Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial.

BACKGROUND: The superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled trials (RCTs). AIM: To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS. DESIGN: Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial is a multicentre, prospective, randomised, open-label, blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS. Patients eligible in BASIS were 35-80 years old, with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis (70%-99%) of a major intracranial artery. The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio. Both groups will receive identical AMM, including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy, intensive risk factor management and life-style modification. All participants will be followed up for 3 years. STUDY OUTCOMES: Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment, is the primary outcome. DISCUSSION: BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients, which may provide an alternative perspective for treating sICAS. TRIAL REGISTRATION NUMBER: NCT03703635; https://www. CLINICALTRIALS: gov.

Incidence, predictors, and impact on outcome of underlying intracranial atherosclerotic disease in acute vertebrobasilar artery occlusion undergoing endovascular therapy: Data from ANGEL-ACT registry.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease (ICAD) is a common etiology of acute vertebrobasilar artery occlusion (VBAO) in Asia, which complicated endovascular treatment (EVT). We aimed to investigate the incidence, impacts, and predictors of ICAD in VBAO. METHODS: Subjects were selected from the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke registry and divided into two groups based on whether underlying ICAD existed. Underlying ICAD was determined when the following situations arise in the occlusion site during EVT: (1) fixed stenosis degree >70% or (2) stenosis >50% with distal blood flow impairment or evidence of repeated reocclusion. Multivariable regression models were used to investigate the effect of underlying ICAD on outcomes measured by modified Rankin Scale (mRS) score at 90 days and to identify baseline characteristics associated with underlying ICAD. RESULTS: Among the 315 patients enrolled, 171 (54.3%) had underlying ICAD. Favorable functional outcomes (mRS 0-3) occurred in 79 of 163 patients (48.5%) with ICAD and 69 of 137 patients (50.4%) without ICAD (p = 0.743). Outcomes were similar between the two groups and remained similar after adjusting for the confounders. History of hypertension and elevated admission neutrophil to lymphocyte ratio were strong predictors of underlying ICAD, whereas history of atrial fibrillation and distal basilar artery occlusion were negative predictors. CONCLUSIONS: In our study, underlying ICAD was recognized in approximately half of the VBAO patients, leading to comparable outcomes after more complex EVT strategies. Some baseline characteristics were identified to be predictors for underlying ICAD, which were helpful to guide the EVT strategies before the procedure.

Medical and Endovascular Treatments for Intracranial Atherosclerotic Stenosis: A Network Meta-Analysis.

Medical treatment and endovascular therapy are widely used for intracranial atherosclerotic stenosis, but the best treatment strategy remains uncertain. The goal of this study was to compare the safety and effectiveness of medical treatment, stenting, and primary balloon angioplasty (PBA). We searched PubMed, MEDLINE, and EMBASE for trials comparing these three treatments for intracranial stenosis up to December 24, 2020. We performed a network meta-analysis with random-effects models. The primary outcome was any stroke or death during a long-term follow-up. Secondary outcomes included ischemic stroke, intracranial hemorrhage, and death. This network meta-analysis included 14 trials with 1520 participants. No significant difference was found between the three groups in the primary outcome, while PBA was probably the best treatment according to the ranking plot. Medical treatment had significantly lower rate of any stroke or death (odds ratio (OR), 0.31; 95% CI, 0.17-0.56), ischemic stroke (OR, 0.43; 95% CI, 0.23-0.81), and intracranial hemorrhage (OR, 0.12; 95% CI, 0.02-0.71) within 30 days than stenting but did not differ from PBA. The ranking plot demonstrated that PBA was also most likely to rank the highest for ischemic stroke during the long-term follow-up and beyond 30 days, although no significant difference was identified. Medical treatment had lower risk of any stroke or death within 30 days than stenting but did not differ from PBA. All the treatments had similar effects on the prevention of long-term stroke, while PBA had the highest probability of being the most effective.

Intracranial Stenting as Rescue Therapy After Failure of Mechanical Thrombectomy for Basilar Artery Occlusion: Data From the ANGEL-ACT Registry.

Background and Purpose: Studies on rescue therapy for acute posterior circulation stroke due to basilar artery occlusion (BAO) are limited in the modern era of mechanical thrombectomy (MT). The aim of this study was to evaluate the safety and efficacy of rescue stenting (RS) following MT failure in patients with BAO. Methods: Data were collected from the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) prospective registry in China. Patients who underwent MT for BAO with failure of recanalization were enrolled in this study. The patients were divided into the RS and non-RS groups. Clinical and laboratory findings, procedural details, and clinical outcomes were compared between the two groups. Results: Overall, 93 patients with acute BAO were analyzed. The RS group included 81 (87.1%) patients, and the non-RS group included 12 patients. A modified treatment in cerebral infarction (mTICI) score of 2b/3 was achieved in 75 (92.6%) patients in the RS group. Compared with the non-RS group, the RS group had a significantly higher rate of successful recanalization and favorable clinical outcomes (modified Rankin Scale score at 90 days post-procedure, 0-3: 16.7 vs. 51.9%, respectively; P = 0.023) without an increase in the rate of symptomatic intracranial hemorrhage and a significantly lower mortality rate (58.3 vs. 18.5%, respectively; P = 0.006). Furthermore, the use of a glycoprotein IIb/IIIa inhibitor improved the rate of recanalization of the target artery without increasing the rate of symptomatic intracranial hemorrhage. Conclusions: Permanent stenting appears to be a feasible rescue modality when MT fails and might provide functional benefits in patients with acute ischemic stroke due to BAO.

Management of endovascular therapy for acute ischemic stroke amid the COVID-2019 pandemic: a multicenter survey in China.

Objectives: The impact of COVID-19 pandemic on endovascular therapy (EVT) for acute ischemic stroke in China is unknown. This study was aimed to verify the volume change of EVT for acute ischemic stroke affected by COVID-19 and its potential factors.Methods: This cross-sectional study was conducted via an online questionnaire survey in China. The questionnaire was mainly composed of descriptive information, volume change of EVT for acute ischemic stroke, and the protection status of medical staff.Results: A total of 103 stroke physicians in 28 provinces across China completed the survey questionnaire. A volume decline in EVT for acute stroke occurred in 93 (90.3%) hospitals after lockdown (23 January 2020). Nearly half of the hospitals (51/103, 49.5%) experienced a volume decline of EVT case more than 50% and 14 (13.6%) hospitals completely ceased offering EVT. Hospitals with decline >50% of EVT case had higher proportion of hospitals with a designated area for COVID-19 screening in the emergency room (44/51, 86.3% vs 34/52, 65.4%, p= 0.01) and medical staff in quarantine (19/51, 37.3% vs 7/52, 13.5%, p< 0.01), with lower proportion of hospitals with personal protective equipment protocol (41/51, 80.4% vs 49/52, 94.2%, p= 0.03) than hospitals with decline ≤50%.Conclusions: The volume of EVT for acute ischemic stroke severely declined after lockdown in China. Designating a specific area for COVID-19 screening, insufficient personal protection and understaffing may exacerbate the volume decline of EVT.

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. METHODS: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. RESULTS: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56-73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55-72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P=0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213-2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065-2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325-3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085-3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098-2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222-13.385]). CONCLUSIONS: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Staged angioplasty versus regular carotid artery stenting in patients with carotid artery stenosis at high risk of hyperperfusion: a randomised clinical trial.

BACKGROUND AND PURPOSE: Hyperperfusion (HP) is a devastating complication associated with carotid artery stenting (CAS) or endarterectomy. The efficacy and safety of staged angioplasty (SAP) in patients with CAS at high risk of HP remains unclear. We sought to determine whether SAP is superior to regular CAS in patients with high risk of HP. METHODS: A randomised, multicentre open-label clinical trial with blinded outcome assessment (STEP) was conducted. Patients with severe carotid stenosis at high risk of HP were randomly assigned (1:1) to the SAP or regular CAS group. The primary endpoint was hyperperfusion syndrome (HPS) and intracerebral haemorrhage (ICH) within 30 days after the procedure. RESULTS: From November 2014 to January 2017, a total of 64 patients were enrolled in 11 centres. 33 patients were allocated to the SAP group and 31 to the regular CAS group. At 30 days, the rate of primary endpoint was 0.0% (0/33) in the SAP group and 9.7% (3/31) in the regular CAS group (absolute risk reduction (ARR), 9.7%; 95% CI -20.1% to 0.7%; p=0.11). As one of the secondary endpoints, the incidence of HP phenomenon (HPP) was lower in the SAP group than the regular CAS group (0.0% vs 22.6%, ARR,-22.6%; 95% CI -36.8% to -10.2%; p=0.04). CONCLUSION: The rate of HPS and ICH was not significantly lower in SAP group; the extended secondary endpoint of HPP, however, significantly reduced, which suggested that SAP may be a safe and effective carotid revascularisation procedure to prevent HP. TRIAL REGISTRATION NUMBER: NCT02224209.

Submaximal primary angioplasty for symptomatic intracranial atherosclerosis: peri-procedural complications and long-term outcomes.

PURPOSE: The aim of our study is to report the peri-procedural complications and long-term stroke recurrent rate of symptomatic intracranial atherosclerosis (ICAS) patients who underwent submaximal primary angioplasty. METHODS: This is a retrospective analysis of consecutive patients in a single center who underwent submaximal primary angioplasty between January 1, 2012 and December 31, 2015. The peri-procedural complications and long-term outcomes are reported. RESULTS: Primary angioplasty was successfully performed in 129 patients (97.0%). The mean degree of pre-procedural stenosis was 81.9 ± 10.2%, and the degree of residual stenosis was 40.7 ± 19.1%. There were nine (6.8%) peri-procedural complications within 30 days, including seven ischemic strokes, one subarachnoid hemorrhage, and one asymptomatic intracerebral hemorrhage. None of them resulted in death. One-year follow-up was available in 122 patients (91.7%). Three more ischemic strokes (2.3%) which were in the territory of the treated artery occurred between 30 days and 1 year. The 1-year stroke and death rate was 9.0%, including peri-procedural stroke. Kaplan-Meier analysis showed a 3-year stroke-free survival of 87.2%. CONCLUSION: Submaximal primary angioplasty can be performed with a low peri-procedural complication rate and relatively good clinical outcome at long-term follow-up for symptomatic ICAS patients.

Tyrosol attenuates pro-inflammatory cytokines from cultured astrocytes and NF-κB activation in in vitro oxygen glucose deprivation.

Subsequent inflammation in stroke plays an important role in the damage of neurons in the perilesional area. Therapeutic intervention targeting inflammation may be a promising complementary strategy to current treatments of stroke. Here, we explored the possible beneficial effects of tyrosol, a derivative of phenethyl alcohol and natural antioxidant, playing an anti-inflammatory role in astrocyte culture and in vitro oxygen glucose deprivation (OGD) model. MTT, western blot, ELISA and EMSA assays were carried out to investigate cell viability, protein expression level, cytokine expression and NF-κB activity. We found tyrosol protected cultured astrocytes against OGD-induced cell viability loss in MTT test. Meanwhile, tyrosol attenuated the released TNF-α and IL-6 level from astrocyte via regulating Janus N-terminal kinase (JNK). The reduction of cytokines from astrocyte might be due to its inhibition of astrocyte activation and regulation of STAT3 signaling pathway since tyrosol attenuated the expression level of GFAP (glial fibrillary acidic protein) and the phosphorylation of STAT3. Additionally, we demonstrated that tyrosol prevented the degradation of IκBα and the increase of IκBα phosphorylation in astrocytes exposed to OGD, which led to the suppression of NF-κB function during ischemia. Collectively, our results showed that tyrosol may be a promising complementary treatment compound for stroke via modulating the inflammatory response in astrocytes during ischemia.

Factors associated with perforator stroke after selective basilar artery angioplasty or stenting.

BACKGROUND AND PURPOSE: Perforator stroke is one of the most common complications of elective intracranial angioplasty and/or stenting, particularly in the basilar artery. Factors associated with the risk of post-procedural perforator stroke remain unexplored. We investigated factors affecting the risk of perforator stroke after basilar artery angioplasty and/or stenting. MATERIALS AND METHODS: Consecutive patients undergoing basilar artery angioplasty and/or stenting due to symptomatic atherosclerotic stenosis were retrospectively included in this single-center study. Analyzed variables including demographic data, risk factors of atherosclerosis, symptoms, characteristics of imaging, and procedure factors were extracted from electronic health records or imaging data. The main outcome was perforator stroke associated with the procedure. Multivariate analysis that correlated factors with the occurrence of perforator stroke in these patients was performed. RESULTS: A total of 255 patients were included in the study. Perforator stroke associated with angioplasty and/or stenting was identified in 13 patients (5.1%). Variables with significant correlation with post-procedural perforator stroke included diabetes (OR 6.496; 95% CI 1.741 to 24.241; p=0.005), time from last symptom to procedure <18 days (OR 5.669; 95% CI 1.174 to 27.371; p=0.031), and pre-procedure stenosis percentage <88.4% (OR 5.882; 95% CI 1.465 to 23.608; p=0.012). CONCLUSIONS: Diabetes, time from last symptom to procedure, and pre-procedure stenosis percentage may be factors affecting the risk of perforator stroke associated with basilar artery angioplasty and/or stenting. These factors should be considered in planning of potential basilar artery angioplasty and/or stenting and prospectively evaluated in future multicenter trials.