Abstract 80: Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease

Stroke ◽

10.1161/str.51.suppl_1.80 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Shyam Prabhakaran ◽

David S Liebeskind ◽

George Cotsonis ◽

Azhar Nizam ◽

Edward Feldmann ◽

...

Keyword(s):

Blood Pressure ◽

Recurrent Stroke ◽

Brain Mri ◽

Management Strategies ◽

Atherosclerotic Disease ◽

Clinical Predictors ◽

Multicenter Observational Study ◽

Radiographic Outcomes ◽

Intracranial Atherosclerotic Disease ◽

Introduction: Prior studies have evaluated risks factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease (ICAD). However, few reports have assessed risk factors for early infarct recurrence in the territory distal to the symptomatic artery. Methods: We analyzed data from patients who underwent study-paid brain MRI at 6-8 weeks after enrollment in the ongoing MyRIAD study, an NIH/NINDS funded prospective multicenter observational study of patients with recent ( < 21 days) stroke or TIA (recurrent or with DWI) caused by ICAD 50-99% without planned angioplasty/stenting. The outcome of interest was new infarcts on brain MRI (on DWI or FLAIR) at 6-8 weeks compared to qualifying brain MRI at time of index stroke or TIA. Qualifying events and clinical and radiographic outcomes are centrally ascertained by 2 independent reviewers. We used logistic regression to identify independent clinical predictors of new infarct in the territory of the symptomatic artery. Results: Among 84 (80%) of 105 enrolled patients in MyRIAD with 6-8 week MRI, the mean age was 63.6 + 12.4 years, 83.1% have stenosis 70-99%, and 51.2% had history of diabetes; those who underwent MRI did not differ from those who did not undergo MRI. A new DWI/FLAIR infarct in the territory of the symptomatic artery was noted in 26.2%. Those with recurrent infarcts were younger (57.7 vs. 65.7 years, p=0.009), more likely to have diabetes (71.4% vs. 44.3%, p=0.043), have greater degree of stenosis (82.5% vs. 76.0%, p=0.099), and have greater decline in systolic blood pressure (SBP) from enrollment to 6-8 week follow-up (+5 vs. -6.2 mm Hg, p=0.074). In adjusted analyses, age (aOR 0.922, 95% CI 0.869-0.979) and change in SBP (aOR 0.967, 95% CI 0.937-0.997) were related to new infarct in the territory. Conclusions: Early recurrent infarcts occur in more than one-quarter of patients with symptomatic ICAD, may be a suitable biomarker of disease activity, and add to the subclinical burden of this high-risk disease. Given the association between SBP lowering and infarct recurrence, studies of early blood pressure management strategies, including extended permissive hypertension, may be warranted in this population.

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Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease

Stroke ◽

10.1161/strokeaha.120.032676 ◽

2021 ◽

Author(s):

Shyam Prabhakaran ◽

David S. Liebeskind ◽

George Cotsonis ◽

Azhar Nizam ◽

Edward Feldmann ◽

...

Keyword(s):

Risk Factors ◽

Diffusion Weighted Imaging ◽

Adjusted Odds Ratio ◽

Recurrent Stroke ◽

Brain Mri ◽

Atherosclerotic Disease ◽

Intracranial Atherosclerotic Disease ◽

Diffusion Weighted ◽

Artery Embolism

Background and Purpose: While prior studies identified risk factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease, few have assessed risk factors for early infarct recurrence. Methods: We performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of intracranial atherosclerotic disease patients with recent (<21 days) stroke/transient ischemic attack, 50% to 99% stenosis and who underwent 6- to 8-week magnetic resonance imaging (MRI) per protocol. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6 to 8 weeks compared to index brain MRI. Qualifying events and clinical and imaging outcomes were centrally ascertained by 2 independent reviewers. We assessed the association between baseline clinical and imaging variables and recurrent infarct in bivariate models and multivariable logistic regression to identify independent predictors of infarct recurrence. Results: Of 105 enrolled patients in MYRIAD, 89 (84.8%) were included in this analysis (mean age, 64±12 years, 54 [60.7%] were male, and 53 [59.6%] were White). The median time from qualifying event to MRI was 51+16 days, on which 22 (24.7%) patients had new or recurrent infarcts. Younger age (57.7 versus 66.0 years; P <0.01), diabetes (32.6% versus 14.6%, P =0.05), index stroke (31.3% versus 4.6%, P =0.01), anterior circulation location of stenosis (29.7% versus 12.0%, P =0.08), number of diffusion-weighted imaging lesions (>1: 40.0%, 1: 26.9% versus 0: 4.4%, P <0.01), and borderzone infarct pattern (63.6% versus 25.0%, P =0.01) on baseline MRI were associated with new or recurrent infarcts. Age (adjusted odds ratio, 0.93 [95% CI, 0.89–0.98], P <0.01) and number of diffusion-weighted imaging lesions (adjusted odds ratio, 3.24 [95% CI, 1.36–7.71], P <0.01) were independently associated with recurrent infarct adjusting for hypertension, diabetes, and stenosis location (anterior versus posterior circulation). Conclusions: An index multi-infarct pattern is associated with early recurrent infarcts, a finding that might be explained by plaque instability and artery-to-artery embolism. Further investigation of plaque vulnerability in intracranial atherosclerotic disease is needed. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02121028.

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Abstract WMP45: Borderzone Infarct Pattern Predicts Recurrent Stroke in Patients With Intracranial Stenosis

Stroke ◽

10.1161/str.51.suppl_1.wmp45 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Shyam Prabhakaran ◽

Rajbeer Sangha ◽

Sameer Ansari ◽

Jose Romano ◽

PN Sylaja ◽

...

Keyword(s):

Ischemic Stroke ◽

Recurrent Stroke ◽

Strong Predictor ◽

Single Center ◽

Anterior Circulation ◽

Nihss Score ◽

Intracranial Atherosclerotic Disease ◽

Index Stroke ◽

Ischemic Attack ◽

Introduction: Despite aggressive medical management, patients with symptomatic intracranial atherosclerotic disease (ICAD) remain at high risk for recurrent stroke. There are no reliable biomarkers to identify those at highest risk and in whom flow restorative procedures may be warranted. We hypothesized that a borderzone infarct pattern would predict 90-day recurrent stroke in the territory of symptomatic ICAD. Methods: Using the prospective registry at a single center, we identified consecutive patients admitted between 2012 and 2017 with confirmed ischemic stroke or transient ischemic attack (TIA) and independently adjudicated symptomatic ICAD with stenosis of >50%. We ascertained clinical events within 3 months of index stroke through telephone interview. Ischemic stroke in the territory of the symptomatic stenotic artery was the primary outcome. A blinded rater assessed infarct pattern: single perforator, territorial, borderzone, or mixed. We evaluated whether infarct pattern was a predictor of recurrent stroke using logistic regression adjusting for age, sex, prior stroke, initial NIHSS score, location of stenosis, degree of stenosis, and use of dual antiplatelet therapy at discharge. Results: Among 212 patients who met study criteria, the mean age was 68.2 (±12.2) years and median initial NIHSS score was 3 (interquartile range 1-6). Symptomatic ICAD was localized to the anterior circulation in 132 (64.2%) patients and 171 (80.7%) had stenosis >70%. Isolated borderzone infarcts were noted in 18 patients (8.5%) while they were present in 34 (16.0%) other patients with mixed pattern. At 3 months, 51 (24.1%) patients experienced recurrent stroke in the territory. Among patients with any borderzone infarct, 20 (38.7%) had recurrent stroke versus 31 (19.4%) in patients with other patterns (p=0.005). In adjusted analysis, presence of any borderzone infarct was independently associated with recurrent stroke (aOR 2.59, 95% CI 1.23-5.48, p=0.012). Conclusions: In a single-center observational cohort study, we found that a borderzone infarct pattern was a strong predictor of recurrent stroke at 3 months in patients with symptomatic ICAD. Our data suggest that hypoperfusion may be an important mechanism of recurrent stroke in this population.

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Abstract TP436: MyRIAD Mechanisms of Recurrent Stroke in Intracranial Atherosclerotic Disease

Stroke ◽

10.1161/str.51.suppl_1.tp436 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

David S Liebeskind ◽

Jose G Romano ◽

Azhar Nizam ◽

Edward Feldmann ◽

Rajbeer S Sangha ◽

...

Keyword(s):

Imaging Modality ◽

Recurrent Stroke ◽

Tissue Perfusion ◽

Perfusion Mri ◽

Atherosclerotic Disease ◽

High Rate ◽

Arterial Blood Flow ◽

Intracranial Atherosclerotic Disease ◽

Background: The NINDS-funded Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study used a battery of MRI and TCD techniques to discern key pathophysiology leading to a relatively high rate of recurrent stroke. Our study objectives aimed to relate imaging abnormalities of limited arterial blood flow, distal tissue perfusion and artery-to-artery emboli with new infarcts on 6-8 week MRI. Methods: MyRIAD is a prospective, multicenter, observational study of patients with recent (<21 days) ischemic stroke or TIA due to 50-99% ICAD. Quantitative MRA (QMRA), perfusion MRI and TCD vasomotor reactivity (VMR) with emboli detection (ED) were acquired at enrollment. Central adjudication of each imaging modality, clinical events and 6-8 week MRI were independently ascertained. Results: MyRIAD enrolled 105 (mean age 63.7 years, SD 11.8 years; 43% women) patients. Primary outcomes of recurrent stroke in the territory occurred in 9/105 (9%) with secondary outcomes of territorial TIA in 7/105 (7%) and new infarcts on 6-8 week MRI in 22/87 (25%). The limited number of clinical stroke and TIA endpoints precluded definitive analysis of mechanism. Pre-specified Tmax>4s 10 cc lesions on perfusion MRI were noted in 40/92 (43%) but did not predict new infarcts at 6-8 week MRI. New infarcts were noted in 12/44 (27%) of those with Tmax>4s 5 cc lesions at baseline compared to 3/26 (12%) when absent. Abnormal volume flow ratio (VFR) on QMRA was noted in 25/98 (26%), abnormal TCD VMR in 25/76 (33%) and ED in 30/74 (41%). Other pre-specified analyses revealed both abnormal VMR and ED in 21/77 (27%) and both abnormal Tmax>4s perfusion and VFR in 16/99 (16%). Two or more imaging abnormalities were noted at baseline in 49/105 (47%) and stenosis ≥ 70% in 76/91 (84%). New infarcts on 6-8 week MRI were more frequent with ≥ 2 abnormalities (33 vs 18%, p=0.1) and ≥ 70% stenosis (29 vs 7%, p=0.2). Conclusions: Early, recurrent infarction on MRI is common in ICAD. Imaging abnormalities of limited arterial blood flow or distal tissue perfusion and artery-to-artery emboli are frequent and the presence of multiple abnormalities may increase risk. Larger ICAD studies are needed to link routinely acquired imaging with covert infarcts and cognitive impairment.

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Abstract MP48: Intracranial Dolichoectasia in Patients With Symptomatic Intracranial Atherosclerotic Disease: The Myriad Study

Stroke ◽

10.1161/str.52.suppl_1.mp48 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Victor J Del Brutto ◽

Azhar Nizam ◽

george cotsonis ◽

Iszet Campo-Bustillo ◽

David S Liebeskind ◽

...

Keyword(s):

Brain Mri ◽

Early Recurrence ◽

Atherosclerotic Disease ◽

Common Finding ◽

Stroke Recurrence ◽

Entire Cohort ◽

Intracranial Atherosclerotic Disease ◽

Study Population ◽

Ischemic Events

Background: It is unknown whether intracranial atherosclerotic disease (IAD), in addition to vessel narrowing, also contributes to the abnormal dilation and increased tortuosity of intracranial vessels, a condition known as intracranial dolichoectasia (IDE). We aim to determine the degree to which these two arteriopathies coexist and whether IDE correlates with subsequent ischemic events in patients with recently symptomatic moderate-to-severe IAD. Methods: The study included 99 patients (mean age 6311 years; 57% men) enrolled in the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study. Intracranial vessels diameter, length, and tortuosity were determined by semiautomatic vessel segmentation and were considered abnormal if ≥2 standard deviations from the study population mean. Either ectasia (increased diameter) or dolichosis (increased tortuosity) defined IDE. We assessed the correlation of IDE in the symptomatic vessel with the composite outcome of either new infarcts in the territory of the affected vessel on brain MRI performed at 6-8 weeks from the index event or stroke recurrence during 12-month follow up. Results: IDE prevalence was 34% (isolated ectasia 8%, isolated dolichosis 18%, and both ectasia and dolichosis 8%) and 14% of symptomatic vessels. Patients with and without IDE had similar demographics and vascular risk factors prevalence (Table). I Twenty-two out of 85 (26%) patients with brain MRI at 6-8 weeks had new infarct(s) in the territory and 9% of the entire cohort had stroke recurrence during follow-up. Coexistence of IAD and IDE in the target vessel was not associated to subsequent ischemic events (21.4% versus 29.4%; P=0.54). Conclusion: IDE is a common finding in patients with moderate-to-severe IAD. Superimposed IDE did not increase the already heightened risk of subsequent ischemic events in patients with symptomatic IAD. ClinicalTrials.gov Identifier: NCT02121028

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Diffuse Cerebral Edema After Moyamoya Disease-Related Intracerebral Hemorrhage: A Case Report

The Neurohospitalist ◽

10.1177/1941874420980611 ◽

2020 ◽

pp. 194187442098061

Author(s):

Alvin S. Das ◽

Robert W. Regenhardt ◽

Nirav Patel ◽

Steven K. Feske ◽

Matthew B. Bevers ◽

...

Keyword(s):

Blood Pressure ◽

Intracerebral Hemorrhage ◽

Moyamoya Disease ◽

Cerebral Edema ◽

Brain Mri ◽

Management Strategies ◽

Anterior Circulation ◽

Strict Adherence ◽

Cerebrospinal Fluid Diversion ◽

Standard Management

Moyamoya disease (MMD) is a rare, progressive occlusive disease characterized by bilateral internal carotid artery hypoplasia that often presents with ischemic stroke and intracerebral hemorrhage (ICH). Although MMD-related ICH is generally managed similarly to spontaneous ICH, we present a case in which standard management strategies may have led to an unprecedented devastating outcome. A 37-year-old female without any previous medical history presented with headache and right-sided weakness. A computed tomography (CT) scan revealed a large left basal ganglia ICH. Vessel imaging revealed diffuse narrowing of the entire anterior circulation with prominent leptomeningeal collaterals consistent with MMD. The patient’s systolic blood pressure was kept under 140 mmHg. During the hospitalization, she became hypocarbic while being trialed on pressure support ventilation. Several hours later, she developed fixed and dilated pupils. Repeat CT head showed new diffuse cerebral edema with tonsillar herniation. Despite hyperosmolar therapy, paralytics, pentobarbital, and cerebrospinal fluid diversion, no improvement was noted. Unfortunately, brain MRI revealed multifocal brainstem infarcts with superimposed Duret hemorrhages. Herein, we report diffuse cerebral edema as a complication of MMD-related ICH. We hypothesize that disruptions of delicate cerebral autoregulatory mechanisms led to extensive hypoxic-ischemic injury. In the setting of ICH, aggressive blood pressure management coupled with relative hypocapnia may have likely caused vasoconstriction of poorly compliant arteries leading to worsened cerebral blood flow and ischemia. Therefore, because of its complex pathophysiology, strict adherence to eucapnia should be maintained in MMD-related ICH.

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Clopidogrel plus Aspirin for Symptomatic Intracranial Atherosclerotic Stenosis: A Pilot Study

Interventional Neurology ◽

10.1159/000447025 ◽

2016 ◽

Vol 5 (3-4) ◽

pp. 157-164 ◽

Author(s):

Tareq Kass-Hout ◽

Melanie Winningham ◽

Omar Kass-Hout ◽

Laura Henriquez ◽

Frank Tong ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Medical Management ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Intracranial Stenosis ◽

Atherosclerotic Disease ◽

Vascular Events ◽

Intracranial Atherosclerotic Disease ◽

Atherosclerotic Stenosis ◽

Aggressive Medical Management

Background and Purpose: There are limited data on the optimal duration of dual antiplatelet therapy for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic disease. Methods: Consecutive patients presenting with high-grade (70-99%) symptomatic intracranial stenosis from January 1, 2011, to December 31, 2013, and evaluated within 30 days of the index event were eligible for this analysis. All patients underwent treatment with aspirin plus clopidogrel for a target duration of 12 months along with aggressive medical management based on the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) protocol; all patients were given gastrointestinal prophylaxis for the duration of their aspirin and clopidogrel treatment. Clinical and safety outcomes of our cohort were compared with the medical arm of the SAMMPRIS trial cohort (n = 227). Results: Our cohort included 25 patients that met the inclusion criteria. Achievement of blood pressure and LDL cholesterol targets were similar between our cohort and the SAMMPRIS cohort. At 1 year, the rates of stroke, myocardial infarction or vascular death were 0% in our cohort and 16% in the SAMMPRIS cohort (p = 0.03). At 1 year, major bleeding rates were similar between our cohort and the SAMMPRIS cohort (4 vs. 2.2%, p = 1.0). Conclusion: A prolonged course of dual antiplatelet therapy for symptomatic intracranial atherosclerotic disease may be associated with less vascular events with no increase in hemorrhagic complications.

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Abstract 68: Impaired Perfusion in Intracranial Atherosclerotic Disease Predicts Cognitive Outcomes

Stroke ◽

10.1161/str.51.suppl_1.68 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

David S Liebeskind ◽

Jose G Romano ◽

George A Cotsonis ◽

Shadi Yaghi ◽

Tristan Honda ◽

...

Keyword(s):

Collateral Circulation ◽

Recurrent Stroke ◽

Cognitive Outcomes ◽

Cognitive Testing ◽

Atherosclerotic Disease ◽

Collateral Flow ◽

Cognitive Changes ◽

Intracranial Atherosclerotic Disease ◽

Background: Poor collateral circulation and hypoperfusion may lead to recurrent stroke in intracranial atherosclerotic disease (ICAD). The role of perfusion in silent strokes and potentially insidious cognitive impairment in ICAD is unknown. We used evidence of impaired perfusion at angiography in SAMMPRIS to predict subsequent cognitive changes. Methods: Angiography at enrollment in the SAMMPRIS trial was independently evaluated, blind to clinical data and cognitive testing. Antegrade flow in the symptomatic arterial territory and corresponding collateral flow were scored. Impaired perfusion was defined by poor antegrade and poor collateral flow. Serial testing with the Montreal Cognitive Assessment (MoCA) was done in subjects without aphasia or neglect at baseline, 4 mo, 12 mo and closeout, or until subjects had a clinical stroke endpoint. Results: 207 subjects (median age 61, range 33-81 years; 37% women) had baseline MoCA scores with angiography data on territorial perfusion. Baseline MoCA scores (mean 24.2±4.1) were similar between categories of antegrade flow and collateral circulation. Impaired perfusion was noted in 33/207 (16%). Serial MoCA revealed that changes in cognition over time were different at 4 mo, 12 mo and closeout based on the presence of impaired perfusion at baseline (p<0.001). After more modest (mean MoCA change = 0.5 increase from baseline, p=0.80) early improved cognitive function at 4 mo, those with impaired perfusion had cognitive decline at 12 mo (mean MoCA change, p<0.01) unlike the continued improvement in other subjects. Cognitive changes in those with impaired perfusion were associated with a higher frequency of subsequent stroke in the territory. Conclusions: Impaired perfusion in the symptomatic arterial territory of ICAD predicts cognitive outcomes that may precede recurrent ischemia. Future studies may define the role of noninvasive perfusion imaging in ICAD to predict cognitive trajectories and recurrent stroke.

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Abstract P569: Adherence to Preventive Therapy and Early Recurrent Cerebral Ischemia in Patients With Symptomatic Intracranial Atherosclerotic Disease: Analysis of the Myriad Study

Stroke ◽

10.1161/str.52.suppl_1.p569 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Victor J Del Brutto ◽

Shyam Prabhakaran ◽

Iszet Campo-Bustillo ◽

george cotsonis ◽

Azhar Nizam ◽

...

Keyword(s):

Physical Activity ◽

Medication Adherence ◽

Brain Mri ◽

Early Recurrence ◽

Preventive Therapy ◽

Atherosclerotic Disease ◽

High Rate ◽

Lipid Lowering ◽

Intracranial Atherosclerotic Disease ◽

Recurrent Ischemia

Background: Intracranial atherosclerotic disease (IAD) is a common cause of stroke with high rate of early recurrence despite maximal medical therapy. We sought to determine adherence to secondary preventive therapy and its association with early recurrent ischemia in patients with symptomatic IAD. Methods: The Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study included patients with recent stroke or transient ischemic attack due to moderate-to-severe IAD. Although MyRIAD did not mandate treatment, patients were recommended to follow standard secondary preventive management including antiplatelet therapy, lipid-lowering medications, antihypertensives for blood pressure (BP) goal <140/90 mmHg, smoking cessation and regular physical activity. Patients underwent 6-8 weeks assessment for medication adherence, smoking status, and physical activity compliance. Adherence to preventive therapy was correlated with new infarcts in the affected vessel territory on brain MRI. Results: Eighty-nine out of 105 patients enrolled in MyRIAD completed 6-8 weeks clinical and brain MRI assessment (mean age 64 +/- 12 years; 57% men). During follow up, 99% were on antiplatelets, 89% on lipid-lowering medications, 81% on antihypertensives, 48% had systolic BP at goal, 79% had diastolic BP at goal, 93% were not active smokers, and 47% were compliant with physical activity. Overall, new infarcts on brain MRI were found in 25% patients. Although no significant differences were found, patients with uncontrolled BP, active smokers and those not compliant with physical activity had a higher frequency of new infarcts in the affected vessel territory (Table). Conclusions: Medication adherence was high after IAD-related stroke. However, a noteworthy fraction of patients had uncontrolled BP, continue to smoke, and were not compliant with physical activity. The latter may represent important therapeutic targets to prevent early recurrent ischemia.

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Management Strategies in Posterior Circulation Intracranial Atherosclerotic Disease

Journal of Endovascular Therapy ◽

10.1583/09-2975.1 ◽

2010 ◽

Vol 17 (3) ◽

pp. 308-313 ◽

Author(s):

Guillermo Povedano ◽

Paz Zuberbuhler ◽

Pedro Lylyk ◽

Sebastian F. Ameriso

Keyword(s):

Management Strategies ◽

Posterior Circulation ◽

Atherosclerotic Disease ◽

Intracranial Atherosclerotic Disease

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Endothelial Shear Stress and Platelet FcγRIIa Expression in Intracranial Atherosclerotic Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.646309 ◽

2021 ◽

Vol 12 ◽

Author(s):

David S. Liebeskind ◽

Jason D. Hinman ◽

Naoki Kaneko ◽

Hiroaki Kitajima ◽

Tristan Honda ◽

...

Keyword(s):

Shear Stress ◽

Recurrent Events ◽

Recurrent Stroke ◽

Atherosclerotic Disease ◽

Arterial Stenosis ◽

Variable Response ◽

Intracranial Atherosclerotic Disease ◽

Elevated Expression ◽

Endothelial Shear Stress ◽

Mechanistic Basis

Intracranial atherosclerotic disease (ICAD) has been characterized by the degree of arterial stenosis and downstream hypoperfusion, yet microscopic derangements of endothelial shear stress at the luminal wall may be key determinants of plaque growth, vascular remodeling and thrombosis that culminate in recurrent stroke. Platelet interactions have similarly been a principal focus of treatment, however, the mechanistic basis of anti-platelet strategies is largely extrapolated rather than directly investigated in ICAD. Platelet FcγRIIa expression has been identified as a potent risk factor in cardiovascular disease, as elevated expression markedly increases the risk of recurrent events. Differential activation of the platelet FcγRIIa receptor may also explain the variable response of individual patients to anti-platelet medications. We review existing data on endothelial shear stress and potential interactions with the platelet FcγRIIa receptor that may alter the evolving impact of ICAD, based on local pathophysiology at the site of arterial stenosis. Current methods for quantification of endothelial shear stress and platelet activation are described, including tools that may be readily adapted to the clinical realm for further understanding of ICAD.

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