels of evidence were low to moderate, precluding definitive recommendations. Based on available data, surgical hematoma evacuation is not recommended to improve functional outcome (Class III; Level B NR). However, based on subgroup analysis, surgical evacuation may be considered in strictly selected patients (Class IIb; Level C-EO): hematoma volume 15-25 cm3, GCS 6-10, and no oral anticoagulation or antiplatelet therapy. Moreover, surgical evacuation is recommended to decrease risk of death (Class IIa; Level B NR) in patients with a hematoma volume >15 cm3 and GCS score <10. CONCLUSION: These guidelines were based on observational studies, limiting the level of evidence. However, except for strictly selected patients, surgical evacuation of cerebellar ICH was not associated with improved functional outcome, limiting indications. Data from RCTs are needed in this field.

Intravenous thrombolysis with tenecteplase versus alteplase combined with endovascular treatment of anterior circulation tandem occlusions: A pooled analysis of ETIS and TETRIS.

BACKGROUND: Tandem occlusions are a singular large vessel occlusion entity involving specific endovascular and perioperative antithrombotic management. In this context, data on safety and efficacy of prior intravenous thrombolysis (IVT) with tenecteplase is scarce. We aimed to compare IVT with tenecteplase or alteplase in patients with acute tandem occlusions intended for endovascular treatment. PATIENTS AND METHODS: A retrospective pooled analysis of two large observational registries (ETIS (Endovascular Treatment of Ischemic Stroke) and TETRIS (Tenecteplase Treatment in Ischemic Stroke)) was performed on consecutive patients presenting with anterior circulation tandem occlusion treated with IVT using either alteplase (ETIS) or tenecteplase (TETRIS) followed by endovascular treatment between January 2015 and June 2022. Sensitivity analyses on atherosclerosis related tandem occlusions and on patient treated with emergent carotid stenting were conducted. Propensity score overlap weighting analyses were performed. RESULTS: We analyzed 753 patients: 124 in the tenecteplase and 629 in the alteplase group. The overall odds of favorable outcome (3-month modified Rankin score 0-2) were comparable between both groups (49.4% vs 47.1%; OR = 1.10, 95%CI 0.85-1.41). Early recanalization, final successful recanalization and mortality favored the use of tenecteplase. The occurrence of any intracranial hemorrhage (ICH) was more frequent after tenecteplase use (OR = 2.24; 95%CI 1.75-2.86). However, risks of symptomatic ICH and parenchymal hematoma remained similar. In atherosclerotic tandems, favorable outcome, mortality, parenchymal hematoma, early recanalization, and final successful recanalization favored the tenecteplase group. In the carotid stenting subgroup, PH were less frequent in the tenecteplase group (OR = 0.18; 95%CI 0.05-0.69). CONCLUSION: In patients with tandem occlusions, IVT with tenecteplase seemed reasonably safe in particular with increased early recanalization rates. These findings remain preliminary and should be further confirmed in randomized trials.

Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial.

RATIONALE: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions. AIM: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion. METHODS: The DISCOUNT trial is a multicenter open-label randomized controlled trial involving French University hospitals. Adult patients (⩾18 years) with an AIS involving the anterior or posterior circulation secondary to a distal vessel occlusion within 6 h of symptom onset or within 24 h if no hyperintense signal on fluid attenuation inversion recovery acquisition will be randomized 1:1 to receive either MT associated with the BMT (experimental group) or BMT alone (control group). The number of patients to be included is 488. STUDY OUTCOMES: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin scale (mRS) ⩽2 and evaluated by an independent assessor blinded to the intervention arm. Secondary outcomes include recanalization of the occluded vessel within 48 h, angiographic reperfusion in the experimental group, 3-month excellent clinical outcome (mRS ⩽ 1), all adverse events, and death. A cost utility analysis will estimate the incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION: If positive, this study will open new insights in the management of AISs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05030142 registered on 1 September 2021.

Intravenous Thrombolysis before Complete Angiographic Reperfusion: Beyond Angiographic Assessment to Target Microvascular Obstruction?

OBJECTIVE: Recent data have suggested that ineffective tissue reperfusion despite successful angiographic reperfusion was partly responsible for unfavorable outcomes after endovascular therapy (EVT) and might be modulated by intravenous thrombolysis (IVT) use before EVT. To specifically decipher the effect played by IVT before EVT, we compared the clinical and safety outcomes of patients who experienced a complete reperfusion at the end of EVT according to IVT use before EVT. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, observational study at 21 centers that perform EVT in France. Patients were included if they had an anterior large vessel occlusion of the intracranial internal carotid artery or middle cerebral artery (M1/M2 segments) and complete reperfusion (expanded Thrombolysis in Cerebral Infarction score = 3) with EVT within 6 hours, between January 2015 and December 2021. The cohort was divided into two groups according to IVT use before EVT, and propensity score matching (PSM) was used to balance the two groups. Primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included favorable outcome (mRS 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Outcomes were estimated with multivariate logistic models adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and time from symptom onset to puncture. RESULTS: Among 5,429 patients included in the ETIS registry, 1,093 were included in the study, including 651 patients with complete recanalization treated with IVT before EVT. After PSM, 488 patients treated with IVT before EVT were compared to 337 patients without IVT. In the matched cohort analysis, the IVT+EVT group had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR] = 1.41, 95% confidence interval [CI] = 1.04-1.91, p = 0.023) and higher rates of favorable outcome (61.1% vs 48.7%, aOR = 1.49, 95% CI = 1.02-2.20, p = 0.041) at 90 days compared with the EVT alone group. Rates of symptomatic intracerebral hemorrhage were comparable between both groups (6.0% vs 4.3%, aOR = 1.16, 95% CI = 0.53-2.54, p = 0.709). INTERPRETATION: In clinical practice, even after complete angiographic reperfusion by EVT, prior IVT use improves clinical outcomes of patients without increasing bleeding risk. ANN NEUROL 2024;95:762-773.

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: The optimal methods for predicting early infarct growth rate (EIGR) in acute ischemic stroke with a large vessel occlusion (LVO) have not been established. We aimed to study the factors associated with EIGR, with a focus on the collateral circulation as assessed by the hypoperfusion intensity ratio (HIR) on perfusion imaging, and determine whether the associations found are consistent across imaging modalities. METHODS: Retrospective multicenter international study including patients with anterior circulation LVO-related acute stroke with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24 hours from symptom onset. To avoid selection bias, patients were selected from (1) the prospective registries of 4 comprehensive stroke centers with systematic use of perfusion imaging and including both thrombectomy-treated and untreated patients and (2) 1 prospective thrombectomy study where perfusion imaging was acquired per protocol, but treatment decisions were made blinded to the results. EIGR was defined as infarct volume on baseline imaging divided by onset-to-imaging time and fast progressors as EIGR ≥10 mL/h. The HIR, defined as the proportion of time-to-maximum (Tmax) >6 second with Tmax >10 second volume, was measured on perfusion imaging using RAPID software. The factors independently associated with fast progression were studied using multivariable logistic regression models, with separate analyses for CT- and MRI-assessed patients. RESULTS: Overall, 1,127 patients were included (CT, n = 471; MRI, n = 656). Median age was 74 years (interquartile range [IQR] 62-83), 52% were male, median NIH Stroke Scale was 16 (IQR 9-21), median HIR was 0.42 (IQR 0.26-0.58), and 415 (37%) were fast progressors. The HIR was the primary factor associated with fast progression, with very similar results across imaging modalities: The proportion of fast progressors was 4% in the first HIR quartile (i.e., excellent collaterals), ∼15% in the second, ∼50% in the third, and ∼77% in the fourth (p < 0.001 for each imaging modality). Fast progression was independently associated with poor 3-month functional outcome in both the CT and MRI cohorts (p < 0.001 and p = 0.030, respectively). DISCUSSION: The HIR is the primary factor associated with fast infarct progression, regardless of imaging modality. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers.

ASPECTS evolution after endovascular successful reperfusion in the early and extended time window.

BACKGROUND: The Alberta Stroke Program Early CT scan Score (ASPECTS) is a reliable imaging biomarker of infarct extent on admission but the value of 24-hour ASPECTS evolution in day-to-day practice is not well studied, especially after successful reperfusion. We aimed to assess the association between ASPECTS evolution after successful reperfusion with functional and safety outcomes, as well as to identify the predictors of ASPECTS evolution. METHODS: We used data from an ongoing prospective multicenter registry. Stroke patients with anterior circulation large vessel occlusion treated with endovascular therapy (EVT) and achieved successful reperfusion (modified thrombolysis in cerebral ischemia (mTICI) 2b-3) were included. ASPECTS evolution was defined as one or more point decrease in ASPECTS at 24 hours. RESULTS: A total of 2366 patients were enrolled. In a fully adjusted model, ASPECTS evolution was associated with lower odds of favorable outcome (modified Rankin Scale (mRS) score 0-2) at 90 days (adjusted odds ratio (aOR) = 0.46; 95% confidence interval (CI) = 0.37-0.57). In addition, ASPECTS evolution was a predictor of excellent outcome (90-day mRS 0-1) (aOR = 0.52; 95% CI = 0.49-0.57), early neurological improvement (aOR = 0.42; 95% CI = 0.35-0.51), and parenchymal hemorrhage (aOR = 2.64; 95% CI, 2.03-3.44). Stroke severity, admission ASPECTS, total number of passes, complete reperfusion (mTICI 3 vs. mTICI 2b-2c) and good collaterals emerged as predictors of ASPECTS evolution. CONCLUSION: ASPECTS evolution is a strong predictor of functional and safety outcomes after successful endovascular therapy. Higher number of EVT attempts and incomplete reperfusion are associated with ASPECTS evolution at day 1.