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This updated second edition of "Acute Ischemic Stroke: Imaging and Intervention" provides a comprehensive account of the state of the art in the diagnosis and treatment of acute ischemic stroke. The basic format of the first edition has been retained, with sections on fundamentals such as pathophysiology and causes, imaging techniques and interventions. However, each chapter has been revised to reflect the important recent progress in advanced neuroimaging and the use of interventional tools. In addition, a new chapter is included on the classification instruments for ischemic stroke.

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to improve the patient's outcome; however, important limitations such as a narrow therapeutic window, the ability to reach brain targets, or drug side effects constitute some of the main aspects that limit the clinical applicability of the current treatments. Nanotechnology has emerged as a promising tool to overcome many of these drug limitations and improve the efficacy of treatments for neurological diseases such as stroke. The use of nanoparticles as a contrast agent or as drug carriers to a specific target are some of the most common approaches developed in nanomedicine for stroke. Throughout this review, we have summarized our experience of using nanotechnology tools for the study of stroke and the search for novel therapies ; This project was supported by the FRQS, ISCIII (AC19/00031 and AC20/00041), and ANR under the framework of EuroNanoMed III_2020 (PLATMED_project); the European Union program FEDER and the European Regional Development Fund–ERDF; and the Xunta de Galicia (IN607D2020/03 and ED431G2019/03). E.P. and B.P acknowledge the AEI grants (PID2019-111218RB-I00 and RyC-2017-23457). Finally, F.C. thanks the ISCIII and Miguel Servet program (CPII19/00020) ; SI

Health care costs continue to rise toward unsustainable levels that will affect our nation's ability to support other key funding priorities for education, military, and infrastructure. Changing the way we deliver health care is critical to mitigating this financial crisis. This review highlights opportunities for redesigning care of acute ischemic stroke and TIA to maintain quality while substantially lowering costs. The recent innovations described are (1) adopting teleneurology networks to improve access to thrombolysis for acute ischemic stroke; (2) improving efficiency of emergency care for acute ischemic stroke; and (3) providing alternatives to inpatient care for TIA. Applying such process innovations will enable us to achieve the goal of patients and the nation—high-quality care at an affordable cost.

Remote ischemic conditioning (RIC) is a promising therapeutic approach for ischemic stroke patients. It has been proven that RIC reduces infarct size and improves functional outcomes. RIC can be applied either before ischemia (pre-conditioning; RIPreC), during ischemia (per-conditioning; RIPerC) or after ischemia (post-conditioning; RIPostC). Our aim was to systematically determine the efficacy of RIC in reducing infarct volumes and define the cellular pathways involved in preclinical animal models of ischemic stroke. A systematic search in three databases yielded 50 peer-review articles. Data were analyzed using random effects models and results expressed as percentage of reduction in infarct size (95% CI). A meta-regression was also performed to evaluate the effects of covariates on the pooled effect-size. 95.3% of analyzed experiments were carried out in rodents. Thirty-nine out of the 64 experiments studied RIPostC (61%), sixteen examined RIPreC (25%) and nine tested RIPerC (14%). In all studies, RIC was shown to reduce infarct volume (− 38.36%; CI − 42.09 to − 34.62%) when compared to controls. There was a significant interaction caused by species. Short cycles in mice significantly reduces infarct volume while in rats the opposite occurs. RIPreC was shown to be the most effective strategy in mice. The present meta-analysis suggests that RIC is more efficient in transient ischemia, using a smaller number of RIC cycles, applying larger length of limb occlusion, and employing barbiturates anesthetics. There is a preclinical evidence for RIC, it is safe and effective. However, the exact cellular pathways and underlying mechanisms are still not fully determined, and its definition will be crucial for the understanding of RIC mechanism of action. ; This study was supported by the Government of Catalonia-Agència de Gestió d'Ajuts Universitaris i de Recerca (FP: 2017 SGR 1628), Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, "Investing in your future") (FP: Project PI17-01725) and the INVICTUS plus Research Network (Carlos III Health Institute). C.T-Q. was supported by a Grant from Contratos predoctorales de formación en investigación en salud (PFIS; FI18/00319).

Objective: Stroke is a major health problem, yet no studies on stroke have been reported from Palestine. This one-year, hospital-based study was conducted to determine the prevalence of risk factors and the in-hospital mortality rate in patients with ischemic stroke. Method: All patients admitted to Al-Watani government hospital and diagnosed with ischemic stroke between September 2006 and August 2007 were included in the study. Data were obtained by retrospective review of medical charts. Pearson Chi-square and independent t test were used in the univariate analysis. Multiple logistic regression analysis was used to determine the independent predictors of in-hospital mortality rates among the patients. Statistical testing and graphics were carried out using SPSS 15. Results: We identified 153 ischemic stroke patients (83 females and 70 males) of whom 92 were having a first-ever stroke (FES). Patients had several prevalent modifiable risk factors such as hypertension (HTN) (66%), diabetes mellitus (DM) (45.8%), and renal reduced renal function (crcl < 60 ml/ min) (33.9%). Twenty-six (17%) of the patients died during hospitalization. Four variables were significantly associated with in-hospital mortality: history of previous stroke (P= 0.004), crcl at admission (P = 0.004), number of post-stroke complications (P = 0.001), and age (P = 0.043). Multiple logistic regression analysis indicated that the number of post-stroke complications (P= 0.001) and previous stroke (P = 0.03) were significant independent predictors of in-hospital mortality. Conclusion: Screening and better control of risk factors, especially HTN, DM and renal dysfunction, are required to decrease the incidence and in-hospital mortality among patients with ischemic stroke.

Post-stroke fatigue (PSF) could have a negative impact on the rehabilitation potential, quality of life, and work capacity of younger ischemic stroke patients. The available quantitative and qualitative research on the prevalence, predictors, and interventions associated with PSF have not explicitly focused on young adults. This scoping review aimed to summarise the available evidence on PSF in young adults after ischemic stroke (prevalence, predictors, and consequences, assessment tools, as well as interventions to reduce fatigue in young stroke survivors). The following methodological procedures were used for this scoping review: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Joanna Briggs Institute updated methodological guidance. A total of 3483 studies were identified through a bibliographic search in the Ovid MEDLINE, PubMed, Scopus, ProQuest Central, APA PsycINFO, SocINDEX, and CINAHL Plus databases. Ten studies that met the inclusion criteria were included in the scoping review. Only four studies explicitly addressed PSF in young adults after ischemic stroke. The prevalence of fatigue among young adults who had suffered an ischemic stroke ranged from 41.0% to 57.8%. Seven studies found a significant association between PSF, depression, and anxiety. Fatigue in young stroke survivors significantly affects their return to work and it is an independent predictor of poor quality of life. The number of research studies on fatigue in young adults after ischemic stroke is small and they mainly focus on fatigue as a predictor of quality of life after stroke. There is a need for further studies that address the phenomenon of fatigue after ischemic stroke and validate the effectiveness of interventions to reduce fatigue in young stroke survivors.

Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection. Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care. Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%. Methods and Design: We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device. Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days. Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS. ; Aquest treball ha estat finançat per: l'Agència de Gestió d'Ajuts Universitaris i de Recerca de la Generalitat de Catalunya 2017 SGR 1628, Instituto de Salud Carlos III, European Union (EU) PI17-01725 i INVICTUS plus Research Network (Carlos III Health Institute)

Background and objective: Anti-hypertensive medications are recommended for prevention of recurrent ischemic stroke in hypertensive and normotensive patients. The objective of this study was to analyze the use of anti-hypertensive therapy in acute ischemic stroke survivors.Methods: All ischemic stroke survivors discharged from Al-watani governmental hospital in Palestine from August 2006 until September 2007 were investigated. Demographic data, clinical characteristics, and different classes of anti-hypertensive medications prescribed to stroke survivors were analyzed using SPSS 15.Results: One hundred and twenty four ischemic stroke survivors were identified, of which 80 (64.5%) had a documented history of hypertension (HTN). Two thirds of the survivors (n = 82; 66.1%) were prescribed anti-hypertensive medications, mostly as mono-therapy, at discharge. Angiotensin-converting enzyme inhibitors (ACEI) 65 (45.6%), followed by diuretics 41 (34.5%) were the most common drug classes prescribed. ACEI were used in combination with diuretics in 29 (23.4%) survivors. Among survivors with a documented history of HTN, 70 (85.5%) were prescribed anti-hypertensive medications at discharge while 12 (8.5%) of survivors with no history of HTN were prescribed anti-hypertensive medications at discharge.Conclusion: In this study, the use of anti-hypertensive medications as a mono-therapy was common among those with a history of hypertension but not among those without a history of hypertension.

Background: It is predicted that stroke's incidence and impact will increase considerably over time. Proper management of stroke depends on a reliable and urgent diagnosis that includes patient / relative - emergency team - hospital chain, so the diagnosis begins with the recognition of the first signs of stroke. In order to act promptly in the acute period and subsequently assess the risk factors, the neurological service needs to be equipped with highperformance neuroimaging and clinical laboratory. The specific treatment of acute ischemic stroke is nowadays the reperfusion procedure, performed by thrombolytic therapy and, since 2015, by the endovascular treatment. Stroke is also a leading cause of severe long-term disability. The rehabilitation of post-stroke patients requires an interdisciplinary approach, in order to prevent recurrences, combat complications and reintegrate the patient into society. Conclusions: Stroke remains one of the leading determinants of death and severe disability worldwide and the Republic of Moldova is not an exception. Considering the narrow window for recognition and administration of outcome-modifying treatment, the management of stroke focuses mainly on rapid reperfusion via intravenous thrombolysis and endovascular thrombectomy. The availability of this specialized treatment in the Stroke Unit could improve the patient's outcome and decrease the disability's level and economical burden. There is clear evidence that preventing a stroke is much more effective than treating it, so we should seize the opportunity and act involving not only the medical staff, but also the government, health decision makers, specialists in public health and international agencies

Abstract: Stroke has a significant prevalence in Romania. The predisposition for this multifactorial disease is partially known. The aim of this study is to investigate the predisposition for stroke in Romanian population. Material and methods. We selected cases with recent ischemic stroke (n=100) and healthy control subjects (n=100). The AGTR1 A1166C (rs5186) polymorphism was genotyped by restriction of amplicons with Dde I endonuclease. Results. Active cigarette smoking (O.R. =6.92, p=0.0001) or presence of the AT1R C variant (O.R. =6.69, p=0.0006) in overweight or obese women significantly increase the risk for ischemic stroke. The diagnosis of stroke (71.5 vs 68 years old) or T2DM (63.39 vs 60.77 years old) was recorded at an older age in women compared to men (p<0.05). Obesity considered independent (O.R. =4.22, p<0.05) or in association with T2DM (O.R. = 10.16, p=0.0002) confers the highest risk of stroke when compared to women. Conclusions. Obesity in association with T2DM confers the highest risk of stroke for men when compared to women. Active cigarette smoking or AT1R C variant significantly increase the risk for stroke in women with a high BMI compared with controls. Keywords: stroke, AT1R, BMI, cigarette smoking

Objective: To discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones. Methods: Metabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited ,24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort. Results: Metabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (,3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described. Conclusions: The use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases. ; Supported by the Autonomous Government of Catalunya (2009SGR- 735), the Spanish Ministry of Health (FIS 11-02033), and the Marató of TV3 Foundation (95/C/2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Samples were obtained with the support of IRBLleida biobank and RETICS BIOBANCOS (RD09/0076/00059)

<p class="Pa7"> <strong>Objective: </strong>Conflicting reports exist about hospital arrival time after stroke onset in Hispanics compared with African Americans and Caucasians. Our current study inves­tigates race-ethnic disparities in hospital arrival times after stroke onset.</p><p class="Pa7"><strong>Methods: </strong>We performed a retrospective analysis of hospital arrival times in Hispanic, African American, and Caucasian acute ischemic stroke patients (N=1790) present­ing to a tertiary-care hospital in the Bronx, New York. A multivariable logistic regression model was used to identify the association between race-ethnicity and hospital arrival time adjusting for age, sex, socioeconomic status (SES), NIH stroke scale (NIHSS), history of stroke, preferred language and transportation mode to the hospital.</p><p class="Pa7"><strong>Results: </strong>There were 338 Caucasians, 662 Hispanics, and 790 African Americans in the cohort. Compared with Caucasians, African Americans and Hispanics were younger (P&lt;.0001 respectively), had lower SES (P&lt;.001 respectively) and were less likely to use EMS (P=.003 and P=.001, respec­tively). A greater proportion of Hispanic and African American women had delayed hos­pital arrival times (≥3 hours) after onset of stroke symptoms compared with Caucasian women (74% of Hispanic, 72% of African American, and 59% of Caucasian women), but this difference between race-ethnicities is no longer present after adjusting for socioeconomic status. Compared with Cau­casian men, hospital arrival ≥3 hours after symptom onset was more likely for African American men (OR 1.72, 95% CI:1.05- 2.79) but not Hispanic men (OR .80, 95% CI .49-1.30).</p><p class="Default"><strong>Conclusions: </strong>African American men and socially disadvantaged women delay in presenting to the hospital after stroke onset. Future research should focus on identify­ing the factors contributing to pre-hospital delay among race-ethnic minorities. <em></em></p><p class="Default"><em>Ethn Dis. </em>2017;27(2):125-132; doi:10.18865/ed.27.2.125.</p>

Background: The discovery of novel biomarkers of stroke etiology would be most helpful in management of acute ischemic stroke patients. Recently, circular RNAs (circRNAs) have been proposed as candidate biomarkers of neurological conditions due to its high stability. circRNAs function as sponges, sequestering miRNAs and are involved in most relevant biological functions. Our aim was to identify differentially expressed circRNAs in acute ischemic stroke patients according to stroke etiology. Methods: A comprehensive expression profile of blood circRNAs was conducted by Arraystar Human circRNA arrays (13,617 probes) on a discovery cohort of 30 stroke patients with different stroke etiologies by TOAST classification. Real-time quantitative PCR (RT-qPCR) was used to validate array results in a cohort of 50 stroke patients. Functional in silico analysis was performed to identify potential interactions with microRNAs (miRNAs) and pathways underlying deregulated circRNAs. Results: A set of 60 circRNAs were found to be upregulated in atherotrombotic versus cardioembolic strokes (fold-change > = 1.5 and p-value ≤ 0.05). Differential expression of hsa_circRNA_102488, originated from UBA52 gene, was replicated in the validation cohort. RNA-binding proteins (RBPs) sites of hsa_circRNA_102488 clustered around AGO2 and FUS proteins. Further functional analysis revealed interactions between deregulated circRNAs and a set of miRNAs involved in stroke-related pathways, such as fatty acid biogenesis or lysine degradation. Conclusion: Different stroke subtypes show specific profiles of circRNAs expression. circRNAs may serve as a new source of biomarkers of stroke etiology in acute ischemic stroke patients. ; This work was supported by Navarre Government Funding (Industry and Health department) through ADITECH and by RED INVICTUS (RD16/0019/0024) from the Institute of Health Carlos III, jointly funded by European Regional Development Fund (ERDF), European Union. AUC received a grant 'Doctorados industriales 2018–2020' founded by Government of Navarra and MM received a grant 'Programa de intensificación' founded by 'LaCaixa Foundation' and Fundación Caja-Navarra.

Ischemic stroke is one of the leading causes of global disease burden. Vietnam, among other low- and middle-income countries, bears nearly 90% of the ischemic stroke burden. This study was a cost-of-illness study conducted from the healthcare system perspective to estimate the direct medical costs and associated factors for acute ischemic stroke patients at Bach Mai Hospital, a major hospital in Hanoi, Vietnam. A total of 500 eligible patients with acute ischemic stroke at the Neurology Department of Bach Mai Hospital from July 2021 to December 2021 were included. Patient characteristics and treatment information were collected via medical records and patient interviews. The majority of the patients were men (65.8%), with a mean age of 65.3 years. The average direct medical cost per patient was 10.5 ± 7.3 million Vietnam Dong (~454.2 ± 313.8 US dollars). The cost of hospital beds accounted for most of the total cost (34.6%), followed by medications and infusion fluid costs (27%) and diagnostic imaging (12.6%). Factors significantly associated with higher direct medical costs were the duration of stay, stroke severity, complications, number of comorbidities, and intravenous thrombolysis treatment. The study highlighted the need for a reduction in the duration of hospital stay and an improvement in onset-to-hospital arrival time.