Warfarin-Aspirin Symptomatic Intracranial Disease Research Articles

Impact of Clonal Hematopoiesis of Indeterminate Potential on the Long-Term Risk of Recurrent Stroke in Patients with a High Atherosclerotic Burden

Clonal hematopoiesis of indeterminate potential (CHIP), which has recently been shown to be an age-related phenomenon, is associated with cardiovascular diseases, including atherosclerosis and stroke. This study focused on the association between CHIP and short- and long-term stroke recurrence in patients with acute ischemic stroke and intracranial atherosclerotic stenosis (ICAS). This study included 4,699 patients with acute ischemic stroke based on data from the Third China National Stroke Registry (CNSR-III), a nationwide prospective hospital-based registry. The ICAS assessment followed the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease Study and Brain Imaging. Atherosclerosis Scores (AS) were used to assess the atherosclerosis burden, as determined by the number and severity of steno-occlusions in the intracranial arteries. The primary outcome was stroke recurrence three months and one year after the event. Among the 4,699 patients, 3,181 (67.7%) were female, and the median age was 63.0 (55.0-71.0) years. We found that CHIP significantly increased the risk of stroke recurrence at the 1-year follow-up in patients with ICAS (adjusted hazard ratio [HR] 2.71, 95% confidence interval [CI] (1.77-4.16), P for interaction, 0.008). Our results revealed that CHIP might have a significant impact on the long-term risk of recurrent stroke, particularly in patients with a higher atherosclerotic burden.

Association of Dental Infections with Intracranial Atherosclerotic Stenosis

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, <50% ICAS, and ≥50% ICAS. Results: Among dentate subjects who underwent vascular imaging, 801 (70%) had no ICAS, 232 (20%) had <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 <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 <50% and ≥50%. Conclusion: We report significant associations between mild-moderate tooth loss, severe tooth loss, and severe PD with <50% ICAS as well as an association between extensive gingivitis and ≥50% ICAS. We did not find an association between dental caries and ICAS.

Arachnoid Granulation Causing Unilateral Pulsatile Tinnitus Treated With Dural Venous Sinus Stenting.

Large arachnoid granulations that protrude into dural venous sinuses and partially obstruct outflow are an underappreciated etiology of pulsatile tinnitus (PT). Endovascular dural venous sinus stenting is thought to diminish turbulent venous outflow and may relieve obstruction caused by arachnoid granulations. Four patients at two institutions were evaluated for unilateral PT. Magnetic resonance imaging and digital subtraction angiography revealed moderate-to-severe stenoses from large arachnoid granulations within the implicated transverse sinus. All patients underwent venous manometry and endovascular sinus stenting. All patients experienced immediate and complete remission of their PT. Stenoses were relieved by a mean of 93% by Warfarin-Aspirin Symptomatic Intracranial Disease criteria. There were no procedural or periprocedural complications. All patients continued to report complete symptom resolution at a mean of 8-month follow-up. PT from arachnoid granulations are an underappreciated pathomechanism. Endovascular dural venous sinus stenting is an effective intervention for treating unilateral PT secondary to large arachnoid granulation.

Abstract TMP76: Association Of Adiposity With Intracranial Atherosclerosis

Introduction: Adiposity, as measured by Body Mass Index (BMI) and Waist-to-Hip Ratio (WHR), is associated with ischemic stroke. However, association with Intercranial Atherosclerosis has not been well-established in the United States. We assessed the hypothesis that adiposity is associated with asymptomatic intracranial atherosclerosis (ICAS). Methods: BMI was calculated as weight (kg)/height (m) 2 . The ratio of waist (umbilical level) to hip (maximum buttocks) circumference (WHR) was calculated as a measure of fat distribution. In the ARIC cohort, a stratified subset (N=1145) 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 trial. In this study, we evaluated the relationship between BMI as well as WHR, and significant asymptomatic ICAS, defined as ≥50% stenosis. Student t-tests were performed to test continuous variables, and X 2 test was used to compare categorical variables. Analysis of covariance (ANCOVA) was used for multivariate testing. Results: Among subjects who underwent vascular imaging, 1033 (90%) had &lt;50% ICAS and 112 (10%) had ≥50% ICAS. At the time of assessment, those with ≥50% ICAS were older (age 79±5 vs. 76±5, p&lt;0.001), and had higher systolic blood pressure or SBP (134±19 vs. 130±18, p=0.02), compared with those with &lt;50% ICAS. The BMI was higher (29.1±6.7 vs. 28.1±5.2), although the difference was statistically borderline significant (p=0.06). The WHR was higher (0.95±0.07 vs. 0.93±0,08), the difference being statistically significant (p=0.01). The difference remained significant after adjustment for age and SBP (p=0.02). Conclusion: We report a significant association between WHR, a measure of central adiposity, and ≥50% ICAS. This may be one of the first reported associations between central adiposity and ICAS. These results emphasize the importance of adiposity distribution in addition to overall adiposity, as a risk factor for significant asymptomatic ICAS.

Development and validation of visual grading system for stenosis in intracranial atherosclerotic disease on time-of-flight magnetic resonance angiography.

Although the overestimation problem of time-of-flight magnetic resonance angiography (TOF-MRA) applying the warfarin-aspirin symptomatic intracranial disease (WASID) method to assess intracranial arterial stenosis has often been suggested, no pertinent grading system for TOF-MRA has been developed. We aimed to develop and evaluate the performance of a visual grading system for intracranial arterial stenosis on TOF-MRA (MRAVICAST). This single-center cohort study analyzed prospective observational registry data from a comprehensive stroke center between January 2014 and February 2020. Patients with confirmed stenosis of the intracranial large arteries who underwent confirmative digital subtraction angiography (DSA) were included; a 4-point grading system was developed based on physical characteristics of TOF-MRA. The overall diagnostic accuracies of MRAVICAST for each grade, interobserver reproducibility, and positive predictive values for > 50% and > 70% stenoses were evaluated. We analyzed 132 segments with intracranial atherosclerotic stenosis from 71 patients (34 men and 37 women; mean age, 61.0 ± 15.25years; range, 21-89years). The overall diagnostic accuracy of MRAVICAST (93.9%, 124/132) was higher than that of MRAWASID (50.8%, 67/132) for each grade. The degree of stenosis did not differ significantly between MRAVICAST and DSAWASID (p = .849). Regarding reproducibility, MRAVICAST demonstrated excellent interobserver agreement (ICC, 0.989; 95% CI, 0.979-0.999). The positive predictive values of MRAVICAST for the diagnosis of > 50% and > 70% stenoses were 97.3% and 100.0%, respectively. The new intuitive grading system accurately and reliably determined the degree of stenosis in intracranial arterial atherosclerosis patients. MRAVICAST could be a versatile alternative to MRAWASID for evaluating intracranial arterial stenosis. • In this retrospective diagnostic study (sample: 132 stenotic segments), the overall accuracy of the visual grading system (MRAVICAST) was 94%, and positive predictive value for > 50% stenosis was 97%. • In the era of medical treatment for intracranial atherosclerotic stenosis, MRAVICAST could be a versatile alternative method to MRAWASID for evaluating intracranial arterial stenosis.

The Role of Stenting in Management of Isolated Symptomatic Basilar Artery Stenosis

Isolated basilar artery stenosis (BAS) is a rare etiology of ischemic neurologic conditions. First-line treatment of symptomatic stenosis is typically medical therapy as outlined in the Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) trial and the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial.1,2 We present the case of a male in his 60s with isolated BAS who failed maximal medical treatment but experienced a decrease in transient ischemic attacks and acute ischemic stroke occurrences after angioplasty and stenting.

Correlation between intracranial vertebral artery stenosis diameter measured by digital subtraction angiography and cross-sectional area measured by optical coherence tomography

BackgroundIntracranial vertebral artery (V4 segment) stenosis quantification traditionally uses the narrowest stenosis diameter. However, the stenotic V4 lumen is commonly irregularly shaped. Optical coherence tomography (OCT) allows a more precise...

Abstract 136: Role of Periodontal Disease on Intracranial Atherosclerosis

Introduction: Periodontal disease (PD) is a chronic inflammatory process that affects gum and teeth. Due to the role of inflammation on atherosclerosis, we assessed the hypothesis that PD is 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 6155 subjects from the Dental Atherosclerosis in Communities Study (DARIC) without prior stroke were used to differentiate seven periodontal profile classes (PPCs). Of this cohort, 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. In this study, we evaluated the relationship between PD status and severe asymptomatic ICAS, defined as ≥50% stenosis. Results: Among dentate subjects who underwent vascular imaging, 1033 (90%) had 0-50% ICAS and 112 (10%) had ≥50% ICAS. Compared to participants without gum disease (PPC-A), participants with gingivitis (PPC-C) had significantly higher odds of having ≥50% ICAS (Figure 1; Crude OR 2.1, 95% CI 1.2-3.8, p=0.015). This association strengthened after adjusting for the significant confounding variables: age, hypertension, and LDL cholesterol (Adjusted OR 2.4, 95% CI 1.3-4.5, p=0.006). Conclusion: We report a significant association between inflammatory PD class and ≥50% asymptomatic ICAS. Because gingivitis is reversible, future studies are needed to determine if treatment of gingivitis can prevent the development and progression of ICAS, thus reducing the risk of stroke.

Stenosis Detection From Time-of-Flight Magnetic Resonance Angiography via Deep Learning 3D Squeeze and Excitation Residual Networks

Intracranial artery stenosis is an important public health concern internationally, due to it being one of the major causes of ischemic stroke. In this study, we aim to provide a computer-aided diagnosis algorithm capable of automatically distinguishing between Internal Carotid Artery (ICA) stenosis and normal to minimize the labor-intensiveness of stenosis detection. Using Time-of-Flight Magnetic Resonance Angiography (TOF-MRA), a novel deep learning detection model via 3D Squeeze and Excitation Residual Networks (SE-ResNet) is proposed. Pre-processing of TOF-MRA, data augmentation, training of 3D SE-ResNet, and testing using patch-based and patient-based methods with cross-validation is described. The proposed network using a database consisting of 50 normal cases (ICA-N) and 41 stenosis cases (ICA-S) with grade level of above 30% was evaluated. All 41 ICA-S cases were categorized according to the diameter (D_stenosis) of the artery at the site of the most severe stenosis by expert radiologists, whereas percent stenosis was measured by Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) method. The proposed 3D SE-ResNet was further compared with more conventional networks including 3D ResNet and 3D VGG. The results showed the capability to detect stenosis achieving overall Area Under the Curve (AUC) and accuracies of 0.947 and 91.0% for patch-based and 0.884 and 81.0% for patient-based testing, respectively. In addition, the proposed 3D SE-ResNet achieved better performance against conventional 3D ResNet and 3D VGG with improvement rates of 0.053 and 0.095 for patch-based and 0.053 and 0.065 for patient-based testing in terms of AUC, respectively.

Color-coded duplex sonography vs. 3.0 Tesla magnetic resonance angiography for detection of intracranial stenosis of the internal carotid artery: A prospective cohort study.

Hemodynamic changes may provide important information for clinical decision-making in internal carotid artery (ICA) stenosis. The degree of stenosis is responsible for the hemodynamic changes. For detection of intracranial stenosis, each diagnostic method has its own advantages and disadvantages. The goal of the present study was to compare the sensitivity and accuracy of color-coded duplex sonography with that of magnetic resonance angiography (MRA) for the detection of intracranial stenosis. Patients with 3 vessels and/or left stem coronary artery disease were subjected to transcranial and extracranial color-coded duplex sonography (n=998), MRA (n=998) and invasive catheter angiography (n=939). The degree of stenosis was defined according to the Warfarin-Aspirin Symptomatic Intracranial Disease methodology. A ≥50% reduction in artery diameter was considered as a positive obstructive lesion. The benefits of each imaging method were assessed by clinical decision-making analysis. Color-coded duplex sonography and MRA, had sensitivities of 0.935 and 0.957 and accuracies of 0.92 and 0.974, respectively, when using invasive catheter angiography as a gold standard. The number of false-positive obstructive lesions detected by MRA was significantly higher than that for color-coded duplex sonography (53 vs. 13, P<0.0001). Color-coded duplex sonography was able to detect an obstructive lesion in one single image for ICAs with ≥57% stenosis, while MRA was only capable of detecting an obstructive lesion in one single image for ICAs with ≥80% stenosis. In conclusion, color-coded duplex sonography is a reliable method for the detection of intracranial stenosis in patients with coronary artery disease.

Comparative Evaluation of North American Symptomatic Carotid Endarterectomy Trial and Warfarin-Aspirin Symptomatic Intracranial Disease Methods for Measurement of Middle Cerebral Artery Stenosis in Digital Subtraction Angiography and Magnetic Resonance Angiography

Comparative Evaluation of North American Symptomatic Carotid Endarterectomy Trial and Warfarin-Aspirin Symptomatic Intracranial Disease Methods for Measurement of Middle Cerebral Artery Stenosis in Digital Subtraction Angiography and Magnetic Resonance Angiography

Accuracy of high resolution MRI in measurement of vascular stenosis ratio in atherosclerotic middle cerebral artery

Objective To evaluate the accuracy of measurements of atherosclerotic middle cerebral artery (MCA) stenosis with 3.0 T high-resolution magnetic resonance imaging (HR-MRI). Methods Forty patients with symptomatic atherosclerotic stenosis of middle cerebral artery (MCA) confirmed by digital subtraction angiography (DSA) in the Affiliated Hospital of Binzhou Medical College from September 2017 to May 2018 were enrolled in the study. Patients were scanned by HR-MRI sequence (including T1WI, T2WI, PDWI). The MCA M1 stenosis rate on HR-MR images was assessed by warfarin-aspirin symptomatic intracranial artery disease (WASID) method and area measurement algorithm, respectively, and based on the stenosis rate the degree of stenosis (semi-quantitative measurement) was determined. The accuracy of the two measurement methods was evaluated with DSA results as the gold standard. Results The HR-MRI images showed the structure of the vessel wall clearly in 30 patients meeting the measurement requirements. The inner edge of the vessel was clearly distinguishable and smooth, showing eccentric stenosis. The stenosis rate of MCA measured by DSA, WASID method and area measurement algorithm were (82±17)%, (70±12)%, (81±16)%, respectively (P>0.05). The result of area measurement algorithm was better correlated with DSA (r=0.893); and the coincidence of the stenosis degree rate of two measurement method was 90%(27/30). Conclusion The area measurement algorithm based on the HS-MRI has high accuracy in measuring the degree of MCA stenosis,which is of high clinical application value. Key words: Magnetic resonance imaging; Middle cerebral artery stenosis; Atherosclerosis

Quantifying Intracranial Internal Carotid Artery Stenosis on MR Angiography.

Intracranial atherosclerosis is a common cause of ischemic stroke. Intracranial stenosis is most commonly quantified by the Warfarin-Aspirin Symptomatic Intracranial Disease method, which involves calculating a ratio of luminal diameter measurements on conventional angiography. Our purpose was to determine whether a single linear measurement of the narrowest caliber of the intracranial ICA on MRA can accurately predict Warfarin-Aspirin Symptomatic Intracranial Disease stenosis measurements. We identified patients from a prospective stroke registry who had undergone head MRAs to quantitatively evaluate the degree of Warfarin-Aspirin Symptomatic Intracranial Disease-derived stenosis in each intracranial ICA. We also made a single linear millimeter measurement at the site of maximal narrowing of the ICA. We calculated a correlation coefficient between the lumen diameter in millimeters and percentage Warfarin-Aspirin Symptomatic Intracranial Disease stenosis. We performed receiver operating characteristic analysis to determine optimal luminal diameter cutoff values. In 386 unique intracranial ICAs, we found a strong linear relationship between single lumen measurements and Warfarin-Aspirin Symptomatic Intracranial Disease-style stenosis measurements (R = -0.84, P < .0001). We found that ICA lumen diameters of ≤2.1 and ≤1.3 mm were optimal cutoffs for identifying patients with ≥50% stenosis and ≥70% stenosis, respectively (area under the curve = 0.96 and 0.99, respectively). There is a strong linear relationship between the narrowest lumen diameter of the intracranial ICA and percentage stenosis. Our results suggest that a single lumen diameter measurement on MRA allows accurate estimation of Warfarin-Aspirin Symptomatic Intracranial Disease stenosis, which may affect risk stratification and treatment decisions.

Wingspan stentの使用経験と文献レビュー

We report three cases that involved the use of the Wingspan stent (WS) system for the treatment of intracranial atherosclerotic disease and review the literature. The first patient was an 80-year-old man who presented with recurrence of a transient ischemic attack and medically refractory restenosis of the left petrous internal carotid artery (ICA). He underwent percutaneous transluminal angioplasty (PTA) and stenting using the WS. There have been no ischemic events and no restenosis after treatment. The second patient was a 73-year-old man who presented with minor stroke due to chronic total occlusion of the left ICA. He underwent PTA and stenting using the WS for dissection of the left ICA. There have been no ischemic events and no restenosis after treatment. The third patient was a 65-year-old woman who presented with minor stroke due to stenosis of the right middle cerebral artery (MCA). She underwent PTA and stenting using the WS for dissection of the right MCA. There have been no ischemic events and no restenosis after treatment. The WS system was useful for the treatment of medically refractory restenosis and dissection of intracranial arteries after PTA.The 1-year risk of recurrence of ischemic stroke in the treatment of symptomatic intracranial arterial stenosis (ICAS) with the WS system was lower than that in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. However, the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial demonstrated that aggressive medical treatment was superior to stenting with the WS system in preventing recurrent ischemic stroke. Further evaluation of clinical outcome is required to confirm the safety and efficacy of the WS system for symptomatic ICAS.

Diagnosis and Treatment of Intracranial Stenoses.

Stroke is one of the most frequent and most significant vascular diseases. According to estimates, 16.9 million people suffered a stroke in 2010, and over one-third of the incidents were lethal. The risk of suffering a stroke due to intracranial stenosis is between 7 and 24%. As opposed to extracranial stenoses of the internal carotid artery, there is no standardized treatment concept for intracranial stenoses. At present, treatment with a low daily dose of 100 mg aspirin is recommended by the guidelines for intracranial stenoses to additionally prevent dose-dependent gastrointestinal side effects and bleeding complications. The WINGSPAN study showed stroke rates and mortality rates amounting to 4.5% after 30 days and 7.0% after 6 months. The Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis study is a randomized, multicenter study that compared endovascular stent treatment in patients with symptomatic arteriosclerotic intracranial stenoses with intensified drug therapy. After the inclusion of 451 of 764 study patients planned initially, study recruitment was terminated prematurely because the stroke rate or mortality rate within 30 days was 14.7% in the endovascular treatment group compared with 5.8% in the drug therapy group and 20% within 12 months compared with 12.2%. Quite recently the results of a second randomized study of intracranial stents were published in the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy study. In an analysis published by Liebeskind et al. concerning the impact of collateral vessels on the stroke risk based on data from the Warfarin-Aspirin Symptomatic Intracranial Disease study, it was demonstrated that a sufficiently formed collateral network in patients with high-degree vascular constrictions (≥ 70%) plays a crucial role in the avoidance of strokes. If there is no system of collateral vessels or if it is insufficient, the stroke risk in the dependent vascular territory is six times higher. So far it has not yet been possible to conclusively answer the question of optimal treatment for intracranial stenoses. There is particularly need for action regarding the treatment of high-degree recurrent symptomatic stenoses, not only in light of the unfavorable prognosis but also within the scope of demographic change.

Reproducibility of Middle Cerebral Artery Stenosis Measurements by DSA: Comparison of the NASCET and WASID Methods

PurposeTo evaluate the intra- and inter-observer variability of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) criteria for the evaluation of middle cerebral artery (MCA) stenosis using digital subtraction angiography (DSA).Materials and MethodsDSA images of 114 cases with 131 stenotic MCAs were retrospectively analyzed. Two radiologists and a researcher measured the degree of MCA stenosis independently using both NASCET and WASID methods. To determine intra-observer agreement, all the observers reevaluated the degree of MCA stenosis 4 weeks later. The linear relation and coefficient of variation (CV) between the measurements made by the two methods were assessed by correlation coefficient and multi-factor analysis of variance (ANOVA), respectively. Intra- and inter-observer variability of the two methods was evaluated by intraclass correlation coefficient (ICC), Spearman’s R value, Pearson correlation coefficient and Bland-Altman plots.ResultsDespite the fact that the degree of MCA stenosis measured by NASCET was lower than measured using the WASID method, there was good linear correlation between the measurements made by the two methods (for the mean measurements of the 3 observers, NASCET% = 0.891 × WASID% - 1.89%; ICC, Spearman’s R value and Pearson correlation were 0.874, 0.855, and 0.874, respectively). The CVs of both intra- and inter-observer measurements of MCA stenosis using WASID were significantly lower than that using NASCET confirmed by the multi-factor ANOVA results, which showed only the measurement methods of MCA stenosis had significant effects on the CVs both in intra- and inter-observer measurements (both P values < 0.001). Intra-observer measurements showed good or excellent agreement with respect to WASID and NASCET evaluation (ICC, 0.656 to 0.817 and 0.635 to 0.761, respectively). Good agreement for the WASID evaluation (ICC, 0.592 to 0.628) and for the NASCET evaluation (ICC, 0.529 to 0.568) was observed for inter-observer measurements. Bland-Altman plots demonstrated that the WASID method had better reproducibility and intra-observer agreement than NASCET method for evaluating MCA stenosis.ConclusionBoth NASCET and WASID methods have an acceptable level of agreement; however, the WASID method had better reproducibility for the evaluation of MCA stenosis, and thus the WASID method may serve as a standard for measuring the degree of MCA stenosis.

Clinical, lifestyle, socioeconomic determinants and rate of asymptomatic intracranial atherosclerosis in stroke free Pakistanis.

BackgroundIntracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region.MethodsThe study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used in the Warfarin–Aspirin Symptomatic Intracranial Disease study. The risk factors associated with asymptomatic ICAD are reported along with prevalence ratios.ResultsOf the 200 participants, ICAD was found in 34.5% (n = 69) of the participants. Mean age was 37.1 (S.D 15.1) years with 62% younger than 45 years. Self-reported hypertension was found in 26.5% subjects, diabetes in 9%, dyslipidemia in 5% and depression in 60%. Smokeless tobacco (Adjusted PR 3.27 (1.07-6.05)), Western diet, high socioeconomic status (Adjusted PR 2.26 (1.99-5.62)) and dyslipidemia (Adjusted PR 1.88 (1.25-2.21)) had significant associations with ICAD after multivariable analysis. Age, gender, diabetes, hypertension, depression and physical activity did not have a significant association.ConclusionICAD was found on MRI in one in three asymptomatic Pakistanis and was associated with modifiable risks. Initiatives targeting primary prevention may be able to decrease the burden of disease caused by stroke due to ICAD.Study Registration NumberNCT02072876 2/25/2014

Infarct Patterns, Collaterals and Likely Causative Mechanisms of Stroke in Symptomatic Intracranial Atherosclerosis

Background: There are limited data on the specific mechanisms of stroke in patients with intracranial atherosclerotic stenosis (ICAS). We undertook this study to describe infarct patterns and likely mechanisms of stroke in a large cohort of patients with ICAS, and to evaluate the relationship of these infarct patterns to angiographic features (collaterals, stenosis location and stenosis severity). Methods: We evaluated infarct patterns in the territory of a stenotic intracranial artery on neuroimaging performed at baseline and during follow-up if a recurrent stroke occurred in patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We defined the likely mechanism of stroke (artery-to-artery embolism, perforator occlusion, hypoperfusion or mixed) according to the site of ICAS and based on the infarct patterns on neuroimaging. Collaterals were assessed using American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grades, and stenosis severity using the WASID trial's measurement technique. We evaluated the association of infarct patterns with angiographic features using χ² tests. Results: The likely mechanisms of stroke based on the infarct patterns at baseline in the 136 patients included in the study were artery-to-artery embolism (n = 69; 50.7%), perforator occlusion (n = 34; 25%), hypoperfusion (n = 12; 8.8%) and mixed (n = 21; 15.5%). Perforator-occlusive infarcts were more frequent in the posterior circulation, and mixed patterns were more prevalent in the anterior circulation (both p < 0.01). Most of the mixed patterns in the anterior circulation combined small pial or scattered multiple cortical infarcts with infarcts in border-zone regions, especially the cortical ones. Isolated border-zone infarcts were not significantly associated with a poor grading for collaterals or the severity of stenosis. Among 47 patients with a recurrent infarct during follow-up, the infarct patterns suggested an artery-to-artery embolic mechanism in 29 (61.7%). Conclusions: Artery-to-artery embolism is probably the most common mechanism of stroke in both the anterior and the posterior circulations in patients with ICAS. An extension of intracranial atherosclerosis at the site of stenosis into adjacent perforators also appears to be a common mechanism of stroke, particularly in the posterior circulation, whereas hypoperfusion as the sole mechanism is relatively uncommon. Further research is important to accurately establish the specific mechanisms of stroke in patients with ICAS, since preliminary data suggest that the underlying mechanism of stroke is an important determinant of prognosis.

Reviving Intracranial Angioplasty and Stenting "SAMMPRIS and beyond".

We review the methods and results of Stenting and Aggressive Medical Management for Preventing Recurrent Stroke (SAMMPRIS) and provide a critical review of its strengths and limitations. In SAMMPRIS, the aggressive medical treatment arm (AMT arm) did substantially better than the Wingspan Stenting plus aggressive medical management arm (WS+ arm). Complications in the first 30 days post intervention led to the disparity between treatment arms. A major contribution of SAMMPRIS was the added value that AMT and lifestyle change may provide, when compared to a precursor trial, Warfarin–Aspirin Symptomatic Intracranial Disease (WASID), designed to prevent stroke in persons with high-grade symptomatic intracranial occlusive disease, however, the results of neither of these two trials have ever been reproduced. On the other hand, we argue that technical limitations of the Wingspan stent system (WS System) and lack of an angioplasty only intervention arm may have led to a premature launch of the trial and early termination of the study. Future randomized trials with different devices and modified patient selection criteria are warranted.

Computed Tomography Angiography in the Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Study

Background: The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) study validated noninvasive imaging tests of intracranial atherosclerosis against catheter angiography in a prospective, blinded, multicenter setting. Critical evaluation of transcranial Doppler (TCD) and magnetic resonance angiography in the SONIA study standardized their performance and interpretation. We performed a similar analysis of computed tomography angiography (CTA) for the detection of intracranial stenosis. Methods: Multicenter standardization of image acquisition and blinded, central interpretation of CTA performance were conducted in concert with the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. Measurements of the intracranial arterial diameter were obtained to derive stenosis values. Correlation with catheter angiography was used to assess CTA performance characteristics. Results: CTA measurements of intracranial stenosis were obtained in 120 vessel segments, with angiographic correlation in 52. CTA was performed as a noninvasive study prior to conventional angiography. CTA stenoses of 50-99% or a flow gap were identified in 15 of 52 vessel segments, stenoses of <50% in 5 of 52, and normal arterial diameters in 32 of 52 vessel segments. Based on the digital subtraction angiography (DSA) stenosis defined as 50-99%, the positive predictive value (PPV) of CTA was only 46.7% (95% CI 21.3-73.4) and the negative predictive value (NPV) was 73.0% (95% CI 55.9-86.2). For DSA stenosis defined as 70-99%, the PPV of CTA was 13.3% (95% CI 1.7-40.5) and the NPV was 83.8% (95% CI 68.0-93.8). Conclusions: CTA can accurately rule out the presence of severe stenosis due to intracranial atherosclerosis and may eliminate the need for angiography in many cases. Further prospective, blinded evaluation of CTA and optimization of cutpoints to predict angiographic disease will facilitate future trials of intracranial atherosclerosis.