Search

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.

Aneurysmal subarachnoid hemorrhage (SAH) continues to be a difficult cerebrovascular disease with limited pharmacologic treatment options. Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are leading causes of morbidity and mortality after SAH. Despite the advances in the understanding of its pathophysiology and tremendous efforts to date, nimodipine is currently the sole Food and Drug Administration-approved treatment for patients with SAH, with benefits that are marginal at best. The neuromodulation therapies are promising, especially those that target CV and DCI to improve functional outcomes. The aim of this review is therefore to summarize the available evidence for each type of neuromodulation for CV and DCI, with a special focus on its pathophysiological mechanisms, in addition to their clinical utility and drawbacks, which we hope will lead to future translational therapy options after SAH.We conducted a comprehensive review of preclinical and clinical studies demonstrating the use of neuromodulation for SAH. The literature search was performed using PubMed, Embase, and ClinicalTrials.gov. A total of 21 articles published from 1992 to 2021 and eight clinical trials were chosen.The studies reviewed provide a compelling demonstration that neuromodulation is a potentially useful strategy to target multiple mechanisms of DCI and thus to potentially improve functional outcomes from SAH. There are several types of neuromodulation that have been tested to treat CV and DCI, including the trigeminal/vagus/facial nerve stimulation, sphenopalatine ganglion and spinal cord stimulation, transcranial direct electrical stimulation, transcutaneous electrical neurostimulation, and electroacupuncture. Most of them are in the preclinical or early phases of clinical application; however, they show promising results.DCI has a complex pathogenesis, making the unique anatomical distribution and pleiotropic capabilities of various types of neuromodulation a promising field of study. We may be at the cusp of a breakthrough in the use of these techniques for the treatment of this stubbornly difficult disease.

A systematic review was conducted to investigate prevalence, management and outcomes of atrial fibrillation (AF) in people with Serious Mental Illnesses (SMI) versus the general population.MEDLINE, EMBASE, and PsycINFO were searched for primary research written in English and published between 2004 and 2022.A total of 1459 studies were identified in the initial search of which 16 met the inclusion criteria. Studies (n = 4) reporting on ischaemic stroke and major bleeding events were included in the meta-analysis.Two independent reviewers extracted data and assessed risk of bias using the Newcastle-Ottawa Scale. Discrepancies were resolved by consulting a third reviewer.Low rates of AF were reported among people with SMI suggesting under-recognition or recording gaps. People with SMI and AF were less likely to receive oral anticoagulation therapy compared to the general population. When receiving warfarin, those with bipolar disorder experienced poor anticoagulation control as measured by time in INR therapeutic range. Pooled analysis of risk estimates showed that in patients with identified AF, SMI was not significantly associated with an increased risk of stroke (HR: 1.09; 95%CI: 0.85 to 1.40; IMore research is needed to examine the prevalence, management and outcomes of AF in this population, and to evaluate the effect of the introduction of the novel anti-coagulants on these metrics over time.

Objective Middle cerebral artery aneurysms (MCAas) with rupture and unruptured IAs are considered good candidates for microsurgery. The objective of the present study was to evaluate the risk of complications and the risk factors for microsurgical treatment of MCAas to better define the indications for microsurgery. Methods We conducted a retrospective cohort study based on data provided from three French tertiary neurosurgical units from January 1, 2013 to May 31, 2020. We first collected data on all the patients who required microsurgical treatment for MCAas. We evaluated the frequency of complications and finally searched for the risk factors for complications after microsurgery. Complications were defined as a composite criterion with the presence of one of the following: procedural-related death, symptomatic cerebral ischemia, impossible exclusion, incomplete exclusion, or (re)bleeding of the treated aneurysm and symptomatic surgical site hematoma. We then compared patients with and without complications using univariate and multivariate analyses. Results Between January 2013 and May 2020, 292 MCAas in 284 patients were treated. A total of 29 (9.9%) MCAas had a complication. The complications were as follows: symptomatic cerebral ischemia: 4.8%, aneurysm rebleeding: 0.3%, surgical site hematoma: 1.0%, impossible exclusion: 0.3%, and incomplete exclusion: 4.1%. However, severe complications, defined as death or a modified Rankin score (mRs) score ≥4 at 3 months, were infrequent and occurred in 7/292 patients (2.4%). In the multivariate analysis, independent risk factors for complications were the following: a ruptured aneurysm, a larger maximum IA size, a larger neck size, and arterial branches passing less than

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.

Cerebral ischemia-reperfusion injury (CI/RI) injury is a common feature of ischemic stroke which occurs when the blood supply is restored after a period of ischemia in the brain. Reduced blood-flow to the brain during CI/RI compromises neuronal cell health as a result of mitochondrial dysfunction, oxidative stress, cytokine production, inflammation and tissue damage. Reperfusion therapy during CI/RI can restore the blood flow to ischemic regions of brain which are not yet infarcted. The long-term goal of CI/RI therapy is to reduce stroke-related neuronal cell death, disability and mortality. A range of drug and interventional therapies have emerged that can alleviate CI/RI mediated oxidative stress, inflammation and apoptosis in the brain. Herein, we review recent studies on CI/RI interventions for which a mechanism of action has been described and the potential of these therapeutic modalities for future use in the clinic.

This study intends to investigate the potential involvement of E3 ubiquitin ligase COP1 in cerebral ischemia-reperfusion (I/R) injury.A mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established, and the ischemic penumbra of mouse brain cortex was collected and subjected to RNA-sequencing (RNA-seq). Primary glial cells, neurons and astrocytes were isolated, and microglia were exposed to oxygen and glucose deprivation/reperfusion (OGD/R).COP1 was poorly expressed in MCAO mice and OGD/R microglia. Restoration of COP1 suppressed the activation of microglia and relieves neuroinflammation in cerebral I/R injury, leading to alleviated brain damage (infraction volume [%]: [31.58 ± 2.96][12.06 ± 1.29], neurological scores: [3.6 ± 0.6][1.2 ± 0.5]). COP1 promoted the ubiquitin-mediated degradation of C/EBPβ in microglia. It was further revealed that COP1 attenuated microglia activation and phagocytosis (Iba + cells [N/mmThis study illuminated a mechanism by which COP1 conferred a neuroprotective role in cerebral I/R injury via enhancing the ubiquitin-mediated degradation of transcriptional factor C/EBPβ in microglia.

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.

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.

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.

Respiratory infection can be an immediate precursor to stroke and myocardial infarction. Influenza vaccination is associated with reduced risk of myocardial infarction and hospitalisation for cardiac disease, and influenza vaccination is strongly recommended for patients with heart disease. Evidence on whether the same protective association exists for stroke, and whether this potential effect is consistent across age and risk groups, is conflicting. We aimed to assess the risk of stroke after influenza vaccination in adults.We obtained administrative data from the Alberta Health Care Insurance Plan (which covers all residents of Alberta, Canada) beginning on Sept 30, 2009, or May 15 of the year in which residents were recorded as being 18 years of age. Individuals were censored at the earliest of three events: death, recorded outmigration, or Dec 31, 2018. The outcome of interest was any stroke event, comprising acute ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and transient ischaemic attack. We used Andersen-Gill Cox models to analyse the hazard of any stroke event for individuals with recent (lt;182 days) influenza vaccination compared with those without recent influenza vaccination, with adjustment for age, sex, anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, hypertension, income quintile, and rural or urban home location. Two-way interaction terms between each individual covariate and vaccination status were used to assess for effect modification by risk factor. The association between vaccination and risk of each type of stroke was also modelled, adjusting for baseline covariates.The study sample consisted of 4 141 209 adults (29 687 899 person-years of observation time) registered under the provincial health-care system between Sept 30, 2009, and Dec 31, 2018. 1 769 565 (42·73%) individuals received at least one vaccination during the study period, and 38 126 stroke events were recorded. Adjusted for demographics and comorbidities, recent influenza vaccination significantly reduced the hazard of stroke (hazard ratio 0·775 [95% CI 0·757-0·793]). This association persisted across all stroke types. We found effect modification by each covariate examined except for home location; however, vaccination was associated with a reduced risk of stroke overall across all ages and risk profiles with the exception of individuals without hypertension.The risk of stroke is reduced among people who have recently been vaccinated against influenza compared with those who have not. This association extended to the entire adult population and was not limited to individuals with a baseline high risk of stroke. Further studies in a variety of settings are needed to evaluate whether influenza vaccination could be used as a public health strategy to prevent stroke.None.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a leading complication of aneurysmal subarachnoid hemorrhage (SAH) and electroencephalography (EEG) is increasingly used to evaluate DCI risk. Our goal is to develop an automated DCI prediction algorithm integrating multiple EEG features over time. METHODS: We assess 113 moderate to severe grade SAH patients to develop a machine learning model that predicts DCI risk using multiple EEG features. RESULTS: Multiple EEG features discriminate between DCI and non-DCI patients when aligned either to SAH time or to DCI onset. DCI and non-DCI patients have significant differences in alpha-delta ratio (0.08 vs 0.05, p < 0.05) and percent alpha variability (0.06 vs 0.04, p < 0.05), Shannon entropy (p < 0.05) and epileptiform discharge burden (205 vs 91 discharges per hour, p < 0.05) based on whole brain and vascular territory averaging. Our model improves predictions by emphasizing the most informative features at a given time with an area under the receiver-operator curve of 0.73, by day 5 after SAH and good calibration between 48–72 hours (calibration error 0.13). CONCLUSIONS: Our proposed model obtains good performance in DCI prediction. SIGNIFICANCE: We leverage machine learning to enable rapid, automated, multi-featured EEG assessment and has the potential to increase the utility of EEG for DCI prediction.

DJ-1 plays a neuroprotective role in cerebral ischemia- reperfusion (I/R) injury and participates in the apoptosis of brain nerve cells, but the underlying mechanism is unclear. We explored the molecular pathways underlying this role using in vivo and in vitro approaches. Middle cerebral artery occlusion- reperfusion (MCAO/R) rat models and oxygen- glucose deprivation- reoxygenation (OGD/R) HAPI cell cultures were used to simulate cerebral ischemia-reperfusion injury. The interaction between DJ-1 and Notch1 was enhanced after MCAO/R in rats. After treatment of rats with DJ-1 siRNA, the expression of Notch1 and Nrf2 was down-regulated, and apoptosis was promoted. In contrast, the DJ-1 based peptide ND-13 upregulated the expression of Notch1 and Nrf2, and prevented apoptosis. In vitro, the Notch1 signaling pathway inhibitor DAPT reversed the neuroprotective effect of ND-13 and promoted apoptosis, weakened the interaction between DJ-1 and Notch1, and decreased the expression of proteins in the Notch1 and Nrf2 pathways. Thus, we found that DJ-1 inhibits apoptosis by regulating the Notch1 signaling pathway and Nrf2 expression in cerebral I/R injury. These results imply that DJ-1 is a potential therapeutic target for cerebral I/R injury.

Efficacy of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) is strongly time dependent in acute stroke management. We investigated the impact of a direct magnetic resonance imaging (MRI) room admission protocol in order to reduce in-hospital delays.We implemented a protocol of direct MRI room admission, bypassing the Emergency Department. We compared in-hospital delays, clinical and functional outcomes using National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores, between patients hospitalized via this protocol and those admitted via the standard workflow and treated by IVT and/or MT. The primary endpoint was the proportion of patients with door-to-needle time (DTN) ≤ 60minutes.Among 308 consecutive patients included, 62 underwent direct MRI room admission. The proportion of patients with DTN ≤ 60minutes was higher in the intervention group compared to the control group (82.5% vs. 17.8%, P0.001), and median DTN was lower (45min vs. 75min, P0.001). Despite a functional benefit at discharge on dichotomized mRS (mRS [0-2, as independence]: 66.1% vs. 51.2%, P=0.003), the difference was no longer statistically significant at six months (68.4% vs. 57.4%, P=0.10).Direct MRI room admission of stroke alerts is associated with an important reduction of treatment times and improves functional outcomes.

Numerous studies report poorer outcomes after mechanical thrombectomy (MT) in elderly patients than in non-elderly patients. We aimed to investigate the changes in neurological symptoms after MT in elderly patients.We included 151 patients with acute stroke who independently performed activities of daily living before admission, underwent MT at our hospital between January 1, 2019 and December 31, 2021, and had successful recanalization (thrombolysis in cerebral infarction grade2b). The subjects were divided into two groups according to whether they were aged ≥80 years (elderly group) or80 years (non-elderly group), and the National Institutes of Health Stroke Scale (NIHSS) scores and deep and subcortical white matter hyperintensity (DSWMH) grades were compared between both groups.There were 57 (38 %) and 94 (62 %) patients in the elderly and non-elderly groups, respectively. After propensity score matching, the median (interquartile range) NIHSS scores were significantly higher in the elderly group than in the non-elderly group at both 24 h (12 [5.5-19] vs 8; [2-14] P = 0.040) and 1 week (8 [3-12] vs 2.5 [0-13.5]; P = 0.041) after MT but not before MT (18 [13.5-22.5] vs 20 [14.5-24]; P = 0.549). DSWMH grades were significantly higher in the elderly group than in the non-elderly group (2 [1-3] vs 1 [0-2]; P = 0.018).MT in the elderly group was associated with poorer improvement in neurological symptoms from the early period after MT than in the non-elderly group, even when successful recanalization was achieved. White matter lesions may contribute to the poor neurological improvement after recanalization in the elderly group.

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.

Ligustrazine is a traditional Chinese herbal medicine that has long been used to treat cerebral ischemic disorders. However, the molecular mechanisms of ligustrazine in cerebral ischemia/reperfusion (I/R) damage have not been clear elucidated. The aim of this study was to examine the neuroprotective mechanisms of ligustrazine in cerebral I/R.9 C57BL/6 mice were randomly divided to three groups: Sham group (n = 3), Middle cerebral artery occlusion (MCAO) group (n = 3), and MCAO + Ligustrazine group (n = 3). The neurological deficit score was evaluated, the cerebral infarct volume was measured by triphenylterazolium chloride (TTC) staining. Differentially expressed (DE) messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were analyzed using the R package DEseq2 based on P-value 0.05 and Log2 |fold change (FC)| ≥ 2 in sham group vs MCAO group and MCAO group vs ligustrazine group by high-throughput sequencing. Function enrichment analysis, the protein-protein interaction (PPI) of neurogenesis related genes were performed. The neurogenesis related competitive endogenous RNA (ceRNA) network was constructed.The expression of circ_0008146 was considerably higher in the MCAO group than the Sham group, and ligustrazine treatment markedly decreased the expression of circ_0008146 in MCAO. Next, the circ_0008146 ceRNA network was established, including circ_0008146-miR-709-Cx3cr1 ceRNA network. Besides, real time quantitative polymerase chain reaction (RT-qPCR) assay identified that miR-709 expression was considerably lower and Cx3cr1 expression was higher in the MCAO group than Sham group, and ligustrazine treatment markedly increased the miR-709 expression and reduced Cx3cr1 expression in MCAO. Further, silencing of circ_0008146 inhibited the concentration of Interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-α) and reduced neuron cell death and up-regulated miR-709 expression and down-regulated Cx3cr1 expression in Lipopolysaccharide (LPS) induced BV-2 cells. Dual-Luciferase reporter gene assay verified that circ_0008146 targeted miR-709.Ligustrazine targets circ_0008146/miR-709/Cx3cr1 axis to inhibit cell apoptosis and inflammation after cerebral ischemia/reperfusion injury.

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.

Reperfusion is critical for improving outcomes of patients experiencing ischemic stroke. Increasing evidence supports tenecteplase as an alternative to alteplase, with many potential benefits. This article discusses the current state of the evidence for intravenous reperfusion and considers strategies for improving access, including possible modifications to efficacy-related regulatory updates.

Objectives This study aimed to determine the incidence and trends of cerebrovascular disease (CVD) in the healthcare district of Lleida. Material and methods We performed a population-based prospective cohort study including the entire population of the healthcare district of Lleida (440 000 people). Information was gathered from the minimum basic data set from the emergency department and hospital discharges for the period from January 2010 to December 2014. All types of stroke were included. We evaluated crude and age-standardised rates using the world population as a reference. Patients without neuroimaging confirmation of the diagnosis were excluded. Results We identified 4397 patients: 1617 (36.8%) were aged 80 years or over; 3969 (90.3%) presented ischaemic stroke, and 1741 (39.6%) were women. The crude incidence rate ranged from 192 (95% confidence interval [CI], 179-205) to 211 (95% CI, 197-224) cases per 100 000 population, in 2012 and 2013, respectively. Age-standardised rates ranged from 93 (95% CI, 86-100) to 104 (95% CI, 96-111) cases per 100 000 population, in 2012 and 2013, respectively. For all years, incidence rates increased with age, and were significantly higher among men than among women. Conclusion The impact of CVD in Lleida is comparable to that observed in other European regions. However, population ageing induces a high crude incidence rate, which remained stable over the five-year study period.

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.

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).

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.

Acute basilar artery occlusions (BAO) are associated with poor outcome despite modern endovascular treatment (EVT). The best anesthetic management during EVT is not known and may affect the procedure and clinical outcome. We compared the efficacy and safety of general anesthesia (GA) and conscious sedation/local anesthesia (CS/LA) in a large cohort of stroke patients with BAO treated with EVT in current clinical practice.Data from the ongoing prospective multicenter Endovascular Treatment In Ischemic Stroke Registry of consecutive acute BAO patients who had EVT indication from January 1st, 2015, to December 31st, 2021, were retrospectively analyzed. Two groups were compared: patients treated with CS/LA versus GA (both types of anesthesia being performed in the angiosuite). Good outcome was defined as modified Rankin Scale (mRS) score 0-3 at 90 days.Among the 524 included patients, 266 had GA and 246 had CS/LA (67 LA). Fifty-three patients finally did not undergo EVT: 15 patients (5.9%) in the GA group and 38 patients (16.1%) in the CS/LA group (P 0.001). After matching, two groups of 129 patients each were retained for primary analysis. The two groups were well balanced in terms of baseline characteristics. After adjustment, CS/LA compared to GA was not associated with good outcome (OR=0.90 [95%CI 0.46-1.77] P=0.769) or mortality (OR=0.75 [0.37-1.49] P=0.420) or modified thrombolysis in cerebral infarction score 2b-3 (OR=0.43 [0.16-1.16] P=0.098). On mixed ordinal logistic regression, the modality of anesthesia was not associated with any significant change in the overall distribution of the 90-day mRS (adjusted OR=1.08 [0.62-1.88] P=0.767).Safety, outcome and quality of EVT under either CS/LA or GA for stroke due to acute BAO appear similar. Further randomized trials are warranted.

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.

Expert physiological and pharmacological care by anaesthetists is required in all stroke endovascular thrombectomy cases. RCTs show clinical benefits in recanalisation rates and functional recovery after endovascular thrombectomy with general anaesthesia compared with sedation. Many stroke centres will require wholesale reorganisation of stroke pathways to ensure anaesthesia services are available for all cases. Anaesthetists have an integral role in improving clinical outcomes in large vessel occlusion stroke.

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.

This study aims to assess the safety of upper extremity access with surgical exposure of the axillary artery in fenestrated and branched endovascular aneurysm repair (F/B-EVAR), evaluating neurological and local complications as well as re-interventions associated with the technique.All patients undergoing an F/B-EVAR procedure with surgical exposure of the axillary artery between January 2010 and March 2020 were included in this retrospective single centre study. Endpoints were neurological and access related complications and re-interventions related to the upper extremity access. Complications related to the technique included stroke/transient ischaemic attack, wound infection, peripheral nerve injury, and arterial complications.264 patients (192 male, mean age 70 ± 7 years) were included. Upper extremity access was performed over the left axillary artery in 257 (97%) of the cases, and over the right axillary artery in the remaining seven cases. Six (2.2%) patients had early complications related to the arterial access: four with post-operative bleeding and two with acute arm ischaemia. Two patients with post-operative bleeding and both patients with ischaemic complications required re-intervention. One of these patients with arm ischaemia died five weeks after the re-intervention due to sepsis complications related to patch infection. Sixteen (6%) patients presented with transient arm paraesthesia or sensory neurological deficit post-operatively. The symptoms completely recovered in all cases with no residual deficits. Peri-operative ischaemic stroke occurred in three (1%) patients (two minor, one major). No other access related complications were recorded during follow up in any of the patients with no cases of late stenosis/occlusion.Upper extremity access with surgical exposure of the axillary artery is a safe method for antegrade catheterisation of fenestrations and branches in complex endovascular aneurysm repair.

Considerable amounts of oxidants are produced in cerebral ischemia, where oxidative stress plays a key role in neuronal damage after ischemia. Klotho, an anti-aging protein, alleviates oxidative stress by activating the transcription of an important antioxidant enzyme, manganese superoxide dismutase (MnSOD), in the nervous system. Thus, increased Klotho expression level could lead to a reduction in neuronal damages after brain ischemia via lowering oxidative stress. It is known that physical activity increases Klotho expressions. In this study, we assessed neuroprotective effects of preconditioning exercise in rats (treadmill running at a speed of 20 m/min,30 min/day, six days/week, for3 weeks) on hippocampal Klotho and MnSOD expression in the brain using an animal model of stroke, middle cerebral artery occlusion (MCAO). Our study revealed a reduction in hippocampal Klotho and MnSOD expression as well as CA1 neuronal activity in MCAO compared to the sham group. Exercise prevented the ischemia-induced decline in Klotho and MnSOD expression levels as well as CA1 neuronal activity in Exercise + MCAO compared to the MCAO group. Also, exercise significantly improved the neurological scores and reduced brain infarction area in Exercise + MCAO in comparison to MCAO group. There was a post-ischemia deficit in the working memory, as measured by spontaneous alternation percentage using Y-maze test, in MCAO compared to the sham group. The latter effect was not observed in the Exercise + MCAO group, which could be related to an increase in the antioxidant capacity as exhibited by Klotho and MnSOD up-regulation. The results were confirmed with a positive correlation between Klotho expression and MnSOD expression which allows proposing Klotho as a potential neuroprotective protein in ischemic stroke with respect to antioxidant defense. In general, the present study suggested that preconditioning exercise induced upregulation of Klotho and MnSOD, as well as attenuated the post-ischemic injuries. The upregulation of Klotho might be an underlying mechanism by which preconditioning exercise plays as a neuroprotective factor against post-ischemic neural injuries in ischemic rats.

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.

Inflammation and oxidative stress are associated with the pathogenesis of cerebral ischemia-reperfusion (I/R) injury. Fraxin, one of the primary active ingredients of Cortex Fraxini, may have potent anti-inflammatory activity. This study intended to investigate the function and mechanism of fraxin in a middle cerebral artery occlusion (MCAO) model.A middle cerebral artery occlusion (MCAO) rat model was engineered. Both in-vivo and in-vitro models were dealt with Fraxin. The profiles of inflammation-concerned cytokines, proteins and oxidative stress factors were determined by RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA), and neuronal apoptosis and reactive oxygen species (ROS) levels were measured. The neurological functions of rats were evaluated by Morris water maze and modified neurological severity scores (mNSS).The data revealed that fraxin abated the OGD/R-mediated release of inflammatory and oxidative stress mediators, enhanced "M2″-like BV2 microglia polarization, and mitigated HT22 cell apoptosis. Mechanistically, fraxin boosted PPAR-γ expression, activated the Nrf2/HO-1 pathway, and suppressed NF-κB, IKK-β，p38 MAPK, ERK1/2 and Keap1 in a dose-dependent manner. Furthermore, attenuating PPAR-γ through pharmacological treatment with GW9662 (a PPAR-γ antagonist) mainly weakened the neuroprotective and anti-inflammatory functions of fraxin.Fraxin could considerably ameliorate cerebral I/R damage by repressing oxidative stress, inflammatory response, and cell apoptosis through abrogating the PPARγ/ NF-κB pathway.

Decreased blood flow to the brain causes stroke and damage to neuronal networks. Neuronal damage occurs not only in the infarct core but also in areas away from the infarcts. This study was aimed to assess alterations of the cortical projection neurons that were distantly connected with the infarcts. Unilateral cortical ischemia was generated by middle cerebral artery occlusion in the right somatosensory cortex. Pre-labeled thalamocortical neurons disappeared, whereas contralateral callosal projection neurons survived 48 h post-ischemia. The unilateral ischemia increased the total length, segment length and the spine volume of dendrites from layer V callosal neurons in the homotopic cortex of the contralateral hemisphere. The morphological remolding of the contralateral cortical neurons cannot be reproduced by the spinal cord hemisection that cuts axons of corticospinal projection neurons of layer V. The data suggest that the retrograde degeneration of axons may not account for the early morphological changes in the contralateral cortex. We hypothesize that the loss of innervations from the ischemic cortex may bring in adaptive changes to the connected neurons, and adult cortical neurons can adjust their morphology to meet the reduction of synaptic inputs. This study may improve our understanding of the re-organization of cortical circuits following focal cerebral ischemia and help the development of new treatments designed to minimize the disability associated with 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.

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.

Objective To investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Methods Retrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour. Results We find that many SAH patients have an increase in ED burden during the first 3–10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5–6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk. Conclusions These results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication. Significance ED burden is a novel biomarker for predicting those at high risk of DCI.

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

Introduction Posterior Circulation (PC) stroke represents one-fifth of all ischemic strokes, with peculiar physiological characteristics. Hemorrhagic Transformation (HT) is a dreaded complication among stroke patients. Many predictive scores of this complication have been proposed, but none is designed specifically for PC stroke patients – therefore, patients who are not eligible to reperfusion therapies (RT) represent about 80% of hospitalized cases. We propose a scoring system to assess the HT risk in PC stroke patients not submitted to RT. Methods We retrospectively evaluated data of patients diagnosed with PC stroke not treated with RT from 5 Comprehensive Stroke Centers (four in Brazil, 1 in the US) from 2015 to 2018. All patients underwent CT scan or MRI at admission and a follow-up neuroimaging within seven days. Independent variables identified in a logistic regression analysis were used to produce a predictive grading score.Results We included 952 patients in the final analysis. The overall incidence of HT was 8.7%. Male gender (1 point), NIH Stroke Scale at admission ≥ 5 points (1), blood glucose at admission ≥ 160mg/dL (1), and cardioembolism (2) were independently associated with HT. The AUC of the grading score (0 to 5 points) was 0.713 (95% CI 0.65-0.78). Subjects with a score ≥ 3 points had an OR of 4.8 (95% CI 2.9-7.9, pConclusions Our score is accurate in identifying patients at higher risk of HT. This score may be useful for evaluating secondary prevention and stratifying patients in the context of even clinical trials.

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.

Subarachnoid haemorrhage (SAH) is the third most common subtype of stroke. Incidence has decreased over past decades, possibly in part related to lifestyle changes such as smoking cessation and management of hypertension. Approximately a quarter of patients with SAH die before hospital admission; overall outcomes are improved in those admitted to hospital, but with elevated risk of long-term neuropsychiatric sequelae such as depression. The disease continues to have a major public health impact as the mean age of onset is in the mid-fifties, leading to many years of reduced quality of life. The clinical presentation varies, but severe, sudden onset of headache is the most common symptom, variably associated with meningismus, transient or prolonged unconsciousness, and focal neurological deficits including cranial nerve palsies and paresis. Diagnosis is made by CT scan of the head possibly followed by lumbar puncture. Aneurysms are commonly the underlying vascular cause of spontaneous SAH and are diagnosed by angiography. Emergent therapeutic interventions are focused on decreasing the risk of rebleeding (ie, preventing hypertension and correcting coagulopathies) and, most crucially, early aneurysm treatment using coil embolisation or clipping. Management of the disease is best delivered in specialised intensive care units and high-volume centres by a multidisciplinary team. Increasingly, early brain injury presenting as global cerebral oedema is recognised as a potential treatment target but, currently, disease management is largely focused on addressing secondary complications such as hydrocephalus, delayed cerebral ischaemia related to microvascular dysfunction and large vessel vasospasm, and medical complications such as stunned myocardium and hospital acquired infections.

Background Hospital on-call neurology shifts are frequently on-site, but some on-call services may be off-site or mixed. Intravenous tissue plasminogen activator (tPA) is one of the main reperfusion treatments for acute ischaemic stroke (AIS). This study assesses door-to-needle times (DNT) when the neurologist is on-site or off-site. Methods We performed a prospective, observational study from 2012 to 2017, including patients with AIS and treated with tPA. Data were collected on sex, age, door-to-scan time, scan-to-needle time, and DNT. The on-duty neurologist was on-site from 08:00 to 20:00, and on call but off-site from 20:00 to 8:00. Three groups were formed: on-site, off-site, and off-site with resident present. Results Our sample included 138 patients. The mean age was 69.7 years, and 45.7% of patients were women. Ninety-six patients were admitted during the on-site shift, 25 during the off-site shift, and 17 during the off-site–resident present shift. Patients admitted during the on-site and off-site shifts presented DNTs of 59 and 72 minutes, respectively (P = .003). DNTs were 59, 74, and 68 minutes (P = .001), respectively, for the on-site, off-site, and off-site–resident present shifts; the difference between DNTs for on-site and off-site shifts was statistically significant. No differences were observed between DNTs according to time of day (morning, afternoon, or night), or between weekdays and weekends. Conclusion DNT is influenced by whether the on-duty neurologist is on- or off-site at the time of code stroke activation. The presence of a neurology resident can reduce DNT.

Chronic cerebral hypoperfusion (CCH) has been gradually regarded as a common etiologic mechanism for cognitive and psychiatric disturbances. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) played an important role in adult hippocampal neurogenesis (AHN), neuronal circuits formation, cognition and psychiatric disorders. Enriched environment (EE) showed a beneficial effect on cognition and depression via effectively regulating AHN and glial reactivity. This study aimed to assess which strategy was feasible to improve cognition and psychiatric disturbances by comparing the TET1 hippocampal microinjection and EE in CCH models and to investigate the possible mechanisms.CCH rats were established via permanent bilateral common carotid artery occlusion (2-VO). Rats were stereotaxically injected with the human catalytic domain of TET1 (hTET1) to overexpress the hTET1 in the hippocampus 10 days before 2-VO. 3 days after 2-VO, rats were subjected to standard environment or EE with free access to food and water. Behavioral tests were used to appraise depression and cognition before sacrifice. Epigenetic molecules, adult neurogenesis, synaptic proteins expression, and glial activation were analyzed using immunofluorescent staining, qRT-PCR and western blot.In the present study, we found both EE and genetical treatment with overexpressing hTET1 were sufficient for stimulating AHN. However, promoting ANH could not deal with the cognitive dysfunction and depressive-like behaviors in CCH rats. Notably, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. Meanwhile, astrocytes were involved in the cognitive regulating process of neurons, presynaptic function and microglia. In general, we held that depressive disturbances were determined by BDNF levels, neuronal and presynaptic function, as well as glial activation containing astrocytes and microglia. To further support this point, we investigated severe depressive symptoms that were strongly correlated with the activation of astroglia and microglia. Importantly, causal mediation analysis showed significant mediation by the presence of reactive glial cells in the relation between neural plasticity and depressive symptoms. Finally, we showed EE performed better than hTET1 treatment for cognitive deficits and depression. EE with less glial reactivity was much more resistant to depression, while hTET1 with more glial activation was more vulnerable to depressive disorders.EE was likely to be superior to TET1 hippocampal administration for cognition and psychiatric behaviors in CCH rats. Furthermore, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. More glial activation, and more vulnerable to depressive disorders. These results were important for our understanding of disease mechanisms and provided valuable tools for the overall management of CCH patients.

To evaluate the radiological features of isolated posterior inferior cerebellar artery dissection (PICAD) and the feasibility of using high-resolution vessel-wall imaging (HR-VWI) for diagnosing PICAD.Three hundred and nine patients with arterial dissection involving the posterior cerebral circulation, who underwent HR-VWI between March 2012 and July 2019 were reviewed retrospectively. Among them, 44 patients (14.2%) were diagnosed with isolated PICAD in consensus among a neuroradiologist, a neurointerventionist, and a neurologist. Two neuroradiologists reviewed the vessel wall images independently for evidence of dissection (dissection flap, outer diameter enlargement on T2-weighted imaging [WI], mural haematoma). Diagnostic confidence was also scored on a five-point scale. Intra- and interobserver agreement for diagnosing PICAD and detecting evidence of dissection were evaluated.Dissection flaps were seen on T2WI in all cases (100%) and on contrast-enhanced T1WI in 34 patients (79.1%). Outer diameter enlargement of the steno-occlusive lesions on angiography was detected in most cases (97.7%). A mural haematoma was detected on three-dimensional (3D) contrast-enhanced motion-sensitised driven-equilibrium T1WI in 97.1% of the cases. The mean diagnostic confidence score derived by two neuroradiologists was 4.72. The two reviewers showed substantial to almost perfect agreement (weighted kappa coefficient: 0.62-0.97).Use of HR-VWI as a diagnostic tool for PICAD is feasible, and a dissection flap with outer wall enlargement on HR-T2WI allows confident dissection diagnosis. The present data suggest that PICAD might be considered as a stroke aetiology in patients with unexplained ischaemic stroke in the PICA territory, and that PICA evaluation with HR-VWI is both necessary and feasible.

Chronic kidney disease (CKD) is associated with a higher mortality rate and a poor prognosis among patients with acute ischemic stroke (AIS) who receive intravenous thrombolysis (IVT); however, it is still unclear whether IVT improves the prognosis of patients with AIS and CKD.We conducted this study to evaluate the impact of IVT in patients with AIS and CKD.We analyzed patients with AIS and CKD in 3 stroke centers who met the indications for IVT between January 2015 and January 2020. The patients were grouped into an IVT group and a non-IVT group according to whether patients received IVT. After propensity score matching at a 1:1 ratio, symptomatic intracranial hemorrhage (sICH) and the modified Rankin Scale (mRS) score at 3 months were compared to assess the safety and efficacy of IVT in patients with AIS with CKD.A total of 888 patients were enrolled: 763 in the IVT group and 125 in the non-IVT group. After matching, 250 patients were analyzed, and no significant differences were found in sICH between the 2 groups. However, the IVT group had a better 90-day mRS (0-2) score (70.4% vs. 57.6; p = 0.048) than the non-IVT group.IVT improved the 3-month prognosis and did not increase the occurrence of sICH among patients with AIS with CKD.

The role of MR imaging in the evaluation and management of ischemic stroke patients is large, and to cover it all is far beyond the scope of one article. Thus, the focus will be on the role of MR imaging in the great leap forward in stroke therapy: endovascular thrombectomy of large vessel occlusions (LVOs). Diffusion MR imaging has played a key role in the research leading to the current standard of care for LVO stroke because it is the most sensitive and reliable method for the early delineation of the ischemic core.

Serum Dickkopf-1 (Dkk-1) levels are associated with poor ischemic stroke prognosis, although their impact on poststroke depression (PSD) remains unclear. This study aimed to examine the association between serum Dkk-1 levels and PSD.Serum Dkk-1 levels were measured in 564 patients with ischemic stroke who participated in the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The patients' depression status at 3 months after stroke was assessed using the Hamilton Rating Scale for Depression (HRSD-24). The HRSD score cutoff point for the diagnosis of depression was ≥8.A total of 224 (39.72%) patients were categorized as having PSD 3 months after ischemic stroke. After adjusting for potential confounders, including age, sex, and other important covariates, elevated Dkk-1 levels were associated with an increased risk of PSD (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.14-3.22; PHigher serum Dkk-1 levels at baseline are independently associated with an increased risk of PSD at 3 months after stroke, suggesting that Dkk-1 levels may be a promising prognostic biomarker for PSD.This study measured serum Dkk-1 levels only in the acute phase of stroke not in different phases; therefore, the relationship between dynamic changes in Dkk-1 levels and PSD could not be evaluated.