Search

A comprehensive evaluation is necessary to identify the etiologic factors in order to select optimal stroke-prevention measures. Atrial fibrillation is one of the most important stroke causes. Although anticoagulant therapy is the treatment of choice for patients with nonvalvular atrial fibrillation, it should not be considered uniformly to treat all patients given the high mortality associated with anticoagulant-related hemorrhages. The authors propose a risk-stratified individualized approach for stroke prevention in patients with nonvalvular atrial fibrillation by considering nonpharmacologic approaches for patients at high hemorrhage risk or otherwise unsuitable for lifelong anticoagulation.

Resumen Introduccion La variabilidad glucemica (VG) hace referencia a las oscilaciones en los niveles de glucosa en sangre y podria influir en el pronostico del ictus. Objetivo: Analizar el efecto de la VG en la evolucion del infarto cerebral agudo (IC). Metodos Analisis exploratorio del estudio GLIAS-II (multicentrico, prospectivo y observacional). Se midieron los niveles de glucemia capilar cada cuatro horas durante las primeras 48 horas y la VG se definio como la desviacion estandar de los valores medios. Variables principales: mortalidad y muerte o dependencia a los tres meses. Variables secundarias: porcentaje de complicaciones intrahospitalarias y de recurrencia de ictus, e influencia de la via de administracion de insulina sobre la VG. Resultados Se incluyeron 213 pacientes. Los pacientes que fallecieron (N = 16;7,8%) presentaron mayores valores de VG (30,9 mg/dL vs. 23,3 mg/dL; p = 0,05). En el analisis de regresion logistica ajustado por edad y comorbilidad, tanto la VG (OR = 1,03; IC del 95%: 1,003-1,06: p = 0,03) como la gravedad del IC (OR = 1,12; IC del 95%: 1,04-1,2; p = 0,004) se asociaron de forma independiente con la mortalidad a los tres meses. No se encontro asociacion entre la VG y las demas variables de estudio. Los pacientes que recibieron tratamiento con insulina subcutanea mostraron una mayor VG que los tratados con insulina intravenosa (38,9 mg/dL vs. 21,3 mg/dL; p Conclusiones Valores elevados de VG durante las primeras 48 horas tras el IC se asociaron de forma independiente con la mortalidad. La administracion subcutanea de insulina podria condicionar una mayor VG que la via intravenosa.

Treatment with alteplase for acute ischemic stroke patients with an unknown time of onset is safe and effective. However, clinical trials have some selection bias. The purpose of this study was to clarify the efficacy and safety of alteplase treatment in patients with unknown time of onset in a real-world clinical setting.We included consecutive patients with acute ischemic stroke visited within 4.5 h of onset or symptom recognition. We divided patients into two groups: onset clear group (C-group) and unknown time of onset group (U-group). We treated patients with an unknown time of onset if the DWI-FLAIR mismatch was positive. We calculated the prevalence of alteplase treatment in each group and compared prognosis between the two groups.Six hundred thirty-two patients arrived within 4.5 h of onset or symptom recognition. Of these, 446 patients (71 %) were in the C-group and 186 (29 %) in the U group. Alteplase treatment was performed in 35 % of patients in the C group and in 18 % in the U group (p 0.001). Favorable outcomes at 90 days in patients treated with alteplase were comparable between the C group (52 %) and the U group (53 %) (p = 0.887). All hemorrhagic complications, including non-symptomatic hemorrhagic transformation, occurred in 11 of 157 patients (7 %) in the C-group and one of 34 patients (3 %) in the U-group (p = 0.696).In a real-world clinical setting, alteplase treatment was performed safe in 18% of patients with an unknown time of stroke onset based on patient selection using the DWI-FLAIR mismatch.

Apolipoproteins are known atherogenic factors that play important roles in many mechanisms related to acute ischemic stroke (AIS). However, it is unclear whether the ApoB/ApoA-Ι ratio is related to the prognosis of patients with AIS.We conducted a prospective cohort study in the Department of Neurology, Yangpu Hospital, School of Medicine, Tongji University and investigated the association between ApoB/ApoA-Ι ratio and poor outcomes at 3 months of AIS.1,247 patients that met the eligibility criteria were enrolled in our study. We found that ApoA-Ι (Adjusted odds ratios (adjOR) 0.529, 95 %CI 0.327-0.855), ApoB (adjOR 3.015, 95 %CI 1.746-5.207), and ApoB/ApoA-Ι ratio (adjOR 3.986, 95 %CI 2.220-7.155) were independently associated with poor outcomes in acute ischemic stroke. During subgroup analysis, the ApoB/ApoA-Ι ratio was more likely associated with poor AIS outcomes in males and patients younger than 80 with SAO(Small Artery Occlusion) and no history of diabetes or statin use. Restricted cubic spline analyses explored the correlation between poor outcomes and ApoB/ApoA-Ι ratio.Higher ApoB, lower ApoA-Ι, and higher ApoB/ApoA-Ι ratios were independently associated with poor outcomes in AIS. However, ApoB and ApoA-Ι were not related to hemorrhagic transformation in AIS.

To examine the association between ethnicity and 90-day post-stroke subjective sleepiness, an important determinant of quality of life, as measured by the Epworth Sleepiness Scale (ESS), among ischemic stroke survivors.Mexican American (MA) and non-Hispanic white (NHW) recent ischemic stroke patients were identified from the population-based Brain Attack Surveillance in Corpus Christi Project (2010-2016). Subjects completed a baseline interview and 90-day outcome assessment that included the ESS. Excessive daytime sleepiness was defined as an ESS10. Tobit regression models were used to assess associations between ethnicity and ESS unadjusted and adjusted for multiple potential confounders.Among 1,181 (62.5% MA) subjects, mean ESS at 90 days was 8.9 (SD 6.0) among MA and 7.4 (SD 4.9) among NHW subjects: 1.45 (95% CI: 0.75, 2.15) points higher among MA than NHW subjects. After adjustment, mean ESS at 90 days was 1.16 (95% CI: 0.38, 1.94) points higher among MAs than NHWs. The prevalence of excessive daytime sleepiness was 39% among MA and 30% among NHW subjects (p = 0.0013).Ninety days after stroke, sleepiness is worse in MAs compared to NHWs, even after accounting for potential confounding variables. Further studies should address ways to reduce this disparity.

The management of acute stroke is challenging. The aim of this meta-analysis was to determine the efficacy and tolerability of edaravone, with or without thrombolytic therapy, in the treatment of patients with acute ischemic stroke.The PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) and cohort studies. Mean differences (MD), risk ratios (RR), 95% confidence interval (CI), and heterogeneity were calculated.Totals of nine RCTs and four cohort studies were included, for a total of 2102 patients. In patients with acute ischemic stroke, edaravone monotherapy was associated with significantly improved Barthel Index of functioning in activities for daily living (MD, 23.95; 95% CI, 18.48 to 29.41; P0.001) and neurologic deficit, (as measured using the National Institutes of Health Stroke Scale score) (MD = -3.49; 95% CI, -5.76 to 1.22; P = 0.003), on short-term follow-up. However, edaravone was not associated with an improved rate of death or disability (RR = 0.75; 95% CI, 0.45 to 1.23; P = 0.25) on long-term follow-up.When plus to thrombolytic therapy, edaravone was associated with significant improvements in recanalization rate (RR = 1.71; 95% CI, 1.05 to 2.77; P = 0.03) and neurologic deficit (MD = 3.97; 95% CI, 5.14 to 2.79; P0.001), without an increase in the prevalence of bleeding events (RR = 1.11; 95% CI, 0.76 to 1.62; P = 0.59). However, edaravone did not have a significant effect on death or disability (RR = 0.85; 95% CI, 0.69 to 1.04; P = 0.12).Based on the findings from the present meta-analysis, edaravone was an effective and well-tolerated neuroprotective agent in these patients with ischemic stroke. With the use of edaravone, activities of daily living and neurologic deficits, along with recanalization rates, were improved on short-term follow-up, but the long-term effects still need confirmation in larger-scale clinical trials.

Intravenous thrombolysis (IVT) use for acute ischemic stroke (AIS) varies among countries, partly due to guidelines and product labeling changes. The study aim was to identify the characteristics of patients with AIS treated with off-label IVT and to determine its safety when performed in a primary stroke center (PSC).This observational, single-center study included all consecutive patients admitted to Perpignan PSC for AIS and treated with IVT and patients transferred for EVT, between January 1, 2015 and December 31, 2019. Data of patients treated with IVT according to ("in-label group") or outside ("off-label") the initial guidelines and manufacturer's product specification were compared. Safety was assessed using symptomatic intracerebral hemorrhage (SIH) as the main adverse event.Among the 892 patients in the database (834 screened by MRI, 93.5%), 746 were treated by IVT: 185 (24.8%) "in-label" and 561 (75.2%) "off-label". In the "off-label" group, 316 (42.4% of the cohort) had a single criterion for "off-label" use, 197 (26.4%) had two, and 48 (6.4%) had three or more criteria, without any difference in IVT safety pattern among them. SIH rates were comparable between the "off-label" and "in-label" groups (2.7% vs. 1.1%, P=0.21); early neurological deterioration and systematic adverse event due to IVT treatment were similar in the 2 groups. "Off-label" patients had higher in-hospital (8.7% vs. 3.8%, P=0.05) and 3-month mortality rates (12.1% vs 5.4%, P0.01), but this is explained by confounding factors as they were older (76 vs 67 years, P0.0001) and more dependent (median modified Rankin scale score 0.4 vs 0.1, P0.0001) at admission."Off-label" thrombolysis for AIS seems to be safe and effective in the routine setting of a primary stroke center.

Cryptogenic stroke (CS) represents 1/3 of ischemic strokes. Atrial fibrillation (AF) can be detected in up to 30% of CS. Therefore, there is a clinical need for predicting AF to guide the optimal secondary prevention strategy. The evidence about the role of advanced echocardiography, including left atrial 3-dimensional (3D) index volume and left atrial strain (LAS) techniques, to predict underlying AF in this setting is lacking. From April 2019 to November 2021, 78 consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography was performed during admission. All patients underwent 15 days of wearable Holter monitoring. The primary outcome measure was AF detection during follow-up. Twenty-two patients (28%) developed AF. Patients in the AF group were older (81 ± 6.3 vs 76.5 ± 7.8 years; p = 0.012). Left atrial (LA) diastolic indexed volume was higher in the AF group (37.2 ± 12.8 vs 29.7 ± 11 ml/m

Our aim was to analyze the incidence of P-wave abnormalities in embolic and non-embolic strokes, and evaluate its clinical usefulness for predicting stroke etiology.We included 376 consecutive patients hospitalized for acute ischemic stroke from January 2015 to September 2021. Among the patients in sinus rhythm at admission, 31 had ischemic stroke due to atrial fibrillation (AF)-related embolism, 59 had embolic stroke of unknown source (ESUS), and 143 had non-embolic stroke. P-wave abnormalities were defined as 1. P-wave axis abnormality (PWAA); 2. P-wave terminal force in Vsub1/sub(PTFV1) ≤ -4000 μV*ms; 3. advanced inter-atrial block (A-IAB).The prevalence of each type of abnormality was consistently lower in patients with non-embolic stroke than in those with AF-related embolism (AF-related vs. ESUS vs. non-embolic; PWAA, 45% vs. 20% vs. 14%; PTFV1, 36% vs. 37% vs. 15%; and A-IAB, 55% vs. 31% vs. 13%, respectively). The identification of at least one type of P-wave abnormality improved the sensitivity compared to using a single abnormality parameter (sensitivity 72%, specificity 62%), while at least two types of abnormality had low sensitivity, but high specificity (sensitivity 29%, specificity 95%). Multivariate regression analysis revealed that identification of at least one type of P-wave abnormality was independently associated with embolic stroke (odds ratio 3.11, 95%CI 1.46-6.63).The incidence of each type of P-wave abnormality was significantly lower in patients with non-embolic stroke. A combination of PWAA, PTFV1, and A-IAB parameters could be useful for distinguishing embolic from non-embolic stroke.

Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS.The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021.A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; IOur meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.

Temporal trends and geographical variations in cardiovascular disease attributable to high systolic blood pressure in China are not yet fully understood. The aim of this study was to quantify the cardiovascular disease burden attributable to high systolic blood pressure at national and provincial levels in China.In this population-based study, we evaluated systolic blood pressure and estimated the number of deaths, age-standardised mortality rates, and years of life lost (YLLs) due to cardiovascular disease and its subcategories (including ischaemic heart disease, ischaemic stroke, haemorrhagic stroke, and other cardiovascular diseases) attributable to high systolic blood pressure, at the national level and by 31 provincial levels, in China, from 2005 to 2018. We pooled blood pressure data of 1·30 million adults aged 25 years and older from the China Chronic Disease and Risk Factor Surveillance project, the China National Nutrition Survey, and the China Hypertension Survey. We applied a temporal-spatial Bayesian hierarchical model to estimate age-specific, sex-specific, province-specific, and year-specific average systolic blood pressure, and a comparative risk assessment method to compute the cardiovascular disease burden attributable to high systolic blood pressure by age, sex, year, and province.Nationally, age-standardised mean systolic blood pressure was 132·5 mm Hg (95% uncertainty interval [UI] 124·6-140·3) in men and 129·4 mm Hg (121·7 to 137·2) in women. 2·67 million (95% UI 2·61 to 2·72) cardiovascular disease deaths in China were attributable to high systolic blood pressure, including 1·12 million deaths (1·07 to 1·16) due to ischaemic heart disease, 0·63 million deaths (0·60 to 0·65) due to ischaemic stroke, 0·58 million deaths (0·57 to 0·60) due to haemorrhagic stroke, and 0·34 million deaths (0·32 to 0·36) due to other cardiovascular disease. The age-standardised cardiovascular disease mortality rates associated with high systolic blood pressure were 268·99 per 100 000 people (95% UI 264·11 to 273·51) in 2005 and 220·84 per 100 000 people (216·30 to 224·76) in 2018, a percentage change of -17·90%; the rate changed by an average of -1·50% (95% UI -1·55% to -1·45%) per year from 2005 to 2018 nationally. YLL rates for total cardiovascular disease caused by high systolic blood pressure varied substantially across provinces, ranging from 3078·33 (95% UI 2807·40 to 3303·57) per 100 000 people in Beijing to 7189·98 (95% UI 6817·18 to 7507·99) per 100 000 people in Heilongjiang in 2018. Age-standardised YLL rates for ischaemic heart disease and ischaemic stroke attributable to high systolic blood pressure were particularly high in northeastern provinces, including Heilongjiang, Liaoning, and Jilin.The deaths and YLLs for cardiovascular disease attributable to high systolic blood pressure in China increased between 2005 and 2018, and age-standardised cardiovascular disease mortality rates decreased in the same timeframe. Our findings could help policy makers in promoting blood pressure control measures and implementing effective and locally adapted preventive interventions to reduce the prevalence of high systolic blood pressure and reduce the burden of systolic blood pressure-related cardiovascular disease in China.China National Key Research and Development Program, China National ScienceTechnology Pillar Program, and National Health Commission of the People's Republic of China.For the Chinese translation of the abstract see Supplementary Materials section.

[Background and Purpose] Clot location and range predict clinical outcomes for acute ischemic stroke (AIS). We developed a new technique for visualizing occlusion clots, namely, the DEpicting blood clot and MRA using Phase contrast angiography with Image Calculation for Thrombectomy (DEPICT) method. The purpose of this study was to assess the clinical usefulness of DEPICT. [Methods] We used DEPICT in 36 AIS patients to obtain MRA and black blood images with 1-min phase contrast angiography (PCA). We created the black blood images by subtracting the MRA from the T1WI using the source image of PCA. We evaluated the motion artifact, detectability of clot, and precision in location and range compared these to that of susceptibility vessel sign in T2*WI and measured contrast ration (CR) of clot between the cistern and brain tissue. Motion artifact was visually evaluated using a 3-point scale. Detectability and precision of the location and range of occlusion clots were assessed by comparison with findings from digital subtraction angiography (DSA). Gwet's AC

To examine the association between comorbid mental disorders and cardiovascular disease (CVD) risk among patients with type 2 diabetes.This retrospective cohort study was conducted using the claims data of 2,227,394 South Korean patients with type 2 diabetes. We analyzed the occurrence of CVD including myocardial infarction (MI) and ischemic stroke, CVD-specific mortality, and all-cause mortality according to comorbid mental disorders including depressive disorders, bipolar and related disorders, schizophrenia spectrum disorders, insomnia, and anxiety disorders.Among the patients, 9.1% had a comorbid mental disorder. The adjusted hazard ratios (aHR) for MI, ischemic stroke, CVD-specific mortality, and all-cause mortality in patients with any mental disorder were 1.20 (95% CI, 1.17-1.24), 1.13 (95% CI, 1.11-1.16), 1.16 (95% CI, 1.12-1.20), and 1.21 (95% CI, 1.19-1.23), respectively. Each mental disorder increased the risk of all outcomes, particularly bipolar and related disorders and schizophrenia spectrum disorders.Comorbid mental disorders increased the CVD risk in patients with type 2 diabetes, with significantly increased risks associated with schizophrenia spectrum disorders (aHR: 1.27 for MI and 1.50 for ischemic stroke) and bipolar and related disorders (aHR: 1.27 for MI and 1.45 for ischemic stroke).

Whether direct endovascular thrombectomy (EVT) is non-inferior to bridging therapy (intravenous thrombolysis [IVT] followed by EVT) in minor acute ischemic stroke due to large vessel occlusions (AIS-LVO) is not clear. Therefore, this study aimed to assess whether direct EVT is non-inferior to bridging therapy in minor AIS-LVO.903 patients with acute ischemic stroke due to large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) score6 receiving EVT treatment were enrolled at Bigdata Observatory Platform for Stroke of China in China from January 1, 2019, to December 31, 2020, with final follow-up on March 31, 2021. The primary efficacy endpoint was a favorable outcome defined as a modified Rankin Scale score of 0 to 2 at three months. In addition, there were three prespecified secondary efficacy endpoints, including symptomatic intracerebral hemorrhage (ICH), in-hospital mortality, and mortality by month 3.A total of 662 patients treated with direct EVT (age 65.9 ± 10.5 years, 71.5 % male, NIHSS score 2.4 [standard deviation {SD}. 1.8]) were compared to 241 bridging-treated patients (age 65.7 ± 10.8, 75.9 % female, NIHSS score 2.5 [1.8]). The rate of symptomatic ICH in the EVT group was lower than in the bridging group (4.2 % vs. 8.3 %; P = 0.02). The in-hospital mortality was not different between the two groups (EVT vs. bridging group: adjusted hazard ratio {HR}, 0.9 [95 % confidence interval {CI}, 0.5 to 1.9]; P = 0.93). There was no significant difference in 3-month poor functional outcome rate (EVT vs. bridging group: 17.1 % vs. 16.2 % [absolute difference, 0.9 % {95 % CI, -0.8 % to 2.4 %}, P = 0.75; adjusted hazard ratio {HR}, 1.0 {95 % CI, 0.6 to 1.7}, P = 0.83]) and mortality rate (13.0 % vs. 11.2 % [absolute difference, 1.5 % {95 % CI, -3.9 % to 6.8 %}, P = 0.47; adjusted HR, 1.1 {95 % CI, 0.8 to 1.9}, P = 0.55]) between those two groups.Among patients with minor AIS-LVO, direct EVT, compared with bridging therapy, met the prespecified statistical threshold for noninferiority for the 3-month prognosis.

Ischemic stroke is a devastating complication of thoracic endovascular aortic repair (TEVAR). This risk may be higher in more proximal aneurysms that require arch manipulation. The purpose of this study is to (1) describe 30-day stroke and death rates in patients undergoing TEVAR, (2) compare stroke rates in patients undergoing TEVAR for arch versus descending aneurysm pathology, and (3) identify predictive factors associated with stroke after TEVAR.The Vascular Quality Initiative registry was queried (2015-2021) for TEVAR procedures performed for degenerative aneurysms. Our primary outcomes were any stroke or death at 30 days. Patient-, procedure-, and hospital-level predictors of stroke were assessed using multivariable Poisson regression.Among 3,072 patients with degenerative aneurysms (197 [6.4%] arch versus 2,875 [93.6%] descending) treated with elective TEVAR, the median age was 73 years (interquartile range 67-79) and 54.8% were male. Within the arch aneurysm group, there were 27.4% zone 0, 22.8% zone 1, and 49.8% zone 2 interventions. Overall 30-day stroke and death rates were 3.2% and 3.8%. The distribution of stroke events was bilateral (52.9%), left carotid (20.7%), left vertebrobasilar (11.5%), right carotid (9.2%), and right vertebrobasilar (5.7%). Although mortality was similar between groups, the rate of ischemic stroke was higher for patients undergoing TEVAR for arch aneurysm versus descending aneurysms (7.1% arch versus 2.9% descending, P = 0.001). Factors that were associated with ischemic stroke after TEVAR included age (79 years, relative risk [RR] 1.79, 95% confidence interval [CI] 1.08-2.98 vs.79 years), dependent functional status (RR 1.73, 95% CI 1.07-2.78), procedural time (RR 1.25, 95% CI 1.15-1.36), and endovascular intervention for supra-aortic trunk revascularization (RR 2.66, 95% CI 1.06-6.70 versus no intervention).Ischemic stroke risk after TEVAR was increased for arch aneurysms compared to descending aneurysms. More proximal zone coverage and endovascular interventions on the supra-aortic trunks were associated with increasing risk for stroke. Adequate preparation for stroke prevention is necessary prior to TEVAR with supra-aortic trunk revascularization.

Understanding the composition of stroke thrombi retrieved by mechanical thrombectomy is essential to clarify the pathogenesis of stroke. However, it is difficult to evaluate thrombus composition precisely and objectively. Immunohistochemical staining was used to evaluate thrombus composition and age.Consecutive thrombi (n = 108) retrieved from patients who underwent mechanical thrombectomy for acute large-vessel ischemic stroke were retrospectively analyzed. Lytic features of granulocytes and CD163 were estimated as indicators of the age of the cardioembolic (CE) thrombus.The stroke subtypes were as follows: CE, 74 cases; large artery atherosclerosis, 11; undetermined etiology, 12; and other determined etiology, 11. There were no statistical differences in thrombi composition according to stroke subtypes. The fibrin area was positively correlated with the red blood cell (RBC) and platelet areas. The following analysis was performed using CE only. Regarding age, the thrombus was judged as fresh in 30.0 % and older in 70.0 % based on the lytic features. The RBC areas of older thrombi were smaller than those of fresh thrombi. The puncture-to-reperfusion time of older thrombi was longer than that of fresh thrombi. Platelet-rich thrombi were associated with a greater number of maneuvers, a smaller prevalence of TICI 3, and unfavorable functional outcomes compared to platelet-poor thrombi. The number of CD163 positive cells in thrombi with anticoagulants was higher than in those without anticoagulants.Thrombus composition correlated with revascularization and clinical outcomes. The composition of an acute ischemic thrombus may reflect the pathophysiology of stroke and influence treatment efficacy.

Earlier administration of intravenous recombinant tissue-type plasminogen activator (rtPA) and mechanical thrombectomy (MT) improves the neurological prognosis of patients with acute ischemic stroke (AIS). We introduced a new protocol that includes head and chest computed tomography (CT) and magnetic resonance imaging (MRI)/ magnetic resonance angiography (MRA) for all patients, which is quite different from previously evaluated protocols. This study aimed to examine whether this protocol could contribute to the prompt therapeutic intervention of AIS.This is a retrospective observational study analyzing patients with AIS who were transported to our hospital by ambulance between January 2015 and November 2021. An AIS initial treatment protocol was introduced in April 2020, under which, CT and MRI/MRA imaging were performed in all patients, and the indication for rtPA and MT were determined. The participants were divided into those who were treated before and after the protocol introduction (conventional treatment and protocol groups, respectively). The time from hospital arrival to the start of rtPA administration (door-to-needle time: DNT) and the time from hospital arrival to the start of endovascular treatment (door-to-puncture time: DPT) were compared between the groups.A total of 121 patients were analyzed, wherein 63 patients received rtPA (18 in the conventional treatment group and 45 in the protocol group) and 98 patients received MT (32 in the conventional treatment group and 66 in the protocol group). The median DNT was 97.0 (IQR 49.0-138.0) min vs. 56.5 (IQR 41.0-72.0) min (p0.001) for the conventional treatment and the protocol groups, respectively. The median DPT was 129.0 (IQR 62.0-196.0) min vs. 55.0 (IQR 40.5-69.5) min (p0.001), respectively. Moreover, DNT was achieved within 60 min in 5.6% vs. 69.9% (p0.001) and DPT within 90 min in 25.0% vs. 85.7% (p0.001), respectively.The introduction of a protocol, including CT/MRI imaging, significantly shortened DNT and DPT.

Chuanzhitongluo (CZTL), a traditional Chinese medicine mixture, is used in the recovery period of acute ischemic stroke (AIS), and effectively improves the prognosis of AIS patients. This study aims to evaluate whether CZTL regulates microglia polarization and inflammatory response to reduce brain damage in the acute phase of AIS.A mouse model of AIS was prepared by the photochemical method. Cerebral infarct volume was detected by 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to assess neuronal apoptosis. Gene expression profile change was explored by Gene chip. Inflammatory factors were analyzed by Protein microarray. The Immunofluorescence double-labeling assay was executed to elucidate the effects of CD16Results revealed that CZTL treatment alleviated the neurological impairment, reduced cerebral infarct volume, and inhibited neuronal apoptosis. CZTL altered gene expression profiles, which indicate that CZTL may be involved in regulating neuroinflammation. CZTL restrained inflammatory responses by down-regulated pro-inflammatory cytokines expression and enhanced anti-inflammatory cytokines level. Further experiments demonstrated that CZTL inhibited the activation of NLRP3 inflammasome, which decreasing the inflammatory response. In addition, CZTL promoted the transformation of microglia from M1 to M2 phenotype.These results indicate that CZTL alleviates neuroinflammation and brain damage after AIS in mice, which may be mediated by modulating microglia polarization.

Post hoc analyses of clinical trials show that PCSK9 inhibitors might lower lipoprotein(a), but whether this effect contributes to reductions in cardiovascular risk remains unknown. We aimed to assess whether genetically proxied PCSK9 inhibition influences lipoprotein(a) (Lp(a)), and whether any such effect could mediate its effects on coronary artery disease (CAD) and ischemic stroke (IS).To explore associations between the genetic proxies for PCSK9 inhibitors and Lp(a) levels, we used UK Biobank data (310,020 individuals). We identified 10 variants in the PCSK9 gene associated with lower PCSK9 and LDL-C levels as proxies for PCSK9 inhibition. We explored the effects of genetically proxied PCSK9 inhibition on Lp(a) levels, as well as on odds of CAD (60,801 cases, 184,305 controls) and IS (60,341 cases, 454,450 controls) in two-sample Mendelian randomization analyses. In mediation analyses, we assessed the effects of genetically proxied PCSK9 inhibition on CAD and IS mediated through reductions in Lp(a) levels.Genetically proxied PCSK9 inhibition (1-SD decrement in PCSK9 concentration; corresponding to 20.6 mg/dl decrement in LDL-C levels) was associated with a 4% decrease in log-Lp(a) levels (beta: -0.038, 95%CI: -0.053 to -0.023). We estimated a 0.8% reduction in the odds for CAD (OR: 0.992, 95%CI: 0.989-0.995) and a 0.5% reduction in the odds for atherosclerotic IS (OR: 0.995, 95%CI: 0.992-0.998) due to reductions in Lp(a) levels through genetically proxied PCSK9 inhibition, corresponding to 3.8% and 3.2% of the total effects, respectively.Genetic proxies for PCSK9 inhibition are associated with lower Lp(a) levels. However, Lp(a) lowering explains only a small proportion of the total effects of genetic proxies for PCSK9 inhibitors on risk of CAD and IS.

l-Carnitine was suggested to prevent the progression of atherosclerosis, myocardial and neurologic injury, and exhibited cardioprotective effects. However, epidemiological data on circulating l-carnitine and risks of cardiovascular events in the setting of stroke is rare. We aimed to explore the relationships between plasma l-carnitine and cardiovascular events and stroke recurrence after ischemic stroke in a nested case-control study.A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 matched controls (free of recurrent cardiovascular events) were included. Study outcomes included cardiovascular events and recurrent stroke after ischemic stroke. Plasma l-carnitine concentrations were measured by ultra-high-performance LC-MS/MS. Conditional logistic regression models were used to estimate odds ratios (ORs) of stroke outcomes. Plasma l-carnitine was inversely associated with cardiovascular events (OR = 0.69, 95% CI: 0.57-0.84 per SD) and recurrent stroke (OR = 0.72, 95% CI: 0.58-0.88 per SD) after adjusting for established risk confounders. Compared with the lowest tertile of l-carnitine, adjusted ORs of cardiovascular events and recurrent stroke for participants in the highest tertiles were 0.35 (95% CI: 0.21-0.57) and 0.36 (95% CI: 0.21-0.62), respectively. In addition, l-carnitine provided incremental predictive ability beyond established risk factors, shown by increase in C statistics, net reclassification improvement and integrated discrimination improvement.Higher l-carnitine levels were associated with lower risks of cardiovascular events and recurrent stroke after ischemic stroke. Our findings provided evidence supporting plasma l-carnitine as a potential prognostic marker in risk discrimination and stratification in patients with ischemic stroke.Clinicaltrials.gov as NCT01840072. URL: https://www.gov.

The contributions of hypoxia, oxygen glucose deprivation (OGD) and oxidative stress, to the pathophysiology of acute ischemic stroke (AIS) are well established and can lead to disruptions in synaptic signaling. Antioxidant compounds have previously been shown to have a preconditioning and neuroprotective effect against an ischemic insult. Therefore, in this study we explored the effects of the reactive oxygen species (ROS) scavenger, MnTMPyP, on synaptic transmission in two models, hypoxia and oxygen glucose deprivation (OGD), in isolated rat hippocampal slices using electrophysiological techniques and organotypic hippocampal slice cultures. We report a novel modulatory effect of MnTMPyP on synaptic transmission post hypoxia and OGD, an effect specific to the CA1 region of the hippocampus. This reduction of the fEPSP by MnTMPyP post hypoxia in the CA1 was attenuated through the co-application of the adenosine A1 receptor antagonist, DPCPX (200 nM), and the NMDA receptor antagonists, AP-5 (10 µM) and DCKA (5 µM). These effects were not observed in the OGD model. Our organotypic data demonstrated a protective role for MnTMPyP, where slices had significantly less cell death in the CA1 region post hypoxia and OGD, compared to controls. Taken together, our results suggest a complex role for MnTMPyP on both synaptic signaling in an hypoxic environment and cell viability. Whether this SOD mimetic will play an important role in ischemia still remains to be determined.

Approximately one-quarter to one-third of patients with ischemic stroke have an embolic stroke of undetermined source (ESUS). An estimated 5% to 10% of patients with ESUS have an active cancer diagnosis. Presence of cancer potentially increases the risk of acute ischemic stroke through various mechanisms such as cancer-related hypercoagulability, intracranial tumors leading to an arterial compression, or intracardiac tumors leading to cardioembolism. Certain cancer therapeutics can also contribute to risk of ischemic stroke. Multiple vascular lesions involving bilateral anterior and posterior circulations, high plasma D-dimer levels, and elevated inflammatory markers might suggest cancer-related ischemic stroke. Patients with ischemic stroke related to malignancy are also at higher risk of stroke recurrence, early neurologic deterioration, and mortality. Cancer screening in acute ischemic stroke patients can be considered when no other etiology for stroke can be established and clinical history such as tobacco use, unexplained constitutional symptoms such as fever or night sweats, or unexplained weight loss suggests an underlying malignancy. Selection of antithrombotics for secondary stroke prevention remains controversial as clinical trial data for use of antiplatelet therapy vs anticoagulation in ESUS and cancer patients is limited. Future clinical trials should specifically focus on patients with ischemic stroke related to malignancy are needed to guide appropriate therapeutic agent selection.

Ischemic stroke (IS) is an acute brain injury and a major cause of disability and mortality worldwide, resulting from permanent or temporary cerebral artery occlusion. Thrombolysis and antithrombotic therapy or thrombectomy over a wider therapeutic window led to reduced stroke mortality. However, the post-stroke pathological mechanism is still elusive, involving sustaining inflammation and cellular dysfunction, which hinders the recovery after IS. Thus, more attention is shifting towards the complex interactions of the neurovascular unit (NVU) and its important role in the progress of inflammation recently. This review summarized the physiological function of each component of the NVU and their functions on blood brain barrier permeability, cerebral blood flow regulation and the inflammation progress after IS. In addition, we described the inflammation-related pathological changes affected by the NVU and concluded that the dysfunction of the NVU contributed to the inflammation progress after IS. This review may provide ideas for the potential therapies targeting the NVU for improving the prognosis of IS.

Ischaemic stroke (IS) is characterized by high morbidity, disability and mortality and lacks effective solutions. MiRNA-27a has been implicated in ferroptosis, but evidence that miRNA-27a regulates ferroptosis in ischaemic stroke is lacking. Nrf2 could reduce brain tissue injury in ischaemic stroke and resist ferroptosis. The current study aimed to investigate the relationship between miRNA-27a/Nrf2 and ferroptosis in ischaemic stroke. In this study, IS was simulated using a permanent middle cerebral artery occlusion (pMCAO) model. The degree of brain tissue injury was assessed by conducting TTC staining and neurological function scoring. MiRNA-27a expression levels were altered via the intracerebroventricular injection of miRNA‑27a agonist or antagonist. Glutathione peroxidase 4 (GPX4), glutathione (GSH), Fe and malondialdehyde (MDA) are considered biomarkers for ferroptosis. The expression of GPX4 and Nrf2 was analysed by Western blot assay. The GSH, Fe and MDA contents were detected by detection kits. We found that the expression levels of Fe and MDA were increased, while GPX4 and GSH were decreased in the pMCAO groups compared with the control group. These results indicated that ferroptosis intensified over time during IS. In addition, the miRNA‑27a agonist significantly aggravated ferroptosis and reduced neurological function scores compared with those of the control group. Subsequently, a luciferase reporter gene system verified the targeted binding of miRNA‑27a to Nrf2. The results showed that miRNA‑27a inhibited Nrf2 in a targeted manner, which also exacerbated the extent of ferroptosis. However, the miRNA‑27a antagonist reversed the miR‑27a agonist‑mediated effects. Therefore, the present study indicated that miRNA‑27a may aggravate brain tissue ferroptosis during ischaemic stroke, potentially by inhibiting Nrf2.

OBJECTIVE: Strokes are among the leading causes of death worldwide and have different characteristics. Different physiopathological mechanisms characterize the -umerous subtypes of ischemic stroke (IS). In this study, we investigated the relationship between serum levels of autophagy-5 protein, apolipoprotein B-48, and oxidative stress markers in patients with ischemic stroke.-METHODS: For this study, 100 participants were recruited, of which 50 were patients with IS and 50 were healthy individuals. We conducted a case-control study at Imam Reza Hospital from March 2019 to April 2020. Serum levels of ATG5, apo B-48, and oxidative stress markers were determined in both groups. Our Receiver Operating Characteristic Analysis evaluated the additional diagnostic value of these factors in both groups. -RESULTS: Diabetes, smoking, age, sex, alcohol con-sumption, weight, and height did not differ significantly between the 2 groups (P > 0.05). However, the 2 groups had significant differences in hypertension and body mass in-dex (P < 0.05). Fifty-four percent (27 patients) of patients with IS had an ischemic stroke in large vessels, while 46% (23 patients) had an ischemic stroke in small vessels. Serum levels of ATG5, apo B-48, and oxidative stress markers were higher in the case group than in the control group (P< 0.0001).-CONCLUSIONS: In patients with IS, serum levels of ATG5, apoB-48, malonaldehyde, total oxidative stress, and total antioxidant capacity can be used as novel biomarkers to predict or treat the disease., Tabriz University of Medical Sciences, Tabriz, IRAN [IR.TBZMED.REC.1399.879], This work was supported by a grant from the Vice Chancellor for Research, Tabriz University of Medical Sciences, Tabriz, IRAN. The grant number is IR.TBZMED.REC.1399.879.

The subventricular zone (SVZ) of the lateral ventricles represents a main region where neural stem cells (NSCs) of the mature central nervous system (CNS) reside. Bone Morphogenetic Proteins (BMPs) are the largest subclass of the transforming growth factor-β (TGF-β) superfamily of ligands. BMP4 is one such member and plays important roles in adult NSC differentiation. However, the exact effects of BMP4 on SVZ adult NSCs in CNS ischemia are still unknown. Using oxygen and glucose deprivation (OGD) as an in vitro model of ischemia, we examined the behavior of adult NSCs. We observed that anoxia resulted in reduced viability of adult NSCs, and that BMP4 treatment clearly rescued apoptotic cell death following anoxia. Furthermore, BMP4 treatment exhibited a strong inhibitory effect on cellular proliferation of the adult NSCs in normoxic conditions. Moreover, such inhibitory effects of BMP4 treatment were also found in OGD conditions, despite the enhanced cellular proliferation of the adult NSCs that was observed under such ischemic conditions. Increased neuronal and astroglial commitment of adult NSCs were found in the OGD conditions, whereas a reduction in differentiated neurons and an increase in differentiated astrocytes were observed following BMP4 treatment. The present data indicate that BMP4 modulates proliferation and differentiation of SVZ-derived adult NSCs and promotes cell survival in the in vitro model of ischemic stroke.

Magnetic resonance (MR) imaging (MRI) is commonly used to diagnose, assess and monitor stroke. Accurate and timely segmentation of stroke lesions provides the anatomico-structural information that can aid physicians in predicting prognosis, as well as in decision making and triaging for various rehabilitation strategies. To segment stroke lesions, MR protocols, including diffusion-weighted imaging (DWI) and T2-weighted fluid attenuated inversion recovery (FLAIR) are often utilized. These imaging sequences are usually acquired with different spatial resolutions due to time constraints. Within the same image, voxels may be anisotropic, with reduced resolution along slice direction for diffusion scans in particular. In this study, we evaluate the ability of 2D and 3D U-Net Convolutional Neural Network (CNN) architectures to segment ischemic stroke lesions using single contrast (DWI) and dual contrast images (T2w FLAIR and DWI). The predicted segmentations correlate with post-stroke motor outcome measured by the National Institutes of Health Stroke Scale (NIHSS) and Fugl-Meyer Upper Extremity (FM-UE) index based on the lesion loads overlapping the corticospinal tracts (CST), which is a neural substrate for motor movement and function. Although the four methods performed similarly, the 2D multimodal U-Net achieved the best results with a mean Dice of 0.737 (95% CI: 0.705, 0.769) and a relatively high correlation between the weighted lesion load and the NIHSS scores (both at baseline and at 90 days). A monotonically constrained quintic polynomial regression yielded R

Hypertension is an independent risk factor for thromboembolic events in patients with atrial fibrillation (AF). However, the association between blood pressure (BP) control and thromboembolic events remains under-evaluated in patients with AF. We aimed to identify the relation between BP control and the risk of ischemic stroke and systemic embolism in hypertensive patients with AF. Data on 13,712 consecutive patients with AF (9,505 with and 4,207 without hypertension) were retrospectively analyzed. The hypertensive group was divided into quartiles according to the initial BP, linearly interpolated mean BP, variability independent of the mean of the BP, and time in therapeutic range (lt;130 mm Hg for systolic BP [SBP] andlt;80 mm Hg for diastolic BP) during follow-up. The primary outcome was ischemic stroke and systemic embolism. The mean follow-up duration of the study population was median 2.7 years (interquartile range 1.1 to 4.9 years), and the median number of BP measurements was 14 (interquartile range 6 to 25) times. Strictly controlled initial and interpolated mean BP and low variability in controlled BP (variability independent of the mean) were associated with a lower risk of ischemic stroke and systemic embolism for both SBP and diastolic BP. A similar risk was observed in patients with strictly controlled SBP (time in therapeutic range under 130 mm Hggt;94%) and those without hypertension. In conclusion, continuous and strict maintenance of SBP under 130 mm Hg with low variability at outpatient clinic follow-up reduces the risk of ischemic stroke and systemic embolism in patients with hypertension and AF.

Anemia is associated with higher morbidity and mortality, but its association with acute ischemic stroke (AIS) is not well established. We aim to determine the association of five-day anemia parameters with clinical outcomes in patients with an AIS, depending on their pre-mechanical thrombectomy (MT) collateral status.We performed a retrospective chart review of patients who underwent MT at a comprehensive stroke center from 7/2014 to 12/2020. The patients were divided into good and poor collateral groups depending on their pre-MT collateral status. A blinded board-certified neuroradiologist used collateral grading scale of Maas ≥ 3 to designate good collaterals on the pre-MT CT Angiogram. A binary logistic regression analysis was performed, controlling for the baseline parameters, with the five-day anemia parameters as predictors. The outcomes were functional independence (mRS 0-2), mortality, and early neurological improvement.A total of 220 met the inclusion criteria. 94 (42.72 %) patients had good collaterals, while 126 (57.27 %) patients had poor collaterals. In the multivariable analysis, for patients with good collaterals, the higher values of five-day mean Hb (12.41 ± 1.87 vs 11.32 ± 1.95; OR, 0.72; 95 % CI, 0.54-0.95; P 0.018), five-day mean HCT (37.43 ± 5.1 vs 34.35 ± 5.5; OR, 0.89; 95 % CI, 0.81-0.98; P 0.018) and lower values of the difference between peak and trough values of Hb (1.75 ± 1.15 vs 2.41 ± 1.35; OR, 1.71; 95 % CI, 1.07-2.74; P 0.025) were associated with functional independence. For patients with poor collaterals, there was no association between five-day mean Hb, mean HCT parameters with functional independence, lower mortality, and early neurological improvement.Our study was suggestive of an association between higher mean values of Hb and HCT over a five-day period and good clinical outcomes in patients with good collaterals who undergo MT for an anterior circulation LVO. This association was not found in the poor collateral group.

Patients with nmoyamoya disease (MMD) who present primarily with ischemic stroke are known to have greater rates of perioperative strokes as compared with those who present with nonstroke symptoms. The optimal timing for revascularization for these patients remains unclear.From 1994 to 2015, 91 patients with MMD presented with signs and symptoms of an acute ischemic stroke with diffusion restriction correlate on magnetic resonance imaging, and these patients were subdivided into those who underwent early revascularization (90 days from last stroke), versus those who underwent delayed revascularization (≥90 days after last stroke), based on evidence that most neurological recovery after stroke occurs during the first three months. Perioperative and long-term outcomes were compared between the 2 surgical cohorts.In total, 27 patients underwent early revascularization, and 64 patients underwent delayed revascularization. Patients who underwent early revascularization had a statistically greater rate of perioperative stroke (P = 0.04) and perioperative mortality (P = 0.03), and overall complication rate (P = 0.049). At last follow-up of 5.2 ± 4.3 years, patients who underwent delayed revascularization had a lower mortality rate (P = 0.01) and a lower overall postoperative stroke incidence (P = 0.002). As a function of time, patients with MMD undergoing delayed revascularization had a statistically higher length of stroke-free survival (P = 0.005).Patients with MMD who present with ischemic stroke are more likely to have perioperative strokes, overall perioperative complications, worse long-term mortality rates, and lower rates of stroke-free survival if revascularization surgery occurred within 90 days of last stroke.

The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only.SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017.513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group.CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution.German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Ischemic stroke is caused by the occlusion of cerebral arteries. In the ischemic stroke, ischemia-reperfusion injury increases the damage in the brain after reperfusion. In the previous study, heme oxygenase-1 (HO1) mRNA was delivered into the ischemic brain, showing that HO1-mRNA had higher therapeutic effect and less side-effect than HO1-plasmid (pHO1). However, mRNA is degraded faster than plasmid DNA reducing the duration of gene expression. In this study, self-replicating mRNA (Rep-mRNA) was developed using a replicon system from Venezuelan Equine Encephalitis virus to compensate this disadvantage of mRNA delivery. Deoxycholic acid-conjugated polyethylenimine (DA-PEI) was used as a carrier of the mRNAs. The Rep-mRNA/DA-PEI complex had a size of around 90 nm and a zeta-potential of 33 mV. In the in vitro transfection assays, gene expression by the HO1-Rep-mRNA/DA-PEI complex persisted at least 14 days, while that by the HO1-mRNA/DA-PEI complex approached basal level at 3 days after transfection. Therapeutic effects of the HO1-Rep-mRNA/DA-PEI complexes were evaluated in the ischemic stroke animal model. The complexes were injected into the brain stereotaxically. HO1 expression by the HO1-Rep-mRNA/DA-PEI complex persisted at least 7 days after injection, but the pHO1/DA-PEI or HO1-mRNA/DA-PEI complex showed basal level of HO1-expression at 7 days after injection. Due to higher and longer expression of HO1, the apoptosis level and infarct size were decreased by the HO1-Rep-mRNA/DA-PEI complexes, compared with the pHO1/DA-PEI and HO1-mRNA/DA-PEI complex. These results suggest that HO1-Rep-mRNA/DA-PEI complex may have a potential as a long-lasting therapeutic system for the treatment of ischemic stroke.

Patients who have had a transient ischaemic attack or minor stroke have an increased risk of cardiovascular events for the following 5 years. We aimed to assess 5-year functional outcomes in patients with transient ischaemic attack or minor ischaemic stroke and to determine the factors associated with long-term disability.We analysed data from patients in TIAregistry.org, an international, prospective, observational registry of patients with transient ischaemic attack or minor ischaemic stroke from 61 specialised centres in 21 countries. Patients aged 18 years or older who had a transient ischaemic attack or minor stroke within the previous 7 days between May 30, 2009, and Dec 30, 2011, with a baseline modified Rankin scale (mRS) score of 0-1, and who had been followed up for 5 years, were eligible for inclusion in this study. We evaluated whether existing comorbidities and stroke recurrence, categorised as disabling (mRS score of1, including death) or non-disabling (mRS score of 0-1), at 5 years after baseline, were associated with poor functional outcome (defined as an mRS score of1). We used multivariable generalised equation models for factors associated with poor functional outcome at 5 years and multivariable cause-specific Cox hazard regression models in case of stroke recurrence.Between May 30, 2009, and Dec 30, 2011, 3847 eligible patients were included in the study, 3105 (80·7%) of whom had an mRS evaluation at 5 years of follow-up. Median follow-up duration was 5·00 years (IQR 4·78-5·00). 710 (22·9%) of 3105 patients had an mRS score greater than 1 at 5 years. Factors associated with poor functional outcome at 5 years were older age (per 10-year increase, odds ratio [OR] 2·18, 95% CI 1·93-2·46; p0·0001), diabetes of any type (1·45, 1·18-1·78; p=0·0001), history of stroke or transient ischaemic attack before the qualifying event (1·74, 1·37-2·22; p0·0001), hypertension (1·38, 1·00-1·92; p=0·050), atrial fibrillation or flutter (1·52, 1·04-1·94; p=0·030), congestive heart failure (1·73, 1·22-2·46; p=0·0024), valvular disease (2·47, 1·70-3·58; p0·0001), stroke as qualifying event (1·31, 1·09-1·57; p=0·0037), history of peripheral artery disease (1·98, 1·28-3·07; p=0·0023), history of coronary artery disease (1·32, 1·00-1·74; p=0·049), intracranial haemorrhage during follow up (4·94, 1·91-12·78; p=0·0013), and living alone (1·32, 1·10-1·59; p=0·0031). Regular physical activity before the index event was associated with reduced risk of poor functional outcome (OR 0·52, 95% CI 0·42-0·66; p0·0001). 345 recurrent strokes had occurred at 5 years of follow-up, 141 (40·9%) of which were disabling or fatal. Stroke recurrence increased the risk of having a disability at 5 years (OR 3·52, 95% CI 2·37-5·22; p0·0001). Recurrent disabling or fatal strokes were independently associated with older age (per 10-year increase, hazard ratio [HR] 1·61, 95% CI 1·35-1·92; p0·0001), diabetes of any type (2·23, 1·56-3·17; p0·0001), National Institutes of Health Stroke Scale score of greater than 5 at discharge (5·11, 2·15-12·13; p=0·0013), history of coronary artery disease (1·76, 1·17-2·65; p=0·0063), history of stroke or transient ischaemic attack before the qualifying event (1·54, 1·03-2·29; p=0·035), congestive heart failure (1·86, 1·01-3·47; p=0·044), stroke as qualifying event (1·73, 1·22-2·45; p=0·0024), mRS score of greater than 1 at discharge (2·48, 1·27-4·87; p=0·0083), and intracranial haemorrhage during follow-up (17·15, 9·95-27·43; p0·0001). Regular physical activity before the index event was associated with reduced risk of recurrent disabling stroke at 5 years (HR 0·56, 95% CI 0·31-0·99; p=0·046), and 5-year disability without recurrent stroke (0·61, 0·47-0·79; p=0·0001).We found a substantial burden of disability (mRS score of1) at 5 years after transient ischaemic attack or minor ischemic stroke, and most predictors of this disability were modifiable risk factors. Patients who did regular physical exercise before the index event had a significantly reduced risk of disability at 5 years compared with patients who did no exercise.AstraZeneca, Sanofi, Bristol Myers Squibb, SOS Attaque Cérébrale Association.

Mechanical thrombectomy (MT) has meant a change in natural history of acute ischemic stroke. Our aim is to assess the possible association between different factors and prognosis in patients treated with MT in a third degree Spanish hospital.Cross-sectional study including 198 patients underwent MT because of acute ischemic stroke between 2012 and 2020. Sociodemographic, vascular risk factors (VRF) and clinical-radiologic factors were recorded. Functional outcome was evaluated based on modified Rankin Scale (mRS) at 90 days, being mRS≤2 favorable and mRS≥3 unfavorable outcome.Mean age 67.7±13.5 years, 50.5% women. Arterial hypertension was the most prevalent VRF (65.7%). National Institute of Health Stroke Scale (NIHSS) median value at admission was 17.0 (8.0; 22.0). 40.9% of cases also received fibrinolytic treatment. Conscious sedation was performed in 66.7% patients. Median passes of MT were 2, and median duration 41min. Successful recanalization was achieved in 79.9% and mRS≤2 at 90 days was registered at 59.5% cases. Age, type 2 diabetes (T2D), number of MT passes and procedure duration were associated with mRS≥3. Successful recanalization was associated with mRS≤2. Regression model confirmed these associations in age (OR: 1.56CI%: 1.11; 2.20); T2D (OR: 3.51CI%: 1.38; 8.97) and successful recanalization (OR: 0.07CI%: 0.02; 0.28).Age, T2D and failed recanalization increase risk for unfavorable outcome at 90 days in patients with AIS treated with MT. Procedure time duration should be considered as a possible determinant factor in functional outcome.

Radiation dose associated with computed tomography (CT) perfusion (CTP) may discourage its use despite its added diagnostic benefit in quantifying ischemic lesion volume. Sparse-view CT reduces scan dose by acquiring fewer X-ray projections per gantry rotation but is contaminated by streaking artifacts using filtered back projection (FBP). We investigated the achievable dose reduction by sparse-view CTP with FBP without affecting CTP lesion volume estimations.Thirty-eight consecutive patients with acute ischemic stroke and CTP were included in this simulation study. CTP projection data was simulated by forward projecting original reconstructions with 984 views and adding Gaussian noise. Full-view (984 views) and sparse-view (492, 328, 246, and 164 views) CTP studies were simulated by FBP of simulated projection data. Cerebral blood flow (CBF) and time-to-maximum of the impulse residue function (Tmax) maps were generated by deconvolution for each simulated CTP study. Ischemic volumes were measured by CBF30% relative to the contralateral hemisphere and Tmax6 s. Volume accuracy was evaluated with respect to the full-view CTP study by the Friedman test with post hoc multiplicity-adjusted pairwise tests and Bland-Altman analysis.Friedman and multiplicity-adjusted pairwise tests indicated that 164-view CBF30%, 246- and 164-view Tmax6 s volumes were significantly different to full-view volumes (p0.001). Mean difference ± standard deviation (sparse minus full-view lesion volume) ranged from -1.0 ± 2.8 ml to -4.1 ± 11.7 ml for CBF30% and -2.9 ± 3.8 ml to -12.5 ± 19.9 ml for Tmax6 s from 492 to 164 views, respectively.By ischemic volume accuracy, our study indicates that sparse-view CTP may allow dose reduction by up to a factor of 3.

Decompressive surgery has proven to be lifesaving in patients with a malignant anterior circulation ischemic stroke. Recently, some studies have shown a high frequency of epileptic seizures in patients undergoing this procedure. However, the quantification of this risk and its associated factors have not been extensively investigated.To determine the frequency of epileptic seizures and epilepsy in patients with an anterior circulation ischemic stroke admitted to our Stroke Unit from January 2006 to March 2019 that have been submitted to craniectomy and to study their associated demographic, clinical, imagiological and neurophysiological features.Retrospective observational study of 56 consecutive patients with an anterior circulation ischemic stroke that have undergone craniectomy. The frequency of seizures was both clinically and neurophysiologically assessed after reviewing clinical records, discharge or death reports and all EEGs performed during the hospital admission. Bivariate analysis was used to compare patients with and without seizures.Sixteen patients (28,6%) had epileptic seizures. Bivariate analysis showed an association between the occurrence of unprovoked seizures and the median ASPECTS from the first CT performed.In this study, the frequency of epileptic seizures after a malignant stroke submitted to craniectomy was high, albeit lower than that reported in previous studies. The size of infarction at hospital admission appears to be a risk factor for the occurrence of epilepsy in this group of patients.

Hemorrhagic transformation (HT) is a common complication of ischemic stroke. A growing number of studies have found that serum calcium levels are lower in HT groups than in control groups. However, the relationship between serum calcium and HT remains controversial. We performed a meta-analysis to assess the relationship between serum calcium levels and HT.Electronic databases were searched for studies on serum calcium and HT from inception to November 6, 2021. Ten studies included in present meta-analysis with a total of 3212 participants. Due to the high heterogeneity (ISerum calcium was related to HT and may be one of the risk factors for HT.

Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26–52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose–response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. Findings: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0–4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79–1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93–1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85–1·32]; t statistic –0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91–2·71]). Interpretation: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. Funding: Bayer AG.

Transradial access has been described for mechanical thrombectomy in acute stroke, and proximal balloon occlusion has been shown to improve recanalization and outcomes. However, sheathed access requires a larger total catheter diameter at the access site. We aimed to characterize the safety of sheathless transradial balloon guide catheter use in acute stroke intervention.Consecutive patients who underwent sheathless right-sided transradial access for thrombectomy with a balloon guide catheter were identified in a prospectively collected dataset from 2019 to 2021. Demographics, procedure details, and short-term outcomes were collected and reported with descriptive statistics.A total of 48 patients (20 women) with a mean age of 72.3 years were identified. Of patients, 56.3% had occlusions in the left-sided circulation; 35 (72.9%) had M1 occlusions, 7 (14.6%) had M2 occlusions, and 6 (12.5%) had internal carotid artery occlusions. Tissue plasminogen activator was administered to 16 (33.3%) patients. Five (10.4%) patients underwent intraprocedural carotid stenting. The cohort had successful reperfusion after a median of 1 (interquartile range: 1, 2) pass. Median time from access to recanalization was 31 (interquartile range: 25, 53) minutes. A postprocedural Thrombolysis In Cerebral Infarction score of ≥2b was achieved in 46 (95.8%) patients. Five patients had wrist access site hematomas. All hematomas resolved with warm compresses, and no further intervention was required.Sheathless radial access using a balloon guide catheter may be safely performed for acute ischemic stroke with excellent radiographic outcomes. Further investigation is warranted to evaluate the comparative effectiveness of sheathless compared with sheathed transradial balloon guide access.

Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death.To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes.We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72-120 h after stroke onset. A 30-min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes.During an estimated median follow-up time of 48 days (IQR, 18-312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D-dimer (HR 1.6; 95% CI 1.2-2.0), P-selectin (HR 1.9; 95% CI 1.4-2.7), sICAM-1 (HR 2.2; 95% CI 1.6-3.1), sVCAM-1 (HR 1.6; 95% CI 1.2-2.1), and microemboli (HR 2.2; 95% CI 1.1-4.5) were associated with the primary outcome, whereas thrombin-antithrombin and thrombomodulin were not. D-dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0-1.5). Results were generally consistent in analyses adjusted for important prognostic variables.Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer-related stroke.

Ischemic stroke is a cerebrovascular disease which is related to brain function loss induced by cerebral ischemia. Translocator protein (TSPO) is an important regulator in inflammatory diseases, while its role in ischemic stroke remains largely unknown. This research aimed to explore the role and action mechanism of TSPO in oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuron cell damage. The differentially expressed genes in ischemic stroke were predicted using GSE140275 dataset, DisGeNet, and GeneCards databases. Differentiated SH-SY5Y cells and primary neurons were subjected to transfection, and stimulated with OGD/R or MCC950 (NLRP3 inhibitor). Proteins were detected by western blotting and ELISA. Cell apoptosis was evaluated through CCK-8, caspase-3 activity and TUNEL assays. TSPO was upregulated in ischemic stroke and in SH-SY5Y cells and primary neurons after OGD/R treatment. TSPO silencing attenuated OGD/R-induced inflammation and apoptosis by decreasing NLRP3 inflammasome activity. TSPO downregulation increased PPARγ expression and decreased HMGB1 expression in OGD/R-treated cells, which was reversed by silencing PPARγ. PPARγ knockdown abolished the effect of TSPO silence on NLRP3 inflammasome activity, inflammation, and cell apoptosis in OGD/R-treated cells, while PPARγ overexpression alleviated OGD/R-induced injury in SH-SY5Y cells. In conclusion, TSPO knockdown attenuates neuroinflammation and neural apoptosis by decreasing NLRP3 inflammasome activity through PPARγ pathway.

Carnitine biosynthesis has been related to fatty acid oxidation, a process probably exerting neuroprotective effects. However, the role of carnitine biosynthesis in the development of ischemic stroke (IS) remains unclear. We aimed to examine the associations between plasma markers of carnitine biosynthesis and the IS risk.We performed a case-control study nested in a community-based cohort (2013-2018, n = 16457). The study included 321 incident cases of IS and 321 controls matched by age and gender. Carnitine, lysine, trimethyllysine (TML), glycine, and their ratios were measured/calculated in the baseline plasma samples using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).Plasma carnitine, lysine, TML, and glycine were not significantly associated with the IS risk, although a gradually reduced risk was observed across the increasing tertiles of glycine. Notably, the ratios of glycine/carnitine, glycine/lysine, and glycine/TML were all inversely associated with the IS risk. Compared to the lowest tertiles, the corresponding odds ratios for the highest tertiles were 0.60 (95% CI: 0.40-0.91), 0.63 (95% CI: 0.42-0.94), and 0.63 (95% CI: 0.42-0.95), respectively, after adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate and total cholesterol. Repeating the analyses by excluding the first two years of follow-up did not materially alter the risk associations for the ratios of glycine/lysine and glycine/carnitine.Increased ratios of plasma glycine to carnitine, lysine, and TML were associated with a lower risk of incident IS. Our observational findings suggest that the homeostasis of circulating carnitine, lysine, TML, and glycine may involve in the pathogenesis of IS.

Long non-coding RNA H19 (lncRNA H19) is transcribed from the H19 gene. We previously reported the role of lncRNA H19 in the pathogenesis of cerebral ischemic stroke. The present study aimed to elucidate the relationship between lncRNA H19 and blood-brain barrier breakdown induced by cerebral ischemic stroke. We observed that plasma levels of lncRNA H19 were positively associated with the extent of blood-brain barrier damage. In cellular co-culture models, neurons expressed and transported lncRNA H19 to astrocytes via exosomes and contributed to an increase in endothelium permeability induced by oxygen-glucose deprivation. Inhibition of neuronal exosomal lncRNA H19 regulated astrocytic microRNA (miR)-18a and vascular endothelial growth factor (VEGF) expression. Further, lncRNA H19 induced a decrease in tight junction proteins expression via the lncRNA H19/miR-18a/VEGF axis. This study highlights the transportation of lncRNA H19 by exosomes and the relationship between lncRNA H19 and blood-brain barrier breakdown.

South Asia is responsible for more than 40% of the stroke burden and stroke mortality in the developing world. South Asia, which is home to one-fourth of the world's population, is the most densely populated and one of the poorest regions. The majority of patients in this region are unable to afford intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). If low-dose alteplase proves effective and safe in South Asians, it may be a more cost-effective treatment option.The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Researchers searched PubMed, EMBASE, and Google Scholar for English literature from 2005 to 2021. END, ENI, good functional outcome, SICH, and all-cause mortality were used to assess efficacy and safety.In the low-dose alteplase treated patients, different studies reported 32 to 57% ENI 24 h after IVT, and 7% to 9.7% END. At 3 months follow-up, good functional outcome was achieved by 48%-76.92% of low-dose alteplase treated patients. SICH rates ranged from 0% to 16.6% across studies. Asymptomatic ICH occurred in 5-14% of patients. The mortality rate in all included studies varied from none to 25%.Our systematic review demonstrates that the use of low-dose alteplase for AIS in the South Asians offer comparable efficacy and reduced risk of SICH at a significantly lower cost than standard alteplase dose. Future well-randomized clinical trials are necessary to validate the findings of our study.

Early glycemic variability (GV) in diabetic patients is a poor prognosis factor following cardiovascular events. However, its influence on the course of acute ischemic stroke (AIS) with large vessel occlusion remains unclear. We investigated the relationship between high GV during acute stroke and three-month functional outcome among patients treated with combined intravenous thrombolysis and endovascular therapy for large vessel occlusion.A single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent thrombolysis and mechanical thrombectomy between January 2015 and May 2017. Early GV was assessed using standard deviation (SD) of blood glucose levels for the first 24hours. The main outcome was functional status at three months as defined by the modified Rankin scale (mRS). Secondary outcomes were change in NIHSS score from baseline to 24hours and occurrence of severe hemorrhagic transformation. Multivariate logistic regression analyses including GV, admission glycemia and mean glycemia were performed.Among the 93 patients evaluated, 26 had early high GV (≥20.9mg/dl). High GV was associated with poor functional outcome (OR=8.00; 95%CI [1.34-47.89]; P=0.02) unlike admission glycemia and mean glycemia (OR=2.92; 95%CI [0.51-16.60]; P=0.23 and OR=0.36; 95%CI [0.05-2.6]; p=0.31, respectively). High GV was not associated with NIHSS at 24hours or hemorrhagic transformation.Acute high GV contributes to poorer functional outcome following AIS related to large vessel occlusion and should be considered as a new target in acute stroke management.

Identifying biomarkers of subclinical atrial fibrillation (AF) is of most interest in patients with cryptogenic stroke (CrS). We sought to evaluate the circulating microRNA (miRNA) profile of patients with CrS and AF compared with those in persistent sinus rhythm.Among 64 consecutive patients with CrS under continuous monitoring by a predischarge insertable monitor, 18 patients (9 with AF and 9 in persistent sinus rhythm) were selected for high-throughput determination of 754 miRNAs. Nine patients with concomitant stroke and AF were also screened to improve the yield of miRNA selection. Differentially expressed miRNAs were replicated in an independent cohort (n=46). Biological markers were stratified by the median and included in logistic regression analyses to evaluate their association with AF at 6 and 12 months.Eight miRNAs were differentially expressed between patients with and without AF. In the replication cohort, miR-1-3p, a gene regulator involved in cardiac arrhythmogenesis, was the only miRNA to remain significantly higher in patients with CrS and AF vs those in sinus rhythm and showed a modest association with AF burden. High (= above the median) miR-1-3p plasma values, together with a low left atrial ejection fraction, were independently associated with the presence of AF at 6 and 12 months.In this cohort, plasma levels of miR-1-3p were elevated in CrS patients with subsequent AF. Our results preliminarily suggest that miR-1-3p could be a novel biomarker that, together with clinical parameters, could help identify patients with CrS and a high risk of occult AF.

Advanced interatrial block has been linked with atrial fibrillation (AF) (Bayes syndrome). On the other hand, the aetiology of the stroke remains unknown in approximately 20-25% of patients admitted due to ischaemic stroke. The aim of this study was to evaluate whether advanced interatrial block and CHADS2-VASC scale is linked to AF in patients admitted due to ischaemic stroke without previous AF history.A prospective analysis of consecutive in-hospital patients admitted with ischemic stroke between January/2018 and April/2019 in a stroke hospital was performed. Patients had to be in sinus rhythm at admission and without previous history of AF/atrial flutter. During follow up patients receive the usual care.A total of 236 patients were included. The median follow-up was 540 days (407-695). 19 patients (8.1%) had advanced interatrial block at admission. Advanced interatrial block was associated with the diagnosis of AF during follow up (5 (26.3%) Vs 21 (9.7%) p=0.027). A CHADS2-VASC score4 at admission was also associated with AF diagnosis during follow up (23(14.6%) vs 3(3.9%) p=0.009).This study confirms the association of advanced interatrial block and CHADS2-VASC4 at admission with the diagnosis of AF during follow up in patients with ischemic stroke. This association could have important implications in patients with ischemic stroke who present advanced interatrial block and without previous history of AF.

BACKGROUND AND PURPOSE In patients with acute ischemic stroke (AIS) and a large vessel occlusion (LVO), thrombus migration (T-Mig) is a common phenomenon before mechanical thrombectomy (MT), revealed by pre-treatment imaging. Previous works have used qualitative scales to define T-Mig. The aim of this study was to evaluate the determinants and impact of quantitatively assessed T-Mig on procedural characteristics and clinical outcome. METHODS Consecutive patients with AIS due to LVO treated by MT at a reference academic hospital were analysed. Distance between vessel origin and beginning of the thrombus on MRI (3D-time-of-flight and/or contrast-enhanced magnetic-resonance-angiography) and digital-substracted-angiography (DSA) were measured in millimeters using a curve tool. Thrombus migration was defined quantitatively as ∆TD calculated as the difference between pre-MT-DSA and MRI thrombus location. ∆TD was rated as significant if above 5mm. RESULTS A total of 267 patients were included (mean age 70±12 years; 46% females) were analyzed. Amongst them, 65 (24.3%) experienced any degree of T-Mig. T-Mig was found to be associated with iv-tPA administration prior to thrombectomy (β-estimate 2.52; 95% CI [1.25-3.79]; p

Effective high density lipoprotein cholesterol (HDL-C) is a measure of HDL functionality. We evaluated if HDL-C is associated with carotid intima-media thickness (cIMT) and incident major adverse cardiovascular events (MACE) in patients with acute ischemic stroke from two prospective cohort studies.In the MARK-STROKE cohort, 299 patients with acute ischemic stroke or TIA were included. Outcome was available in 219 patients during a median follow-up of 294 days. In CIRCULAS, 382 acute ischemic stroke patients were included and a 90-day follow-up was available in 213 patients. HDL-C was calculated based on symmetric dimethylarginine (SDMA) and HDL cholesterol concentrations. Main outcome was incident MACE (death, stroke, and myocardial infarction) and the main measure was cIMT.In both studies, HDL-C was inversely associated with cIMT in linear regression analysis adjusted for age, sex and creatinine. In MARK-STROKE, the adjusted hazard for MACE was significantly reduced for patients with one unit increase (mg/dL) of HDL-C (hazard ratio 0.95 [95% confidence interval (CI): 0.92, 0.99]). In the CIRCULAS cohort, stroke patients with higher HDL-C had less incident MACE during 90 days of follow-up (odds ratio: 0.97 [95% CI: 0.94, 0.99] for one unit increase). Neither SDMA nor HDL cholesterol predicted outcome.Our findings imply a protective role of biologically effective HDL after acute cerebral ischemia for secondary events and emphasize the relevance of lipoprotein functionality in these patients.