Journal: J Stroke

Sorted by: date / impact
Abstract

External Validation of the ELAPSS Score for Prediction of Unruptured Intracranial Aneurysm Growth Risk.

Kammen MSV, Greving JP, Kuroda S, Kashiwazaki D, ... Rinkel GJE, Vergouwen MDI
Background and purpose
Prediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for prediction of the risk of unruptured intracranial aneurysm growth.
Methods
From 11 international cohorts of patients ≥18 years with ≥1 unruptured intracranial aneurysm and ≥6 months of radiological follow-up, we collected data on the predictors of the ELAPSS score, and calculated 3- and 5-year absolute growth risks according to the score. Model performance was assessed in terms of calibration (predicted versus observed risk) and discrimination (c-statistic).
Results
We included 1,072 patients with a total of 1,452 aneurysms. During 4,268 aneurysm-years of follow-up, 199 (14%) aneurysms enlarged. Calibration was comparable to that of the development cohort with the overall observed risks within the range of the expected risks. The c-statistic was 0.69 (95% confidence interval [CI], 0.64 to 0.73) at 3 years, compared to 0.72 (95% CI, 0.68 to 0.76) in the development cohort. At 5 years, the c-statistic was 0.68 (95% CI, 0.64 to 0.72), compared to 0.72 (95% CI, 0.68 to 0.75) in the development cohort.
Conclusion
s The ELAPSS score showed accurate calibration for 3- and 5-year risks of aneurysm growth and modest discrimination in our external validation cohort. This indicates that the score is externally valid and could assist patients and physicians in predicting growth of unruptured intracranial aneurysms and plan follow-up imaging accordingly.



J Stroke: 30 Aug 2019; 21:340-346
Kammen MSV, Greving JP, Kuroda S, Kashiwazaki D, ... Rinkel GJE, Vergouwen MDI
J Stroke: 30 Aug 2019; 21:340-346 | PMID: 31590478
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Abstract

Selection of Candidates for Endovascular Treatment: Characteristics According to Three Different Selection Methods.

Chung JW, Kim BJ, Jeong HG, Seo WK, ... Bae HJ, Bang OY
Background and purpose
To investigate the number and characteristics of patients eligible for endovascular treatment (EVT) determined using three different selection methods clinical-core mismatch, target mismatch, and collateral status.
Methods
Using the data of consecutive patients from two prospectively maintained registries of university medical centers, the number and characteristics of patients according to the three selection methods were investigated and their correlation was analyzed. Patients with anterior circulation stroke due to occlusion of the middle cerebral and/or internal carotid artery and a National Institute of Health Stroke Scale (NIHSS) score of ≥6 points, who arrived within 8 hours or between 6 and 12 hours of symptom onset and underwent magnetic resonance imaging prior to EVT, were included. Collateral status was assessed using magnetic resonance perfusion-derived collateral flow maps.
Results
Three hundred thirty-five patients were investigated; the proportions of patients who were eligible and ineligible for EVT in all three selection methods were both small (n=85, 25.4%; n=54, 16.1%, respectively). The intercorrelation among the three selection methods was low (κ=0.235). The baseline NIHSS score and onset-to-selection time interval were associated with the presence of clinical-core mismatch, while the penumbra/core volume ratio and onset-to-selection time interval were related to target mismatch; none of these variables were associated with collateral status. The infarct core volume was associated with favorable profiles in all three selection methods.
Conclusion
s Although the application of individual selection methods resulted in favorable outcomes after EVT in clinical trials, there is a significant discrepancy in EVT eligibility depending on the selection method used.



J Stroke: 30 Aug 2019; 21:332-339
Chung JW, Kim BJ, Jeong HG, Seo WK, ... Bae HJ, Bang OY
J Stroke: 30 Aug 2019; 21:332-339 | PMID: 31590477
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Abstract

Calcium Intake and Serum Calcium Level in Relation to the Risk of Ischemic Stroke: Findings from the REGARDS Study.

Dibaba DT, Xun P, Fly AD, Bidulescu A, ... Unverzagt FW, He K
Background and purpose
Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke.
Methods
The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a case-cohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed.
Results
During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented. Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; Plinear-trend=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke (Pnon-linear=0.006). In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; Plinear-trend=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol.
Conclusion
s These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.



J Stroke: 30 Aug 2019; 21:312-323
Dibaba DT, Xun P, Fly AD, Bidulescu A, ... Unverzagt FW, He K
J Stroke: 30 Aug 2019; 21:312-323 | PMID: 31590475
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Abstract

Duration of Implantable Cardiac Monitoring and Detection of Atrial Fibrillation in Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Tsivgoulis G, Katsanos AH, Köhrmann M, Caso V, ... Schellinger PD, Alexandrov AV
Background and purpose
Current guidelines do not provide firm directions on atrial fibrillation (AF) screening after ischemic stroke (IS). We sought to investigate the association of implantable cardiac monitoring (ICM) duration with the yield of AF detection in IS patients.
Methods
We included studies reporting AF detection rates by ICM in IS patients with negative initial AF screening. We excluded studies reporting prolonged cardiac monitoring with devices other than ICM, not providing AF detection rates or monitoring duration, and reporting overlapping data for the same population. The random-effects model was used for all pooled estimates and meta-regression analyses.
Results
We included 28 studies (4,531 patients, mean age 65 years). In meta-regression analyses, the proportion of AF detection by ICM was independently associated with monitoring duration (coefficient=0.015; 95% confidence interval [CI], 0.005 to 0.024) and mean patient age (coefficient=0.009; 95% CI, 0.003 to 0.015). No associations were detected with other patient characteristics, including IS subtype (cryptogenic vs. embolic stroke of undetermined source) or time from IS onset to CM implantation. In subgroup analyses, significant differences (P<0.001) in the AF detection rates were found for ICM duration (<6 months: 5% [95% CI, 3% to 6%]; ≥6 and ≤12 months: 21% [95% CI, 16% to 25%]; >12 and ≤24 months: 26% [95% CI, 22% to 31%]; >24 months: 34% [95% CI, 29% to 39%]).
Conclusion
s Extended duration of ICM monitoring and increased patient age are factors that substantially increase AF detection in IS patients with initial negative AF screening.



J Stroke: 30 Aug 2019; 21:302-311
Tsivgoulis G, Katsanos AH, Köhrmann M, Caso V, ... Schellinger PD, Alexandrov AV
J Stroke: 30 Aug 2019; 21:302-311 | PMID: 31590474
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Abstract

The Incidence of Perioperative Stroke: Estimate Using State and National Databases and Systematic Review.

Al-Hader R, Al-Robaidi K, Jovin T, Jadhav A, Wechsler LR, Thirumala PD
Background and purpose
Perioperative stroke remains a devastating complication after surgical procedures, due to hemodynamic and inflammatory changes that increase the risk of strokes within 30 days following surgery. We aimed to assess the incidence of perioperative strokes in patients undergoing various surgical procedures and reach a national estimate.
Methods
A retrospective cohort study was conducted using California State Inpatient Databases, State Emergency Department Databases, State Ambulatory Surgery and Services Databases, and the National Inpatient Sample (NIS) during the period 2008 to 2011 from the Healthcare Cost and Utilization Project. A systematic review was conducted using PubMed, Embase, and Web of Science databases to obtain published articles that reported the incidence of perioperative stroke in various surgical procedures.
Results
Analysis of 3,694,410 surgical encounters from the state of California (mean±standard deviation age: 52.4±21.1 years) yielded an overall rate of perioperative stroke of 0.32% (n=11,759). The incidence of perioperative strokes was highest following neurological (1.25%), vascular (1.07%), and cardiac (0.98%) surgeries. The NIS database contained a total of 48,672,974 weighted hospitalizations and yielded a rate of perioperative stroke of 0.42% (n=204,549). The systematic review completed yielded 187 articles, which had an overall sample size of 184,922 and an incidence of perioperative stroke ranging from 0% to 13.86%. It is estimated that in any given year, there would be approximately 40,000 to 55,000 (0.33% to 0.46%) perioperative strokes nationally.
Conclusion
s Our findings support further strategies to identify and stratify patients undergoing surgical procedures with a high incidence of perioperative strokes to improve patient counseling and a future potential treatment plan.



J Stroke: 30 Aug 2019; 21:290-301
Al-Hader R, Al-Robaidi K, Jovin T, Jadhav A, Wechsler LR, Thirumala PD
J Stroke: 30 Aug 2019; 21:290-301 | PMID: 31590473
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Abstract

Clinical Variables and Genetic Risk Factors Associated with the Acute Outcome of Ischemic Stroke: A Systematic Review.

Torres-Aguila NP, Carrera C, Muiño E, Cullell N, ... Fernandez-Cadenas I,

Stroke is a complex disease and one of the main causes of morbidity and mortality among the adult population. A huge variety of factors is known to influence patient outcome, including demographic variables, comorbidities or genetics. In this review, we expound what is known about the influence of clinical variables and related genetic risk factors on ischemic stroke outcome, focusing on acute and subacute outcome (within 24 to 48 hours after stroke and until day 10, respectively), as they are the first indicators of stroke damage. We searched the PubMed data base for articles that investigated the interaction between clinical variables or genetic factors and acute or subacute stroke outcome. A total of 61 studies were finally included in this review. Regarding the data collected, the variables consistently associated with acute stroke outcome are: glucose levels, blood pressure, presence of atrial fibrillation, prior statin treatment, stroke severity, type of acute treatment performed, severe neurological complications, leukocyte levels, and genetic risk factors. Further research and international efforts are required in this field, which should include genome-wide association studies.



J Stroke: 30 Aug 2019; 21:276-289
Torres-Aguila NP, Carrera C, Muiño E, Cullell N, ... Fernandez-Cadenas I,
J Stroke: 30 Aug 2019; 21:276-289 | PMID: 31590472
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Abstract

Non-Vitamin K Antagonist Oral Anticoagulants in Medical Conditions at High Risk of Thromboembolism beyond Atrial Fibrillation.

Hong KS

Non-Vitamin K antagonist oral anticoagulants (NOACs) have been extensively investigated in medical conditions at high risk of venous or arterial thrombosis other than atrial fibrillation (AF), including hip or knee arthroplasty, acute venous thromboembolism (VTE), cancer-associated VTE, acute coronary syndrome (ACS), stable atherosclerotic vascular disease, chronic heart failure, and embolic stroke of undetermined source (ESUS). Two large ESUS trials failed to show the benefit of rivaroxaban or dabigatran, and large randomized controlled trial (RCT) data of NOACs are lacking for another potential candidates of patent foramen ovale-related stroke, acute ischemic stroke, and cerebral venous thrombosis. On the other hand, high quality evidences of NOACs have been compiled for VTE prophylaxis after hip or knee arthroplasty, acute VTE, cancer-associated VTE, and concomitant ACS and AF, which have been reflected in clinical practice guidelines. In addition, RCTs showed the benefit of very low dose rivaroxaban in combination with antiplatelet therapy in patients with ACS and in those with stable cardiovascular disease. This article summarizes the accumulated evidences of NOACs in cardiovascular diseases beyond AF, and aims to inform healthcare providers of optimal regimens tailored to individual medical conditions and help investigators design future clinical trials.



J Stroke: 30 Aug 2019; 21:259-275
Hong KS
J Stroke: 30 Aug 2019; 21:259-275 | PMID: 31590471
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Abstract

Digital Therapeutics: Emerging New Therapy for Neurologic Deficits after Stroke.

Choi MJ, Kim H, Nah HW, Kang DW

Digital therapeutics is an evidence-based intervention using high-quality software, with the sole purpose of treatment. As many healthcare systems are encountering high demands of quality outcomes, the need for digital therapeutics is gradually increasing in the clinical field. We conducted review of the implications of digital therapeutics in the treatment of neurological deficits for stroke patients. The implications of digital therapeutics have been discussed in four domains: cognition, speech and aphasia, motor, and vision. It was evident that different forms of digital therapeutics such as online platforms, virtual reality trainings, and iPad applications have been investigated in many trials to test its feasibility in clinical use. Although digital therapeutics may deliver high-quality solutions to healthcare services, the medicalization of digital therapeutics is accompanied with many limitations. Clinically validated digital therapeutics should be developed to prove its efficacy in stroke rehabilitation.



J Stroke: 30 Aug 2019; 21:242-258
Choi MJ, Kim H, Nah HW, Kang DW
J Stroke: 30 Aug 2019; 21:242-258 | PMID: 31587534
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Abstract

Early Functional Connectivity Predicts Recovery from Visual Field Defects after Stroke.

Kim YH, Cho AH, Kim D, Kim SM, ... Kim JS, Kang DW
Background and purpose
We aimed to assess whether early resting-state functional connectivity (RSFC) changes measured via functional magnetic resonance imaging (fMRI) could predict recovery from visual field defect (VFD) in acute stroke patients.
Methods
Patients with VFD due to acute ischemic stroke in the visual cortex and age-matched healthy controls were prospectively enrolled. Serial resting-state (RS)-fMRI and Humphrey visual field (VF) tests were performed within 1 week and at 1 and 3 months (additional VF test at 6 months) after stroke onset in the patient group. The control group also underwent RS-fMRI and a Humphrey VF test. The changes in RSFCs and VF scores (VFSs) over time and their correlations were investigated.
Results
In 32 patients (65±10 years, 25 men), the VFSs were lower and the interhemispheric RSFC in the visual cortices was decreased compared to the control group (n=15, 62±6 years, seven men). The VFSs and interhemispheric RSFC in the visual cortex increased mainly within the first month after stroke onset. The interhemispheric RSFC and VFSs were positively correlated at 1 month after stroke onset. Moreover, the interhemispheric RSFCs in the visual cortex within 1 week were positively correlated with the follow-up VFSs.
Conclusions
Interhemispheric RSFCs in the visual cortices within 1 week after stroke onset may be a useful biomarker to predict long-term VFD recovery.



J Stroke: 29 Apr 2019; 21:207-216
Kim YH, Cho AH, Kim D, Kim SM, ... Kim JS, Kang DW
J Stroke: 29 Apr 2019; 21:207-216 | PMID: 31161764
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Abstract

Anticoagulants in Older Patients with Nonvalvular Atrial Fibrillation after Intracranial Hemorrhage.

Perreault S, Côté R, White-Guay B, Dorais M, Oussaïd E, Schnitzer ME
Background and purpose
Patients with nonvalvular atrial fibrillation (NVAF) who survive an intracranial hemorrhage (ICH) have an increased risk of ischemic stroke and systemic embolism (IS/ SE). We investigated whether starting oral anticoagulants (OACs) among older NVAF patients after an ICH was associated with a lower risk of IS/SE and mortality but offset by an increase in major bleeding.
Methods
We assembled a patient cohort from the Quebec Régie de l\'Assurance Maladie du Québec (RAMQ) and Med-Echo administrative databases. We identified older adults with NVAF from 1995 to 2015. All patients with incident ICH and discharged in community were included. Patients were categorized according to OAC exposure. Outcomes included IS/SE, all-cause mortality, recurrent ICH and major bleeding after a quarantine period of 6 weeks. Crude event rates were calculated at 1-year of follow-up, and Cox proportional hazard models with a time-dependent binary exposure were used to assess adjusted hazard ratios (AHRs).
Results
The cohort of 683 NVAF patients with ICH aged 83 years on average. The rates (per 100 person-years) for IS/SE, death, ICH and major bleeding were 3.3, 40.6, 11.4, and 2.7 for the no OAC group; and 2.6, 16.3, 5.2, and 5.2 for OAC group, respectively. The AHR for IS/SE and death was 0.10 (95% confidence interval [CI], 0.05 to 0.21), 0.43 (95% CI, 0.19 to 0.97) for recurrent ICH and 1.73 (95% CI, 0.71 to 4.20) for major extracranial bleeding comparing OAC exposure to non-exposed.
Conclusions
Initiating OAC after ICH in older individuals with NVAF is associated with a reduction of IS/SE and mortality and a trend in recurrent ICH supporting its use after ICH.



J Stroke: 29 Apr 2019; 21:195-206
Perreault S, Côté R, White-Guay B, Dorais M, Oussaïd E, Schnitzer ME
J Stroke: 29 Apr 2019; 21:195-206 | PMID: 31161763
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Abstract

Family History, Tobacco Smoking, and Risk of Ischemic Stroke.

Fan M, Lv J, Yu C, Guo Y, ... Li L,
Background and purpose
Both genetic factors and smoking are associated with ischemic stroke (IS) risk. However, little is known about the potential interaction of these factors. We aimed to assess whether smoking and a positive family history interact to increase the risk of IS.
Methods
The nationwide prospective study recruited 210,000 men and 300,000 women in 2004 to 2008 at ages 30 to 79 years. During 9.7 years of follow-up, we documented 16,923 and 20,656 incident IS cases in men and women without major chronic diseases at baseline, respectively. Multivariable Cox regression models were used to examine associations between family history and IS. Likelihood ratio tests were used to test the smoking-family history interactions on IS.
Results
About 67.8% (n=135,168) of men ever smoked regularly compared with 2.7% (n=7,775) of women. Among men, a significant interaction between family history and smoking on IS was observed (P for interaction=0.03), with more pronounced association between family history and IS among ever-regular smokers (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.16 to 1.27) than among never-smokers (HR, 1.11; 95% CI, 1.01 to 1.23). The association between family history and IS among ex-smokers after more than 10 years of cessation (HR, 1.01; 95% CI, 0.85 to 1.20) appeared similar to that among never-smokers. Among women, a similar but not significant interaction between family history and smoking on IS was observed. Ever-regular smokers who had a family history of stroke had the highest risk of IS.
Conclusions
Among Chinese men, the association of family history with IS was accentuated by smoking, and such accentuation tended to be lowered by cessation.



J Stroke: 29 Apr 2019; 21:175-183
Fan M, Lv J, Yu C, Guo Y, ... Li L,
J Stroke: 29 Apr 2019; 21:175-183 | PMID: 31161762
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Abstract

tPA Helpers in the Treatment of Acute Ischemic Stroke: Are They Ready for Clinical Use?

Kim JS

Tissue plasminogen activator (tPA) is the only therapeutic agent approved to treat patients with acute ischemic stroke. The clinical benefits of tPA manifest when the agent is administered within 4.5 hours of stroke onset. However, tPA administration, especially delayed administration, is associated with increased intracranial hemorrhage (ICH), hemorrhagic transformation (HT), and mortality. In the ischemic brain, vascular remodeling factors are upregulated and microvascular structures are destabilized. These factors disrupt the blood brain barrier (BBB). Delayed recanalization of the vessels in the presence of relatively matured infarction appears to damage the BBB, resulting in HT or ICH, also known as reperfusion injury. Moreover, tPA itself activates matrix metalloproteases, further aggravating BBB disruption. Therefore, attenuation of edema, HT, or ICH after tPA treatment is an important therapeutic strategy that may enable clinicians to extend therapeutic time and increase the probability of excellent outcomes. Recently, numerous agents with various mechanisms have been developed to interfere with various steps of ischemia/ reperfusion injuries or BBB destabilization. These agents successfully reduce infarct volume and decrease the incidence of ICH and HT after delayed tPA treatment in various animal stroke models. However, only some have entered into clinical trials; the results have been intriguing yet unsatisfactory. In this narrative review, I describe such drugs and discuss the problems and future directions. These \"tPA helpers\" may be clinically used in the future to increase the efficacy of tPA in patients with acute ischemic stroke.



J Stroke: 29 Apr 2019; 21:160-174
Kim JS
J Stroke: 29 Apr 2019; 21:160-174 | PMID: 31161761
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Abstract

Gut Microbiota and Ischemic Stroke: The Role of Trimethylamine N-Oxide.

Nam HS

Trimethylamine N-oxide (TMAO) is produced when trimethylamine, a waste product of gut microbes, is converted via hepatic flavin monooxygenases. As TMAO is a potential causative factor in various cardiovascular diseases (CVDs) considerable research interest has arisen on its use as a biomarker. Higher TMAO levels are associated with future risk of both incident CVD in the general population and established CVD, including stroke. The addition of TMAO into models with traditional risk factors significantly improved the prediction of future CVD risk. TMAO promotes atherosclerosis and is associated with platelet hyperreactivity and inflammation, which are in turn associated with the development of stroke and its secondary consequences. Additionally, TMAO may play a key mediator role in the relationship between the diet, gut microbiota, and CVD development. Compelling evidence suggesting that TMAO is both a risk factor and prognostic marker of stroke and CVD. Potential therapeutic strategy of diet and drugs in reducing TMAO levels have emerged. Thus, TMAO is a novel biomarker and target in stroke and CVD prevention.



J Stroke: 29 Apr 2019; 21:151-159
Nam HS
J Stroke: 29 Apr 2019; 21:151-159 | PMID: 31161760
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Abstract

Effects of Thiazolidinedione and New Antidiabetic Agents on Stroke.

Ahn CH, Lim S

Patients with hyperglycemia are at a high risk of cardio- and cerebrovascular diseases. Diabetes patients also have poor outcomes after cerebrovascular disease development. Several classes of drugs are used for diabetes management in clinical practice. Thiazolidinedione (TZD) was introduced in the late 1990s, and new antidiabetic agents have been introduced since 2000. After issues with rosiglitazone in 2007, the U.S. Food and Drug Administration strongly recommended that trials investigating cardiovascular risk associated with new antidiabetic medications should be conducted before drug approval in the United States, to prove the safety of these new drugs and to determine their superiority to previous medications. Currently, results are available from two studies with TZD focusing on cardiovascular diseases, including stroke, and from 12 cardiovascular outcome trials focusing on major adverse cardiovascular events associated with new antidiabetic agents (four with dipeptidyl peptidase-4 inhibitors, three with sodium-glucose cotransporter-2 inhibitors, and five with glucagon-like peptide-1 analogues). These studies showed different results for primary cardiovascular outcomes and stroke prevention. It is important to determine whether prescription of TZD or new antidiabetic medications compared to conventional treatment, such as sulfonylurea or insulin, is better for stroke management. Furthermore, it is unclear whether drugs in the same class show greater safety and efficacy than other drugs for stroke management.



J Stroke: 29 Apr 2019; 21:139-150
Ahn CH, Lim S
J Stroke: 29 Apr 2019; 21:139-150 | PMID: 31161759
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Abstract

2019 Update of the Korean Clinical Practice Guidelines of Stroke for Endovascular Recanalization Therapy in Patients with Acute Ischemic Stroke.

Ko SB, Park HK, Kim BM, Heo JH, ... Yoon BW, Hong KS

Endovascular recanalization therapy (ERT) has been a standard of care for patients with acute ischemic stroke due to large artery occlusion (LAO) within 6 hours after onset, since five landmark ERT trials conducted by 2015 demonstrated its clinical benefit. Recently, two randomized clinical trials demonstrated that ERT, even in the late time window of up to 16 hours or 24 hours after last known normal time, improved the outcome of patients who had a target mismatch, defined as either clinical-core mismatch or perfusion-core mismatch, which prompted the update of national guidelines in several countries. Accordingly, to provide evidence-based and up-to-date recommendations for ERT in patients with acute LAO in Korea, the Clinical Practice Guidelines Committee of the Korean Stroke Society decided to revise the previous Korean Clinical Practice Guidelines of Stroke for ERT. For this update, the members of the writing group were appointed by the Korean Stroke Society and the Korean Society of Interventional Neuroradiology. After thoroughly reviewing the updated evidence from two recent trials and relevant literature, the writing members revised recommendations, for which formal consensus was achieved by convening an expert panel composed of 45 experts from the participating academic societies. The current guidelines are intended to help healthcare providers, patients, and their caregivers make well-informed decisions and to improve the quality of care regarding ERT. The ultimate decision for ERT in a particular patient must be made in light of circumstances specific to that patient.



J Stroke: 29 Apr 2019; 21:231-240
Ko SB, Park HK, Kim BM, Heo JH, ... Yoon BW, Hong KS
J Stroke: 29 Apr 2019; 21:231-240 | PMID: 30991800
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Abstract

Asymptomatic Cerebral Small Vessel Disease: Insights from Population-Based Studies.

Das AS, Regenhardt RW, Vernooij MW, Blacker D, Charidimou A, Viswanathan A

Cerebral small vessel disease (CSVD) is a common group of neurological conditions that confer a significant burden of morbidity and mortality worldwide. In most cases, CSVD is only recognized in its advanced stages once its symptomatic sequelae develop. However, its significance in asymptomatic healthy populations remains poorly defined. In population-based studies of presumed healthy elderly individuals, CSVD neuroimaging markers including white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and cerebral microinfarcts are frequently detected. While the presence of these imaging markers may reflect unique mechanisms at play, there are likely shared pathways underlying CSVD. Herein, we aim to assess the etiology and significance of these individual biomarkers by focusing in asymptomatic populations at an epidemiological level. By primarily examining population-based studies, we explore the risk factors that are involved in the formation and progression of these biomarkers. Through a critical semi-systematic review, we aim to characterize \"asymptomatic\" CSVD, review screening modalities, and draw associations from observational studies in clinical populations. Lastly, we highlight areas of research (including therapeutic approaches) in which further investigation is needed to better understand asymptomatic CSVD.



J Stroke: 29 Apr 2019; 21:121-138
Das AS, Regenhardt RW, Vernooij MW, Blacker D, Charidimou A, Viswanathan A
J Stroke: 29 Apr 2019; 21:121-138 | PMID: 30991799
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Abstract

Long-Term Stroke Recurrence after Transient Ischemic Attack: Implications of Etiology.

Ois A, Cuadrado-Godia E, Giralt-Steinhauer E, Jimenez-Conde J, ... Fernandez-Perez I, Roquer J
Background and purpose
To analyze long-term stroke recurrence (SR) characteristics after transient ischemic attack (TIA) according to initial etiological classification.
Methods
A prospective cohort of 706 TIA patients was followed up in a single tertiary stroke center. Endpoint was SR. Etiologic subgroup was determined according to the evidence-based causative classification system. Location of TIA and SR was recorded as right, left, or posterior territory. Disability stroke recurrence (DSR) was defined as modified Rankin Scale (mRS) score >1 or a onepoint increase in those with previous mRS >1 at 3-month follow-up.
Results
During a follow-up of 3,493 patient-years (mean follow-up of 58.9±35.9 months), total SR was 125 (17.7%), corresponding to 3.6 recurrences per 100 patient-years. The etiology subgroups with a higher risk of SR were the unclassified (more than one cause) and large-artery atherosclerosis (LAA) categories. Of the SR cases, 88 (70.4%) had the same etiology as the index TIA; again, LAA etiology was the most frequent (83.9%). Notably, cardioaortic embolism was the most frequent cause (62.5%) of SR in the subgroup of 24 patients with undetermined TIA. Overall, SR occurred in the same territory in 74 of 125 patients (59.2%), with significant differences between etiological TIA subgroups (P=0.015). Eighty-two of 125 (65.6%) with SR had DSR, without differences between etiologies (P=0.453).
Conclusions
SR occurred mainly with the same etiology and location as initial TIA, although undetermined TIA was associated with a high proportion of cardioaortic embolism SR. More than half of the recurrences caused some disability, regardless of etiology.



J Stroke: 29 Apr 2019; 21:184-189
Ois A, Cuadrado-Godia E, Giralt-Steinhauer E, Jimenez-Conde J, ... Fernandez-Perez I, Roquer J
J Stroke: 29 Apr 2019; 21:184-189 | PMID: 30991798
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Abstract

Unrecognized History of Transient Atrial Fibrillation at the Time of Discharge from an Index Stroke Hospitalization Is Associated with Increased Recurrent Stroke Risk.

Hsu CY, Singer DE, Kamel H, Wu YL, ... Lee M, Ovbiagele B
Background and purpose
Preceding episodes of paroxysmal atrial fibrillation (AF) among stroke patients can be easily overlooked in routine clinical practice. We aim to determine whether an unrecognized history of paroxysmal AF is associated with an increased risk of recurrent stroke.
Methods
We retrospectively identified all adult patients hospitalized with a primary diagnosis of ischemic stroke who had no AF diagnosis on their discharge records, using the Taiwan National Health Insurance Research Database between January 2001 and December 2012. Patients were categorized into two groups: unrecognized AF history and no AF. Patients with unrecognized AF history were defined as having documented AF preceding the index ischemic stroke hospitalization, but not recording at the index ischemic stroke. Primary endpoint was recurrent stroke within 1 year after the index stroke.
Results
Among 203,489 hospitalized ischemic stroke patients without AF diagnosed at discharge, 6,731 patients (3.3%) had an unrecognized history of prior transient AF. Patients with an unrecognized AF history, comparing to those without AF, had higher adjusted risk of all recurrent stroke ([original cohort: hazard ratio (HR), 1.41; 95% confidence interval [CI], 1.30 to 1.53], [matched cohort: HR, 1.51; 95% CI, 1.37 to 1.68]) and recurrent ischemic stroke ([original cohort: HR, 1.42; 95% CI, 1.30 to 1.55], [matched cohort: HR, 1.56; 95% CI, 1.40 to 1.74]) during the 1-year follow-up period.
Conclusions
Unrecognized history of AF among patients discharged after an index ischemic stroke hospitalization is associated with higher recurrent stroke risk. Careful history review to uncover a paroxysmal AF history is important for ischemic stroke patients.



J Stroke: 29 Apr 2019; 21:190-194
Hsu CY, Singer DE, Kamel H, Wu YL, ... Lee M, Ovbiagele B
J Stroke: 29 Apr 2019; 21:190-194 | PMID: 30991797
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Impact:
Abstract

History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS).

Giuli VD, Besana M, Grassi M, Zedde M, ... Pezzini A,
Background and purpose
Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated.
Methods
In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status.
Results
A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm3 [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54).
Conclusion
s These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.



J Stroke: 30 Dec 2018; 21:324-331
Giuli VD, Besana M, Grassi M, Zedde M, ... Pezzini A,
J Stroke: 30 Dec 2018; 21:324-331 | PMID: 31590476
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Impact:
Abstract

Does Clot Burden Score on Baseline T2*-MRI Impact Clinical Outcome in Acute Ischemic Stroke Treated with Mechanical Thrombectomy?

Derraz I, Bourcier R, Soudant M, Soize S, ... Naggara O,
Background and purpose
A long clot, defined by a low (0-6) clot burden score (CBS) assessed by T2*-MR sequence, is associated with worse clinical outcome after intravenous thrombolysis (IVT) for acute ischemic stroke than is a small clot (CBS, 7-10). The added benefit of mechanical thrombectomy (MT) might be higher in patients with long clot. The aim of this pre-specified post hoc analysis of the THRombectomie des Artères CErebrales (THRACE) trial was to assess the association between T2*-CBS, successful recanalization and clinical outcome.
Methods
Of 414 patients randomized in the THRACE trial, 281 patients were included in this analysis. Associations between T2*-CBS and clinical outcome on the modified Rankin Scale (mRS) at 3 months were tested.
Results
High T2*-CBS, i.e., small clot, was associated with a shift toward better outcome on the mRS; proportional odds ratio (POR) per point CBS was 1.19 (95% confidence interval [CI], 1.05 to 1.34) in the whole population, 1.34 (95% CI, 1.13 to 1.59) in IVT group, and 1.04 (95% CI, 0.87 to 1.23) in IVTMT group. After adjustment for baseline prognostic variables, the effect of the full scale T2*-CBS was not statistically significant in the whole population and for the IVTMT group but remains significant for the IVT group (POR, 1.32; 95% CI, 1.11 to 1.58).
Conclusion
s A small clot, as assessed using T2*-CBS, is associated with improved outcome and may be used as a prognostic marker. Despite the worst outcome with long clot, the relative benefit of MT over IVT seemed to increase with low T2*-CBS and longer clot.



J Stroke: 30 Dec 2018; 21:91-100
Derraz I, Bourcier R, Soudant M, Soize S, ... Naggara O,
J Stroke: 30 Dec 2018; 21:91-100 | PMID: 30732444
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Impact:
Abstract

Association of Elevated Blood Pressure Levels with Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis: A Systematic Review and Meta-Analysis.

Malhotra K, Ahmed N, Filippatou A, Katsanos AH, ... Alexandrov AV, Tsivgoulis G
Background and purpose
Although arbitrary blood pressure (BP) thresholds exist for acute ischemic stroke (AIS) patients eligible for intravenous thrombolysis (IVT), current international recommendations lack clarity on the impact of mean pre- and post-IVT BP levels on clinical outcomes.
Methods
Eligible studies involving IVT-treated AIS patients were identified that reported the association of mean systolic BP (SBP) or diastolic BP levels before and after IVT with the following outcomes: 3-month favorable functional outcome (modified Rankin Scale [mRS] scores of 0-1) and 3-month functional independence (mRS scores of 0-2), 3-month mortality and symptomatic intracranial hemorrhage (sICH). Unadjusted analyses of standardized mean differences and adjusted analyses of studies reporting odds ratios (ORadj) per 10 mm Hg BP increment were performed using random-effects models.
Results
We identified 26 studies comprising 56,513 patients. Higher pre- (P=0.02) and posttreatment (P=0.006) SBP levels were observed in patients with sICH. Patients with 3-month functional independence had lower post-treatment (P<0.001) SBP whereas trended towards lower pre-treatment (P=0.06) SBP. In adjusted analyses, elevated pre- (ORadj, 1.08; 95% confidence interval [CI], 1.01 to 1.16) and post-treatment (ORadj, 1.13; 95% CI, 1.01 to 1.25) SBP levels were associated with increased likelihood of sICH. Increasing pre- (ORadj, 0.91; 95% CI, 0.84 to 0.98) and post-treatment (ORadj, 0.70; 95% CI, 0.57 to 0.87) SBP values were also related to lower odds of 3-month functional independence.
Conclusion
s We found that elevated BP levels adversely impact AIS outcomes in patients receiving IVT. Future randomized-controlled clinical trials will provide definitive data on the aforementioned association.



J Stroke: 30 Dec 2018; 21:78-90
Malhotra K, Ahmed N, Filippatou A, Katsanos AH, ... Alexandrov AV, Tsivgoulis G
J Stroke: 30 Dec 2018; 21:78-90 | PMID: 30732443
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Impact:
Abstract

Estimation of Acute Infarct Volume with Reference Maps: A Simple Visual Tool for Decision Making in Thrombectomy Cases.

Kim DE, Ryu WS, Schellingerhout D, Jeong HG, ... Lee YS, Bae HJ
Background and purpose
Thrombectomy within 24 hours can improve outcomes in selected patients with a clinical-infarct mismatch. We devised an easy-to-use visual estimation tool that allows infarct volume estimation in centers with limited resources.
Methods
We identified 1,031 patients with cardioembolic or large-artery atherosclerosis infarction on diffusion-weighted images (DWIs) obtained before recanalization therapy and within 24 hours of onset, and occlusion of the internal carotid or middle cerebral artery. Acute DWIs were mapped onto a standard template and used to create visual reference maps with known lesion volumes, which were then used in a validation study (with 130 cases) against software estimates of infarct volume.
Results
The DWI reference map chart comprises 144 maps corresponding to 12 different infarct volumes (0.5, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mL) in each of 12 template slices (Montreal Neurological Institute z-axis -15 to 51 mm). Infarct volume in a patient is estimated by selecting a slice with a similar infarct size at the corresponding z-axis level on the reference maps and then adding up over all slices. The method yielded good correlations to software volumetrics and was easily learned by both experienced and junior physicians, with approximately 1 to 2 minutes spent per case. The sensitivity, specificity, and accuracy for detecting threshold infarct volumes (<21, <31, and <51 mL) were very high (all about >90%).
Conclusion
s We developed easy-to-use reference maps that allow prompt and reliable visual estimation of infarct volumes for triaging patients to thrombectomy in acute stroke.



J Stroke: 30 Dec 2018; 21:69-77
Kim DE, Ryu WS, Schellingerhout D, Jeong HG, ... Lee YS, Bae HJ
J Stroke: 30 Dec 2018; 21:69-77 | PMID: 30732442
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Impact:
Abstract

Biomarker for Ischemic Stroke Using Metabolome: A Clinician Perspective.

Sidorov E, Sanghera DK, Vanamala JKP

Finding ischemic stroke biomarker is highly desirable because it can improve diagnosis even before a patient arrives to the hospital. Metabolome is one of new technologies that help to find biomarkers. Most metabolome-related ischemic stroke studies were done in Asia and had exploratory designs. Although failed to find specific biomarkers, they discovered several important metabolite-stroke associations which belong to three pathophysiological mechanisms: Excitotoxicity with activation of glutamate, resulting in the increase of glutamate derivatives proline and pyroglutamate; Oxidative stress with production of free radicals and perturbed concentrations of uric acid, matrix metalloproteinase-9, branch-chained amino acids, sphingolipids, homocysteine, asymmetric dimethylarginine, nitric oxide and folate cycle metabolites; and Stroke mediated inflammation, affecting phospholipid metabolism with perturbed levels of lysophosphatidylethanolamine and lysophosphatidylcholine. The discovered metabolite-stroke associations need further evaluation in prospective, high-quality studies with patients matched for age, risk factors, and medications.



J Stroke: 30 Dec 2018; 21:31-41
Sidorov E, Sanghera DK, Vanamala JKP
J Stroke: 30 Dec 2018; 21:31-41 | PMID: 30732441
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Impact:
Abstract

Patent Foramen Ovale: Story Closed?

Köhrmann M, Schellinger PD, Tsivgoulis G, Steiner T

The optimal treatment strategy for secondary prevention in patients with cryptogenic stroke and patent foramen ovale (PFO) has been a matter of controversy for decades. After three randomized trials failed to show a benefit of closure with an excess of complications in the interventional arm, two large recent trials suggest a benefit with regard of preventing further ischemic strokes. With this discrepancy in results it is important to discuss recent trials in detail and evolve an informed clinical approach for daily practice.



J Stroke: 30 Dec 2018; 21:23-30
Köhrmann M, Schellinger PD, Tsivgoulis G, Steiner T
J Stroke: 30 Dec 2018; 21:23-30 | PMID: 30732440
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Impact:
Abstract

Frontline Contact Aspiration Treatment for Emergent Large Vessel Occlusion: A Review Focused on Practical Techniques.

Kang DH, Hwang YH

Endovascular thrombectomy (EVT) as the standard care for acute stroke due to large vessel occlusion has recently been validated through several randomized controlled trials (RCTs). Contact aspiration (CA) and stent retriever (SR) are the two major EVT methods currently used. Because the RCTs have mostly evaluated SR devices, there was a demand to test CA in relation to SR as a frontline EVT treatment method. Recently, the Contact Aspiration vs Stent Retriever for Successful Recanalization (ASTER) study, the first RCT to compare CA and SR, demonstrated similar efficacy between them as a frontline EVT for patients with large vessel occlusions. This facilitates further investigation to confirm better frontline EVT for patients with acute stroke. In this review, we discuss past and recent developments in CA techniques, focusing on related literature. Additionally, we describe practical skills to overcome technical difficulties that can be encountered during the CA procedure. Finally, we review the evolution of device technologies, including a newer version of using a large-bore aspiration catheter.



J Stroke: 30 Dec 2018; 21:10-22
Kang DH, Hwang YH
J Stroke: 30 Dec 2018; 21:10-22 | PMID: 30732439
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Impact:
Abstract

The Aspirations of Direct Aspiration for Thrombectomy in Ischemic Stroke: A Critical Analysis.

Andersson T, Wiesmann M, Nikoubashman O, Gopinathan A, Bhogal P, Yeo LLL

The treatment of acute ischemic stroke by mechanical thrombectomy has been revolutionary, however most of the clinical trials were done with the use a stent retriever. At the same time, an alternative technique of thrombectomy through direct aspiration with a large bore distal access catheter at the face of the clot is rapidly gaining popularity. Nonetheless, the data supporting this new technique is not yet as mature as that available on stent retrievers. This review is a critical analysis of the evidence supporting the principle of direct aspiration thrombectomy and a discussion of its potential strengths and weaknesses in comparison to the available studies on stent retrievers. While this is by no means a conclusive review, it should serve as a yardstick of where the science is currently, and what are the next trials that are necessary.



J Stroke: 30 Dec 2018; 21:2-9
Andersson T, Wiesmann M, Nikoubashman O, Gopinathan A, Bhogal P, Yeo LLL
J Stroke: 30 Dec 2018; 21:2-9 | PMID: 30732438
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Impact:
Abstract

Early Life Body Size in Relation to First Intracerebral or Subarachnoid Hemorrhage.

Gjærde LK, Truelsen TC, Sørensen TIA, Baker JL
Background and purpose
As risk of hemorrhagic stroke may have early life origins, we investigated associations of birth weight and childhood body mass index (BMI) with adult intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH).
Methods
We included 240,234 Danish schoolchildren, born 1936 to 1989, with information on birth weight and measured weights and heights from 7 to 13 years. We calculated hazard ratios (HRs) and confidence intervals (CIs) for the associations between early life anthropometrics and ICH or SAH, identified through linkage with national registers.
Results
During the study period, 1,947 individuals (39% women) experienced an ICH and 797 individuals (64% women) experienced a SAH. Per 500 g increase in birth weight, women had a 10% decreased risk of SAH (HR, 0.90; 95% CI, 0.83 to 0.97) and men had a 10% decreased risk of ICH (HR, 0.90; 95% CI, 0.85 to 0.95). Birth weight was not associated with risks of ICH in women or SAH in men. In men, a childhood BMI below average (BMI z-score <0) was associated with increased risks of ICH. The association was stronger at older childhood ages, and at 13 years a BMI z-score of -1 was associated with a HR of 1.17 (95% CI, 1.06 to 1.28), and a BMI z-score of -2 with a HR of 1.46 (95% CI, 1.17 to 1.82) for ICH. Childhood BMI was not associated with risks of ICH in women or with risks of SAH in both sexes.
Conclusion
s Early life body size is associated with ICH and SAH, and the associations differ by sex.



J Stroke: 30 Dec 2018; 21:60-68
Gjærde LK, Truelsen TC, Sørensen TIA, Baker JL
J Stroke: 30 Dec 2018; 21:60-68 | PMID: 30558401
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Impact:
Abstract

Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society.

Kim JY, Kang K, Kang J, Koo J, ... Lee J, Bae HJ

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the \"Stroke Statistics in Korea\" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.



J Stroke: 30 Dec 2018; 21:42-59
Kim JY, Kang K, Kang J, Koo J, ... Lee J, Bae HJ
J Stroke: 30 Dec 2018; 21:42-59 | PMID: 30558400
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Impact:
Abstract

Prognosis of Acute Intracranial Atherosclerosis-Related Occlusion after Endovascular Treatment.

Lee JS, Lee SJ, Yoo JS, Hong JH, ... Sohn SI, Hwang YH
Background and purpose
Little is known about prognosis after endovascular therapy (EVT) for acute large artery occlusion (LAO) caused by underlying intracranial atherosclerotic stenosis (ICAS). Therefore, we investigated the prognosis following EVT according to the underlying etiology of LAO.
Methods
Patients from the Acute Stroke due to Intracranial Atherosclerotic occlusion and Neurointervention-Korean Retrospective (ASIAN KR) registry (n=720) were included if their occlusion was in the intracranial anterior circulation and their onset-to-puncture time was <24 hours. Occlusion was classified according to etiology as follows: no significant stenosis after recanalization (Embolic group), and fixed significant focal stenosis in the occlusion site with flow impairment or re-occlusion observed during EVT (ICAS group). Patients were excluded when significant extracranial carotid lesions existed, and when the intracranial occlusion was intractable to EVT so that the etiology was undetermined. The effect of angiographic etiologic classification on outcomes was evaluated using multivariable analysis that was adjusted for potential confounders.
Results
Among eligible patients (n=520), 421 and 99 were classified in the Embolic and ICAS groups, respectively. Patients in the Embolic and ICAS groups had similar successful reperfusion rates with EVT (79.6% vs. 76.8%, P=0.537) and 3-month functional independence (54.5% vs. 45.5%, P=0.104). In multivariable analysis, ICAS-related occlusion (odds ratio, 0.495; 95% confidence interval, 0.269 to 0.913; P=0.024) showed poorer 3-month functional independence compared to embolic occlusion.
Conclusion
s After EVT, patients with acute ICAS-related occlusion have relatively poor functional outcomes compared to those with embolic occlusion. Novel strategies need to be developed to improve EVT outcomes for ICAS occlusion.



J Stroke: 30 Aug 2018; 20:394-403
Lee JS, Lee SJ, Yoo JS, Hong JH, ... Sohn SI, Hwang YH
J Stroke: 30 Aug 2018; 20:394-403 | PMID: 30309234
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Impact:
Abstract

Intravenous Thrombolysis Prior to Mechanical Thrombectomy in Acute Ischemic Stroke: Silver Bullet or Useless Bystander?

Di Maria F, Mazighi M, Kyheng M, Labreuche J, ... Gory B, Lapergue B
Background and purpose
Recent single-center series and meta-analyses suggest that mechanical thrombectomy (MT) without prior intravenous thrombolysis (IVT) might be equally effective to bridging therapy. We analyzed, within the Endovascular Treatment in Ischemic Stroke (ETIS) prospective observational registry, the angiographic and clinical outcomes after IVT+MT versus MT alone.
Methods
From December 2012 to December 2016, a total of 1,507 consecutive patients with a proximal arterial occlusion of the anterior circulation were treated by MT. Of these, 975 (64.7%) received prior IVT. Immediate angiographic and clinical outcomes at 90 days (modified Rankin Scale [mRS]) were compared between the two groups while checking for propensity score, matched-propensity score and by inverse probability of treatment weighting (IPTW) propensity score method.
Results
Favorable outcome (mRS 0 to 2) was more frequently achieved after IVT+MT (n=523, 53.6%) than after MT alone (n=222, 41.8%) with an unadjusted odds ratio (OR) for bridging therapy of 1.61 (95% confidence interval [CI], 1. 29 to 2.01). This difference remained not significant in matched-propensity score cohort (OR, 1.21; 95% CI, 0.90 to 1.63) although it remained according to adjusted propensity score (OR, 1.31; 95% CI, 1.02 to 1.68) and IPTW (OR, 1.37; 95% CI, 1.09 to 1.73) analyses. A significant difference was found in terms of excellent outcome (mRS 0 to 1) (adjusted OR, 1.63; 95% CI, 1.25 to 2.11) and successful reperfusion (adjusted OR, 1.58; 95% CI, 1.33 to 2.15). No differences in intracerebral hemorrhage or in allcause mortality within 90 days were found between groups.
Conclusion
s IVT prior to MT is associated with increased excellent outcome and successful reperfusion rates. These findings support the use of bridging therapy.



J Stroke: 30 Aug 2018; 20:385-393
Di Maria F, Mazighi M, Kyheng M, Labreuche J, ... Gory B, Lapergue B
J Stroke: 30 Aug 2018; 20:385-393 | PMID: 30309233
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Impact:
Abstract

Higher Blood Pressure during Endovascular Thrombectomy in Anterior Circulation Stroke Is Associated with Better Outcomes.

Pikija S, Trkulja V, Ramesmayer C, Mutzenbach JS, ... Füssel MU, Sellner J
Background and purpose
Reports investigating the relationship between in-procedure blood pressure (BP) and outcomes in patients undergoing endovascular thrombectomy (EVT) due to anterior circulation stroke are sparse and contradictory.
Methods
Consecutive EVT-treated adults (modern stent retrievers, BP managed in line with the recommendations, general anesthesia, invasive BP measurements) were evaluated for associations of the rate of in-procedure systolic BP (SBP) and mean arterial pressure (MAP) excursions to >120%/<80% of the reference values (serial measurements at anesthesia induction) and of the reference BP/weighted in-procedure mean BP with post-procedure imaging outcomes (ischemic lesion volume [ILV], hemorrhages) and 3-month functional outcome (modified Rankin Scale [mRS], score 0 to 2 vs. 3 to 6).
Results
Overall 164 patients (70.7% pharmacological reperfusion, 80.5% with good collaterals, 73.8% with successful reperfusion) were evaluated for ILV (range, 0 to 581 cm3) and hemorrhages (incidence 17.7%). Higher rate of in-procedure SBP/MAP excursions to >120% was independently associated with lower ILV, while higher in-procedure mean SBP/MAP was associated with lower odds of hemorrhages. mRS 0-2 was achieved in 75/155 (48.4%) evaluated patients (nine had missing mRS data). Higher rate of SBP/MAP excursions to >120% and higher reference SBP/MAP were independently associated with higher odds of mRS 0-2, while higher ILV was associated with lower odds of mRS 0-2. Rate of SBP/MAP excursions to <80% was not associated with any outcome.
Conclusion
s In the EVT-treated patients with BP managed within the recommended limits, a better functional outcome might be achieved by targeting in-procedure BP that exceeds the preprocedure values by more than 20%.



J Stroke: 30 Aug 2018; 20:373-384
Pikija S, Trkulja V, Ramesmayer C, Mutzenbach JS, ... Füssel MU, Sellner J
J Stroke: 30 Aug 2018; 20:373-384 | PMID: 30309232
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Impact:
Abstract

Outcome Prediction Using Perfusion Parameters and Collateral Scores of Multi-Phase and Single-Phase CT Angiography in Acute Stroke: Need for One, Two, Three, or Thirty Scans?

Schregel K, Tsogkas I, Peter C, Zapf A, ... Knauth M, Psychogios MN
Background and purpose
Collateral status is an important factor determining outcome in acute ischemic stroke (AIS). Hence, different collateral scoring systems have been introduced. We applied different scoring systems on single- and multi-phase computed tomography (CT) angiography (spCTA and mpCTA) and compared them to CT perfusion (CTP) parameters to identify the best method for collateral evaluation in patients with AIS.
Methods
A total of 102 patients with AIS due to large vessel occlusion in the anterior circulation who underwent multimodal CT imaging and who were treated endovascularly were included. Collateral status was assessed on spCTA and mpCTA using four different scoring systems and compared to CTP parameters. Logistic regression was performed for predicting favorable outcome.
Results
All collateral scores correlated well with each other and with CTP parameters. Comparison of collateral scores stratified by extent of perfusion deficit showed relevant differences between groups (P<0.01 for each). An spCTA collateral score discriminated best between favorable and unfavorable outcome as determined using the modified Rankin Scale 3 months after stroke.
Conclusion
s Collateral status evaluated on spCTA may suffice for outcome prediction and decision making in AIS patients, potentially obviating further imaging modalities like mpCTA or CTP.



J Stroke: 30 Aug 2018; 20:362-372
Schregel K, Tsogkas I, Peter C, Zapf A, ... Knauth M, Psychogios MN
J Stroke: 30 Aug 2018; 20:362-372 | PMID: 30309231
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Impact:
Abstract

Aberrant Promoter Hypomethylation of Sortilin 1: A Moyamoya Disease Biomarker.

Sung HY, Lee JY, Park AK, Moon YJ, ... Ahn JH, Kim SK
Background and purpose
The pathogenesis of moyamoya disease (MMD) remains poorly understood, and no reliable molecular biomarkers for MMD have been identified to date. The present study aimed to identify epigenetic biomarkers for use in the diagnosis of MMD.
Methods
We performed integrated analyses of gene expression profiles and DNA methylation profiles in endothelial colony forming cells (ECFCs) from three patients with MMD and two healthy individuals. Candidate gene mRNA expression and DNA methylation status were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and pyrosequencing analysis of an expanded ECFC sample set from nine patients with MMD and ten controls. We evaluated the diagnostic accuracy of the potential biomarkers identified here using receiver operating characteristic curve analyses and further measured major angiogenic factor expression levels using a tube formation assay and RT-qPCR.
Results
Five candidate genes were selected via integrated analysis; all five were upregulated by hypomethylation of specific promoter CpG sites. After further validation in an expanded sample set, we identified a candidate biomarker gene, sortilin 1 (SORT1). DNA methylation status at a specific SORT1 promoter CpG site in ECFCs readily distinguished patients with MMD from the normal controls with high accuracy (area under the curve 0.98, sensitivity 83.33%, specificity 100%). Furthermore, SORT1 overexpression suppressed endothelial cell tube formation and modulated major angiogenic factor and matrix metalloproteinase-9 expression, implying SORT1 involvement in MMD pathogenesis.
Conclusion
s Our findings suggest that DNA methylation status at the SORT1 promoter CpG site may be a potential biomarker for MMD.



J Stroke: 30 Aug 2018; 20:350-361
Sung HY, Lee JY, Park AK, Moon YJ, ... Ahn JH, Kim SK
J Stroke: 30 Aug 2018; 20:350-361 | PMID: 30309230
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Impact:
Abstract

Correlation of Adventitial Vasa Vasorum with Intracranial Atherosclerosis: A Postmortem Study.

Zheng L, Yang WJ, Niu CB, Zhao HL, ... Leung TWH, Chen XY
Background and purpose
Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis.
Methods
We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions.
Results
Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P<0.001), severer luminal stenosis (25%±21% vs. 12%±9%, P=0.002), higher rate of concentric lesions (79% vs. 36%, P=0.002), and denser intraplaque calcification (44% vs. 0%, P=0.003). Histologically, intracranial VA with VV had a larger diameter (3.40±0.79 mm vs. 2.34±0.58 mm, P<0.001), thicker arterial wall (0.31±0.13 mm vs. 0.23±0.06 mm, P=0.002), and a larger intima-media (0.19±0.09 mm vs. 0.13± 0.04 mm, P=0.003) than VA without VV.
Conclusion
s Our study demonstrated the distribution of adventitial VV within brain vasculature and association between vertebral VV and progressive atherosclerotic lesions with a heavier plaque load and denser intraplaque calcification.



J Stroke: 30 Aug 2018; 20:342-349
Zheng L, Yang WJ, Niu CB, Zhao HL, ... Leung TWH, Chen XY
J Stroke: 30 Aug 2018; 20:342-349 | PMID: 30309229
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Impact:
Abstract

Cognitive Functions in Children and Adults with Moyamoya Vasculopathy: A Systematic Review and Meta-Analysis.

Kronenburg A, van den Berg E, van Schooneveld MM, Braun KPJ, ... van der Zwan A, Klijn CJM
Background and purpose
Patients with moyamoya vasculopathy (MMV) may experience cognitive impairment, but its reported frequency, severity, and nature vary. In a systematic review and metaanalysis, we aimed to assess the presence, severity, and nature of cognitive impairments in children and adults with MMV.
Methods
We followed the MOOSE guidelines for meta-analysis and systematic reviews of observational studies. We searched Ovid Medline and Embase for studies published between January 1, 1969 and October 4, 2016. Independent reviewers extracted data for mean intelligence quotient (IQ) and standardized z-scores for cognitive tests, and determined percentages of children and adults with cognitive deficits, before and after conservative or surgical treatment. We explored associations between summary measures of study characteristics and cognitive impairments by linear regression analysis.
Results
We included 17 studies (11 studies reporting on 281 children, six on 153 adults). In children, the median percentage with impaired cognition was 30% (range, 13% to 67%); median IQ was 98 (range, 71 to 107). Median z-score was -0.39 for memory, and -0.43 for processing speed. In adults, the median percentage with impaired cognition was 31% (range, 0% to 69%); median IQ was 95 (range, 94 to 99). Median z-scores of cognitive domains were between -0.9 and -0.4, with multiple domains being affected. We could not identify determinants of cognitive impairment.
Conclusion
s A large proportion of children and adults with MMV have cognitive impairment, with modest to large deficits across various cognitive domains. Further studies should investigate determinants of cognitive deficits and deterioration, and the influence of revascularization treatment on cognitive functioning.



J Stroke: 30 Aug 2018; 20:332-341
Kronenburg A, van den Berg E, van Schooneveld MM, Braun KPJ, ... van der Zwan A, Klijn CJM
J Stroke: 30 Aug 2018; 20:332-341 | PMID: 30309228
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Impact:
Abstract

Consensus Guides on Stroke Thrombolysis for Anticoagulated Patients from Japan: Application to Other Populations.

Toyoda K, Yamagami H, Koga M

Development of direct oral anticoagulants and their antidotes has led to the need to reconsider the eligibility of acute stroke patients who have been taking oral anticoagulants for intravenous thrombolysis. Officially authorized Japanese guidelines on this issue were revised twice at the time of approval for clinical use of direct oral anticoagulants and idarucizumab, a specific reversal agent for dabigatran. A unique recommendation in the latest Japanese clinical guides was that thrombolysis can be recommended if the time of the last dose of direct oral anticoagulants exceeds 4 hours and if commonly available anticoagulation markers are normal or subnormal, i.e., international normalized ratio of prothrombin time <1.7 and activated partial thromboplastin time <1.5 times the baseline value (≤40 seconds only as a guide). These criteria are partly supported by the findings of domestic multicenter and single-center surveys that symptomatic or asymptomatic intracranial hemorrhage following thrombolysis was rare under the conditions of the criteria. Even for dabigatran users, stroke thrombolysis can be considered without pretreatment by idarucizumab if patients meet the above criteria. If not, direct mechanical thrombectomy can be considered without pretreatment by idarucizumab or thrombolysis, and use of idarucizumab, followed immediately by thrombolysis, can be considered only when thrombectomy cannot be quickly performed. These clinical guides are practical and to some extent economical, but they have some limitations, including lack of corroborating information from sufficient numbers of relevant cases. The guides will be further modified based on the results of future research.



J Stroke: 30 Aug 2018; 20:321-331
Toyoda K, Yamagami H, Koga M
J Stroke: 30 Aug 2018; 20:321-331 | PMID: 30309227
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Impact:
Abstract

Cerebral Small Vessel Disease: A Review Focusing on Pathophysiology, Biomarkers, and Machine Learning Strategies.

Cuadrado-Godia E, Dwivedi P, Sharma S, Ois Santiago A, ... Khanna NN, Suri JS

Cerebral small vessel disease (cSVD) has a crucial role in lacunar stroke and brain hemorrhages and is a leading cause of cognitive decline and functional loss in elderly patients. Based on underlying pathophysiology, cSVD can be subdivided into amyloidal and non-amyloidal subtypes. Genetic factors of cSVD play a pivotal role in terms of unraveling molecular mechanism. An important pathophysiological mechanism of cSVD is blood-brain barrier leakage and endothelium dysfunction which gives a clue in identification of the disease through circulating biological markers. Detection of cSVD is routinely carried out by key neuroimaging markers including white matter hyperintensities, lacunes, small subcortical infarcts, perivascular spaces, cerebral microbleeds, and brain atrophy. Application of neural networking, machine learning and deep learning in image processing have increased significantly for correct severity of cSVD. A linkage between cSVD and other neurological disorder, such as Alzheimer\'s and Parkinson\'s disease and non-cerebral disease, has also been investigated recently. This review draws a broad picture of cSVD, aiming to inculcate new insights into its pathogenesis and biomarkers. It also focuses on the role of deep machine strategies and other dimensions of cSVD by linking it with several cerebral and non-cerebral diseases as well as recent advances in the field to achieve sensitive detection, effective prevention and disease management.



J Stroke: 30 Aug 2018; 20:302-320
Cuadrado-Godia E, Dwivedi P, Sharma S, Ois Santiago A, ... Khanna NN, Suri JS
J Stroke: 30 Aug 2018; 20:302-320 | PMID: 30309226
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Impact:
Abstract

Non-Vitamin K Oral Anticoagulants Associated Bleeding and Its Antidotes.

Steiner T, Köhrmann M, Schellinger PD, Tsivgoulis G

Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase. The mortality and complication rates of OAC-ICH are high and therefore they are the most feared complication of OAT. Immediate normalization of coagulation is the main goal and therefore knowledge of pharmacodynamics and coagulation status is essential. Laboratory measurements of anticoagulant activity in NOAC patients is challenging as specific tests are not widely available. More accessible tests such as the prothrombin time and activated partial thromboplastin time have important limitations. In dabigatran-associated ICH 5 g Idarucizumab should be administered. In rivaroxaban and apixaban-associated ICHs administration of andexanet alpha should be considered. Prothrombin complex concentrate may be considered if andexanet alpha is not available or in case of an ICH associated with edoxaban.



J Stroke: 30 Aug 2018; 20:292-301
Steiner T, Köhrmann M, Schellinger PD, Tsivgoulis G
J Stroke: 30 Aug 2018; 20:292-301 | PMID: 30309225
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Abstract

Percutaneous Left Atrial Appendage Occlusion for the Prevention of Stroke in Patients with Atrial Fibrillation: Review and Critical Appraisal.

Schellinger PD, Tsivgoulis G, Steiner T, Köhrmann M

The authors review the current status of percutaneous left atrial appendage (LAA) occlusion therapy in patients with atrial fibrillation with the goal to prevent ischemic stroke and systemic embolism and to reduce oral anticoagulation associated bleeding. While we cover the historical and also surgical background, and all tested devices, the main focus rests on the single currently U.S. Food and Drug Administration (FDA) approved LAA occluder, the WATCHMAN device, and its approval process. The authors also give a critical appraisal beyond the review of mere facts, trying to put the current data into perspective.



J Stroke: 30 Aug 2018; 20:281-291
Schellinger PD, Tsivgoulis G, Steiner T, Köhrmann M
J Stroke: 30 Aug 2018; 20:281-291 | PMID: 30309224
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Impact:
Abstract

Neuroprotectants in the Era of Reperfusion Therapy.

Chamorro Á

For decades, numerous pharmacological and non-pharmacological strategies have been evaluated without success to limit the consequences of the ischemic cascade, but more rarely the therapies were explored as add on remedies on individuals also receiving reperfusion therapies. It is plausible that these putative neuroprotectants never reached the ischemic brain in adequate concentrations. Currently, the concept of neuroprotection incorporates cerebral perfusion as an obligatory substrate upon which ischemic brain survival depends, and it is plausible that some of the compounds tested in previous neuroprotection trials might have resulted in more favorable results if reperfusion therapies had been co-administered. Nonetheless, pharmacological or mechanical thrombectomy are frequently powerless to fully reperfuse the ischemic brain despite achieving a high rate of recanalization. This review covers in some detail the importance of the microcirculation, and the barriers that may hamper flow reperfusion at the microcirculatory level. It describes the main mechanisms leading to microcirculatory thrombosis including oxidative/nitrosative stress and refers to recent efforts to ameliorate brain perfusion in combination with the co-administration of neuroprotectants mainly aimed at harnessing oxidative/nitrosative brain damage.



J Stroke: 29 Apr 2018; 20:197-207
Chamorro Á
J Stroke: 29 Apr 2018; 20:197-207 | PMID: 29886725
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Impact:
Abstract

Differences in Therapeutic Responses and Factors Affecting Post-Stroke Depression at a Later Stage According to Baseline Depression.

Lee EJ, Kim JS, Chang DI, Park JH, ... Lee JS,
Background and purpose
The pathophysiology of post-stroke depression (PSD) is complex and may differ according to an individual\'s mood immediately after stroke. Here, we compared the therapeutic response and clinical characteristics of PSD at a later stage between patients with and without depression immediately after stroke.
Methods
This study involved aanalysis of data from EMOTION (ClinicalTrials.gov NCT01278498), a placebo-controlled, double-blind trial that examined the efficacy of escitalopram (10 mg/day) on PSD and other emotional disturbances among 478 patients with acute stroke. Participants were classified into the Baseline-Blue (patients with baseline depression at the time of randomization, defined per the Montgomery-Asberg Depression Rating Scale [MADRS] ≥8) or the Baseline-Pink groups (patients without baseline depression). We compared the efficacy of escitalopram and predictors of 3-month PSD (MADRS ≥8) between these groups.
Results
There were 203 Baseline-Pink and 275 Baseline-Blue patients. The efficacy of escitalopram in reducing PSD risk was more pronounced in the Baseline-Pink than in the Baseline-Blue group ( for interaction=0.058). Several risk factors differentially affected PSD development based on the presence of baseline depression ( for interaction <0.10). Cognitive dysfunction was an independent predictor of PSD in the Baseline-Blue, but not in the Baseline-Pink group, whereas the non-use of escitalopram and being female were more strongly associated with PSD in the Baseline-Pink group.
Conclusions
Responses to escitalopram and predictors of PSD 3 months following stroke differed based on the presence of baseline depression. Our data suggest that PSD pathophysiology is heterogeneous; therefore, different therapeutic strategies may be needed to prevent PSD emergence following stroke.



J Stroke: 29 Apr 2018; 20:258-267
Lee EJ, Kim JS, Chang DI, Park JH, ... Lee JS,
J Stroke: 29 Apr 2018; 20:258-267 | PMID: 29886724
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Impact:
Abstract

Serum Neurofilament Light Chain Levels Are Related to Small Vessel Disease Burden.

Duering M, Konieczny MJ, Tiedt S, Baykara E, ... de Leeuw FE, Peters N
Background and purpose
Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment.
Methods
Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale [NIHSS]) and disability (modified Rankin scale [mRS]).
Results
Serum NfL levels were elevated in both SVD samples (<1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R=0.52, =1.2e-09; sporadic SVD, R=0.21, <1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R=0.27, =7.6e-05; sporadic SVD, R=0.06, =4.8e-08), focal neurological symptoms (CADASIL, NIHSS, =4.2e-05) and disability (CADASIL, mRS, =3.0e-06).
Conclusions
We found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.



J Stroke: 29 Apr 2018; 20:228-238
Duering M, Konieczny MJ, Tiedt S, Baykara E, ... de Leeuw FE, Peters N
J Stroke: 29 Apr 2018; 20:228-238 | PMID: 29886723
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Abstract

Prevalence and Risk Factors of Cerebral Small Vessel Disease in a Chinese Population-Based Sample.

Han F, Zhai FF, Wang Q, Zhou LX, ... Jin ZY, Zhu YC
Background and purpose
Epidemiological data of cerebral small vessel disease (CSVD) in the general population of China are lacking. We report on the prevalence of lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) in a community-based sample in China and compare the results with those of other studies.
Methods
This was a cross-sectional analysis of the population-based Shunyi Study in China. A total of 1,211 stroke-free participants (mean age, 55.6±9.3 years; 37.4% men) with available 3 Tesla (3T) magnetic resonance images were included in this analysis. Demographic information and risk factor data were assessed. The overall and age-specific prevalence of lacunes, WMH, and CMBs was evaluated. Associations between cardiovascular risk factors and the presence of these lesions were analyzed by multiple logistic regression.
Results
Our study showed a prevalence of 14.5% for lacunes, 72.1% for periventricular hyperintensity (PVH), 65.4% for deep white matter hyperintensity (DWMH), and 10.6% for CMBs. When compared with other community-based samples, individuals in the same age group showed a higher burden of lacunes and a relatively lower prevalence of CMBs. Advanced age was independently associated with the prevalence of these CSVD markers, while the presence of hypertension increased the risk of lacunes, PVH/DWMH, and CMBs in deep or infratentorial locations.
Conclusions
A higher burden of lacunes but a relatively lower prevalence of CMBs was observed in this Chinese population. This notable result highlights the challenge of CSVD prevention in China. Chinese have a risk factor profile for CSVD similar to those in other populations.



J Stroke: 29 Apr 2018; 20:239-246
Han F, Zhai FF, Wang Q, Zhou LX, ... Jin ZY, Zhu YC
J Stroke: 29 Apr 2018; 20:239-246 | PMID: 29886722
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Abstract

Self-Rated Health Status and Risk of Incident Stroke in 0.5 Million Chinese Adults: The China Kadoorie Biobank Study.

Dong W, Pan XF, Yu C, Lv J, ... Li L,
Background and purpose
Self-rated health (SRH) is a consistent and strong predictor of all-cause and cardiovascular mortality in various populations. However, the associations between SRH measures and risk of first-ever or recurrent stroke were rarely explored. We thus aim to prospectively investigate the associations between SRH measures and risk of total and subtypes of stroke in Chinese population.
Methods
A total of 494,113 participants from the China Kadoorie Biobank without prior heart diseases or cancer (486,541 without stroke and 7,572 with stroke) were followed from baseline (2004 to 2008) until December 31, 2013. General and age-comparative SRH were obtained from baseline questionnaires. First-ever stroke or recurrent events were ascertained through linkage to disease registry system and health insurance data.
Results
We identified 27,662 first-ever stroke and 2,909 recurrent events during an average of 7.0 years of follow-up. Compared with excellent general SRH, the hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever stroke associated with good, fair, and poor general SRH were 1.04 (1.00 to 1.08), 1.19 (1.15 to 1.23), and 1.49 (1.42 to 1.56) in the multivariate model, respectively. Compared with better age-comparative SRH, the HRs (95% CIs) of same and worse age-comparative SRH were 1.13 (1.10 to 1.17) and 1.51 (1.45 to 1.58), respectively. The relations of SRH measures with ischemic stroke, hemorrhagic stroke, and recurrent stroke were similar to that with total first-ever stroke. However, the magnitude of associations was much stronger for fatal stroke than for non-fatal stroke.
Conclusions
This large-scale prospective cohort suggests that self-perceived health status is associated with incident stroke, regardless of stroke subtype.



J Stroke: 29 Apr 2018; 20:247-257
Dong W, Pan XF, Yu C, Lv J, ... Li L,
J Stroke: 29 Apr 2018; 20:247-257 | PMID: 29886721
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Abstract

Alcohol Intake and Risk of Ischemic and Haemorrhagic Stroke: Results from a Mendelian Randomisation Study.

Christensen AI, Nordestgaard BG, Tolstrup JS
Background and purpose
To test whether alcohol intake, both observational and estimated by genetic instruments, is associated with risk of ischemic and haemorrhagic stroke.
Methods
We used data from the Copenhagen City Heart Study 1991 to 1994 and 2001 to 2003, and the Copenhagen General Population Study 2003 to 2012 (n=78,546). As measure of alcohol exposure, self-reported consumption and genetic variation in alcohol metabolizing genes (alcohol dehydrogenaseand ) as instrumental variables were used. Stroke diagnoses were obtained from a validated hospital register.
Results
During follow-up 2,535 cases of ischemic and haemorrhagic stroke occurred. Low and moderate alcohol intake (1 to 20 drinks/week) was associated with reduced risk of stroke. The hazard ratios associated with drinking 1 to 6, 7 to 13, and 14 to 20 drinks/week were 0.84 (95% confidence interval [CI], 0.76 to 0.92), 0.83 (95% CI, 0.73 to 0.94), and 0.84 (95% CI, 0.73 to 0.97), respectively, compared with drinking <1 drink/day.andgenotypes were not associated with risk of stroke. Further analysis to test the included measures revealed that increasing alcohol intake (per 1 drink/day) was positively associated with risk of alcoholic liver cirrhosis, but not associated with risk of stroke, and that increasing blood pressure (per systolic 10 mm Hg) was not associated with risk of alcoholic liver cirrhosis, but positively associated with risk of stroke.
Conclusions
Low and moderate self-reported alcohol intake was associated with reduced risk of stroke. The result was not supported by the result from the causal genetic analysis.



J Stroke: 29 Apr 2018; 20:218-227
Christensen AI, Nordestgaard BG, Tolstrup JS
J Stroke: 29 Apr 2018; 20:218-227 | PMID: 29886720
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Impact:
Abstract

Updates on Prevention of Hemorrhagic and Lacunar Strokes.

Tsai HH, Kim JS, Jouvent E, Gurol ME

Intracerebral hemorrhage (ICH) and lacunar infarction (LI) are the major acute clinical manifestations of cerebral small vessel diseases (cSVDs). Hypertensive small vessel disease, cerebral amyloid angiopathy, and hereditary causes, such as Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), constitute the three common cSVD categories. Diagnosing the underlying vascular pathology in these patients is important because the risk and types of recurrent strokes show significant differences. Recent advances in our understanding of the cSVD-related radiological markers have improved our ability to stratify ICH risk in individual patients, which helps guide antithrombotic decisions. There are general good-practice measures for stroke prevention in patients with cSVD, such as optimal blood pressure and glycemic control, while individualized measures tailored for particular patients are often needed. Antithrombotic combinations and anticoagulants should be avoided in cSVD treatment, as they increase the risk of potentially fatal ICH without necessarily lowering LI risk in these patients. Even when indicated for a concurrent pathology, such as nonvalvular atrial fibrillation, nonpharmacological approaches should be considered in the presence of cSVD. More data are emerging regarding the presentation, clinical course, and diagnostic markers of hereditary cSVD, allowing accurate diagnosis, and therefore, guiding management of symptomatic patients. When suspicion for asymptomatic hereditary cSVD exists, the pros and cons of prescribing genetic testing should be discussed in detail in the absence of any curative treatment. Recent data regarding diagnosis, risk stratification, and specific preventive approaches for both sporadic and hereditary cSVDs are discussed in this review article.



J Stroke: 29 Apr 2018; 20:167-179
Tsai HH, Kim JS, Jouvent E, Gurol ME
J Stroke: 29 Apr 2018; 20:167-179 | PMID: 29886717
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Impact:
Abstract

Updates on Prevention of Cardioembolic Strokes.

Topcuoglu MA, Liu L, Kim DE, Gurol ME

Cardiac embolism continues to be a leading etiology of ischemic strokes worldwide. Although pathologies that result in cardioembolism have not changed over the past decade, there have been significant advances in the treatment and stroke prevention methods for these conditions. Atrial fibrillation remains the prototypical cause of cardioembolic strokes. The availability of new long-term monitoring devices for atrial fibrillation detection such as insertable cardiac monitors has allowed accurate detection of this leading cause of cardioembolism. The non-vitamin K antagonist oral anticoagulants have improved our ability to prevent strokes for many patients with non-valvular atrial fibrillation (NVAF). Advances in left atrial appendage closure and the U.S. Food and Drug Administration approval of the WATCHMAN (Boston Scientific) device for stroke prevention in NVAF patients who have an appropriate rationale for a nonpharmacological alternative, have revolutionized the field and provided a viable option for patients at higher hemorrhagic risk. The role of patent foramen ovale closure for secondary prevention in selected patients experiencing cryptogenic ischemic strokes at a relatively young age has become clearer thanks to the very recent publication of long-term outcomes from three major studies. Advances in the management of infective endocarditis, heart failure, valvular diseases, and coronary artery disease have significantly changed the management of such patients, but have also revealed new concerns related to assessment of ischemic versus hemorrhagic risk in the setting of antithrombotic use. The current review article aims to discuss these advances especially as they pertain to the stroke neurology practice.



J Stroke: 29 Apr 2018; 20:180-196
Topcuoglu MA, Liu L, Kim DE, Gurol ME
J Stroke: 29 Apr 2018; 20:180-196 | PMID: 29886716
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Impact:
Abstract

Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke.

Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV

Atherosclerosis is a major cause of ischemic stroke that can be effectively prevented with appropriate lifestyle modifications and control of cardiovascular risk factors. Medical advances in recent years along with aggressive cardiovascular risk factor modifications have resulted in decreased recurrence rates of atherosclerotic stroke. Non-statin lipid-lowering molecules have recently shown clinical benefit and are recommended for very high-risk patients to reduce their risk of stroke. Aggressive hypertension treatment is crucial to reduce atherosclerotic stroke risk. Advances in antithrombotic treatments include combinations of antiplatelets and new antiplatelet agents in the acute phase post-stroke, which carries a high risk of recurrence. Intensive medical treatment has also limited the indications for carotid interventions, especially for asymptomatic disease. Intracranial atherosclerotic disease may provoke stroke through various mechanisms; it is increasingly recognized as a cause of ischemic stroke with advanced imaging and is best managed with lifestyle modifications and medical therapy. The diagnostic search for the vulnerable culprit atherosclerotic plaque is an area of intense research, from the level of the intracranial arteries to that of the aortic arch. Ultrasonography and novel magnetic resonance imaging techniques (high-resolution vessel-wall imaging) may assist in the identification of vulnerable atherosclerotic plaques as the underlying cause in cryptogenic or misdiagnosed non-atherosclerotic ischemic stroke. Vertebrobasilar atherosclerotic disease is less common than carotid artery disease; thus, high-quality data on effective prevention strategies are scarcer. However, aggressive medical treatment is also the gold standard to reduce cerebrovascular disease located in posterior circulation.



J Stroke: 29 Apr 2018; 20:145-166
Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV
J Stroke: 29 Apr 2018; 20:145-166 | PMID: 29886715
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Impact:
Abstract

Susceptibility Vessel Sign in the ASTER Trial: Higher Recanalization Rate and More Favourable Clinical Outcome after First Line Stent Retriever Compared to Contact Aspiration.

Bourcier R, Mazighi M, Labreuche J, Fahed R, ... Lapergue B,
Background and purpose
In the Aspiration vs. Stent Retriever for Successful Revascularization (ASTER) trial, which evaluated contact aspiration (CA) versus stent retriever (SR) use as first-line technique, the impact of the susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) was studied to determine its influence on trial results.
Methods
We included patients having undergone CA or SR for M1 or M2 occlusions, who were screened by MRI with T2 gradient recalled echo. Occlusions were classified as SVS (+) or SVS (-) in each randomization arm. Modified thrombolysis in cerebral infarction (mTICI) 2b, 2c, or 3 revascularization rates were recorded and clinical outcomes assessed by the overall distribution of modified Rankin scale (mRS) at 90 days.
Results
Among the 202 patients included, 143 patients were SVS (+) (70.8%; 95% confidence interval [CI], 64.5% to 77.1%). Overall, there was no difference in angiographic and clinical outcomes according to SVS status. However, compared to SR, CA achieved a lower mTICI 2c/3 rate in SVS (+) patients (risk ratio [RR] for CA vs. SR, 0.60; 95% CI, 0.51 to 0.71) but not in SVS (-) (RR, 1.11; 95% CI, 0.69 to 1.77;for interaction=0.018). A significant heterogeneity in favor of superiority of first-line SR strategy in SVS (+) patients was also found regarding the overall mRS distribution (common odds ratio for CA vs. SR, 0.40 vs. 1.32; 95% CI, 0.21 to 0.74 in SVS (+) vs. 95% CI, 0.51 to 3.35 in SVS (-);for interaction=0.038).
Conclusions
As a first line strategy, SR achieved higher recanalization rates and a more favourable clinical outcome at 3 months compared to CA when MRI shows SVS within the thrombus.



J Stroke: 29 Apr 2018; 20:268-276
Bourcier R, Mazighi M, Labreuche J, Fahed R, ... Lapergue B,
J Stroke: 29 Apr 2018; 20:268-276 | PMID: 29886714
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Impact:
Abstract

Intracranial Large Artery Disease of Non-Atherosclerotic Origin: Recent Progress and Clinical Implications.

Bang OY, Toyoda K, Arenillas JF, Liu L, Kim JS

Intracranial large artery disease (ILAD) is the major cause of stroke worldwide. With the application of recently introduced diagnostic techniques, the prevalence of non-atherosclerotic ILAD is expected to increase. Herein, we reviewed recent reports and summarized progress in the diagnosis and clinical impact of differentiation between ILAD of atherosclerotic and non-atherosclerotic origin. Our review of the literature suggests that more careful consideration of non-atherosclerotic causes and the application of appropriate diagnostic techniques in patients with ILAD may not only provide better results in the treatment of patients, but it may also lead to more successful clinical trials for the treatment of intracranial atherosclerosis.



J Stroke: 29 Apr 2018; 20:208-217
Bang OY, Toyoda K, Arenillas JF, Liu L, Kim JS
J Stroke: 29 Apr 2018; 20:208-217 | PMID: 29886713
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Impact:
Abstract

Air Pollution and Stroke.

Lee KK, Miller MR, Shah ASV

The adverse health effects of air pollution have long been recognised; however, there is less awareness that the majority of the morbidity and mortality caused by air pollution is due to its effects on the cardiovascular system. Evidence from epidemiological studies have demonstrated a strong association between air pollution and cardiovascular diseases including stroke. Although the relative risk is small at an individual level, the ubiquitous nature of exposure to air pollution means that the absolute risk at a population level is on a par with \"traditional\" risk factors for cardiovascular disease. Of particular concern are findings that the strength of this association is stronger in low and middle income countries where air pollution is projected to rise as a result of rapid industrialisation. The underlying biological mechanisms through which air pollutants exert their effect on the vasculature are still an area of intense discussion. A greater understanding of the effect size and mechanisms is necessary to develop effective strategies at individual and policy levels to mitigate the adverse cardiovascular effects of air pollution.



J Stroke: 30 Dec 2017; 20:2-11
Lee KK, Miller MR, Shah ASV
J Stroke: 30 Dec 2017; 20:2-11 | PMID: 29402072
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Impact:
Abstract

Sleep Disturbances as a Risk Factor for Stroke.

Koo DL, Nam H, Thomas RJ, Yun CH

Sleep, a vital process of human being, is carefully orchestrated by the brain and consists of cyclic transitions between rapid eye movement (REM) and non-REM (NREM) sleep. Autonomic tranquility during NREM sleep is characterized by vagal dominance and stable breathing, providing an opportunity for the cardiovascular-neural axis to restore homeostasis, in response to use, distress or fatigue inflicted during wakefulness. Abrupt irregular swings in sympathovagal balance during REM sleep act as phasic loads on the resting cardiovascular system. Any causes of sleep curtailment or fragmentation such as sleep restriction, sleep apnea, insomnia, periodic limb movements during sleep, and shift work, not only impair cardiovascular restoration but also impose a stress on the cardiovascular system. Sleep disturbances have been reported to play a role in the development of stroke and other cardiovascular disorders. This review aims to provide updated information on the role of abnormal sleep in the development of stroke, to discuss the implications of recent research findings, and to help both stroke clinicians and researchers understand the importance of identification and management of sleep pathology for stroke prevention and care.



J Stroke: 30 Dec 2017; 20:12-32
Koo DL, Nam H, Thomas RJ, Yun CH
J Stroke: 30 Dec 2017; 20:12-32 | PMID: 29402071
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Impact:
Abstract

Heart Failure as a Risk Factor for Stroke.

Kim W, Kim EJ

Heart failure (HF) is one of the major causes of death worldwide. Despite the high incidence of stroke in patients with HF, there has been a controversy as to whether HF itself is a risk factor for stroke. Recently, there is a great deal of evidence that HF itself increases the risk of stroke. In previous studies, the benefit of warfarin for stroke prevention in patients with HF was offset by the risk of bleeding. In the era of non-vitamin K antagonist oral anticoagulants with low bleeding profiles, we can expect a more effective stroke prevention in patients with HF by selective anticoagulation. The purpose of this review is to describe the relationship between stroke and HF, which could be an unconventional risk factor and a potential intervention target for stroke prevention.



J Stroke: 30 Dec 2017; 20:33-45
Kim W, Kim EJ
J Stroke: 30 Dec 2017; 20:33-45 | PMID: 29402070
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Impact:
Abstract

Treatments to Promote Neural Repair after Stroke.

Cramer SC

Stroke remains a major cause of human disability worldwide. In parallel with advances in acute stroke interventions, new therapies are under development that target restorative processes. Such therapies have a treatment time window measured in days, weeks, or longer and so have the advantage that they may be accessible by a majority of patients. Several categories of restorative therapy have been studied and are reviewed herein, including drugs, growth factors, monoclonal antibodies, activity-related therapies including telerehabilitation, and a host of devices such as those related to brain stimulation or robotics. Many patients with stroke do not receive acute stroke therapies or receive them and do not derive benefit, often surviving for years thereafter. Therapies based on neural repair hold the promise of providing additional treatment options to a majority of patients with stroke.



J Stroke: 30 Dec 2017; 20:57-70
Cramer SC
J Stroke: 30 Dec 2017; 20:57-70 | PMID: 29402069
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Abstract

Association of MicroRNA Biogenesis Genes Polymorphisms with Ischemic Stroke Susceptibility and Post-Stroke Mortality.

Kim JO, Bae J, Kim J, Oh SH, ... Kim OJ, Kim NK
Background and purpose
MicroRNA (miRNA) expression has been examined in multiple conditions, including various cancers, neurological diseases, and cerebrovascular diseases, particularly stroke. Existing evidence indicates that miRNA biosynthesis and function play crucial roles in ischemic stroke physiology and pathology. In this study, we selected six known polymorphisms in miRNA-biogenesis genes;rs13078A>T, rs3742330A>G;rs10719T>C, rs6877842G>C; Ran GTPase () rs14035C>T; exportin 5 () rs11077A>C.
Methods
We analyzed the associations between these polymorphisms and disease status and clinical factors in 585 ischemic stroke patients and 403 controls. Genotyping was performed with the polymerase chain reaction-restriction fragment length polymorphism method.
Results
Thers3742330A>G (AA vs. AG+GG: adjusted odds ratio [AOR], 1.360; 95% confidence interval [CI], 1.024 to 1.807; =0.034) andrs10719T>C polymorphisms (TT vs. CC: AOR, 2.038; 95% CI, 1.113 to 3.730; =0.021) were associated with ischemic stroke prevalence. During a mean follow-up of 4.80±2.11 years, 99 (5.91%) of the stroke patients died. In multivariate Cox proportional hazard regression models, a significant association was found betweenrs14035 and survival of large artery disease patients with ischemic stroke (CC vs. TT: adjusted hazard ratio, 5.978; =0.015).
Conclusions
An association was identified between theandpolymorphisms and ischemic stroke. Specifically, polymorphisms (rs3742330 and rs10719) were more common in stroke patients, suggesting that they may be associated with an increased risk of ischemic stroke.



J Stroke: 30 Dec 2017; 20:110-121
Kim JO, Bae J, Kim J, Oh SH, ... Kim OJ, Kim NK
J Stroke: 30 Dec 2017; 20:110-121 | PMID: 29402068
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Abstract

Differences between the Molecular Mechanisms Underlying Ruptured and Non-Ruptured Carotid Plaques, and the Significance of ABCA1.

Heo SH, Lee EH, Park HH, Kim BJ, ... Koh SH, Chang DI
Background and purpose
Carotid plaques are a strong risk factor for ischemic stroke, and plaque rupture poses an even higher risk. Although many studies have investigated the pathogenic mechanisms of carotid plaque formation, few have studied the differences in molecular mechanisms underlying the rupture and non-rupture of carotid plaques. In addition, since early diagnosis and treatment of carotid plaque rupture are critical for the prevention of ischemic stroke, many studies have sought to identify the important target molecules involved in the rupture. However, a target molecule critical in symptomatic ruptured plaques is yet to be identified.
Methods
A total of 79 carotid plaques were consecutively collected, and microscopically divided into ruptured and non-ruptured groups. Quantitative polymerase chain reaction array, proteomics, and immunohistochemistry were performed to compare the differences in molecular mechanisms between ruptured and non-ruptured plaques. Enzyme-linked immunosorbent assay was used to measure the differences in ATP-binding cassette subfamily A member 1 (ABCA1) levels in the serum.
Results
The expression of several mRNAs and proteins, including ABCA1, was higher in ruptured plaques than non-ruptured plaques. In contrast, the expression of other proteins, including β-actin, was lower in ruptured plaques than non-ruptured plaques. The increased expression of ABCA1 was consistent across several experiments, ABCA1 was positive only in the serum of patients with symptomatic ruptured plaques.
Conclusions
This study introduces a plausible molecular mechanism underlying carotid plaque rupture, suggesting that ABCA1 plays a role in symptomatic rupture. Further study of ABCA1 is needed to confirm this hypothesis.



J Stroke: 30 Dec 2017; 20:80-91
Heo SH, Lee EH, Park HH, Kim BJ, ... Koh SH, Chang DI
J Stroke: 30 Dec 2017; 20:80-91 | PMID: 29402067
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Abstract

Development of New Endovascular Devices for Aneurysm Treatment.

Jia ZY, Shi HB, Miyachi S, Hwang SM, ... Lee DH, Suh DC

Since the first use of the Guglielmi detachable coil system for cerebral aneurysm embolization in 1990, various endovascular methods have been developed to treat large numbers of aneurysms. The main strategic and technical modifications introduced to date include balloon-assisted coil embolization, stent-assisted coil embolization, flow diverters, and flow disrupters. The development and introduction of such devices have been so persistent and rapid that new devices are being approved worldwide even before the earlier ones become available in some countries. However, even if some patient populations may possibly benefit from earlier introduction of new devices, the approval authorities should balance the available evidence of the safety and effectiveness of novel devices. This review aims to provide an overview of the recent innovations in endovascular treatment of cerebral aneurysms and a brief review of market access policies and regulations for importing high-risk medical devices, such as those used for endovascular aneurysm management, which correspond to class III devices, as defined by the U.S. Food and Drug Administration. We focus on the current situation in Korea and compare it with that in other Asian countries, such as China and Japan.



J Stroke: 30 Dec 2017; 20:46-56
Jia ZY, Shi HB, Miyachi S, Hwang SM, ... Lee DH, Suh DC
J Stroke: 30 Dec 2017; 20:46-56 | PMID: 29402066
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Abstract

Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer.

Addison D, Lawler PR, Emami H, Janjua SA, ... Hoffmann U, Neilan TG
Background and purpose
Interventions to reduce the risk for cerebrovascular events (CVE; stroke and transient ischemic attack [TIA]) after radiotherapy (RT) for head and neck cancer (HNCA) are needed. Among broad populations, statins reduce CVEs; however, whether statins reduce CVEs after RT for HNCA is unclear. Therefore, we aimed to test whether incidental statin use at the time of RT is associated with a lower rate of CVEs after RT for HNCA.
Methods
From an institutional database we identified all consecutive subjects treated with neck RT from 2002 to 2012 for HNCA. Data collection and event adjudication was performed by blinded teams. The primary outcome was a composite of ischemic stroke and TIA. The secondary outcome was ischemic stroke. The association between statin use and events was determined using Cox proportional hazard models after adjustment for traditional and RT-specific risk factors.
Results
The final cohort consisted of 1,011 patients (59±13 years, 30% female, 44% hypertension) with 288 (28%) on statins. Over a median follow-up of 3.4 years (interquartile range, 0.1 to 14) there were 102 CVEs (89 ischemic strokes and 13 TIAs) with 17 in statin users versus 85 in nonstatins users. In a multivariable model containing known predictors of CVE, statins were associated with a reduction in the combination of stroke and TIA (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 to 0.8; =0.01) and ischemic stroke alone (HR, 0.4; 95% CI, 0.2 to 0.8; =0.01).
Conclusions
Incidental statin use at the time of RT for HNCA is associated with a lower risk of stroke or TIA.



J Stroke: 30 Dec 2017; 20:71-79
Addison D, Lawler PR, Emami H, Janjua SA, ... Hoffmann U, Neilan TG
J Stroke: 30 Dec 2017; 20:71-79 | PMID: 29402065
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Abstract

Low- versus Standard-Dose Intravenous Alteplase in the Context of Bridging Therapy for Acute Ischemic Stroke: A Korean ENCHANTED Study.

Kim JS, Kim YJ, Lee KB, Cha JK, ... Chalmers J, Anderson CS
Background and purpose
Following the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown.
Methods
In this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616).
Results
Of 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; =0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, =0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; =0.149).
Conclusions
There was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.



J Stroke: 30 Dec 2017; 20:131-139
Kim JS, Kim YJ, Lee KB, Cha JK, ... Chalmers J, Anderson CS
J Stroke: 30 Dec 2017; 20:131-139 | PMID: 29402064
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Abstract

Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials.

Hsu CY, Chiu SW, Hong KS, Saver JL, ... Lee M, Ovbiagele B
Background and purpose
Additional folic acid (FA) treatment appears to have a neutral effect on reducing vascular risk in countries that mandate FA fortification of food (e.g., USA and Canada). However, it is uncertain whether FA therapy reduces stroke risk in countries without FA food fortification. The purpose of this study was to comprehensively evaluate the efficacy of FA therapy on stroke prevention in countries without FA food fortification.
Methods
PubMed, EMBASE, and clinicaltrials.gov from January 1966 to August 2016 were searched to identify relevant studies. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between FA supplementation and risk of stroke, after pooling data across trials in a random-effects model.
Results
The search identified 13 randomized controlled trials (RCTs) involving treatment with FA that had enrolled 65,812 participants, all of which stroke was reported as an outcome measure. After all 13 RCTs were pooled, FA therapy versus control was associated with a lower risk of any future stroke (RR, 0.85; 95% CI, 0.77 to 0.95). FA alone or combination of FA and minimal cyanocobalamin (≤0.05 mg/day) was associated with a lower risk of future stroke (RR, 0.75; 95% CI, 0.66 to 0.86) whereas combination of FA and cyanocobalamin (≥0.4 mg/day) was not associated with a lower risk of future stroke (RR, 0.95; 95% CI, 0.86 to 1.05).
Conclusions
FA supplement reduced stroke in countries without mandatory FA food fortification. The benefit was found mostly in patients receiving FA alone or combination of FA and minimal cyanocobalamin.



J Stroke: 30 Dec 2017; 20:99-109
Hsu CY, Chiu SW, Hong KS, Saver JL, ... Lee M, Ovbiagele B
J Stroke: 30 Dec 2017; 20:99-109 | PMID: 29402063
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Abstract

Basilar Artery Plaque and Pontine Infarction Location and Vascular Geometry.

Kim BJ, Lee KM, Kim HY, Kim YS, ... Heo SH, Chang DI
Background and purpose
Subclinical atherosclerotic plaques are common in patients with pontine infarctions (PIs) but without basilar artery (BA) stenosis. We hypothesized that BA plaque locations may differ by PI type and vertical location as well as vertebrobasilar artery geometry.
Methods
Ninety-six patients with PI but without BA stenosis on magnetic resonance imaging (MRI) and magnetic resonance angiography were enrolled. PIs were classified by type (paramedian, deep, or lateral) and vertical location (rostral, middle, or caudal). Patients underwent high-resolution MRI to evaluate BA plaque location (anterior, posterior, or lateral). The mid-BA angle on anteroposterior view and angle between the BA and dominant vertebral artery (BA-VA angle) on lateral view were measured.
Results
The PIs were paramedian (72.9%), deep (17.7%), and lateral (9.4%) type with a rostral (32.3%), middle (42.7%), and caudal (25.0%) vertical location. The BA plaque locations differed by PI type (=0.03) and vertical location (<0.001); BA plaques were most frequent at the posterior wall in paramedian (37.1%) and caudal (58.3%) PIs and at the lateral wall in lateral (55.5%) and middle (34.1%) PIs. The BA-VA and mid-BA angles differed by BA plaque and PI vertical location; the greatest BA-VA angle was observed in patients with posterior plaques (<0.001) and caudal PIs (<0.001). Greatest mid-BA angles were observed with lateral BA plaques (=0.03) and middlelocated PIs (=0.03).
Conclusions
Greater mid-BA angulation may enhance lateral plaque formation, causing lateral and middle PIs, whereas greater BA-VA angulation may enhance posterior plaque formation, causing paramedian or caudal PIs.



J Stroke: 30 Dec 2017; 20:92-98
Kim BJ, Lee KM, Kim HY, Kim YS, ... Heo SH, Chang DI
J Stroke: 30 Dec 2017; 20:92-98 | PMID: 29402062
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Abstract

Penumbral Imaging-Based Thrombolysis with Tenecteplase Is Feasible up to 24 Hours after Symptom Onset.

Kate M, Wannamaker R, Kamble H, Riaz P, ... Emery D, Butcher K
Background and purpose
Thrombolysis >4.5 hours after ischemic stroke onset is unproven. We assessed the feasibility of tenecteplase (TNK) treatment in patients with evidence of an ischemic penumbra 4.5 to 24 hours after onset.
Methods
Acute ischemic stroke patients underwent perfusion computed tomography (CT)/magnetic resonance imaging. Patients with cerebral blood volume (CBV) or diffusion weighted imaging Alberta Stroke Program Early CT Scores (ASPECTS) >6 and mismatch score >2 (defined as >2 ASPECTS regions with delay on mean transit time maps and normal CBV) were eligible for treatment with TNK (0.25 mg/kg). Patients with mismatch patterns enrolled in non-endovascular/non-thrombolysis trials and those without mismatch patterns served as comparators.
Results
The median (interquartile range) baseline National Institutes of Health Stroke Scale (NIHSS) in TNK treated patients (n=16) was 12 (range, 8 to 15). In the untreated mismatch (n=18) and nonmismatch (n=23) groups, the baseline NIHSS was 12 (range, 7 to 12) and 16 (range, 8 to 20; =0.09) respectively. There was one symptomatic hemorrhage each in the TNK group (parenchymal hematoma [PH] 2) and non-mismatch group (PH 2). Penumbral salvage volumes were higher in TNK treated patients (48.3 mL [range, 24.9 to 80.4]) than the non-mismatch (-90.8 mL [range, -197 to -20]; <0.0001) patients.
Conclusions
This prospective, non-randomized study supports the feasibility of TNK therapy in patients with evidence of ischemic penumbra 4 to 24 hours after onset.



J Stroke: 30 Dec 2017; 20:122-130
Kate M, Wannamaker R, Kamble H, Riaz P, ... Emery D, Butcher K
J Stroke: 30 Dec 2017; 20:122-130 | PMID: 29402060
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Abstract

Comparison of Spot Sign, Blend Sign and Black Hole Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage.

Sporns PB, Schwake M, Kemmling A, Minnerup J, ... Schmidt R, Hanning U
Background and purpose
Blend sign (BS) and black hole sign (BHS) on non-contrast computed tomography (NCCT) and spot sign (SS) on CT-angiography (CTA) are indicators of early hematoma expansion in spontaneous intracerebral hemorrhage (ICH). However, their independent contributions to outcome have not been well explored.
Methods
In this retrospective study, inclusion criteria were: 1) spontaneous ICH and 2) NCCT and CTA performed on admission within 6 hours after onset of symptoms. Discharge outcome was dichotomized as good (modified Rankin Scale [mRS] 0-3) and poor (mRS 4-6) outcomes. The impacts of BHS, BS and SS on outcome were assessed in univariate and multivariable logistic regression models.
Results
Of 182 patients with spontaneous ICH, 26 (14.3%) presented with BHS, 37 (20.3%) with BS and 39 (21.4%) with SS. There was a substantial correlation between SS and BS (κ=0.701) and a moderate correlation between SS and BHS (κ=0.424). In univariable logistic regression, higher baseline hematoma volume (<0.001), intraventricular hemorrhage (=0.002) and the presence of BHS/BS/SS (all <0.001) on admission CT scan were associated with poor outcome. Multivariable analysis identified intraventricular haemorrhage (odds ratio [OR] 2.22 per mL, =0.022), baseline hematoma volume (OR 1.03 per mL, <0.001) and SS on CTA (OR 11.43, <0.001) as independent predictors of poor outcome, showing that SS compared to BS and BHS was more powerful to predict poor outcome.
Conclusions
The NCCT BHS and BS are correlated with the CTA SS and are reliable predictors of poor outcome in patients with ICH. Of the CT variables indicating early hematoma expansion, SS on CTA was the most reliable outcome predictor. However, given their correlation with SS on CTA, BS and BHS on NCCT can be useful for predicting outcome if CTA is not obtainable.



J Stroke: 30 Aug 2017; 19:333-339
Sporns PB, Schwake M, Kemmling A, Minnerup J, ... Schmidt R, Hanning U
J Stroke: 30 Aug 2017; 19:333-339 | PMID: 29037015
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Abstract

Deep into the Brain: Artificial Intelligence in Stroke Imaging.

Lee EJ, Kim YH, Kim N, Kang DW

Artificial intelligence (AI), a computer system aiming to mimic human intelligence, is gaining increasing interest and is being incorporated into many fields, including medicine. Stroke medicine is one such area of application of AI, for improving the accuracy of diagnosis and the quality of patient care. For stroke management, adequate analysis of stroke imaging is crucial. Recently, AI techniques have been applied to decipher the data from stroke imaging and have demonstrated some promising results. In the very near future, such AI techniques may play a pivotal role in determining the therapeutic methods and predicting the prognosis for stroke patients in an individualized manner. In this review, we offer a glimpse at the use of AI in stroke imaging, specifically focusing on its technical principles, clinical application, and future perspectives.



J Stroke: 30 Aug 2017; 19:277-285
Lee EJ, Kim YH, Kim N, Kang DW
J Stroke: 30 Aug 2017; 19:277-285 | PMID: 29037014
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Abstract

Angioplasty, Stenting and Other Potential Treatments of Atherosclerotic Stenosis of the Intracranial Arteries: Past, Present and Future.

Wabnitz A, Chimowitz M

Although there is an intuitive appeal to treat symptomatic stenotic intracranial arteries with endovascular therapies such as angioplasty and stenting, current data from randomized trials show intensive medical therapy is far superior for preventing stroke. This is in large part due to the high risk of peri-procedural stroke from angioplasty and stenting. If angioplasty and stenting is to emerge as a proven treatment for intracranial stenosis, endovascular techniques will need to become much safer, identification of patients with intracranial stenosis who are at particularly high risk of stroke despite intensive medical therapy will need to be targeted, and well-designed randomized trials will be necessary to show endovascular therapy is superior to medical therapy in these high-risk patients.



J Stroke: 30 Aug 2017; 19:271-276
Wabnitz A, Chimowitz M
J Stroke: 30 Aug 2017; 19:271-276 | PMID: 29037013
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Abstract

Medical Treatment of Intracranial Atherosclerosis: An Update.

Kim JS, Bang OY

For patients with symptomatic intracranial atherosclerosis (ICAS), antithrombotic agents are the mainstay of therapy. Anticoagulation (warfarin) is not widely used since it is not more effective than aspirin and carries a high risk of bleeding. New oral anticoagulants are showing promise, but their use has not been investigated in appropriate clinical trials. Since the recurrent stroke risk is high with aspirin monotherapy, dual antiplatelets are considered in the early stage of symptomatic ICAS. Based on the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) results, aspirin plus clopidogrel has been recommended. However, this combination was not superior to aspirin monotherapy in patients with ICAS in the CHANCE substudy. Progression of ICAS is common, and it is associated with recurrent strokes. In the Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis (TOSS) study, aspirin plus cilostazol was more effective than aspirin monotherapy in preventing progression. The TOSS II trial showed that the overall change in stenosis was better with aspirin plus cilostazol than with aspirin plus clopidogrel. Aside from antithrombotic therapy, risk factor management is critical for secondary prevention, and high blood pressure is clearly linked to recurrent stroke. However, blood pressure may have to be cautiously managed in the early stage of stroke. Considering that ICAS is the major cause of stroke worldwide, further investigations are needed to establish optimal management strategies for patients with ICAS.



J Stroke: 30 Aug 2017; 19:261-270
Kim JS, Bang OY
J Stroke: 30 Aug 2017; 19:261-270 | PMID: 29037012
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Abstract

Visibility of CT Early Ischemic Change Is Significantly Associated with Time from Stroke Onset to Baseline Scan beyond the First 3 Hours of Stroke Onset.

Gao J, Parsons MW, Kawano H, Levi CR, ... Lin L, Bivard A
Background and purpose
Non-contrast brain computed tomography (NCCT) remains the most common imaging modality employed to select patients for thrombolytic therapy in acute ischemic stroke. The current study used the Alberta Stroke Program Early CT Score (ASPECTS) to identify early ischemic changes on brain NCCT imaging with the aim to investigate whether a relationship exists between time from symptoms onset to NCCT with the presence of early ischaemic change quantified by ASPECTS.
Methods
We studied 1,329 ischemic stroke patients who had NCCT within 8 hours of stroke onset. Patients were assessed to see if they had any ASPECTS lesion and if the rate of patients with a lesion increased with time using logistic regression.
Results
30% patients had an ASPECTS <10 within the first 3 hours from symptom onset. Within the first 3 hours, the odds for a CT change (ASPECTS <10) per minute of time was 1.00 with 95% confidence interval (CI) (0.99 to 1.00) (=0.266). After 3 hours, there was a significant increase in odds of ASPECTS <10 with increasing time. The odds of being ASPECTS positive increased 1% (odds ratio=1.01) per 1 minute of time with 95% CI (1.00 to 1.01) (=0.002).
Conclusions
We have identified that prior to first 3 hours of stroke there was no effect of time on odds of CT ischemic change; after the first 3 hours of stroke the odds increased with increasing time to CT scan. The occurrence of early ischemic change may be a marker of time from stroke onset rather than severity.



J Stroke: 30 Aug 2017; 19:340-346
Gao J, Parsons MW, Kawano H, Levi CR, ... Lin L, Bivard A
J Stroke: 30 Aug 2017; 19:340-346 | PMID: 29037011
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Abstract

Effects of Triflusal and Clopidogrel on the Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping.

Han SW, Kim YJ, Ahn SH, Seo WK, ... Bushnell CD, Lee KY
Background and purpose
To compare the efficacy and safety of antiplatelet agents for the secondary prevention of ischemic stroke based on cytochrome P450 2C19 (CYP2C19) polymorphisms.
Methods
This study was a prospective, multicenter, randomized, parallel-group, open-label, blind genotype trial. First time non-cardiogenic ischemic stroke patients were enrolled and screened within 30 days. Participants were randomized to receive either triflusal or clopidogrel for secondary stroke prevention. The primary outcome was the time from randomization to first recurrent ischemic stroke or hemorrhagic stroke.
Results
The required sample size was 1,080 but only 784 (73%) participants were recruited. In patients with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of recurrent stroke among those who received triflusal treatment was 2.9% per year, which was not significantly different from those who received clopidogrel treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.60-2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke in patients with a good CYP2C19 genotype was 1.6% per year, which was not significantly different from those with a poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26-1.79).
Conclusions
Whilst there were no significant differences between the treatment groups in the rates of stroke recurrence, major vascular events, or coronary revascularization, the efficacy of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype status remains unclear.



J Stroke: 30 Aug 2017; 19:356-364
Han SW, Kim YJ, Ahn SH, Seo WK, ... Bushnell CD, Lee KY
J Stroke: 30 Aug 2017; 19:356-364 | PMID: 29037010
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Abstract

MicroRNA 150-5p Improves Risk Classification for Mortality within 90 Days after Acute Ischemic Stroke.

Scherrer N, Fays F, Mueller B, Luft A, ... Devaux Y, Katan M
Background and purpose
Micro ribonucleic acid-150-5p (miR-150-5p) regulates proinflammatory cytokines as well as vessel integrity. We evaluated the incremental prognostic value of logarithm (log) of miR-150-5p plasma levels after ischemic stroke.
Methods
In a prospective cohort study, levels of miR-150-5p were measured within 72 hours of symptom onset in 329 ischemic stroke patients. The outcome measures were unfavorable functional outcome (assessed by the modified Rankin Scale score >2) and mortality within 90 days. Logistic regression and Cox proportional hazards models were fitted to estimate odds ratio (OR), respectively hazard ratio (HR) and 95% confidence interval (CI) for the association between log-miR-150-5p and the outcome measures. The discriminatory accuracy was assessed with the area under the receiver-operating-characteristic curve (AUC) and the incremental prognostic value was estimated with the net reclassification index.
Results
After adjusting for demographic and vascular risk factors, lower log-miR-150-5p levels were independently associated with mortality (HR 0.21 [95% CI, 0.08-0.51], =0.001) but not functional outcome (OR 1.10 [95% CI, 0.54-2.25], =0.79). Adding log-miR-150-5p improved the discriminatory accuracy of the best multivariate model to predict mortality from an AUC of 0.91 (95% CI, 0.88-0.95) to 0.92 (95% CI, 0.88-0.96 Likelihood-ratio test-<0.001), and resulted in a net reclassification index of 37.3% (95% CI, 0.28-0.52).
Conclusions
In patients with ischemic stroke, log-miR-150-5p is a novel prognostic biomarker, highly associated with mortality within 90 days, improving risk classification beyond traditional risk factors.



J Stroke: 30 Aug 2017; 19:323-332
Scherrer N, Fays F, Mueller B, Luft A, ... Devaux Y, Katan M
J Stroke: 30 Aug 2017; 19:323-332 | PMID: 29037006
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Abstract

Stroke Epidemiology in South, East, and South-East Asia: A Review.

Venketasubramanian N, Yoon BW, Pandian J, Navarro JC

Asia, which holds 60% of the world\'s population, comprises some developing countries which are in economic transition. This paper reviews the epidemiology of stroke in South, East and South-East Asia. Data on the epidemiology of stroke in South, East, and South-East Asia were derived from the Global Burden of Disease study (mortality, disability-adjusted life-years [DALYs] lost because of stroke), World Health Organization (vascular risk factors in the community), and publications in PubMed (incidence, prevalence, subtypes, vascular risk factors among hospitalized stroke patients). Age- and sex-standardized mortality is the lowest in Japan, and highest in Mongolia. Community-based incidence data of only a few countries are available, with the lowest rates being observed in Malaysia, and the highest in Japan and Taiwan. The availability of prevalence data is higher than incidence data, but different study methods were used for case-finding, with different age bands. For DALYs, Japan has the lowest rates, and Mongolia the highest. For community, a high prevalence of hypertension is seen in Mongolia and Pakistan; diabetes mellitus in Papua New Guinea, Pakistan, and Mongolia; hypercholesterolemia in Japan, Singapore, and Brunei; inactivity in Malaysia; obesity in Brunei, Papua New Guinea, and Mongolia; tobacco smoking in Indonesia. Hypertension is the most frequent risk factor, followed by diabetes mellitus and smoking. Ischemic stroke occurs more frequently than hemorrhagic stroke, and subarachnoid hemorrhages are uncommon. There are variations in the stroke epidemiology between countries in South, East, and South-East Asia. Further research on stroke burden is required.



J Stroke: 30 Aug 2017; 19:286-294
Venketasubramanian N, Yoon BW, Pandian J, Navarro JC
J Stroke: 30 Aug 2017; 19:286-294 | PMID: 29037005
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Abstract

Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis.

Park JH, Ovbiagele B, Hong KS, Kwon SU
Background and purpose
Elevated blood pressure (BP) is associated with greater severity of intracranial atherosclerotic stenosis (ICAS) and increased risk of ischemic stroke. Because little is known about the relationship of maintained BP level with progression of symptomatic ICAS (sICAS), we evaluated the independent association of maintained systolic BP (SBP) with risk of sICAS progression.
Methods
We analyzed the Trial of cilOstazol in Symptomatic intracranial Stenosis 2, which evaluated 402 stroke patients with sICAS (mean age, 64.5±11.3 years; male, 52.2%). Study participants were categorized into four groups according to mean SBP level: low-normal (<120 mm Hg), normal to high-normal (120 to 139 mm Hg), high (140 to 159 mm Hg), and very-high (≥160 mm Hg). Progression of sICAS was defined as worsening in the degree of stenosis by ≥1 grade on the 7-month magnetic resonance angiography follow-up.
Results
sICAS progression was observed in 52 (12.9%) subjects. Percentages of sICAS progression by mean SBP category showed a J-shape pattern: low-normal (21.4%), normal to high-normal (10.7%), high (11.4%), and very-high (38.9%). In multivariable analysis, compared to the normal to high-normal SBP group, odds ratios (95% confidence intervals) were low-normal, 1.88 (0.62-5.67); high, 1.06 (0.47-2.37); and very-high, 8.75 (2.57-29.86). Rate of sICAS progression by 10-mm Hg strata showed a similar pattern to findings from mean SBP category (9.47; 2.58-34.73 for SBP ≥160 mm Hg).
Conclusions
Among individuals with a recent ICAS stroke, very-high SBP level during the short-term period after the index stroke was associated with significantly greater odds of sICAS progression.



J Stroke: 30 Aug 2017; 19:304-311
Park JH, Ovbiagele B, Hong KS, Kwon SU
J Stroke: 30 Aug 2017; 19:304-311 | PMID: 29037004
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Impact:
Abstract

Effects of Temperature and Pressure on Acute Stroke Incidence Assessed Using a Korean Nationwide Insurance Database.

Lim JS, Kwon HM, Kim SE, Lee J, Lee YS, Yoon BW
Background and purpose
Many studies have evaluated the association between weather and stroke, with variable conclusions. Herein we determined the relationships between daily meteorological parameters and acute stroke incidence in South Korea.
Methods
Patients with acute stroke (2,894) were identified by standard sampling of a nationwide insurance claims database from January to December 2011. We used multiple Poisson regression analyses of stroke incidence and meteorological parameters (mean temperature, diurnal temperature change, temperature differences over the preceding 24 hours, atmospheric pressure, humidity, wind speed, and physiologically equivalent temperature) to calculate the relative risk of stroke incidence associated with meteorological parameters.
Results
There were no seasonal variations in the incidences of ischemic (2,176) or hemorrhagic (718) stroke. Temperature change during the day was positively correlated with ischemic stroke in men (relative risk [RR] 1.027; 95% confidence interval [CI] 1.006-1.05) and older patients (≥65 years) (RR 1.031, 95% CI 1.011-1.052). Temperature differences over the preceding 24 hours had a negative correlation with all strokes (RR 0.968, 95% CI 0.941-0.996), especially among older women. Diurnal variation of atmospheric pressure was also significantly associated with the incidence of ischemic stroke (age<65 years, RR 1.051, 95% CI 1.011-1.092; age≥65 years, RR 0.966, 95% CI 0.936-0.997).
Conclusions
Diurnal temperature change, temperature differences over the preceding 24 hours, and diurnal variation of atmospheric pressure were associated with daily stroke incidence. These findings may enhance our understanding of the relationship between stroke and weather.



J Stroke: 30 Aug 2017; 19:295-303
Lim JS, Kwon HM, Kim SE, Lee J, Lee YS, Yoon BW
J Stroke: 30 Aug 2017; 19:295-303 | PMID: 29037003
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Impact:
Abstract

Prognostic Significance of Troponin Elevation for Long-Term Mortality after Ischemic Stroke.

Ahn SH, Lee JS, Kim YH, Kim BJ, ... Kim JS, Kwon SU
Background and purpose
Troponin, a marker of myocardial injury, frequently increases and is related with poor outcome in ischemic stroke patients. However, the long-term outcome of this elevation remains uncertain. We, therefore, investigated the prognostic significance of troponin elevation for long-term mortality, and explored factors affecting troponin elevation after ischemic stroke.
Methods
We retrospectively analyzed the medical data of stroke patients who were admitted within 24 hours of symptom onset and underwent a serum cardiac troponin I test at admission during a five-year period. Information on mortality as the outcome was obtained from the National Death Certificate system.
Results
A total of 1,692 patients were eligible for inclusion with 33 months of median follow-up. Troponin elevation that exceeded the 99th percentile (>0.04 ng/mL) of values was detected in 166 patients (9.8%). After adjusting for baseline characteristics, troponin elevation was associated with previous ischemic heart disease and congestive heart failure, comorbid atrial fibrillation and active cancer, and increased National Institutes of Health Stroke Scale score. Patients with troponin elevation had a high risk of overall death (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.40-2.40), including stroke-related (HR 1.71, 95% CI 1.14-2.55), cardiac-related (HR 3.17, 95% CI 1.49-6.74), and cancer-related (HR 1.98, 95% CI 1.14-3.45) death than those without troponin elevation.
Conclusions
Troponin elevation in the acute stage of ischemic stroke was associated with long-term mortality, mainly due to increased stroke- and cancer-related death in the first year and cardiacrelated death in the later period.



J Stroke: 30 Aug 2017; 19:312-322
Ahn SH, Lee JS, Kim YH, Kim BJ, ... Kim JS, Kwon SU
J Stroke: 30 Aug 2017; 19:312-322 | PMID: 28877565
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Impact:
Abstract

Intracranial Atherosclerosis: From Microscopy to High-Resolution Magnetic Resonance Imaging.

Yang WJ, Wong KS, Chen XY

Intracranial atherosclerosis is one of the leading causes of ischemic stroke and occurs more commonly in patients of Asian, African or Hispanic origin than in Caucasians. Although the histopathology of intracranial atherosclerotic disease resembles extracranial atherosclerosis, there are some notable differences in the onset and severity of atherosclerosis. Current understanding of intracranial atherosclerotic disease has been advanced by the high-resolution magnetic resonance imaging (HRMRI), a novel emerging imaging technique that can directly visualize the vessel wall pathology. However, the pathological validation of HRMRI signal characteristics remains a key step to depict the plaque components and vulnerability in intracranial atherosclerotic lesions. The purpose of this review is to describe the histological features of intracranial atherosclerosis and to state current evidences regarding the validation of MR vessel wall imaging with histopathology.



J Stroke: 30 Aug 2017; 19:249-260
Yang WJ, Wong KS, Chen XY
J Stroke: 30 Aug 2017; 19:249-260 | PMID: 28877564
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Impact:
Abstract

Multidisciplinary Approach to Decrease In-Hospital Delay for Stroke Thrombolysis.

Jeon SB, Ryoo SM, Lee DH, Kwon SU, ... Suh DC, Kim JS
Background and purpose
Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day.
Methods
We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016.
Results
A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation (<0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36-57 min) to 20.5 min (IQR 15.8-32.5 min; <0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5-212.5 min) to 86.5 min (IQR 67.5-102.3 min; <0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; =0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; =0.035).
Conclusions
SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.



J Stroke: 29 Apr 2017; 19:196-204
Jeon SB, Ryoo SM, Lee DH, Kwon SU, ... Suh DC, Kim JS
J Stroke: 29 Apr 2017; 19:196-204 | PMID: 28592785
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Impact:
Abstract

Nationwide \"Hospital Emergent Capability Accreditation by Level-Stroke\" Improves Stroke Treatment in Taiwan.

Cheng TJ, Peng GS, Jhao WS, Lee JT, Wang TH
Background and purpose
Recombinant tissue plasminogen activator (rtPA) is one of the proven therapies that improve the outcome of patients with acute ischemic stroke (AIS). In 2009, the Ministry of Health and Welfare, Executive Yuan, Republic of China, launched the project \"Hospital Emergent Capability Accreditation by Level-Stroke (HECAL-Stroke)\" to improve AIS treatment in Taiwan. The current study was performed to determine whether the project launched by the government was effective in promoting rtPA therapy among AIS patients.
Methods
All participating hospitals were verified and designated as \"heavy duty (HD),\" \"moderate duty (MoD),\" or \"medium duty (MeD)\" according to the stroke center criteria. Four annual indices (rates of treatment, protocol adherence, in-time treatment, and complications) were recorded from 2009 to 2014 as outcome measures. The data were analyzed using the χ test for significance.
Results
The number of certified hospitals progressively increased from 74 to 112 during the 6-year period and finally consisted of 33 HD, 9 MoD and 70 MeD hospitals in 2014. The annual intravenous rtPA treatment rate increased significantly from 3.0% in 2009 to 4.5% in 2014. The protocol adherence rates were 95.7% in the HD group, 92.4% in the MoD group and 72.8% in the MeD group. The annual in-time treatment rate significantly improved from 26.0% in 2009 to 60.1% in 2014. The overall symptomatic intracranial hemorrhagic rate after rtPA treatment was 8.6%.
Conclusions
Initiation of the HECAL-Stroke project by the government significantly improved rtPA treatment in Taiwan.



J Stroke: 29 Apr 2017; 19:205-212
Cheng TJ, Peng GS, Jhao WS, Lee JT, Wang TH
J Stroke: 29 Apr 2017; 19:205-212 | PMID: 28592784
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Impact:
Abstract

Association of Optimal Combination Drug Treatment with Obesity Status among Recent Ischemic Stroke Patients: Results of the Vitamin Intervention for Stroke Prevention (VISP) Trial.

Park JH, Lee J, Ovbiagele B
Background and purpose
One explanation for the \'obesity paradox\', where obese patients seem to have better cardiovascular outcomes than lean patients, is that obese patients display an identifiable high cardiovascular risk phenotype that may lead to receiving or seeking earlier/more aggressive treatment.
Methods
We analyzed a clinical trial dataset comprising 3643 recent (<120 days) ischemic stroke patients followed up for 2 years. Subjects were categorized as lean (body mass index [BMI], <25 kg/m, n=1,006), overweight (25-29.9 kg/m, n=1,493), or obese (≥30 kg/m, n=1,144). Subjects were classified as level 0 to III depending on the number of secondary prevention prescriptions divided by the number of potentially indicated drugs (0=none of the indicated medications and III=all indicated medications as optimal combination drug treatment [OCT]). Independent associations between each BMI category and stroke/myocardial infarction/vascular death (major vascular events [MVEs]) and all-cause death were assessed.
Results
MVEs occurred in 17.4% of lean, 16.1% of overweight, and 17.1% of obese patients; death occurred in 7.3%, 5.5%, and 5.1%, respectively. Individuals with a higher BMI status received more OCT (45.8%, 51.7%, and 55.3%, respectively; <0.001). In the lean patient group, multivariable adjusted Cox analyses, showed that compared with levels 0-I, level II and level III were linked to lower risk of MVEs (hazard ratio [HR] 0.55; 95% confidence interval [CI]: 0.32-0.95 and HR 0.48; 95% CI: 0.28-0.83, respectively) and death (0.44; 0.21-0.96 and 0.23; 0.10-0.54, respectively).
Conclusions
OCT for secondary prevention after an ischemic stroke is less frequent in lean (vs. obese) subjects, but when implemented is related to significantly better clinical outcomes.



J Stroke: 29 Apr 2017; 19:213-221
Park JH, Lee J, Ovbiagele B
J Stroke: 29 Apr 2017; 19:213-221 | PMID: 28592783
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Impact:
Abstract

Family History and Stroke Risk in China: Evidence from a Large Cohort Study.

Tian T, Jin G, Yu C, Lv J, ... Li L,
Background and purpose
Large cohort studies on relationship between family history of stroke (FHS) and stroke risk are lacking in Asians. We aimed to systematically evaluate the association of FHS with stroke risk in a cohort study of 0.5 million Chinese adults.
Methods
Information about FHS was self-reported. The median follow-up time was 7.16 years and the end-point of follow-up was incident stroke, which was entered directly into the China Kadoorie Biobank system. Multivariate analyses were performed with Cox proportional hazards model, and interaction analyses were carried using likelihood-ratio tests.
Results
Compared with participants without FHS, the hazard ratio (HR) (95% confidence interval, CI) of stroke for participants with FHS was 1.50 (1.46-1.55). The HRs increased with the number of first degree relatives with stroke (HRs=1.41, 1.98 and 2.47 for 1, 2 and ≥3 relatives, respectively,<0.001). The HRs were 1.57 (95% CI: 1.50-1.66) and 1.49 (95% CI: 1.45-1.54) for sibling history and parental history, respectively. Similar associations with offspring stroke risk were observed between paternal history (HR=1.48, 95% CI: 1.43-1.54) and maternal history (HR=1.49, 95% CI: 1.43-1.55). Moreover, significant interactions were detected between FHS and health-risk behaviors (tobacco smoking and alcohol drinking).
Conclusions
FHS is an independent risk factor for stroke in Chinese. The more first degree relatives are affected by stroke, the higher are individuals\' risk of suffering from stroke. The management of the health-risk behaviors for reducing stroke should be highlighted, especially for the individuals with FHS.



J Stroke: 29 Apr 2017; 19:188-195
Tian T, Jin G, Yu C, Lv J, ... Li L,
J Stroke: 29 Apr 2017; 19:188-195 | PMID: 28592782
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Impact:
Abstract

Thrombectomy in Acute Ischemic Stroke: Challenges to Procedural Success.

Yoo AJ, Andersson T

The overwhelming clinical benefit of intra-arterial stroke therapy owes to the major advance in revascularization brought on by the current generation of thrombectomy devices. Nevertheless, there remains a sizeable proportion of patients for whom substantial reperfusion cannot be achieved or is achieved too late. This article addresses the persistent challenges that face neurointerventionists and reviews technical refinements that may help to mitigate these obstacles to procedural success. Insights from in vitro modeling and clinical research are organized around a conceptual framework that examines the interaction between the device, the thrombus and the vessel wall.



J Stroke: 29 Apr 2017; 19:121-130
Yoo AJ, Andersson T
J Stroke: 29 Apr 2017; 19:121-130 | PMID: 28592779
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Impact:
Abstract

Diagnostic and Therapeutic Strategies for Acute Intracranial Atherosclerosis-related Occlusions.

Lee JS, Hong JM, Kim JS

Intracranial atherosclerosis-related occlusion (ICAS-O) is frequently encountered at the time of endovascular revascularization treatment (ERT), especially in Asian countries. However, because baseline angiographic findings are similar between ICAS-O and embolism-related occlusion (EMB-O), it is difficult to differentiate the etiologies before the ERT procedure. Moreover, despite successful randomized trials on ERT, results from studies examining the optimal treatment protocol in ICAS-O patients remain unclear. In this review, we describe the clinical and imaging factors that may possibly differentiate ICAS-O from EMB-O. We will also discuss some current hurdles for treating ICAS-O in the hyperacute period and suggest the optimal ERT strategy for ICAS-O patients.



J Stroke: 29 Apr 2017; 19:143-151
Lee JS, Hong JM, Kim JS
J Stroke: 29 Apr 2017; 19:143-151 | PMID: 28592778
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Impact:
Abstract

Causes and Solutions of Endovascular Treatment Failure.

Kim BM

In a meta-analysis of individual patient data from 5 randomized controlled trials, endovascular treatment (EVT) mainly using a stent retriever achieved successful recanalization in 71.1% of patients suffering from acute stroke due to anterior circulation large artery occlusion (LAO). However, EVT still failed in 28.9% of LAO cases in those 5 successful trials. Stent retriever failure may occur due to anatomical challenges (e.g., a tortuous arterial tree from the aortic arch to a target occlusion site), a large quantity of clots, tandem occlusion, clot characteristics (fresh versus organized clots), different pathomechanisms (embolic versus non-embolic occlusion), etc. Given that recanalization success is the most important factor in the neurological outcome of acute stroke patients, it is important to seek solutions for such difficult cases. In this review, the basic technique of EVT is briefly summarized and then various difficult cases with diverse conditions are discussed along with suggested solutions.



J Stroke: 29 Apr 2017; 19:131-142
Kim BM
J Stroke: 29 Apr 2017; 19:131-142 | PMID: 28592777
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Impact:
Abstract

Blood Pressure Management for Stroke Prevention and in Acute Stroke.

Hong KS

Elevated blood pressure (BP) is the leading modifiable risk factor for stroke and the benefit of BP lowering therapy on the stroke risk reduction is well established. The optimal BP target for preventing stroke and other vascular events have been controversial, but the evidences from epidemiological studies and randomized controlled trials (RCTs) support intensive BP lowering for greater vascular protection, particularly for stroke prevention. For secondary stroke prevention, the evidence of intensive BP lowering benefit is limited since only a single RCT for patients with lacunar infarctions was conducted and most data were driven by exploratory analyses. In acute intracerebral hemorrhage, immediate BP lowering targeting systolic BP<140 mm Hg is recommended by guidelines based on the results from RCTs. In contrast, in acute ischemic stroke, early BP lowering is not usually recommended because of no benefit on functional outcome and future vascular events and potential harm of stroke progression. This review aims to summarize the updated evidence for optimal BP management for primary and secondary stroke prevention and in patients with acute stroke.



J Stroke: 29 Apr 2017; 19:152-165
Hong KS
J Stroke: 29 Apr 2017; 19:152-165 | PMID: 28592775
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Impact:
Abstract

Emerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic Agents.

Khoshnam SE, Winlow W, Farbood Y, Moghaddam HF, Farzaneh M

Stroke is one of the leading causes of death and physical disability worldwide. The consequences of stroke injuries are profound and persistent, causing in considerable burden to both the individual patient and society. Current treatments for ischemic stroke injuries have proved inadequate, partly owing to an incomplete understanding of the cellular and molecular changes that occur following ischemic stroke. MicroRNAs (miRNA) are endogenously expressed RNA molecules that function to inhibit mRNA translation and have key roles in the pathophysiological processes contributing to ischemic stroke injuries. Potential therapeutic areas to compensate these pathogenic processes include promoting angiogenesis, neurogenesis and neuroprotection. Several miRNAs, and their target genes, are recognized to be involved in these recoveries and repair mechanisms. The capacity of miRNAs to simultaneously regulate several target genes underlies their unique importance in ischemic stroke therapeutics. In this Review, we focus on the role of miRNAs as potential diagnostic and prognostic biomarkers, as well as promising therapeutic agents in cerebral ischemic stroke.



J Stroke: 29 Apr 2017; 19:166-187
Khoshnam SE, Winlow W, Farbood Y, Moghaddam HF, Farzaneh M
J Stroke: 29 Apr 2017; 19:166-187 | PMID: 28480877
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Impact:
Abstract

Blood Pressure May Be Associated with Arterial Collateralization in Anterior Circulation Ischemic Stroke before Acute Reperfusion Therapy.

Jiang B, Churilov L, Kanesan L, Dowling R, ... Davis S, Yan B
Background and purpose
Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by computer tomography (CT) perfusion in acute ischemic stroke.
Methods
We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT).
Results
Two hundred and seventy patients were included. We found that increment of 10 mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in systolic BP (SBP) (=0.001), by 73.9% in diastolic BP (DBP) (<0.001) and by 68.5% in mean BP (MBP) (<0.001). For patients with rFTD not necessarily equal to 0 seconds, every 10 mm Hg increase in BP, there was a 7% decrease in expected count of seconds for rFTD in SBP (=0.002), 10% decrease for rFTD in DBP and 11% decrease for rFTD in MBP. The arterial occlusion location and OCT showed no significant interaction in the BP-rFTD relationship (>0.05).
Conclusions
In acute ischemic stroke, higher ABP is possibly associated with improved leptomeningeal collaterals as identified by decreased rFTD.



J Stroke: 29 Apr 2017; 19:222-228
Jiang B, Churilov L, Kanesan L, Dowling R, ... Davis S, Yan B
J Stroke: 29 Apr 2017; 19:222-228 | PMID: 28460496
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Impact:
Abstract

Intravenous Thrombolysis in Patients with Stroke Taking Rivaroxaban Using Drug Specific Plasma Levels: Experience with a Standard Operation Procedure in Clinical Practice.

Seiffge DJ, Traenka C, Polymeris AA, Thilemann S, ... Tsakiris DA, Engelter ST
Background and purpose
Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis (IVT) or endovascular treatment (EVT).
Methods
This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban (September 2012 to November 2016). The SOP included recommendation, consideration, and avoidance of IVT if rivaroxaban plasma levels were <20 ng/mL, 20‒100 ng/mL, and >100 ng/mL, respectively, measured with a calibrated anti-factor Xa assay. Patients with intracranial artery occlusion were recommended IVT+EVT or EVT alone if plasma levels were ≤100 ng/mL or >100 ng/mL, respectively. We evaluated the frequency of IVT/EVT, door-to-needle-time (DNT), and symptomatic intracranial or major extracranial hemorrhage.
Results
Among 114 acute stroke patients taking rivaroxaban, 68 were otherwise eligible for IVT/EVT of whom 63 had plasma levels measured (median age 81 years, median baseline National Institutes of Health Stroke Scale 6). Median rivaroxaban plasma level was 96 ng/mL (inter quartile range [IQR] 18‒259 ng/mL) and time since last intake 11 hours (IQR 4.5‒18.5 hours). Twenty-two patients (35%) received IVT/EVT (IVT n=15, IVT+EVT n=3, EVT n=4) based on SOP. Median DNT was 37 (IQR 30‒60) minutes. None of the 31 patients with plasma levels >100 ng/mL received IVT. Among 14 patients with plasma levels ≤100 ng/mL, the main reason to withhold IVT was minor stroke (n=10). No symptomatic intracranial or major extracranial bleeding occurred after treatment.
Conclusions
Determination of rivaroxaban plasma levels enabled IVT or EVT in one-third of patients taking rivaroxaban who would otherwise be ineligible for acute treatment. The absence of major bleeding in our pilot series justifies future studies of this approach.



J Stroke: 30 Dec 2016; 19:347-355
Seiffge DJ, Traenka C, Polymeris AA, Thilemann S, ... Tsakiris DA, Engelter ST
J Stroke: 30 Dec 2016; 19:347-355 | PMID: 28877563
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Impact:
Abstract

Spontaneous Intracerebral Hemorrhage: Management.

Kim JY, Bae HJ

Spontaneous non-traumatic intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. To improve the devastating course of ICH, various clinical trials for medical and surgical interventions have been conducted in the last 10 years. Recent large-scale clinical trials have reported that early intensive blood pressure reduction can be a safe and feasible strategy for ICH, and have suggested a safe target range for systolic blood pressure. While new medical therapies associated with warfarin and non-vitamin K antagonist oral anticoagulants have been developed to treat ICH, recent trials have not been able to demonstrate the overall beneficial effects of surgical intervention on mortality and functional outcomes. However, some patients with ICH may benefit from surgical management in specific clinical contexts and/or at specific times. Furthermore, clinical trials for minimally invasive surgical evacuation methods are ongoing and may provide positive evidence. Upon understanding the current guidelines for the management of ICH, clinicians can administer appropriate treatment and attempt to improve the clinical outcome of ICH. The purpose of this review is to help in the decision-making of the medical and surgical management of ICH.



J Stroke: 30 Dec 2016; 19:28-39
Kim JY, Bae HJ
J Stroke: 30 Dec 2016; 19:28-39 | PMID: 28178413
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Impact:
Abstract

Computed Tomography-Based Thrombus Imaging for the Prediction of Recanalization after Reperfusion Therapy in Stroke.

Heo JH, Kim K, Yoo J, Kim YD, Nam HS, Kim EY

The prediction of successful recanalization following thrombolytic or endovascular treatment may be helpful to determine the strategy of recanalization treatment in acute stroke. Thrombus can be detected using noncontrast computed tomography (CT) as a hyperdense artery sign or blooming artifact on a T2-weighted gradient-recalled image. The detection of thrombus using CT depends on slice thickness. Thrombus burden can be determined in terms of the length, volume, and clot burden score. The thrombus size can be quantitatively measured on thin-section CT or CT angiography/magnetic resonance angiography. The determination of thrombus size may be predictive of successful recanalization/non-recanalization after intravenous thrombolysis and endovascular treatment. However, cut-offs of thrombus size for predicting recanalization/non-recanalization are different among studies, due to different methods of measurements. Thus, a standardized method to measure the thrombus is necessary for thrombus imaging to be useful and reliable in clinical practice. Software-based measurements may provide a reliable and accurate assessment. The measurement should be easy and rapid to be more widely used in practice, which could be achieved by improvement of the user interface. In addition to prediction of recanalization, sequential measurements of thrombus volume before and after the treatment may also be useful to determine the efficacy of new thrombolytic drugs. This manuscript reviews the diagnosis of thrombus, prediction of recanalization using thrombus imaging, and practical considerations for the measurement of thrombus burden and density on CT.



J Stroke: 30 Dec 2016; 19:40-49
Heo JH, Kim K, Yoo J, Kim YD, Nam HS, Kim EY
J Stroke: 30 Dec 2016; 19:40-49 | PMID: 28178411
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Impact:
Abstract

Strategies to Extend Thrombolytic Time Window for Ischemic Stroke Treatment: An Unmet Clinical Need.

Peña ID, Borlongan C, Shen G, Davis W

To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment. We reviewed the pharmacological agents which reduced the risk of HT associated with delayed (beyond 4.5 hours post-stroke) tPA treatment in preclinical studies, which we classified into those that putatively preserve the blood-brain barrier (e.g., minocycline, cilostazol, fasudil, candesartan, and bryostatin) and/or enhance vascularization and protect the cerebrovasculature (e.g., coumarin derivate IMM-H004 and granulocyte colony-stimulating factor). Recently, other new therapeutic modalities (e.g., oxygen transporters) have been reported which improved delayed tPA-associated outcomes by acting through other mechanisms. While the above-mentioned interventions unequivocally reduced delayed tPA-induced HT in stroke models, the long-term efficacy of these drugs are not yet established. Further optimization is required to expedite their future clinical application. The findings from this review indicate the need to explore the most ideal adjunctive interventions that will not only reduce delayed tPA-induced HT, but also preserve neurovascular functions. While waiting for the next breakthrough drug in acute stroke treatment, it is equally important to allocate considerable effort to find approaches to address the limitations of the only FDA-approved stroke therapy.



J Stroke: 30 Dec 2016; 19:50-60
Peña ID, Borlongan C, Shen G, Davis W
J Stroke: 30 Dec 2016; 19:50-60 | PMID: 28178410
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Impact:
Abstract

Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update.

An SJ, Kim TJ, Yoon BW

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke and a critical disease usually leading to severe disability or death. ICH is more common in Asians, advanced age, male sex, and low- and middle-income countries. The case fatality rate of ICH is high (40% at 1 month and 54% at 1 year), and only 12% to 39% of survivors can achieve long-term functional independence. Risk factors of ICH are hypertension, current smoking, excessive alcohol consumption, hypocholesterolemia, and drugs. Old age, male sex, Asian ethnicity, chronic kidney disease, cerebral amyloid angiopathy (CAA), and cerebral microbleeds (CMBs) increase the risk of ICH. Clinical presentation varies according to the size and location of hematoma, and intraventricular extension of hemorrhage. Patients with CAA-related ICH frequently have concomitant cognitive impairment. Anticoagulation related ICH is increasing recently as the elderly population who have atrial fibrillation is increasing. As non-vitamin K antagonist oral anticoagulants (NOACs) are currently replacing warfarin, management of NOAC-associated ICH has become an emerging issue.



J Stroke: 30 Dec 2016; 19:3-10
An SJ, Kim TJ, Yoon BW
J Stroke: 30 Dec 2016; 19:3-10 | PMID: 28178408
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Impact:
Abstract

Predictive Factors for Good Outcome and Mortality After Stent-Retriever Thrombectomy in Patients With Acute Anterior Circulation Stroke.

Yoon W, Kim SK, Park MS, Baek BH, Lee YY
Background and purpose
Predictive factors associated with stent-retriever thrombectomy for patients with acute anterior circulation stroke remain to be elucidated. This study aimed to investigate clinical and procedural factors predictive of good outcome and mortality after stent-retriever thrombectomy in a large cohort of patients with acute anterior circulation stroke.
Methods
We analyzed clinical and procedural data in 335 patients with acute anterior circulation stroke treated with stent-retriever thrombectomy. A good outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The associations between clinical, imaging, and procedural factors and good outcome and mortality, respectively, were evaluated using logistic regression analysis.
Results
Using multivariate analysis, age (odds ratio [OR], 0.965; 95% confidence interval [CI], 0.944-0.986; =0.001), successful revascularization (OR, 4.658; 95% CI, 2.240-9.689; <0.001), parenchymal hemorrhage (OR, 0.150; 95% CI, 0.049-0.460; =0.001), and baseline NIHSS score (OR, 0.908; 95% CI, 0.855-0.965; =0.002) were independent predictors of good outcome. Independent predictors of mortality were age (OR, 1.043; 95% CI, 1.002-1.086; =0.041), successful revascularization (OR, 0.171; 95% CI, 0.079-0.370; <0.001), parenchymal hemorrhage (OR, 2.961; 95% CI, 1.059-8.276; =0.038), and a history of previous stroke/TIA (OR, 3.124; 95% CI, 1.340-7.281; =0.008).
Conclusions
Age, revascularization status, and parenchymal hemorrhage are independent predictors of both good outcome and mortality after stent retriever thrombectomy for acute anterior circulation stroke. In addition, NIHSS score on admission is independently associated with good outcome, whereas a history of previous stroke is independently associated with mortality.



J Stroke: 30 Dec 2016; 19:97-103
Yoon W, Kim SK, Park MS, Baek BH, Lee YY
J Stroke: 30 Dec 2016; 19:97-103 | PMID: 28178407
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