Computational fluid dynamics modeling of symptomatic intracranial atherosclerosis may predict risk of stroke recurrence.

BackgroundPatients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.MethodsPatients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.ResultsOverall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.ConclusionsHemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis

Safety and Efficacy of Heparinization During Mechanical Thrombectomy in Acute Ischemic Stroke

Background: The benefits of heparization during mechanical thrombectomy (MT) with newer generation thrombectomy devices, and if it is counterbalanced by the increased risk of intracranial hemorrhage (ICH) remain unknown.Methods: We included eligible patients who underwent MT from the ANGEL registry study (2015-2017) in China. Subjects in the current analysis were dichotomized into two groups according to whether adequate heparinization during MT was performed. In the heparinization group, unfractionated heparin was infused at 50–100 IU/Kg at first and additional 1,000 IU at intervals of an hour during the operation. Safety outcomes (symptomatic intracerebral hemorrhage [sICH], ICH and distal embolization) and efficacy outcomes (artery recanalization and functional outcomes at 3-month follow-up) were compared between groups.Results: We included 619 patients from the entire cohort of 917 patients. The average age of them was 63.9 ± 13.7 years, 269 (43.5%) were treated with heparinization during MT. Heparinization during MT didn't significantly influence recanalization rates, total ICH and long-term mortality (adjusted p > 0.05 for all). But sICH and distal embolization occurred more frequently (9.3 vs. 5.1%, adjusted p = 0.02; 7.1 vs. 3.1%, adjusted p = 0.04, respectively), while functional independence appeared less likely (39.8 vs. 47.4%, adjusted p = 0.01) in heparinization group than that in non-heparinization group. Multivariable logistic regression analyses showed that heparinization during MT was an independent predictor for sICH (Odds ratio 2.36 [1.19–4.67], p = 0.01) in addition to cardio-embolism stroke and posterior circulation stroke (PCS), and an independent predictor for poor outcome (Odds ratio 1.79 [1.23–2.59], p < 0.01) besides age, bridging intravenous thrombolysis, admission NIHSS, drinking and PCS.Conclusion: Heparinization during MT may be associated with increased risk of safety outcomes over sICH and distal embolization, as well as efficacy outcomes over long-term poor outcome. Further randomized controlled trials are needed

Endovascular Recanalization for Chronic Symptomatic Intracranial Vertebral Artery Total Occlusion

Purpose. The outcome of recanalization in patients with chronic symptomatic intracranial vertebral artery (ICVA) total occlusion is poor. This paper reports the technical feasibility and long-term outcome of ICVA stenting in patients with chronic symptomatic total occlusion. Methods. Retrospective review of our prospectively maintained intracranial intervention database to identify patients with symptomatic total occlusion of ICVA with revascularization attempted >1 month after index ischemic event. Results. Eight patients (mean age 58 years) were identified. One had stroke and 7 had recurrent transient ischemic attacks. Four had bilateral ICVA total occlusion and 4 had unilateral ICVA total occlusion with severe stenosis contralaterally. Seven of 8 patients underwent endovascular recanalization, which was achieved in 6. Periprocedural complications included cerebellum hemorrhage, arterial dissection, perforation, and subacute in-stent thrombosis which occurred in 3 patients. One patient died of cerebellum hemorrhage. The other patients improved clinically after endovascular therapy. Conclusions. Stent-supported recanalization of ICVA total occlusion is technically feasible, and may become a viable treatment option in selected patients

Association Between Cerebral Hypoperfusion and Cognitive Impairment in Patients With Chronic Vertebra-Basilar Stenosis

Objective: This study aimed to investigate the association between cognitive impairment and cerebral haemodynamic changes in patients with chronic vertebra-basilar (VB) stenosis.Methods: Patients with severe posterior circulation VB stenosis and infarction or a history of infarction for more than 2 weeks from January 2014 to January 2015 were enrolled (n = 96). They were divided into three groups, namely, the computed tomography perfusion (CTP) normal group, the CTP compensated group, and the CTP decompensated group. Cognitive function was assessed using a validated Chinese version of the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regression models were used to identify independent risk factors for cognitive impairment.Results: The MMSE and FAB scores of patients in the CTP decompensated group were significantly lower than those of patients in the CTP normal and CTP compensated groups (all p < 0.05). The RBANS total and its domain scores, including immediate memory, visual acuity, and delayed memory, in the CTP compensated and CTP decompensated groups were significantly lower than those in the CTP normal group (all p < 0.05). Multiple regression analyses showed that CTP compensation, CTP decompensation, severe VB tandem stenosis, and multiple infarctions were independent risk factors for cognitive impairment.Conclusions: Low perfusion caused by severe VB stenosis can lead to extensive cognitive impairments in areas such as immediate memory, visual span, and delayed memory

Perceived acceptable uncertainty regarding comparability of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment.

BACKGROUND Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown. OBJECTIVE To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers. METHODS A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results. RESULTS There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1-5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67). CONCLUSION Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT

Does MRI add value in selecting patients for thrombectomy beyond the 6 h window? A matched-control analysis

BackgroundControversy exists regarding the need of advanced imaging for patient selection in the extended window.AimsTo analyze the effect of initial imaging modalities on clinical outcomes of patients underwent MT in the extended window.MethodsThis was a retrospective analysis of a prospective registry, the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke (ANGEL-ACT) registry which was conducted at 111 hospitals between November 2017 and March 2019 in China. Primary study cohort and Guideline like cohort were identified, in each cohort, two imaging modalities for patient selection in 6 to 24 h window were defined: (1) NCCT ± CTA, (2) MRI. Guideline-like cohort were further screened based on key features of the DAWN and DEFUSE 3 trials. The primary outcome was 90 day mRS. The safety outcomes were sICH, any ICH and 90-day mortality.ResultsAfter adjusting for covariates, there were no significant differences in 90 day mRS or any safety outcomes between two imaging modalities groups in both cohorts. All outcome measures of mixed-effects logistic regression model were consistent with propensity score matching model.ConclusionOur results indicate that patients presented with anterior large vessel occlusion in the extended time window can potentially benefit from MT even in the absence of MRI selection. This conclusion needs to be verified by the prospective randomized clinical trials

The impact of intraarterial, intravenous, and combined tirofiban on endovascular treatment for acute intracranial atherosclerotic occlusion

Background and purposeAdjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD).MethodsPatients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0–1, 0–2, and 0–3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population.ResultsA total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0–5) vs. 1(0–4) vs. 1(0–4) vs. 3(0–5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45–1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78–2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64–1.64, P = 0.912). The adjusted OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27–0.98, P = 0.042) and 0.50 (95% CI, 0.26–0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18–0.94, P = 0.036), and the OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11–0.74, P = 0.011) and 0.25 (95% CI, 0.09–0.67, P = 0.006).ConclusionsIntra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO.Clinical trial registrationhttp://www.clinicaltrials.gov, Unique identifier: NCT03370939

Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p > 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy

Effect of Hyperglycemia at Presentation on Outcomes in Acute Large Artery Occlusion Patients Treated With Solitaire Stent Thrombectomy

Background: Sporadic data showed hyperglycemia at presentation is associated with poor outcomes in patients with acute ischemic stroke (AIS) under mechanical thrombectomy (MT) treatment.Objective: This study aims to evaluate the relationship of admission hyperglycemia and outcomes in patients treated with solitaire stent thrombectomy.Methods: This multicenter prospective study registered patients with AIS due to anterior circulation large vessel occlusion (LVO) suitable for MT with Solitaire stent retriever. We analyzed the influence of admission hyperglycemia (≥7.8 mmol/L) and serum glucose on functional independence which is defined as modified Rankin Scale score (mRS) of 0–2, symptomatic intracranial hemorrhage (sICH) and several outcomes of interest using univariable and multiple logistic regression analysis.Results: This study involved 17 stroke centers across China and consecutively recruited 149 patients. Patients with hyperglycemia at presentation less frequently exhibited a functional independence at 3 months than patients without hyperglycemia (22.2 vs. 66.4%; odds ratio 0.75, 95% confidence interval 0.61–0.92; P = 0.005). Higher glucose levels were correlated with worse outcome (per 1 mmol/L increase in glucose: odds ratio for mRS score 0–2 at 3 months 0.17, 95% confidence interval 0.06–0.45; P < 0.001) at 3 months and sICH (per 1 mmol/L increase in glucose: odds ratio for sICH was 8.2, 95% confidence interval 1.13–29.57; P < 0.001) after thrombectomy.Conclusions: Higher admission serum glucose and hyperglycemia were independently correlated with lower functional independence at 3 months in patients treated with Solitaire stent thrombectomy of anterior circulation LVO. Higher admission serum glucose was also associated with sICH after thrombectomy

Current Opinions on Optimal Management of Basilar Artery Occlusion: After the BEST of BASICS Survey

Background The best management of basilar artery occlusion (BAO) remains uncertain. The BASICS (Basilar Artery International Cooperation Study) and the BEST (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment) trials reported neutral results. We sought to understand physicians’ approaches to BAOs and whether further BAO randomized controlled trials were warranted. Methods We conducted an online international survey from January to March 2022 to stroke neurologists and neurointerventionalists. Survey questions were designed to examine clinical and imaging parameters under which clinicians would offer (or rescind) a patient with BAO to endovascular therapy (EVT) or best medical management versus enrollment into a randomized clinical trial. Results Of >3002 invited participants, 1245 responded (41.4% response rate) from 73 countries, including 54.7% stroke neurologists and 43.6% neurointerventionalists. More than 95% of respondents would offer EVT to patients with BAO, albeit in various clinical circumstances. There were 70.0% of respondents who indicated that the BASICS and BEST trials did not change their practice. Only 22.1% of respondents would perform EVT according to anterior circulation occlusion criteria. The selection of patients for BAO EVT by clinical severity, timing, and imaging modality differed according to geography, specialty, and country income level. Over 80% of respondents agreed that further randomized clinical trials for BAO were warranted. Moreover, 45.6% of respondents indicated they would find it acceptable to enroll all trial‐eligible patients into the medical arm of a BAO trial, whereas 26.3% would not enroll. Conclusion Most stroke physicians continue to believe in the efficacy of EVT in selected patients with BAO in spite of BEST and BASICS. There is no consensus on which selection criteria to use, and few clinicians would use anterior circulation occlusion criteria for BAOs. Further randomized clinical trials for BAO are warranted