Strokes Averted by Intravenous Thrombolysis: A Secondary Analysis of a Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.

Race-ethnicity, age, and heart failure in ischemic stroke.

OBJECTIVES: Race-ethnic disparities contribute to cardiovascular morbidity. Heart failure (HF) is highly prevalent in acute ischemic stroke (AIS) and associated with worse outcomes. We hypothesized race-ethnic differences exist in the prevalence of HF among patients with AIS, particularly in younger patients, and in a manner not fully explained by cardiovascular profiles. METHODS: Patients with AIS in the National Inpatient Sample (2016-2019) were categorized as young (<50 years), middle (50-64) and older (≥65) age. Interaction between age and race-ethnicity on the presence of comorbid HF was examined, adjusting for vascular risk factors. Effect modification on in-hospital mortality and prolonged hospitalization across race-ethnic groups and age was also examined. RESULTS: Of 398,470 AIS patients, 16.2 % had HF. HF patients were older (73.7 vs. 69.5 years, P < 0.001), had a lower proportion of White, Hispanic and Asian/PI individuals but a larger proportion of patients of Black race (21.0 vs. 16.4 %, P < 0.001). Race-ethnicity modified the relationship between HF and age (Pinteraction < 0.001). Stroke patients of Black race had the greatest odds of having HF across all age groups, however differences between Black and White patients were most pronounced in young adults (OR: 2.08, 95 % CI: 1.91-2.27) after adjusting for vascular risk factors. Among patients with HF, Black race was associated with reduced risk of in-hospital mortality but greater likelihood of prolonged hospitalization at middle and older age. CONCLUSION: HF is highly prevalent in stroke patients of Black race, particularly in younger cohorts, and in a manner not fully explained by cardiovascular profiles.

Physical Activity Is Inversely Associated With Severe Intracranial Stenosis in Stroke-Free Participants of NOMAS.

BACKGROUND: Although protective in secondary stroke prevention of intracranial arterial stenosis (ICAS), it is uncertain if the benefits of leisure time physical activity (LTPA) extend to asymptomatic ICAS or extracranial carotid stenosis (ECAS). Therefore, we sought to determine LTPA's relationship with ECAS and ICAS in a stroke-free, race-ethnically diverse cohort. METHODS: This cross-sectional study included participants from the magnetic resonance imaging substudy of the Northern Manhattan Study, of whom 1274 had LTPA assessments at enrollment. LTPA was represented continuously as metabolic equivalent score (MET-score) and ordinally as model-based cluster analysis (LTPA-cluster), both based on the same LTPA assessments. We evaluated ECAS sonographically using carotid intima-media thickening and number of carotid plaques. ICAS was assessed with time-of-flight magnetic resonance angiograph and defined as ≥50% or ≥70% stenosis. We applied regression analyses to evaluate the association between LTPA with ECAS and ICAS, adjusting for confounders. RESULTS: Of 1274 included participants (mean age 71±9 years; 60% women; 65% Hispanic), the mean MET-score was 10±16 and 60% were in a LTPA-cluster with any activity. Among those with carotid ultrasound (n=1234), the mean carotid intima-media thickening was 0.97±0.09 mm, and 56% of participants had at least one carotid plaque identified. Among those with magnetic resonance angiograph (n=1211), 8% had ≥50% ICAS and 5% had ≥70% ICAS. For ICAS, MET-score was associated with ≥70% ICAS (adjusted odds ratio per unit increase in MET-score [95% CI, 0.97 [0.94-0.99]) but not with ECAS measures (carotid intima-media thickening, adjusted ß-estimate per unit increase in MET-score [95% CI], 0.002 [-0.003 to 0.006] or number of plaques, adjusted ß-estimate [95% CI], 0.0001 [-0.0001 to 0.0003]). Substituting MET-score with LTPA-clusters replicated the association between ≥70% ICAS and LTPA (adjusted odds ratio per each increased LTPA-cluster [95% CI], 0.83 [0.70-0.99]). CONCLUSIONS: In this diverse stroke-free population, we found LTPA most strongly associated with asymptomatic ≥70% ICAS. Given the high-risk nature of ≥70% ICAS, these findings may emphasize the role of LTPA in people at risk for ICAS.

Effect of chronic antiplatelet therapy on clinical outcomes of endovascular thrombectomy for treatment of acute ischemic stroke.

OBJECTIVE: The objective of this study was to investigate the prognostic significance of chronic antiplatelet therapy (APT) usage in acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Long-term APT may enhance recanalization but may also predispose patients to an increased risk of hemorrhagic transformation. METHODS: Weighted hospitalizations for anterior-circulation AIS treated with EVT were identified in a large United States claims-based registry. Baseline clinical characteristics and outcomes were compared between patients with and without chronic APT usage prior to admission. Multivariable logistic regression analysis was performed to assess adjusted associations between APT and study endpoints. RESULTS: This analysis identified 36,560 patients, of whom 8170 (22.3%) were on a chronic APT regimen prior to admission. These patients were older and demonstrated a higher burden of comorbid disease, but had similar stroke severity on presentation in comparison with those not on APT. On unadjusted analysis, patients with prior APT demonstrated higher rates of favorable outcomes (24.3% vs 21.5%, p < 0.001), lower rates of mortality (7.0% vs 10.1%, p < 0.001), and lower rates of any intracranial hemorrhage (ICH; 20.3% vs 24.2%, p < 0.001), but no difference in rates of symptomatic ICH (sICH). Following multivariable adjustment for baseline clinical characteristics including age, acute stroke severity, and comorbidity burden, prior APT was associated with favorable outcome (adjusted odds ratio [aOR] 1.21, 95% CI 1.17-1.24, p < 0.001) and a lower likelihood of mortality (aOR 0.73, 95% CI 0.70-0.77, p < 0.001), without an increased likelihood of ICH (any ICH aOR 0.84, 95% CI 0.81-0.87, p < 0.001; sICH aOR 0.92, 95% CI 0.82-1.03, p = 0.131). CONCLUSIONS: Retrospective evaluation of patients with AIS treated with EVT using registry-based data demonstrated an association of prior APT usage with favorable outcomes, without an increased risk of hemorrhagic transformation.

Stroke and Mechanical Circulatory Support in Adults.

PURPOSE OF THE REVIEW: Short-term and durable mechanical circulatory support (MCS) devices represent life-saving interventions for patients with cardiogenic shock and end-stage heart failure. This review will cover the epidemiology, risk factors, and treatment of stroke in this patient population. RECENT FINDINGS: Short-term devices such as intra-aortic balloon pump, Impella, TandemHeart, and Venoatrial Extracorporal Membrane Oxygenation, as well as durable continuous-flow left ventricular assist devices (LVADs), improve cardiac output and blood flow to the vital organs. However, MCS use is associated with high rates of complications, including ischemic and hemorrhagic strokes which carry a high risk for death and disability. Improvements in MCS technology have reduced but not eliminated the risk of stroke. Mitigation strategies focus on careful management of anti-thrombotic therapies. While data on therapeutic options for stroke are limited, several case series reported favorable outcomes with thrombectomy for ischemic stroke patients with large vessel occlusions, as well as with reversal of anticoagulation for those with hemorrhagic stroke. Stroke in patients treated with MCS is associated with high morbidity and mortality. Preventive strategies are targeted based on the specific form of MCS. Improvements in the design of the newest generation device have reduced the risk of ischemic stroke, though hemorrhagic stroke remains a serious complication.

Stroke epidemiology and outcomes in the modern era of left ventricular assist devices.

The care for the patients with end-stage heart failure has been revolutionized by the introduction of durable left ventricular assist devices, providing a substantial improvement in patient survival and quality of life and an alternative to heart transplantation. The newest devices have lower instances of mechanical dysfunction and associated pump thrombosis. Despite these improvements in complications, the use of continuous flow assist devices is still associated with high rates of thrombotic and hemorrhagic complications, most notably stroke in approximately 10% of continuous flow assist devices patients per year. With the newest HeartMate 3 devices, there have been lower observed rates of stroke, which has in part been achieved by both improvements in pump technology and knowledge of the risk factors for stroke and neurological complications. The therapeutic options available to clinicians to reduce the risk of stroke, including management of hypertension and antithrombotics, will be reviewed in this manuscript.

Rural-Urban Differences in Diagnosed Cervical Artery Dissection in New York State.

BACKGROUND: Cervical artery dissection (CeAD) is a leading cause of stroke in young adults. Incidence estimates may be limited by under- or overdiagnosis. OBJECTIVE: We aimed to investigate if CeAD diagnosis would be higher in urban centers compared to rural regions of New York State (NYS). METHODS: For this ecological study, administrative codes were used to identify CeAD discharges in the NYS Statewide Planning and Research Cooperative System (SPARCS) from 2009 to 2014. Rural Urban Commuting Area (RUCA) codes were taken from the US Department of Agriculture and included the classifications metropolitan, micropolitan, small town, and rural. Negative binomial models were used to calculate effect estimates and 95% confidence limits (eß; 95% CL) for the association between RUCA classification and the number of dissections per ZIP code. Models were further adjusted by population. RESULTS: Population information was obtained from the US Census Bureau on 1,797 NYS ZIP codes (70.7% of NYS ZIP codes), 826 of which had at least 1 CeAD-related discharge from 2009 to 2014. Nonrural ZIP codes were more likely to report more CeAD cases relative to rural areas even after adjusting for population (metropolitan effect = eß 5.00; 95% CI: 3.75-6.66; micropolitan effect 3.02; 95% CI: 2.16-4.23; small town effect 2.34; 95% CI: 1.58-3.47). CONCLUSIONS: CeAD diagnosis correlates with population density as defined by rural-urban status. Our results could be due to underdiagnosis in rural areas or overdiagnosis with increasing urbanicity.

Dolichoectasia: a brain arterial disease with an elusive treatment.

INTRODUCTION: Dolichoectasia is a form of brain large artery disease associated with a high risk of mortality and morbidity. Progressive enlargement of arterial size is a predictor of mortality, but there are no specific treatments for arresting or slowing down dilatation. Additionally, dilated brain arteries can cause flow stagnation, which can trigger thrombosis and cause stroke. Pathology and genetic studies indicate a possible role for increased matrix metalloproteinase activation in arterial dilatation and thus in the pathophysiology of dolichoectasia. Therefore, therapeutic interventions aimed at slowing down arterial dilatation and preventing thrombosis could hypothetically play a role in treating patients with dolichoectasia. METHODS: We present four patients with dolichoectasia that exemplify therapeutic challenges worth discussing in the context of the current literature. Two patients were treated off-label with doxycycline (based on its antiMMP properties) and with apixaban, one patient was put on warfarin and later switched to aspirin, and the fourth patient underwent endovascular treatment. RESULTS: We report four cases, all men 50 years or older. Of the two patients treated with doxycycline, we noted a slowdown of the basilar artery (BA) growth, but the BA continued to grow in the other patient. Of the two patients who received apixaban, none had a subsequent stroke in 5 and 4 years of follow-up, respectively. One patient was admitted with a fatal BA thrombosis and rupture, and pathological examination of the brain arteries demonstrated advanced arterial wall degeneration but no atherosclerosis. DISCUSSION: These cases exemplify the challenges of treating people with dolichoectasia and highlight the need for better evidence regarding the best possible treatment for this population.

Stroke patterns and cannulation strategy during veno-arterial extracorporeal membrane support.

Stroke has potentially devastating consequences for patients receiving veno-arterial extracorporeal membrane support (VA-ECMO). Arterial cannulation sites for VA-ECMO include the ascending aorta, axillary artery, and femoral artery. However, the influence of cannulation site on stroke risk has not been well described. The purpose of this study was to investigate the association between occurrence and patterns of stroke with ECMO arterial cannulation sites. We retrospectively reviewed 414 consecutive patients who received VA-ECMO support for cardiogenic shock between March 2007 and May 2018. Patients were categorized by cannulation strategy. The rates, subtype and location of strokes as assessed by neuroimaging during and after VA-ECMO support were analyzed. Median age was 61 years (IQR 50-69); 67% were men. 77 patients were cannulated via the ascending aorta (17%), 31 via the axillary artery (7%), and 306 (69%) via the femoral artery. In total, 26 patients (6.3%) developed 30 stroke lesions at a median of 6.0 (IQR 3.1-8.7) days after ECMO cannulation. Ischemic stroke was the most common subtype (64%), followed by hemorrhagic transformation (20%) and hemorrhagic stroke (16%). Location by CT was right hemispheric in 38%, left hemispheric in 24%, bilateral in 21%, and vertebrobasilar in 17%. The incidence of stroke was similar across cannulation strategies: aorta (n = 5, 6.5%), axillary artery (n = 2, 6.5%), and femoral artery (n = 19, 6.2%), (p = 0.99). Incidence of stroke does not appear to differ among patients cannulated via the ascending aorta, axillary artery, or femoral artery. Ischemic stroke was the most common subtype of stroke.

STATISTICAL INFERENCE IN QUANTILE REGRESSION FOR ZERO-INFLATED OUTCOMES.

An extension of quantile regression is proposed to model zero-inflated outcomes, which have become increasingly common in biomedical studies. The method is flexible enough to depict complex and nonlinear associations between the covariates and the quantiles of the outcome. We establish the theoretical properties of the estimated quantiles, and develop inference tools to assess the quantile effects. Extensive simulation studies indicate that the novel method generally outperforms existing zero-inflated approaches and the direct quantile regression in terms of the estimation and inference of the heterogeneous effect of the covariates. The approach is applied to data from the Northern Manhattan Study to identify risk factors for carotid atherosclerosis, measured by the ultrasound carotid plaque burden.