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.).

Arterial Recanalization During Interhospital Transfer for Thrombectomy.

BACKGROUND: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes. METHODS: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis. RESULTS: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; Ptrend<0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; Ptrend<0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization. CONCLUSIONS: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes.

Combined Technique for Internal Carotid Artery Terminus or Middle Cerebral Artery Occlusions in the ASTER2 Trial.

BACKGROUND: The aim of this study was to report the results of a subgroup analysis of the ASTER2 trial (Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion) comparing the safety and efficacy of the combined technique (CoT) and stent retriever as a first-line approach in internal carotid artery (ICA) terminus±M1-middle cerebral artery (M1-MCA) and isolated M1-MCA occlusions. METHODS: Patients enrolled in the ASTER2 trial with ICA terminus±M1-MCA and isolated M1-MCA occlusions were included in this subgroup analysis. The effect of first-line CoT versus stent retriever according to the occlusion site was assessed on angiographic (first-pass effect, expanded Treatment in Cerebral Infarction score ≥2b50, and expanded Treatment in Cerebral Infarction score ≥2c grades at the end of the first-line strategy and at the end of the procedure) and clinicoradiological outcomes (24-hour National Institutes of Health Stroke Scale, ECASS-III [European Cooperative Acute Stroke Study] grades, and 3-month modified Rankin Scale). RESULTS: Three hundred sixty-two patients were included in the postsubgroup analysis according to the occlusion site: 299 were treated for isolated M1-MCA occlusion (150 with first-line CoT) and 63 were treated for ICA terminus±M1-MCA occlusion (30 with first-line CoT). Expanded Treatment in Cerebral Infarction score ≥2b50 (odds ratio, 11.83 [95% CI, 2.32-60.12]) and expanded Treatment in Cerebral Infarction score ≥2c (odds ratio, 4.09 [95% CI, 1.39-11.94]) were significantly higher in first-line CoT compared with first-line stent retriever in patients with ICA terminus±M1-MCA occlusion but not in patients with isolated M1-MCA. CONCLUSIONS: First-line CoT was associated with higher reperfusion grades in patients with ICA terminus±M1-MCA at the end of the procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03290885.

A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke.

BACKGROUND: The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. METHODS: We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. RESULTS: The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P = 0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). CONCLUSIONS: In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, ISRCTN80619088.).

Determinants of Infarct Core Growth During Inter-hospital Transfer for Thrombectomy.

OBJECTIVE: Patients with acute ischemic stroke harboring a large vessel occlusion who present to primary stroke centers often require inter-hospital transfer for thrombectomy. We aimed to determine clinical and imaging factors independently associated with fast infarct growth (IG) during inter-hospital transfer. METHODS: We retrospectively analyzed data from acute stroke patients with a large vessel occlusion transferred for thrombectomy from a primary stroke center to one of three French comprehensive stroke centers, with an MRI obtained at both the primary and comprehensive center before thrombectomy. Inter-hospital IG rate was defined as the difference in infarct volumes on diffusion-weighted imaging between the primary and comprehensive center, divided by the delay between the two MRI scans. The primary outcome was identification of fast progressors, defined as IG rate ≥5 mL/hour. The hypoperfusion intensity ratio (HIR), a surrogate marker of collateral blood flow, was automatically measured on perfusion imaging. RESULTS: A total of 233 patients were included, of whom 27% patients were fast progressors. The percentage of fast progressors was 3% among patients with HIR < 0.40 and 71% among those with HIR ≥ 0.40. In multivariable analysis, fast progression was independently associated with HIR, intracranial carotid artery occlusion, and exclusively deep infarct location at the primary center (C-statistic = 0.95; 95% confidence interval [CI], 0.93-0.98). IG rate was independently associated with good functional outcome (adjusted OR = 0.91; 95% CI, 0.83-0.99; P = 0.037). INTERPRETATION: Our findings show that a HIR > 0.40 is a powerful indicator of fast inter-hospital IG. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers. ANN NEUROL 2023;93:1117-1129.

Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study.

BACKGROUND: The efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO. METHODS: In this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts. RESULTS: Among 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0-2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15). CONCLUSION: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.

Value of intravenous alteplase before thrombectomy among patients with tandem lesions and emergent carotid artery stenting: A subgroup analysis of the SWIFT DIRECT trial.

BACKGROUND AND PURPOSE: The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting. METHODS: SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes. RESULTS: Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage  among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05). CONCLUSIONS: No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.

Infarct Core Growth During Interhospital Transfer For Thrombectomy Is Faster At Night.

BACKGROUND: Preclinical stroke models have recently reported faster infarct growth (IG) when ischemia was induced during daytime. Considering the inverse rest-activity cycles of rodents and humans, faster IG during the nighttime has been hypothesized in humans. METHODS: We retrospectively evaluated acute ischemic stroke patients with a large vessel occlusion transferred from a primary to 1 of 3 French comprehensive stroke center, with magnetic resonance imaging obtained at both centers before thrombectomy. Interhospital IG rate was calculated as the difference in infarct volumes on the 2 diffusion-weighted imaging, divided by the time elapsed between the 2 magnetic resonance imaging. IG rate was compared between patients transferred during daytime (7:00-22:59) and nighttime (23:00-06:59) in multivariable analysis adjusting for occlusion site, National Institutes of Health Stroke Scale score, infarct topography, and collateral status. RESULTS: Out of the 329 patients screened, 225 patients were included. Interhospital transfer occurred during nighttime in 31 (14%) patients and daytime in 194 (86%). Median interhospital IG was faster when occurring at night (4.3 mL/h; interquartile range, 1.2-9.5) as compared to the day (1.4 mL/h; interquartile range, 0.4-3.5; P<0.001). In multivariable analysis, nighttime transfer remained independently associated with IG rate (P<0.05). CONCLUSIONS: Interhospital IG appeared faster in patients transferred at night. This has potential implications for the design of neuroprotection trials and acute stroke workflow.

Endovascular Therapy or Medical Management Alone for Isolated Posterior Cerebral Artery Occlusion: A Multicenter Study.

BACKGROUND: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown. METHODS: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0-2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage, and early neurological deterioration. RESULTS: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63-82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4-10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66-1.01]; P=0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95-1.43]; P=0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35-4.67]; P=0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64-3.84]; P<0.0001). CONCLUSIONS: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis.

BACKGROUND: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. METHODS: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. FINDINGS: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). INTERPRETATION: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. FUNDING: Stryker Neurovascular.

Endovascular Thrombectomy Outcomes with and without Intravenous Thrombolysis for Large Ischemic Cores Identified with CT or MRI.

Background Whether intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) provides additional benefits in patients with acute ischemic stroke (AIS) and a large infarct core (LIC) remains unclear. Purpose To examine whether treatment with IVT before EVT is beneficial in patients with LIC identified with CT or MRI (Alberta Stroke Program Early CT score 0-5). Materials and Methods This retrospective study included consecutive adult patients diagnosed with AIS due to large vessel occlusion (LVO) and LIC treated with EVT who were enrolled in the ETIS (Endovascular Treatment in Ischemic Stroke) Registry in France between January 2015 and January 2022. The primary outcome measure was a favorable outcome (modified Rankin Scale [mRS] score 0-3) at 90 days. Secondary outcomes included functional independence (mRS score 0-2) at 90 days, improvement in degree of disability (ordinal shift in mRS score toward a better outcome) at 90 days, early neurologic improvement at 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b or higher). Safety outcomes included symptomatic intracerebral hemorrhage within 24 hours and mortality at 90 days. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to assess the treatment effect of IVT adjusted for baseline variables. Results Of 1408 patients (mean age, 68.3 years ± 15.4 [SD]; 789 men), 654 (46.4%) were treated with IVT prior to EVT. In the IPTW-adjusted data set, IVT plus EVT was associated with a higher rate of favorable outcome at 90 days (odds ratio [OR], 1.24 [95% CI: 1.05, 1.46]; P = .01), functional independence at 90 days (OR, 1.47 [95% CI: 1.22, 1.77]; P < .001), improvement in degree of disability at 90 days (common OR, 1.30 [95% CI: 1.13, 1.49]; P < .001), early neurologic improvement (OR, 1.26 [95% CI: 1.07, 1.49]; P = .005), and successful reperfusion (OR, 1.43 [95% CI: 1.14, 1.79]; P = .002) than EVT alone. Rates of brain hemorrhage within 24 hours and mortality at 90 days were similar between groups. Conclusion In patients with AIS due to LVO with LIC identified with CT or MRI, treatment with IVT before EVT appeared to provide a clinical benefit over EVT alone. Clinical trial registration no. NCT03776877 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kallmes and Rabinstein in this issue.

Negative susceptibility vessel sign might be predictive of complete reperfusion in patients with acute basilar artery occlusion managed with thrombectomy.

OBJECTIVES: Negative susceptibility vessel sign (SVS) on pre-thrombectomy MRI has been linked to fibrin-rich thrombus and difficult retrieval in anterior ischemic stroke. However, its impact in posterior circulation-large vessel occlusion stroke (PC-LVOS) has not yet been elucidated. We aim to investigate the relationship of SVS parameters with stroke subtypes and their influence on angiographic and functional outcomes. METHODS: Prospective thrombectomy registries at two-comprehensive stroke centers were retrospectively reviewed between January 2015 and December 2019 for consecutive MRI-selected patients with PC-LVOS. Two groups were assigned by two independent readers, based on the presence or absence of the SVS (SVS +, SVS -) on MRI-GRE sequence. Multivariate logistic regression analysis was utilized to study primarily the impact of the SVS on the rate of complete recanalization (defined as mTICI 2c/3) at the final series following endovascular thrombectomy (EVT) and whether or not it might influence the efficacy of the frontline EVT strategy. Secondarily, we studied whether the absence of the SVS was predictive of the rate of 90-day functional independence (defined as mRS score < 2). Lastly, both qualitative (SVS +, SVS-) and quantitative (SVS length and diameter) parameters of the SVS were analyzed in association with the puncture to recanalization interval and various stroke etiological subtypes based on TOAST criteria. RESULTS: Among 1823 patients, 116 were qualified for final analysis (median age, 68 (59-75) years; male, 65%); SVS was detected in 62.9% (73/116) of cases. SVS length was an independent predictor of procedural duration (p = .01) whilst two-layered SVS was inversely associated with the atherosclerosis etiological subtype (aOR = 0.27, 95% CI 0.08-0.89; p = .03). Successful recanalization was achieved in 82% (60/73) vs. 86% (37/43), p = .80 of patients with SVS (+, -) respectively. Only in SVS (+), stentriever (RR 0.59 (0.4-0.88), p = .009), and contact-aspiration (RR 0.82 (0.7-0.96), p = .01) achieved a lower rate of successful recanalization compared to combined technique. SVS (-) was significantly associated with a higher rate of mTICI 2c/3 (aOR = 4.444; 95% CI 1.466-13.473; p = .008) and showed an indirect effect of 9% towards functional independence mediated by mTICI 2c/3. CONCLUSION: SVS parameters in PC-LVOS might predict stroke subtype and indirectly influence the functional outcome by virtue of complete recanalization. KEY POINTS: • Negative susceptibility vessel sign (SVS) in patients with basilar occlusion independently predict complete recanalization that indirectly instigated a 3-month favorable outcome following thrombectomy. • The longer the SVS, the higher likelihood of large artery atherosclerosis and the longer the thrombectomy procedure. • Two-layered SVS might be negatively associated with the presence of atherosclerosis, yet already-known limitations of TOAST classification and the absence of pathological analysis should be taken into consideration.

Endovascular Treatment for Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of acute ischemic stroke worldwide. Patients with acute large vessel occlusion due to underlying ICAD (ICAD-LVO) often do not achieve successful recanalization when undergoing mechanical thrombectomy (MT) alone, requiring rescue treatment, including intra-arterial thrombolysis, balloon angioplasty, and stenting. Therefore, early detection of ICAD-LVO before the procedure is important to enable physicians to select the optimal treatment strategy for ICAD-LVO to improve clinical outcomes. Early diagnosis of ICAD-LVO is challenging in the absence of consensus diagnostic criteria on noninvasive imaging and early digital subtraction angiography. In this review, we summarize the clinical and diagnostic criteria, prediction of ICAD-LVO prior to the procedure, and EVT strategy of ICAD-LVO and provide recommendations according to the current literature.

Angioplasty, stenting, or both - rescue maneuvers and reperfusion after endovascular therapy for intracranial atherosclerosis-related occlusion.

PURPOSE: Data concerning reperfusion strategies of intracranial atherosclerosis-related occlusion (ICARO) and clinico-angiographic outcomes remain scarce, particularly in Caucasians. We aim to compare the reperfusion rate and functional outcome between reperfusion strategies in the setting of the ICARO. METHODS: Retrospective analysis of prospectively maintained endovascular thrombectomy (EVT) registries at three high-volume stroke centers were retrospectively analyzed for consecutive ICARO patients from January 2015 to December 2019. We defined ICARO as any fixed high-degree (> 70%) focal narrowing or stenosis of any degree with a perpetual tendency for reocclusion. We categorized reperfusion strategies into four groups: EVT [group 1], balloon angioplasty [(BAp), group 2], placement of self-expandable stents [(SES), group 3], and BAp combined with implantation of SES; or direct placement of balloon mounted stents (BMS) [(BAp-SES/BMS), group 4]. We evaluated the association with the successful reperfusion [mTICI 2b - 3] and favorable outcome [mRS 0-2] with logistic regression analysis. RESULTS: Out of 2550 EVT, 124 patients (median age, 70 (61-80) years; 76 men) with ICARO and 130 reperfusion attempts [36 EVT, 38 BAp, 17 SES, and 39 BAp + SES/BMS] were analyzed. SES implantation showed the highest frequency of post-procedural symptomatic intracranial hemorrhage [(18%, 3/17), p = .03]; however, we observed no significant differences in the mortality rate. Overall, we achieved successful reperfusion in 71% (92/130) and favorable outcomes in 42% (52/124) of the patients. BAp + SES/BMS was the only independent predictor of the final successful reperfusion [aOR, 4.488 (95% CI, 1.364-14.773); p = .01], which was significantly associated with the 90-day favorable outcome [aOR, 10.837 (95% CI, 3.609-32.541); p = < .001] after adjustment for confounding variables between the reperfusion strategies. CONCLUSION: Among patients with ICARO, the rescue angioplasty stenting effectively contributed to higher odds of successful reperfusion with no increased risk for intracranial hemorrhage.

Anterior cerebral artery dilation to increase cerebral perfusion in a patient with chronic internal carotid artery occlusion.

Chronic internal carotid artery occlusions (CICAO) increase the risk of stroke recurrence and cognitive dysfunction. Here, we describe the case of an adult patient with ipsilateral CICAO who underwent endovascular treatment of anterior cerebral artery stenosis to improve cerebral perfusion. First, the patient presented ataxia and left facial palsy. Magnetic resonance imaging (MRI) showed right hemispherpe cerebral infarct, right CICAO, and sub-occlusive stenosis of the left bulbar internal carotid artery. Stenting of the left carotid artery was performed. One year later, she experienced acute walking imbalance and left hemiparesis. MRI showed new watershed and anterior cerebral artery infarctions, worsening of the right hemisphere hypoperfusion, and a new severe stenosis of the right anterior cerebral artery. Dilation of this stenosis was performed. Perfusion parameters, clinical deficit, and cognitive functions improved after the endovascular treatment, and the patient had no stroke recurrence.

Ticagrelor versus clopidogrel dual antiplatelet therapy for unruptured intracranial aneurysms treated with flowdiverter.

BACKGROUND AND PURPOSE: Antiplatelet therapy (APT) is a key element limiting the risk of thromboembolic events (TEE) in neuroendovascular procedures, including aneurysm treatment with flowdiverter. Clopidogrel combined with aspirin is the mostly reported dual APT (DAPT). However, resistance phenomenon and intraindividual efficacy fluctuation are identified limitations. In recent years, ticagrelor has been increasingly used in this indication. We compared these two DAPT regimens for intracranial aneurysm treated with flowdiverter. METHODS: We conducted a multicentric retrospective study from prospectively maintained databases in two high volume centers extracting consecutive patients presenting unruptured intracranial aneurysm treated with flowdiverter and receiving DAPT (May 2015 to December 2019).  Two groups were compared according to their DAPT regimen: "ticagrelor+aspirin" and "clopidogrel+aspirin". Clopidogrel group was systematically checked with platelet test inhibition before endovascular procedure. The primary endpoint was composite, defined as any thrombo-embolic event (TEE) or major hemorrhagic event occurring the first 6 months during and after embolization RESULTS: 260 patients met our inclusion criteria. Baseline patients and aneurysms characteristics were comparable between groups, except for aneurysm location, median size and pre-treatment modified Rankin scale. No significant difference was observed regarding the primary composite outcome: 11.5% (12/104) in the ticagrelor group versus 10.9% (17/156) in the clopidogrel group (p = 1.000). There was also no significant difference in secondary outcomes including TEE (10.5 vs 9.0%; p = 0.673), major hemorrhage (0.9 vs 1.2%; p = 0.651) and clinical outcome (at least 1-point mRS worsening during follow up: 6.7% vs 8.3%; p = 0.813). CONCLUSION: First-line DAPT with ticagrelor+aspirin seems as safe and effective as clopidogrel+aspirin regimen.

Complete recanalization predicts favorable outcome in patients with distal M2-M3 middle cerebral artery occlusions following endovascular thrombectomy.

BACKGROUND: - scanty articles illustrate the prognostic factors for favorable outcome after endovascular thrombectomy (EVT) in distal vessel occlusion (DMVO). Moreover, the current literature is diversified; conglomerating both primary, secondary, and anterior, posterior circulations embolic strokes in the same shell. PURPOSE: to identify the association between complete reperfusion and favorable outcome following EVT for DMVO in the middle cerebral artery (MCA) territory. METHODS: -we performed a retrospective analysis of prospectively maintained EVT registries at two comprehensive stroke centers between January 2015 and December 2019 for consecutive stroke patients with MCA-DMVO. DMVO was defined as an occlusion of distal M2 and M3 segments of the MCA. Only patients with primary isolated occlusions were included. A multivariate logistic regression was utilized to identify clinical and procedural-related factors associated with the 90-day favorable clinical outcome [defined as modified Rankin score (mRS) 0-2] after EVT. RESULTS: -Out of 1823 within the registries; 66 patients (median age was 72 (60-78) and 59% were males) with primary isolated DMVO of the MCA were eligible for inclusion in the current study. Complete reperfusion was achieved in 56% (37/66) of the patients with no difference among the reperfusion strategies while the favorable outcome was observed in 68% (45/66). In the multivariate analysis, final complete reperfusion [modified Thrombolysis In Cerebral Infarction (mTICI) score 2c-3] was significantly associated with favorable outcome [aOR=7.69; (95% CI 1.73-34.17); p=.01], while higher baseline NIHSS score [aOR=0.82; (95% CI 0.69-0.98); p=.03] and increased imaging to puncture interval [aOR=0.99; (95% CI 0.98, 1.00); p=.01] decreased the probability of the favorable outcome. CONCLUSION: according to our results, complete reperfusion was the most significant predictor of the favorable outcome, while higher baseline NIHSS and longer imaging to puncture interval decreased the probability of the favorable outcome.

Perfusion Imaging and Clinical Outcome in Acute Minor Stroke With Large Vessel Occlusion.

BACKGROUND: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy. METHODS: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume). RESULTS: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P=0.03. However, mismatch volume modified the effect of bridging on clinical outcome (Pinteraction=0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only (Pinteraction=0.002). CONCLUSIONS: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Impact of White Matter Hyperintensity Burden on Outcome in Large-Vessel Occlusion Stroke.

Background White matter hyperintensity (WMH) has been linked to poor clinical outcomes after acute ischemic stroke. Purpose To assess whether the WMH burden on pretreatment MRI scans is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) or poor functional outcome in patients with acute ischemic stroke treated with endovascular thrombectomy (EVT). Materials and Methods In this retrospective study, consecutive patients treated with EVT for anterior circulation acute ischemic stroke at a comprehensive stroke center (where MRI was the first-line pretreatment imaging strategy; January 2015 to December 2017) were included and analyzed. WMH volumes were assessed with semiautomated volumetric analysis at fluid-attenuated inversion recovery MRI by readers who were blinded to clinical data. The associations of WMH burden with sICH and 3-month functional outcome (modified Rankin Scale [mRS] score) were assessed. Results A total of 366 patients were included (mean age, 69 years ± 19 [SD]; 188 women [51%]). Median total WMH volume was 3.61 cm3 (IQR, 1.10-10.83 cm3). Patients demonstrated higher mRS scores with increasing WMH volumes (odds ratio [OR], 1.020 [95% CI: 1.003, 1.037] per 1.0-cm3 increase for each mRS point increase; P = .018) after adjustment for patient and clinical variables. There were no significant associations between WMH severity and 90-day mortality (OR, 1.007 [95% CI: 0.990, 1.024]; P = .40) or the occurrence of sICH (OR, 1.001 [95% CI: 0.978, 1.024]; P = .94). Conclusion Higher white matter hyperintensity burden was associated with increased risk for poor 3-month functional outcome after endovascular thrombectomy for large-vessel occlusive stroke. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mossa-Basha and Zhu in this issue.