Embolic Stroke of Undetermined Source: New Data and New Controversies on Cardiac Monitoring and Anticoagulation.

Embolic strokes of undetermined source (ESUS) represent 9%-25% of all ischemic strokes. Based on the suspicion that a large proportion of cardioembolic sources remain undetected among embolic stroke of undetermined source patients, it has been hypothesized that a universal approach of anticoagulation would be better than aspirin for preventing recurrent strokes. However, 4 randomized controlled trials (RCTs), with different degrees of patient selection, failed to confirm this hypothesis. In parallel, several RCTs consistently demonstrated that prolonged cardiac monitoring increased atrial fibrillation detection and anticoagulation initiation compared with usual care in patients with ESUS, and later in individuals with ischemic stroke of known cause (e.g., large or small vessel disease). However, none of these trials or subsequent meta-analyses of all available RCTs have shown a reduction in stroke recurrence associated with the use of prolonged cardiac monitoring. In this article, we review the clinical and research implications of recent RCTs of antithrombotic therapy in patients with ESUS and in high-risk populations with and without stroke, with device-detected asymptomatic atrial fibrillation.

The effect of sodium-glucose transporter 2 inhibitors on stroke in patients with type 2 diabetes: A meta-analysis.

OBJECTIVES: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D). METHODS: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95 % confidence intervals (CIs). RESULTS: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59 %) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95 % CI 0.89-1.04), ischemic stroke (RR 0.89; 95 % CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95 % CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95 % CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95 % CI 0.56-0.97). CONCLUSION: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.

Improving Stroke Risk Factor Management Focusing on Health Disparities and Knowledge Gaps.

Stroke is a leading cause of death and disability in the United States and worldwide, necessitating comprehensive efforts to optimize stroke risk factor management. Health disparities in stroke incidence, prevalence, and risk factor management persist among various race/ethnic, geographic, and socioeconomic populations and negatively impact stroke outcomes. This review highlights existing literature and guidelines for stroke risk factor management, emphasizing health disparities among certain populations. Moreover, stroke risk factors for special groups, including the young, the very elderly, and pregnant/peripartum women are outlined. Strategies for stroke risk factor improvement at every level of the health care system are discussed, from the individual patient to providers, health care systems, and policymakers. Improving stroke risk factor management in the context of the social determinants of health, and with the goal of eliminating inequities and disparities in stroke prevention strategies, are critical steps to reducing the burden of stroke and equitably improving public health.

Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.

Predictors and Temporal Trends of Withdrawal of Life-Sustaining Therapy After Acute Stroke in the Florida Stroke Registry.

Temporal trends and factors associated with the withdrawal of life-sustaining therapy (WLST) after acute stroke are not well determined. DESIGN: Observational study (2008-2021). SETTING: Florida Stroke Registry (152 hospitals). PATIENTS: Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Importance plots were performed to generate the most predictive factors of WLST. Area under the curve (AUC) for the receiver operating curve were generated for the performance of logistic regression (LR) and random forest (RF) models. Regression analysis was applied to evaluate temporal trends. Among 309,393 AIS patients, 47,485 ICH patients, and 16,694 SAH patients; 9%, 28%, and 19% subsequently had WLST. Patients who had WLST were older (77 vs 70 yr), more women (57% vs 49%), White (76% vs 67%), with greater stroke severity on the National Institutes of Health Stroke Scale greater than or equal to 5 (29% vs 19%), more likely hospitalized in comprehensive stroke centers (52% vs 44%), had Medicare insurance (53% vs 44%), and more likely to have impaired level of consciousness (38% vs 12%). Most predictors associated with the decision to WLST in AIS were age, stroke severity, region, insurance status, center type, race, and level of consciousness (RF AUC of 0.93 and LR AUC of 0.85). Predictors in ICH included age, impaired level of consciousness, region, race, insurance status, center type, and prestroke ambulation status (RF AUC of 0.76 and LR AUC of 0.71). Factors in SAH included age, impaired level of consciousness, region, insurance status, race, and stroke center type (RF AUC of 0.82 and LR AUC of 0.72). Despite a decrease in the rates of early WLST (< 2 d) and mortality, the overall rates of WLST remained stable. CONCLUSIONS: In acute hospitalized stroke patients in Florida, factors other than brain injury alone contribute to the decision to WLST. Potential predictors not measured in this study include education, culture, faith and beliefs, and patient/family and physician preferences. The overall rates of WLST have not changed in the last 2 decades.

Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows.

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. RESULTS: Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. CONCLUSIONS: In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.

Direct Bypass Surgery for Moyamoya and Steno-occlusive Vasculopathy: Clinical Outcomes, Intraoperative Blood Flow Analysis, Long-term Follow-up, and Long-term Bypass Patency in a Single Surgeon Case Series of 162 Procedures.

BACKGROUND: Cerebral extracranial-intracranial (EC-IC) direct bypass is a commonly used procedure for the treatment of cerebral hypoperfusion secondary to chronic steno-occlusive vasculopathy. We sought to determine clinical outcomes, intraoperative blood flow analysis, long term follow up, and long term patency rates from a single surgeon's series of direct cerebral bypass for moyamoya disease, moyamoya syndrome, and steno-occlusive disease. METHODS: We reviewed clinical, demographic, operative and neuroimaging records for all patients who underwent a direct EC-IC bypass by the senior author between August 1999 and November 2020. Primary outcomes analyzed were functional long-term outcomes (by modified Rankin score [mRS]), surgical complications, and short-term and long-term bypass patency. RESULTS: A total of 162 revascularization procedures in 124 patients were performed. Mean clinical follow up time was 2 years 11 months. The combined immediate and long term postoperative stroke and/or intracerebral hemorrhage rate was 6.2%. There were 17 bypasses (10%) that were found to be occluded at long-term follow-up, all but one were asymptomatic. Long-term graft occlusion was correlated with presence of complete collateralization on preoperative angiography but not cut flow index (CFI). Overall, patients had a significant clinical improvement with a mean mRS score 1.8 preoperatively and 1.2 postoperatively. CONCLUSIONS: In our consecutive series of patients treated with direct EC-IC cerebral bypass, there was significant improvement in functional outcome as measured by the mRS. The long term patency rate was 90%. There was a statistically significant correlation between complete or incomplete angiographic collateralization patterns and long-term bypass occlusion. There was no correlation between bypass type, clinical syndrome, or CFI and long-term occlusions. The role of bypass surgery and the need for surgical expertise remain strong in the treatment of moyamoya variants and a select group of atherosclerotic steno-occlusive patients.

Development of an Equity, Diversity, Inclusion, and Anti-racism Pledge as the Foundation for Action in an Academic Department of Neurology.

Racial inequities as illustrated by the health disparities in COVID19 infections and deaths, the recent killings of Black men and women by law enforcement, and the widening socioeconomic inequality and have brought systemic racism into a national conversation. These unprecedented times may have deleterious consequences, increasing stress, and trauma for many members of the neurology workforce. The Equity, Diversity, Inclusion and Anti-Racism Committee within our Department of Neurology provides infrastructure and guidance to foster a culture of belonging and addresses the well-being of faculty, staff, and trainees. Here, we present the creation and implementation of our Equity, Diversity, Inclusion, and Anti-Racism (EDIA) Pledge which was central to our committee's response to these unprecedented times. We outline the process of developing this unique EDIA Pledge and provide a roadmap for approaching these important topics through a CME Neurology Grand Rounds aimed at fostering a diverse, inclusive, equitable and antiracist work environment. Through the lived experiences of 4 faculty members, we identify the impact of bias and microaggressions, and encourage allyship and personal development for cultural intelligence. We hope these efforts will inspire Neurology departments and other academic institutions across the globe to make a similar pledge.

Ten-Year Trend in Age, Sex, and Racial Disparity in tPA (Alteplase) and Thrombectomy Use Following Stroke in the United States.

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, 1.20­1.35] per unit increase in year, P interaction <0.001). Frequency of utilization of IV tPA and MT was lower in Black patients compared with White patients in most age groups. Usage of both procedures increased over time in all races and after 2015, IV tPA utilization was >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, 1.01­1.03]) and MT (odds ratio, 1.08 [95% CI,1.05­1.12]) declined over time (both P interaction <0.01). Sex-related differences in IV tPA use were noted, but this gap also declined over time. 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.

The Proportion of Preventable Thrombectomy Procedures with Improved Atrial Fibrillation Stroke Prevention.

BACKGROUND: Large vessel occlusion (LVO) strokes can in part be prevented with better atrial fibrillation (AF) stroke prevention strategies; thus we evaluated the rate of AF in patients presenting with acute LVO strokes undergoing mechanical thrombectomy (MT) and assessed patterns of oral anticoagulant (OAC) use prior to the index stroke. METHODS AND RESULTS: We identified 347 MT cases from February 2015 to September 2018. A retrospective chart review was conducted to identify patient sociodemographics, presence of AF, use of anticoagulation, stroke severity, CHA2DS2-VASc scores, and functional outcomes. AF was present in 161 (46%) cases. Patients with AF were older (mean 76 ± 11 years vs. 66 ± 15 years) and more likely to be female (56% vs. 46%) with higher rates of hypertension, dyslipidemia, heart failure and smoking. Of the 100 patients with known AF, 59 were not on anticoagulation prior to the index stroke. Of 39 patients with known AF on OAC, 57% were not therapeutic on warfarin and 20% were not taking prescribed direct OACs. A total of 72 (21%) thrombectomy cases were performed on patients with known AF who were not effectively anticoagulated. After multivariate adjustments, there was no significant difference in modified Rankin Scale score at discharge, in-hospital mortality, or symptomatic intracranial hemorrhage between the AF and non-AF groups. CONCLUSION: In our study, 21% of patients with LVO stroke had known AF and were not effectively anticoagulated. Improved stroke preventive measures could potentially reduce the occurrence of stroke and avoid unnecessary procedures for patients with AF.

Emergency Medicine Physician Attitudes toward Anticoagulant Initiation for Patients with Atrial Fibrillation.

BACKGROUND AND AIM: Guidelines for the primary prevention of stroke recognize the emergency department as a location for physicians to identify atrial fibrillation and to initiate oral anticoagulants. Numerous studies have shown low anticoagulant prescription rates-approximately 18%-in OAC-naïve patients with atrial fibrillation discharged from the emergency department. We sought to obtain the opinions of Emergency Medicine physicians regarding anticoagulant decision-making for patients with atrial fibrillation seen in the emergency department. METHODS: 14-item paper surveys were distributed to emergency department physicians within a single hospital system. The survey consisted of single-, multi- answer and open-ended questions regarding knowledge and usage frequency of the CHA2DS2-VASc score, knowledge of anticoagulant options and reasons for why an anticoagulant was not initiated. RESULTS: 55 emergency department physicians completed the survey (overall response rate 59%). 89% (49/55) agreed the emergency department is an important location to initiate anticoagulation depending on comorbidities. A lower proportion reported ever starting a patient in the emergency department on a new anticoagulant prescription upon discharge (55% (30/55) p <.0001). The belief that a new anticoagulant prescription is the responsibility of the PCP/ Cardiologist/ Neurologist (52%; 15/29), not wanting to be held responsible in the event of a life-threatening bleeding event (41%; 12/29), and concerns about inadequate follow-up and/or lack of insurance (24%; 7/29) were the most commonly cited reasons for not starting an appropriate patient with atrial fibrillation on an anticoagulant. CONCLUSION: Emergency Medicine physicians support initiating oral anticoagulants in the ED for patients with atrial fibrillation; however, discrepancies exist between their intentions and actual practice.

Intravenous tPA for Acute Ischemic Stroke in Patients with COVID-19.

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19) is associated with increased risk of acute ischemic stroke (AIS), however, there is a paucity of data regarding outcomes after administration of intravenous tissue plasminogen activator (IV tPA) for stroke in patients with COVID-19. METHODS: We present a multicenter case series from 9 centers in the United States of patients with acute neurological deficits consistent with AIS and COVID-19 who were treated with IV tPA. RESULTS: We identified 13 patients (mean age 62 (±9.8) years, 9 (69.2%) male). All received IV tPA and 3 cases also underwent mechanical thrombectomy. All patients had systemic symptoms consistent with COVID-19 at the time of admission: fever (5 patients), cough (7 patients), and dyspnea (8 patients). The median admission NIH stroke scale (NIHSS) score was 14.5 (range 3-26) and most patients (61.5%) improved at follow up (median NIHSS score 7.5, range 0-25). No systemic or symptomatic intracranial hemorrhages were seen. Stroke mechanisms included cardioembolic (3 patients), large artery atherosclerosis (2 patients), small vessel disease (1 patient), embolic stroke of undetermined source (3 patients), and cryptogenic with incomplete investigation (1 patient). Three patients were determined to have transient ischemic attacks or aborted strokes. Two out of 12 (16.6%) patients had elevated fibrinogen levels on admission (mean 262.2 ± 87.5 mg/dl), and 7 out of 11 (63.6%) patients had an elevated D-dimer level (mean 4284.6 ±3368.9 ng/ml). CONCLUSIONS: IV tPA may be safe and efficacious in COVID-19, but larger studies are needed to validate these results.