Elevated triglyceride-glucose index predicts poor outcome in patients with intracranial atherosclerotic stenosis after extracranial and intracranial bypass.

BACKGROUND AND PURPOSE: The triglyceride-glucose (TyG) index, a novel reliable biomarker for IR that incorporates blood glucose and triglyceride, is linked to intracranial atherosclerotic stenosis (ICAS). In this study, we aimed to further investigate the association between the TyG index and the outcomes of ICAS patients following extracranial-to-intracranial (EC-IC) bypass grafting. METHODS: 489 ICAS patients who underwent EC-IC bypass between Jan 2009 and Jan 2022 at our hospital were retrospectively collected. The major adverse cardiac and cerebrovascular events (MACCEs), and anastomotic restenosis, both of which are critical factors leading to poor prognosis of ICAS patients after EC-IC bypass, were mainly recorded and analyzed. Kaplan-Meier survival curve and Log-rank tests were sequentially conducted. Cox regression model was used to investigate the association between the TyG index and MACCEs & anastomotic stenosis. C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated the incremental predictive value of the TyG index. RESULTS: A higher incidence of MACCEs and anastomotic stenosis was found in higher-tertile TyG index group. The TyG index was significantly associated with an increased risk of MACCEs and anastomotic stenosis, independent of confounding factors, with a value of HR (1.30, 95%CI 1.10-1.51, p < 0.001) and (1.27, 95%CI 1.16-1.40, p < 0.001) respectively. The area under the curve (AUC) in the model with the TyG index for predicting the occurrence of MACCEs and anastomotic stenosis were 0.708 (95%CI 0.665-0.748) and 0.731 (95%CI 0.689-0.770) respectively. The addition of the TyG index significantly improved the global performance of the baseline model according to the C-statistics, NRI, and IDI (All p < 0.05). CONCLUSIONS: Higher TyG levels were associated with poorer outcomes in ICAS patients after EC-IC bypass. TyG could be a key factor in managing ICAS risk and standardizing the indications for EC-IC bypass.

Nomogram for predicting asymptomatic intracranial atherosclerotic stenosis in a neurologically healthy population.

Asymptomatic intracranial atherosclerotic stenosis (aICAS) is a major risk factor for cerebrovascular events. The study aims to construct and validate a nomogram for predicting the risk of aICAS. Participants who underwent health examinations at our center from September 2019 to August 2023 were retrospectively enrolled. The participants were randomly divided into a training set and a testing set in a 7:3 ratio. Firstly, in the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were performed to select variables that were used to establish a nomogram. Then, the receiver operating curves (ROC) and calibration curves were plotted to assess the model's discriminative ability and performance. A total of 2563 neurologically healthy participants were enrolled. According to LASSO-Logistic regression analysis, age, fasting blood glucose (FBG), systolic blood pressure (SBP), hypertension, and carotid atherosclerosis (CAS) were significantly associated with aICAS in the multivariable model (adjusted P < 0.005). The area under the ROC of the training and testing sets was, respectively, 0.78 (95% CI: 0.73-0.82) and 0.65 (95% CI: 0.56-0.73). The calibration curves showed good homogeneity between the predicted and actual values. The nomogram, consisting of age, FBG, SBP, hypertension, and CAS, can accurately predict aICAS risk in a neurologically healthy population.

Long-term outcome followed for more than 5 years after revascularization surgery for the treatment of atherosclerotic steno-occlusive disease: poor outcome prediction using machine learning and analysis of the results.

Cerebral revascularization for the treatment of atherosclerotic steno-occlusive disease (ASOD) was found to have no benefit compared with medical treatment. However, there is also criticism that with sufficiently long-term follow-up, a crossover might emerge demonstrating the advantages of surgery. Therefore, we examined the long-term outcome of cerebral revascularization performed on patients with carefully selected ASOD at our center. Patients undergoing bypass surgery for non-moyamoya ischemic disease were retrospectively identified. The inclusion criteria were symptomatic ASOD with hemodynamic insufficiency, follow-up of more than 5 years, and stroke or surgical complications during follow-up. The clinical course and radiological findings were investigated. Poor outcomes were predicted using machine learning (ML) models, and Shapley additive explanation (SHAP) values and feature importance of each model were analyzed. A total of 109 patients were included from 2007 to 2018. The 30-day risk of any stroke or death was 6.4% (7/109). The risk of ipsilateral ischemic stroke during median follow-up of 116 months was 7.3% (8/109). The SHAP values showed that previously and empirically known stroke risk factors exert a relatively consistent effect on the prediction of models. The number of lesions with stenosis > 50% (odds ratio [OR] 5.77), age (OR 1.13), and coronary artery disease (OR 5.73) were consistent risk factors for poor outcome. We demonstrated an acceptable long-term outcome of cerebral revascularization surgery for patients with hemodynamically insufficient and symptomatic ASOD. Multicenter studies are encouraged to predict poor outcomes and suitable patients with large numbers of quantitative and qualitative data.

A case report of effective treatment of intracranial atherosclerotic stenosis treated with the integration of traditional Chinese medicine and Western medicine.

RATIONALE: Intracranial atherosclerotic stenosis (ICAS) represents a prevalent global cause of stroke, posing a notably higher risk of stroke recurrence than other stroke etiologies. Herein, we report a case of a 39-year-old male patient diagnosed with ICAS, treated through an integrated approach incorporating Chinese and Western medicine with significant efficacy and satisfied clinical safety. PATIENT CONCERNS: This patient presented with 1 transient ischemic attack and prolonged headache, dizziness and poor sleep quality. In addition, the patient refused to undergo surgery due to the high cost and postoperative risks. DIAGNOSES: Diagnostic methods used to identify ICAS include conventional cerebral angiography, magnetic resonance angiography (MRA), CT angiography (CTA), transcranial Doppler ultrasound (TCD), and High-Resolution Magnetic resonance imaging. Considering the cost and risks associated with conventional angiography, noninvasive imaging has emerged as the method of choice for diagnosing ICAS. After a series of noninvasive examinations (CTA, TCD, and HR-MRI), the patient was diagnosed with ICAS. INTERVENTIONS: The western medical regimen includes antiplatelet coagulation, blood pressure control, lipid regulation, plaque stabilization, and lifestyle modifications such as exercise, weight loss, and adherence to low-salt, low-fat diets. Complementing this, traditional Chinese medicine (TCM) treatment was guided by the principle of strengthening the spleen, resolving dampness, nourishing blood and harmonizing ying, resolving blood stasis and clearing collaterals. This involved the administration oral Chinese medicine such as modified Shenling Baizhu powder and modified Si Wu decoction. OUTCOMES: The efficacy of the treatment was assessed by evaluating the degree of luminal stenosis and peak systolic blood flow velocity in the M1 segment of the left middle cerebral artery (MCA) before and after the intervention. Encouragingly, posttreatment results demonstrated the disappearance of the plaque in the left MCA-M1 segment, with no significant lumen stenosis observed. Moreover, a notable and smooth reduction in blood flow velocity was achieved in the left MCA, indicating positive outcomes from the integrated traditional Chinese and Western medicine approach. CONCLUSION: This case report shows that a combination of traditional Chinese and Western medicine is safe and effective in the treatment of ICAS and is worthy of promotion in the clinic.

Comparative analysis of imaging features and stroke-related factors between posterior circulation atherosclerosis and intramural hematoma-type dissection.

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.

Lipoprotein-associated phospholipase A2 activity levels is associated with artery to artery embolism in symptomatic intracranial atherosclerotic disease.

BACKGROUND: Lipoprotein-associated phospholipase A2 activity (Lp-PLA2-A) is a pivotal enzyme involved in the inflammatory process and atherosclerotic plaque vulnerability. This study aimed to investigate the potential of Lp-PLA2-A as a biomarker for reflecting artery-to-artery embolism (AAE), a critical mechanism with high risk of stroke recurrence in symptomatic intracranial atherosclerotic disease (sICAD). METHODS: The current analysis included a cohort of 1,908 patients with sICAD and baseline levels of Lp-PLA2-A from the Third China National Stroke Registry (CNSR-III). The baseline Lp-PLA2-A levels were quantified centrally using an automatic enzyme assay system. Diagnosis of sICAD was made by experienced stroke neurologists based on the presence of a cerebral infarction within the territory of a stenotic (>50 %) or occluded artery, or when clinical symptoms were consistent with the diagnosis. Infarct lesions affecting the cortex serve as imaging biomarkers for stroke mechanism involving AAE.The relationship between baseline Lp-PLA2-A quartile levels and the presence of cortical infarction was analyzed using multivariate logistic regression. RESULTS: Compared to patients in the first Lp-PLA2-A quartile, those in the second, third and fourth quartiles demonstrated a significantly higher proportion of AAE. The proportion of patients with cortical infarction increased with rising Lp-PLA2-A quartiles, observed at 39.3 %, 47.1 %, 47.4 %, and 50.7 % for the first, second, third and fourth quartiles respectively (P for trend=0.004). Compared with the first quartile, the odds ratios (ORs) were 1.38 (95 % CI = 1.06-1.79) for the second, 1.33 (95 % CI = 1.02-1.72) for the third quartile and 1.48 (95 % CI = 1.14-1.92) for the fourth quartile. The association between higher Lp-PLA2-A and increased proportion of cortical infarction was also present in the subgroups defined by age <65 years, male, and high-sensitivity C-reactive protein ≥2 mg/L. In sensitivity analyses, the positive correlation between Lp-PLA2-A levels and proportion of cortical infarction remained consistent. CONCLUSIONS: This research highlights the significance of Lp-PLA2-A as a biomarker for reflecting stroke mechanism in sICAD. Additional studies are warranted to explore the potential of targeting Lp-PLA2-associated inflammatory pathways as a pivotal approach in arresting the advancement of intracranial atherosclerotic stenosis and reducing the incidence of embolic strokes.

Effects of intracranial artery stenosis of anterior circulation on cognition-A CT perfusion-based study.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most important independent risk factors for stroke that is closely related to the occurrence of cognitive impairment. The relationship between ICAS and vascular cognitive impairment (VCI) remains unclear. Cerebral hemodynamic changes are one of the main causes of cognitive impairment. Computed tomographic perfusion (CTP) imaging can quantitatively analyze cerebral blood perfusion and quantify cerebral hemodynamic changes. Previous research on the relationship between hypoperfusion induced by ICAS and cognitive impairment, as well as its underlying mechanisms, remains relatively insufficient. This study is dedicated to elucidating the characteristics and potential mechanisms of cognitive impairment in ICAS patients with abnormal perfusion, utilizing CTP imaging as our primary investigative tool. METHODS: This study recruited 82 patients who suffer from non-disabling ischemic stroke (IS group) and 28 healthy controls. All participants underwent comprehensive neuropsychological assessments both collectively and individually, in addition to CTP imaging. Within the patient group, we further categorized individuals into two subgroups: the ischemic penumbra group (IP, N = 28) and the benign oligemia group (BO, N = 54), based on CTP parameters-Tmax. The correlations between cognitive function and abnormal perfusion were explored. RESULTS: The cognitive function, including the overall cognitive, memory, attention, executive functions, and language, was significantly impaired in the IS group compared with that in the control group. Further, there are statistical differences in the stroop color-word test-dot (Stroop-D) and Montreal Cognitive Assessment (MoCA) sub-items (memory + language) between the BO and IP groups. In the BO group, the score of Stroop-D is lower, and the MoCA sub-items are higher than the IP group. There is no correlation between CTP parameters and cognitive function. CONCLUSION: Cognitive function is significantly impaired in patients with ICAS, which is related to cerebral perfusion. Executive, memory, and language function were better preserved in ICAS patients without IP. Hence, this study posits that managing hypoperfusion induced by ICAS may play a pivotal role in the development of VCI.

Lipid on stroke in intracranial artery atherosclerotic stenosis: a mediation role of glucose.

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.

Balloon Angioplasty vs Medical Management for Intracranial Artery Stenosis: The BASIS Randomized Clinical Trial.

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.

Rare RNF213 variants is related to early-onset intracranial atherosclerosis: A Chinese community-based study.

BACKGROUND: The relationship between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) remained unelucidated. Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between rare RNF213 variants and ICAS within a Chinese community-dwelling population. METHODS: The present study included 821 participants from Shunyi cohort. Genetic data of rare RNF213 variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial atherosclerosis were assessed by brain HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of rare RNF213 variants on atherosclerosis. Stratification by age were conducted with 50 years old set as the cutoff value. RESULTS: Ninety-five participants were identified as carriers of rare RNF213 variants. Carotid plaques were observed in 367 (44.7 %) participants, while ICAS was identified in 306 (37.3 %). Rare variants of RNF213 was not associated with ECAS. Employing HR-MRI, both the presence of rare variants (ß = 0.150, P = 0.025) and numerical count of variants (ß = 0.182, P = 0.003) were significantly correlated with ICAS within the group of age ≤50 years. Both variant existence (ß = 0.154, P = 0.014) and variant count (ß = 0.188, P = 0.003) were significantly associated with plaques in middle cerebral arteries within younger subgroup, rather than basilar arteries. Furthermore, a significant association was observed between variants that located outside the N-arm domain and ICAS in the younger subgroup (OR = 2.522, P = 0.030). Statistical results remained robust after adjusted for age, gender, and cardiovascular risk factors. CONCLUSIONS: Rare variants of RNF213 is associated with age-related ICAS in general Chinese population, highlighting the potential role of RNF213 as a genetic contributor to early-onset ICAS.

Endovascular treatment for proximal middle cerebral artery occlusion due to underlying intracranial atherosclerotic disease: A retrospective single-center case series.

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.

Association between metabolic syndrome and outcomes of large-artery atherosclerosis stroke treated with reperfusion therapy.

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.

Intracranial artery calcification: Frequency, determinants, and modification of outcomes from endovascular thrombectomy.

INTRODUCTION: Intracranial artery calcification (ICAC) is a common finding on computed tomography (CT) in patients presenting with large vessel occlusion acute ischemic stroke (LVO-AIS) and could serve as a useful biomarker of intracranial atherosclerosis and altered intracranial vessel pliability in patients undergoing endovascular thrombectomy (EVT). METHODS: This was a retrospective cohort study analyzing consecutive patients undergoing CT head prior to EVT between 2016 and 2020. Extent of ICAC proximal to the target vessel was scored using a validated grading scale examining thickness and circumferential extent of calcifications. The relationship between 3 levels of ICAC burden and procedural, clinical, and safety outcomes was analyzed. RESULTS: Among 86 patients meeting inclusion criteria, ICAC of any degree was present in 72.1 %. Median ICAC score was 3 [IQR 0-4]. There was a U-shaped association between ICAC score and successful reperfusion: 90.9 %, 65.7 %, and 94.4 % in the low, intermediate, and high ICAC score groups, respectively (p = 0.008). Use of rescue intervention, most often angioplasty and stenting, was greatest in the high ICAC score group: 3.0 % vs. 5.7 % vs. 22.2 % (p = 0.05). Functional independence at 90 days did not differ significantly among groups (41.7 % vs. 31.0 % vs. 15.4 %, p = 0.26), nor did rates of symptomatic intracranial hemorrhage (15.2 % vs. 14.3 % vs. 16.7 %, p = 0.97). CONCLUSIONS: ICAC is seen on CT in nearly three-quarters of patients with LVO-AIS. Extent of ICAC has a U-shaped association with successful reperfusion, in part due to more frequent use of rescue interventions in patients with extensive ICAC.

Adjunctive rescue therapy in acute large vessel occlusion secondary to underlying intracranial atherosclerotic disease.

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.

The gut microbiome and serum metabolome are altered and interrelated in patients with intracranial atherosclerotic stenosis.

OBJECTIVES: To evaluate the relationship among the gut microbiome, serum metabolites and the Intracranial atherosclerosis stenosis. MATERIALS AND METHODS: Integrated analysis of 16S rDNA sequencing of fecal samples and untargeted serum metabolomics was applied to identify alterations in the gut microbiome and serum metabolome in 29 Intracranial atherosclerosis stenosis patients and 29 healthy control individuals. RESULTS: Compared to healthy control individuals, the abundances of forty-five genera and one hundred seventy-seven metabolites were significantly altered in Intracranial atherosclerosis stenosis patients. At the species level, the Intracranial atherosclerosis stenosis group exhibited higher abundances of Bacteroidetes and lower abundances of Megaphaera and Muribacoccaceae. Microbial functional prediction analysis revealed enhanced activity of bacterial chemotaxis and oxidative phosphorylation within the Intracranial atherosclerosis stenosis group. In terms of metabolomic findings, the levels of dulcitol were significantly increased in the Intracranial atherosclerosis stenosis group. The levels of specific metabolites within the phosphatidylcholine and lysophosphatidylcholine families, such as PC (14:0e/24:4) and LPC 20:5, were increased, while the levels of certain other specific metabolites were decreased. Dysregulation of certain pathways, such as unsaturated fatty acid metabolism, arginine and proline metabolism may be involved in the development of Intracranial atherosclerosis stenosis. Correlation analysis of the gut microbiome and metabolites revealed a positive correlation between Bacteroides and multiple metabolites, such as Acar 12:3 and PC (8:0/22:6). CONCLUSIONS: Our analysis revealed that Bacteroides is a key bacterial genus in gut dysbiosis and may be related to the development of Intracranial atherosclerosis stenosis.

Small vessel disease burden and prognosis of recent subcortical ischaemic stroke differ by parent artery atherosclerosis.

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.

Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities).

BACKGROUND: Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general population. The objective of this study was to determine the risk of incident dementia from ICAD after adjusting for CSVD and cardiovascular risk factors in a US community-based cohort. METHODS: We acquired brain magnetic resonance imaging examinations from 2011 through 2013 in 1980 Black and White participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective cohort conducted in 4 US communities. Magnetic resonance imaging examinations included high-resolution vessel wall magnetic resonance imaging and magnetic resonance angiography to identify ICAD. Of these participants, 1590 without dementia, without missing covariates, and with adequate magnetic resonance image quality were followed through 2019 for incident dementia. Associations between ICAD and incident dementia were assessed using Cox proportional hazard ratios adjusted for CSVD (characterized by white matter hyperintensities, lacunar infarctions, and microhemorrhages), APOE4 genotype (apolipoprotein E gene ε4), and cardiovascular risk factors. RESULTS: The mean age (SD) of study participants was 77.4 (5.2) years. ICAD was detected in 34.6% of participants. After a median follow-up of 5.6 years, 286 participants developed dementia. Compared with participants without ICAD, the fully adjusted hazard ratios (95% CIs) for incident dementia in participants with any ICAD, with ICAD only causing stenosis ≤50%, and with ICAD causing stenosis >50% in ≥1 vessel were 1.57 (1.17-2.11), 1.41 (1.02-1.95), and 1.94 (1.32-2.84), respectively. ICAD was associated with dementia even among participants with low white matter hyperintensities burden, a marker of CSVD. CONCLUSIONS: ICAD was associated with an increased risk of incident dementia, independent of CSVD, APOE4 genotype, and cardiovascular risk factors. The increased risk of dementia was evident even among participants with low CSVD burden, a group less likely to be affected by vascular dementia, and in participants with ICAD causing only low-grade stenosis. Our results suggest that ICAD may partially mediate the effect that cardiovascular risk factors have on the brain leading to dementia. Both ICAD and CSVD must be considered to understand the vascular contributions to cognitive decline.

Design of the "EAST" strategy in patients with asymptomatic intracranial atherosclerotic stenosis.

INTRODUCTION: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive medical therapy. Asymptomatic ICAS (aICAS) is a frequent finding on neuroimaging, and it's an independent risk factor for future stroke. Alirocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and effectively lower low-density lipoprotein cholesterol levels. We hypothesize that extra alirocumab in addition to statin therapy (EAST) could stabilize intracranial plaques in patients with aICAS. METHODS AND ANALYSIS: In this prospective, randomized, open-label, blinded end-point study, we will use high-resolution vessel-wall magnetic resonance imaging (HR-vwMRI) to evaluate the efficacy and safety of alirocumab in patients with asymptomatic ICAS. Eighty patients with aICAS (50 %-99 %) caused by unstable plaques will be assigned to the arm of alirocumab plus statin therapy, or the arm of statin therapy in a 1:1 ratio. Patients will undergo HR-vwMRI at recruitment and after 6 months. The primary outcome is changes in plaque features evaluated by HR-vwMRI after 6 months' treatment. This trial is being conducted at the first affiliated hospital of Nanjing medical university, China. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. Written informed consents will be obtained from all participants. Study results will be published as peer-reviewed articles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, Identifier: NCT06080256.

High-resolution MR vessel wall imaging and cardiovascular health for evaluating the occurrence of ischemic stroke.

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.