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

Stroke ◽  
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 ◽  
Antegrade Flow

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.

scholarly journals Collateral Circulation in Symptomatic Intracranial Atherosclerosis

2010 ◽  
Vol 31 (5) ◽  
pp. 1293-1301 ◽  
Author(s):  
David S Liebeskind ◽  
George A Cotsonis ◽  
Jeffrey L Saver ◽  
Michael J Lynn ◽  
Harry J Cloft ◽  
...  
Keyword(s):  
Collateral Circulation ◽  
Internal Carotid ◽  
Multicenter Trial ◽  
Collateral Flow ◽  
Intracranial Atherosclerosis ◽  
Intracranial Atherosclerotic Disease ◽  
Basilar Arteries ◽  
Antegrade Flow ◽  
Arterial Stenoses ◽  
Arterial Patency

Collateral circulation in intracranial atherosclerosis has never been systematically characterized. We investigated collaterals in a multicenter trial of symptomatic intracranial atherosclerotic disease. Baseline angiography was reviewed for information on collaterals in stenoses of the internal carotid, middle cerebral, vertebral, and basilar arteries. A battery of angiographic scales was utilized to evaluate lesion site, arterial patency, antegrade flow, downstream territorial perfusion, and collateral circulation, blinded to all other data. Collateral circulation was adequately available for analysis in 287/569 (50%) subjects with proximal arterial stenoses ranging from 50% to 99%. Extent of collaterals was absent or none in 69%, slow or minimal in 10%, more rapid, yet incomplete perfusion of territory in 7%, complete but delayed perfusion in 11%, and rapid, complete collateral perfusion in 4%. Extent of collateral flow correlated with percentage of stenosis ( P < 0.0001), with more severe stenoses exhibiting greater compensation via collaterals. Overall, collateral grade increased with diminished antegrade flow across the lesion (thrombolysis in myocardial ischemia) and resultant downstream perfusion (thrombolysis in cerebral infarction) (both P<0.001). Our findings provide the initial detailed description of collaterals across a variety of stenoses, suggesting that collateral perfusion is a pivotal component in pathophysiology of intracranial atherosclerosis and implicating the need for further evaluation in ongoing studies.

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

Stroke ◽  
2021 ◽  
Author(s):  
Shyam Prabhakaran ◽  
David S. Liebeskind ◽  
George Cotsonis ◽  
Azhar Nizam ◽  
Edward Feldmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Odds Ratio ◽  
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.

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

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
David S Liebeskind ◽  
Jose G Romano ◽  
Azhar Nizam ◽  
Edward Feldmann ◽  
Rajbeer S Sangha ◽  
...  
Keyword(s):  
Blood Flow ◽  
Imaging Modality ◽  
Recurrent Stroke ◽  
Tissue Perfusion ◽  
Perfusion Mri ◽  
Atherosclerotic Disease ◽  
High Rate ◽  
Arterial Blood Flow ◽  
Intracranial Atherosclerotic Disease ◽  
Arterial Blood

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.

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

Stroke ◽  
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 ◽  
Index Stroke

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.

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

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.

scholarly journals The Evolving Paradigm in the Management of Intracranial Atherosclerotic Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Ali K. Ozturk ◽  
Ketan R. Bulsara
Keyword(s):  
English Literature ◽  
Treatment Options ◽  
Atherosclerotic Disease ◽  
Endovascular Techniques ◽  
Intracranial Atherosclerotic Disease ◽  
History Of ◽  
Recurrent Strokes ◽  
Rigorous Treatment ◽  
Significant Health

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke worldwide and represents a significant health problem. The pathogenesis and natural history of ICAD are poorly understood, and rigorous treatment paradigms do not exist as they do for extracranial atherosclerosis. Currently, the best treatment for ICAD remains aspirin therapy, but many patients who are placed on aspirin continue to experience recurrent strokes. As microsurgical and endovascular techniques continue to evolve, the role of extracranial to intracranial bypass operations and stenting are increasingly being reconsidered. We performed a PubMed review of the English literature with a particular focus on treatment options for ICAD and present evidence-based data for the role of surgery and stenting in ICAD against medical therapy alone.

scholarly journals Risk of mechanical thrombectomy recanalization failure: Intraoperative nuances and the role of intracranial atherosclerotic disease

2021 ◽  
Vol 24 ◽  
pp. 101029
Author(s):  
Joshua H. Weinberg ◽  
Ahmad Sweid ◽  
Ashlee Asada ◽  
Rawad Abbas ◽  
Keenan Piper ◽  
...  
Keyword(s):  
Mechanical Thrombectomy ◽  
Atherosclerotic Disease ◽  
Intracranial Atherosclerotic Disease

scholarly journals Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease

2021 ◽  
pp. svn-2021-001157
Author(s):  
Mengmeng Shi ◽  
Xinyi Leng ◽  
Ying Li ◽  
Zihan Chen ◽  
Ye Cao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Candidate Genes ◽  
Genome Sequencing ◽  
Atherosclerotic Disease ◽  
Chinese Patients ◽  
Genomic Variants ◽  
Stroke Subtypes ◽  
Intracranial Atherosclerotic Disease ◽  
Shared Risk

ObjectivesThe predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.MethodsUnrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis.ResultsAmong 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.ConclusionsOur GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

scholarly journals Endothelial Shear Stress and Platelet FcγRIIa Expression in Intracranial Atherosclerotic Disease

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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