Cerebral hemodynamics in symptomatic anterior circulation intracranial stenosis measured by angiography-based quantitative flow ratio: association with CT perfusion.

OBJECTIVES: Cerebral hemodynamics is important for the management of intracranial atherosclerotic stenosis (ICAS). This study aimed to determine the utility of angiography-based quantitative flow ratio (QFR) to reflect cerebral hemodynamics in symptomatic anterior circulation ICAS by evaluating its association with CT perfusion (CTP). METHODS: Sixty-two patients with unilateral symptomatic stenosis in the intracranial internal carotid artery or middle cerebral artery who received percutaneous transluminal angioplasty (PTA) or PTA with stenting were included. Murray law-based QFR (µQFR) was computed from a single angiographic view. CTP parameters including cerebral blood flow, cerebral blood volume, mean transit time (MTT), and time to peak (TTP) were calculated, and relative values were obtained as the ratio between symptomatic and contralateral hemispheres. Relationships between µQFR and perfusion parameters, and between µQFR and perfusion response after intervention, were analyzed. RESULTS: Thirty-eight patients had improved perfusion after treatment. µQFR was significantly correlated with relative values of TTP and MTT, with correlation coefficients of -0.45 and -0.26, respectively, on a per-patient basis, and -0.72 and -0.43, respectively, on a per-vessel basis (all p < 0.05). Sensitivity and specificity for µQFR to diagnose hypoperfusion at a cut-off value of 0.82 were 94.1% and 92.1%, respectively. Multivariate analysis revealed that µQFRpost (adjusted odds ratio [OR], 1.48; p = 0.002), collateral score (adjusted OR, 6.97; p = 0.01), and current smoking status (adjusted OR, 0.03; p = 0.01) were independently associated with perfusion improvement after treatment. CONCLUSIONS: µQFR was associated with CTP in patients with symptomatic anterior circulation ICAS and may be a potential marker for real-time hemodynamic evaluation during interventional procedures. KEY POINTS: • Murray law-based QFR (µQFR) is associated with CT perfusion parameters in intracranial atherosclerotic stenosis and can differentiate hypoperfusion from normal perfusion. • Post-intervention µQFR, collateral score, and current smoking status are independent factors associated with improved perfusion after treatment.

Recurrence risk in symptomatic intracranial stenosis treated medically in the real world.

BACKGROUND: The risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. METHODS: We used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50-99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. RESULTS: Among 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%-5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. CONCLUSIONS: In patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.

New Diffusion Abnormalities Following Endovascular Treatment for Intracranial Atherosclerosis.

Background There are limited data on new ischemic brain lesions after endovascular treatment for symptomatic intracranial atherosclerotic stenosis (ICAS). Purpose To investigate the (a) characteristics of new ischemic brain lesions at diffusion-weighted MRI (new diffusion abnormalities) after endovascular treatment, (b) characteristics between those treated with balloon angioplasty and stent placement procedures, and (c) predictors of new ischemic brain lesions. Materials and Methods Patients with symptomatic ICAS in whom maximum medical therapy failed were prospectively enrolled between April 2020 and July 2021 from a national stroke center and underwent endovascular treatment. All study participants underwent thin-section diffusion-weighted MRI (voxel size, 1.4 × 1.4 × 2 mm3 with no section gap) before and after treatment. The characteristics of new ischemic brain lesions were recorded. Multivariable logistic regression analysis was performed to determine potential predictors of new ischemic brain lesions. Results A total of 119 study participants (mean age, 59 years ± 11 [SD]; 81 men; 70 treated with balloon angioplasty and 49 with stent placement) were enrolled. Of the 119 participants, 77 (65%) had new ischemic brain lesions. Five of the 119 participants (4%) had symptomatic ischemic stroke. New ischemic brain lesions were located in (61%, 72 of 119) and/or beyond (35%, 41 of 119) the territory of the treated artery. Of the 77 participants with new ischemic brain lesions, 58 (75%) had lesions located in peripheral brain areas. There was no evidence of a difference in the frequency of new ischemic brain lesions between the balloon angioplasty and stent groups (60% vs 71%, P = .20). In adjusted models, cigarette smoking (odds ratio [OR], 3.6; 95% CI: 1.3, 9.7) and more than one operative attempt (OR, 2.9; 95% CI: 1.2, 7.0) were independent predictors of new ischemic brain lesions. Conclusion New ischemic brain lesions on diffusion-weighted MRI scans were common after endovascular treatment for symptomatic intracranial atherosclerotic stenosis, and occurrence may be associated with cigarette smoking and the number of operative attempts. Clinical trial registration no. ChiCTR2100052925 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Russell in this issue.

Mechanical thrombectomy first versus direct angioplasty or stenting for the treatment of intracranial atherosclerotic stenosis-related large vessel occlusion: protocol for a systematic review and meta-analysis.

INTRODUCTION: Mechanical thrombectomy (MT) using stent retrievers or a direct aspiration first-pass technique has proven to yield better results over intravenous thrombolysis in treating acute ischaemic stroke caused by large vessel occlusion (LVO). However, the treatment of intracranial atherosclerotic stenosis-related LVO remains unclear and has been a critical problem in daily clinical practice, as it can cause a relatively high failure rate for MT. Whether direct angioplasty and/or stenting is clinically feasible and shows advantage in reducing delay to revascularisation with better functional outcome compared with MT with rescue angioplasty and/or stenting remains unclear. This study seeks to provide direct and practical clinical evidence for clinicians. METHODS AND ANALYSIS: The main databases of PubMed, the Cochrane library, Embase and Web of Science will be screened for related studies published after1 January 2015. Primary outcomes include successful recanalisation and 90-day favourable outcome. Secondary outcomes include puncture to revascularisation time, vascular complication (perforation, dissection and vasospasm), intracerebral haemorrhage, hospital-related complications and 90-day mortality. The Newcastle-Ottawa Scale will be adopted to assess risk bias of observational studies. The I 2 statistic will be used to assess heterogeneity. ETHICS AND DISSEMINATION: No primary data of patients are needed. Therefore, ethics approval is unnecessary. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021268061.

Intracranial atherosclerotic disease and acute ischaemic stroke: A review of diagnosis and management.

Intracranial atherosclerotic disease is highly prevalent and a common cause of ischaemic stroke globally. With the increasing use of endovascular treatment for acute stroke management, computed tomography and magnetic resonance imaging have become an essential part of patient selection. In this review, we present the typical imaging findings of intracranial atherosclerosis and an overview of management as relevant to diagnostic and interventional radiologists.

Risk Factors Control and Early Recurrent Cerebral Infarction in Patients with Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND: The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD. METHODS: We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event. RESULTS: Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01). CONCLUSIONS: Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD.

Nilotinib-Associated Atherosclerosis Presenting as Multifocal Intracranial Stenosis and Acute Stroke.

Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with progressive peripheral artery occlusive disease (PAOD), and only a few cases of coronary artery disease (CAD), and cerebrovascular disease (CVD) have been reported. The mechanisms by which nilotinib promotes atherosclerosis are poorly understood but endothelial and perivascular factors, mast cell depletion, and metabolic factors such as promotion of dyslipidemia and impaired glucose metabolism are thought to play a role. We present a case of a patient with chronic myelogenous leukemia (CML) treated with nilotinib who developed intracranial atherosclerosis leading to acute onset of stroke. Our patient had no cardiovascular risk factors prior to treatment with nilotinib and developed accelerated atheromatous cerebrovascular disease with severe left middle cerebral artery (MCA) stenosis. These findings suggest that nilotinib may be associated with the development of intracranial atherosclerotic disease (ICAD) independently of any preexisting vascular risk factors leading to acute stroke. Clinicians should have increased awareness of the association between nilotinib and the development of progressive atheromatous disease and vascular adverse events including PAOD, CAD, and CVD. In certain patients, these events can be severe and life threatening. Thus, screening for vascular risk factors including CVD prior to starting nilotinib and close follow up during treatment is crucial.

Encephaloduroarteriosynangiosis Averts Stroke in Atherosclerotic Patients With Border-Zone Infarct: Post Hoc Analysis From a Performance Criterion Phase II Trial.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is one of the leading causes of stroke worldwide. Patients with ICAD who initially present with ischemia in border-zone areas and undergo intensive medical management (IMM) have the highest recurrence rates (37% at 1 yr) because of association with hemodynamic failure and poor collaterals. OBJECTIVE: To evaluate the effect of encephaloduroarteriosynagiosis (EDAS) on stroke recurrence in patients with ICAD and border-zone stroke (BDZS) at presentation. METHODS: A phase II clinical trial of EDAS revascularization for symptomatic ICAD failing medical management (EDAS Revascularization for Symptomatic Intracranial Atherosclerosis Steno-occlusive [ERSIAS]) was recently concluded. We analyze the outcomes of the subgroup of patients with BDZS at presentation treated with EDAS vs the previously reported Stenting versus Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) IMM subgroup with BDZS at presentation. RESULTS: Of 52 patients included in the ERSIAS trial, 35 presented with strokes at baseline, and 28 had a BDZ pattern, including 15 (54%) with exclusive BDZS and 13 (46%) with mixed patterns (BDZ plus other distribution). Three of the 28 (10.7%) had recurrent strokes up to a median follow-up of 24 months. The rate of recurrent stroke in ICAD patients with BDZS at presentation after EDAS was significantly lower than the rate reported in the SAMMPRIS IMM subgroup with BDZS at presentation (10.7% vs 37% P = .004, 95% CI = 0.037-0.27). CONCLUSION: ICAD patients with BDZS at presentation have lower rates of recurrent stroke after EDAS surgery than those reported with medical management in the SAMMPRIS trial. These results support further investigation of EDAS in a randomized clinical trial.

The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes.

BACKGROUND: Prior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate. OBJECTIVE: This WOVEN study assesses the 1-year follow-up from this cohort. METHODS: Twelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis. RESULTS: In the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up. CONCLUSIONS: The WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients.

Medical Management Versus Surgical Bypass for Symptomatic Intracranial Atherosclerotic Disease: A Systematic Review.

INTRODUCTION: Intracranial atherosclerotic disease (ICAD) is a major cause of stroke worldwide. The optimal management of patients with symptomatic ICAD is controversial. Therefore, the aim of this systematic review is to compare medical management versus surgical bypass for the treatment of symptomatic ICAD. METHODS: A literature review was performed to identify studies reporting outcomes of patients with ICAD who were managed medically or surgically with either direct or indirect bypass. Baseline, treatment, and outcomes data were analyzed. Complications included ischemic stroke, intracranial hemorrhage, and cerebrovascular death. Secondary analyses of the surgically treated cohort were performed to compare the outcomes of direct versus indirect bypass. RESULTS: The pooled analysis was derived from 18 studies, comprising a total of 2160 patients with ICAD, including 1790 managed medically and 370 treated with surgical bypass. The rates of ischemic stroke, intracranial hemorrhage, and cerebrovascular death were 16%, 1%, and 4.5% in the medical cohort, respectively, versus 8%, 0.6%, and 1.9% in the surgical cohort, respectively. Among patients with ICAD who underwent bypass surgery, the rates of ischemic stroke and cerebrovascular death were 7% and 1.9% in the direct bypass group, respectively, versus 19% and 2.1% in the indirect bypass group, respectively. CONCLUSIONS: Direct or indirect bypass surgery is a reasonable treatment option for appropriately selected patients with ICAD. Careful preoperative evaluation of hemodynamic parameters and the relevant donor and recipient vessels is crucial to maximizing the success of bypass for ICAD. Further studies remain necessary to clarify the roles of medical versus surgical management for ICAD.

Predictors of response to endovascular treatment of posterior circulation stroke.

BACKGROUND: Endovascular treatment is considered a reasonable approach for patients with acute posterior circulation stroke, but it remains uncertain which patients will benefit the most from it. OBJECTIVE: To find independent clinical and angiographic predictors of outcome after endovascular treatment for posterior circulation stroke. METHODS: We evaluated consecutive patients with acute posterior circulation stroke who underwent endovascular treatment in our comprehensive stroke center from January 2015 to December 2017. Good outcome was defined as a modified Rankin score of 0-3 at 90 days. Intracranial atheromatous disease was established on focal stenosis recorded during endovascular treatment. Associations were sought between a good outcome and clinical and angiographic factors. Adjusted logistic regression models were used to define independent outcome predictors. RESULTS: Forty-seven consecutive patients were included: mean age 70.9 ± 12.1 years, median admission NIHSS score, 16 (IQR: 8-30). On univariate analysis, age (p = 0.01), smoking (p = 0.04), hypertension (p = 0.03), successful reperfusion (p = 0.04), presence of extracranial atherosclerosis (p = 0.02), and absence of atherosclerosis (p = 0.03) were significantly associated with a good outcome. On multivariate analysis, age <70 years (odds ratio = 6.20, 95%CI 1.52-25.47, p = 0.01) and absence of intracranial atherosclerosis (odds ratio = 6.45, 95% CI 1.09-38.24, p = 0.04) were independently associated with a good outcome. CONCLUSIONS: Pretreatment determination of the presence or absence of intracranial atherosclerosis can aid management of posterior circulation stroke patients. The absence of intracranial atherosclerosis may have value as a positive selection criterion for endovascular treatment in future trials. The presence of intracranial atherosclerosis could be used as a selection tool in future studies investigating new treatment protocols for this population.

Association of Perforator Stroke After Basilar Artery Stenting With Negative Remodeling.

Background and Purpose- We try to evaluate whether plaque features and perforator stroke after intracranial stenting is associated with the arterial remodeling patterns in patients with severe basilar artery stenosis. Methods- We studied patients with symptomatic intracranial arterial stenosis who underwent high-resolution magnetic resonance imaging from September 2014 to January 2017. Among them, patients with basilar artery stenosis underwent angioplasty and stenting were recruited. Arterial remodeling patterns were divided into negative or nonnegative remodeling. Plaque features were investigated by high-resolution magnetic resonance imaging, which includes plaque distribution, intraplaque hemorrhage, calcification, as well as enhancement patterns. Incidence of perforator strokes after intracranial stenting was recorded. Plaque features and incidence of poststenting perforator stroke were compared between negative and nonnegative remodeling. Results- Two hundred ninety-eight consecutive patients were enrolled. Among them, 30 patients fulfilled the inclusion criteria. There were 11 patients (36.7%) with negative remodeling and 19 (63.3%) with nonnegative remodeling. Twenty-six patients (86.7%) had diffuse distribution, 5 patients (16.7%) had intraplaque hemorrhage, 2 patients (6.7%) had calcification, and 17 patients (65.4%) had enhancement. Three patients had perforator stroke after stenting. Plaque features were similar between negative and nonnegative remodeling groups. Patients with negative remodeling were more likely to have perforator stroke after stenting comparing with patients with nonnegative remodeling (27.3% versus 0%, P=0.041). Conclusions- Perforator stroke after basilar artery stenting may be related to negative remodeling on high-resolution magnetic resonance imaging. The finding needs to be confirmed in future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02705599.

Drug-coated balloons for the treatment of symptomatic intracranial atherosclerosis: initial experience and follow-up outcome.

BACKGROUND: The optimal treatment for patients with symptomatic severe intracranial atherosclerotic disease is not well established. Angioplasty and stenting have been attempted, with controversial results, mainly attributed to perioperative complications and a high incidence of restenosis or in-stent restenosis. Drug-coated balloons (DCBs) have shown encouraging results for coronary and peripheral artery disease, without convincing data for intracranial vasculature. OBJECTIVES: To assess the feasibility, clinical and angiographic outcomes of DCBs for patients with intracranial de novo atherosclerotic disease. METHODS: Between September 2016 and September 2017, details of 30 patients with 31 arteries treated with DCBs for symptomatic severe intracranial atherosclerotic disease (≥70% stenosis or chronic total occlusion) were retrospectively collected in our centre. All lesions were predilated with conventional balloons. Periprocedural complications and clinical and vascular imaging follow-up outcomes were analysed. RESULTS: All arteries were successfully dilated with DCBs and 29 (93.5%) arteries achieved good antegrade perfusion, with remedial stenting for two arteries. Two patients presented with new ischemic stroke after the procedure. Over a mean follow-up of 9.8±2.6 months, no patient had recurrent ischemic symptoms. Repeat vascular imaging was performed at 7.0±1.1 months, with cerebral angiography in 24 patients (25 arteries) and MR angiography in six patients (six arteries). Only one (3.2%) artery presented with angiographic asymptomatic restenosis. CONCLUSIONS: This study suggests that DCB dilatation may be a safe and effective alternative for intracranial de novo atherosclerotic disease.

Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

BACKGROUND: Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A165 isoforms in ICAD and MMD. METHODS: Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A165a and VEGF-A165b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment. RESULTS: A significantly higher baseline VEGF-A165a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A165a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A165a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A165a/b ratio, P = .028). CONCLUSIONS: Our study shows an increased VEGF-A165a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A165a/b ratio in ICAD patients.

Percutaneous transluminal angioplasty using the novel drug-coated balloon catheter SeQuent Please NEO for the treatment of symptomatic intracranial severe stenosis: feasibility and safety study.

OBJECTIVES: Intracranial arteriosclerotic disease is a relevant cause of ischemic stroke worldwide with a high recurrence rate despite best medical treatment. Following the SAMMPRIS trial, endovascular treatment has remained a second-line therapy. Meanwhile, there has been significant advances in device technology. SeQuent Please NEO is a novel polymer-free, drug-coated (paclitaxel/iopromide) balloon (DCB) primarily designed for cardiology. Because of its high flexibility and pushability, it may also be suitable for intracranial use. The aim of this study was to assess the feasibility and safety of SeQuent Please NEO DCB in symptomatic intracranial severe stenosis. METHODS: A single-center retrospective cohort study of patients with symptomatic intracranial severe stenosis treated with SeQuent Please NEO DCB was performed at a tertiary stroke center. RESULTS: Ten patients (all men, median age 73 years (IQR 69-77)) were included. Median pre-treatment stenosis grade was 78% (IQR 75-80%) with four internal carotid artery, two mid-basilar artery, and four vertebral artery lesions. Median post-treatment stenosis grade was 50% (IQR 45-53%). Successful angioplasty was achieved in all cases without technical failure. There were no cases of peri-procedural reocclusion and no deaths at median follow-up of 3 months (IQR 2-3). CONCLUSION: In this pilot study, SeQuent Please NEO DCB was feasible and safe in the treatment of symptomatic intracranial severe stenosis. It might represent a promising alternative to medical treatment in selected cases.

Neuro Elutax SV drug-eluting balloon versus Wingspan stent system in symptomatic intracranial high-grade stenosis: a single-center experience.

BACKGROUND: Intracranial atherosclerotic disease is a well-known cause of ischemic stroke. Following the SAMMPRIS trial, medical treatment is favored over stenting. Drug-eluting balloons (DEB) are widely used in coronary angioplasty, showing better results than bare-surface balloons. There is little evidence of DEB employment in intracranial stenosis, especially of paclitaxel-eluted balloons (pDEB). The Neuro Elutax SV (Aachen Resonance) is the first CE certificated pDEB for intracranial use. OBJECTIVE: To compare pDEB Neuro Elutax SV (ElutaxDEB) with the Wingspan/Gateway stent system (WingspanStent). MATERIALS AND METHODS: A single-center, open-label, retrospective cohort study of 19 patients with symptomatic atherosclerotic intracranial high-grade stenosis treated with either ElutaxDEB or WingspanStent from a tertiary stroke center in Switzerland. RESULTS: Eight patients (42%) received ElutaxDEB. Median clinical follow-up was 10 months for the WingspanStent and 9.5 months for ElutaxDEB (P=0.36). No differences were found in the clinical baseline characteristics, with a median stenosis grade of 80% for the WingspanStent and 81% for the ElutaxDEB (P=0.87). The compound endpoint 'ischemic re-event and/or restenosis' was significantly lower for ElutaxDEB (13% vs 64%; P=0.03, OR 0.08 (95% CI 0.007 to 0.93; P=0.043) than for the WingspanStent. CONCLUSIONS: The ElutaxDEB may be a promising alternative treatment for patients with symptomatic high-grade intracranial stenosis showing a significantly lower rate of ischemic re-events or restenosis in comparison with the WingspanStent-treated patients with a similar safety profile. Further studies will be needed to definitively elucidate the role of pDEB in the management of symptomatic intracranial high-grade stenosis.

Mechanical thrombectomy and rescue therapy for intracranial large artery occlusion with underlying atherosclerosis.

OBJECTIVE: To investigate the safety and efficacy of mechanical thrombectomy plus rescue therapy for intracranial large artery occlusion (ILAO) with underlying intracranial atherosclerosis (ICAS). METHODS: Patients enrolled in the intervention group of EAST (Endovascular Therapy for Acute ischemic Stroke Trial) were analyzed. For underlying ICAS identified during the stent retrieval procedure, rescue treatment was required for those with (1) a degree of arterial stenosis >70% or (2) any degree of arterial with blood flow impairment or (3) evidence of re-occlusion. Outcomes were compared between the ICAS group and the embolic group. Multivariate logistic regression was performed to determine independent predictors of functional independence at 90 days. RESULTS: Among the 140 patients included in the analysis, underlying ICAS was identified in 47 (34%), and 30 patients (21.4%) were considered to be eligible to receive rescue treatment. Of the 30 patients, 27 (90%) actually received rescue therapy. Recanalization rate (95.7% vs 96.8%, P=0.757) and functional independence at 90 days (63.8% vs 51.6%, P=0.169) were comparable between the ICAS group and the embolic group. No significant difference in symptomatic hemorrhage (4.3% vs 4.3%, P=1.000) or death (12.8% vs 12.9%, P=0.982) was found between the two groups. National Institutes of Health Stroke Scale score at presentation (OR=0.865, 95% CI 0.795 to 0.941; P=0.001) and modified Thrombolysis in Cerebral Infarction after the procedure (OR=2.864, 95% CI 1.018 to 8.061; P=0.046) were independently associated with functional independence at 90 days. CONCLUSIONS: Mechanical thrombectomy is safe in patients with ILAO with underlying ICAS. By employing a standard rescue therapy, favorable outcomes could be achieved in such patients. CLINICAL TRIAL REGISTRATION: NCT02350283 (Post-results).

Antiangiogenesis and medical therapy failure in intracranial atherosclerosis.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.

Stroke Caused by Atherosclerosis of the Major Intracranial Arteries.

Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and intracranial atherosclerosis. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics, and Asians compared with whites. Diabetes mellitus, hypertension, metabolic syndrome, smoking, hyperlipidemia, and a sedentary lifestyle are the major modifiable risk factors associated with intracranial atherosclerotic disease. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with intracranial atherosclerotic disease. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serological, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients.

The Design and Rationale of a Clinical Trial Evaluating Limb Postconditioning in Young Patients with Intracranial Arterial Stenosis.

OBJECTIVES: To examine the effectiveness of bilateral arm remote ischemic postconditioning (RIPC) on the rehabilitation of nerve function and collateral circulation in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). SETTING: Open, controlled, prospective trial (EPIC-sICAS trial) in Xi'an, Shaanxi, China. PARTICIPANTS: Up to 100 sICAS patients (age: 18-45 years, gender balance) who fulfill the inclusion and exclusion criteria will be enrolled and randomized to intervention group and control group (n ~ 50/group). INTERVENTIONS: The intervention group will undergo ischemia and reperfusion on both arms twice a day for 6 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Mean changes in collateral circulation from baseline to the end of the 6-month RIPC treatment period, measured by dynamic contrast-enhanced magnetic resonance imaging, will be the primary outcome. Clinical symptoms, serum levels of vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) will be compared as secondary outcome. RESULTS: A safety evaluation and preliminary experiment of the EPIC-sICAS trial were completed in November 2014 and March 2015, respectively. Overall and regional brain hemodynamics remained stable throughout RIPC. Activities of daily living score and serum VEGF and bFGF levels were significantly higher (P < .05) in the intervention group. CONCLUSIONS: Repetitive bilateral arm RIPC appears to have protective effects in the brain related to angiogenesis promotion and neuroprotection in the acute phase of sICAS. Assessment of the role of RIPC in collateral circulation requires imaging tests and longer follow-up, as planned in the EPIC-sICAS trial.