Acute Ischemic Stroke Events Research Articles

Glucagonlike peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors in ischemic strokes with diabetes 2.

Cardiovascular outcome trials demonstrate that glucagonlike peptide-1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes (T2D), whereas dipeptidyl peptidase-4 inhibitors (DPP-4is) have not shown cardiovascular benefits. We compared acute ischemic stroke (AIS) with T2D treated with either a GLP-1RA or DPP-4i prior to the index stroke. This national cohort study included AIS patients with T2D from 2017 to 2020 in Denmark who were users of a GLP-1RA or DPP-4i. To be categorized as a user, we required at least 12 months of exposure and no concurrent treatment with another newer glucose-lowering medication during the last 3 months prior to the index stroke. GLP-1RA users were compared to users of DPP-4i while adjusting for the calendar year of index stroke, age, sex, comorbidity, and socioeconomic factors. The study included 1567 AIS events with T2D; 593 were users of GLP-1RA and 974 of DPP-4i. The absolute risk of a very severe stroke was 2.4% (95% confidence interval [CI] = 1.2-3.7) in GLP-1RA users and 6.1% (95% CI = 4.6-7.7) in DPP-4i users. The corresponding adjusted risk ratio (aRR) of GLP-1RA versus DPP-4i was 0.49 (95% CI = 0.24-1.00). The aRRs of 30-day and 365-day mortality were 0.55 (95% CI = 0.32-0.94) and 0.72 (95% CI = 0.53-0.98), respectively. The risk of a very severe stroke as well as the 30-day and 365-day poststroke mortality rates were lower among the AIS patients with comorbid T2D receiving GLP-1RA prior to the index stroke compared to those receiving DPP-4i. Hence, GLP-1RA may improve stroke outcomes in comparison with DPP-4i.

Current and Future Cost Burden of Ischemic Stroke in Australia: Dynamic Model

Background: Stroke remains one of the leading causes of morbidity and mortality in Australia. The objective of this study was to estimate the current and future cost burden of ischemic stroke (IS) in Australia. Method: First, the annual chronic management cost per person following IS were derived for all people aged ≥30 years discharged from a public or private hospital in Victoria, Australia between July 2012 and June 2017 (with follow-up data until June 2018 [n = 34,471]). Then extrapolated the data from from Victoria to the whole Australian population aged between 30 years and 99 years to project the total healthcare costs following IS (combination of acute event and chronic management cost) over a 20-year period (2019–2038) using a dynamic multistate life table model. Data for the dynamic model were sourced from the Victorian Admitted Episodes Dataset (VAED) and supplemented with other published data. Result: The estimated annual total chronic management cost following IS was 13,525 Australian dollars (AUD) per person (95% CI: AUD 13,380, AUD 13,670) for cohorts in the VAED between July 2012 and June 2017. The annual chronic management cost was estimated to decline following IS. The highest cost was incurred in the first year of follow-up post-IS (AUD 14,309 per person) and declined to AUD 9,776 in the sixth year of follow-up post-IS. The total healthcare cost for people aged 30–99 years was projected to be AUD 47.7 billion (95% UI: AUD 44.6 billion, AUD 51.0 billion) over the 20-year period (2019–2038) Australia-wide, of which 91.3% (AUD 43.6 billion) was attributed to chronic management costs and the remaining 8.7% (AUD 4.2 billion) were due to acute IS events. Conclusion: IS has and will continue to have a considerable financial impact in the next 2 decades on the Australian healthcare system. Our estimated and projected cost burden following IS provides important information for decision making in relation to IS.

Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity.

Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events. We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO2) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate. Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P<0.001) for recurrent ischemic stroke. Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.

Abstract WP151: Prevailing Income-Based Disparities in Acute Ischemic Stroke and Cardiovascular Events in Young Hospitalized Adults With Cannabis Use Disorder: Insights From a Population-Based Analysis

Introduction: Cannabis use and low socioeconomic status are recognized as distinct risk factors for stroke and cardiovascular pathologies. This observational study aims to investigate the association between income status in acute ischemic stroke (AIS) and cardiovascular events among young, hospitalized adults with dependent cannabis use or cannabis use disorder (CUD). Methods: We analyzed young adult hospitalizations (18-44 years) with known CUD from the 2020 National Inpatient Sample. Propensity score-matched analysis (1:1) was used to compare comorbidities, including AIS and cardiovascular events, between the high-income quartile (HIQ) and low-income quartile (LIQ) within the CUD cohort. Results: Out of the young adult admissions, a total of 286,855 individuals were identified as dependent cannabis users. After propensity matching, we divided the CUD cohort into 63,355 patients with HIQ (41.1% female) and LIQ (41.4% female). While both cohorts exhibited comparable ages and racial distribution (&gt;65% white), the individuals from LIQ cohort were predominantly from South (45.7% vs. 27.9%), visiting rural hospitals (13.9% vs. 1.3%), with Medicaid (56.3% vs. 41.1%) as the predominant payer. Additionally, LIQ cohort had a higher prevalence of drug abuse (65.5% vs. 58.4%), tobacco use (24.9% vs. 22.6%), HTN (17% vs. 14.7%), chronic pulmonary disease (13.2% vs. 12.7%), DM (8% vs. 6.6%), and obesity (10.9% vs. 10.0%). Additionally, in-hospital outcomes like AIS (0.5% vs. 0.3%) and MACCE (2% vs. 0.8%) were higher in the LIQ cohort. After adjusting for confounding factors, the risk of AIS in the HIQ cohort was 37% lower than in the LIQ cohort (OR: 0.63 [95% CI: 0.42-0.96]). (all-p&lt;0.05). Conclusion: Higher prevalence of CVD risk factors in the LIQ-CUD group and lower odds of AIS-related admissions in the HIQ-CUD group warrant targeted interventions and policy measures to understand and address behavioral risk of cannabis use by economic status and disparities in MACCE.

Abstract TMP104: Timing of Recurrence After Ischemic Stroke by Subtype: A Population-Based Study

Introduction: Prior work suggests stroke recurrence timing may vary by subtype, with large vessel disease being associated with earlier recurrence; however, these studies were conducted prior to the current era of secondary stroke prevention strategies. We examined whether the timing of recurrence after ischemic stroke varied by subtype in a large population-based study. Methods: In 2015, we identified all acute ischemic stroke events from hospitals in the Greater Cincinnati and Northern Kentucky area. Events in the last 6 months of 2014 were oversampled for black patients. Trained nurses extracted clinical data, and stroke specialists subtyped and adjudicated cases. We tracked events for 3 years, considering only ischemic strokes after day 14 as a recurrence. To assess recurrence timing variations, we stratified strokes by subtype and analyzed their restricted mean survival times (RMST) at 1, 3, 12, 24, and 36 months. RMST is the area under the survival curve up to a specific follow up point, denoting the average event-free time during that interval. Results: Of 2577 patients with index stroke, 332 recurrent strokes were seen over the ensuing 3 years. Half of the recurrences occurred within 8 months from the index event. At 12 months, large vessel (LV), undetermined, and other identified cause showed a statistically significant smaller RMST compared to small vessel (SV). This difference was nonsignificant at later time points, suggesting later recurrence for SV. There were no statistically significant differences in RMST between cardioembolic, LV, undetermined, and other identified at any time point. Conclusions: Recurrence after initial SV stroke was less likely to occur in the first year when compared to LV, undetermined etiology, or other identified causes of stroke. There was no evidence of difference in recurrence timing between cardioembolic, LV, other identified, and undetermined etiology.

Abstract 11711: Factors Predicting Acute Ischemic Stroke Following Surgical Repair of Acute Type A Aortic Dissection (ATAAD) in Adults

Introduction: Acute type A Aortic dissection (ATAAD) may require urgent surgical repair, and a major complication is acute ischemic stroke (AIS) post-surgery. Aim: To explore characteristics associated with AIS in ATAAD patients post-surgical repair (PSR). Hypothesis: We assessed the hypothesis that multiple factors influence events of AIS in ATAAD patients PSR. Method: Multivariate regression analysis for factors influencing AIS in adults with a principal diagnosis of ATAAD and undergoing surgical repair was performed via the 2016-2020 National Inpatient Sample. Results: Among the 20335 ATAAD cases with surgical repair, 14.7%(2985 cases) reported an event of AIS. Individuals ≥60 years (vs. ages 18-39 years, aOR 1.323, p=0.007) and presence of hypertension (aOR 1.228, P&lt;.001), acute kidney injury (AKI) (aOR 1.353, P&lt;.001), Charlson Comorbidity Index (CCI) ≥3 (aOR 15.129, p&lt;.001), and Private insurances (vs. Medicare, aOR 1.454, p&lt;.001) or Medicaid (vs. Medicare, aOR 1.673, p&lt;.001) showed higher odds of developing AIS. On the contrary, smoking (aOR 0.613, p&lt;.001), obesity (aOR 0.882, p=0.027), cirrhosis (aOR 0.309, p&lt;.001), dyslipidemia (aOR 0.732, p&lt;.001), diabetes (DM) (aOR 0.508, p&lt;.001), peripheral vascular disease (PVD) (aOR 0.615, p&lt;.001), Chronic Kidney Disease (CKD) (aOR 0.446, p&lt;.001), prior MI (aOR 0.461, p&lt;.001) and prior stroke (aOR 0.788, p=0.04) and Black race (aOR 0.736, p&lt;.001) indicated lower odds. No significant difference was seen in age 40-59 (aOR 1.06, p=0.545), drug abuse (aOR 1.093, p=0.451), alcohol abuse (aOR 0.925, p=0.476), Females (vs. Males, aOR 0.973, p=0.579), and Hispanics (vs. Whites, aOR 1.102, p=0.285). Conclusion: In conclusion, a 14.7% rate of AIS in ATAAD PSR was observed. Ages ≥60, hypertension, AKI, CCI ≥3, and Private and Medicaid insurance holders appeared prone to AIS following such events, while smoking, obesity, cirrhosis, dyslipidemia, DM, PVD, CKD, prior MI, prior stroke, and Blacks had reduced odds.

Prevalence, Risk Factors, and Clinical Outcomes of New Cerebral Microbleeds After Intravenous Thrombolysis in Acute Ischemic Stroke: aSystematic Review and Meta-analysis.

Cerebral microbleeds (CMBs) are common in the elderly population, and are associated with an increased risk of stroke and dementia. An acute ischemic stroke event can make CMBs develop rapidly. However, the progression of CMBs after intravenous thrombolysis is not well understood. Following apreviously registered protocol, PubMed, Web of Science, and Embase databases were systematically searched to identify relevant literature up to August 2022. Cohort studies that reported new CMBs in patients with acute ischemic stroke undergoing intravenous thrombolysis were included. Random effects models were used to calculate the pooled estimates. Seven studies with 1079 patients were included in the meta-analysis. The pooled new CMBs prevalence was 7.6% (95% CI 3.9-14.3%) and 63.6% new CMBs were located in the cerebral lobes. Compared with patients without new CMBs, those with new CMBs were older, had ahigher proportion of hypertension, and had higher systolic blood pressure and baseline CMBs burden. The presence of new CMBs increased the likelihood of remote intracerebral hemorrhage (OR 28.75, 95% CI 8.58-96.38) and symptomatic intracerebral hemorrhage (OR 15.49, 95% CI 3.21-74.73) but was not related to functional outcomes or hemorrhagic transformation. The prevalence of new CMBs after intravenous thrombolysis was approximately 7.6%. The presence of new CMBs is associated with remote and symptomatic intracerebral hemorrhage following intravenous thrombolysis. Considering the potential long-term adverse effects of CMBs progression, patients at ahigh risk of developing new CMBs should be identified based on potential risk factors.

236 Assessing communication of duration of Dual Antiplatelet Therapy on discharge letters: an acute stroke unit audit

Abstract Background Short term Dual Anti-Platelet Therapy (DAPT) is commonly used for secondary prevention of major acute ischemic stroke events. However, long-term DAPT is associated with increased risk of bleeding without reduction in cardiovascular events. Proton pump inhibitors (PPI) are often co-prescribed for prevention of gastroduodenal toxicity of DAPT, but long-term use has potential side effects. This audit aims to assess if clear instructions are provided regarding to duration of DAPT prescription in stroke medicine unit in tertiary referral hospital. Methods Retrospective analysis Electronic Medical Records (EMRs; discharge and clinical letters) who were admitted with TIA or AIS in 3-month period, excluding those who were transferred back to their referring hospital. Results 100 patients’ EMRs were reviewed. 34 were discharged on DAPT. 21 patients were reviewed in stroke OPD while 6 were readmitted to hospital. DAPT duration was documented in Discharge Letters (DL) of 28 patients (82%). In 28 (82%) patients, recommended durations of DAPT were documented in DL, 5(18%) of those were still inappropriately on DAPT on returning to OPD/readmission. 1 out of the 6 patients with no clear documentation of DAPT duration on DL were still inappropriately on DAPT. 22 patients were co-prescribed PPI, 19 of those had no documented recommended plan for PPI post completion of DAPT, and 12 of those were still on PPI on returning to OPD/readmission. 3 patients had a documented plan for PPI post completion of DAPT, 2 were still on PPI on returning to OPD/readmission. Conclusion Results were presented in stroke unit teaching. Key recommendations included education of NCHDs regarding clear documentation and communication with patients, pharmacists and GPs. Improvement in EMRs to highlight DAPT plan. Regular audits in this area.

Identifying optimal cut points of National Institutes of Health Stroke Scale to Predict Mortality: A Population-based Assessment (P11-5.016)

Identifying optimal cut points of National Institutes of Health Stroke Scale to Predict Mortality: A Population-based Assessment (P11-5.016)

Editors' Note: Acute Arterial Ischemic Stroke Following COVID-19 Vaccination: A Systematic Review and Meta-analysis.

Dr. Stefanou et al. analyzed the risk of acute ischemic stroke (AIS) after COVID-19 vaccination and its potential association with thrombotic-thrombocytopenia syndrome (TTS) in a systematic review and meta-analysis of 2 randomized-controlled trials (RCTs), 3 cohort studies, and 11 registry-based studies. They found 17,481 AIS cases among 782,989,363 COVID-19 vaccinations, giving a pooled proportion of postvaccination AIS of 4.7 cases per 100,000 vaccinations, with no difference observed between mRNA-based and adenovirus-based vaccinations. The pooled proportion of TTS in AIS cases was 3.1%. In response, Dr. Du notes that the rate of AIS cases was lower than the age-standardized global AIS prevalence and incidence rates per 100,000 individuals per year, suggesting that the vaccinations may be associated with a lower risk of AIS. In this regard, Dr. Du cites a previous study that found a significant association between COVID-19 vaccination and lower risks of myocardial infarction and ischemic stroke. Responding to these comments, the authors caution that their crude estimate of new AIS events per 100,000 vaccination, without age standardization or annualization, was not directly comparable with age-standardized AIS estimates per 100,000 individuals per year in the general population. These exchange raises demonstrate relevant complexities when seeking to compare the risk of postvaccination AIS with the “background” risk in the general population while motivating additional studies to investigate whether COVID-19 vaccination might reduce AIS risk at a population level. Dr. Stefanou et al. analyzed the risk of acute ischemic stroke (AIS) after COVID-19 vaccination and its potential association with thrombotic-thrombocytopenia syndrome (TTS) in a systematic review and meta-analysis of 2 randomized-controlled trials (RCTs), 3 cohort studies, and 11 registry-based studies. They found 17,481 AIS cases among 782,989,363 COVID-19 vaccinations, giving a pooled proportion of postvaccination AIS of 4.7 cases per 100,000 vaccinations, with no difference observed between mRNA-based and adenovirus-based vaccinations. The pooled proportion of TTS in AIS cases was 3.1%. In response, Dr. Du notes that the rate of AIS cases was lower than the age-standardized global AIS prevalence and incidence rates per 100,000 individuals per year, suggesting that the vaccinations may be associated with a lower risk of AIS. In this regard, Dr. Du cites a previous study that found a significant association between COVID-19 vaccination and lower risks of myocardial infarction and ischemic stroke. Responding to these comments, the authors caution that their crude estimate of new AIS events per 100,000 vaccination, without age standardization or annualization, was not directly comparable with age-standardized AIS estimates per 100,000 individuals per year in the general population. These exchange raises demonstrate relevant complexities when seeking to compare the risk of postvaccination AIS with the “background” risk in the general population while motivating additional studies to investigate whether COVID-19 vaccination might reduce AIS risk at a population level.

Abstract WP184: Identifying Optimal Cut Points Of National Institutes Of Health Stroke Scale To Predict Mortality: A Population-based Assessment

Background: Ischemic stroke is the 5 th leading cause of death in the US. As a measure of stroke severity, initial NIHSS has been used to predict clinical outcome. We sought to identify the optimal cut-points of NIHSS at initial presentation that are associated with higher 30-day mortality. Methods: In 2005, 2010, and 2015 all hospitalized, first acute ischemic stroke events occurring within the Greater Cincinnati area were ascertained. Potential ischemic stroke cases underwent chart abstraction and physician adjudication, including retrospective NIHSS score (range 0 - 42) based on clinical findings at initial presentation. Descriptive statistics for NIHSS were estimated by study year, demographics, and medical history. Data regarding mortality was obtained from the National Death Index. The Contal and O’Quigley method based on a modified log-rank test statistic was used to determine cut-points of the NIHSS score associated with 30-day mortality, and hazard ratios were obtained from Cox models with adjustment for sex, race, and age. Results: In 2005, 2010, and 2015 there were 1704, 1818 and 1852 ischemic stroke events with 30-day mortality rates of 10.5%, 9.6% and 9.0%, respectively. Optimal cut-points of NIHSS &lt;9, 9-16 and &gt;16 were identified. Across all 3 periods, 3431 (84.5%) cases had NIHSS 0-8, 352 (8.7%) had NIHSS 9-16 and 274 (6.8%) &gt;16. Kaplan Meier Survival Curves for the 3 NIHSS groups are shown in the Figure. Strokes with NIHSS &gt;16 at initial presentation were associated with a 15-fold (HR with 95% CI: 13, 19) increase in the risk of death at 30-days compared to those with NIHSS &lt;9. Discussion: NIH Stroke Scale scores are a reliable predictor of mortality, with higher NIHSS scores having higher risk of death. The cut points reported identify subgroups of stroke patients with dramatically different prognoses. Future studies should assess if this excess mortality risk among severe strokes persists after the more widespread implementation of thrombectomy beyond 2015.

Abstract 10621: Prediction of Incident Atherosclerotic Cardiovascular Disease Using Traditional and Polygenic Risk Score Modeling: The Million Veteran Program Experience

The prediction of myocardial infarction (MI), acute ischemic stroke (AIS), cardiovascular (CVD) death, and 3-point MACE (MI, AIS, or CVD death) in Million Veteran Program (MVP) participants over 8 years of follow up was evaluated using environmental/traditional risk factors (“E”), polygenic risk scores (“G”), and a combination of both approaches (“GxE”). Individuals free of atherosclerotic cardiovascular disease (ASCVD) at baseline were included. Risk factor levels for the participants close to the time of MVP enrollment for age, sex, systolic blood pressure, cholesterol, HDL cholesterol, smoking status, and diabetes status were analyzed. Outcomes were determined from VA electronic record data, Medicare/Medicaid data, and the National Death Index. Analyses were undertaken separately for non-Hispanic European (EUR), African American (AFR), and Hispanic (HIS) participants. There were 157,941 veterans at risk with 8,157 MI events, 2,024 AIS events, 1,778 CVD deaths, and 9,350 3-pt MACE events over 8 years of follow-up. The overall results showed good performance with the environmental model for all three racial-ethnic groups, with C-statistics ranging from 0.69 to 0.77. The G models showed very modest prediction capabilities and similarly modest improvement in the combined GxE models. In conclusion, traditional risk factor modeling has been shown to be highly effective and, in the MVP experience, the additional impact of genetic or genetic interaction information was small.

The Natural History and Stroke Risk of Carotid Artery Occlusion

Limited available data suggests the incidence of carotid artery occlusion (CAO) is declining, and if detected, the association with acute stroke is very low. We report our long-term stroke outcomes in patients with CAO in an integrated health system. We identified adult patients with evidence of CAO at initial imaging from 2008 to 2012 or identified during follow-up through 2017 without prior carotid intervention. The primary outcome was acute ischemic stroke (AIS) attributed to the carotid artery (any ipsilateral stroke within the anterior circulation, including internal capsule, basal ganglia, and thalamus). Timing of stroke was assessed in three intervals: >6 months prior to CAO imaging, within 6 months of CAO including the time of imaging study acquisition, and in follow-up until study endpoint. Secondary outcomes include ischemic stroke of other etiology and/or location, and survival. Among over 94,800 eligible patients with carotid imaging, 2084 arteries in 2044 patients were identified with CAO, including 1787 arteries (85.8%) occluded at baseline and 297 arteries (14.3%) that occluded in follow-up. The mean age was 71 ± 11 years, and 35.6% of patients were female. The mean maximal follow-up was 4.8 ± 3.1 years. Of patients that occluded in follow-up, 37, 60, and 189 CAO were seen with baseline arteries with mild/none, moderate, and severe stenosis, respectively. The mean time of progression to occlusion (without interceding intervention) was 3.2 ± 2.2 years for arteries with no/mild stenosis, 3.5 ± 2.4 years for arteries with moderate stenosis, and 1.5 ± 2.0 years for arteries with severe stenosis. In total, 366 ipsilateral AIS events (17.6%) occurred in 346 arteries, with 297 strokes in arteries occluded at baseline and 69 in arteries that occluded in follow-up. The majority of carotid-related strokes (79.2%) occurred within 6 months prior to CAO (Table). After ipsilateral AIS, 5 patients (11.6%) died within 30 days, an additional 8 patients (18.6%) within 1 year, and 16 patients (37.2%) were alive at the end of follow-up. The overall mortality rate was 43.5%, with 13.9% of patients lost to follow-up. There were 370 other strokes (17.8%) observed in 350 arteries, including 308 contralateral strokes in 288 arteries and 62 ipsilateral strokes not attributable to carotid disease. The observed incidence of CAO is low in this select cohort of patients; however, the incidence of carotid-related stroke and associated short- and long-term mortality is high. Further investigation is needed to identify patients at risk of progression to CAO to prevent the associated morbidity and mortality of stroke.TableCharacteristics of occlusion and stroke outcomes by initial artery statusTotalN = 2084, No. (%)Occlusion at baseline n = 1787, No. (%)Occluded during follow-up n = 297, No. (%)Ipsilateral carotid-related stroke366 (17.6)297 (16.6)69 (23.2) >6 months prior to occlusiona30 (8.2)20 (6.7)10 (14.5) ≤6 months prior to occlusiona290 (79.2)243 (81.8)47 (68.1)In follow-up (after occlusion)a46 (12.6)34 (11.4)12 (17.4)aPercentages derived from the total number of ipsilateral carotid-related strokes in each column. Open table in a new tab

Gadolinium enhancement of atherosclerotic plaque in the intracranial artery

ABSTRACT Background: Gadolinium enhancement on high resolution magnetic resonance imaging (HR-MRI) has been considered a sign of instability and inflammation of intracranial atherosclerotic plaques. Our research objective was to explore the relationship between the extent of plaque enhancement (PE), the degree of intracranial artery stenosis, and acute ischemic stroke events. Methods: HR-MRI was performed in 91 patients with intracranial vascular stenosis to determine the existence and intensity of PE. Results: Among 91 patients enrolled in the trial, there were 43 patients in the acute/subacute group (≤1 month from ischemic stroke event), 15 patients in the chronic group (>1 month from ischemic stroke event), and 33 patients in the non-culprit plaques group (no ischemic stroke event). A total of 105 intracranial atherosclerotic plaques were detected in 91 patients. 14 (13.3%) were mild-stenosis plaques, 22 (21.0%) were moderate-stenosis plaques, and 69 (65.7%) were severe-stenosis plaques. There were 12 (11.4%), 18 (17.1%), and 75 (71.4%) plaques in the non-enhanced plaque group, the mild-enhancement group, and the significant-enhancement group, respectively. The degree of PE among the acute/subacute group, the chronic group, and the non-culprit plaque group had a significant difference (P = 0.005). Enhanced plaques were more often observed in culprit plaques (acute/subacute group and chronic group) than non-culprit plaques (96.7% vs 77.3%). Non-enhanced plaques were more often observed in non-culprit plaques than culprit plaques (acute/subacute group and chronic group) (22.7% vs 3.3%). And 36.6% of the enhanced plaques were non-culprit plaques. After performing univariate and multivariate logistic regression analysis, the results showed that strong plaque enhancement (P = 0.025, odds ratio [OR] 3.700, 95% confidence interval [95% CI] 1.182–11.583) and severe stenosis (P = 0.008, OR 4.393, 95%CI 1.481–13.030) were significantly associated with acute ischemic events. Conclusion: Enhanced plaques were more often observed in culprit plaques, and non-enhanced plaques were more often observed in non-culprit plaques. Moreover, significant plaque enhancement and severe ICAS were closely associated with acute ischemic events.

Predicting stroke severity with a 3-min recording from the Muse portable EEG system for rapid diagnosis of stroke

In this study, we demonstrated the use of low-cost portable electroencephalography (EEG) as a method for prehospital stroke diagnosis. We used a portable EEG system to record data from 25 participants, 16 had acute ischemic stroke events, and compared the results to age-matched controls that included stroke mimics. Delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DBATR) and pairwise-derived Brain Symmetry Index (pdBSI) were investigated, as well as head movement using the on-board accelerometer and gyroscope. We then used machine learning to distinguish between different subgroups. DAR and DBATR increased in ischemic stroke patients with increasing stroke severity (p = 0.0021, partial η2 = 0.293; p = 0.01, partial η2 = 0.234). Also, pdBSI decreased in low frequencies and increased in high frequencies in patients who had a stroke (p = 0.036, partial η2 = 0.177). Using classification trees, we were able to distinguish moderate to severe stroke patients and from minor stroke and controls, with a 63% sensitivity, 86% specificity and accuracy of 76%. There are significant differences in DAR, DBATR, and pdBSI between patients with ischemic stroke when compared to controls, and these effects scale with severity. We have shown the utility of a low-cost portable EEG system to aid in patient triage and diagnosis as an early detection tool.

Stroke identification using a portable EEG device – A pilot study

Changes in EEG patterns during stroke are almost immediate; however, a full EEG test takes time and requires highly qualified staff. In this study, we examined whether a short recording using a portable EEG device can differentiate between a stroke and control group. EEG samples were collected from patients with an acute ischemic stroke event. The control group comprised healthy volunteers. EEG recordings were recorded using a portable brain wave sensor device. The Revised Brain Symmetry Index (rsBSI) was used to quantify the symmetry of spectral power between the two hemispheres. The investigation group included 33 patients (ages 46-96, mean age 72 years, 66% male) who were diagnosed with ischemic stroke. The control group included 25 healthy individuals. Scores for the rsBSI of non-stroke patients (M=0.1686, SD=0.10) differed significantly from those of ischemic stroke patients (P<0.05, M=0.363, SD=0.25). A statistically significant difference was observed between a group of stroke patients and a matched group of healthy controls with a short recording using a portable EEG device.

Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions.

In the event of acute ischemic stroke (AIS) due to anterior large vessel occlusion (aLVO), leptomeningeal collaterals (LMCs) status is a key factor to define the severity and functional prognosis of this disease. However, the extent of LMCs exhibits substantial variability among the patients, which is genetic determined. Long non-coding RNAs (lncRNAs) expression profiles in human peripheral blood have been found to be altered after AIS. But whether there are specific lncRNAs correlated with LMC status in aLVO has not yet been investigated. Differential lncRNA expression panels in peripheral blood mononuclear cells (PBMCs) were assessed by microarray analysis and individual quantitative real-time polymerase chain reaction (RT-PCR) in three independent sets consist of 134 patients with aLVO and 73 healthy controls (HCs). LMCs Status in those patients was assessed based on baseline computed tomographic angiography (CTA). Microarray analysis showed 23 differentially expressed lncRNAs in patients with poor LMCs status. After independent validations by RT-PCR, lncRNA ENST00000422956 was found to be significantly downregulated in patients with poor LMCs status. Receiver-operating characteristic (ROC) analysis revealed the area under the ROC curve (AUC) for ENST00000422956 to predict poor LMCs status was 0.749. Moreover, ENST00000422956 expression level and baseline National Institutes of Health Stroke Scale (NIHSS) score were identified as independent predictors for impaired LMCs, and a significantly positive correlation was observed between ENST00000422956 expression level and LMCs status. Via cis-regulatory analysis, paired box 8 (Pax8) was identified as the target gene for ENST00000422956. The dysregulated lncRNA ENST00000422956 in PBMCs was associated with impairment of LMCs in patients with aLVO, suggesting that measurement of circulatory lncRNAs might be included as possible biomarkers for evaluation of LMCs status in AIS. More importantly, this might be the foundation for understand the potential roles of lncRNAs in LMCs formation after ischemic stroke.

Abstract TP262: Factor VIII Elevation Associated With Worse Functional Outcomes Among Patients With Suspected Large Vessel Occlusion

Background: Evidence suggests that elevation of clotting factor VIII (FVIII) increases incidence of acute ischemic stroke (AIS) and may be associated with worse outcomes following an AIS event. The extent of this relationship has not been studied among patients with suspected large vessel occlusion (LVO). Methods: This study is a retrospective case-control study using prospectively collected data from a single high-volume stroke center. Patients over 18 years old diagnosed with AIS between 2008-2015 were included if they had FVIII levels drawn during the acute hospitalization. A positive or negative VAN (vision, aphasia, neglect) score, highly sensitive for LVO, was determined for all patients via abstraction from the NIHSS score. After adjusting for key covariates, we analyzed whether VAN+ patients with elevated FVIII (VAN+/eFVIII), defined as FVIII over 150%, experienced worse outcomes compared to VAN+ patients with normal FVIII and VAN- patients. The primary outcome of interest was poor functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or greater at discharge. Results: Of the 430 patients included, 155 patients (36.04%) were VAN+. Among those, 124 patients (80.0%) were in the VAN+/eFVIII group. The median FVIII level was higher in VAN+ patients than VAN- patients (207% vs. 192%, p=0.019). After adjustment for age, baseline NIHSS, and tPA exposure, the odds of poor functional outcome was 1.91 times greater in the VAN+/eFVIII group compared to all others (OR 1.91, 95% CI 1.03-3.57). Discussion: Among patients with suspected LVO, FVIII levels are higher and elevation is associated with increased odds of poor functional outcome. These findings support the utility of FVIII as a biomarker in the development of stroke patient risk profiles.

A High-Resolution MRI Study of the Relationship Between Plaque Enhancement and Ischemic Stroke Events in Patients With Intracranial Atherosclerotic Stenosis.

Purpose: To investigate the relationships among the degree of intracranial atherosclerotic stenosis (ICAS), plaque enhancement (PE), and ischemic stroke events (ISEs) using 3. 0 T high-resolution magnetic resonance imaging (HR-MRI).Materials and Methods: Fifty-two ICAS patients who underwent HR-MRI were retrospectively analyzed. The patients were divided into two groups according to the results of whole-brain digital subtraction angiography (DSA): the mild-moderate stenosis group (group MID) and the severe stenosis group (group SEV). According to the onset time of the ISEs, the plaques were divided into the acute/sub-acute phase culprit plaque group (group ACU, within 1 month), the chronic-phase culprit plaque group (group CHR, more than 1 month), and the non-culprit plaque group (group NON). Two neuroradiologists independently measured the signal intensity of PE and pituitary enhancement in the HR-MRI and calculated the ratio of the two indices. According to the ratio, the patients were divided into three groups: the marked enhancement group (group MA), the mild enhancement group (group ME), and the no enhancement plaque group (group NO). The relationships among the degree of ICAS, the degree of PE and ISEs were analyzed.Results: Seventy-two ICAS plaques were identified in 52 patients. The multiple independent samples Kruskal-Wallis H test showed that the differences among group ACU, CHR, and NON were significant in the degree of PE (P = 0.002). Group CHR and group NON were combined as the non-acute phase group (group non-ACU). Group NO and group ME were combined as the non-marked enhancement group (group non-MA). The comparison between group ACU and group non-ACU showed significant differences in the degree of both ICAS (P = 0.014) and PE (P = 0.006) according to the univariate logistic regression. The multivariate logistic regression model was used to analyze the impact of the degree of ICAS and PE on ISEs, and the results showed that severe stenosis (P = 0.036) and marked PE (P = 0.013) were independent risk factors for acute ISEs, respectively.Conclusion: Severe intracranial arterial stenosis and marked plaque enhancement are independent risk factors for acute ischemic stroke events, respectively. The study provides new ideas for further exploring the pathogenesis of stroke caused by intracranial atherosclerotic stenosis.

Circulating Troponin I Level in Patients with Acute Ischemic Stroke

Cardiac troponin levels in the blood are an important biomarker of acute coronary events, but may also be elevated in the context of acute ischemic stroke without an obvious concurrent myocardial insult. The objective of this study and systematic review is to determine how high the circulating troponin I level can rise due to ischemic stroke. Anonymized medical records from Vanderbilt University Medical Center were reviewed identifying 151,972 unique acute ischemic stroke events, of which 1226 met criteria for inclusion in this study. Included patients had at least one measurement of troponin I level documented during the hospital visit when an acute ischemic stroke was diagnosed and were free of known cardiac/coronary disease, renal impairment, sepsis, or other confounders. In this group, 20.6% had a circulating troponin I level elevated over the reference range, but 99% were below 2.13ng/mL. This is significantly lower than the distribution observed in a cohort of 89,423 unique cases of acute coronary syndrome (p < 2.2-16). A systematic review of published literature further supported the conclusion that troponin I level may increase due to an acute ischemic stroke, but rarely rises above 2ng/mL. Because of the shared risk factors between stroke and coronary artery disease, clinicians caring for patients with acute ischemic stroke should always have a high index of suspicion for comorbid cardiac and cardiovascular disease. In general, troponin I levels greater than 2ng/mL should not be attributed to an acute ischemic stroke, but should prompt a thorough evaluation for coronary artery disease.