Magnesium and Hematoma Expansion in Intracerebral Hemorrhage: A FAST-MAG Randomized Trial Analysis.

BACKGROUND: Observational studies suggest that magnesium may have hemostatic effects. FAST-MAG (Field Administration of Stroke Therapy-Magnesium) was a pragmatic clinical trial of magnesium sulfate administered prehospital for acute clinical stroke syndromes and included patients with intracerebral hemorrhage. Exploratory secondary analysis by the treatment group found no reduction in hematoma expansion (HE) associated with magnesium treatment in intracerebral hemorrhage but did not consider serum magnesium levels achieved. We analyzed FAST-MAG intracerebral hemorrhage data for associations between serum magnesium level, HE, and early neurological deterioration, accounting for groupwise biases. METHODS: HE was defined as hematoma volume increase ≥3 mL within 24 hours and early neurological deterioration as ≥1-point Glasgow Coma Scale decline from arrival to hospital day 4. Comparing treatment and placebo groups confirmed biased availability of neuroimaging data. Therefore, HE and neurological deterioration were analyzed and stratified by treatment and placebo groups using univariate tests and adjusted logistic regression. RESULTS: Spontaneous intracerebral hemorrhage was present in 381 patients. Placebo patients had fewer serial neuroimaging studies available (123 [65.4%] versus 145 [75.1%]; P=0.038). Necessary data were available in 104 magnesium- and 85 placebo-treated patients (age, 64.9 [13.0] years; 67.7% male). In the magnesium group, higher magnesium level was associated with less HE (adjusted odds ratio, 0.64 per mg/dL [95% CI, 0.42-0.93]) and less neurological deterioration (adjusted odds ratio, 0.54 per mg/dL [95% CI, 0.33-0.82]). In the placebo group, magnesium level was not associated with either HE or neurological deterioration. CONCLUSIONS: Magnesium may exhibit a hemostatic effect that was only observable in the FAST-MAG magnesium treatment group. Equipoise should be maintained, and specific trials are needed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00059332.

2024 AHA/ASA Performance and Quality Measures for Spontaneous Intracerebral Hemorrhage: A Report From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released a revised spontaneous intracerebral hemorrhage guideline in 2022. A working group of stroke experts reviewed this guideline and identified a subset of recommendations that were deemed suitable for creating performance measures. These 15 performance measures encompass a wide spectrum of intracerebral hemorrhage patient care, from prehospital to posthospital settings, highlighting the importance of timely interventions. The measures also include 5 quality measures and address potential challenges in data collection, with the aim of future improvements.

MRI Investigation of the Association of Left Atrial and Left Atrial Appendage Hemodynamics with Silent Brain Infarction.

BACKGROUND: Left atrial (LA) myopathy is thought to be associated with silent brain infarctions (SBI) through changes in blood flow hemodynamics leading to thrombogenesis. 4D-flow MRI enables in-vivo hemodynamic quantification in the left atrium (LA) and LA appendage (LAA). PURPOSE: To determine whether LA and LAA hemodynamic and volumetric parameters are associated with SBI. STUDY TYPE: Prospective observational study. POPULATION: A single-site cohort of 125 Participants of the multiethnic study of atherosclerosis (MESA), mean age: 72.3 ± 7.2 years, 56 men. FIELD STRENGTH/SEQUENCE: 1.5T. Cardiac MRI: Cine balanced steady state free precession (bSSFP) and 4D-flow sequences. Brain MRI: T1- and T2-weighted SE and FLAIR. ASSESSMENT: Presence of SBI was determined from brain MRI by neuroradiologists according to routine diagnostic criteria in all participants without a history of stroke based on the MESA database. Minimum and maximum LA volumes and ejection fraction were calculated from bSSFP data. Blood stasis (% of voxels <10 cm/sec) and peak velocity (cm/sec) in the LA and LAA were assessed by a radiologist using an established 4D-flow workflow. STATISTICAL TESTS: Student's t test, Mann-Whitney U test, one-way ANOVA, chi-square test. Multivariable stepwise logistic regression with automatic forward and backward selection. Significance level P < 0.05. RESULTS: 26 (20.8%) had at least one SBI. After Bonferroni correction, participants with SBI were significantly older and had significantly lower peak velocities in the LAA. In multivariable analyses, age (per 10-years) (odds ratio (OR) = 1.99 (95% confidence interval (CI): 1.30-3.04)) and LAA peak velocity (per cm/sec) (OR = 0.87 (95% CI: 0.81-0.93)) were significantly associated with SBI. CONCLUSION: Older age and lower LAA peak velocity were associated with SBI in multivariable analyses whereas volumetric-based measures from cardiac MRI or cardiovascular risk factors were not. Cardiac 4D-flow MRI showed potential to serve as a novel imaging marker for SBI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Endovascular Thrombectomy with or without Bridging Thrombolysis in Acute Ischemic Stroke: A Cost-Effectiveness Analysis.

BACKGROUND: There is unclear added benefit of intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT). We performed a cost-effectiveness analysis to assess the cost-effectiveness of comparing EVT with IVT versus EVT alone. METHODS: We used a decision tree to examine the short-term costs and outcomes at 90 days after the occurrence of index stroke to compare the cost-effectiveness of EVT alone with EVT plus IVT for patients with stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1-year, 5-year, and 20-year time horizons. We estimated total and incremental cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. RESULTS: The average costs per patient were estimated to be $47,304, $49,510, $59,770, and $76,561 for EVT-only strategy and $55,482, $57,751, $68,314, and $85,611 for EVT with IVT over 90 days, 1 year, 5 years, and 20 years, respectively. The cost saving of EVT-only strategy was driven by the avoided medication costs of IVT (ranging from $8,178 to $9,050). The additional IVT led to a slight decrease in QALY estimate during the 90-day time horizon (loss of 0.002 QALY), but a small gain over 1-year and 5-year time horizons (0.011 and 0.0636 QALY). At a willingness-to-pay threshold of $50,000 per QALY gained, the probabilities of EVT only being cost-effective were 100%, 100%, and 99.3% over 90-day, 1-year, and 5-year time horizons. CONCLUSION: Our cost-effectiveness model suggested that EVT only may be cost-effective for patients with acute ischemic stroke secondary to large vessel occlusion.

External Validation of a Tool to Identify Low-Risk Patients With Isolated Subdural Hematoma and Preserved Consciousness.

STUDY OBJECTIVE: The SafeSDH Tool was derived to identify patients with isolated (no other type of intracranial hemorrhage) subdural hematoma who are at very low risk of neurologic deterioration, neurosurgical intervention, or death. Patients are low risk by the tool if they have none of the following: use of anticoagulant or nonaspirin antiplatelet agent, Glasgow Coma Score (GCS) <14, more than 1 discrete hematoma, hematoma thickness >5 mm, or midline shift. We attempted to externally validate the SafeSDH Tool. METHODS: We performed a retrospective chart review of patients aged ≥16 with a GCS ≥13 and isolated subdural hematoma who presented to 1 of 6 academic and community hospitals from 2005 to 2018. The primary outcome, a composite of neurologic deterioration (seizure, altered mental status, or symptoms requiring repeat imaging), neurosurgical intervention, discharge on hospice, and death, was abstracted from discharge summaries. Hematoma thickness, number of hematomas, and midline shift were abstracted from head imaging reports. Anticoagulant use, antiplatelet use, and GCS were gathered from the admission record. RESULTS: The validation data set included 753 patients with isolated subdural hematoma. Mortality during the index admission was 2.1%; 26% of patients underwent neurosurgical intervention. For the composite outcome, sensitivity was 99% (95% confidence interval [CI] 97 to 100), and specificity was 31% (95% CI 27 to 35). The tool identified 162 (21.5%) patients as low risk. Negative likelihood ratio was 0.03 (95% CI 0.01 to 0.11). CONCLUSION: The SafeSDH Tool identified patients with isolated subdural hematoma who are at low risk for poor outcomes with high sensitivity. With prospective validation, these low-risk patients could be safe for management in less intensive settings.

Real-World Outcomes for Basilar Artery Occlusion Thrombectomy With Mild Deficits: The National Inpatient Sample.

BACKGROUND: Thrombectomy for basilar artery occlusion (BAO) has proven efficacy in patients with moderate-to-severe deficits, but has unclear benefits for those with mild symptoms. METHODS: Using an observational cohort design, the US National Inpatient Sample (2018-2020) was queried for adult patients with basilar artery occlusion and National Institutes of Health Stroke Scale (NIHSS) <10 for patients treated with thrombectomy versus medical management. The primary outcome of routine discharge (to home or self-care) was evaluated using multivariable logistic regression and propensity score matching, adjusted for baseline characteristics, stroke severity, and treatment with thrombolysis. RESULTS: Of 17 019 with basilar artery occlusion, 5795 patients met the criteria for inclusion criteria for our study, and 880 (15.4%) were treated with endovascular thrombectomy. In the propensity score-matched cohort, 880 patients were treated with medical management and endovascular thrombectomy, respectively. In multivariable regression, endovascular thrombectomy was associated with both an increased odds of routine discharge (odds ratio, 1.95 [95% CI, 1.31-2.90]; P=0.001) and a decreased length of hospital stay (B, -0.74 [95% CI, -1.36 to -0.11]; P=0.02) compared with medical management. In the propensity score matched cohort, endovascular thrombectomy remained associated with greater odds of routine discharge (2.01 [95% CI, 1.21-3.34]; P=0.007) but no difference in length of hospital stay (B, -0.22 [95% CI, -0.90 to 0.46]; P=0.53). CONCLUSIONS: Routine discharge was more common in this representative US cohort of patients with basilar artery occlusion and National Institutes of Health Stroke Scale <10 who underwent thrombectomy compared to conventional medical management. These findings suggest thrombectomy may be associated with better functional outcomes despite lower National Institutes of Health Stroke Scale and should be validated in a clinical trial setting.

Door-in-Door-out Times for Interhospital Transfer of Patients With Stroke.

Importance: Treatments for time-sensitive acute stroke are not available at every hospital, often requiring interhospital transfer. Current guidelines recommend hospitals achieve a door-in-door-out time of no more than 120 minutes at the transferring emergency department (ED). Objective: To evaluate door-in-door-out times for acute stroke transfers in the American Heart Association Get With The Guidelines-Stroke registry and to identify patient and hospital factors associated with door-in-door-out times. Design, Setting, and Participants: US registry-based, retrospective study of patients with ischemic or hemorrhagic stroke from January 2019 through December 2021 who were transferred from the ED at registry-affiliated hospitals to other acute care hospitals. Exposure: Patient- and hospital-level characteristics. Main Outcomes and Measures: The primary outcome was the door-in-door-out time (time of transfer out minus time of arrival to the transferring ED) as a continuous variable and a categorical variable (≤120 minutes, >120 minutes). Generalized estimating equation (GEE) regression models were used to identify patient and hospital-level characteristics associated with door-in-door-out time overall and in subgroups of patients with hemorrhagic stroke, acute ischemic stroke eligible for endovascular therapy, and acute ischemic stroke transferred for reasons other than endovascular therapy. Results: Among 108 913 patients (mean [SD] age, 66.7 [15.2] years; 71.7% non-Hispanic White; 50.6% male) transferred from 1925 hospitals, 67 235 had acute ischemic stroke and 41 678 had hemorrhagic stroke. Overall, the median door-in-door-out time was 174 minutes (IQR, 116-276 minutes): 29 741 patients (27.3%) had a door-in-door-out time of 120 minutes or less. The factors significantly associated with longer median times were age 80 years or older (vs 18-59 years; 14.9 minutes, 95% CI, 12.3 to 17.5 minutes), female sex (5.2 minutes; 95% CI, 3.6 to 6.9 minutes), non-Hispanic Black vs non-Hispanic White (8.2 minutes, 95% CI, 5.7 to 10.8 minutes), and Hispanic ethnicity vs non-Hispanic White (5.4 minutes, 95% CI, 1.8 to 9.0 minutes). The following were significantly associated with shorter median door-in-door-out time: emergency medical services prenotification (-20.1 minutes; 95% CI, -22.1 to -18.1 minutes), National Institutes of Health Stroke Scale (NIHSS) score exceeding 12 vs a score of 0 to 1 (-66.7 minutes; 95% CI, -68.7 to -64.7 minutes), and patients with acute ischemic stroke eligible for endovascular therapy vs the hemorrhagic stroke subgroup (-16.8 minutes; 95% CI, -21.0 to -12.7 minutes). Among patients with acute ischemic stroke eligible for endovascular therapy, female sex, Black race, and Hispanic ethnicity were associated with a significantly higher door-in-door-out time, whereas emergency medical services prenotification, intravenous thrombolysis, and a higher NIHSS score were associated with significantly lower door-in-door-out times. Conclusions and Relevance: In this US registry-based study of interhospital transfer for acute stroke, the median door-in-door-out time was 174 minutes, which is longer than current recommendations for acute stroke transfer. Disparities and modifiable health system factors associated with longer door-in-door-out times are suitable targets for quality improvement initiatives.

Borderzone infarction and recurrent stroke in intracranial atherosclerosis.

BACKGROUND: Intracranial stenosis (ICAS) is a common cause of stroke worldwide and patients with symptomatic ICAS exhibit a high rate of recurrence, particularly in the early period after the initial event. In this study, we aimed to study the association between borderzone infarct and recurrent ischemic stroke in patients hospitalized with symptomatic ICAS. METHODS: This is a retrospective single center study that included patients hospitalized with acute ischemic stroke in the setting of intracranial stenosis (50% or more and an acute ischemic stroke in the territory supplied by the stenosed artery) over a 32-month period. We excluded patients who did not receive a brain MRI or did not have an infarct on brain imaging. The primary predictor is infarct pattern (any borderzone vs. no borderzone infarct) and the primary outcome was recurrent cerebrovascular events (RCVE) within 90 days. We used unadjusted, and age and sex adjusted logistic regression models to determine associations between infarct pattern and RCVE at 90-days. RESULTS: Among 99 patients who met the inclusion criteria (4 tandem), the mean age was 70.1 ± 11.2 years and 41.4% were women; 43 had borderzone infarcts and 19 had RCVE. In adjusted binary logistic regression analysis, borderzone infarct was associated with increased risk of RCVE (adjusted OR 4.00 95% CI 1.33-11.99, p=0.013). The association between borderzone infarction and RCVE was not different among anterior circulation ICAD (adjusted HR 2.85 95% CI 0.64-12.76, p=0.172) vs. posterior circulation ICAD (adjusted HR 6.69 95% CI 1.06-42.11, p=0.043), p-value for interaction = 0.592. CONCLUSION: In real world post-SAMMPRIS medically treated patients with ICAD, the borderzone infarct pattern was associated with 90-day RCVE. Borderzone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for high-risk cohorts.

Underlying intracranial atherosclerotic disease is associated with worse outcomes in acute large vessel occlusion undergoing endovascular thrombectomy.

BACKGROUND: Data on large vessel occlusion (LVO) management due to intracranial atherosclerotic disease (ICAD) are scarce. OBJECTIVE: To compare clinical outcomes between patients with ICAD and those without ICAD following mechanical thrombectomy (MT). METHODS: We performed a retrospective analysis of consecutive patients who underwent MT for LVO in a large academic comprehensive stroke center, and compared in-hospital mortality, 90-day mortality, favorable functional outcome at 90 days, and symptomatic intracranial hemorrhage (ICH) using chi-squared tests and multivariate logistic regression analyses. We defined ICAD as observable plaque at occlusion site post-thrombectomy. RESULTS: Among 215 patients (mean age 67.1 ± 16.0 years; 60.5% female; 83.6% Black, median NIHSS score 16), ICAD was present in 38 patients (17.7%). Diabetes and dyslipidemia were more common in those with ICAD (57.9% vs. 38.4%, p = 0.027 and 29.0% vs. 14.7%, p = 0.035, respectively). Substantial reperfusion (TICI ≥2b) was achieved less often (84.2% vs. 94.4%, p = 0.031) but symptomatic ICH was also less common in ICAD patients (0% vs. 9.0%, p = 0.081). In-hospital and 90-day mortality were more common (36.8% vs. 15.8%, p = 0.003 and 52.6% vs. 26.6%, p = 0.002, respectively) and favorable functional outcome (mRS 0-2) at 90 days was less common (7.9% vs. 33.9%, p = 0.001) in ICAD patients. After adjusting for prognostic variables, ICAD was independently associated with in-hospital mortality (OR=4.1, 95% CI 1.7-9.7), 90-day mortality (OR=3.7, 95% CI 1.6-8.6), and poor functional outcome at 90 days (OR=5.5, 95% CI 1.6-19.4). CONCLUSION: Symptomatic ICAD in a predominantly African American cohort is associated with increased odds of mortality and poor functional outcome at 90 days in patients with LVO undergoing MT.

Recurrence risk in symptomatic intracranial stenosis treated medically in the real world.

BACKGROUND: The risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. METHODS: We used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50-99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. RESULTS: Among 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%-5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. CONCLUSIONS: In patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.

Effect of Intensive Blood Pressure Control on Incident Stroke Risk in Patients With Mild Cognitive Impairment.

BACKGROUND: Patients with mild cognitive impairment may be at higher risk of incident stroke, but the effect of intensive blood pressure (BP) control on that risk has not been explored. METHODS: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) and included patients with a baseline Montreal Cognitive Assessment score of 19 to 25 and without a prior history of stroke. The primary outcome was incident stroke (ischemic and hemorrhagic) during follow-up. We report the unadjusted cumulative risk of our primary outcome by SPRINT randomization arm (intensive versus standard BP control) and also fit Cox models to the primary outcome and adjusted for patient age at randomization, race/ethnicity, sex, baseline BP, atrial fibrillation, diabetes, and smoking. RESULTS: We included 5091 patients (mean age 68.2, 44% female, 56.7% non-Hispanic White, and 50.2% randomized to intensive BP control), of which 95/5091 (1.9%) had an incident stroke during a mean of 3.8±0.9 years of follow-up. The risk of incident stroke in patients randomized to standard BP control was 57/2536 (2.3%) and to intensive BP control was 38/2555 (1.5%; P=0.045). In the adjusted Cox model, the hazard ratio for incident stroke events with intensive BP control was 0.65 (95% CI, 0.43-0.98; P=0.040). CONCLUSIONS: Although the SPRINT trial failed to show a reduction in stroke with intensive BP control for all subjects, those with a Montreal Cognitive Assessment score consistent with mild cognitive impairment at baseline had an association between intensive BP control and lower risk of incident stroke. Future trials of primary prevention of stroke may benefit from enrichment using baseline vascular biomarkers of elevated risk, such as mild cognitive impairment.

Effect of Antihypertensives by Class on Cerebral Small Vessel Disease: A Post Hoc Analysis of SPRINT-MIND.

BACKGROUND: Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, although it is unclear whether this reduction occurs due to blood pressure control or class-specific pleiotropic effects, such as improved beat-to-beat arterial pressure variability with calcium channel blockers. The goal of this study was to investigate the influence of antihypertensive medication class, particularly with calcium channel blocker, on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. METHODS: We completed an observational cohort analysis of the SPRINT-MIND trial (Systolic Blood Pressure Trial Memory and Cognition in Decreased Hypertension), a large randomized controlled trial of participants who completed a baseline and 4-year follow-up brain magnetic resonance image with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the magnetic resonance images. A percentage of follow-up time participants were prescribed each of the 11 classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between 2 scans and, to address skew, dichotomized into a top tertile of the distribution compared with the remaining. RESULTS: Among 448 individuals, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 versus 65.7±7.3 years; P<0.001) and systolic blood pressure (128.3±11.0 versus 126.2±9.4 mm Hg; P=0.039). Seventy-two (48.3%) of the top tertile cohort and 177 (59.2%) of the remaining cohort were in the intensive blood pressure arm. Those within the top tertile of progression had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL (P<0.001). Use of angiotensin-converting enzyme inhibitors (odds ratio, 0.36 [95% CI, 0.16-0.79]; P=0.011) and dihydropyridine calcium channel blockers (odds ratio, 0.39 [95% CI, 0.19-0.80]; P=0.011) was associated with less WMH progression, although dihydropyridine calcium channel blockers lost significance when WMH was treated as a continuous variable. CONCLUSIONS: Among participants of SPRINT-MIND trial, angiotensin-converting enzyme inhibitor was most consistently associated with less WMH progression independent of blood pressure control and age.

Self-Reported Race as a Social Determinant of Stroke Risk in Observational Versus Clinical Trial Datasets.

OBJECTIVES: Self-reported Black (SRB) Americans are approximately twice as likely to have a stroke as self-reported White (SRW) Americans. While social determinants of health and vascular risk factors account for some of the disparity, half the increased risk remains unexplained and may be related to unmeasured real-world factors of the racialized experience. MATERIALS: and Methods In this cohort study, we compared SRB and SRW participants in the Systolic Blood Pressure Intervention Trial (SPRINT) to the same groups in the observational Atherosclerosis Risk in Communities (ARIC) study to evaluate if clinical trial participation mitigates disparities in stroke risk. We set the ARIC baseline at visit 4 and excluded participants with prior stroke to create an ARIC cohort similar in age to SPRINT participants. The study outcome was incident primary stroke. We report hazard ratios from Cox models and inverse-probability weighted Cox models with propensity score matching on participant age, sex, diabetes, atrial fibrillation, and smoking. RESULTS: We included 10,094 patients from ARIC and 8,869 from SPRINT, of which 26.1% were SRB. The risk of stroke between SRW participants in SPRINT versus ARIC was not significantly different (IPW-Weighted HR 0.78 [0.52-1.19]). SRB ARIC participants were twice as likely to have a stroke as SRW ARIC participants (IPW-Weighted HR = 1.96 [1.41-2.71]). However, SRB SPRINT participants did not have higher stroke risk compared to SRW SPRINT or ARIC participants (IPW-Weighted HR 0.99 [0.68--1.77] and 0.95 [.57-1.59], respectively). SRB SPRINT participants in the intensive BP control group had a lower risk of stroke compared to SRB ARIC participants (IPW-Weighted HR = 0.39 [0.20-0.75]). CONCLUSIONS: SRB race, compared to SRW race, is associated with an increase in primary stroke risk in the ARIC study but not in the SPRINT trial. The absence of the racial disparity in stroke incidence in SPRINT indicates that aspects of the disparity are modifiable. Population-based interventions that test this hypothesis deserve further attention.

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

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association of Proportional Recovery After Stroke With Health-Related Quality of Life.

Background and Purpose: No data exists on whether proportional recovery (PR) is associated with health-related quality of life (HRQOL) domains. We evaluated whether PR was associated with domain-specific HRQOL scores at 3 months after ischemic stroke. Methods: This prospective cohort study enrolled patients with ischemic stroke between January 2017 and June 2018. Impaired strength was assessed using the Fugl-Meyer Upper Extremity (range, 0­66 points) and Motricity Index (range, 0­100 points) during index hospitalization and 3 months. Both measures are well-validated and reliable in patients with stroke to assesses motor functioning. PR (defined as 70% of difference between initial score and maximum possible recovery) was calculated from the initial measurements. HRQOL was measured using Neuro-QOL domains: upper extremity, depression, and cognition domains. PR was evaluated with HRQOL domains using binomial logistic regression. Results: Final analysis included 84 patients (mean age 67.8±16.4 years; 44% male; 51.2% White). For both Fugl-Meyer Upper Extremity and Motricity Index, the PR threshold was met for 48.8% of patients. Failure to meet Motricity Index PR was only associated with increased odds of HRQOL depression impairment (adjusted odds ratio, 11.8 [95% CI, 1.23­112.7]). Failure to meet Fugl-Meyer Upper Extremity PR threshold was not associated with HRQOL impairment after adjustment. Conclusions: Our findings suggest that reaching the PR threshold provides poor discrimination of HRQOL. Despite not meeting expected PR thresholds, patients can still maintain un-impaired HRQOL, suggesting other factors play a role in preserved HRQOL.

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 (<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.

Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial.

BACKGROUND AND PURPOSE: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (Tmax) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for Tmax delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. METHODS: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume-baseline core infarct volume)/(Tmax 6 or 10 s volume-baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. RESULTS: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%-87.7%) versus 5.3% (1.1%-14.6%) of penumbral tissue was consumed based on Tmax >6 s (P<0.001). In the same comparison for Tmax>10 s, we saw a difference of 165.4% (interquartile range, 56.1%-479.8%) versus 25.7% (interquartile range, 3.2%-72.1%; P<0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on Tmax >6 s (P=0.52) or Tmax >10 s (P=0.92). CONCLUSIONS: Among extended window endovascular thrombectomy patients, Tmax >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the Tmax >6-s mismatch volume may remain viable in untreated patients at 24 hours.

Improving Prehospital Stroke Diagnosis Using Natural Language Processing of Paramedic Reports.

Background and Purpose: Accurate prehospital diagnosis of stroke by emergency medical services (EMS) can increase treatments rates, mitigate disability, and reduce stroke deaths. We aimed to develop a model that utilizes natural language processing of EMS reports and machine learning to improve prehospital stroke identification. Methods: We conducted a retrospective study of patients transported by the Chicago EMS to 17 regional primary and comprehensive stroke centers. Patients who were suspected of stroke by the EMS or had hospital-diagnosed stroke were included in our cohort. Text within EMS reports were converted to unigram features, which were given as input to a support-vector machine classifier that was trained on 70% of the cohort and tested on the remaining 30%. Outcomes included final diagnosis of stroke versus nonstroke, large vessel occlusion, severe stroke (National Institutes of Health Stroke Scale score >5), and comprehensive stroke center-eligible stroke (large vessel occlusion or hemorrhagic stroke). Results: Of 965 patients, 580 (60%) had confirmed acute stroke. In a test set of 289 patients, the text-based model predicted stroke nominally better than models based on the Cincinnati Prehospital Stroke Scale (c-statistic: 0.73 versus 0.67, P=0.165) and was superior to the 3-Item Stroke Scale (c-statistic: 0.73 versus 0.53, P<0.001) scores. Improvements in discrimination were also observed for the other outcomes. Conclusions: We derived a model that utilizes clinical text from paramedic reports to identify stroke. Our results require validation but have the potential of improving prehospital routing protocols.

Investigation of Aortic Wall Thickness, Stiffness and Flow Reversal in Patients With Cryptogenic Stroke: A 4D Flow MRI Study.

BACKGROUND: Stroke etiology is undetermined in approximately one-sixth to one-third of patients. The presence of aortic flow reversal and plaques in the descending aorta (DAo) has been identified as a potential retrograde embolic mechanism. PURPOSE: To assess the relationships between aortic stiffness, wall thickness, and flow reversal in patients with cryptogenic stroke and healthy controls. STUDY TYPE: Prospective. POPULATION: Twenty one patients with cryptogenic stroke and proven DAo plaques (69 ± 9 years, 43% female), 18 age-matched controls (age: 65 ± 8 years, 61% female), and 14 younger controls (36 ± 9 years, 57% female). FIELD STRENGTH/SEQUENCE: 1.5T; 4D flow MRI and 3D dark blood T1 -weighted turbo spin echo MRI of the aorta. ASSESSMENT: Noncontrast aortic 4D flow MRI to measure 3D flow dynamics and 3D dark blood aortic wall MRI to assess wall thickness. 4D flow MRI analysis included automated quantification of aortic stiffness by pulse wave velocity (PWV) and voxelwise mapping of the flow reversal fraction (FRF). STATISTICAL TESTS: Analysis of variance (ANOVA) or Kruskal-Wallis tests, Student's unpaired t-tests or Wilcoxon rank-sum tests, regression analysis. RESULTS: Aortic PWV and FRF were statistically higher in patients (8.9 ± 1.7 m/s, 18.4 ± 7.7%) than younger controls (5.3 ± 0.8 m/s, P < 0.0167; 8.5 ± 2.9%, P < 0.0167), but not age-matched controls (8.2 ± 1.6 m/s, P = 0.22; 15.6 ± 5.8%, P = 0.22). Maximum aortic wall thickness was higher in patients (3.1 ± 0.7 mm) than younger controls (2.2 ± 0.2 mm, P < 0.0167) and age-matched controls (2.7 ± 0.5 mm) (P < 0.0167). For all subjects, positive relationships were found between PWV and age (R2 = 0.71, P < 0.05), aortic wall thickness (R2 = 0.20, P < 0.05), and FRF (R2 = 0.47, P < 0.05). Patients demonstrated relationships between PWV and FRF in the ascending aorta (R2 = 0.32, P < 0.05) and arch (R2 = 0.24, P < 0.05). DATA CONCLUSION: This study showed the utility of 4D flow MRI for evaluating aortic PWV and voxelwise flow reversal. Positive relationships between aortic PWV, wall thickness, and flow reversal support the hypothesis that aortic stiffness is involved in this retrograde embolic mechanism. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Renin Angiotensin System Inhibitors Reduce Aortic Stiffness and Flow Reversal After a Cryptogenic Stroke.

BACKGROUND: Blood flow reversal is a possible mechanism for retrograde embolism in the setting of high-risk atherosclerotic plaques in the descending aorta (DAo). Evidence suggests that pulse wave velocity (PWV) is a determinant of blood flow reversal and can be reduced by the destiffening effect of renin-angiotensin system inhibitors (RASI). PURPOSE: To evaluate the impact of antihypertensive therapy on in vivo changes in PWV and flow reversal in patients with cryptogenic stroke. STUDY TYPE: Prospective. POPULATION: Sixteen patients (69 ± 9 years; 10 males) included after cryptogenic stroke. FIELD STRENGTH/SEQUENCE: 3T. 4D flow sequence (temporal resolution = 19.6 msec) ASSESSMENT: Patients underwent aortic MRI at baseline and at 6-month follow-up. Patients received standard-of-care antihypertensive therapy that were classified as RASI vs. non-RASI medications (ie, destiffening vs. nondestiffening).We compared aortic PWV, flow reversal fraction (FRF), aortic measurements, cardiac function, and other aortic and cardiac measurements in the antihypertensive therapy groups. STATISTICAL TESTS: Two-tailed paired or unpaired Student's t-tests (normal distributions) or Wilcoxon tests (nonnormal distribution). Univariate correlations using Pearson correlation coefficients. RESULTS: There was a significant decrease in PWV in the RASI (n = 10) group (9.4 ± 1.6 m/s vs. 8.3 ± 1.9 m/s; P < 0.05), as well as FRF (18.6% ± 4.1% vs. 16.3% ± 4.0%; P < 0.05) between baseline and the 6-month MRI studies. There were no changes in PWV or FRF in the non-RASI (n = 6) group (P = 0.146 and P = 0.32). A decrease in FRF was significantly correlated with a decrease in PWV (r = 0.53; P < 0.05). DATA CONCLUSION: The findings of our study suggest that RASI therapy after cryptogenic stroke resulted in a decrease of blood flow reversal and aortic stiffness. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 4.