Abstract WP499: Cognitive Function in Patients With Symptomatic Intracranial Stenosis

Introduction: Compared to recurrent stroke risk, data are scarce on cognitive outcomes in patients with symptomatic intracranial atherosclerotic disease (ICAD). We evaluated cognition in patients with symptomatic ICAD at 90 days and factors that predict cognitive function. Methods: Using a 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%. A blinded rater assessed infarct pattern: single perforator, territorial, borderzone, or mixed. At 90 days post-stroke, patients or proxies were emailed Neuro-QOL surveys for cognitive and motor function. We also collected data on recurrent stroke in the territory of the stenosis within 3 months. We evaluated baseline and imaging predictors of 90-day cognition T-score using stepwise linear regression adjusting for age, sex, prior stroke, initial NIHSS score, location of stenosis, degree of stenosis, use of dual antiplatelet therapy at discharge, and recurrent stroke. Results: Among 212 patients who met study criteria, 125 (59.0%) completed cognition surveys; those who completed surveys were similar to those who did not across demographic, clinical, and imaging characteristics. In the analyzed cohort, the mean age was 68.3 (±12.6) years and median initial NIHSS score was 3 (interquartile range 1-6). Symptomatic ICAD was localized to the anterior circulation in 84 (67.2%) patients and 102 (81.6%) had stenosis >70%. At 90 days, the mean cognition T-score was 50.1 (±10.4) and 25 (20%) had scores <40. In adjusted analysis, increasing age (b=-0.15, p=0.031), higher initial NIHSS score (b=-0.69, p<0.001), and a mixed or territorial infarct pattern (b=-0.39, p=0.028) were associated with lower cognition T-scores. Conclusions: In a single-center observational cohort study, cognitive impairment was noted in 20% of patients with symptomatic ICAD at 3 months. Besides age and NIHSS score, baseline infarct pattern was a strong predictor of worse cognitive function. Our data suggest that cognitive impairment is common in patients with symptomatic ICAD and baseline clinical and imaging characteristics may identify those at risk

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

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

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

Lipid Levels and Short-Term Risk of Recurrent Brain Infarcts in Symptomatic Intracranial Stenosis

•Recurrent infarcts on brain magnetic resonance imaging are common 6-8 weeks after index presentation in patients with symptomatic intracranial stenosis despite relatively high adherence to aggressive medical management.•Low-density lipoprotein and triglyceride levels at time of index stroke or transient ischemic attack predict recurrent infarcts independent of other clinical and imaging factors.•More aggressive and rapid reduction of lipid levels may be required to reduce the burden of early clinical and subclinical recurrence in patients with symptomatic intracranial stenosis. Hyperlipidemia is a strong risk factor for intracranial atherosclerotic disease (ICAD) and clinical stroke recurrence. We explored the effect of serum lipid levels on subclinical infarct recurrence in the Mechanisms of earlY Recurrence in Intracranial Atherosclerotic Disease (MYRIAD) study. We included enrolled MYRIAD patients with lipid measurements and brain MRI at baseline and brain MRI at 6-8 weeks. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6-8 weeks compared to baseline brain MRI. We assessed the association between baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and recurrent infarct at 6-8 weeks using multivariable logistic regression. Among 74 patients (mean age 64.2±12.9 years, 59.5% were white, 60.8% men), 20 (27.0%) had new or recurrent infarcts. Mean HDL-C (37.2 vs. 43.9 mg/dL, P=0.037) was lower and TG (113.5 vs. 91.3 mg/dL, P=0.008) was higher while TC (199.8 vs. 174.3 mg/dL, P=0.061) and LDL-C (124.3 vs. 101.2 mg/dL, P=0.053) were nominally higher among those with recurrent infarcts than those without. LDL-C (adj. OR 1.022, 95% CI 1.004-1.040, P=0.015) and TG (adj. OR 1.009, 95% CI 1.001-1.016, P=0.021) were predictors of recurrent infarct at 6-8 weeks adjusting for other clinical and imaging factors. Baseline cholesterol markers can predict early infarct recurrence in patients with symptomatic ICAD. More intensive and rapid lipid lowering drugs may be required to reduce risk of early recurrence

Imaging Patterns of Recurrent Infarction in the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) Study

Introduction: While much is known about recurrent clinical events in patients with intracranial atherosclerotic disease (ICAD), there is limited data on characteristics of recurrent infarcts. Methods: The NIH-funded MyRIAD prospective, observational study was designed to identify mechanisms of ischemia and predictors of recurrence in ICAD. Recurrent infarction was assessed on MRI at 6–8 weeks. We reviewed the DWI/ADC and FLAIR sequences in patients with recurrent stroke and characterized the number of infarcts, infarct location, size, and patterns based on whether they were borderzone (BZ), perforator (SC/P), cortical or territorial (C/T), and mixed. Temporal characteristics were delineated by ADC/FLAIR correlation. Results: Of the 89 patients with 6–8 weeks MRI, 22 (24.7%) had recurrent infarcts in the territory of the symptomatic artery. Recurrent infarcts were evident on DWI in 63.6% and single infarcts in 54.5%. The median recurrent infarct volume was 2.0 cm 3 compared to median index infarct volumes of 2.5 cm 3 . A mixed infarct pattern was most common (40.9%), followed by borderzone (22.7%), cortical or territorial (27.3%), while only 9.1% were in a perforator artery distribution. Amongst those with a mixed pattern, 8/9 had a borderzone distribution infarct as part of their mixed infarct pattern. Conclusion: These findings provide novel data on the characteristics of early recurrent infarcts in patients with symptomatic ICAD

Abstract 79: Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) Study: Participants, Clinical and Imaging Outcomes

Introduction: ICAD is a common cause of stroke. MyRIAD is designed to identify mechanisms of ischemia and predictors of recurrence in ICAD. Here we present the study population baseline characteristics and key outcomes. Methods: MyRIAD is an NIH/NINDS funded prospective multicenter observational study of patients with recent ( < 21 days) stroke or TIA (recurrent or with DWI) caused by IAD 50-99% without planned angioplasty/stenting. The primary outcome is ischemic stroke in the territory within 1 year of follow up; secondary outcomes are TIA at 1 year and new infarcts on MRI at 6-8 weeks. Qualifying events and clinical and imaging outcomes are centrally adjudicated. Results: MyRIAD enrolled 105 participants. The MyRIAD cohort (Table) had significant atherosclerotic risk factors and received aggressive medical therapy. Of 101 participants with clinical follow up (mean 243 + 126 days), the primary outcome of stroke in the territory at 1 year occurred in 9 (8.6%, 13.4/100 person-years), while 7 (6.7%, 10.4/100 person-years) had a TIA. A study MRI at 6-8 weeks was available for comparison to baseline MRI in 87 participants (mean time from qualifying event to follow up imaging 51 + 16 days). A new DWI/FLAIR infarct in the territory of the symptomatic vessel was noted in 22 participants (25.3%). Conclusions: MyRIAD detected an 8.6% 1-year stroke recurrence and a much higher 25.3% rate of recurrent infarction in the first weeks after qualifying stroke/TIA, emphasizing the need to develop better therapeutic interventions for ICAD

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

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 (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

Mechanisms of early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD): Rationale and design

RationaleIntracranial atherosclerotic disease (ICAD) is the most common cause of ischemic stroke with the highest rate of recurrence, despite aggressive medical management. Diverse mechanisms may be responsible for ICAD-related cerebral ischemia, with potential therapeutic implications. Here we present the rationale, design and methods of the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study. The aim of MyRIAD is to determine the mechanisms of stroke in ICAD through physiologic imaging biomarkers that evaluate impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, artery to artery embolism, and their interaction.Methods and designThis is a prospective observational study of patients with recently symptomatic (&lt;21 days) ICAD with 50-99% stenosis treated medically and monitored for up to 1 year. An estimated 110 participants are recruited at 10 sites to identify the association between the presence of each mechanism of ischemia and recurrent stroke. The primary outcome is ischemic stroke in the territory of the symptomatic artery. Secondary outcomes include new cerebral infarction on MRI at 6-8 weeks and recurrent TIA in the territory of the symptomatic artery.DiscussionMyRIAD is positioned to define the role of specific mechanisms of recurrent ischemia in patients with symptomatic ICAD. This knowledge will allow the development and implementation of effective and specific treatments for this condition