Search

Background: Risk stratification based on intracranial plaque characteristics is crucial for patients with intracranial atherosclerosis (ICAS). Nonetheless, there remains a significant deficit of validated imaging markers capable of predicting recurrent strokes. Consequently, we conducted a systematic review and meta-analysis to investigate the prognostic significance of high-risk plaque characteristics (HPCs) in relation to recurrent stroke., Methods: The systematic review was registered in PROSPERO (CRD420245820945). We systematically searched PubMed, Ovid Medline, and Web of Science for studies evaluating the association between HPCs and risk of stroke recurrence. Data were aggregated and pooled using a random-effects meta-analysis. Heterogenicity and publication bias were assessed, with subgroup and sensitivity analyses performed where appropriate., Results: Eighteen studies, comprising 13 prospective and 5 retrospective, involving a total of 4967 patients (3594 symptomatic, and 1373 asymptomatic), were included in the analysis. Among symptomatic patients, those with HPCs exhibited a higher incidence of stroke recurrence compared to those without HPCs (adjusted HR, 3.90 ([95% CI, 2.15-7.08]). ICAS patients with baseline plaque enhancement (adjusted HR, 5.20 [95% CI, 3.12-8.66]), calcification (adjusted HR, 2.92 [95% CI, 1.32-6.45]), high plaque steepness (adjusted HR, 110.27 [95% CI, 4.75-2559.74]), and progression in plaque burden (adjusted HR, 6.29 [95% CI, 1.62-24.45]) were identified as being at an increased risk of stroke recurrence. Subgroup analyses revealed that traditional cerebrovascular risk factors, including increasing age, hypertension, diabetes mellitus, and smoking, further elevated the risk of HPC-related stroke recurrence in ICAS patients., Conclusion: The identification of HPCs confers independent prognostic value for the prediction of stroke recurrence in ICAS patients, which could be instrumental for patients risk stratification., Competing Interests: Declarations. Conflicts of interest: On behalf of all the authors, the corresponding author states that there is no conflict of interest., (© 2025. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Branch atheromatous disease (BAD) is prone to early neurological deterioration (END), leading to a poor prognosis. The most common arteries causing END are the lenticulostriate arteries (LSA) and the paramedian pontine arteries (PPA). To gain insight into the characteristics of symptomatic plaques and their association with poor prognosis in patients with BAD, we conducted a prospective study using high-resolution magnetic resonance imaging (HRMRI)., Methods: A total of 75 patients with BAD in the vascular range of LSA or PPA were recruited for this study. The vascular and plaque features of the carrier middle cerebral artery (MCA) and basilar artery (BA) were evaluated through the application of HRMRI, and the local cerebral blood flow (CBF) of the lesion was assessed through pseudo-continuous arterial spin-labeling (pCASL), and the number and location of cerebral microbleeds (CMBs) were documented by susceptibility-weighted imaging (SWI). Univariable and multivariable logistic regression analyses were performed to analyze the factors that affected the prognosis., Results: A poor prognosis was observed in 24 patients (32%) with BAD. A total of 28 patients (37%) developed END. Multifactorial analysis showed statistically significant differences in the dorsal plaque of BA (OR: 19.15, 95% CI 1.72-385.37, p=0.028), male (OR: 26.22, 95% CI 3.18-406.31, p=0.007), and NIHSS at 7 days of onset (OR: 2.24, 95% CI 1.4-4.45, p=0.004)., Conclusions: In patients with BAD in LSA and PPA areas, the dorsal plaque of BA, male, and NIHSS at 7 days of onset were independent risk factors for poor prognosis., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy., Methods: This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged ≥40 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study., Results: A total of 101 participants were randomized. Average enrollment was 10 participants/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (±10.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32-1.93]; P =0.59) favoring the intervention., Conclusions: A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04142125., Competing Interests: Dr Perera reports grants from Bayer AG. Dr Sharma reports grants from Bayer to others; compensation from Bayer for consultant services; and employment by McMaster University. Dr Eikelboom reports compensation from Anthos Pharmaceuticals for consultant services; compensation from Servier Pharmaceuticals LLC for other services; compensation from GlaxoSmithKline for other services; compensation from Janssen Biotech for other services; compensation from Bayer for other services; compensation from Pfizer Canada, Inc for other services; compensation from Bristol-Myers Squibb Canada for other services; compensation from Eli Lilly and Company for consultant services; compensation from Pfizer Canada, Inc for other services; employment by McMaster University; compensation from Daiichi Sankyo Company for other services; compensation from Sanofi Pasteur, Inc for other services; compensation from Merck for other services; compensation from Boehringer Ingelheim for other services; and compensation from AstraZeneca for other services. Dr Ng reports employment by McMaster University. Dr Field reports compensation from Novartis for consultant services; compensation from Bayer for consultant services; service as a Board Member for Destine Health; compensation from AstraZeneca Canada for consultant services; compensation from HLS Therapeutics for consultant services; and compensation from the Canadian Medical Protective Association for expert witness services. Dr Hill reports grants from Boehringer Ingelheim; employment by the University of Calgary; grants from the Canadian Institutes of Health Research; grants from NoNO, Inc; and compensation from Merck for end point review committee services. Dr Shoamanesh reports grants from Bayer; compensation from Bayer for consultant services; compensation from Bayer for data and safety monitoring services; and grants from Bayer. Dr Swartz reports compensation from F. Hoffmann-La Roche for consultant services and stock holdings in FollowMD, Inc. Dr Katsanos reports employment by McMaster University and grants from the Heart and Stroke Foundation of Canada. The other authors report no conflicts.

Background: Atherosclerosis (AS) is the main cause of macrovascular disease. Previous studies have found sex differences in the prevalence of type 2 diabetes mellitus (T2DM) and its associated macrovascular disease outcomes. However, the relationship between sex differences, T2DM, and AS is not fully understood. This study attempts to explore possible associations between sex, treatment, and the burden of intracranial atherosclerosis (ICAS) in patients with T2DM who have experienced an acute ischemic cerebrovascular disease., Methods: We focused on patients with T2DM with acute ischemic stroke or transient ischemic attack due to intracranial atherosclerotic stenosis. ICAS was assessed by 3T cardiovascular magnetic resonance vascular wall imaging. Plaque counts of the total, proximal, and distal intracranial arteries were used to assess plaque burden. Patients with a history of T2DM and currently taking hypoglycemic drugs were defined as being treated. Poisson regression models or negative binomial regression models were used to analyze the interaction between sex and treatment in relation to plaque burden., Results: A total of 495 plaques were detected in 120 patients (75 male; mean age, 60.77 ± 11.01 years), including 311 proximal and 184 distal plaques. The intracranial culprit plaque was located proximal to the artery in both male (85.3%) and female (88.9%) patients. The adjusted total and proximal intracranial plaque burdens were 1.261 times (95% confidence interval [CI], 1.050-1.515, P=0.013) and 1.322 times (95%CI, 1.055-1.682, P=0.016) higher in male than in female patients. The risk ratio for proximal plaque burden in untreated male versus female patients was 0.966 (95%CI, 0.704-1.769). However, the proximal plaque risk ratio for treated male versus female patients was 1.530 (95%CI, 1.076-2.174). The interaction of sex and treatment significantly affected the proximal plaque burden., Conclusion: Male patients with T2DM and acute cerebrovascular disease have a significantly higher adjusted risk of total and proximal intracranial plaque burden compared to female patients. Female patients undergoing antidiabetic treatment have a significantly reduced risk of proximal plaque to males. Considering that culprit plaques tend to accumulate in the proximal arteries, understanding how to reduce the burden of proximal plaques may help reduce the risk of adverse cerebrovascular events., Competing Interests: Author KA was employed by the company Philips Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Yan, Li, Gao, Wang, Ai, Lei, Tang, Zhang and Zhang.)

Hypertension, a major modifiable risk factor for cardiovascular diseases, is linked to late-life neurocognitive disorders such as vascular dementia and Alzheimer's disease (AD). This study explores the associations between hypertension, intracranial atherosclerotic disease (ICAD), cerebral small vessel disease (cSVD), and Alzheimer's disease neuropathologic change (ADNC) in a large community-based autopsy study. This cross-sectional study used data from the Biobank for Aging Studies of the University of São Paulo Medical School. Sociodemographic and clinical information was gathered from a reliable next-of-kin informant. Neurofibrillary tangles, neuritic plaques, lacunar infarcts, hyaline arteriolosclerosis, and cerebral amyloid angiopathy were evaluated. Causal mediation analyses with natural effect models were performed to examine indirect associations of hypertension with cerebrovascular pathologies and ADNC through morphometric measurements of intracranial artery lumen obstruction. Hypertensive participants (n = 354) presented a higher rate of stenosed arteries (obstruction ≥ 50 %), critically stenosed arteries (obstruction ≥ 70 %), and more severe ICAD, shown by higher maximum and mean obstruction indexes compared to nonhypertensive participants (n = 166). These measurements of atherosclerosis were associated with neurofibrillary tangles and cSVD lesions. Hypertension was indirectly associated with hyaline arteriolosclerosis and lacunar infarcts through the pathway of ICAD. Presenting hypertension indirectly increased the odds of displaying hyaline arteriolosclerosis by 26 % (95 % CI: 1.08, 1.45, p = 0.002) and lacunar infarcts by 17 % (95 % CI: 1.01, 1.35, p = 0.029). Cognitive and APOE ε4 carrier status did not alter the investigated associations. In this community sample, hypertension was indirectly associated with cSVD through ICAD., Competing Interests: Competing interests and disclosures The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Intravascular enhancement sign (IVES) at three-dimensional T1-weighted turbo spin echo (3D T1W TSE) sequence may be a simple hemodynamic maker. This study aims to investigate the association between IVES and features of intracranial atherosclerotic stenosis (ICAS)., Method: Retrospective analysis of clinical and imaging data of patients who underwent high resolution-vessel wall imaging (HR-VWI) examination from May 2021 to May 2023. The number of IVES vessels and ICAS features at HR-VWI were extracted by two neuroradiologists. Paired comparisons and correlation analysis on these indicators were performed., Results: A total of 118 patients with ICAS in the first segment of the middle cerebral artery and accompanied by unilateral IVES were enrolled. Compared to the non-IVES side, a higher incidence of ischemic events and intraplaque hemorrhage (IPH), higher degree of vascular stenosis and enhancement, lower remodeling index, and lower signal intensity ratio (SIR) were found in subjects with IVES. In the ICAS with IVES, 79.66 % showed severe stenosis and occlusion; in the ICAS with severe stenosis and occlusion, 89.5 % showed IVES in the distal. A multivariable logistic regression model identified the vascular stenosis degree (OR = 1.922; 95 %CI [1.37-2.692]; P < 0.001), enhanced-degree (OR = 2.486; 95 %CI [1.315-4.698]; P = 0.005), position (OR = 2.869; 95 %CI [1.255-6.560]; P = 0.012), and SIR (OR = 0.032; 95 %CI [0.004-0.275]; P = 0.002) were independent association with the presence of IVES. The area under the curve was 0.911 for the use of IVES vessel quantities to identify severe stenosis and occlusion of arterial lumen., Conclusion: The number of IVES vessels was associated with the local features of ICAS, which may indicate severe stenosis and occlusion in the major branches of the proximal artery., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Tirofiban has emerged as an adjunct therapy for acute ischemic stroke (AIS) patients undergoing endovascular treatment (EVT). However, its benefits for AIS patients with intracranial atherosclerotic disease (ICAD) remains unclear. This meta-analysis evaluates its efficacy and safety in ICAD-related AIS patients undergoing EVT., Methods: We searched PubMed, Cochrane, and Embase up to September, 2024, for studies comparing tirofiban to placebo or no intervention in ICAD-related AIS. Primary outcome was modified Rankin Scale (mRS) 0-2 at 90 days. Secondary outcomes included 90-day mRS 0-1, mRS score at 90 days, successful reperfusion, 90-day mortality, postprocedural reocclusion, and symptomatic/non-symptomatic intracranial hemorrhage (ICH). Subgroup analyses evaluated tirofiban administration routes (intravenous, intra-arterial, or combined)., Results: Thirteen studies comprising 3,572 patients were included. Intravenous tirofiban significantly increased mRS 0-2 (RR 1.26 [95% CI 1.13; 1.42]; p < 0.0001, I²= 0%), mRS 0-1(RR 1.24 [95% CI 1.05; 1.45]; p = 0.0098, I² = 0%), reduced mRS score by 0.58 points ([95% CI -0.99; -0.17]; p = 0.006, I²= 66%) and decreased mortality (RR 0.68 [95% CI 0.57; 0.80]; p < 0.0001, I²= 8%) at 90 days compared to control. Tirofiban overall reduced postprocedural reocclusion relative to control (RR 0.36 [95% CI 0.14; 0.94]; p = 0.036, I²= 73%). No significant differences were observed in successful reperfusion or ICH., Conclusion: Intravenous tirofiban demonstrated an efficacy and safety profile, improving functional recovery and reducing mortality. Tirofiban overall reduced postprocedural reocclusion compared to control. No significant differences were found between groups in successful reperfusion or ICH. These findings support tirofiban as a safe and effective EVT adjunct., Systematic Review Protocol: PROSPERO (CRD42024606522)., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Intracranial atherosclerotic disease (ICAD) has been identified as a major cause of acute basilar artery occlusion (BAO).This study compared the characteristics and treatment outcomes in acute BAO patients with and without ICAD., Methods: A prospective cohort study was conducted at 115 People's Hospital, Ho Chi Minh city, Vietnam from August 2021 to June 2023. Patients with acute BAO who underwent endovascular treatment within 24 h from symptom onset were included (thrombectomy alone or bridging with intravenous alteplase). The baseline characteristics and outcomes were analyzed and compared between patients with and without ICAD. Good functional outcome was defined as mRS ≤3 at 90 days., Results: Among the 208 patients enrolled, 112 (53.8%) patients were categorized in the ICAD group, and 96 (46.2%) in the non-ICAD group. Occlusion in the proximal segment of the basilar artery was more common in patients with ICAD (55.4% vs. 21.9%, p < 0.001), whereas the distal segment was the most common location in the non-ICAD group (58.3% vs. 10.7%, p < 0.001). Patients in the ICAD group were more likely to undergo treatment in the late window, with a higher mean onset-to-treatment time compared to the non-ICAD group (11.6 vs. 9.5 h, p = 0.01). In multivariable logistic regression analysis, distal segment BAO was negatively associated with ICAD (aOR 0.13, 95% CI: 0.05-0.32, p < 0.001), while dyslipidemia showed a positive association (aOR 2.44, 95% CI: 1.15-5.17, p = 0.02). There was a higher rate for rescue stenting in the ICAD compared to non-ICAD group (15.2% vs. 0%, p < 0.001). However, no significant differences were found between the two groups in terms of good outcome (45.5% vs. 44.8%, p = 0.91), symptomatic hemorrhage rates (4.5% vs. 8.3%, p = 0.25), and mortality (42% vs. 50%, p = 0.25)., Conclusion: ICAD was a common etiology in patients with BAO. The location segment of BAO and dyslipidemia were associated with ICAD in patients with BAO. There was no difference in 90-day outcomes between BAO patients with and without ICAD undergoing endovascular therapy., (© 2024 S. Karger AG, Basel.)

Background and Purpose: Patients with stroke due to large artery atherosclerosis are at risk of early progression and recurrence. The efficacy and safety of argatroban in stroke patients who did not receive reperfusion therapy, and which patients may benefit from it, are uncertain., Methods: We conducted a cohort study to assess whether argatroban given within 72 hours of symptom onset, combined with antiplatelet therapy, improved neurological outcomes of patients with acute mild to moderate ischemic stroke in China. Patients were divided into the combined treatment group and the control group. Inverse probability of treatment weighting was used to balance baseline covariates. The primary efficacy outcome is the proportion of mRS score 0-2 at 90 days. The secondary efficacy outcomes included END proportion, change in NIHSS score from the baseline to day 7, recurrent cardiovascular events, and cardiovascular death. The safety outcomes were hemorrhagic transformation (HT) of infarction and organ hemorrhage at 7 days., Results: Compared with the control group, a higher proportion of mRS (0-2) at 90 days was found in patients in the combined treatment group (85.3% vs 74.5%, p=0.042). There was no significant difference in the safety outcomes between the two groups. Exploratory subgroup analysis showed positive associations with argatroban combined therapy and good prognosis in NIHSS score ≥5 and age ≥70 subgroups., Conclusions: Our study suggested that argatroban can improve neurological outcomes for mild to moderate LAA patients but not increase the risk of bleeding., Competing Interests: Declaration of competing interest All the authors declare that they have no competing financial interests in this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cerebral vasospasm is a well-known complication after aneurysmal subarachnoid hemorrhage (aSAH) and occurs more commonly in younger patients. We hypothesized that intracranial atherosclerosis, which is seen predominantly in older patients, affects vasospasm risk. We sought to determine association between intracranial atherosclerosis burden with vasospasm and outcomes in aSAH., Methods: We retrospectively reviewed a cohort of consecutive patients with aSAH admitted to a Comprehensive Stroke Center between 2016 and 2023. Intracranial atherosclerosis burden was quantified by using modified Woodcock (MW) score on CT angiograms. Vasospasm was defined based on transcranial Doppler (TCD) criteria. Poor outcome was defined as 3-month modified Rankin Scale 3-6., Results: We reviewed 392 patients and included 302 (mean age 56.8 years [SD 13.3], 65 % female and 70 % white) in the final analysis. MW scores were measured with excellent intra-rater and inter-rater reliability (Cohen's kappa coefficient 0.9 and 0.83 respectively) ranging from 0 to 3 (mean 0.59, SD 0.83) with higher scores in older patients (beta coefficient 0.019, 95 % CI 0.009-0.028; p < 0.001). Higher MW calcification score was associated with lower risk of vasospasm (OR 0.52 per point increase, 95 % CI 0.36-0.78; p = 0.001). There was an inverse correlation between MW scores and severity of vasospasm (beta coefficient -0.29, 95 % CI -0.48, -0.1; p = 0.003). However, MW score was not independently associated with poor functional outcome (p = 0.62)., Conclusions: Intracranial atherosclerosis is a potential mechanism for lower TCD-based vasospasm in older patients with aSAH; however, it may not impact functional outcomes. Larger prospective studies are needed to confirm our findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Intracranial atherosclerotic disease (ICAD) large vessel occlusion (LVO) is responsible for up to 30% of LVO. In this study, we aimed to determine the likelihood of favorable functional outcomes (modified Rankin Scale 0-3) in acute ICAD-LVO basilar occlusion compared with embolic basilar occlusion., Methods: This is an analysis of the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy Registry in which patients with acute basilar artery occlusions from 8 comprehensive stroke centers were included from 2015 to 2021. Patients were dichotomized into with (ICAD-LVO) or without underlying ICAD (embolic). Descriptive statistics for each group and multivariate logistic analysis were performed on the primary outcome., Results: Three hundred forty-six patients were included. There were 215 patients with embolic (62%) and 131 patients with ICAD-LVO (38%). Baseline demographics were equivalent between the 2 groups except for sex (male 47% vs 67%; P < .001), history of stroke (12% vs 25%; P = .002), and atrial fibrillation (31% vs 17%; P = .003). At 90 days, patients in the ICAD-LVO cohort were less likely to achieve favorable functional outcomes (odds ratio [OR] 0.41, 95% CI 0.22-0.72; P = .003) after adjusting for potentially confounding factors. In addition, ICAD-LVO strokes were less likely to achieve thrombolysis in cerebral infarction ≥2b (OR 0.29, 95% CI 0.14-0.57; P < .001). ICAD-LVO lesions were more likely to require stent placement (OR 14.94, 95% CI 4.91-45.49; P < .001). Subgroup analysis demonstrated favorable functional outcomes in patients who underwent stenting and angioplasty compared with failed recanalization cohort (OR 4.96, 95% CI 1.68-14.64; P < .004)., Conclusion: Patients with acute basilar ICAD-LVO have higher morbidity and mortality compared with patients with embolic source. Lower rates of successful recanalization in the ICAD-LVO cohort support this finding. Our subgroup analysis demonstrates that stenting should be considered in patients with recanalization failure. Rates of symptomatic intracranial hemorrhage were similar between the ICAD-LVO and embolic cohorts., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Object: The treatment results of combination of arterial injection of tirofiban with endovascular therapy (EVT) for acute large vessel occlusion (LVO) stroke due to intracranial atherosclerotic disease (ICAD) were inconsistent. This meta-analysis aims to assess the safety and efficacy of ICAD-LVO treatment by intra-arterial injection of tirofiban combined with EVT., Methods: Relevant studies were identified through a systematic literature search in Pubmed, EMBASE, Web of Science and Cochrane Library databases, covering articles published from January 2010 to July 2024. The efficacy outcomes assessed in the meta-analysis included favorable functional outcome and recanalization rates. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH)., Results: The meta-analysis consisted of data from 11 studies, which included 1 randomised controlled trial (RCT), 5 prospective cohort studies, and 5 retrospective cohort studies, encompassing a total of 2869 patients. The findings showed that tirofiban+EVT for ICAD-LVO was associated with significant improvements in favorable functional outcomes (RR, 1.12; 95 %CI, 1.04-1.21; P=0.005) and reductions in mortality rates (RR, 0.72; 95 %CI, 0.62-0.83; P<0.0001), despite no significant differences in the incidence of sICH (RR, 0.75; 95 % CI, 0.55-1.02; P=0.07) and recanalization rates (RR, 1.02; 95 % CI, 0.99-1.05; P=0.15). Subgroup analysis showed that the application of tirofiban significantly increased favorable functional outcomes in patients with anterior circulation stroke (RR, 1.23; 95 % CI, 1.06-1.42; P=0.005), but there was no significant difference in posterior circulation stroke (RR, 1.08; 95 % CI, 0.83-1.41; P=0.55). In addition, the use of tirofiban in patients with posterior circulation stroke might reduce the incidence of sICH (RR, 0.50; 95 % CI, 0.26-0.96; P=0.04)., Conclusion: Tirofiban combined with EVT may be an effective treatment strategy for the treatment of ICAD-LVO, but only for patients with anterior circulation and remains unclear for patients with posterior circulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting., Materials and Methods: We conducted a historical, multicenter registry study at 51 centers that enrolled patients with AT-LVO. We divided the patients into 3 groups based on the endovascular therapy technique: mechanical thrombectomy alone, percutaneous transluminal angioplasty (PTA), and stent deployment. Mechanical thrombectomy alone was classified into the mechanical thrombectomy-only group; PTA and mechanical thrombectomy-PTA, into the PTA group; and mechanical thrombectomy-stent deployment, mechanical thrombectomy-PTA-stent deployment, PTA-stent deployment, and stent deployment-only into the stent group. The primary outcome was incidence of reocclusion of the treated vessels within 90 days of endovascular therapy completion., Results: We enrolled 770 patients and analyzed 509 patients. The rates in the mechanical thrombectomy-only, PTA, and stent deployment groups were 40.7%, 44.4%, and 14.9%, respectively. Incidence rate of residual stenosis >70% of final angiography was significantly higher in the mechanical thrombectomy-only group than in the PTA and stent deployment groups (mechanical thrombectomy-only versus PTA versus stent deployment: 34.5% versus 26.3% versus 13.2%, P = .002). Reocclusion rate was significantly lower in the PTA group than in the mechanical thrombectomy-only group (adjusted hazard ratio, 0.48; 95% CI, 0.29-0.80). Of the patients, 83.5% experienced reocclusion within 10 days after endovascular therapy. Alarmingly, a substantial subset (approximately 62.0%) of patients experienced reocclusion within 2 days of endovascular therapy. Incidence of mRS scores of 0-2 ninety days after endovascular therapy was not significantly different among the 3 groups. Incidences of symptomatic intracranial hemorrhage, any other intracranial hemorrhage, and death were not significantly different., Conclusions: Incidence rate of reocclusion was significantly lower in the PTA group than in the mechanical thrombectomy-only group. We found no meaningful difference in reocclusion rates between the stent deployment and mechanical thrombectomy-only groups. In Japan, glycoprotein IIb/IIIa inhibitors are not reimbursed. Therefore, PTA might be the preferred choice for AT-LVOs due to the higher reocclusion risk with mechanical thrombectomy-only. Reocclusion was likely to occur within 10 days, particularly within 2 days post-endovascular therapy., (© 2024 by American Journal of Neuroradiology.)

Rationale: The effect of the head position as a non-pharmacological therapy on acute ischaemic stroke (AIS) remains inconclusive. Our recent Head dOwn-Position for acutE moderate ischaemic Stroke with large artery atherosclerosis (HOPES 2) suggested the safety, feasibility and potential benefit of the head-down position (HDP) in AIS., Aim: To investigate the benefit of HDP in acute moderate ischaemic stroke patients with large artery atherosclerosis (LAA)., Sample Size Estimates: Based on a two-sided 0.05 level of significance, 600 patients are expected to yield the superiority hypothesis with 80% power, stratified by age, sex, history of diabetes, baseline systolic blood pressure, location of index vessel, National Institutes of Health Stroke Scale Score at randomisation, onset to randomisation time, progression to moderate neurological deficit due to early neurological deterioration and degree of responsible vessel stenosis., Design: Head dOwn-Position for acutE moderate ischaemic Stroke with large artery atherosclerosis(HOPES 3) is a prospective, randomised, open-label, blinded endpoint and multicentre study. Eligible patients who had an ischaemic stroke will be randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg plus standard medical care in compliance with national guidelines, or control group only receiving standard medical care in compliance with national guidelines., Outcome: The primary outcome is favourable functional outcome, defined as modified Rankin Scale 0-2 at 90 days. Safety outcomes are HDP-related adverse events. All outcomes will have blinded assessment and will be analysed on the intention-to-treat basis., Conclusions: The results of HOPES 3 will provide evidence for the effect of HDP in acute moderate ischaemic stroke patients with LAA within 24 hours of onset or in patients with progression from mild neurological deficit within 24 hours., Trial Registration Number: NCT06010641., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare treatment outcomes between patients who received a front-line stent-retriever thrombectomy (SRT) or first stenting without retrieval (FRESH) for treating proximal M1 occlusion due to underlying intracranial atherosclerotic disease (ICAD)., Methods: We retrospectively reviewed consecutive acute ischemic stroke (AIS) patients with intracranial large vessel occlusion (LVO) in the anterior circulation who underwent endovascular treatment (EVT) between January 2017 and August 2021 at Yeungnam University Medical Center. LVO in the anterior circulation was classified according to etiology as follows: Embolic group and ICAD group. Occlusion of the proximal M1 due to ICAD were enrolled in this study. The ICAD group was divided into SRT and FRESH groups according to the treatment method., Results: Among the 72 patients in the ICAD group, 55 patients had occlusion of the M1, and 27 had occlusion of the proximal M1 (27/55, 49.1 %). Among the 27 patients, 11 (40.7 %) underwent SRT and 16 (59.3 %) underwent FRESH. The puncture-to-recanalization time was significantly shorter in the FRESH group (28 min vs. 52 min, p = 0.023). Symptomatic ICH tended to occur more frequently in the SRT group than in the FRESH group (27.3 % vs. 0.0 %, p=0.056). There was a nonsignificant trend towards a good functional outcome in the FRESH group compared to the SRT group (81.3 % vs. 45.5 %, p=0.097)., Conclusion: In the FRESH group, the puncture-to-recanalization time was significantly shorter, symptomatic ICH tended to occur less frequently, and good functional outcomes were more common., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To compare the features detected by high resolution magnetic resonance vessel wall imaging (HR-VWI) between posterior circulation atherosclerosis and intramural hematoma (IMH)-type dissection, and to identify indicators related to cerebral ischemic events., Materials and Methods: Clinical and HR-VWI data of 55 patients with posterior circulation IMH-type dissection and 132 patients with posterior circulation atherosclerosis collected between October 2017 and October 2023 were analyzed retrospectively. Two radiologists independently extracted the imaging features. Multivariable logistic regression was used to identify factors independently associated with stroke., Results: Compared with patients with atherosclerosis, those with IMH-type dissection were younger, with a lower prevalence of diabetes and hypertriglyceridemia, lower hypertension grade, enhanced grade, remodeling index (RI), vertebrobasilar artery/brainstem ratio, and prevalence of nonsmooth surface, and higher prevalence of intraluminal thrombus (ILT), lumen (LA), wall area (WA), and total vessel area (TVA). In patients with stroke, those with IMH-type dissection were younger, with a lower prevalence of diabetes, and degree of hypertension, and higher RI, WA, TVA, and the prevalence of ILT. Multivariable logistic regression showed that RI (odds ratio [OR], 0.37; 95% CI, 0.17-0.77) and normalized wall index (NWI) (OR, 39.02; 95% CI, 2.19-695.35) were risk factors for stroke in patients with dissection, and LA (OR, 1.52; 95% CI, 1.12-2.06) and NWI (OR, 60.84; 95% CI 3.70-998.06) were risk factors for atherosclerotic stroke., Conclusion: Patients with posterior circulation IMH-type dissection had greater potential for positive remodeling than those with atherosclerosis. The arterial remodeling capacity was closely related to stroke risk., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: The optimal treatment for patients with acute large vessel occlusion (LVO) secondary to intracranial atherosclerotic disease (ICAD) is unclear. Adjunctive rescue therapy with balloon angioplasty or stenting may be necessary to ensure vessel patency. We aimed to compare the safety and clinical outcomes of adjunctive rescue therapy vs lone thrombectomy for ICAD-related-LVO., Methods: A retrospective propensity score matching analysis was performed in acute stroke patients who had endovascular thrombectomy between 2008 and 2021. We included patients with acute ICAD-related-LVO. The location of ICAD and exposure to thrombolysis were used to generate propensity score matching to estimate the likelihood of treatment by adjunctive rescue therapy. The primary clinical outcome (90-day modified rankin scale 0-2) and safety outcomes (symptomatic intracerebral hemorrhage) were assessed between the two groups., Results: One-hundred and forty-four patients were included. The median (IQR) age was 68(59-76) and 52(36 %) were females. The baseline NIHSS was 12.5(8-19). Sixty-seven (47 %) patients had ICAD in M1 or M2 segments. Forty-six patients (67 %) had lone thrombectomy and twenty-one (28 %) had adjunctive rescue therapy. Propensity score matching did not demonstrate significant differences in 90-day modified Rankin Score 0-2 between lone thrombectomy (38.8 %) and adjunctive rescue therapy (39.3 %) (p = 0.3). Lone thrombectomy, compared to adjunctive rescue therapy, did not result in significantly more symptomatic intracerebral hemorrhages (2.8 % vs 8.3 %, p = 0.6), nor progressive occlusion (17 % vs 19 %, p = 0.8)., Conclusion: We did not find significant differences in clinical outcomes and safety between lone thrombectomy and adjunctive rescue therapy. Randomized controlled studies are required to resolve the equipoise in treatment of ICAD-related-LVO., Competing Interests: Declaration of competing interest All authors disclose no real or potential conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Aim: We aimed to investigate the impact of metabolic syndrome (MetS) on the outcomes of stroke patients with large-artery atherosclerosis who underwent reperfusion therapy., Methods: A retrospective analysis was carried out on patients receiving reperfusion therapy for atherothrombotic stroke between January 2019 and May 2021. MetS was diagnosed according to the AHA/NHLBI criteria. The primary outcome was the composite outcome of disability (modified Rankin Scale [mRS] score 3-5), death or stroke recurrence within 3 months of stroke onset. Secondary outcomes included disability and death within 3 months as well as hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 hours after reperfusion treatment. The independent association of MetS with the above outcomes and the highly correlated components of MetS was examined using binary logistic regression analysis., Results: A total of 174 patients were enrolled. MetS patients had a higher proportion of the composite outcome (p = 0.012), disability (p = 0.029) and HT (p = 0.049) than those without MetS, except for death (p = 0.375) and sICH (p = 0.306). Following adjustments, MetS remained independently associated with the composite outcome (adjusted OR, 3.011 [95 %CI 1.372-6.604]; p = 0.006) and disability (adjusted OR, 2.727 [95 %CI 1.220-6.098]; p = 0.015), but not HT (adjusted OR, 1.872 [95 %CI 0.854-4.104]; p = 0.117). Hypertriglyceridemia was remarkedly associated with the composite outcome (adjusted OR, 9.746 [95 % CI 2.402-39.536]; p = 0.001) and disability (adjusted OR, 6.966 [95 % CI 1.889-25.692]; p = 0.004)., Conclusion: MetS is independently associated with an increased risk of composite outcome and disability in patients with large-artery atherosclerosis stroke receiving reperfusion therapy, and hypertriglyceridemia is the main component that drives the effect of MetS on outcomes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mild asymptomatic intracranial atherosclerotic stenosis (aICAS) is common in Chinese patients with hypertension. However, there are no data on its prognostic value in this population. The aim of the present study was to clarify the prevalence and associated cardiovascular risk factors of mild aICAS and determine its prognostic value for overall and cardiovascular mortality in patients with hypertension., Methods: In total, 1,813 participants were evaluated for aICAS using computed tomographic angiography. The predictive effect of mild to severe aICAS on all-cause and cardiovascular mortality was evaluated using Kaplan-Meier survival curves and Cox regression analyses., Results: The prevalence rate of mild aICAS was 35.7%. Poorly controlled hypertension, in combination with diabetes and dyslipidemia, was associated with aICAS. Patients with aICAS had an independently significant increase in the risk of all-cause and cardiovascular death, with adjusted hazard ratios (HRs) for mild to severe stenosis ranging from 1.56 to 3.30 for all-cause death and from 2.48 to 6.38 for cardiovascular death. Among the patients with mild aICAS, only those with more than two stenoses had increased mortality after adjustment, with an HR of 2.44 (95% CI: 1.42-4.18) for total death and 4.49 (95% CI: 1.82-11.05) for cardiovascular death., Conclusions: A significant association between mild aICAS and mortality in stroke-free patients with hypertension was revealed. The results indicate that mild aICAS might be an imaging marker for cerebrovascular lesions in patients with hypertension and poor control of blood pressure and lipids in this population requires further research., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Relatively little is known about the plaque characteristics of border-zone infarcts and how they differ between cortical border-zone (CBZ) and internal border-zone (IBZ) infarcts., Methods: We conducted a retrospective observational cohort study of patients with intracranial atherosclerotic disease who underwent high-resolution magnetic resonance imaging (HR-MRI) examination. Individuals with border-zone infarcts in the middle cerebral artery (MCA) territory, detected by diffusion-weighted imaging, were enrolled. Plaque morphological and compositional parameters of both IBZ and CBZ groups were compared. Independent predictors were identified using a binary logistic regression model, and the sensitivity and specificity of the model were assessed using a receiver operating characteristic curve. Kaplan-Meier survival analysis further explored differences in stroke recurrence between BZ patients with mono or dual antiplatelet therapy., Results: We reviewed 101 symptomatic patients with border-zone infarcts (BZ) within the MCA territory in the study. Out of the patients meeting the imaging eligibility criteria, we detected 34 cases with isolated IBZ, 23 cases with isolated CBZ, and six cases with both IBZ and CBZ infarcts. Those with IBZ infarcts had a higher plaque burden than those without (p < 0.001), and those with CBZ infarcts exhibited a complicated plaque less frequently than those without (37.9% vs 67.6%, p = 0.018). In those with isolated IBZ or CBZ infarcts, plaque burden was independently associated with isolated IBZ infarcts (odd ratio=1.08; 95% CI, 1.02-1.15; p = 0.023). During the median follow-up period of 37 (27, 50) months, 13.8% of patients receiving early dual antiplatelet treatment and 30.4% of those on single antiplatelet therapy experienced stroke recurrence (p = 0.182)., Conclusion: Intracranial atherosclerotic plaque morphology and composition differ between patients with IBZ and those with CBZ infarcts. Higher plaque burden is more associated with IBZ infarcts., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial., Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS., Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023)., Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control., Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment., Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients., Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice., Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Background and Purpose: Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking., Methods: Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups., Results: A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604)., Conclusions: Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Acute basilar artery occlusion (ABAO) accounts for 1% of all ischemic stroke cases, but has a high rate of severe complications and mortality (75-91%). Intracranial atherosclerosis is an significant cause of ischemic stroke. Revascularization using stents has shown good efficacy. However, intra-stent thrombosis and in-stent restenosis (ISR) are significant complications following stent placement. Drug-coated balloons (DCB), coated with the anti-proliferative drug paclitaxel (an inhibitor of endothelial proliferation), can prevent in-stent restenosis. Successful use of DCB dilation in the coronary and lower extremity vasculature has been reported. In our case, a 68-year-old Chinese male with ABAO was successfully revascularized by DCB dilation and showed dramatic improvement in stroke symptoms. This report may inform future treatment of patients with ABAO.

Objectives: To explore the value of high-resolution MR vessel wall imaging (HR-VWI) based plaque characteristics combined with cardiovascular health (CVH) metrics in the risk evaluation of ischemic stroke attributed to middle cerebral artery (MCA) atherosclerotic stenosis., Methods: Retrospective analysis of 209 participants with middle cerebral atherosclerosis, 146 patients with high signal in the MCA area on DWI were included in the symptomatic group, and 63 patients were included in the asymptomatic group. The degree of stenosis, enhancement ratio, plaque burden, remodeling index, and intraplaque hemorrhage were measured and compared between groups. Seven CVH metrics and other clinical data were obtained. The association between these factors and ischemic stroke was investigated by univariate and multivariate analysis., Results: The degree of stenosis [OR, 1.036 (95 % CI, 1.014-1.058); P = 0.001], plaque burden [OR, 0.958 (95 % CI, 0.928-0.989); P = 0.009], intraplaque hemorrhage [OR, 3.530 (95 % CI, 1.233-10.110); P = 0.019], physical activity [OR, 4.321 (95 % CI, 1.526-12.231); P = 0.006], and diet [OR, 8.986 (95 % CI, 2.747-29.401); P < 0.001] were the independent characteristics associated with the occurrence of ischemic stroke. ROC curve showed that the combination of plaque characteristics, diet, and physical activity achieved the highest AUC of 0.828 (95 % CI 0.770-0.877; P < 0.001), with sensitivity and specificity being 86.30 % and 66.67 %, respectively., Conclusion: Plaque characteristics combined with CVH metrics may identify high-risk populations for ischemic stroke and offer novel insights into risk evaluation and stratification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The diagnostic workup of stroke doesn't identify an underlying cause in two-fifths of ischemic strokes. Intracranial arteriosclerosis is acknowledged as a cause of stroke in Asian and Black populations, but is underappreciated as such in whites. We explored the burden of Intracranial Artery Calcification (IAC), a marker of intracranial arteriosclerosis, as a potential cause of stroke among white patients with recent ischemic stroke or TIA., Patients and Methods: Between December 2005 and October 2010, 943 patients (mean age 63.8 (SD ± 14.0) years, 47.9% female) were recruited, of whom 561 had ischemic stroke and 382 a TIA. CT-angiography was conducted according to stroke analysis protocols. The burden of IAC was quantified on these images, whereafter we assessed the presence of IAC per TOAST etiology underlying the stroke and assessed associations between IAC burden, symptom severity, and short-term functional outcome., Results: IAC was present in 62.4% of patients. Furthermore, IAC was seen in 84.8% of atherosclerotic strokes, and also in the majority of strokes with an undetermined etiology (58.5%). Additionally, patients with larger IAC burden presented with heavier symptoms (adjusted OR 1.56 (95% CI [1.06-2.29]), but there was no difference in short-term functional outcome (1.14 [0.80-1.61])., Conclusion: IAC is seen in the majority of white ischemic stroke patients, aligning with findings from patient studies in other ethnicities. Furthermore, over half of patients with a stroke of undetermined etiology presented with IAC. Assessing IAC burden may help identify the cause in ischemic stroke of undetermined etiology, and could offer important prognostic information., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Expanding on previous investigations, this study aims to elucidate the role of lipid metabolism disorders in the development of intracranial atherosclerotic stenosis (ICAS) and the determination of stroke risk. The primary objective is to explore the connections between lipid parameters and acute ischemic stroke (AIS), while also examining the potential mediating influence of fasting glucose levels., Methods: Retrospectively, we collected data from symptomatic ICAS patients at the First Affiliated Hospital of Soochow University, including their baseline information such as medical histories and admission blood biochemical parameters. Stenotic conditions were evaluated using magnetic resonance imaging, computed tomography angiography, or digital subtraction angiography. The associations between lipid parameters and AIS risks were investigated via multivariate logistic regression analysis., Results: A total of 1103 patients with symptomatic ICAS were recruited, among whom 441 (40.0%) suffered new ischemic events during hospitalization. After adjusting for confounding factors, the RCS curves exhibited a dose-response relationship between the atherogenic index of plasma (AIP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and AIS. Further multivariate analysis revealed significant associations between these parameters and AIS. Furthermore, mediation analysis indicated that fasting blood glucose (FBG) acted as a mediator in the association between lipid parameters (AIP, TC, and TG) and AIS., Conclusion: Higher lipid parameters in ICAS patients, particularly AIP, TC, and TG, were associated with an increased AIS risk. Additionally, FBG may mediate stroke risk in ICAS patients, highlighting the need for further exploration of underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Zhu, Zheng, Ni, Li and Yang.)

Background: This study investigated the long-term clinical and angiographic outcomes of encephaloduroarteriosynangiosis treatment for symptomatic intracranial atherosclerotic arterial steno-occlusive disease to further evaluate the potential therapeutic role of encephaloduroarteriosynangiosis in this population., Methods and Results: A total of 152 adult patients with symptomatic intracranial atherosclerotic arterial steno-occlusive disease who were treated with encephaloduroarteriosynangiosis and intensive medical management across 3 tertiary centers in China between January 2011 and September 2019 were retrospectively included. The primary outcomes were defined as postoperative cerebrovascular events, including ischemic and hemorrhagic stroke. The postoperative neovascularization was analyzed qualitatively and quantitatively by using angiography. Clinical, radiological, and long-term follow-up data were analyzed using Cox regression, logistic regression, and linear regression analyses. Primary outcome rates were 3.2% (5/152) within 30 days, 6.6% (10/152) within 2 years, 9.2% (14/152) within 5 years, and 11.1% (17/152) during a median 9.13 years follow-up. Initial infarction symptoms were positively associated with recurrent ischemic stroke. Additionally, posterior circulation involvement and coexisting cardiac disease indicated poorer neurological status, whereas encephaloduroarteriosynangiosis neovascularization efficacy was negatively associated with older age and vascular risk factors but positively associated with posterior circulation involvement., Conclusions: Encephaloduroarteriosynangiosis plus intensive medical management appears efficacious and safe for symptomatic intracranial atherosclerotic arterial steno-occlusive disease, with low perioperative risk and favorable long-term results. Further prospective trials are needed to verify its efficacy and determine the optimal patient selection criteria.

Background: The influence of burden of atherosclerosis in the brain supplying arteries on mortality in patients with acute ischemic stroke or transient ischemic attack is poorly known. We assessed whether total burden of atherosclerosis within cervicocerebral arteries is associated with long-term mortality., Methods and Results: A total of 406 patients (median age, 71.8 years; 57.9% male) with acute ischemic stroke or transient ischemic attack were included and their cervicocerebral arteries imaged with computed tomography angiography. The presence of atherosclerotic findings was scored for 25 artery segments and points were summed as a Cervicocerebral Atherosclerosis Burden (CAB) score, analyzed as quartiles. Data on all-cause mortality came from Statistics Finland. After a median follow-up of 7.3 years, 147 (33.5%) patients had died. Compared with surviving patients, those who died had a higher median CAB score (5, interquartile range 2-10 versus 11, 7-16; P <0.001). Cumulative mortality increased from 8.9% (95% CI, 7.0-10.8) in the lowest to 61.4% (95% CI, 55.4-67.4) in the highest quartile of CAB score. Adjusted for demographics, cardiovascular risk factors, secondary preventive medication, and admission National Institute of Health Stroke Scale score, every CAB score point increased probability of death by 3%. Analyzed in quartiles, the highest CAB quartile was associated with a 2.5-fold likelihood of all-cause mortality., Conclusions: The main findings of our study were the increasing mortality with the total burden of computed tomography angiography-defined atherosclerosis in the brain supplying arteries after ischemic stroke or transient ischemic attack and that the CAB score-integrating this pathology-independently increased all-cause mortality.

Purpose: To investigate the association between the intravascular enhancement sign (IVES) and intraluminal thrombus (ILT) detected by high-resolution magnetic resonance vessel wall imaging (HR-VWI) in patients with middle cerebral artery (MCA) atherosclerosis., Method: The data of patients who underwent HR-VWI between May 2021 and May 2023, including clinical information, the number of IVES vessels, stenosis degree, ILT, plaque features on 3D T1-weighted turbo spin echo sequences, and signal intensity ratio (SIR) on 3D time-of-flight magnetic resonance angiography, were retrospectively analyzed. Correlation and logistic regression analyses were performed., Results: A total of 194 MCA plaques were identified in 132 patients (103 [53 %] on the left). Atherosclerosis with, relative to without, ILT was associated with a higher incidence of ischemic events, higher plaque enhancement and stenosis degrees, more vessels with IVES, and lower remodeling ratio, lumen area, wall area, total vessel area, and SIR. Multivariate logistic regression analysis showed significant and independent associations of the number of IVES vessels (OR = 1.089; 95 % CI [1.013-1.170]; P = 0.020) and SIR (OR = 0.007; 95 % CI [0.0004-0.124]; P < 0.001) with ILT. The number of vessels with the IVES (AUC = 0.81, 95 % CI [0.75-0.87]; P < 0.001) and SIR (AUC = 0.88, 95 % CI [0.82-0.94]; P < 0.001) sufficiently diagnosed ILT, and the AUC of the combination of the IVES and SIR was 0.89 (95 % CI [0.84-0.94]; P < 0.001)., Conclusion: The number of IVES vessels and SIR are independent risk factors for ILT. They may provide new monitoring targets for stroke prevention in patients with atherosclerotic stenosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment., Methods: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018. The major exposures were translesional systolic blood pressure (SBP) drop and poststenotic mean arterial pressure (MAP), and the major study outcomes were cortex-involved infarcts and borderzone-involved infarcts, respectively. Multivariate logistic regression models and the bootstrap resampling method were utilized, adjusting for demographics and medical histories., Results: In all, 184 (54.3%) cortex-involved infarcts and 70 (20.6%) borderzone-involved infarcts were identified. In multivariate logistic model, the upper quartile of SBP drop correlated with increased cortex-involved infarcts (odds ratio, 1.92 [95% CI, 1.03-3.57]; bootstrap analysis odds ratio, 2.07 [95% CI, 1.09-3.93]), and the lower quartile of poststenotic MAP may correlate with increased borderzone-involved infarcts (odds ratio, 2.07 [95% CI, 0.95-4.51]; bootstrap analysis odds ratio, 2.38 [95% CI, 1.04-5.45]). Restricted cubic spline analysis revealed a consistent upward trajectory of the relationship between translesional SBP drop and cortex-involved infarcts, while a downward trajectory between poststenotic MAP and borderzone-involved infarcts. SBP drop correlated with poststenotic MAP negatively (r s =-0.765; P <0.001). In generating hemodynamic impairment, simulating blood pressure modifications suggested that ensuring adequate blood pressure to maintain sufficient poststenotic MAP appears preferable to the reverse approach, due to the prolonged plateau period in the association between the translesional SBP drop and cortex-involved infarcts and the relatively short plateau period characterizing the correlation between poststenotic MAP and borderzone-involved infarcts., Conclusions: This research elucidates the role of hemodynamic impairment of blood pressure in symptomatic intracranial atherosclerotic stenosis-related stroke mechanisms, underscoring the necessity to conduct hemodynamic assessments when managing blood pressure in symptomatic intracranial atherosclerotic stenosis., Competing Interests: Disclosures None.

Background: High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) is a promising technique for identifying intracranial vulnerable plaques beyond lumen narrowing. However, the association between HRMR-VWI characteristics and recurrent stroke remains uncertain., Aims: This study aimed to investigate the association between HRMR-VWI characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS)., Methods: This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (>50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multiparametric magnetic resonance imaging (MRI) including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HRMR-VWI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HRMR-VWI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis., Results: Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12 month ipsilateral recurrence incidence was 4.1% (95% confidence interval (CI): 1.6-6.6%). Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs 6.5%) and eccentric plaque (90.0% vs 48.2%), and lower occurrence of occlusive thrombus (10.0% vs 23.7%). Plaque length (5.69 ± 2.21 mm vs 6.67 ± 4.16 mm), plaque burden (78.40 ± 7.37% vs 78.22 ± 8.32%), degree of stenosis (60.25 ± 18.95% vs 67.50% ± 22.09%) and remodeling index (1.07 ± 0.27 vs 1.03 ± 0.35) on HRMR-VWI did not differ between patients with and without recurrent ipsilateral stroke. In the multivariable Cox regression analysis, IPH (hazard ratio: 6.64, 95% CI: 1.23-35.8, p  = 0.028) was significantly associated with recurrent ipsilateral stroke after adjustment.Conclusions:Our results suggest intraplaque hemorrhage (IPH) is significantly associated with recurrent ipsilateral stroke and has potential value in the selection of patients for aggressive treatment strategies., Data Access Statement: Data from this study are available and can be accessed upon request., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Artery-to-artery embolism (AAE) is a common stroke mechanism in intracranial atherosclerotic disease (ICAD), associated with a considerable risk of recurrent stroke. We aimed to investigate cerebral hemodynamic features associated with AAE in symptomatic ICAD. Patients with anterior-circulation, symptomatic ICAD confirmed in CT angiography (CTA) were recruited. We classified probable stroke mechanisms as isolated parent artery atherosclerosis occluding penetrating artery, AAE, hypoperfusion, and mixed mechanisms, largely based on infarct topography. CTA-based computational fluid dynamics (CFD) models were built to simulate blood flow across culprit ICAD lesions. Translesional pressure ratio (PR = Pressure post-stenotic /Pressure pre-stenotic ) and wall shear stress ratio (WSSR = WSS stenotic-throat /WSS pre-stenotic ) were calculated, to reflect the relative, translesional changes of the two hemodynamic metrics. Low PR (PR ≤ median) and high WSSR (WSSR ≥ 4th quartile) respectively indicated large translesional pressure and elevated WSS upon the lesion. Among 99 symptomatic ICAD patients, 44 had AAE as a probable stroke mechanism, 13 with AAE alone and 31 with coexisting hypoperfusion. High WSSR was independently associated with AAE (adjusted OR = 3.90; P = 0.022) in multivariate logistic regression. There was significant WSSR-PR interaction on the presence of AAE (P for interaction = 0.013): high WSSR was more likely to associate with AAE in those with low PR (P = 0.075), but not in those with normal PR (P = 0.959). Excessively elevated WSS in ICAD might increase the risk of AAE. Such association was more prominent in those with large translesional pressure gradient. Hypoperfusion, commonly coexisting with AAE, might be a therapeutic indicator for secondary stroke prevention in symptomatic ICAD with AAE., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS., (© 2024. The Author(s).)

Background: Endovascular therapy (EVT) reduces functional disability in patients with acute large vessel occlusion (LVO). However, the early neurological change after EVT may be limited in patients with intracranial atherosclerotic disease (ICAD)., Methods: We analyzed the Japanese Registry of NeuroEndovascular Therapy (JR-NET) 4 which was a retrospective, nationwide, multicenter registry of patients with LVO between 2015 and 2019. We compared the early neurological change, efficacy and safety of EVT for acute LVO in ICAD and other etiologies. The primary outcome was NIHSS improvement ≥10 points, and secondary outcome were NIHSS worsening ≥4 points 7 days after EVT, effective reperfusion rate, 30-day functional outcomes, and safety outcomes., Results: Among the 6710 enrolled patients, 610 (9.1%) had ICAD. The ICAD group was younger (mean 72.0 vs. 75.8 years) and predominantly male (63.4% vs. 56.0%), had lower NIHSS scores before EVT (median 16 vs. 18), and underwent percutaneous transluminal angioplasty and stenting more frequently (43.0% vs. 4.4%, 12.3% vs. 4.4%). In the ICAD group, NIHSS improvement was significantly lower (adjusted odds ratio (aOR) [95% confidence interval (95%CI)] 0.52 [0.41-0.65]), NIHSS worsening was significantly higher (aOR [95%CI] 1.76 [1.31-2.34]), and effective reperfusion was significantly lower (aOR [95%CI] 0.47 [0.36-0.60]). Fewer patients with ICAD had modified Rankin scale 0-2 at 30 days (aOR [95%CI] 0.60 [0.47-0.77]). The risk of acute reocclusion was more prominent in the ICAD group (aOR [95%CI] 4.03 [1.98-8.21])., Conclusions: Improvement in neurological severity after EVT was lower in patients with LVO and ICAD., Competing Interests: Declaration of competing interest Dr. Uchida reports lecturer's fees from Daiichi Sankyo, Bristol-Myers Squibb, Stryker, and Medtronic. Dr. Yamagami discloses research grants from Bristol-Myers Squibb; lecturer's fees from Daiichi Sankyo, Stryker, Medtronic, Johnson & Johnson, and Medico's Hirata. Dr. Sakai N reports a research grant from Biomedical Solutions, Medtronic, Terumo and TG Medical; lecturer's fees from Asahi-Intec, Biomedical Solutions, Daiichi-Sankyo, Kaneka, Medtronic, and Terumo; membership on the advisory boards for Johnson&Johnson, Medtronic and Terumo outside the submitted work. Dr. Iiharai reports a research grant from Idorsia Pharamaceutical Japan outside the submitted work. Dr. Imamura reports the lecturer's fees from Medtronic, Daiichi Sankyo, Stryker, Johnson & Johnson, Terumo, and Asahi Intecc. Dr. Ishii received a reserach grant from Fuji Film and lecture fees from Medtronic, Stryker, Terumo and Johnson and Johnson. Dr. Matsumaru discloses lecturer fees from Medtronic, Stryker, Terumo, Kaneka, Biomedical solution, E.P. Medical, B Braun, Daiichi Sankyo and Idorcia outside the submitted work. Dr. Chiaki Sakai reports no conflict of interest. Dr. Satow reports research grants from CANON medical systems, lecturer's fees from Medtronic, and consulting fees from Kaneka Medix. Dr. Sakakibara reports a manuscript fee from Medicus Shuppan. Dr. Shirakawa reports lecturer's fees from Stryker, Terumo, Johnson & Johnson and Medtronic. Dr. Yoshimura reports research grants from Medico's Hirata, Medtronic, and Terumo; and lecturer fees from Medtronic, Kaneka, Stryker, Daiichi Sankyo, Bristol-Meyers Squibb, and Johnson & Johnson., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Symptomatic intracranial atherosclerotic stenosis (ICAS) is prone to cause early recurrent stroke (ERS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels and prevent cardiovascular events. This multicentre, hospital-based prospective cohort study was designed to investigate whether PCSK9 inhibitors would prevent ERS in patients with symptomatic ICAS., Methods: From 1 October 2020 to 30 September 2022, consecutive patients with acute ischaemic stroke attributed to ICAS admitted within 1 week after onset were enrolled and followed up for 1 month. Patients were divided into two groups, the PCSK9 inhibitors group receiving PCSK9 inhibitors add-on therapy, and the control group receiving statins and/or ezetimibe. The primary outcome was ERS. Cox proportional hazard models and Kaplan-Meier survival curve were used to estimate the association between PCSK9 inhibitors and ERS., Results: At the end of follow-up, the LDL-C levels were further lowered by PCSK9 inhibitors add-on therapy (n=232, from 3.06±1.16 mmol/L to 2.12±1.19 mmol/L) than statins and/or ezetimibe treatment (n=429, from 2.91±1.05 mmol/L to 2.64±0.86 mmol/L, p<0.001). The Kaplan-Meier survival curves showed that PCSK9 inhibitors add-on therapy significantly reduced ERS (5.59%, 24/429, vs 2.16%, 5/232; log-rank test, p=0.044). The multivariate Cox regression analysis revealed that, after adjusting for confounders with a p value less than 0.05 in univariate analysis or of particular importance, the HR was 0.335 (95% CI 0.114 to 0.986, p=0.047), compared with the control group., Conclusions: In our study, PCSK9 inhibitors add-on therapy further reduced LDL-C levels and ERS in patients with symptomatic ICAS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the correlation between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and intracranial atherosclerotic stenosis-related emergent large vessel occlusion (ICAS-ELVO) in acute ischemic stroke patients with endovascular thrombectomy., Methods: Included in this study were 215 patients who underwent endovascular thrombectomy. They were randomly assigned to training and testing datasets. The patients in training dataset (n=128) were divided into ICAS group (n=65) and embolism group (n=63). MHR was compared between the two groups. According to the cut-off value, patients in testing dataset (n=87) were divided into low-MHR group (n=54) and high-MHR group (n=33). MHR was compared between the two groups., Results: In training dataset, the proportion of male patients, diabetic patients and smokers in ICAS group was significantly higher than that in embolism group [(50 (76.9%) vs. 30 (47.6%), P=0.001; 29 (44.6%) vs. 14(22.2%), P=0.007; 37(56.9%) vs. 14 (22.2%), P=0.001; 37 (56.9%) vs. 14 (22.2%), P=0.001], while the mean age and the proportion of patients with coronary heart disease (CHD), stroke and atrial fibrillation were significantly lower [(64.74±9.13 vs. 71.38±13.34, P=0.001; 6 (9.2%) vs. 14 (22.2%), P=0.043; 12 (18.5%) vs. 22 (34.9%), P=0.035; 5 (7.7%)vs. 56 (88.9%), P<0.001)]. The laboratory test results showed that monocyte count was significantly higher and high-density lipoprotein level was significantly lower in ICAS group than those in embolism group (0.61±0.26 vs. 0.45±0.13, P=0.001; 1.17±0.28 vs. 1.37±0.27, P=0.001). MHR in ICAS group was significantly higher than that in embolism group (0.55±0.26 vs. 0.34±0.11, P=0.001). In training set, MHR was found to be an independent predictor for the occurrence of ICAS-ELVO with an adjusted OR of 2.39 (95%CI 1.29-4.48, P=0.006). ROC curve analysis showed that the area under the curve (AUC) of MHR was 0.8 (95% CI, 0.72-0.87, p < 0.001), with a sensitivity of 0.60 and a specificity of 0.873. The optimal cut-off value of the MHR level was 0.46. In testing dataset, the rate of ICAS-ELVO in higher quartile was significantly higher than that in the lower quartile (81.8% vs. 33.3%, P<0.001). Patients with a low MHR had a higher rate of cerebral hemorrhagic than those with a high MHR., Conclusion: MHR was associated with ICAS-ELVO in acute ischemic stroke patients with endovascular thrombectomy, and the higher level of MHR does benefit to differentiate ICAS from intracranial embolism, suggesting that MHR may prove to be an independent predictor for ICAS-ELVO., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships, (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To assess the predictive value of hemodynamic features for stroke relapse in patients with intracranial vertebrobasilar atherosclerotic stenosis treated with percutaneous transluminal angioplasty and stenting (PTAS) using quantitative digital subtraction angiography (q-DSA)., Methods: In this retrospective longitudinal study, patients with intracranial vertebrobasilar atherosclerotic stenosis and who underwent PTAS treatment between January 2012 and May 2020 were enrolled. The q-DSA assessment was performed before and after PTAS. ROIs 1-4 were placed along the vertebral artery, proximal and distal basilar artery, and posterior cerebral artery; ROIs 5-8 were in 5 mm and 10 mm proximal and distal to the lesion, respectively. Relative time to peak (rTTP) was defined as the difference in TTP between ROIs. Cox regression analyses were performed to determine risk factors for recurrent stroke., Results: A total of 137 patients (mean age, 62 years ± 10 [standard deviation], 83.2% males) were included, and 26 (19.0%) patients had stroke relapse during follow-up (median time of 42.6 months [interquartile range, 19.7-60.7]). Preprocedural rTTP 4-1 (adjusted hazard ratio (HR) = 2.270; 95% CI 1.371-3.758; p = 0.001) and preprocedural rTTP 8-5 (adjusted HR = 0.240; 95% CI 0.088-0.658; p = 0.006) were independently associated with the recurrent stroke. These hemodynamic parameters provided an incremental prognostic value for stroke relapse (AUC, 0.817 [0.704-0.931]; the net reclassification index, 0.431 [0.057-0.625]; and the integrated discrimination index, 0.140 [0.035-0.292])., Conclusions: In patients with intracranial vertebrobasilar atherosclerosis treated with PTAS, preprocedural prolonged TTP of the target vessel and shortened trans-stenotic TTP difference were associated with stroke relapse. Q-DSA-defined hemodynamic parameters provided incremental predictive value over conventional parameters for stroke recurrence., Clinical Relevance Statement: Quantitative DSA analysis enables intuitive observation and semi-quantitative evaluation of peri-therapeutic cerebral blood flow. More importantly, quantitative DSA-defined hemodynamic parameters have the potential for risk stratification of patients with intracranial atherosclerotic stenosis., Key Points: Semi-quantitative angiography-based parameters can reflect pre- and postprocedural subtle changes in blood flow in patients with intracranial atherosclerotic stenosis. Although angioplasty procedures can significantly improve blood flow status, patients with more restricted baseline blood flow still show a higher risk of stroke recurrence. Angiography-based hemodynamic features possess prognostic value and can serve as clinical markers to assess stroke risk of patients with intracranial atherosclerotic stenosis., (© 2023. The Author(s).)

Objective: To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis. Methods: A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated. Results: The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P >0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P >0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P >0.05). Conclusions: The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Aim: We aimed to investigate the relationship between systemic inflammatory response index (SIRI) and intracranial plaque features, as well as the risk factors related to the severity and recurrence of cerebral ischemic events., Methods: We enrolled 170 patients with cerebral ischemic events. Baseline demographic characteristics and laboratory indicators were collected from all participants. All patients were assessed by high-resolution magnetic resonance vessel wall imaging for culprit plaque characteristics and intracranial atherosclerotic burden. Outpatient or telephone follow-up were conducted at 1, 3, and 6 months after discharge., Results: SIRI levels were significantly associated with the enhanced plaque number (r = 0.205, p = 0.007), total plaque stenosis score (r = 0.178, p = 0.020), total plaque enhancement score (r = 0.222, p = 0.004), intraplaque hemorrhage (F = 5.630, p = 0.004), and plaque surface irregularity (F = 3.986, p = 0.021). Higher SIRI levels (OR = 1.892), total plaque enhancement score (OR = 1.392), intraplaque hemorrhage (OR = 3.370) and plaque surface irregularity (OR = 2.846) were independent risk factors for moderate-severe stroke, and these variables were significantly positively correlated with NIHSS (P < 0.05 for all). In addition, higher age (HR = 1.063, P = 0.015), higher SIRI levels (HR = 2.003, P < 0.001), and intraplaque hemorrhage (HR = 4.482, P = 0.008) were independently associated with recurrent stroke., Conclusions: Higher SIRI levels may have adverse effects on the vulnerability and burden of intracranial plaques, and links to the severity and recurrence of ischemic events. Therefore, SIRI may provide important supplementary information for evaluating intracranial plaque stability and risk stratification of patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: This study sought to scrutinize the clinical outcomes associated with first-pass mechanical thrombectomy strategies in the management of intracranial atherosclerosis (ICAS)-related large vessel occlusion (LVO)., Methods: Within this post-hoc analysis of the The Endovascular Treatment With vs Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial, we compared data pertaining to patients with ICAS-LVO situated in the anterior circulation who underwent initial therapeutic interventions utilizing either aspiration thrombectomy or stent-retriever thrombectomy. The analysis encompassed the assessment of intraprocedural recanalization, rescue procedures involving balloon angioplasty or stenting, 48-hour reocclusion rates, occurrences of cerebral hemorrhagic complications, and 90-day Modified Rankin Scale scores., Results: Among the 948 patients encompassed in the RESCUE BT trial, a total of 230 patients with ICAS-LVO in the anterior circulation were enrolled in the study. Of these, 111 underwent aspiration thrombectomy as the first-pass therapy, while 119 patients underwent stent-retriever thrombectomy as the initial intervention. The difference in first pass recanalization rates between aspiration thrombectomy and stent-retriever thrombectomy was not statistically significant (17.1% vs. 14.3%, P = 0.555), and mechanical thrombectomy success rates (90.1% vs. 90.8%, P = 0.864), the use of balloon angioplasty or stenting for rescue therapy (54.6% vs. 45.9%, P = 0.189; 23.4% vs. 25.2%, P = 0.752), and favorable 90-day Modified Rankin Scale outcomes (53.2% vs. 40.3%, P = 0.051) showed no statistically significant differences., Conclusions: Both aspiration thrombectomy and stent-retriever thrombectomy can be considered as primary therapeutic options for patients presenting with ICAS-LVO in the anterior circulation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The optimal primary recanalization strategy for intracranial atherosclerosis-related emergent large vessel occlusion (ICAS-ELVO) remains controversial. We aimed to explore the safety and efficacy of balloon angioplasty as the first-choice recanalization strategy for ICAS-ELVO with small clot burden., Methods: Consecutive ICAS-ELVO patients presenting with microcatheter "first-pass effect" during endovascular treatment (EVT) were retrospectively analyzed. Patients were divided into preferred balloon angioplasty (PBA) and preferred mechanical thrombectomy (PMT) groups based on the first-choice recanalization strategy. The reperfusion and clinical outcomes between the two groups were compared., Results: Seventy-six patients with ICAS-ELVO involving the microcatheter "first-pass effect" during EVT were enrolled. Compared with patients in the PMT group, those in the PBA group were associated with (i) a higher rate of first-pass recanalization (54.0% vs. 28.9%, p = .010) and complete reperfusion (expanded thrombolysis in cerebral ischemia ≥ 2c; 76.0% vs. 53.8%, p = .049), (ii) shorter puncture-to-recanalization time (49.5 min vs. 89.0 min, p < .001), (iii) lower operation costs (¥48,499.5 vs. ¥ 99,086.0, p < .001), and (iv) better 90-day functional outcomes (modified Rankin scale:0-1; 44.0% vs. 19.2%, p = .032). Logistic regression analysis revealed that balloon angioplasty as the first-choice recanalization strategy was an independent predictor of 90-day excellent functional outcomes for ICAS-ELVO patients with microcatheter "first-pass effect" (adjusted odds ratio = 6.01, 95% confidence interval: 1.15-31.51, p = .034)., Conclusion: Direct balloon angioplasty potentially improves 90-day functional outcomes for ICAS-ELVO patients with small clot burden, and may be a more appropriate first-choice recanalization strategy than mechanical thrombectomy for these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The impact of intracranial arteriosclerosis on dementia remains largely unclear., Methods: In 2339 stroke-free and dementia-free participants (52.2% women, mean age 69.5 years) from the general population, we assessed intracranial carotid artery calcification (ICAC) and vertebrobasilar artery calcification (VBAC) as proxy for arteriosclerosis. Associations with dementia were assessed using Cox models. In addition, indirect effects through cerebral small vessel disease (cSVD) and subcortical brain structure volumes were assessed using causal mediation analyses., Results: During a median of 13.4 years (25th-75th percentiles 9.9-14.5) of follow-up, 282 participants developed dementia. Both ICAC presence (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: 1.00-2.32]) and volume (HR per standard deviation: 1.19, 95% CI: 1.01-1.40) increased dementia risk. For VBAC, severe calcifications increased dementia risk (HR for third vs first volume tertile: 1.89, 95% CI: 1.00-3.59). These effects were mediated partly through increased cSVD (percentage mediated for ICAC: 13% and VBAC: 24%)., Discussion: Intracranial arteriosclerosis increases the risk of dementia., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: To evaluate the relationship between different angiographic patterns of middle cerebral artery M1 segment stenosis and related territorial stroke in patients receiving aggressive medical treatment without stenting., Methods: We retrospectively reviewed our patient registry database to identify ICAS patients diagnosed by digital subtraction angiography between January 2017 and December 2020 and identified 3 different angiographic patterns (normal, shift, and dilation) in 124 patients with M1 stenosis. The association between these patterns and recurrent ischemic stroke in the M1 territory was analyzed., Results: The rates of recurrent M1 territorial stroke and transient ischemic attack in the normal group, shift group, dilation group and shift-dilation group were 34.5%, 35.0%, 78.3%, and 44.4% respectively. In patients with the shift pattern, the rate of recurrent stroke is significantly higher at a deflection angle ≥9.32° than at a deflection angle <9.32°(P < 0.05). In patients with dilation pattern, the rate of recurrent stroke is significantly higher than patients with non-dilation pattern (72.3% vs. 36.8%, P < 0.05)., Conclusions: Angiographic patterns of M1 stenosis may predict recurrent territorial strokes, thus providing a surrogate marker to identify high-risk patients for potential endovascular treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Intracranial atherosclerotic stenosis is a prevalent cause of ischemic stroke worldwide. Its association with silent cerebral infarcts and its contribution to cognitive impairment and dementia emphasize the critical need for disease prevention and effective management strategies. Despite extensive research on secondary stroke prevention treatment over the past several decades, intracranial atherosclerotic stenosis continues to exhibit a notably higher recurrent stroke rate compared with other causes. This review focuses on randomized secondary prevention trials involving antithrombotic therapy, endovascular treatment, open surgical therapy, and remote ischemic conditioning. It aims to provide an insightful overview of the major findings from each trial and their implications for future research efforts., Competing Interests: Disclosures None.

Background: Mechanical thrombectomy is an effective treatment method for large-vessel occlusion stroke (LVOS); however, it has limited efficacy for intracranial atherosclerotic disease (ICAD)-related LVOS. We investigated the use of cerebral blood volume (CBV) maps for identifying ICAD as the underlying cause of LVOS before the initiation of endovascular treatment (EVT)., Methods and Results: We reviewed clinical and imaging data from patients who presented with LVOS and underwent endovascular treatment between January 2011 and May 2021. The CBV patterns were analyzed to identify an increase in CBV within the hypoperfused area and estimate infarct patterns within the area of decreased CBV. Comparisons were made between the patients with an increase in CBV and those without, and among the estimated infarct patterns: territorial, cortical wedge, basal ganglia-only, subcortical, and normal CBV. Overall, 243 patients were included. CBV increase in the hypoperfused area was observed in 23.5% of patients. A significantly higher proportion of ICAD was observed in those with increased CBV than in those without (56.4% versus 19.8%; P <0.001). Regarding the estimated infarct patterns on the CBV, ICAD was most frequently observed in the normal CBV group (territorial, 14.9%; cortical wedge, 10.0%; basal ganglia-only, 43.8%; subcortical, 35.7%; normal, 61.7%). CBV parameters, including "an increase in CBV," "normal CBV infarct pattern," and "an increase in CBV or normal CBV infarct pattern composite," were independently associated with ICAD., Conclusions: An increased CBV or normal CBV pattern may be associated with ICAD LVOS on the pretreatment perfusion imaging.

Background: Intracranial atherosclerotic stenosis (ICAS) can cause either transient ischemic attack (TIA) or acute ischemic stroke (AIS). Pathogenesis of ICAS-AIS can be divided into artery-to-artery embolism(A-A), hypoperfusion(HP), and parent-artery atherosclerosis occluding penetrating artery(POPA). However, the prognosis of each type remains uncertain. Our study aimed to investigate potential disparities in the recurrent risk among these four subtypes of symptomatic ICAS., Methods: From a prospective, single-center cohort study of acute cerebrovascular diseases from January 2017 to November 2021, we recruited 120 ICAS patients and classified them into four groups based on diffusion weighted imaging. Patients were retrospectively followed up for recurrence in December 2022. The primary outcome was recurrent cerebral vascular events (RCVE) in the same territory., Results: Among 120 recruited patients, POPA(33%) was the most common subtype, followed by A-A(32%), HP(29%), and TIA(6%). Cumulative recurrent rate was 31.2% with median months of follow-up as 27(20-45.5). There was no significant difference in the risk of RCVE in the same territory among four subgroups within three months. However, when considering the risk after three months, TIA(57%) had the highest risk of RCVE, followed by A-A(26%), while HP(4%) and POPA(8%) had lower risks (P = 0.001). Cox regression model indicated that symptom and pathogenesis was an independent risk factor for RCVE in long-term prognosis (P = 0.022), after adjusting for a history of hypertension and cerebral infarction., Conclusions: Distinctive symptoms and pathogenesis of ICAS exhibit varying risks of RCVE in long-term prognosis. The differentiation in recurrent risk may provide valuable insights for guiding secondary prevention strategies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The diagnosis of intracranial atherosclerosis (ICAS) associated with large vessel occlusion (LVO) before endovascular treatment (EVT) remains a clinical challenge. This study was aimed at developing a predictive model for ICAS-LVO in the anterior circulation preceding EVT., Methods: Patients from two national stroke centers who had undergone EVT for acute ischemic stroke in the anterior circulation were evaluated. Those from one center served as the derivation cohort, whereas patients from another center functioned as the external validation cohort. ICAS-LVO was characterized as stenosis exceeding 70% or stenosis surpassing 50% accompanied by distal blood flow disruption or recurrent occlusion evidence during the intervention. A random forest algorithm helped to identify key predictors within the derivation cohort. Utilizing these predictors, the authors formulated a logistic regression model from the derivation cohort data, and the model was then internally validated through a bootstrapping method. Subsequently, a predictive score based on this model was constructed and evaluated in both cohorts., Results: Among all the patients, 470 from the derivation cohort and 147 from the external validation cohort met the inclusion criteria. After random forest regression, the key predictors of ICAS-LVO included the absence of atrial fibrillation, the presence of truncal-type occlusion, the absence of a hyperdense artery sign, and a lower baseline examination National Institutes of Health Stroke Scale (NIHSS) score (ATHE Scale). Incorporating these variables into the logistic regression model yielded an area under the curve (AUC) of 0.920 (95% CI 0.894-0.947) for ICAS-LVO prediction. After bootstrapping validation, the model produced a mean AUC of 0.915. Subsequently, the ATHE score, derived from these predictors, registered an AUC of 0.916 (95% CI 0.887-0.939, p < 0.001) in the derivation cohort and 0.890 (95% CI 0.828-0.936, p < 0.001) in the external validation cohort., Conclusions: The ATHE Scale, incorporating atrial fibrillation, truncal-type occlusion, hyperdense artery sign, and baseline examination NIHSS score, is an accurate, objective tool for predicting ICAS-LVO prior to EVT.

Introduction: Periodontal disease (PD) and dental caries are oral infections leading to tooth loss that are associated with atherosclerosis and cerebrovascular disease. We assessed the hypothesis that PD and caries are associated with asymptomatic intracranial atherosclerosis (ICAS) in the Atherosclerosis Risk in Communities (ARIC) study., Methods: Full-mouth clinical periodontal measurements (7 indices) collected at 6 sites per tooth from 6,155 subjects from the Dental Atherosclerosis Risk in Communities Study (DARIC) without prior stroke were used to differentiate seven PD stages (Periodontal Profile Class [PPC]-I to -VII) and dental caries on coronal dental surface (DS) and dental root surface (DRS). A stratified subset underwent 3D time-of-flight MR angiogram and 3D high isotropic-resolution black blood MRI. ICAS was graded according to the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We evaluated the relationship between PD stage and dental caries with asymptomatic ICAS, graded as no ICAS, &lt;50% ICAS, and ≥50% ICAS., Results: Among dentate subjects who underwent vascular imaging, 801 (70%) had no ICAS, 232 (20%) had &lt;50% ICAS, and 112 (10%) had ≥50% ICAS. Compared to participants without gum disease (PPC-I), participants with mild-moderate tooth loss (PPC-VI), severe tooth loss (PPC-VII), and severe PD (PPC-IV) had higher odds of having &lt;50% ICAS. Participants with extensive gingivitis (PPC-V) had significantly higher odds of having ≥50% ICAS. This association remained significant after adjusting for confounding variables: age, gender, race, hypertension, diabetes, dyslipidemia, 3-level education, and smoking status. There was no association between dental caries (DS and DRS) and ICAS &lt;50% and ≥50%., Conclusion: We report significant associations between mild-moderate tooth loss, severe tooth loss, and severe PD with &lt;50% ICAS as well as an association between extensive gingivitis and ≥50% ICAS. We did not find an association between dental caries and ICAS., (© 2023 S. Karger AG, Basel.)