Ischemic Stroke with Comorbid Cancer Has Specific miRNA-mRNA Networks in Blood That Vary by Ischemic Stroke Mechanism.

OBJECTIVE: Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer. METHODS: We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS. RESULTS: A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic. INTERPRETATION: We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581.

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.

Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

Stroke Risk After Emergency Department Treat-and-Release Visit for a Fall.

BACKGROUND: Previous cohort studies of hospitalized patients with a delayed diagnosis of ischemic stroke found that these patients often had an initial emergency department (ED) diagnosis of a fall. We sought to evaluate whether ED visits for a fall resulting in discharge to home (ie, treat-and-release visits) were associated with increased short-term ischemic stroke risk. METHODS: A case-crossover design was used to compare ED visits for falls during case periods (0-15, 16-30, 31-90, and 91-180 days before stroke) and control periods (equivalent time periods exactly 1 year before stroke) using administrative data from the Healthcare Cost and Utilization Project on all hospital admissions and ED visits across 10 states from 2016 to 2020. To identify ED treat-and-release visits for a fall and patients hospitalized for acute ischemic stroke, we used previously validated International Classification of Diseases, Tenth Revision, Clinical Modification codes. Odds ratios and 95% CIs were calculated using conditional logistic regression. RESULTS: Among 90 592 hospitalized patients with ischemic stroke, 5230 (5.8%) had an ED treat-and-release visit for a fall within 180 days before their stroke. Patients with an ED treat-and-release visit for a fall were older (mean age, 74.7 [SD, 14.6] versus 70.8 [SD, 15.1] years), more often female (61.9% versus 53.4%), and had higher rates of vascular comorbidities than other patients with stroke. ED treat-and-release visits for a fall were significantly more common in the 15 days before stroke compared with the 15-day control period 1 year earlier (odds ratio, 2.7 [95% CI, 2.4-3.1]). The association between stroke and a preceding ED treat-and-release visit for a fall decreased in magnitude with increasing temporal distance from stroke. CONCLUSIONS: ED treat-and-release visits for a fall are associated with significantly increased short-term ischemic stroke risk. These visits may be opportunities to improve stroke diagnostic accuracy and treatment in the ED.

Association of Assisted Reproductive Technology and Stroke During Hospitalization for Delivery in the United States.

INTRODUCTION: Infertility treatment with assisted reproductive technologies (ARTs) has been associated with adverse vascular events in some but not all previous studies. Endothelial damage, prothrombotic factor release, and a higher prevalence of cardiovascular risk factors in those receiving ART have been invoked to explain this association. We sought to explore the relationship between ART and stroke risk using population-level data. METHODS: We conducted a retrospective cohort study using data from the National Inpatient Sample registry from 2015 to 2020, including all delivery hospitalizations for patients aged 15 to 55 years. The study exposure was use of ART. The primary end point was any stroke defined as ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral venous thrombosis during index delivery hospitalization. Individual stroke subtypes (ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral venous thrombosis) were evaluated as secondary end points. Standard International Classification of Diseases, Tenth Revision, Clinical Modification algorithms were used to define study exposure, comorbidities, and prespecified end points. In addition to reporting population-level estimates, propensity score adjustment by inverse probability weighting was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between ART and non-ART users. RESULTS: Among 19 123 125 delivery hospitalizations identified, patients with prior ART (n=202 815, 1.1%) experienced significantly higher rates of any stroke (27.1/100 000 versus 9.1/100 000), ischemic stroke (9.9/100 000 versus 3.3/100 000), subarachnoid hemorrhage (7.4/100 000 versus 1.6/100 000), intracerebral hemorrhage (7.4/100 000 versus 2.0/100 000), and cerebral venous thrombosis (7.4/100 000 versus 2.7/100 000) in comparison to non-ART users (all P<0.001 for all unadjusted comparisons). Following inverse probability weighting analysis, ART was associated with increased odds of any stroke (adjusted odds ratios, 2.14 (95% CI, 2.02-2.26); P<0.001). CONCLUSIONS: Using population-level data among patients hospitalized for delivery in the United States, we found an association between ART and stroke after adjustment for measured confounders.

Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).

Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for Treatment.

Ischemic stroke is an important cause of morbidity and mortality in cancer patients. The underlying mechanisms linking cancer and stroke are not completely understood. Long-standing and more recent evidence suggests that cancer-associated prothrombotic states, along with treatment-related vascular toxicity, such as with chemotherapy and immunotherapy, contribute to an increased risk of ischemic stroke in cancer patients. Novel biomarkers, including coagulation, platelet and endothelial markers, cell-free DNA, and extracellular vesicles are being investigated for their potential to improve risk stratification and patient selection for clinical trials and to help guide personalized antithrombotic strategies. Treatment of cancer-related stroke poses unique challenges, including the need to balance the risk of recurrent stroke and other thromboembolic events with that of bleeding associated with antithrombotic therapy. In addition, how and when to restart cancer treatment after stroke remains unclear. In this review, we summarize current knowledge on the mechanisms underlying ischemic stroke in cancer, propose an etiological classification system unique to cancer-related stroke to help guide patient characterization, provide an overview of promising biomarkers and their clinical utility, and discuss the current state of evidence-based management strategies for cancer-related stroke. Ultimately, a personalized approach to stroke prevention and treatment is required in cancer patients, considering both the underlying cancer biology and the individual patient's risk profile.

Acute ischaemic stroke in active cancer versus non-cancer patients: stroke characteristics, mechanisms and clinical outcomes.

BACKGROUND AND PURPOSE: Demographics, clinical characteristics, stroke mechanisms and long-term outcomes were compared between acute ischaemic stroke (AIS) patients with active cancer (AC) versus non-cancer patients. METHODS: Using data from 2003 to 2021 in the Acute STroke Registry and Analysis of Lausanne, a retrospective cohort study was performed comparing patients with AC, including previously known and newly diagnosed cancers, with non-cancer patients. Patients with inactive cancer were excluded. Outcomes were the modified Rankin Scale (mRS) score at 3 months, death and cerebrovascular recurrences at 12 months before and after propensity score matching. RESULTS: Amongst 6686 patients with AIS, 1065 (15.9%) had a history of cancer. After excluding 700 (10.4%) patients with inactive cancer, there were 365 (5.5%) patients with AC and 5621 (84%) non-cancer AIS patients. Amongst AC patients, 154 (42.2%) strokes were classified as cancer related. In multivariable analysis, patients with AC were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.03), had fewer vascular risk factors and were 48% less likely to receive reperfusion therapies (aOR 0.52, 95% CI 0.35-0.76). Three-month mRS scores were not different in AC patients (aOR 2.18, 95% CI 0.96-5.00). At 12 months, death (adjusted hazard ratio 1.91, 95% CI 1.50-2.43) and risk of cerebrovascular recurrence (sub-distribution hazard ratio 1.68, 95% CI 1.22-2.31) before and after propensity score matching were higher in AC patients. CONCLUSIONS: In a large institutional registry spanning nearly two decades, AIS patients with AC had less past cerebrovascular disease but a higher 1-year risk of subsequent death and cerebrovascular recurrence compared to non-cancer patients. Antithrombotic medications at discharge may reduce this risk in AC patients.

Ischemic events are infrequent in patients with ovarian hyperstimulation syndrome.

BACKGROUND: Case reports describe arterial thrombosis including ischemic stroke associated with severe ovarian hyperstimulation syndrome (OHSS), but the prevalence of major ischemic events during or shortly after OHSS is unknown. METHODS: Using publicly available administrative datasets in the United States between 2015 and 2020, we conducted two separate cross-sectional studies of patients with OHSS. We included all patients with OHSS. Our study outcome was any hospitalization for acute ischemic stroke, acute myocardial infarction, cerebral venous sinus thrombosis, pulmonary embolism, or acute deep venous thrombosis during the index hospitalization or within 90 days of OHSS diagnosis. RESULTS AND CONCLUSIONS: We found very few major ischemic events in patients with OHSS.

Cancer and left atrial enlargement in patients with ischemic stroke.

BACKGROUND: Cancer is associated with an increased risk of atrial fibrillation. Whether cancer is also associated with atrial cardiopathy, another atrial pathology associated with heightened ischemic stroke risk, is uncertain. METHODS: We conducted a retrospective cross-sectional study among consecutive patients hospitalized with acute ischemic stroke at a quaternary care center in New York, United States from 2011 through 2016. The study exposure was active cancer. The study outcome was atrial cardiopathy, defined as a left atrial volume index ≥35 mL/m2 on echocardiography. We used multivariable logistic regression, adjusting for baseline characteristics, to evaluate the relationship between cancer (active or historical) and atrial cardiopathy. We performed a subgroup analysis among patients with embolic stroke of undetermined source (ESUS). RESULTS: The final cohort included 1104 patients with acute ischemic stroke, of whom 10 % had active cancer and 47 % had atrial cardiopathy. Patients with atrial cardiopathy, compared to those without, were older (median age, 77 versus 68 years), and more frequently had hypertension, coronary disease, and atrial fibrillation. Active cancer was present in 9.6 % of patients with atrial cardiopathy (n = 50/520) and 10.4 % of patients without (n = 61/584). There was no association between active cancer and atrial cardiopathy among the overall ischemic stroke cohort (adjusted odds ratio [OR], 0.91; 95 % confidence interval [CI], 0.60-1.37) nor in patients with ESUS (aOR, 0.64; 95 % CI, 0.30-1.36). When the cancer exposure was broadened to include any history of cancer (n = 236, 21.4 %), there still was no significant association with atrial cardiopathy (aOR, 0.93; 95 % CI, 0.68-1.25). CONCLUSIONS: When defining atrial cardiopathy by left atrial volume, we did not find an association between cancer and atrial cardiopathy in patients with ischemic stroke, including among those with ESUS. Future studies, evaluating other atrial cardiopathy biomarkers and settings, are needed to further investigate any potential link between cancer and atrial cardiopathy.

Factors impacting D-dimer levels in patients with acute ischemic cerebrovascular events.

BACKGROUND AND OBJECTIVES: A better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). METHODS: Data on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed. RESULTS: In total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381-1468] versus 442 µg/L [interquartile range 244-800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [ß] 0.728; 95% confidence interval [CI] 0.324-1.121). This was followed by an immediate decrease (ß -13.022; 95% CI -20.401 to -5.643) and then by a second, late increase after 35 h (ß 11.750; 95% CI 4.71-18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients. CONCLUSION: The time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker.

Mortality in acute ischemic stroke patients with new cancer diagnosed during the index hospitalization versus after discharge.

BACKGROUND: Early diagnosis of previously unknown cancer (i.e., occult cancer) after an acute ischemic stroke (AIS) could result in faster initiation of cancer therapy and potentially improve clinical outcomes. Our study aimed to compare mortality rates between AIS patients with occult cancer diagnosed during the index stroke hospitalization versus those diagnosed after hospital discharge. METHODS: Among consecutive AIS patients treated at our stroke center from 2015 through 2020, we identified new cancer diagnoses made within the year after the AIS. We used multivariable Cox regression analyses to evaluate the association between the timing of occult cancer diagnosis (during the AIS hospitalization versus after discharge) and long-term survival. RESULTS: Of 3894 AIS patients with available long-term follow-up data, 59 (1.5 %) were diagnosed with a new cancer within one year after index stroke. Of these, 27 (46 %) were diagnosed during the index hospitalization and 32 (54 %) were diagnosed after discharge. During a median follow-up of 406 days (interquartile range, 89-1073), 70 % (n = 19) of patients whose cancer was diagnosed during hospitalization had died, compared to 63 % (n = 20) of patients whose cancer was diagnosed after discharge (p= 0.58). In our main multivariable model, there was no difference in long-term mortality between patient groups (adjusted hazard ratio, 1.16; 95 % confidence interval, 0.53-2.52; p= 0.71). CONCLUSIONS: In this analysis, timing of a new cancer diagnosis after AIS did not seem to influence patients' long-term survival. Given the fairly small number of included patients with previously occult cancer, larger multicenter studies are needed to confirm our results.

Cost-Effectiveness of Smoking Cessation Interventions in Patients With Ischemic Stroke and Transient Ischemic Attack.

BACKGROUND: Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population. METHODS: We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty. RESULTS: From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168/QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs. CONCLUSIONS: For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

Golden Hour Treatment With tPA (Tissue-Type Plasminogen Activator) in the BEST-MSU Study.

BACKGROUND: Treatment of patients with acute ischemic stroke on mobile stroke units (MSUs) improves outcomes compared with management by standard emergency medical services ambulances and is associated with more patients treated with intravenous tPA (tissue-type plasminogen activator) in the first golden hour after last known normal. We explored the predictors and outcomes of first-hour treatment (FHT) compared with later treatment in an alternating-week cluster-controlled trial of MSUs. METHODS: We analyzed all patients treated with intravenous tPA in the BEST-MSU Study (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). After stratifying by treatment timeframe, we identified factors associated with FHT. We performed adjusted analyses of the association between FHT and clinical outcome and modeled the shape of the relationship between last known normal-to-treatment time and excellent outcome. RESULTS: Among 941 tPA-treated patients, 206 (21.8%) had lytic started within 60 minutes. Treatment on the MSU, older age, male sex, alert by 911, faster arrival on-scene and imaging, more severe stroke, atrial fibrillation, and absence of heart failure and pretreatment antihypertensive treatment were associated with FHT. Compared with later treatment, FHT was associated with higher adjusted odds ratio for 90-day modified Rankin Scale score of 0 to 1 (odds ratio, 1.87 [95% CI, 1.25-2.84]; P=0.003). Among FHT patients, 68% achieved a 90-day modified Rankin Scale of 0 or 1 or returned to their baseline status. FHT was not associated with higher risk of hemorrhage and was associated with reduced risk of treating neurovascular mimics. CONCLUSIONS: FHT almost doubles the odds of excellent clinical outcome without increased risk compared with later treatment, which supports the use of MSUs.

Prevalence of neurological complaints among emergency department patients with severe hypertension.

OBJECTIVE: Severe hypertension can accompany neurological symptoms without obvious signs of target organ damage. However, acute cerebrovascular events can also be a cause and consequence of severe hypertension. We therefore use US population-level data to determine prevalence and clinical characteristics of patients with severe hypertension and neurological complaints. METHODS: We used nationally representative data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) collected in 2016-2019 to identify adult ED patients with severely elevated blood pressure (BP) defined as systolic BP ≥ 180 mmHg and/or diastolic BP ≥120 mmHg. We used ED reason for visit data fields to define neurological complaints and used diagnosis data fields to define acute target organ damage. We applied survey visit weights to obtain national estimates. RESULTS: Based on 5083 observations, an estimated 40.4 million patients (95% CI: 37.5-43.0 million) in EDs nationwide from 2016 to 2019 had severe hypertension, equating to 6.1% (95% CI: 5.7-6.5%) of all ED visits. Only 2.8% (95% CI: 2.0-3.9%) of ED patients with severe hypertension were diagnosed with acute cerebrovascular disease; hypertensive urgency was diagnosed in 92.0% (95% CI: 90.3-93.4%). Neurological complaints were frequent in both patients with (75.6%) and without (19.9%) cerebrovascular diagnoses. Hypertensive urgency patients with neurological complaints were more often older, female, had prior stroke/TIA, and had neuroimaging than patients without these complaints. Non-migraine headache and vertigo were the most common neurological complaints recorded. CONCLUSION: In a nationally representative survey, one-in-sixteen ED patients had severely elevated BP and one-fifth of those patients had neurological complaints.

Quality-of-life, concerns, and treatment priorities in patients with cancer-related ischemic stroke: A prospective survey study.

OBJECTIVES: Comorbid cancer with stroke is a complex situation with multiple factors affecting quality of life (QoL). No specific questionnaire exists to assess current drivers of QoL and future concerns and priorities in patients with cancer-related stroke. METHODS: After developing a structured survey instrument, we prospectively interviewed patients with recent ischemic stroke and active cancer to assess views about their condition, factors currently impacting QoL, concerns for the future, and preferences regarding antithrombotic treatment strategy. RESULTS: In 2021-2022, at two quaternary-care stroke and cancer centers, we surveyed 50 patients with cancer-related stroke (mean age 70 years, 42% women). Most (87%) had solid cancers with lung, prostate, and breast cancers being the most prevalent. The most frequent adverse feelings were sadness and anxiety about another stroke. Disability from stroke, pain from cancer, and dependency were the items rated to have the highest current effect on patients' QoL and were ranked as the number one effector on QoL in 25%, 23%, and 16% of surveys, respectively; bleeding was ranked the lowest. Cognitive/memory impairment (ranked first in 28% of surveys), dependency on others (ranked first in 18%), and speech disturbance (ranked first in 16%) were the highest ranked future concerns; bleeding and pain were ranked the lowest. When questioned about antithrombotic treatment preferences to prevent further stroke, 50% favored a more aggressive approach with anticoagulant therapy, 16% favored a less aggressive approach with antiplatelet therapy, and 34% were neutral/unsure. CONCLUSIONS: Patients with cancer-related stroke reported that stroke disability and cancer pain were their most impactful current issues, while long-term cognitive impairment, functional dependence, and speech disturbance were their most important future concerns. These patients seemed to be more concerned about future stroke than bleeding events and tended to prefer a more aggressive antithrombotic strategy, although considerable variability existed.

Smoking Cessation in Stroke Survivors in the United States: A Nationwide Analysis.

BACKGROUND: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized. METHODS: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities. RESULTS: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59-76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%-61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67-0.79]) after accounting for differences in demographics and smoking-related comorbidities. CONCLUSIONS: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

Mobile Stroke Units: Evidence, Gaps, and Next Steps.

Mobile stroke units (MSUs) are specialized ambulances equipped with the personnel, equipment, and imaging capability to diagnose and treat acute stroke in the prehospital setting. Over the past decade, MSUs have proliferated throughout the world, particularly in European and US cities, culminating in the formation of an international consortium. Randomized trials have demonstrated that MSUs increase stroke thrombolysis rates and reduce onset-to-treatment times but until recently it was uncertain if these advantages would translate into better patient outcomes. In 2021, 2 pivotal, large, controlled clinical trials, B_PROUD and BEST-MSU, demonstrated that as compared with conventional emergency care, treatment aboard MSUs was safe and led to improved functional outcomes in patients with stroke. Further, the observed benefit of MSUs appeared to be primarily driven by the higher frequency of ultra-early thrombolysis within the golden hour. Nevertheless, questions remain regarding the cost-effectiveness of MSUs, their utility in nonurban settings, and optimal infrastructure. In addition, in much of the world, MSUs are currently not reimbursed by insurers nor accepted as standard care by regulatory bodies. As MSUs are now established as one of the few proven acute stroke interventions with an effect size that is comparable to that of intravenous thrombolysis and stroke units, stroke leaders and organizations should work with emergency medical services, governments, and community stakeholders to determine how MSUs might benefit individual communities, and their optimal organization and financing. Future research to explore the effect of MSUs on intracranial hemorrhage and thrombectomy outcomes, cost-effectiveness, and novel models including the use of rendezvous transports, helicopters, and advanced neuroimaging is ongoing. Recommended next steps for MSUs include reimbursement by insurers, integration with ambulance networks, recognition by program accreditors, and inclusion in registries that monitor care quality.

Early Deterioration, Hematoma Expansion, and Outcomes in Deep Versus Lobar Intracerebral Hemorrhage: The FAST Trial.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. METHODS: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). RESULTS: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P=0.001) and early neurological deterioration (31 versus 17%, P=0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P<0.001) and 24 hours (14 versus 38mL, P<0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P=0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P=0.01). CONCLUSIONS: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Risk of Stroke After Posterior Reversible Encephalopathy Syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke. METHODS: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes. We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded. RESULTS: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0-7.4) after PRES, 1.0 (95% CI, 0.62-1.8) after renal colic, and 9.7 (95% CI, 9.4-10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7-3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54-0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4-2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4-2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38-0.63]). Results were similar with 2-week washout. CONCLUSIONS: Patients with PRES had an elevated risk of incident stroke.