Intracranial Atherosclerotic Stroke Research Articles

Association between glycated hemoglobin and functional outcomes in patients with intracranial large artery atherosclerotic disease-related acute ischemic stroke: identifying the magic number.

This study aimed to investigate the effect of the glycated hemoglobin A1c (HbA1c) level on the functional outcome (FOC) in patients with intracranial large artery atherosclerotic disease (ICLAD)-related acute ischemic stroke (AIS). This retrospective study enrolled patients with ICLAD-related AIS who were admitted to King Fahd University Hospital between January 2017 and September 2021. Patients were divided into two groups based on the optimal cutoff HbA1c level determined using receiver operating characteristic curve analysis-those with HbA1c ≤6.9% and those with HbA1c >6.9%. Demographic and other clinical characteristics were compared between the two groups using chi-square tests. The association between HbA1c and 90-day FOC was assessed using the chi-square test and odds ratios (ORs). Multivariate analysis was performed to adjust for confounding factors. A total of 140 patients were included in the analysis. A significant association was observed between the HbA1c level and FOC. Compared to patients with HbA1c ≤6.9%, patients with HbA1c >6.9% were more likely to have an unfavorable FOC [p = <0.001, OR = 2.05, 95% confidence interval (CI) = 1.33-3.14]. The association between HbA1c >6.9% and unfavorable FOC was sustained even after adjusting for confounding factors (p = 0.008) and atherosclerosis risk factors (p = 0.01). HbA1c >6.9% was also associated with higher ORs for in-hospital complications (p = 0.06, OR = 1.34, 95% CI = 1.02-1.77) and mortality (p = 0.07, OR = 1.42, 95% CI = 1.06-1.92) although these associations did not attain significant p-values. HbA1c >6.9% was significantly associated with unfavorable FOC in ICLAD-related AIS. However, further studies with larger sample sizes are required to verify whether HbA1c is an independent predictor of poor FOC. Nevertheless, targeting HbA1c <7% should be the goal of physicians when managing patients at high risk of ICLAD.

Intravenous tirofiban following successful reperfusion in intracranial large artery atherosclerotic stroke: A secondary analysis of a randomized clinical trial.

This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0-2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90-day mortality. Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02-2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; p = 0.44) or 90-day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; p = 0.27). Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

Stent reconstruction in intracranial atherosclerotic disease related acute ischemic stroke results in high revascularization rates

ObjectivesIntracranial atherosclerotic disease (ICAD) is a major cause of large vessel occlusion (LVO) in acute ischemic stroke (AIS). Our study aimed to analyze the effect of percutaneous transluminal angioplasty and stenting (PTAS) in patients with ICAD undergoing rescue treatment in terms of functional outcome and mortality rate at 90 days and compare the results to LVO with thromboembolic origins. Materials and methodsA retrospective review of a mechanical thrombectomy (MT) single center database from 01/2019 to 09/2021 was carried out using chart review and angiogram analysis. From 469 acute stroke patients, 361 patients were enroled in the study, of whom twenty-four (6.6%) were diagnosed with underlying ICAD and treated with angioplasty and stent reconstruction (PTAS) with a standardized medication protocol. Successful reperfusion, peri-procedural complications, and functional independence at 90 days were collected as outcomes. ResultsThere was no difference in age or admission National Institutes of Health Stroke Scale (NIHSS). Onset to groin puncture (median 460 vs 277 min, P = 0.019) was significantly longer in the ICAD group. The procedure time (median 73 vs 60 min, P = 0.137) did not differ. Successful reperfusion was achieved in 95.8% of ICAD and 91.1% of the remaining patients (P = 0.445). Functional independence (mRS ≤ 2) at 90 days was achieved in 45.8% (11/24) and 42.7% (144/337, (P = 0.767)). The mortality rates (mRS 6) at 90 days were similar (29.2% vs 29.4% (P = 0.983)). ConclusionDespite significantly longer treatment delays, the outcome and revascularization rates of ICAD patients were similar to the thromboembolic cohort. Our proposed protocol of PTAS and medication protocol in ICAD was effective with a similar safety profile as MT in general.

Abstract 93: Effect Of Intravenous Tirofiban Following Successful Endovascular Thrombectomy On Functional Outcomes In Large Artery Atherosclerotic Stroke: Secondary Analysis Of A Randomized Clinical Trial

Background: Incomplete reperfusion contributes to reduced neurological recovery of patients with acute large vessel occlusion and successful reperfusion after endovascular thrombectomy. Intravenous tirofiban might enhance macrocirculatory and microcirculatory reperfusion in these patients, especially in those with large artery atherosclerotic stroke. We aimed to investigate whether treatment with adjunct intravenous tirofiban is associated improved outcomes following successful reperfusion in patients with acute large artery atherosclerotic stroke. Methods: In this subgroup analysis of RESCUE BT trial, patients with intracranial large artery atherosclerotic stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 were included. The primary outcome was the difference in proportion of independent functional outcome, defined as a modified Rankin score of 0 to 2 at 90 days. Safety outcomes included the rates of symptomatic intracranial hemorrhage and 90-day mortality. Results: Among the 382 patients with intracranial large artery atherosclerosis stroke and successful reperfusion (median [IQR] age, 65 (55-72) years; 105 [27.5%] women), 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95/175) with tirofiban and 44.0% (91/207) with placebo (adjusted odds ratio [aOR], 1.59; 95% CI, 1.03-2.45; P = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of symptomatic intracranial hemorrhage within 48 hours (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; P = 0.44) or 90-day mortality (21/175 [12.0] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; P = 0.27). Conclusions: Among patients with acute large artery atherosclerotic stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of symptomatic intracranial hemorrhage or mortality. Confirmatory randomized trials in these patients are desirable.

Refined imaging features of culprit plaques improve the prediction of recurrence in intracranial atherosclerotic stroke within the middle cerebral artery territory

Recurrence is a significant adverse outcome of ischemic stroke (IS), particularly in cases of intracranial arteriosclerosis (ICAS). In this study, we investigated the impact of imaging features of culprit plaque using high-resolution magnetic resonance vessel wall imaging (HR-MR-VWI) on the prediction of IS recurrence. A total of 86 patients diagnosed with ICAS-related IS within the middle cerebral artery (MCA) territory were included, of which 23.25% experienced recurrent IS within one year. Our findings revealed significant differences between the recurrence and non-recurrence groups in terms of age (p = 0.007), diabetes mellitus (p = 0.031), hyperhomocysteinemia (p = 0.021), artery-artery embolism (AAE) infarction (p = 0.019), prominent enhancement (p = 0.013), and surface irregularity of the culprit plaque (p = 0.009). Age (HR = 1.063, p = 0.005), AAE infarction (HR = 5.708, p = 0.008), and prominent enhancement of the culprit plaque (HR = 4.105, p = 0.025) were identified as independent risk factors for stroke recurrence. The areas under the receiver operating characteristic curve (AUCs) for predicting IS recurrence using clinical factors, conventional imaging findings, HR-MR-VWI plaque features, and a combination of clinical and conventional imaging models were 0.728, 0.645, 0.705, and 0.814, respectively. Notably, the combination model demonstrated superior predictive performance with an AUC of 0.870. Similarly, AUC of combination model for predicting IS recurrence in validation cohort which enrolled another 37 patients was 0.865. In conclusion, the presence of obvious enhancement in culprit plaque on HR-MR-VWI is a valuable factor in predicting IS recurrence in ICAS-related strokes within the MCA territory. Furthermore, our combination model, incorporating plaque features, exhibited improved prediction accuracy.

Persisting cognitive impairment predicts functional dependence at 1 year after stroke and transient ischemic attack: a longitudinal, cohort study

ObjectiveMinor stroke or transient ischemic attack (TIA) usually have mild and nondisabling symptoms, and these functional deficits may recover fully e.g., TIA, however, part of them still suffer from cognitive impairment and poor outcomes. We conducted a study to determine the relationship between cognition evaluated by Montreal Cognitive Assessment (MoCA) and poor functional outcomes assessed by the Modified Rankin Scale (mRS) (mRS ≥ 2) and Stroke Impact Scale (SIS)-16(SIS-16<25%).MethodsThe data of this study come from the impairment of cognition and Sleep (ICONS) after acute ischemic stroke or transient ischemic attack in Chinese patients study. A total of 1675 minor stroke patients and TIA patients were finally recruited. Patients’ cognition were evaluated by Montreal Cognitive Assessment (MoCA) scale at 2-week (2w), 3 months (3 m) and 1 year(1y). Cognitive impairment (CI) was defined as MoCA score ≤ 22. According to MoCA score, patients were divided into 4 groups: no PSCI group: with MoCA-2w>22 and MoCA-3 m>22; improved PSCI group: with MoCA-2w ≤ 2 and MoCA-3 m>22;delayed PSCI group: MoCA-2w>22 and MoCA-3 m ≤ 22; persisting PSCI group: with MoCA-2w ≤ 22 and MoCA-3 m ≤ 22.ResultsA total of 1675 stroke patients were recruited in this study. There were 818 patients (48.84%) who had PSCI at baseline. Of these, 123 patients (15%) had mRS ≥2 at 3 months. The persisting PSCI group was a significant predictor of functional dependence at 3 months and 1 year after stroke and when adjusted for covariates such as gender, age, history of stroke, depression and intracranial atherosclerotic stenosis, stroke subtype and acute infarction type.ConclusionPersisting PSCI increased the risk of poor functional outcome after 3 months and 1 year follow-up. These high-risk individuals should be identified for targeted rehabilitation and counseling to improve longer-term post-stroke outcome.

Abstract TP92: Inappropriately Prolonged Dual Antiplatelet Therapy In The Treatment Of Stroke And Transient Ischemic Attack At An Urban Safety Net Hospital

Introduction: Time-limited dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has emerged as an important treatment modality for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic disease, minor stroke, or high-risk transient ischemic attack. However, continuation beyond the indicated treatment period may expose patients to bleeding risk without additional benefit. Methods: We conducted a retrospective study of a prospectively maintained registry (the Get-With-The-Guidelines database at our hospital) evaluating patients discharged on time-limited DAPT for secondary stroke prevention between January 1st, 2019 and July 31st, 2020. Intended and actual duration of therapy were extracted from clinical notes and prescription records. We assessed the frequency of inappropriate continuation within the entire cohort and performed univariate analyses to assess for differences in outcome with respect to clinical and demographic characteristics, including social determinants of health (such as race and primary spoken language). Results: Of the 127 patients included, 17 (13%) had inappropriately prolonged treatment with DAPT. Black patients had a significantly higher incidence of inappropriate continuation than non-Black patients and individuals speaking languages other than English or Spanish exhibited a trend toward more frequent occurrence. Patients intended to transition to monotherapy with clopidogrel and those initially presenting with stroke (rather than transient ischemic attack) had similar trends toward more frequent occurrence. Conclusions: Our study represents the first attempt to approximate the incidence of inappropriate prolongation of time-limited DAPT for secondary stroke prevention at a hospital caring for a large underserved population. Our results suggest that social determinants of health may contribute to this phenomenon, but further studies are required to replicate our observations in larger multicenter cohorts. Systems-based interventions should be aimed at ensuring proper duration of therapy to minimize bleeding risk and other side effects.

High-Resolution Intracranial Vessel Wall MRI Findings Among Different Middle Cerebral Artery Territory Infarction Types.

ObjectiveIntracranial atherosclerotic stroke occurs through various mechanisms, mainly by artery-to-artery embolism (AA) or branch occlusive disease (BOD). This study evaluated the spatial relationship between middle cerebral artery (MCA) plaques and perforating arteries among different MCA territory infarction types using vessel wall magnetic resonance imaging (VW-MRI).Materials and MethodsWe retrospectively enrolled patients with acute MCA infarction who underwent VW-MRI. Thirty-four patients were divided into three groups according to infarction pattern: 1) BOD, 2) both BOD and AA (BOD-AA), and 3) AA. To determine the factors related to BOD, the BOD and BOD-AA groups were combined into one group (with striatocapsular infarction [BOD+]) and compared with the AA group. To determine the factors related to AA, the BOD-AA and AA groups were combined into another group (with cortical infarction [AA+]) and compared with the BOD group. Plaque morphology and the spatial relationship between the perforating artery orifice and plaque were evaluated both quantitatively and qualitatively.ResultsThe plaque margin in the BOD+ group was closer to the perforating artery orifice than that in the AA group (p = 0.011), with less enhancing plaque (p = 0.030). In the BOD group, plaques were mainly located on the dorsal (41.2%) and superior (41.2%) sides where the perforating arteries mainly arose. No patient in the AA group had overlapping plaques with perforating arteries at the cross-section where the perforator arose. Perforating arteries associated with culprit plaques were most frequently located in the middle two-thirds of the M1 segment (41.4%). The AA+ group had more stenosis (%) than the BOD group (39.73 ± 24.52 vs. 14.42 ± 20.96; p = 0.003).ConclusionThe spatial relationship between the perforating artery orifice and plaque varied among different types of MCA territory infarctions. In patients with BOD, the plaque margin was closer and blocked the perforating artery orifice, and stenosis degree and enhancement were less than those in patients with AA.

Intravenous Tirofiban Infusion After Angioplasty and Stenting in Intracranial Atherosclerotic Stenosis-Related Stroke.

This study aimed to investigate the effectiveness and safety of intravenous infusion of tirofiban after emergent angioplasty with or without stenting in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke. We performed a retrospective case series study of 98 patients who underwent thrombectomy followed by angioplasty with or without stenting to treat intracranial atherosclerotic stenosis-related large-vessel occlusion. Patients were divided into 2 groups: those who received continuous intravenous infusion of tirofiban for 12 hours after procedure (intravenous tirofiban group, n=30) and those who did not receive postprocedural intravenous tirofiban (control group, n=68). The following treatment outcomes in the 2 groups were compared: early reocclusion of treated arteries on computed tomography angiography, parenchymal hematoma, symptomatic hemorrhage, and 90-day functional outcome. Early reocclusion occurred in 18 patients (18.4%). The rate of early reocclusion was significantly lower in the intravenous tirofiban group than in the control group (3.3% versus 25%, P<0.001). The rates of parenchymal hematoma, symptomatic hemorrhage, 90-day good outcome, and mortality were not significantly different between the 2 groups. In multivariate logistic analysis, the only independent predictor of early reocclusion was no use of intravenous tirofiban (odds ratio, 9.212 [95% CI, 1.155-73.495], P=0.036). A good outcome (90-day modified Rankin Scale score of 0-2) was significantly less frequent in patients with early reocclusion than in those without it (16.7% versus 72.5%, P<0.001). The use of intravenous tirofiban for 12 hours was associated with decreased risk of early reocclusion of treated arteries, with no increased risk of hemorrhage after emergent angioplasty, with or without stenting, in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke. Early reocclusion was associated with a poor outcome in such cases.

Imaging of intracranial atherosclerotic plaques using 3.0 T and 7.0 T magnetic resonance imaging-current trends and future perspectives.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke and carries a relatively high risk of stroke recurrence. Advances in high-resolution magnetic resonance imaging (HRMRI) techniques of intracranial arteries now have made it possible to directly visualize atherosclerotic plaque itself, allowing detailed assessments of plaque morphology and components. Currently available intracranial HRMRI could be performed with 2-dimensional (2D) and 3D acquisitions, and multicontrast weightings in clinically reasonable scan times. Until now, HRMRI research of ICAD has focused on the identification of plaque vulnerability, and the relationship between plaque characteristics and ischemic stroke. HRMRI at ultra-high-field strength (7.0 T) holds promise in better visualizing intracranial vessel walls, as well as identifying early lesions and total burden of ICAD. As a result, intracranial HRMRI provides great insights into pathology of intracranial atherosclerotic plaques, stroke mechanisms, and future stroke risk. In this article, we will review the technical implementation, preclinical research, clinical applications, and future directions of HRMRI for the evaluation of ICAD at 3.0 T and 7.0 T.

Ring Finger Protein 213 Variant and Plaque Characteristics, Vascular Remodeling, and Hemodynamics in Patients With Intracranial Atherosclerotic Stroke: A High-Resolution Magnetic Resonance Imaging and Hemodynamic Study.

BackgroundIntracranial atherosclerotic stroke is prevalent in Asians. We hypothesized that patients with the ring finger protein 213 (RNF213) variant, a susceptibility locus for moyamoya disease in Asians, have different neuroimaging characteristics in terms of the vessel wall and hemodynamics.Methods and ResultsWe analyzed consecutive patients with ischemic events in middle cerebral artery distribution and relevant plaques of the distal internal carotid artery or proximal middle cerebral artery on high‐resolution magnetic resonance imaging. Patients with carotid/cardiac sources of embolism or moyamoya disease were excluded. High‐resolution magnetic resonance imaging features (eg, outer vessel diameters and plaque characteristics) and fractional flow (as measured by adjusted signal intensity ratio on time‐of‐flight magnetic resonance angiography) were compared between RNF213 p.Arg4810Lys variant carriers and noncarriers. Among 144 patients included, 44 (29.9%) had the RNF213 variant. Clinical characteristics, including age, sex, body mass index, and vascular risk factors, were not significantly different between RNF213 variant carriers and noncarriers. However, the outer vessel diameter was smaller in RNF213 variant carriers than in noncarriers (P<0.0001 for middle cerebral artery of relevant stenosis [2.05‐mm analysis of RNF213 gene for moyamoya disease in the Chinese HAN population 2.75 mm]; P<0.0001 for contralateral side [2.42 versus 3.00 mm] and P<0.001 for basilar artery [3.19 versus 3.53 mm]). Other high‐resolution magnetic resonance imaging features, including plaque morphology and eccentricity, were not significantly different. Fractional flow was diminished in patients with smaller‐diameter intracranial arteries with a similar degree of stenosis.ConclusionsThe RNF213 variant may be associated with vasculogenesis, but not with atherogenesis. Patients with this variant had small intracranial arteries predisposing hemodynamic compromise in the presence of intracranial atherosclerosis. In addition to antiatherosclerotic strategies, further studies are warranted to develop novel therapeutic strategies against RNF213 vasculopathy in Asians.

Abstract TP160: The Ring Finger Protein 213 Variant and Characteristics of Plaque, Vascular Remodeling and Hemodynamics in Patients With Intracranial Atherosclerotic Stroke: A High-Resolution Mri and Hemodynamic Study

Background: Intracranial atherosclerotic stroke is prevalent in Asians. We hypothesized patients with the Ring Finger protein 213 ( RNF213 ) variant, a susceptibility locus for moyamoya disease in East Asians, have different neuroimaging characteristics in terms of vessel wall and hemodynamics. Methods: We analyzed consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant plaque on the distal internal carotid artery or proximal MCA on high-resolution MRI (HR-MRI). Patients with carotid/cardiac sources of embolism or angiographic features of moyamoya disease were excluded. HR-MRI features (e.g., outer vessel diameters and plaque characteristics) and fractional flow (as measured by adjusted signal intensity ratio on time-of-flight MRA) were compared between RNF213 p.Arg4810Lys variant carriers and non-carriers. Results: Of 144 patients included, 44 (29.9%) patients had the RNF213 variant. Clinical characteristics including age, gender, and vascular risk factors were not different between RNF213 variant carriers and non-carriers. However, outer vessel diameter was smaller in RNF213 variant carriers than in non-carriers (p&lt;0.0001 for MCA of relevant stenosis, p&lt;0.0001 for contralateral side, and p&lt;0.001 for basilar artery). Other HR-MRI features including plaque morphology were not different. Fractional flow was diminished in patients with a smaller diameter of the intracranial arteries with the similar degree of stenosis. Conclusions: The RNF213 variant may be associated with vasculogenesis but not with atherogenesis. Patients with this variant had small intracranial arteries predisposing hemodynamic compromise in the presence of intracranial atherosclerosis. Beside anti-atherosclerotic strategies, further studies are warranted to develop a novel therapeutic strategies against RNF213 vasculopathy in Asians.

Cav-1 (Caveolin-1) and Arterial Remodeling in Adult Moyamoya Disease.

Background and Purpose- Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that cav-1 (caveolin-1)-a protein that controls the regulation of endothelial vesicular trafficking and signal transduction-is associated with negative remodeling in MMD. Methods- We prospectively recruited 77 consecutive patients with MMD diagnosed via conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. The outer distal ICA diameters were examined using high-resolution magnetic resonance imaging. We evaluated whether the degree of negative remodeling in the patients with MMD was associated with RNF213 polymorphism, cav-1 levels, or various clinical and vascular risk factors. We also investigated whether the derived factor was associated with negative remodeling at the cellular level using the tube formation and apoptosis assays. Results- The serum cav-1 level was lower in the patients with MMD than in the controls (0.47±0.29 versus 0.86±0.68 ng/mL; P=0.034). The mean ICA diameter was 2.48±0.98 mm for the 126 affected distal ICAs in patients with MMD and 3.84±0.42 mm for the asymptomatic ICAs in the controls ( P<0.001). After adjusting for confounders, cav-1 levels (coefficient, 1.018; P<0.001) were independently associated with the distal ICA diameter in patients with MMD. In vitro analysis showed that cav-1 downregulation suppressed angiogenesis in the endothelial cells and induced apoptosis in the smooth muscle cells. Conclusions- Our findings suggest that cav-1 may play a major role in negative arterial remodeling in MMD.

Features of branch occlusive disease-type intracranial atherosclerotic stroke in young patients

BackgroundYoung ischemic stroke patients are common while classification and analysis based upon imaging characteristics are rarely reported. We intend to compare the clinical and MRI characteristics of cerebral stroke induced by intracranial atherosclerosis between young patients with branch occlusive disease (BOD) and those with non-branch occlusive disease (non-BOD) or small artery disease (SAD).MethodsA total of 151 subjects with acute infarction within the middle cerebral artery (MCA) territory were included and patients with ipsilateral internal carotid artery stenosis or cardioembolism were excluded. Based on the distribution characteristics of infarction and the presence of ipsilateral MCA stenosis, the patients were divided into three groups: BOD-striatocapsular area infarction with ipsilateral MCA stenosis; non-BOD -infarction size exceeds the striatocapsular area and accompanied by ipsilateral MCA stenosis; SAD. The clinical and MCA stenosis characteristics of the three groups were compared.ResultsThe number of BOD patients with hypertension was significantly higher than that of SAD (92.9% vs 53.7%, p = 0.000) and non-BOD (92.9% vs 57.1%, p = 0.001); subjects with smoking history significantly exceeded that of SAD (50% vs 26.9%, p = 0.03) and subjects with family history of cardiovascular disease was significantly less than that of non-BOD (14.3% vs 41.1%). Baseline NIHSS scores and mRS scores at discharge in patients with BOD were significantly lower than those with non-BOD (p = 0.000, p = 0.001). Majority of patients in non-BOD group displayed severe MCA stenosis (39 cases, 69.6%) while that in BOD group displayed mild stenosis (26 cases, 92.9%), and the difference was statistically significant (p = 0.000). Compared with non-BOD group, the stenosis in BOD group located at a relatively distal end in the M1 segment of MCA (S/M1, 58% vs 40%, p = 0.000) and was more localized (stenosis level/ (SL/M1), 1.86 (1.35–2.6) vs 2.9 (2.0–5.0), p = 0.002).ConclusionBOD in young patients with ischemic stroke induced by intracranial atherosclerosis is not rare (33.3%) and its clinical manifestations and prognosis are similar to those of SAD. This may be related to the mild localized stenosis at the distal end in the M1 segment of MCA. Control of hypertension might play a positive role in secondary prevention.

Distinct Roles of Endothelial Dysfunction and Inflammation in Intracranial Atherosclerotic Stroke

Background/Aims: The aim of the study was to evaluate the differential roles of endothelial dysfunction and inflammation in intracranial atherosclerotic stroke (ICAS). Methods: We prospectively recruited 262 patients with acute cerebral infarcts caused by ICAS and 75 individuals with no history of stroke as controls. Markers of endothelial dysfunction (asymmetric dimethylarginine, ADMA) and inflammation (lipoprotein-associated phospholipase A2, Lp-PLA₂) were measured. Acute ischemic lesions were measured in terms of their size, composition, and patterns. Subclinical microangiopathy (degree of leukoaraiosis) and macroangiopathy (presence/number of asymptomatic stenoses) were graded in each patient. Results: Compared to normal controls, serum levels of ADMA (0.69 ± 0.14 vs. 0.47 ± 0.10, p < 0.001) and Lp-PLA₂ (138.1 ± 116.8 vs. 19.0 ± 58.0, p < 0.001) were elevated in patients with ICAS. A high ADMA serum level was associated with greater prevalence of preclinical microangiopathy and macroangiopathy. Contrastingly, an elevated serum Lp-PLA₂ level was associated with larger ischemic lesions, a greater number of lesions, and a larger cortical pattern. Conclusions: Endothelial dysfunction and inflammation have distinct effects in ICAS patents; endothelial dysfunction is associated with the underlying micro- and macro-atherosclerotic burden, whereas inflammation is associated with acute infarct volume and pattern.

Abstract TP125: Distinct Roles of Endothelial Dysfunction and Inflammation in Intracranial Atherosclerotic Stroke

Aims: Endothelial dysfunction and inflammation play a major role in the progression of atherosclerosis. This study aimed to evaluate the differential roles of endothelial dysfunction and inflammation in intracranial atherosclerotic stroke (ICAS). Methods: We prospectively recruited 262 patients with acute cerebral infarcts caused by ICAS and 75 individuals with no history of stroke as controls. Markers of endothelial dysfunction (asymmetric dimethylarginine, ADMA) and inflammation (lipoprotein-associated phospholipase A2, Lp-PLA 2 ) were measured. Acute ischemic lesions were measured in terms of their size, composition, and patterns. Subclinical microangiopathy (degree of leukoaraiosis) and macroangiopathy (presence/number of tandem stenoses) were graded in each patient. Results: Compared to normal controls, serum levels of ADMA (0.69 ± 0.14 vs. 0.47 ± 0.10, P &lt; 0.001) and Lp-PLA 2 (138.1 ± 116.8 vs. 19.0 ± 58.0, P &lt; 0.001) were elevated in patients with ICAS. Although there was a significant correlation between ADMA and Lp-PLA 2 levels in patients with ICAS (r 2 = 0.235, P &lt;0.001), some patients showed high Lp-PLA 2 but low ADMA levels, while others showed high ADMA but low Lp-PLA 2 levels. A high ADMA serum level was associated with a greater prevalence of preclinical microangiopathy and macroangiopathy. Contrastingly, an elevated serum Lp-PLA 2 level was associated with larger ischemic lesions, a greater number of lesions, and a larger cortical pattern. Conclusion: Endothelial dysfunction and inflammation have distinct effects in ICAS patents: endothelial dysfunction is associated with the underlying micro- and macro-atherosclerotic burden, whereas inflammation is associated with acute infarct volume and pattern.

Abstract 110: Caveolin-1 and Arterial Remodeling in Adult Moyamoya Disease

Background and purpose: Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease that is characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that caveolin-1, a protein that controls the regulation of endothelial vesicular trafficking and signal transduction, is associated with negative remodeling in MMD. Methods: We prospectively recruited 77 consecutive patients with MMD (49 bilateral and 28 unilateral MMD) diagnosed by conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. Distal ICA outer diameters were examined with high-resolution MRI. We evaluated whether the degree of negative remodeling in MMD patients was associated with RNF213 polymorphism, caveolin-1 levels, or various clinical and vascular risk factors. Results: The RNF213 variant was observed in 49 (63.6%) patients with MMD. The serum caveolin-1 (ng/mL) level was lower in MMD patients than in controls (0.47±0.29 vs. 0.86±0.68, P =0.034). The mean ICA diameter was 2.48±0.98 mm (range 0.00-4.76) for the 126 affected distal ICAs in MMD patients and 3.84±0.42 mm for asymptomatic ICAs in controls. After adjusting for possible confounders, male sex (coefficient, 0.396; P =0.029), clinical presentation with ischemic stroke (coefficient, -0.733; P &lt;0.001), and caveolin-1 level (coefficient, 1.018; P &lt;0.001) were independently associated with distal ICA diameter in MMD patients. Conclusion: Our findings suggest that caveolin-1 may play a major role in arterial negative remodeling in MMD patients. Future studies exploring caveolin-1 as a therapeutic target in MMD are warranted.

Caveolin-1, Ring finger protein 213, and endothelial function in Moyamoya disease.

Moyamoya disease is a unique cerebrovascular occlusive disease of unknown etiology. Ring finger protein 213 (RNF213) was identified as a susceptibility gene for Moyamoya disease in East Asian countries. However, the pathogenesis of Moyamoya disease remains unclear. We prospectively analyzed clinical data for 139 patients with Moyamoya disease (108 bilateral Moyamoya disease, 31 unilateral Moyamoya disease), 61 patients with intracranial atherosclerotic stroke, and 68 healthy subjects. We compared the genetic (RNF213 variant) and protein biomarkers for caveolae (caveolin-1), angiogenesis (vascular endothelial growth factor (VEGF) and receptor (VEGFR2), and antagonizing cytokine (endostatin)) and endothelial dysfunction (asymmetric dimethylarginine (ADMA), and nitric oxide and its metabolites (nitrite and nitrate)) between patients with Moyamoya disease and intracranial atherosclerotic stroke. We then performed path analysis to evaluate whether a certain protein biomarker mediates the association between genes and Moyamoya disease. Caveolin-1 level was decreased in patients with Moyamoya disease and markedly decreased in RNF213 variant carriers. Circulating factors such as VEGF and VEGFR2 did not differ among the groups. Markers for endothelial dysfunction were significantly higher in patients with intracranial atherosclerotic stroke but normal in those with Moyamoya disease. Path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 levels that could lead to Moyamoya disease. The level of combined marker of Moyamoya disease (caveolin-1) and intracranial atherosclerotic stroke (ADMA, an endothelial dysfunction marker) predicted Moyamoya disease with good sensitivity and specificity. Our results suggest that Moyamoya disease is a caveolae disorder but is not related to endothelial dysfunction or dysregulation of circulating cytokines.

Previous Statin Use and High-Resolution Magnetic Resonance Imaging Characteristics of Intracranial Atherosclerotic Plaque

Although statin use has been linked to the stabilization of systemic atherosclerosis, its effect on symptomatic intracranial atherosclerotic plaques has yet to be explored. We hypothesized that premorbid statin use is associated with plaque instability in intracranial arteries and may lead to differential patterns (size and distribution) of ischemic lesions in patients with acute intracranial atherosclerotic stroke. One hundred and thirty-six patients with acute infarcts caused by intracranial atherosclerotic stroke underwent high-resolution magnetic resonance imaging. Patients were categorized into 3 groups based on their premorbid statin use: nonuser, low-dose user, and high-dose user, according to the 2013 American College of Cardiology/American Heart Association guidelines on blood cholesterol. Symptomatic lesions in intracranial arteries were analyzed using high-resolution magnetic resonance imaging for vascular morphology (degree of stenosis, remodeling index, and wall index) and plaque activation (pattern and volume of enhancement). The cortical distribution and volume of ischemic brain lesions were measured using diffusion-weighted imaging. Among the enrolled patients, 38 (27.94%) were taking statins before the index stroke (22 low-dose statins and 16 high-dose statins). The degree of stenosis, remodeling index, and wall index did not differ between the 3 groups. However, the volume of plaque enhancement was significantly lower in statin users (nonuser, 33.26±40.72; low-dose user, 13.15±17.53; high-dose user, 3.13±5.26; P=0.002). Premorbid statin use was associated with a higher prevalence of nonembolic stroke and a decrease in large cortical infarcts (P=0.012). Premorbid statin usage is independently associated with reduced plaque enhancement and a decrease in large cortical lesions in patients with intracranial atherosclerotic stroke.

Risk factors, topographic patterns and mechanism analysis of intracranial atherosclerotic stenosis ischemic stroke

Background: The association between topographic patterns, risk factors and stroke mechanisms of ICAS in first-ever stroke remains unknown. Methods: A large sample sized retrospective study was performed on first-ever ICAS ischemic stroke using DWI and MRA. Results: Hypertension (60.92%), cigarette smoking (26.82%), MCA (76.65%) and multiple vessels (65.37%) stenosis, were the major factors favoring different mechanisms. Subcortical lesions were the most occurring topographic patterns (41.4%). The common mechanism was LBO (66.3%). Statistical analysis showed a significant relationship between lesion patterns and mechanisms (r = 0.384, P = 0.001). Single mechanism had the higher apoB/apoAI ratio (P = 0.005) and levels of plasma apoB (P = 0.007) compared with multiple mechanisms. The anterior circulation stroke were more multiple mechanisms as compared to the posterior circulation stroke (P = 0.001). LBO was more prevalent in posterior circulation stroke than in anterior circulation stroke (P = 0.001). Conclusions: The topographic patterns of ischemic lesions is helpful in early identification of different mechanisms of ICAS. Monitoring apoB and apoB/apoA1 may help to predict the mechanism of stroke with ICAS. The prevalence of mechanisms differ between anterior and posterior circulation stroke with ICAS.