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Optimal blood pressure targets following successful mechanical thrombectomy remain uncertain. While some observational studies suggest that the relationship between blood pressure and outcomes follows a U -shaped curve, others suggest a linear relationship where lower is better. The recent BP-TARGET study (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) did not find a benefit to intensive blood pressure lowering regarding the risk of symptomatic intracranial hemorrhage, but it was not sufficiently powered to detect differences in functional outcomes. On its heels arrived the ENCHANTED2 (Enhanced Control of Hypertension and Thrombectomy Stroke Study)/mechanical thrombectomy trial, the first trial of intensive blood pressure lowering in patients with hypertension following successful mechanical thrombectomy powered to detect a difference in functional outcomes. The trial randomized patients to either a systolic blood pressure less than 120 or 140 to 180 mm Hg. The trial was terminated early due to safety concerns in the more intensive blood pressure–lowering group. In this emerging therapy critique, we explore concerns regarding the generalizability of ENCHANTED2/mechanical thrombectomy, including the high prevalence of intracranial atherosclerosis in the studied population. We survey mechanisms for poor outcomes in patients who receive overly aggressive blood pressure reduction following successful thrombectomy, such as poststroke autoregulatory compromise and persistent microcirculatory hypoperfusion. Finally, we advocate for a more moderate approach, pending further research.

Objectives: To evaluate current trends in the utilization of intravenous thrombolysis (IV-tPA) and mechanical thrombectomy (MT) in acute ischemic stroke (AIS) in various age groups of children in the United States. Methods: We conducted a serial cross-sectional study using primary AIS admissions in children ⩽ 17 years (weighted n = 2807) contained in the 2009–2019 KIDS Inpatient Database. Age-specific utilization frequency of IV-tPA and MT were calculated. Multivariable-adjusted models were used to evaluate demographic predictors of treatment. Results: From 2009 to 2019, there were 2807 AIS admissions in children in the KID of which 55.9% were in boys and 29.9% were 15–17 years old.128 (4.6%) received IV-tPA. IV-tPA utilization differed by age (5–9 years: 3.1%, 15–17 years 8.1% p value Conclusion: IV-tPA and MT utilization in pediatric AIS increased in the United States over the past decade mainly in older children 10–17 years. Utilization increased mainly in patients hospitalized in nonchildren’s hospitals. Usage in children’s hospitals did not change significantly over time.

BackgroundHow the incidence of infective endocarditis (IE) changed in various age, sex and racial/ethnic subgroups of the United States along with the worsening opioid epidemic over the last decade is unknown.MethodsWe utilized data from the 2007-2018 State Inpatient Databases (SID)) of two large demographically diverse states (Florida and New York) to conduct a retrospective cohort study. Cases of incident IE identified using validated International Classification of Diseases codes were combined with census data to compute age, sex- and race-specific incidence. Joinpoint regression was used to quantify the annualized percentage change (APC) in incidence over time.ResultsOf 98,221 incident IE admissions, 70.0% were Non-Hispanic White (NHW) and 60.6% were ≥ 65 years old (yo). The average annual age and sex-standardized incidence of IE in cases/100,000 population was 19.2 (95%CI 18.7-19.6) but this varied by age, sex and race. Incidence was ≈20% higher in men (20.9 [95%CI 20.2-21.7]) compared to women (17.5 [95%CI 16.8-18.2]) and increased with age in both sexes. Incidence was higher in Non-Hispanic Blacks (NHB); 22.5(95%CI 21.0-23.9) compared to NHW: 20.0(95%CI 19.3 to 20.6), Hispanic: 13.2(95%CI 12.3-14.1) and Asian/Pacific Islander patients: 5.9(95%CI 4.7 to 7.1). The age and sex-standardized incidence did not change over time (APC 0.5%,p=0.646). However, incidence increased in women 18-44 (APC 11.0%,p<0.001), men 18-44 (APC 7.3,p<0.001) and 45-64 yo (APC 1.5%,p=0.002) but declined in women ≥ 65 yo (APC −2.8,p=0.049). Most of this increased incidence occurred in NHW women 18-44 (APC 16.6%,p<0.001), NHW men 18-44 (APC 10.6%,p<0.001), NHW men 45-64 (APC 2.8%,p<0.001) and Hispanic Men 18-44 yo (APC 5.6%,p<0.001). Incidence did not change over time in these age/sex groups of NHB and in other age/sex groups. Prevalence of opioid use disorder increased by >2-fold in all age/sex groups over time but the pace of increase was faster in NHW women and men 18-44 yo compared to other races of similar demography (p-for-time interaction ConclusionOver the last two decades, among residents of Florida and New York, incidence of IE increased in several demographic groups, but the most prominent rise was among young NHWs, particularly young NHW women.

Background and Objectives:In the United States, Black, Hispanic, and Asian Americans suffer from excessively high incidence rates of hemorrhagic stroke compared to White Americans. Women suffer from higher rates of subarachnoid hemorrhage than men. Previous reviews detailing racial, ethnic, and sex disparities in stroke have focused on ischemic stroke. We performed a scoping review of disparities in the diagnosis and management of hemorrhagic stroke in the United States to identify areas of disparities, research gaps, and evidence to inform efforts aimed at health equity.Methods:We included studies published after 2010 that assessed racial and ethnic or sex disparities in the diagnosis or management of patients 18 years or older in the United States with a primary diagnosis of spontaneous intracerebral hemorrhage or aneurysmal subarachnoid hemorrhage. We did not include studies assessing disparities in incidence, risks, or mortality and functional outcomes of hemorrhagic stroke.Results:After reviewing 6161 abstracts and 441 full texts, 59 studies met our inclusion criteria. Four themes emerged. First, few data address disparities in acute hemorrhagic stroke. Second, racial and ethnic disparities in blood pressure control following intracerebral hemorrhage exist and likely contribute to disparities in recurrence rates. Third, racial and ethnic differences in end-of-life-care exist, but further work is required to understand whether these differences represent true disparities in care. Fourth, very few studies specifically address sex disparities in hemorrhagic stroke care.Discussion:Further efforts are necessary to delineate and correct racial, ethnic, and sex disparities in the diagnosis and management of hemorrhagic stroke.

The past decade has seen significant advances in stroke prevention. These advances include new antithrombotic agents, new options for dyslipidemia treatment, and novel techniques for surgical stroke prevention. In addition, there is greater recognition of the benefits of multifaceted interventions, including the role of physical activity and dietary modification. Despite these advances, the aging of the population and the high prevalence of key vascular risk factors pose challenges to reducing the burden of stroke. Using a cause-based framework, current approaches to prevention of cardioembolic, cryptogenic, atherosclerotic, and small vessel disease stroke are outlined in this paper. Special emphasis is given to recent trials of antithrombotic agents, including studies that have tested combination treatments and responses according to genetic factors.

Background:Cerebral venous sinus stenting (VSS) has emerged as a new surgical procedure for the treatment of severe IIH, and its popularity has been anecdotally on the rise. This study explores recent temporal trends of VSS and other surgical IIH treatments in the United States.Methods:Adult IIH patients were identified from the 2016-20 National Inpatient Sample databases, and surgical procedures and hospital characteristics were recorded. Temporal trends of procedure numbers for VSS, cerebrospinal fluid (CSF) shunts, and optic nerve sheath fenestrations (ONSF) were assessed and compared.Results:46,065 [95%CI: 44,710-47,420] IIH patients were identified, of whom 7,535 patients [95%CI: 6,982-8,088] received surgical IIH treatments. VSS procedures increased 80% (150 [95%CI: 55-245] to 270 [95%CI: 162-378] per year, pConclusions:Practice patterns for surgical IIH treatment in the United States are rapidly evolving, and VSS is becoming increasingly common. These findings highlight the urgency of randomized controlled trials to investigate the comparative effectiveness and safety of VSS, CSF shunts, ONSF, and standard medical treatments.

Background and ObjectivesTo test the hypothesis that the age and sex-specific prevalence of infectious (pneumonia, sepsis, and urinary tract infection [UTI]) and noninfectious (deep venous thrombosis [DVT], pulmonary embolism [PE], acute renal failure [ARF], acute myocardial infarction [AMI], and gastrointestinal bleeding [GIB]) complications increased after acute ischemic stroke (AIS) hospitalization in the United States from 2007 to 2019.MethodsWe conducted a serial cross-sectional study using the 2007–2019 National Inpatient Sample. Primary AIS admissions in adults (aged 18 years or older) with and without complications were identified usingInternational Classification of Diseasescodes. We quantified the age/sex-specific prevalence of complications and used negative binomial regression models to evaluate trends over time.ResultsOf 5,751,601 weighted admissions, 51.4% were women. 25.1% had at least 1 complication. UTI (11.8%), ARF (10.1%), pneumonia (3.2%), and AMI (2.5%) were the most common complications, while sepsis (1.7%), GIB (1.1%), DVT (1.2%), and PE (0.5%) were the least prevalent. Marked disparity in complication risk existed by age/sex (UTI: men 18–39 years 2.1%; women 80 years or older 22.5%). Prevalence of UTI (12.9%–9.7%) and pneumonia (3.8%–2.7%) declined, but that of ARF increased by ≈3-fold (4.8%–14%) over the period 2007–2019 (allp< 0.001). AMI (1.9%–3.1%), DVT (1.0%–1.4%), and PE (0.3%–0.8%) prevalence also increased (p< 0.001), but that of sepsis and GIB remained unchanged over time. After multivariable adjustment, risk of all complications increased with increasing NIH Stroke Scale (pneumonia: prevalence rate ratio [PRR] 1.03, 95% CI 1.03–1.04, for each unit increase), but IV thrombolysis was associated with a reduced risk of all complications (pneumonia: PRR 0.80, 85% CI 0.73–0.88; AMI: PRR 0.85, 95% CI 0.78–0.92; and DVT PRR 0.87, 95% CI 0.78–0.98). Mechanical thrombectomy was associated with a reduced risk of UTI, sepsis, and ARF, but DVT and PE were more prevalent in MT hospitalizations compared with those without. All complications except UTI were associated with an increased risk of in-hospital mortality (sepsis: PRR 1.97, 95% CI 1.78–2.19).DiscussionInfectious complications declined, but noninfectious complications increased after AIS admissions in the United States in the last decade. Utilization of IV thrombolysis is associated with a reduced risk of all complications.

Background and ObjectivesStroke in young adults constitutes 15%–18% of all ischemic stroke cases. Black individuals have an excess risk of ischemic stroke especially in young adults. Although it is known that Black patients have a higher prevalence of hypertension and diabetes, few studies have addressed the association of concurrent multiple vascular risk factors with the excess risk of early-onset stroke among Black individuals.MethodsA population-based case-control study of early-onset ischemic stroke, ages 15–49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Presence of the risk factors of obesity, hypertension, diabetes, and current smoking were obtained from both cases and controls by an in-person interview. Risk factor groups were defined as (1) 1 risk factor, (2) 2 risk factors, (3) 3 risk factors, and (4) 4 risk factors. Logistic regression analysis adjusting for age and sex was used to evaluate the association between each risk factor group and ischemic stroke compared with the reference group with no risk factors.ResultsThe study included 1,034 cases and 1,091 controls. Of the cases, 47% were Black, 54% were men, and the mean (±SD) age was 41.0 (±6.9) years. The odds of having a stroke increased exponentially as the number of risk factors increased, 2.1, 2.6, 7.6, 16.5, allp< 0.001, for groups 1–4, respectively. When stratified by race, Black individuals were approximately 6 times more likely to have all 4 risk factors.DiscussionThe risk of stroke in young adults increased exponentially with the number of risk factors. Young Black patients with ischemic stroke were approximately 6 times more likely to have the co-occurrence of obesity, hypertension, diabetes, and smoking compared with their White counterparts. Targeting public health interventions to identify and improve care to Black young adults with multiple stroke risk factors may have substantial impact on lowering risk of stroke.

Background: Initiation of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel plays a significant role in the secondary prevention of recurrent acute ischemic events following high risk transient ischemic attack (TIA) and minor acute ischemic stroke (AIS). However, some patients do not receive the same targeted therapy on discharge and are only maintained on single antiplatelet therapy. Our aim was to identify the variations in single vs dual antiplatelet prescribing practices at the time of discharge within a Stroke Clinical Network consisting of nine stroke centers located in rural, suburban, and urban geographical regions. Methods: The GWTG registry was queried for all patients >18 years old with a TIA or a minor AIS (admission NIHSS ≤5), who were admitted to a single hospital network between January 2018 and December 2021. Demographics collected including age, race, gender, and BMI. Patients on concurrent anticoagulation were excluded. We evaluated antiplatelet discharge practices at the tertiary stroke center vs the entire network, among men vs. women, African Americans (AA) vs whites, age 18-70 vs >70 years, and across BMI. Chi squared and generalized linear models were used to test significant relationships between subgroups. Results: Among 2953 patients with a TIA or minor AIS, the mean age was 67.3 (SD +/- 13.8 years), with 42% >70 years of age. 47.8% were women; 37% were AA and 60% were white. DAPT was prescribed at the time of discharge to 40% of patients overall. Gender was a significant factor with men (43%) more likely to get prescribed DAPT than females (37%) (p=.002). While BMI did not have a lone effect on number of antiplatelets (AP) prescribed, when it was included as a covariate, there was a significant effect on the number of AP prescribed; with the higher the BMI, the less likely patients were to receive DAPT. Differences according to age, race, and effect of whether the patient was discharged from a tertiary center were not significant. Conclusion: We identified underutilization of DAPT following TIA and minor stroke across a health system, especially in women. Targeted intervention to increase DAPT use could lead to reduced rate of short-term stroke recurrence.

Introduction: Hyperlipidemia is a modifiable risk factor for stroke, with the magnitude of LDL-C reduction correlating to risk of recurrent ischemic stroke. A high-intensity statin is considered standard of care in addition to dietary modification. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are used if the LDL-C target is not achieved despite maximally tolerated statins with ezetimibe. We investigated the role for PCSK9 inhibitors in our ischemic stroke population. Methods: An IRB approved retrospective review of patients admitted for acute ischemic stroke between 2019 – 2020 was performed. We estimated the probability of benefit from PCSK9 treatment with the following criteria: LDL > 190 regardless of treatment, LDL 161-190 on any dose statin therapy, and LDL 131-160 on high intensity statin therapy. Results: 774 patients with ischemic stroke were admitted during this time frame. Mean age 62.8 +/- 13.2 with 57% male (52% Black, 42% White). 584 (75%) of these patients had LDL above goal. One patient was on PCSK9 therapy on admission. Although the majority of our patients had uncontrolled cholesterol, only one additional patient would meet the strict prescription criteria for PCSK9 therapy of being adherent to maximal tolerated statin dose and ezetimibe with LDL above goal. Other potential patients with estimated benefit include LDL >190 (20 patients), LDL 161-190 (16 patients), LDL 131-160 (13 patients). In total this amounts to 6.7% of stroke patients who we would expect to need PCSK9 inhibitors in the future. Conclusion: Using conservative projections, we estimate that about 1 in 14 patients with ischemic stroke could benefit from PCSK9 therapy. Achieving LDL targets more consistently is a promising approach to decreasing the recurrent stroke rate. Further prospective data evaluating outcomes after initiating PCSK9 inhibitor treatment are needed to validate these findings.

Background and Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles ( P P =0.015). Lower performance was attributed largely to Word List Recall ( P P ≤0.01). The scores for left versus right carotid disease were similar. Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02089217.

Malignant cerebral edema (MCE) and intracranial hemorrhage (ICH) are associated with poor neurological outcomes despite revascularization after mechanical thrombectomy (MT). The factors associated with the development of MCE and ICH after MT are not well understood.To determine periprocedural factors associated with MCE, ICH, and poor functional outcome.We retrospectively analyzed anterior cerebral circulation large vessel occlusion cases that underwent MT from 2012 to 2019 at a single Comprehensive Stroke Center. Multivariate logistic regression analyses were performed to determine significant predictors of MCE, ICH, and poor functional outcome (modified Rankin Scale, 3-6) at 90 d.Four hundred patients were included. Significant independent predictors of MCE after MT included initial stress glucose ratio (iSGR) (odds ratio [OR], 14.26; 95% CI, 3.82-53.26; P.001), National Institutes of Health Stroke Scale (NIHSS) (OR, 1.10; 95% CI, 1.03-1.18; P = .008), internal carotid artery compared with M1 or M2 occlusion, and absence of successful revascularization (OR, 0.16; 95% CI, 0.06-0.44; P.001). Significant independent predictors of poor functional outcome included MCE (OR, 7.47; 95% CI, 2.20-25.37; P = .001), iSGR (OR, 5.15; 95% CI, 1.82-14.53; P = .002), ICH (OR, 4.77; 95% CI, 1.20-18.69; P = .024), NIHSS (OR, 1.10; 95% CI, 1.05-1.16; P.001), age (OR, 1.04; 95% CI, 1.03-1.07; P.001), and thrombolysis in cerebral infarction 2C/3 recanalization (OR, 0.12; 95% CI, 0.05-0.29; P.001).Elevated iSGR significantly increases the risk of MCE and ICH and is an independent predictor of poor functional outcome. Thrombolysis in cerebral infarction 2C/3 revascularization is associated with reduced risk of MCE, ICH, and poor functional outcome. Whether stress hyperglycemia represents a modifiable risk factor is uncertain, and further investigation is warranted.

Background: The incidence of cerebral venous thrombosis (CVT) in children of the United States is unknown, and it is uncertain how the burden of CVT hospitalizations in children changed over the last decade. Methods: We conducted a retrospective cohort study using the State Inpatient Database and Kid’s inpatient database. All new CVT cases in children (0–19 years) in the New York 2006 to 2018 State Inpatient Database (n=705), and all cases of CVT in the entire US contained in the 2006 to 2019 Kid’s inpatient database (weighted n=6115) were identified using validated International Classification of Diseases (ICDs ) codes. Incident counts were combined with census data to compute incidence. Between-group differences in incidence were tested using 2-proportions Z -test, and Joinpoint regression was used to trend incidence over time. Results: Across the study period, 48.2% of all incident CVT cases and 44.6% of all CVT admissions nationally were in girls. Of all incident cases, 27.2% were infants and 65.8% of these infants were neonates. Average incidence across the study period was (1.1/100 000/year, SE:0.04) but incidence in infants (6.4/100 000/year) was at least 5 times the incidence in other age groups (1–4 years: 0.7/100 000/year, 15–19 years: 1.2/100 000/year). Incidence and national burden of CVT admissions was higher in girls in adolescents 15 to 19 years, but overall burden was higher in boys in other age groups. Age- and sex-standardized CVT incidence increased by 3.8% annually (95% CI, 0.2%–7.6%), while the overall burden of admissions increased by 4.9% annually (95% CI, 3.6%–6.2%). Conclusions: CVT incidence in New York and national burden of CVT increased significantly over the last decade.

Background: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recently published studies. Methods: The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel. Results: For asymptomatic patients, we recommend low-dose aspirin (75–100 mg/day) or clopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAPT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAPT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking. Conclusions: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAPT (ticagrelor instead of clopidogrel) should be evaluated in future trials.

Background and Purpose: IV tPA (intravenous thrombolysis with alteplase) and mechanical thrombectomy (MT) utilization increased in acute ischemic stroke hospitalizations in the United States over the last decade. It is uncertain whether this increase occurred equally across all age, sex, and racial groups. Methods: Adult acute ischemic stroke hospitalizations (weighted n=4 442 657) contained in the 2008 to 2017 National Inpatient Sample were identified using International Classification of Diseases codes. Proportions of hospitalizations with IV tPA and MT were computed according to age, sex, and race. Joinpoint and multivariable-adjusted logistic regression models were used to evaluate trends over time. Results: Across this period, 32.4% of all hospitalizations were in patients ≥80 years, and 64.7% of these were women. IV tPA and MT use differed by age with highest proportion of utilization of both treatments in patients aged 18 to 39 years (IV tPA, 12.3%) and lowest percentage in patients aged ≥90 years (IV tPA, 7.9%). Utilization of both procedures increased over time in all age groups, but the pace of increase was faster in patients ≥90 years compared with patients aged 18 to 39 years (MT: odds ratio, 1.25 [95% CI, 1.20–1.35] per unit increase in year, P interaction 10% in all demographic subgroups except in Black patients 60 to 79 years and Black patients ≥80 years. Analysis of race-by-time interaction revealed the Black-vs-White treatment gaps for IV tPA (odds ratio, 1.02 [95% CI, 1.01–1.03]) and MT (odds ratio, 1.08 [95% CI,1.05–1.12]) declined over time (both P interaction Conclusions: Age- and sex-related treatment gaps in IV tPA and MT reduced over the last decade. Racial disparity in IV tPA and MT utilization persists with particularly lower frequency of usage of both acute stroke treatments in Black patients compared with White patients, but race-associated treatment gaps also declined over time.

Background: IL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study). Methods: Duplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P >0.05 for variable removal. To assess model stability, we computed the E -value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples. Results: There were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β=0.09, P =1.3×10 −3 ), vulnerability (OR, 1.21 [95% CI, 1.05–1.40]; P =7.4×10 −3 , E -value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P =9.1×10 −6 , E -value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models. Conclusions: Circulating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.

BackgroundElevated International Normalized Ratio (INR) is a marker of coagulopathy, but its impact on outcomes following mechanical thrombectomy (MT) in patients with stroke is unclear. This study investigates the impact of mild INR elevations on clinical outcomes following MT.MethodsIn this retrospective cohort study, consecutive patients with stroke treated with MT were identified from 2015 to 2020 at a Comprehensive Stroke Center. Demographic information, past medical history, INR, National Institutes of Health Stroke Scale score, use of tissue plasminogen activator, and last known normal to arteriotomy time were recorded. Outcome measures included modified Thrombolysis in Cerebral Infarction (mTICI) score, modified Rankin Scale (mRS) score at 90 days, and intracerebral hemorrhage (ICH). Patients were divided into two groups: normal INR (0.8–1.1) and mildly elevated INR (1.2–1.7).ResultsA total of 489 patients were included for analysis, of which 349 had normal INR and 140 had mildly elevated INR. After multivariable adjustments, mildly elevated INR was associated with lower odds of excellent outcomes (mRS 0–1, OR 0.24, p=0.009), lower odds of functional independence (mRS 0–2, OR 0.38, p=0.038), and higher odds of 90-day mortality (OR 3.45, p=0.018). Elevated INR was not associated with a higher likelihood of ICH, and there were no differences in rates of HI1, HI2, PH1, or PH2 hemorrhagic transformations; however, elevated INR was associated with significantly higher odds of 90-day mortality in patients with ICH (OR 6.22, p=0.024). This effect size was larger than in patients without ICH (OR 3.38, pConclusionIn patients with stroke treated with MT, mildly elevated INR is associated with worse clinical outcomes after recanalization and may worsen the mortality risk of hemorrhagic transformations.

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.

Brainstem strokes can present with an array of ophthalmologic findings depending on the location of the lesion. Eye movements are recorded on electrooculogram during polysomnography for sleep staging. We present the case of a patient with a dorsal midbrain hemorrhagic stroke and nystagmus with distinct findings on the electrooculogram during polysomnography. These eye movements from nystagmus differed in many aspects (frequency and amplitude) from the classic findings of other eye movements recorded during different stages of sleep. These polysomnography findings have not been reported in the setting of midbrain stroke. Future studies comparing nystagmus in multiple sleep stages in stroke patients would be of interest. CITATION: Shoukat U, Glick DR, Chaturvedi S, Diaz-Abad M. Images: Polysomnographic findings of nystagmus caused by a midbrain hemorrhagic stroke. J Clin Sleep Med. 2022;18(5):1479–1482.

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%-20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques.

© The Author(s) 2022. Sage Publications, Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients

Background and ObjectiveTo test the hypothesis that age-specific, sex-specific, and race-specific and ethnicity-specific incidence of nontraumatic subarachnoid hemorrhage (SAH) increased in the United States over the last decade.MethodsIn this retrospective cohort study, validated International Classification of Diseases codes were used to identify all new cases of SAH (n = 39,475) in the State Inpatients Databases of New York and Florida (2007–2017). SAH counts were combined with Census data to calculate incidence. Joinpoint regression was used to compute the annual percentage change (APC) in incidence and to compare trends over time between demographic subgroups.ResultsAcross the study period, the average annual age-standardized/sex-standardized incidence of SAH in cases per 100,000 population was 11.4, but incidence was significantly higher in women (13.1) compared with that in men (9.6),p< 0.001. Incidence also increased with age in both sexes (men aged 20–44 years: 3.6; men aged 65 years or older: 22.0). Age-standardized and sex-standardized incidence was greater in Black patients (15.4) compared with that in non-Hispanic White (NHW) patients (9.9) and other races and ethnicities,p< 0.001. On joinpoint regression, incidence increased over time (APC 0.7%,p< 0.001), but most of this increase occurred in men aged 45–64 years (APC 1.1%,p= 0.006), men aged 65 years or older (APC 2.3%,p< 0.001), and women aged 65 years or older (APC 0.7%,p= 0.009). Incidence in women aged 20–44 years declined (APC −0.7%,p= 0.017), while those in other age/sex groups remained unchanged over time. Incidence increased in Black patients (APC 1.8%,p= 0.014), whereas that in Asian, Hispanic, and NHW patients did not change significantly over time.DiscussionNontraumatic SAH incidence in the United States increased over the last decade predominantly in middle-aged men and elderly men and women. Incidence is disproportionately higher and increasing in Black patients, whereas that in other races and ethnicities did not change significantly over time.

The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Atrial fibrillation (AF) can be newly detected in approximately one-fourth of patients with ischemic stroke and transient ischemic attack without previously recognized AF. We present updated evidence supporting that AF detected after stroke or transient ischemic attack (AFDAS) may be a distinct clinical entity from AF known before stroke occurrence (known atrial fibrillation). Data suggest that AFDAS can arise from the interplay of cardiogenic and neurogenic forces. The embolic risk of AFDAS can be understood as a gradient defined by the prevalence of vascular comorbidities, the burden of AF, neurogenic autonomic changes, and the severity of atrial cardiopathy. The balance of existing data indicates that AFDAS has a lower prevalence of cardiovascular comorbidities, a lower degree of cardiac abnormalities than known atrial fibrillation, a high proportion (52%) of very brief (

To compare in-hospital mortality between intracerebral hemorrhage (ICH) patients in rural hospitals to those in urban hospitals of the USA. We used the National Inpatient Sample to retrospectively identify all cases of ICH in the USA over the period 2004–2014. We used multivariable-adjusted models to compare odds of mortality between rural and urban hospitals. Joinpoint regression was used to evaluate trends in age- and sex-adjusted mortality in rural and urban hospitals over time. From 2004 to 2014, 5.8% of ICH patients were admitted in rural hospitals. Rural patients were older (mean [SE] 76.0 [0.44] years vs. 68.8 [0.11] years in urban), more likely to be white and have Medicare insurance. Age- and sex-adjusted mortality was greater in rural hospitals (32.2%) compared to urban patients (26.5%) (p value

Few studies have addressed Black-White differences in left ventricular hypertrophy (LVH) in young stroke patients without a history of hypertension.A case-only cross-sectional analysis performed in 2019 of data from the Stroke Prevention in Young Adults Study, a population-based case-control study of ischemic stroke patients ages 15-49. The main outcomes were hypertension indicators at the time of stroke hospitalization: self-reported history of hypertension, LVH by echocardiography (Echo-LVH) and LVH by electrocardiogram (ECG-LVH). The prevalence of Echo-LVH was further determined in those with and without a history of hypertension. Adjusted odds ratios and 95% confidence intervals comparing blacks and whites were calculated by logistic regression.The study population included 1028 early-onset ischemic stroke patients, 48% Black cases, 54% men, median age 43 years (interquartile range, 38-46 years). Overall, the prevalence of hypertension history, Echo-LVH and ECG-LVH were 41.3%, 34.1% and 17.5%, respectively. Each of the hypertension indicators were more frequent in men than in women and in Black cases than in White cases. Black patients without a history of hypertension had higher rates of Echo-LVH than their white counterparts, 40.3% vs 27.7% (age and obesity adjusted OR 1.8; 95% CI 1.02-3.4) among men and 20.9% vs 7.6% (adjusted OR 2.7; 95% CI 1.2-6.2) among women.LVH was common in young patients with ischemic stroke, regardless of self-reported history of hypertension. These findings emphasize the need for earlier screening and more effective treatment of hypertension in young adults, particularly in the Black population.

Background: Despite the association of statin use and lowered recurrent stroke and mortality, some studies suggest young stroke patients do not receive the same intense targeted treatment medical therapies for secondary stroke prevention as older patients. Our specific objective was to determine if there were differences in statin medication discharge practices provided to young ischemic stroke patients within a Stroke Clinical Network. The Stroke Clinical Network consists of nine stroke centers located in rural, suburban and urban geographical regions. Methods: The GWTG registry was queried (FY 2017-2021) to identify ischemic stroke patients to determine statin discharge practices using the following criteria: sex, race, age groups ≥18-39 and ≥40-49, LDL levels < 100, 101-129 and > 130, diabetes, HTN, and smoking status. Chi squared tests of proportions were used to evaluate significant relationships between subgroups. Results: Among 1,294 young ischemic stroke patients: 53% (682/1294) were Black and 38% (493/1294) White; mean age 40.9 years (SD +/-7.21years). Men, blacks, patients older than 40 and diabetics were more likely to be discharged on a statin. There was a direct correlation between sex, race, age, LDL level and diabetes with statin discharge practices. There was no difference in statin discharge practices between smokers and nonsmokers. Conclusions: Opportunities to improve compliance with obtaining LDL levels upon admission and prescribing statins at discharge exist. Increasing statin administration in the young stroke patient population reflects best practice and will decrease mortality and morbidity.

Background: Obesity is a known risk factor for acute ischemic stroke (AIS) in both the adult and young ( Methods: All patients with AIS, younger than 50 years, admitted to the University of Maryland Medical System hospitals between Jan 2017 and December 2020, were included. Patients were categorized into 3 BMI categories - 1) Normal (18.5-24.9), 2) Overweight (25-29) and 3) Obese (≥30). Lifestyle-related risk factor (HTN, DM, DLD, and sleep apnea) burden and distribution was analyzed across the three groups using Chi-squared tests of association. One-way Welch’s ANOVA was utilized to test mean differences in number of risk factors across BMI categories. Results: We identified 1272 patients with young stroke. A total of 797/1272 (63%) of our young stroke patients were obese and 23.1% (n=294) were in the overweight category. In the obese category: mean age was 41.4 years (SD +/- 6.75), 49.4% were women and 53.4% were Black. Risk factor burden was significantly higher in the obese vs. the overweight and normal weight categories (Table 1)(p = Conclusions: A majority of young stroke patients were obese, and the obese and overweight patients were predominantly African American. Obese patients had the highest proportion of all medical risk factors, as well as a risk factor burden nearly twice as high as those with normal BMI. Efforts to reduce obesity hold promise in mitigating the burden of stroke in young adults.

Background and Purpose: Existing data shows that IV thrombolysis (tPA) and mechanical thrombectomy (MT) use in acute ischemic stroke (AIS) patients and malignancy is Methods: All admissions with a primary diagnosis of AIS (weighted n=5,554,161) were identified from the 2007-2018 Nationwide Inpatient Sample. Cancer-associated strokes (CAS) were categorized into hematologic (hem), solid and metastatic (met) cancers. Joint point regression and multivariable-adjusted logistic regression models with interaction terms were used to evaluate rate of change in t-PA and MT use in CAS compared to non-CAS admissions. Results: Across this period, 4.0% of AIS admissions had comorbid CAS. The proportion of AIS hospitalizations with CAS increased from 3.8% in 2007 to 4.4% in 2018. Mean age of CAS was 72.9 (47.6% women) vs. 70.6 years (51.8% women) among non-CAS. CAS patients had fewer vascular risk factors. Highest t-PA usage was in non-CAS pts (7.8%) and lowest use in met-CAS pts (3.8%) and this difference was significant. In contrast MT usage was highest in met-CAS (2.0%) vs non-CAS (1.6%) and hem-CAS (1.2%). A race-by-time interaction revealed an increase in utilization of both therapies in all CAS groups. Pace of the increase was slower in met CAS (OR 0.97, 95%CI 0.95-0.99) per unit increase in year. MT use increased at a faster pace in met-CAS patients (OR 1.07, 95%CI 1.02-1.12) compared to non-CAS. Although overall mortality rates for patients with cancer has decreased for all cancer types, CAS had significantly higher in hospital mortality as compared to NCS (8.9% vs 4.4%, p Conclusions: Utilization of both t-PA and MT has increased over the last decade. Contrary to prior studies, the current frequency and pace of increase in MT use is greater in met-CAS admissions compared to non-CAS. Patients with CAS have fewer traditional vascular risk factors and significantly higher in hospital mortality. Future studies should address longer term outcomes in CAS versus non-cancer strokes.