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Inherited thrombophilic disorders are well‐established predisposing factors for venous thromboembolism, but their role in arterial ischaemic stroke is uncertain. The exact mechanism of arterial thrombosis in thrombophilias remains elusive. Herein, we report a case of a 30-year-old woman who was admitted to our facility with sudden-onset right-sided ptosis and ophthalmoplegia. Detailed clinical features, neuroimaging and laboratory evaluation clinched the diagnosis of ischaemic stroke in midbrain due to microvascular obstruction associated with isolated protein S deficiency. She was treated with oral anticoagulant (warfarin) and physiotherapy; without any improvement of her symptoms at 2 months of follow-up. A high index of clinical suspicion is needed in any case of young ischaemic stroke in absence of common cardiac and vascular risk factors, to recognise the presence of inherited thrombophilia.

Background A considerable proportion of stroke patients have unfavorable outcomes despite substantial reperfusion during mechanical thrombectomy for large vessel occlusion. This study aimed to determine predictors of unfavorable outcomes despite substantial reperfusion (modified thrombolysis in cerebral infarction score of ≥2b). Methods We conducted a post hoc analysis of Analysis of Revascularization in Ischemic Stroke With EmboTrap, a prospective, multicenter study on the efficacy of the EmboTrap revascularization device. We included patients with anterior large vessel occlusion, substantial reperfusion within three passes, and 3-month follow-up. Univariate and multivariate logistic regression analyses were performed to determine independent predictors of dependency or death (modified Rankin Score 3–6) at 90 days. Results Of the 176 patients included in the study, 124 (70.45%) achieved modified Rankin Score of 0–2 at 90 days and 52 (29.6%) had modified Rankin Score of 3–6. On univariate analysis, patient age and initial National Institutes of Health Stroke Scale score were significantly higher in the modified Rankin Score of 3–6 groups (71.4 ± 11.3 years vs. 66.0 ± 13.1 years, 0.01; 18.9 ± 4.13 vs. 14.6 ± 4.36, p Conclusion More severe initial neurologic deficit and higher number of passes in patients with substantial reperfusion were independent predictors of dependency or death. These findings highlight a reduction in the number of passes required to achieve reperfusion as a therapeutic target to improve the outcome after thrombectomy.

Eosinophilia can occur due to a plethora of allergic, infective, neoplastic and idiopathic conditions. Hypereosinophilic syndrome (HES) is characterised by sustained eosinophilia and multiorgan dysfunction in the absence of an identifiable cause. It may range from a self-limiting condition to a rapidly progressive life-threatening disorder, of which ischaemic stroke is a rare presentation. Such episodes can rarely be the presenting manifestation, and may develop before any other laboratory abnormality or organ involvement. We report a case of HES presented with multiorgan (neurological and renal) involvement, managed successfully with steroids and cytoreductive therapy. High initial absolute eosinophil count can be a clue to the diagnosis and early treatment should be initiated in such patients, to prevent fatal outcomes.

Eight-and-a-half syndrome is a rare entity characterised by conjugate horizontal gaze palsy, ipsilateral internuclear ophthalmoplegia and ipsilateral lower motor neuron type facial palsy. It is due to a lesion affecting median longitudinal fasciculus, paramedian pontine reticular formation and facial nerve fascicle on the same side at the level of pons. The diagnosis is easily missed as it needs detailed ocular movement examination. It is mainly caused due to infarction or demyelinating conditions. We are reporting an interesting case of a 54-year-old man with right-side eight-and-a-half syndrome due to acute ischaemic stroke and ST-elevation myocardial infarction of the inferior wall.

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.

Background: Stroke is a serious neurovascular problem and the leading cause of disability and death worldwide. The disrupted demand to supply ratio of blood and glucose during cerebral ischemia develops hypoxic shock, and subsequently necrotic neuronal death in the affected regions. Multiple causal factors like age, sex, race, genetics, diet, and lifestyle play an important role in the occurrence as well as progression of post-stroke deleterious events. These biological and environmental factors may be contributed to vasculature variable architecture and abnormal neuronal activity. Since recombinant tissue plasminogen activator is the only clinically effective clot bursting drug, there is a huge unmet medical need for newer therapies for the treatment of stroke. Innumerous therapeutic interventions have shown promise in the experimental models of stroke but failed to translate it into clinical counterparts. Methods: Original publications regarding pathophysiology, preclinical experimental models, new targets and therapies targeting ischemic stroke have been reviewed since the 1970s. Results: We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Results : We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Conclusion: There are still many inter-linked pathophysiological alterations with regards to stroke, animal models need not necessarily mimic the same conditions of stroke pathology and newer targets and therapies are the need of the hour in stroke research.

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.

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

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.

We report a 69 year old who suffered a cardioembolic ischaemic stroke on 23 September 2019, which resulted in a left hemiplegia with motor impairment in upper and lower extremities that made impossible for her to use the affected arm in daily living activities. The person commenced her comprehensive physiotherapy programme based on functional electrical stimulation (FES) in Fesia Clinic rehabilitation centre in October 2020. A multifield technology-based FES device was used, which allowed to train different selective movements in isolation and combined with mirror therapy, achieving excellent functional outcomes.

We describe a patient presented with clinically a small cerebellar ischaemic stroke but required emergency decompression within 24 hours of symptoms onset after incidental finding of severe mass effect on imaging without any change in her mild clinical symptoms. Her initial multimodal acute stroke imaging, non-contrast CT of the brain and CT angiography from aortic arch to vertex were normal. CT perfusion showed a very small deficit only. The malignant mass effect was picked on an MRI scan performed routinely as part of a clinical trial, 32 hours after stroke. Our case highlights stroke evolution, and mass effect may be insidious and faster than anticipated in the posterior fossa. Cerebellar stroke of any severity diagnosed clinically and radiologically may benefit from routine follow-up imaging at 24 hours from onset.

A man in his early 40s with no significant vascular risk factors was managed within a period of 6 months for recurrent vascular events: ischaemic stroke, transient ischaemic attack and isolated third nerve palsy. He was extensively investigated throughout the course of illness. The only potential aetiological factor identified was a positive janus kinase 2 (JAK 2) mutation after screening on account of mildly elevated platelet count noted during his most recent admission. Bone marrow aspiration confirmed essential thrombocythaemia. He was started on hydroxycarbamide and has remained relatively symptom free since then.This case reiterates the known associations between thrombosis and JAK 2 mutation even without overt myeloproliferative neoplasms. It also highlights the need for specialists in stroke to consider screening for JAK 2 mutation in a young patient with cryptogenic stroke with or without polycythemia or thrombocytosis.

A 76-year-old man was admitted to the hospital with acute onset of involuntary movements of the left side of his body. His neurological examination revealed he was oriented only to himself, and aforementioned movements of his left arm and leg. CT head demonstrated old infarcts in his right aspect of his pons and basal ganglia. Cerebrospinal fluid analysis was unremarkable. He initially had a normal blood glucose with an elevated anion gap and elevated creatine kinase. Brain MRI showed a small lacunar-type ischaemic infarct within the anteromedial aspect of the right cerebral peduncle, which localised to his haemiballism. To prevent worsening rhabdomyolysis associated with his haemiballism, the primary team initiated both tetrabenazine and diazepam. His movements improved after 1 week of medication therapy. This report discusses a thorough workup for this movement disorder and when to intervene for this distressing condition.

Introduction The benefits of mechanical thrombectomy in the treatment of patients with acute stroke due to large vessel occlusions (LVOs) have been extensively demonstrated by randomized trials and registries in developed countries. However, data on thrombectomy outside controlled trials are scarce in developing countries. The aim of this study was to assess the safety and efficacy, and to investigate the predictors for good and poor outcomes of thrombectomy for treatment of AIS due to anterior circulation LVOs in Brazil. Materials and Methods This was a single center registry of thrombectomy in the treatment of stroke caused by anterior circulation LVOs. Between 2011 and 2019, a total of 565 patients were included. Results the mean baseline NIHSS score on admission was 17.2. The average baseline ASPECTS was 8, and 91.0% of patients scored ≥6. Half of the patients received intravenous thrombolysis. The mean time from symptom onset to arterial puncture was 296.4 minutes. The mean procedure time was 61.4 minutes. The rates of the main outcomes were recanalization (TICI 2b-3) 85.6%, symptomatic intracranial hemorrhage (sICH) 8,1%, good clinical outcome (mRS=0-2) 43,5%, and mortality 22.1% at three months. Conclusions This study demonstrates the efficacy and safety of mechanical thrombectomy for treatment of patients with AIS of the anterior circulation in real-life conditions under limited facilities and resources. The results of the present study were relatively similar to those of large trials and population registers of developed countries.

Aims: To investigate the efficacy and safety of Cerebrolysin and Cerebrolysin plus nootropics in the routine treatment of patients with acute ischemic stroke (AIS). Background: Acute ischemic stroke (AIS) is a leading cause of disability with unmet treatment needs lacking effective drug therapy. Multimodal drugs modulating stroke pathophysiology as Cerebrolysin constitute a good therapeutic option. Objective: In this study, we assessed the effects of Cerebrolysin and Cerebrolysin plus nootropics, in comparison with other nootropic drugs alone, on functional, neurological and cognitive recovery of patients with AIS in Vietnam. Methods.: This non-interventional, controlled, open-label, prospective and multicenter study included 398 AIS patients (234 males) treated with Cerebrolysin (n=190; 20 i.v. infusions of 10 ml), other nootropics (comparator group; n=86), or a combination of both (n=122). The study primary endpoint was the modified Ranking Scale (mRS) score on day 90. Secondary endpoints included study-period change in NIHSS score; percentage of well-recovered (mRS 0-2) patients, the proportion of good NIHSS response (≥6 points) cases, and MoCA scores at day 90; and safety indicators. Results: Compared with other nootropics, both Cerebrolysin and combined therapy induced significant improvements (p11) cases only. No drug-related adverse events were reported. Conclusion: Cerebrolysin alone or combined with other nootropics was effective and safe in routine AIS treatment, during both acute and recovery phases, which supports its use in daily clinical practice. Other: According to the results of this multicenter study, the importance of reducing differences in the treatment regimens of AIS in Vietnam should be further emphasized.

Spontaneous subarachnoid hemorrhage (SAH) accounts for 5-10% of all strokes and is a subtype of hemorrhagic stroke that places a heavy burden on health care. Despite great progress in surgical clipping and endovascular treatment for ruptured aneurysms, cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) threaten the long-term outcomes of patients with SAH. Moreover, there are limited drugs available to reduce the risk of DCI and adverse outcomes in SAH patients. New insight suggests that early brain injury (EBI), which occurs within 72 h after the onset of SAH, may lay the foundation for further DCI development and poor outcomes. The mechanisms of EBI mainly include excitotoxicity, oxidative stress, neuroinflammation, blood-brain barrier (BBB) destruction, and cellular death. Mitochondria are a double-membrane organelle, and they play an important role in energy production, cell growth, differentiation, apoptosis, and survival. Mitochondrial dysfunction, which can lead to mitochondrial membrane potential (ΔΨm) collapse, overproduction of reactive oxygen species (ROS), release of apoptogenic proteins, disorders of mitochondrial dynamics, and activation of mitochondria-related inflammation, is considered a novel mechanism of EBI related to DCI as well as post-SAH outcomes. In addition, mitophagy is activated after SAH. In this review, we discuss the latest perspectives on the role of mitochondria in EBI and DCI after SAH. We emphasize the potential of mitochondria as therapeutic targets and summarize the promising therapeutic strategies targeting mitochondria for SAH.

BACKGROUND AND PURPOSE Delayed cerebral ischemia (DCI) and angiographic vasospasm following subarachnoid hemorrhage (SAH) have been associated for more than 50years. We aimed to examine whether the knowledge gained by theoretical research on vasospasm has actually translated into better patient outcomes in practice. METHODS This is a narrative review of the concept of vasospasm as a cause of DCI after SAH. We discuss recent studies that have assessed the accuracy and reliability of the diagnostic tests (transcranial Doppler ultrasound [TCD], CT angiography, and catheter angiography), which are used to identify SAH patients at-risk of DCI. RESULTS Both the diagnostic accuracy of TCD and the reliability of CT angiography to identify patients in severe vasospasm are poor. For the gold standard catheter angiography, the repeatability of the diagnosis of vasospasm, made by multiple raters, is only fair. Interventions on angiographic vasospasm have never been proven to improve patient outcomes. A pragmatic trial integrating the meaning of the diagnosis of vasospasm into a study protocol that assesses the value of endovascular interventions in the prevention of DCI after SAH seems to be in order. Such a trial could provide a pragmatic definition of clinically meaningful vasospasm. CONCLUSION We must move beyond research conceived as an enterprise aiming to acquire theoretical knowledge to one where research is integrated into clinical practice to improve clinical outcomes in real time.

Background and Purpose The goal of this study was to systematically review the utility of serum biomarkers in the setting of ischemic stroke (IS) to predict long-term outcome. Methods A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986-2018. All studies assessing long-term functional outcome (defined as 30 days or greater) following IS with respect to serum biomarkers were included. Data were extracted and pooled using a meta-analysis of odds ratios. Results Of the total 2928 articles in the original literature search, 183 studies were ultimately selected. A total of 127 serum biomarkers were included. Biomarkers were grouped into several categories: inflammatory (32), peptide/enzymatic (30), oxidative/metabolic (28), hormone/steroid based (23), and hematologic/vascular (14). The most commonly studied biomarkers in each category were found to be CRP, S100β, albumin, copeptin, and D-dimer. With the exception of S100β, all were found to be statistically associated with >30-day outcome after ischemic stroke. Conclusions Serum-based biomarkers have the potential to predict functional outcome in IS patients. This meta-analysis has identified CRP, albumin, copeptin, and D-dimer to be significantly associated with long-term outcome after IS. These biomarkers have the potential to serve as a platform for prognosticating stroke outcomes after 30 days. These serum biomarkers, some of which are routinely ordered, can be combined with imaging biomarkers and used in artificial intelligence algorithms to provide refined predictive outcomes after injury. Ultimately these tools will assist physicians in providing guidance to families with regards to long-term independence of patients.

Artificial intelligence (AI) is having a disruptive and transformative effect on clinical medicine. Prompt clinical diagnosis and imaging are critical for minimizing the morbidity and mortality associated with ischemic strokes. Clinicians must understand the current strengths and limitations of AI to provide optimal patient care. Ischemic stroke is one of the medical fields that have been extensively evaluated by artificial intelligence. Presented herein is a review of artificial intelligence applied to clinical management of stroke, geared toward clinicians. In this review, we explain the basic concept of AI and machine learning. This review is without coding and mathematical details and targets the clinicians involved in stroke management without any computer or mathematics' background. Here the AI application in ischemic stroke is summarized and classified into stroke imaging (automated diagnosis of brain infarction, automated ASPECT score calculation, infarction segmentation), prognosis prediction, and patients' selection for treatment.

Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5–3.2], P P =0.04). No significant association was found between trajectory group and hemorrhagic transformation. Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Introduction The aim of this study was to assess the outcomes of endovascular treatment for acute ischaemic stroke in Mater Dei Hospital, Malta and compare them with international data. Methods A prospective review of all patients who underwent mechanical thrombectomy from 2015 to the end of 2019 was performed. Eligible patients had large vessel occlusion confirmed on computed tomography angiography. Demographical data, the National Institutes of Health stroke scale at presentation, endovascular procedure details and process times were analysed. The thrombolysis in cerebral infarction score was used to assess the degree of reperfusion. A thrombolysis in cerebral infarction score of 2b–3 was considered as successful recanalisation. Functional outcome (modified Rankin scale score) and mortality at 90 days were measured. Functional independence was defined as a modified Rankin scale score of 2 or less. Results A total of 132 patients underwent endovascular treatment, one patient was excluded due to incomplete data. The mean age was 71 (range 25–94) years, and the mean National Institutes of Health stroke scale at presentation was 14. Of the 131 patients treated, 69 received intravenous thrombolysis. Successful recanalisation (thrombolysis in cerebral infarction score 2b–3) was achieved in 80% of patients (105/131); 53% of patients (69/131) achieved functional independence at 90 days, with a mortality of 21% at 90 days. Symptomatic intracranial haemorrhage was recorded in 16 patients (12%) There was a statistical difference in the functional independence and mortality rate in favour of the successful recanalisation group. Conclusion Our data are consistent with a favourable clinical outcome after successful recanalisation. Service in Malta is achieving favourable outcomes for patients treated with mechanical thrombectomy for acute ischaemic stroke.

Background: Inhalational anesthetics were associated with reduced incidence of angiographic vasospasm and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH). Whether intravenous anesthetics provide similar level of protection is not known. Methods: Anesthetic data were collected retrospectively for patients with SAH who received general anesthesia for aneurysm repair between January 1, 2014 and May 31, 2018, at 2 academic centers in the United States (one employing primarily inhalational and the other primarily intravenous anesthesia with propofol). We compared the outcomes of angiographic vasospasm, DCI, and neurological outcome (measured by disposition at hospital discharge), between the 2 sites, adjusting for potential confounders. Results: We compared 179 patients with SAH receiving inhalational anesthetics at one institution to 206 patients with SAH receiving intravenous anesthetics at the second institution. The rates of angiographic vasospasm between inhalational versus intravenous anesthetic groups were 32% versus 52% (odds ratio, 0.49 [CI, 0.32–0.75]; P =0.001) and DCI were 21% versus 40% (odds ratio, 0.47 [CI, 0.29–0.74]; P =0.001), adjusting for imbalances between sites/groups, Hunt-Hess and Fisher grades, type of aneurysm treatment, and American Society of Anesthesiology status. No impact of anesthetics on neurological outcome at time of discharge was noted with rates of good discharge outcome between inhalational versus intravenous anesthetic groups at (78% versus 72%, P =0.23). ConclusionS: Our data suggest that those who received inhalational versus intravenous anesthetic for ruptured aneurysm repair had significant protection against SAH-induced angiographic vasospasm and DCI. Although we cannot fully disentangle site-specific versus anesthetic effects in this comparative study, these results, when coupled with preclinical data demonstrating a similar protective effect of inhalational anesthetics on vasospasm and DCI, suggest that inhalational anesthetics may be preferable for patients with SAH undergoing aneurysm repair. Additional investigations examining the effect of inhalational anesthetics on other SAH outcomes such as early brain injury and long-term neurological outcomes are warranted.

Promoting neurogenesis and proliferation of endogenous neural stem/progenitor cells (NSPCs) is considered a promising strategy for neurorehabilitation after stroke. Our previous study revealed that a moderate dose of artesunate (ART, 150mg/kg) could enhance functional recovery in middle cerebral artery occlusion (MCAO) mice. This study aimed to investigate the effects of ART treatment on neurogenesis and proliferation of NSPCs using a rodent MCAO model. MRI results indicated that the ischemic brain volume of MCAO mice was reduced by ART treatment. The results of diffusion tensor imaging, electron microscopic, and immunofluorescence of Tuj-1 also revealed that ischemia-induced white matter lesion was alleviated by ART treatment. After ischemia/reperfusion, endogenous NSPCs were activated by ART, which was displayed by comparing the proportion of Brdu+ neuronal precursor cells in the ipsilateral subventricular zone and peri-infarct cortex. Furthermore, the neuro-restorative effects of ART were abolished by the overexpression of FOXO3a. These findings suggested that ART could rescue penumbra damage and alleviate white matter injury, subsequently contributing to post-stroke functional recovery by promoting neurogenesis and proliferation of endogenous NSPCs via the FOXO3a/p27Kip1 pathway.

Background and purpose Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Methods We performed a systematic review and meta-analysis of studies that randomised patients to novel oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) and reported outcomes stratified by presence of hypertension. Collected outcomes were: ischaemic stroke or systemic embolism (SE), haemorrhagic stroke, intracranial haemorrhage and major bleeding. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71.527 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8-2.8 years. Compared with patients without hypertension, those with hypertension had higher adjusted risk for ischaemic stroke/SE (HR: 1.25, 95%-CI:1.09, 1.43) and haemorrhagic stroke (HR:1.98, 1.24-3.16). On a continuous scale, the risk of ischaemic stroke/SE increased 6-7% per 10 mmHg increase in systolic blood pressure. No interactions were found between the efficacy or safety of NOACs versus VKAs in the presence or absence of hypertension. In both groups, the use of NOACs led to a lower risk of ischaemic stroke/SE, haemorrhagic stroke and intracranial haemorrhage compared with patients that used VKAs. Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

BACKGROUND Stroke and diabetes (DM) are significant interrelated healthcare issues but there is a dearth of data on the prevalence of DM among Australia's regional stroke population. AIMS We aimed to determine the prevalence of DM in stroke patients at a large regional centre, including sub-analyses on stroke subtypes, glycaemic control and renal function in ischaemic stroke (IS). METHODS We conducted a retrospective analysis of all patients (n = 323) with IS or transient ischaemic attack (TIA) admitted to Ballarat Base Hospital from January 2015 to December 2016. Demographic data, cardiovascular risk factors, aetiology/territory of IS, pre-morbid DM status, indicators of glycaemic control and renal impairment were recorded. RESULTS DM was present in 28.5% of IS and TIA patients including 4% being newly diagnosed. Among diabetic IS patients, 45.3% had poor glycaemic control (HbA1c ≥7.0%) while 16% had moderate to severe renal impairment (eGFR of

Background: Retrievable stents and aspiration catheters have been developed to provide more effective arterial recanalisation in acute ischaemic stroke. Aims: The aim of this analysis was to test the effect of mechanical thrombectomy on mortality and longterm neurological outcome in patients presenting with acute large-vessel anterior circulation ischaemic stroke. Methods: A structured search identified randomised controlled trials of thrombectomy (using a retrievable stent or aspiration catheter) versus control on a background of medical therapy which included intravenous thrombolysis if appropriate. The primary endpoint was disability at 90-day follow-up as assessed by the modified Rankin scale (mRS). Secondary endpoints included all-cause mortality and symptomatic intracranial haemorrhage. A Bayesian mixed-effects model was used for analysis. Results: Twelve (12) trials met the inclusion criteria, comprising a total of 1,276 patients randomised to thrombectomy and 1,282 patients to control. Randomisation to thrombectomy significantly reduced disability at 90 days (OR 0.52, 95% credible interval 0.46 to 0.61, probability(control better)2 (OR 0.44, CrI 0.37 to 0.52, pr

INTRODUCTION Ischaemic stroke is the most common neurological complication of cardiac catheterisation. This study aims to analyse the clinical and prognostic differences between post-catheterisation stroke code (SC) and all other in-hospital and prehospital SC. METHODS We prospectively recorded SC activation at our centre between March 2011 and April 2016. Patients were grouped according to whether SC was activated post-catheterisation, in-hospital but not post-catheterisation, or before arrival at hospital; groups were compared in terms of clinical and radiological characteristics, therapeutic approach, functional status, and three-month mortality. RESULTS The sample included 2224 patients, of whom 31 presented stroke post-catheterisation. Baseline National Institutes of Health Stroke Scale score was lower for post-catheterisation SC than for other in-hospital SC and pre-hospital SC (5, 10, and 7, respectively; P=.02), and SC was activated sooner (50, 100, and 125minutes, respectively; P

Introduction Converting a high-volume primary stroke center (PSC) into a stroke center that can perform emergency endovascular treatment (EVT) could reduce the time to thrombectomy . We report the first results of a newly established EVT facility at the Perpignan PSC and their comparison with the targets defined by the established guidelines. Patients and method For this comprehensive observational study, data of patients with acute ischemic stroke (AIS) due to proximal large vessel occlusion (LVO) and treated by EVT at the Perpignan PSC from December 5, 2019 to September 15, 2020 were extracted from an ongoing prospective database. Results During the study period, 37 patients underwent EVT at the Perpignan PSC. The median (range) symptom-onset to recanalization time was 262 min (100–485 min). The median (range) intra-hospital times were: 20 min (2–58 min) for door-to-imaging, 57 min (30–155 min) for imaging-to-puncture, 55 min (15–180 min) for puncture-to-recanalization, and 137 min (59–319 min) for door-to-recanalization. At 3 months post-AIS, the favorable outcome (modified Ranking Score: 0–2) rate was 50% and the mortality rate was 19.4%. These results are comparable to those of previous clinical trials, and meet the targets defined by the current consensus statements for EVT. Discussion and conclusion Our results show the feasibility and safety of EVT in a PSC for patients with AIS due to LVO. The implementation of this strategy may be important for shortening the time to thrombectomy.

Background: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients.ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS.A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p = 0.001) and good functional outcome (p = 0.003).CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging marker of collateral status in patients with delayed presentation of AIS.

Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns regarding effective and targeted therapies for maintaining BBB integrity during ischemia/reperfusion (I/R) injury. In this study, we demonstrate that the circular RNA of FoxO3 (circ-FoxO3) promotes autophagy via mTORC1 inhibition to attenuate BBB collapse under I/R. Upregulation of circ-FoxO3 and autophagic flux were detected in brain microvessel endothelial cells in patients with hemorrhagic transformation and in mice models with middle cerebral artery occlusion/reperfusion. In vivo and in vitro studies indicated that circ-FoxO3 alleviated BBB damage principally by autophagy activation. Mechanistically, we found that circ-FoxO3 inhibited mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity. These results demonstrate that circ-FoxO3 plays a novel role in protecting against BBB damage, and that circ-FoxO3 may be a promising therapeutic target for neurological disorders associated with BBB damage.

Background: Stroke is a major challenge in neurology due to its multifactorial genesis and irreversible consequences. Processes of endogenous post-stroke neurogenesis, although insufficient, may indicate possible direction of future therapy. Multiple research considers stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke deficits. Objective: Aim of this study is to review current literature considering post-stroke stem-cell- based therapy and possibilities of inducing neuroregeneration after brain vascular damage. Methods: Papers included in this article were obtained from PubMed and MEDLINE databases. The following medical subject headings (MeSH) were used: “stem cell therapy”, “post-stroke neurogenesis”, “stem-cells stroke”, “stroke neurogenesis”, “stroke stem cells”, “stroke”, “cell therapy”, “neuroregeneration”, “neurogenesis”, “stem-cell human”, “cell therapy in human”. Ultimate inclusion was made after manual review of the obtained reference list. Results: Attempts of stimulating neuroregeneration after stroke found in current literature include supporting endogenous neurogenesis, different routes of exogenous stem cells supplying and extracellular vesicles used as a method of particle transport. Conclusion: Although further research in this field is required, post stroke brain recovery supported by exogenous stem cells seems to be promising future therapy revolutionizing modern neurology.

Background and Purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease–related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke. Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes ( DNMT3A , TET2 , and ASXL1 ) with any stroke, ischemic stroke, and hemorrhagic stroke. Results: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03–1.27]; P =0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01–1.51]; P =0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke. Conclusions: CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.

Coronavirus disease 2019 (COVID-19) has been associated with Acute Ischemic Stroke (AIS). Here, we characterize our institutional experience with management of COVID-19 and AIS. Baseline demographics, clinical, imaging, and outcomes data were determined in patients with COVID-19 and AIS presenting within March 2020 to October 2020, and November 2020 to August 2021, based on institutional COVID-19 hospitalization volume. Of 2512 COVID-19 patients, 35 (1.39%, mean age 63.3 years, 54% women) had AIS. AIS recognition was frequently delayed after COVID-19 symptoms (median 19.5 days). Four patients (11%) were on therapeutic anticoagulation at AIS recognition. AIS mechanism was undetermined or due to multiple etiologies in most cases (n = 20, 57%). Three patients underwent IV TPA, and three underwent mechanical thrombectomy, of which two suffered re-occlusion. Three patients had incomplete mRNA vaccination course. Fourteen (40%) died, with 26 (74%) having poor outcomes. Critical COVID-19 severity was associated with worsened mortality (p = 0.02). More patients (12/16; 75%) had either worsened or similar 3-month functional outcomes, than those with improvement, indicating the devastating impact of co-existing AIS and COVID-19. Comparative analysis showed that patients in the later cohort had earlier AIS presentation, fewer stroke risk factors, more comprehensive workup, more defined stroke mechanisms, less instance of critical COVID-19 severity, more utilization of IV TPA, and a trend towards worse outcomes for the sub-group of mild-to-moderate COVID-19 severity. AIS incidence, NIHSS, and overall outcomes were similar. Further studies should investigate outcomes beyond 3 months and their predictive factors, impact of completed vaccination course, and access to neurologic care.

Takayasu's arteritis is an inflammatory disease of unknown etiology that causes stenosis, occlusion, or dilatation of the aorta and its major branches, the pulmonary arteries, and the coronary arteries. The incidence of extracranial carotid artery aneurysm in patients with Takayasu's arteritis is reportedly 1.8%-3.9%. We herein report a patient with Takayasu's arteritis who presented with transient left hemiplegia immediately after neck massage. Carotid ultrasonography revealed a thrombus within the fusiform aneurysm on the right common carotid artery. We speculated that fragmentation from the intra-aneurysmal thrombus was caused by neck massage.

Stroke is one of the leading causes of patients' death and long‐term disability worldwide, and ischaemic stroke (IS) accounts for nearly 80% of all strokes. Differential genes and weighted gene co‐expression network analysis (WGCNA) in male and female patients with IS were compared. The authors used cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) to analyse the distribution pattern of immune subtypes between male and female patients. In this study, 141 up‐regulated and 61 down‐regulated genes were gathered and distributed into five modules in response to their correlation degree to clinical traits. The criterion for Gene Ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway indicated that detailed analysis had the potential to enhance clinical prediction and to identify the gender‐related mechanism. After that, the expression levels of hub genes were measured via the quantitative real‐time PCR (qRT‐PCR) method. Finally, CCL20, ICAM1 and PTGS2 were identified and these may be some promising targets for sex differences in IS. Besides, the hub genes were further verified by rat experiments. Furthermore, these CIBERSORT results showed that T cells CD8 and Monocytes may be the target for the treatment of male and female patients, respectively.

BACKGROUND Ischemic stroke is a prevalent, devastating disease with high morbidity and mortality. Despite extensive research using animal models, significant gaps remain in understanding the pathological processes in human stroke. We previously developed a tissue bank to analyze the blood immediately proximal and distal to an intracranial thrombus in patients undergoing mechanical thrombectomy (ClinicalTrials.gov identifier, NCT03153683). Our goal for the present project was to evaluate the blood gas changes and acid/base balance during stroke and determine how vascular collateralization affects these changes. METHODS We analyzed the blood samples and computed tomography angiography collateral scores from the first 62 patients in the BACTRAC (Blood and Clot Thrombectomy Registry and Collaboration) registry. The bicarbonate, partial pressure of oxygen, and partial pressure of carbon dioxide (pCO2) values of the intracranial (distal) and systemic (proximal) arterial blood relative to the occlusive thrombus were analyzed. Analysis of the group differences in systemic and intracranial blood gas values was also performed. RESULTS The partial pressure of oxygen, pCO2, and bicarbonate levels were all significantly higher in the systemic blood than in the intracranial blood (P < 0.001 for all) at thrombectomy. Collateralization did not significantly affect the distal blood gas values. Compared with the female patients, the male patients had had higher systemic pCO2 values (39.8 vs. 36.6 mm Hg; P = 0.0065) and lower systemic and intracranial pH values (7.351 vs. 7.392; P = 0.0047). CONCLUSIONS The arterial blood gases differed immediately proximal and distal to thrombi in large vessel occlusive stroke. Although vascular collateralization did not appear to affect the blood gas changes, some blood gas values differed between men and women. The changes in bicarbonate and pCO2 suggested a compensatory acid-base process occurring at the time of infarction.

Epigenetics, including histone modifications, play a significant role in central nervous system diseases, but the underlying mechanism remains to be elucidated. The aim of this study was to evaluate the role of H3K27me3 in regulating transcriptomic and pathogenic mechanisms following global ischemic stroke. Here, we found that in vivo ischemic/reperfusion (I/R) injury induced marked upregulation of H3K27me3 in the hippocampus. The administration of GSK-126 to rat brains decreased the levels of H3K27me3 in the hippocampus and reduced neuronal apoptosis after experimental stroke. Furthermore, ChIP-seq data demonstrated that the primary role of GSK-126 in the ischemic brain is to reduce H3K27me3 enrichment, mediating negative regulation of the execution phase of apoptosis and the MAPK signaling pathway. Further study suggested that the protective role of GSK-126 in ischemic rats was antagonized by U0126, an inhibitor of ERK1/2. Collectively, we demonstrated the potential of H3K27me3 as a novel stroke therapeutic target, and GSK-126 exerted a neuroprotective function in ischemic brain injury, which might be associated with activation of the MAPK/ERK pathway. Graphical Abstract

Aims To explore the practice effect of establishing an integrated treatment process by stroke emergency nurses in general hospitals for acute ischaemic stroke (AIS). Design Compared the time spent in each link before and after the establishment of AIS integrated treatment. Methods Since March 2016, we set up a team of emergency stroke nurses (ESN), trained and assessed the knowledge of emergency stroke, and set up a post of ESN. Results The median time of admission‐judgement, admission‐establishment of venous access, admission‐cranial CT examination and admission‐intravenous thrombolytic therapy was statistically significantly shortened after the implementation of the integrated treatment process of AIS coordinated by stroke emergency nurses (p

Objective To explore the association between early neutrophil-to-lymphocyte ratio (ENLR) and prognosis of anterior circulation large-vessel occlusion stroke (LVOS) after patients undergo endovascular treatment (EVT) with successful revascularization. Methods Patients who experienced acute anterior circulation LVOS and underwent EVT at Changzhou Second People's Hospital Affiliated to Nanjing Medical University between May 2017 and May 2020 were included in this retrospective study. We collected information about patients' baseline characteristics, medical history, laboratory test results, imaging data, and endovascular treatment outcomes, as well as data from follow-up at 3 months. Univariate and multivariate logistic regression models were used to evaluate the association between ENLR and functional disease prognosis. A piecewise linear regression model was also applied to compute the threshold effect of ENLR on poor prognosis (defined as modified Rankin Scale score 3–6) at 3 months using a smoothing plot. Results Of 224 patients who received EVT during the study period, 160 patients were included in the analysis. After adjustments were made for potential confounders, multivariate analysis demonstrated a significant association between ENLR and poor prognosis at 3 months (odds radio 1.19; 95% confidence interval 1.07–1.32; P = 0.0016). An ENLR ≥9.75 was found to be significantly associated with poor prognosis at 3 months (odds ratio 1.54; 95% confidence interval 1.19–2.00; P = 0.0119). Conclusions Increased ENLR after successful revascularization is independently associated with poor prognosis. These findings suggest that ENLR could be used to inform treatment strategies for patients who experience anterior circulation LVOS.

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Background and Purpose: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. Methods: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. Results: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82–88] years, baseline National Institutes of Health Stroke Scale score of 19 [15–23], Alberta Stroke Program Early CT Score 9 [7–9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P =0.04) and less frequent hypertension (78.9% versus 90.3%, P =0.01) but more atrial fibrillation (64.5% versus 44.1%, P =0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409–1.974], P =0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715–2.618], P =0.34). Conclusions: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

Background and Purpose: The occurrence of pneumonia after stroke is associated with a higher risk of poor outcome or death. We assessed the temporal profile of pneumonia after stroke and its association with poor outcome at several time points to identify the most optimal period for testing pneumonia prevention strategies. Methods: We analyzed individual patient data stored in the VISTA (Virtual International Stroke Trials Archive) from randomized acute stroke trials with an inclusion window up to 24 hours after stroke onset and assessed the occurrence of pneumonia in the first 90 days after stroke. Adjusted odds ratios and hazard ratios were calculated for the association between pneumonia and poor outcome and death by means of logistic and Cox proportional hazard regression, respectively, at different times of follow-up. Results: Of 10 821 patients, 1017 (9.4%) had a total of 1076 pneumonias. Six hundred eighty-nine (64.0%) pneumonias occurred in the first week after stroke. The peak incidence was on the third day and the median time of onset was 4.0 days after stroke (interquartile range, 2–12). The presence of a pneumonia was associated with an increased risk of poor outcome (adjusted odds ratio, 4.8 [95% CI, 3.8–6.1]) or death (adjusted hazard ratio, 4.1 [95% CI, 3.7–4.6]). These associations were present throughout the 90 days of follow-up. Conclusions: Two out of 3 pneumonias in the first 3 months after stroke occur in the first week, with a peak incidence on the third day. The most optimal period to assess pneumonia prevention strategies is the first 4 days after stroke. However, pneumonia occurring later was also associated with poor functional outcome or death.

Background and Purpose: Stem cell–based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell–based therapy in patients with ischemic stroke. Methods: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging. Results: For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference. Conclusions: Stem cell–based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01716481.

Introduction Patients hospitalized for acute ischemic stroke have an increased risk of venous thromboembolism (VTE) that may persist beyond the currently recommended period of 6 to 14 days of thromboprophylaxis. This systematic review evaluated the efficacy and safety of extended venous thromboprophylaxis in patients hospitalized for acute ischemic stroke. Materials and methods MEDLINE, EMBASE and Clinicaltrials.gov were searched up to December 2020 for randomized controlled trials comparing extended versus standard venous thromboprophylaxis in patients hospitalized for acute ischemic stroke. The efficacy outcome was a composite of asymptomatic or symptomatic deep vein thrombosis, symptomatic pulmonary embolism, and VTE-related death. The safety outcome was major bleeding. Summary risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Results Four randomized controlled trials enrolling 33718 patients were included. Of 4330 (12.8%) patients hospitalized for acute ischemic stroke, 2152 (49.7%) received extended thromboprophylaxis for four to five weeks with betrixaban (n = 405, 18.8%), enoxaparin (n = 198, 9.2%), or rivaroxaban (n = 1549, 72.0%), and 2178 (50.3%) received standard venous thromboprophylaxis with enoxaparin. VTE risk was lower in acute ischemic stroke patients receiving extended thromboprophylaxis (RR 0.67; 95% CI, 0.43 to 1.04; 13 fewer per 1000), whereas the increase in major bleeding seemed trivial when compared with standard prophylaxis (RR 1.10; 95% CI, 0.31 to 3.95; 1 more per 1000). Conclusion In patients hospitalized for acute ischemic stroke, the net clinical benefit may favor extended venous thromboprophylaxis for four to five weeks over standard thromboprophylaxis.

Background Selecting best candidates for prolonged poststroke cardiac monitoring in acute ischemic stroke (AIS) patients is still challenging. We aimed to develop a machine learning (ML) model to select AIS patients at high risk of poststroke atrial fibrillation (AF) for prolonged cardiac monitoring and then to compare ML model with traditional risk scores and classic statistical logistic regression (classic-LR) model. Methods AIS patients from July 2012 to September 2020 across Nanjing First Hospital were collected. We performed the LASSO regression for selecting the critical features and built five ML models to assess the risk of poststroke AF. The SHAP and partial dependence plot (PDP) method were introduced to interpret the optimal model. We also compared ML model with CHADS2 score, CHA2DS2-VASc score, AS5F score, HAVOC score, and classic-LR model. Results A total of 3929 AIS patients were included. Among the five ML models, deep neural network (DNN) was the model with best performance. It also exhibited superior performance compared with CHADS2 score, CHA2DS2-VASc score, AS5F score, HAVOC score and classic-LR model. The results of SHAP and PDP method revealed age, cardioembolic stroke, large-artery atherosclerosis stroke, and NIHSS score at admission were the top four important features and revealed the DNN model had good interpretability and reliability. Conclusion The DNN model achieved best performance and improved prediction performance compared with traditional risk scores and classic-LR model. The DNN model can be applied to identify AIS patients at high risk of poststroke AF as best candidates for prolonged poststroke cardiac monitoring.

Supplemental Digital Content is available in the text., Background and Purpose: Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design. Methods: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression. Results: In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms (P=0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]). Conclusions: Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Multimodal Magnetic Resonance Imaging (MRI) techniques of Perfusion-Weighted Imaging (PWI) and Diffusion-Weighted Imaging (DWI) data are integral parts of the diagnostic workup in the acute stroke setting. The visual interpretation of PWI/DWI data is the most likely procedure to triage Acute Ischemic Stroke (AIS) patients who will access reperfusion therapy, especially in those exceeding 6 h of stroke onset. In fact, this process defines two classes of tissue: the ischemic core, which is presumed to be irreversibly damaged, visualized on DWI data and the penumbra which is the reversibly injured brain tissue around the ischemic tissue, visualized on PWI data. AIS patients with a large ischemic penumbra and limited infarction core have a high probability of benefiting from endovascular treatment. However, it is a tedious and time-consuming procedure. Consequently, it is subject to high inter- and intra-observer variability. Thus, the assessment of the potential risks and benefits of endovascular treatment is uncertain. Fast, accurate and automatic post-processing of PWI and DWI data is important for clinical diagnosis and is necessary to help the decision making for therapy. Therefore, an automated procedure that identifies stroke slices, stroke hemisphere, segments stroke regions in DWI, and measures hypoperfused tissue in PWI enhances considerably the reproducibility and the accuracy of stroke assessment. In this work, we draw an overview of several applications of Artificial Intelligence (AI) for the automation processing and their potential contributions in clinical practices. We compare the current approaches among each other's with respect to some key requirements.

Ischemia injury can cause cell death or impairment of neuron and astrocytes, and thus induce loss of nerve function. central nervous systems injury induces an aberrant activation of astrocytes called astrogliosis. Pyroptosis, which is a kind of programmed cell death, was proved play an important role in ischemia injury. Zinc Finger E-Box Binding Homeobox 2 (ZEB2) promoted neuron astrogliosis, which play a protected role in neuron regeneration. However, its precise mechanism remains unclear. This study investigated the mechanism of ZEB2 on astrogliosis and neuron regeneration after cerebral ischemia reperfusion condition. To confirm our hypothesis, Neurons and astrocytes were isolated from fetal Sprague Dawley rats, in vivo Middle Cerebral Artery Occlusion/reperfusion (MCAO/R) rat model and in vitro oxygen-glucose deprivation/reperfusion (OGD/R)-treated astrocytes and neurocytes model were constructed. Our results showed that ZEB2 was expressed in nucleus of astrocyte and upregulated after OGD/R induction, ZEB2 promoted astrogliosis. Further upregulation of ZEB2 promoted the astrogliosis, which promoted neuron proliferation and regeneration by decreased pyroptosis. Moreover, this finding was further confirmed in vivo MCAO/R rat model. Overexpression of ZEB2 promoted astrogliosis, which decreased infarct volume and accumulated recovery of neurological function by alleviated pyroptosis. This finding revealed that ZEB2 was a regulator of the astrogliosis after ischemia/reperfusion injury, and then astrogliosis promoted neuron regeneration via decreased neuron pyroptosis. Therefore, ZEB2 may be a potential therapeutic target for ischemia/reperfusion injury.

BackgroundIn patients with stroke, current guidelines recommend non-invasive vascular imaging to identify intracranial vessel occlusions (VO) that may benefit from endovascular treatment (EVT). However, VO can be missed in CT angiography (CTA) readings. We aim to evaluate the impact of consistently including CT perfusion (CTP) in admission stroke imaging protocols.MethodsFrom April to October 2020 all patients admitted with a suspected acute ischemic stroke underwent urgent non-contrast CT, CTA and CTP and were treated accordingly. Hypoperfusion areas defined by time-to-maximum of the tissue residue function (Tmax) >6 s, congruent with the clinical symptoms and a vascular territory, were considered VO (CTP-VO). In addition, two experienced neuroradiologists blinded to CTP but not to clinical symptoms retrospectively evaluated non-contrast CT and CTA to identify intracranial VO (CTA-VO).ResultsOf the 338 patients included in the analysis, 157 (46.5%) presented with CTP-VO (median Tmax >6s: 73 (29–127) mL). CTA-VO was identified in 83 (24.5%) of the cases. Overall CTA-VO sensitivity for the detection of CTP-VO was 50.3% and specificity was 97.8%. Higher hypoperfusion volume was associated with increased CTA-VO detection (OR 1.03; 95% CI 1.02 to 1.04). EVT was performed in 103 patients (30.5%; Tmax >6s: 102 (63–160) mL), representing 65.6% of all CTP-VO. Overall CTA-VO sensitivity for the detection of EVT-VO was 69.9% and specificity was 95.3%. Among patients who received EVT, the rate of false negative CTA-VO was 30.1% (Tmax >6s: 69 (46–99.5) mL).ConclusionSystematically including CTP in acute stroke admission imaging protocols may increase the diagnosis of VO and rate of EVT.