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Background: The effects of blood pressure (BP) lowering in patients treated with intravenous tissue plasminogen activator (IV tPA) before endovascular thrombectomy (EVT) are unclear., Aims: This study aims to investigate whether intensive and conventional BP management affect outcomes differently, depending on IV tPA administration before EVT., Methods: In this subgroup analysis of the Outcome in Patients Treated with Intra-Arterial Thrombectomy-Optimal Blood Pressure Control (OPTIMAL-BP; ClinicalTrials.gov Identifier: NCT04205305) trial, patients were divided into groups based on IV tPA use before EVT. Clinical outcomes of intensive (systolic BP target <140 mm Hg) or conventional BP management (systolic BP target 140-180 mm Hg) were compared among group. The primary efficacy outcome was a favorable outcome at 3 months (modified Rankin Scale score of 0-2). Primary safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 36 hours and stroke-related death within 3 months., Results: Among the 302 patients, the IV tPA group included 98 (32.5%) and the non-IV tPA group comprised 204 subjects (67.5%). In the IV tPA group, intensive BP management significantly lowered the favorable outcome rate (intensive, 27.3% vs. conventional, 51.9%; adjusted odds ratio [aOR], 0.36; 95% confidence interval [CI], 0.13-0.93; p = 0.04). In the non-IV tPA group, the risk difference rate of favorable outcome was not significantly different between intensive and conventional BP management (44.1% vs. 55.9%; aOR, 0.62; 95% CI, 0.31-1.22; p = 0.17). Notably, the proportion of malignant cerebral edema within 36 hours in the IV tPA group was significantly higher in the intensive management group (18.2%) than in the conventional management group (1.9%; aOR, 10.72; 95% CI, 1.24-92.29; p = 0.03). sICH and mortality rates were not significantly different between intensive and conventional BP management in either study groups., Conclusions: Intensive BP management worsen 3-month functional outcomes after successful EVT without reducing sICH among patients who received IV tPA before EVT, indicating that BP lowering in this population should be cautious.

Background: Intensive blood pressure (BP) management within 24 h after successful reperfusion following endovascular thrombectomy (EVT) is associated with worse functional outcomes than conventional BP management in Asian randomized controlled trials. Given the high prevalence of intracranial atherosclerotic stenosis (ICAS) in Asia, ICAS may influence these outcomes., Aims: We aimed to assess whether ICAS affects the outcomes of intensive BP management after successful EVT., Methods: We conducted a secondary analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, which enrolled participants from June 2020 to November 2022. Patients with anterior circulation large vessel occlusion (LVO) were stratified into ICAS-related and embolic LVO groups. Clinical outcomes for intensive (target systolic BP < 140 mm Hg) and conventional BP management (target systolic BP = 140-180 mm Hg) were analyzed in each group. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0 to 2 at 3 months. Safety outcomes included symptomatic intracerebral hemorrhage within 36 h and stroke-related death within 3 months., Results: Among 192 patients, 59 were in the ICAS-related LVO group, and 133 were in the embolic LVO group. In the ICAS-related LVO group, the rate of achieving a favorable outcome at 3 months was 37.5% with intensive BP management and 55.6% with conventional management (adjusted odds ratio (OR) = 0.49 (95% confidence interval (CI) = 0.14 to 1.75); P  = 0.27). In the embolic LVO group, these rates were 29.9% and 42.4%, respectively (adjusted OR = 0.64 (95% CI = 0.28 to 1.45); P  = 0.29). No significant interaction was found ( P for interaction = 0.68). In addition, the ICAS-related LVO group receiving intensive BP management had lower rates of successful reperfusion at 24 h compared to conventional management (67.7% vs. 91.7%; P  = 0.03), while no significant difference was found in the embolic LVO group. A significant interaction effect on successful reperfusion at 24 h was observed between ICAS-related and embolic LVO groups ( P for interaction = 0.04). No significant differences in safety outcomes were observed between intensive BP management and conventional management within both ICAS-related LVO and embolic LVO groups., Conclusions: ICAS did not significantly affect outcomes of intensive BP management within 24 h after successful EVT. After successful reperfusion by EVT, intensive BP management should be avoided regardless of ICAS presence., Data Access Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain., Aims: This study aimed to investigate whether conventional and intensive BP managements differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups., Methods: In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target: <140 mm Hg) and conventional (systolic BP target = 140-180 mm Hg) BP managements during the 24 h after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 h and mortality within 3 months., Results: Of the 305 patients (median = 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs conventional, 54.9%, adjusted odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12-0.90, p  = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs conventional, 54.2%, adjusted OR = 0.73, 95% CI = 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups., Conclusions: Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 h resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Late hospital arrival keeps patients with stroke from receiving recanalization therapy and is associated with poor outcomes. This study used a nationwide acute stroke registry to investigate the trends and regional disparities in prehospital delay and analyze the significant factors associated with late arrivals., Methods: Patients with acute ischemic stroke or transient ischemic attack between January 2012 and December 2021 were included. The prehospital delay was identified, and its regional disparity was evaluated using the Gini coefficient for nine administrative regions. Multivariate models were used to identify factors significantly associated with prehospital delays of >4.5 h., Results: A total of 144,014 patients from 61 hospitals were included. The median prehospital delay was 460 min (interquartile range, 116-1912), and only 36.8% of patients arrived at hospitals within 4.5 h. Long prehospital delays and high regional inequality (Gini coefficient > 0.3) persisted throughout the observation period. After adjusting for confounders, age > 65 years old (adjusted odds ratio [aOR] = 1.23; 95% confidence interval [CI], 1.19-1.27), female sex (aOR = 1.09; 95% CI, 1.05-1.13), hypertension (aOR = 1.12; 95% CI, 1.08-1.16), diabetes mellitus (aOR = 1.38; 95% CI, 1.33-1.43), smoking (aOR = 1.15, 95% CI, 1.11-1.20), premorbid disability (aOR = 1.44; 95% CI, 1.37-1.52), and mild stroke severity (aOR = 1.55; 95% CI, 1.50-1.61) were found to independently predict prehospital delays of >4.5 h., Conclusion: Prehospital delays were lengthy and had not improved in Korea, and there was a high regional disparity. To overcome these inequalities, a deeper understanding of regional characteristics and further research is warranted to address the vulnerabilities identified., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment., Methods: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis., Results: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups., Conclusion: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain., Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months., Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea., Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups., Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months., Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46)., Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Background and Purpose: We have commonly observed prominent cerebral veins on susceptibility-weighted angiography (SWAN) in acute meningoencephalitis. This study aimed to investigate the clinical significance of these findings., Methods: Cerebral veins on SWAN of 98 patients with acute meningoencephalitis diagnosed from February 2016 through October 2020 were classified into three groups according to the degree of venous prominence (mild, 23; moderate, 53; and prominent, 22). Clinical variables and laboratory findings were compared between these groups. The influence of variables on the prediction of prominent cerebral veins was measured by random forest (RF) and gradient boosting machine (GBM)., Results: As cerebral veins became more prominent, cerebrospinal fluid (CSF) glucose level decreased (69.61 ± 29.05 vs. 59.72 ± 22.57 vs. 48.36 ± 20.29 mg/dL, p = .01) and CSF protein level increased (100.73 ± 82.98 vs. 104.73 ± 70.99 vs. 159.12 ± 118.15 mg/dL, p = .03). The etiology of meningoencephalitis, neurological symptoms, and increased intracranial pressure (ICP) signs differed between groups (p < .05). RF and GBM demonstrated that CSF protein level was the variable with the highest power to predict the prominent cerebral vein (mean decrease in node impurity: 4.19, relative influence: 50.66)., Conclusion: The presence of prominent cerebral veins on SWAN in acute meningoencephalitis was significantly associated with a low CSF glucose level and a high CSF protein level, as well as ICP. Thus, the visual grade of the cerebral veins on SWAN may be utilized for the management of patients with acute meningoencephalitis., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

We present a case of delayed migration of an open-cell design carotid stent, which is a rare complication following carotid artery stenting (CAS). A 65-year-old patient with carotid artery stenosis underwent CAS with an open-cell stent, initially achieving successful deployment. However, 4 months later, the stent migrated and resulted in restenosis. The patient underwent balloon angioplasty and received an additional stent, leading to improved blood flow. The rarity of stent migration, particularly in the absence of risk factors, highlights the need for clinicians to be vigilant and consider early imaging follow-up for patients at risk of this complication after CAS.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear., Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT., Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion)., Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment., Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months., Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31)., Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke., Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Background: Ischemic stroke with active cancer is thought to have a unique mechanism compared to conventional stroke etiologies. There is no gold standard guideline for secondary prevention in patients with cancer-related stroke, hence, adequate type of antithrombotic agent for treatment is controversial., Methods: Subjects who were enrolled in National Health Insurance System Customized Research data during the period between 2010 and 2015 were observed until 2019. Subject diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis was defined as cancer-related stroke patient. To solve immeasurable time bias, the drug exposure evaluation was divided into daily units, and each person-day was classified as four groups: antiplatelet, anticoagulant, both types, and unexposed to antithrombotic drugs. To investigate bleeding risk and mortality, Cox proportional hazards regression model with time-dependent covariates were used., Results: Two thousand two hundred eighty-five subjects with cancer-related stroke were followed and analyzed. A group with anticoagulation showed high estimated hazard ratios (HRs) of all bleeding events compared to a group with antiplatelet (major bleeding HR, 1.35; 95% confidence interval [CI], 1.20-1.52; p < 0.001). And the result was also similar in the combination group (major bleeding HR, 1.54; 95% CI, 1.13-2.09; p = 0.006). The combination group also showed increased mortality HR compared to antiplatelet group (HR, 1.72; 95% CI, 1.47-2.00; p < 0.001)., Conclusions: Bleeding risk increased in the anticoagulant-exposed group compared to antiplatelet-exposed group in cancer-related stroke patients. Thus, this result should be considered when selecting a secondary prevention drug., (© 2023. The Author(s).)

Although clinical studies have demonstrated that prior use of antiplatelets was associated with decreased blood viscosity (BV) in patients with acute ischemic stroke, the impact of previous anticoagulant use on blood viscosity in cardioembolic stroke with non-valvular AF (NVAF) has not yet been clearly studied. This single-center retrospective observational study aimed to determine the impact of prior antithrombotic (antiplatelet and anticoagulant) use on BV in patients with cardioembolic stroke (CES) due to NVAF. Patients with CES and NVAF were analyzed with the following inclusion criteria: (1) patients over 20 years of age admitted within five days of stroke onset; (2) ischemic stroke presumably due to an NVAF-derived embolus; (3) compatible cortical/subcortical lesion on brain computed tomography or magnetic resonance imaging; (4) hemoglobin level of 10-18 mg/dL; and (5) receiving antiplatelets within five days or anticoagulants within two days if previously medicated. From the screening of 195 patients (22% of the total stroke population during the study period) who had experienced ischemic stroke with AF, 160 were included for the final analysis. Eighty-nine patients (56%) were taking antithrombotics (antiplatelet, 57%; warfarin, 13%; NOACs, 30%) regularly. Compared to patients without previous antithrombotic use, those with previous antithrombotic use (antiplatelets, warfarin, and NOACs) were significantly associated with decreased systolic BV (SBV) and diastolic BV (DBV) ( p < 0.036). In multiple linear regression analysis, hematocrit (Hct) level and prior antithrombotic use were significantly associated with decreased SBV and DBV. Hct was positively correlated with increased SBV and DBV. In Hct-adjusted partial correlation analysis, prior uses of any antithrombotic agents were associated with decreased SBV (r < -0.270, p < 0.015) and DBV (r < -0.183, p < 0.044). In conclusion, this study showed that prior antithrombotic use (antiplatelets, VKAs, and NOACs) was associated with decreased SBV and DBV in patients presenting with acute CES secondary to NVAF. Our results indicated that previous use of NOACs may be a useful hemorheological parameter in patients with acute CES due to NVAF. Accumulation of clinical data from a large number of patients with the risk of stroke occurrence, initial stroke severity, and functional outcome is necessary to assess the usefulness of BV.

Background: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy., Methods: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR., Results: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P <0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P =0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P =0.001). These associations persisted regardless of treatment modality or various baseline characteristics., Conclusions: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3−6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290−1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041−1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.

Background Early-stage unilateral moyamoya disease (MMD) is difficult to discriminate from isolated intracranial atherosclerotic stenosis, and identification of contralateral progression may aid in the diagnosis of MMD. The RNF213 (ring finger protein 213) R4810K variant is a strong genetic susceptibility factor for MMD; however, the role of contralateral progression in unilateral MMD is unknown. Methods and Results Patients who had undergone RNF213 R4810K genotyping with suspected unilateral MMD between January 2017 and August 2021 from 2 tertiary university hospitals were retrospectively reviewed. We compared the clinical features and radiographic outcomes of patients with and without this variant. The risk factors of contralateral progression in patients with suspected unilateral MMD were evaluated. The RNF213 R4810K variant was observed in 72 of 123 patients with suspected unilateral MMD, all of which were heterozygous. The allele frequency of the R4810K variant was significantly higher in the suspected unilateral MMD group compared with the historical control group (29.3% versus 1.2%; P <0.0001). Family history of MMD was significantly more common in patients with the variant than in those without (17% versus 4%; P =0.003). Eleven of 72 patients with the variant developed contralateral progression, whereas only 1 of 51 patients without the variant developed contralateral progression during a median follow-up period of 28 months (log-rank test; P =0.03). The presence of the RNF213 R4810K variant significantly correlated with contralateral progression (adjusted odds ratio, 6.39 [95% CI, 1.11-36.63]; P =0.04). Conclusions Contralateral progression is more likely to occur in patients with suspected unilateral MMD with the RNF213 R4810K variant than in those without the variant. However, because our study used a small sample size, this finding should be carefully interpreted and requires further studies with more patients and longer follow-up periods.

Background: Whether nonsustained atrial tachycardia (NSAT) has a causative role similar to paroxysmal atrial fibrillation (AF) in ischemic stroke is unclear. We investigated the clinical and imaging features of ischemic stroke patients with NSAT to demonstrate that these patients would have a higher proportion of embolic strokes., Methods: We retrospectively reviewed ischemic stroke patients who underwent Holter monitoring and selected patients with NSAT. The clinical and imaging characteristics were compared between patients with and without NSAT, and the risk factors for embolic stroke were evaluated. Moreover, the images of the selected patients were analyzed according to the Trials of Org 10172 in Acute Stroke Treatment classification., Results: From a total of 1,051 patients who had 24-hour Holter monitoring, 681 patients were selected for the study. Among the selected patients, NSAT was detected in 243 patients. The patients with NSAT had a significantly higher proportion of imaging findings suggestive of cerebral embolism compared with patients without NSAT (27% vs. 14%, P<0.001). Moreover, the presence of NSAT was a statistically significant factor associated with imaging findings suggestive of cerebral embolism in the univariate (OR, 2.22; 95% CI, 1.51-3.27; P<0.001) and multivariate (OR, 2.26; 95% CI, 1.53-3.34; P<0.001) analyses. The patients with NSAT had a significantly older age at diagnosis, higher proportion of female sex, higher proportion of hypertension, lower proportion of smokers, higher CHA 2 DS 2 -VASc score, and higher left atrium index value compared with patients without NSAT., Conclusions: The embolic pattern of acute ischemic stroke in patients with NSAT was frequently observed and shared clinical characteristics of AF rather than those of atherosclerosis. As NSAT may be a potential source of cardiac embolism, we suggest a more intensive search for modifiable risk factors such as AF in ischemic stroke in patients with NSAT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-5245/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Patients with ischemic stroke are vulnerable to heart failure with preserved ejection fraction (HFpEF) because these conditions share common risk factors. Although evaluation of the ascending aorta, aortic arch, and proximal descending thoracic aorta is an essential step to determine the source of the causative embolism, the relationship between the degree of aortic atheroma and left ventricular (LV) diastolic function has not been extensively investigated., Methods: We analyzed the transesophageal and transthoracic echocardiography in ischemic stroke patients. Patients with previous coronary artery disease, valvular heart disease of more than moderate degree, and an LV ejection fraction of less than 50% were excluded. The relationships between the grade of the aortic atheroma, aortic stiffness indexes, and diastolic functional indexes were evaluated., Results: In 295 patients, the atheroma grade was significantly correlated with aortic stiffness index, ratio of mitral annular and inflow velocities (E/e'), left atrial volume index, and LV diastolic elastance. With further adjustment for age, hypertension, diabetes, estimated glomerular filtration rate, left atrial volume index, and LV mass index, the significance of the atheroma grade was attenuated. In the subgroup analysis, the atheroma grade was significantly and independently related to E/e' in women (β = 0.181, p = 0.032), but not in men. However, atheroma grade was not associated with poor clinical outcomes in either sex., Conclusions: Aortic atheroma grade was significantly and independently related to LV diastolic function, especially in women. This suggests that aortic atheroma is an index of arterial stiffness and a potential risk factor for HFpEF through ventricular-vascular interactions, especially in women., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Background: The CHADS 2 , CHA 2 DS 2 -VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT)., Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient., Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS 2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198-2.009, p = 0.001; CHA 2 DS 2 VASc score: OR 1.269, 95% CI 1.080-1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011-1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167-1.849, p = 0.001). The CHADS 2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS 2 score; 0.618, 95% CI 0.554-0.681)., Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

Rationale: Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain., Aim: We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment., Sample-Size Estimates: We aim to randomize 668 patients (334 per arm), 1:1., Methods and Design: We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP < 140 mm Hg) group or the conventional BP-lowering (systolic BP, 140-180 mm Hg) group., Study Outcomes: The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0-2 vs. 3-6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months., Discussion: The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP < 140 mmHg during 24 h in patients with successful recanalization after intra-arterial treatment., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Background and Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy., Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment. Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke., Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively. Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01)., Conclusions: Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment., Competing Interests: Drs. Jung-Sun Kim, Yat-yin Lam, Xavier Freixa, Apostolos Tzikas, and Jai-Wun Park are consultants for the Amplatzer Cardiac Plug and Amulet, Abbott Vascular., (Copyright © 2021. The Korean Society of Cardiology.)

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke., Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy., Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245])., Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Background and Purpose: We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion., Methods: Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization., Results: Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032)., Conclusions: The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p < 0.001). Six out of the 19 comorbidities were included for developing the reperfusion comorbidity index on the basis of the odds ratios in the multivariate logistic regression analysis. This index showed good prediction of 6-month mortality in the retrospective cohort (area under the curve [AUC], 0.747; 95% CI, 0.704-0.790) and in 333 patients in the prospective cohort (AUC, 0.784; 95% CI, 0.709-0.859). Consideration of comorbidities might be helpful for the prediction of the 6-month mortality in patients with acute ischemic stroke who receive reperfusion therapy.

Introduction: Prior use of direct oral anticoagulants has been associated with reduced stroke severity in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the impact of prothrombin time (PT) and activated partial thromboplastin time (aPTT) on stroke severity in patients who were receiving dabigatran or rivaroxaban at the time of stroke onset., Materials and Methods: We enrolled 107 patients with NVAF who developed acute ischemic stroke while on dabigatran or rivaroxaban and presented within 24 hours to nine hospitals between January 2014 and December 2018. The results of PT and aPTT assays were obtained within 24 hours of stroke onset in all patients. We analyzed PT and aPTT in relation to stroke severity and ischemic lesion volume using correlation and multivariable regression analyses., Results: Of the 107 patients included, 46 (43.0%) were on dabigatran and 61 (57.0%) were on rivaroxaban. In patients with prior dabigatran use, while aPTT was inversely correlated with admission National Institutes of Health Stroke Scale (NIHSS) score (r = -0.369, p = 0.012) and ischemic lesion volume (r = -0.480, p = 0.005), there was no correlation between PT and either of these variables. Multivariable analysis confirmed the existence of a significant independent inverse relationship between aPTT and NIHSS score at admission (B, -0.201; 95% confidence interval [CI], -0.370 to -0.032; p = 0.005) and between aPTT and ischemic lesion volume (B, -0.076; 95% CI, -0.130 to -0.023; p = 0.007). In patients with prior rivaroxaban use, neither PT nor aPTT was associated with admission NIHSS score or ischemic lesion volume in the correlation and multivariable analyses., Conclusions: In patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Atrial fibrillation (AF) is the leading cause of ischemic stroke. Preventive antithrombotic use, especially for anticoagulation, reduces the incidence of ischemic stroke in patients with AF. Using data from the nationwide multicenter stroke registry, we investigated the trends of preceding antithrombotic medication use in patients with acute ischemic stroke (AIS) with AF and its association with initial stroke severity and in-hospital outcomes., Methods: This study included 6786 patients with AIS with known AF before stroke admission across 39 hospitals between June 2008 and December 2018. We collected the data on antithrombotic medication use (no antithrombotic/antiplatelet/anticoagulant) preceding AIS. Initial stroke severity was measured using the National Institutes of Health Stroke Scale, and in-hospital outcome was determined by modified Rankin Scale score at discharge., Results: During the study period, anticoagulant use continued to increase. However, nearly one-third of patients with AIS with known AF did not receive antithrombotics before stroke. Initial National Institutes of Health Stroke Scale scores varied according to preceding antithrombotic therapy ( P <0.001). It was higher in patients who did not receive antithrombotics than in those who received antiplatelets or anticoagulants (median National Institutes of Health Stroke Scale score: 8 versus 7 and 8 versus 6, respectively). Favorable outcome at discharge (modified Rankin Scale score, 0-2) was more prevalent in patients who received antiplatelets or anticoagulants ( P <0.001). Use of antiplatelets (odds ratio, 1.23 [95% CI, 1.09-1.38]) and anticoagulants (odds ratio, 1.31 [95% CI, 1.15-1.50]) was associated with a mild initial neurological deficit (National Institutes of Health Stroke Scale score ≤5) in patients with AIS with AF., Conclusions: Throughout the study period, the proportion of patients taking anticoagulants increased among patients with AIS with known AF. However, a large portion of AF patients still did not receive antithrombotics before AIS. Furthermore, prehospitalization use of anticoagulants was associated with a significantly higher likelihood of a mild initial neurological deficit and favorable outcome at discharge.

Introduction: Clopidogrel is an antiplatelet agent that is widely used for the secondary prevention of cardiovascular and cerebrovascular events. The genotype of cytochrome P450 2C19 ( CYP2C19 ) differentially affects the liver's metabolism of clopidogrel, which may influence the drug's response and efficacy for cardiovascular event prevention. In contrast to prior studies of patients with coronary artery diseases, little is known about whether the CYP2C19 genotype influences the preventive efficacy of clopidogrel in patients who had a stroke. We hypothesise that, among patients who had an acute ischaemic stroke who are prescribed clopidogrel, the patients with a loss-of-function CYP2C19 genotype (poor and intermediate metabolisers) may be at a higher risk of composite cardiovascular events than those who are non-carriers (extensive metabolisers)., Methods and Analysis: This prospective observational multicentre study was designed to determine whether composite cardiovascular events would differ among patients who had an ischaemic stroke prescribed clopidogrel according to CYP2C19 genotype (poor or intermediate vs extensive metabolisers). Inclusion criteria were patients who had an acute ischaemic stroke who underwent CYP2C19 genotype evaluation and received clopidogrel within 72 hours of stroke onset. The primary outcome is composite cardiovascular events (stroke, myocardial infarction, or cardiovascular death) within 6 months after acute ischaemic stroke between patients categorised as poor or intermediate metabolisers and those categorised as extensive metabolisers according to their CYP2C19 genotype., Ethics and Dissemination: The Institutional Review Board of Severance Hospital, Yonsei University College of Medicine approved this study (3-2019-0195). We received study approval from the institutional review board of each participating hospital. We plan to disseminate our findings at relevant conferences and meetings and through peer-reviewed journals., Trial Registration Number: NCT04072705., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We investigated whether there was an annual change in outcomes in patients who received the thrombolytic therapy or endovascular treatment (EVT) in Korea. This analysis was performed using data from a nationwide multicenter registry for exploring the selection criteria of patients who would benefit from reperfusion therapies in Korea. We compared the annual changes in the modified Rankin scale (mRS) at discharge and after 90 days and the achievement of successful recanalization from 2012 to 2017. We also investigated the determinants of favorable functional outcomes. Among 1230 included patients, the improvement of functional outcome at discharge after reperfusion therapy was noted as the calendar year increased ( p < 0.001). The proportion of patients who were discharged to home significantly increased (from 45.6% in 2012 to 58.5% in 2017) ( p < 0.001). The successful recanalization rate increased over time from 78.6% in 2012 to 85.1% in 2017 ( p = 0.006). Time from door to initiation of reperfusion therapy decreased over the years ( p < 0.05). These secular trends of improvements were also observed in 1203 patients with available mRS data at 90 days ( p < 0.05). Functional outcome was associated with the calendar year, age, initial stroke severity, diabetes, preadmission disability, intervals from door to reperfusion therapy, and achievement of successful recanalization. This study demonstrated the secular trends of improvement in functional outcome and successful recanalization rate in patients who received reperfusion therapy in Korea.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia among adults. Despite the proven advantages in primary and secondary stroke prevention in patients with AF, oral anticoagulation (OAC) therapy is still underused in many countries. In this study, we investigated the incidence of AF-related ischemic stroke over the past decade in South Korea and trends of preventive antithrombotic therapy use before stroke in a nationwide cohort., Methods and Findings: The data source for this study was a nationwide sample cohort comprising 1,025,340 individuals that was established by the nationwide health insurance system in 2002. A total of 10,215 patients with acute ischemic stroke (AIS) were selected from the cohort between 2004 and 2013. AF was identified in 1,662 patients, and 979 patients had preexisting AF before AIS. The annual proportion of patients with AIS with AF gradually increased from 13.4% to 22.6% over the study period (p for trends <0.001). Only 14.0% of patients with high risk AF were receiving OAC before the stroke, and this proportion remained relatively constant during the study period. However, the proportion of patients treated with antiplatelet agents had increased from 18.8% in 2004 to 45.3% in 2013, while that of patients receiving no antithrombotic agent decreased from 64.6% in 2004 to 43.9% in 2013. As a limitation, no information was available about non-vitamin K antagonist oral anticoagulants, because they were widely used since late 2014 in Korea., Conclusions: The number of patients with AIS and AF has steadily increased over the last 10 years in Korea. However, a small portion of patients with AF were receiving OAC therapy before the stroke and about half of the patients did not receive any antithrombotic medication. Our study demonstrates that there is huge gap between clinical practice and treatment guidelines for patients with AF in Korea., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Discontinuation of oral anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) may induce a hypercoagulable state, leading to severe stroke and poor outcomes. This study aimed to compare stroke outcomes between NOACs withdrawal and other prior medication statuses in patients with non-valvular atrial fibrillation (NVAF). Methods: Consecutive patients who had pre-existing NVAF and were admitted for an acute ischemic stroke or transient ischemic attack- at five hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with subtherapeutic intensity, warfarin with therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groups Results: Among 719 patients with NVAF, The median NIHSS score at admission was 5 (IQR 1-13). The NOAC withdrawal group had the highest median NIHSS scores at stroke onset [16, interquartile range, IQR (1-17)], followed by the warfarin withdrawal group [11, IQR (1-14, 18)], the no antithrombotic group [5, IQR (1-13, 18, 19)], and the warfarin with subtherapeutic intensity group [5, IQR (1-10, 18, 19)]. A Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% confidence interval 0.384-8.906, P = 0.033). The median interval from drug withdrawal to ischemic stroke or TIA was 7 days (IQR 4-15) in the NOAC group. Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes.

Background:  The stroke severity or functional outcomes could differ because the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) could be different according to the dose. We investigated whether there was any difference in the stroke outcomes in patients with non-valvular atrial fibrillation (NVAF) by their prior medication status, including standard-dosed versus under-dosed NOACs., Materials and Methods:  We enrolled 858 patients with acute ischaemic stroke with chronic NVAF admitted at six hospitals in Korea. We categorized their prior medication status as follows: (1) no anti-thrombotics ( n  = 219), (2) only anti-platelet ( n  = 347), (3) warfarin with a sub-therapeutic intensity ( n  = 185), (4) warfarin with a therapeutic intensity ( n  = 37), (5) under-dosed NOAC ( n  = 27) and (6) standard-dosed NOAC ( n  = 43). We compared the initial stroke severity between groups., Results:  Among the 858 patients, the patients on standard-dosed NOACs had the lowest initial National Institute of Health Stroke Scale (NIHSS) score, followed by those on warfarin with a therapeutic intensity and those on only anti-platelet ( p  < 0.05). Multivariate analysis demonstrated that the NIHSS score was significantly low in the patients on warfarin with a therapeutic intensity ( B , -5.602; 95% confidence interval [CI], -8.636 to -2.568; p  < 0.001) or those on standard-dosed NOACs ( B , -3.588; 95% CI, -6.405 to -0.771; p  = 0.013), while there was no difference in the NIHSS score between the patients not taking any anti-thrombotics and those on warfarin with a sub-therapeutic intensity or under-dosed NOACs., Conclusion:  Use of warfarin with a therapeutic intensity or standard-dosed NOACs was associated with a relatively mild stroke in the patients with NVAF., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Magnetic resonance imaging (MRI) is a useful tool to predict the diagnosis and progression of Alzheimer's disease (AD), especially for primary physicians. However, the correlation between baseline MRI findings and AD progression has not been fully established., Objective: To investigate the correlation between hippocampal atrophy (HA) and white matter hyperintensities (WMH) on initial brain MRI images and the degree of cognitive decline and functional changes over 1 year., Methods: In this prospective, 12-month observational study, dementia outpatients were recruited from 29 centers across South Korea. Baseline assessments of HA and WMH on baseline brain MRI were derived as well as cognitive function, dementia severity, activities of daily living, and acetylcholinesterase inhibitor (AChEI) use. Follow-up assessments were conducted at 6 and 12 months., Results: Among 899 enrolled dementia patients, 748 were diagnosed with AD of whom 654 (87%) were taking AChEIs. Baseline WMH showed significant correlations with age, current alcohol consumption, and Clinical Dementia Rating score; baseline HA was correlated with age, family history, physical exercise, and the results of cognitive assessments. Among the AChEI group, changes in the Korean version of the Instrumental Activities of Daily Living (K-IADL) were correlated with the severity of HA on baseline brain MRI, but not with the baseline severity of WMH. In the no AChEI group, changes in K-IADL were correlated with the severity of WMH and HA at baseline., Conclusion: Baseline MRI findings could be a useful tool for predicting future clinical outcomes by primary physicians, especially in relation to patients' functional status.

Background: Metabolic syndrome is associated with cardiovascular diseases and is characterized by insulin resistance. Recent studies suggest that the triglyceride/high-density lipoprotein cholesterol (TG/HDLC) ratio predicts insulin resistance better than individual lipid levels, including TG, total cholesterol, low-density lipoprotein cholesterol (LDLC), or HDLC. We aimed to elucidate the relationship between the TG/HDLC ratio and metabolic syndrome in the general Korean population., Methods: We evaluated the data of adults ≥20 years old who were enrolled in the Korean National Health and Nutrition Examination Survey in 2013 and 2014. Subjects with angina pectoris, myocardial infarction, stroke, or cancer were excluded. Metabolic syndrome was defined by the harmonized definition. We examined the odds ratios (ORs) of metabolic syndrome according to TG/HDLC ratio quartiles using logistic regression analysis (SAS ver. 9.4; SAS Institute Inc., Cary, NC, USA). Weighted complex sample analysis was also conducted., Results: We found a significant association between the TG/HDLC ratio and metabolic syndrome. The cutoff value of the TG/HDLC ratio for the fourth quartile was ≥3.52. After adjustment, the OR for metabolic syndrome in the fourth quartile compared with that of the first quartile was 29.65 in men and 20.60 in women (P<0.001)., Conclusion: The TG/HDLC ratio is significantly associated with metabolic syndrome., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Background Stroke outcomes can differ by women's legal or socioeconomic status. Aim We investigated whether differences in women's rights or gender inequalities were associated with stroke mortality at the country-level. Methods We used age-standardized stroke mortality data from 2008 obtained from the World Health Organization. We compared female-to-male stroke mortality ratio and stroke mortality rates in women and men between countries according to 50 indices of women's rights from Women, Business and the Law 2016 and Gender Inequality Index from the Human Development Report by the United Nations Development Programme. We also compared stroke mortality rate and income at the country-level. Results In our study, 176 countries with data available on stroke mortality rate in 2008 and indices of women's rights were included. There were 46 (26.1%) countries where stroke mortality in women was higher than stroke mortality in men. Among them, 29 (63%) countries were located in Sub-Saharan African region. After adjusting by country income level, higher female-to-male stroke mortality ratio was associated with 14 indices of women's rights, including differences in getting a job or opening a bank account, existence of domestic violence legislation, and inequalities in ownership right to property. Moreover, there was a higher female-to-male stroke mortality ratio among countries with higher Gender Inequality Index (r = 0.397, p < 0.001). Gender Inequality Index was more likely to be associated with stroke mortality rate in women than that in men (p < 0.001). Conclusions Our study suggested that the gender inequality status is associated with women's stroke outcomes.

Background Expenditure on research and development is a macroeconomic indicator representative of national investment. International organizations use this indicator to compare international research and development activities. Aim We investigated whether differences in expenditures on research and development at the country level may influence the incidence of stroke and stroke mortality. Methods We compared stroke metrics with absolute amount of gross domestic expenditure on R&D (GERD) per-capita adjusted for purchasing power parity (aGERD) and relative amount of GERD as percent of gross domestic product (rGERD). Sources included official data from the UNESCO, the World Health Organization, the World Bank, and population-based studies. We used correlation analysis and multivariable linear regression modeling. Results Overall, data on stroke mortality rate and GERD were available from 66 countries for two periods (2002 and 2008). Age-standardized stroke mortality rate was associated with aGERD (r = -0.708 in 2002 and r = -0.730 in 2008) or rGERD (r = -0.545 in 2002 and r = -0.657 in 2008) (all p < 0.001). Multivariable analysis showed a lower aGERD and rGERD were independently and inversely associated with higher stroke mortality (all p < 0.05). The estimated prevalence of hypertension, diabetes, or obesity was higher in countries with lower aGERD. The analysis of 27 population-based studies showed consistent inverse associations between aGERD or rGERD and incident risk of stroke and 30-day case fatality. Conclusions There is higher stroke mortality among countries with lower expenditures in research and development. While this study does not prove causality, it suggests a potential area to focus efforts to improve global stroke outcomes.

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.

Stroke is one of the leading causes of death and morbidity worldwide. The occurrence of stroke is strongly dependent on well-known vascular risk factors. After rapid modernization, urbanization, and mechanization, East Asian countries have experienced growth in their aged populations, as well as changes in lifestyle and diet. This phenomenon has increased the prevalence of vascular risk factors among Asian populations, which are susceptible to developing cardiovascular risk factors. However, differing patterns of stroke risk factor profiles have been noted in East Asian countries over the past decades. Even though the prevalence of vascular risk factors has changed, hypertension is still prevalent and the burden of diabetes and hypercholesterolemia will continue to increase. Asia remains a high tobacco-consuming area. Although indicators of awareness and management of vascular risk factors have increased in many East Asian countries, their rates still remain low. Here we review the burdens of traditional risk factors, such as hypertension, diabetes, hypercholesterolemia, and smoking in East Asia. We will also discuss the different associations between these vascular risk factors and stroke in Asian and non-Asian populations., Competing Interests: The authors have no financial conflicts of interest.

Background: Although early neurological deterioration (END) during the acute stroke period is known to be directly associated with poor short- and long-term outcomes, few studies have investigated the ability to predict END. The aim of this study was to investigate whether there are differences in the occurrence of END according to the ischemic stroke predictive risk score (iScore), which was developed to predict short- and long-term mortality., Methods: We collected data from 2150 consecutive ischemic stroke patients who were admitted to 3 study hospitals between January 2012 and June 2014. END was defined as an increase (≥4) in the National Institutes of Health Stroke Scale score within the first 72 hours of stroke onset. We calculated the 30-day iScore for each patient to determine the relationship between the iScore and occurrence of END., Results: Among 2150 patients, END was observed in 146 patients (6.8%). There was a positive correlation between the iScore and occurrence of END. After adjusting for potential confounders, the iScore was independently associated with END (odds ratio: 1.217 per 20-point increase in iScore, 95% confidence interval: 1.121-1.321, P < .001). There was good correlation between observed and expected outcomes predicted by the iScore (Pearson correlation coefficient: r = .950, P < .001)., Conclusions: The iScore can predict the risk of END development within the acute stroke stage., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Purpose: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin., Materials and Methods: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases., Results: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA₂DS₂-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS₂ score or ≥3 points of other components of CHA₂DS₂-VASc score was a significant predictor for development of ischemic stroke., Conclusion: NVAF patients with high CHADS₂/CHA₂DS₂-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.

Background and Purpose: Process improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process., Methods: After determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared., Results: The median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)]., Conclusions: PI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients.

Purpose: Continuous cardiac monitoring in a stroke unit (SU) may improve detection of atrial fibrillation (AF), and SU care may improve the rate of anticoagulation by better adherence to a standardized treatment protocol in patients with AF. We investigated the effects of the SU on the detection of AF and the rate of warfarin therapy in patients with AF., Materials and Methods: Acute stroke patients who had been admitted before or after the opening of the SU were included in our study. SU patients were monitored continuously with electrocardiography. Rates of AF and warfarin therapy were compared between patients admitted to the SU (SU group) and those admitted to the general ward (GW) prior to the opening of the SU (GW group)., Results: Total 951 patients had been admitted to the GW prior to the opening of the SU (from January 2000 to November 2002), and 2349 patients to the SU (from January 2003 to December 2008). AF was found in 149 patients (15.7%) in the GW group and in 487 (20.7%) in the SU group. Most of AF detected during admission was paroxysmal AF (84.8%). The frequency of newly detected AF was higher in the SU group than the GW group (2.5% vs. 0.7%, p=0.001). The rate of anticoagulation consideration was also higher in the SU group., Conclusion: SU care improved the detection of AF and the rate of anticoagulation consideration in acute stroke patients. Our findings support the benefits of continuous cardiac monitoring in the SU for stroke patients.

Background and Purpose: The blood supply to the medulla oblongata is distinct from that of other areas of the brainstem, and thus the mechanism underlying medullary infarctions may be distinct. However, few studies have investigated this., Methods: Of 3833 stroke patients who were on the stroke registry between February 1999 and April 2008, those with medullary infarctions demonstrated on diffusion-weighted magnetic resonance imaging were enrolled. We analyzed the topography, the involved arterial territories, and the etiologic mechanisms of the lesions., Results: In total, 142 patients were enrolled in the study. Bilateral medullary infarctions were rare (2.2%). Lesions involving the anteromedial or lateral territories were common in the upper medulla oblongata, whereas lateral territorial involvements were common in the middle and lower regions of the medulla oblongata. Significant stenosis (>50%) or occlusion of the vertebral artery was common (52.2%). Among stroke subtypes, large-artery atherosclerosis was most common (34.5%), while lacunae and cardioembolism were rare (3.5% and 4.2%, respectively). Vertebral artery dissection was frequent. The stroke mechanisms differed with the involved vascular territories. Large-artery atherosclerosis produced lesions in the lateral, anteromedial, and posterior territories. None of the cardioembolisms or other etiologies involved anteromedial or anterolateral territories, but all involved the lateral and/or posterior territories. Lacunar infarction was found only in the anteromedial and anterolateral territories., Conclusions: The topography and mechanisms of infarctions involving the medulla oblongata are different with the involved arterial territories. These findings may be associated with the distinct pattern of arterial supply to the medulla oblongata.

Background: Hemorrhage is a major complication of thrombolytic treatment. Concerns have been raised about the risk of hemorrhage in patients having received warfarin. Therefore, different indications for thrombolytic treatment are in use for stroke patients on warfarin. However, it remains uncertain whether the prior warfarin use actually increases their risk of bleeding in patients treated with thrombolysis., Methods: This study included 179 consecutive patients who had high-risk cardioembolic sources and received thrombolytic treatment. Patients were treated with intravenous thrombolytic agents, or underwent intraarterial thrombolysis if their international normalized ratio (INR) was ≤1.7. We compared the frequency of bleeding complications between patients with prior warfarin use and those without. We also investigated whether there were differences in functional outcome and recanalization rates between them., Results: A prior warfarin use was present in 28 patients (15.6%). Although INR levels were higher in the prior warfarin group, the frequency of bleeding complications was not different between patients who received prior warfarin and those who did not. No differences were observed in patients with or without prior warfarin use, for successful recanalization rate (Thrombolysis in Myocardial Infarction grade 2 or 3), mortality, or modified Rankin score (≤2) at 3months., Conclusions: Thrombolytic therapy for patients who previously received warfarin and had an INR≤1.7 did not affect bleeding risk, clinical outcome, or recanalization rate. Our data suggest that patients with a history of prior warfarin use may be safely treated with thrombolytic agents when their INR levels are low., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: In patients with a middle cerebral artery (MCA) occlusion, the involvement of the cortex may be affected by the presence of leptomeningeal anastomoses between the cerebral arteries., Methods: The authors enrolled consecutive patients with acute infarctions in the MCA territory and MCA occlusion on angiographic studies. Infarct patterns were classified into three categories based on the extent of cortical surface involvement: total cortex (TC), partial cortex (PC) and no cortex (NC). The authors analysed the infarction patterns by stroke subtype, and investigated factors that resulted in cortex sparing., Results: Out of 73 total patients, cortex-sparing infarctions were seen in 53 patients (72.6%, NC in 39 (53.5%) and PC in 14 (19.1%)). The extent of cortical involvement differed according to stroke subtype (p=0.036). TC was more frequent (42.9% vs 22.2%), and PC was less frequent (10.7% vs 27.9%, p=0.037) in cardioembolism than large-artery atherosclerosis. However, the proportion of patients with complete cortical sparing (NC) was similar between cardioembolism and large-artery atherosclerosis (46.4% vs 49.9%). In the upstream of leptomeningeal collateral arteries, the extent of cortical involvement was associated with significant stenosis of the ipsilateral anterior or posterior cerebral artery (p=0.011)., Conclusion: This study suggests that pre-existing arteriolar connections, which may cover almost entire cortical surfaces of the MCA territory, exist in many patients. The findings also suggest that the extent of cortical involvement is different between stroke subtypes, and is critically affected by the status of upstream collateral arteries.

Purpose: To evaluate the long-term efficacy and tolerability of topiramate (TPM) as add-on therapy in patients with refractory partial epilepsy., Methods: This is a retrospective, single-center, long-term observational study. Patients fulfilling the criteria of medical intractability proposed by Berg et al. were entered into the study if they were newly prescribed TPM as add-on therapy between January 2000 and June 2002. The usual starting dosage of TPM was 50 mg/day and optimal-dose adjustments were made according to individual clinical responses. Efficacy and tolerability were analyzed every year during 5-year follow-up in the "intention-to-treat (ITT) population." Retention rate was estimated by Kaplan-Meyer analysis., Results: A total of 125 patients were included in the study and 107 patients (85.6%) were followed for 5 years. Retention rate was 87.2% at 1 year and 64% at 5 years. At the end of 5 years, the median seizure frequency reduction rate was 69.0% and responder rate was 43.2% in the ITT population. Cumulative seizure-free rate (SFR) was 30.4% and the terminal 1-year SFR was 12.8% in the ITT population (20.0% in completers) at 5-year follow-up. Adverse events (AEs) occurred in 39.2% of patients, including significant AEs leading to antiepileptic drug (AED) withdrawal in 14.4%. The most common AEs were anorexia (16.0%), weight loss (10.4%), and gastrointestinal symptoms (8.8%). Concomitant AEDs were reduced in 25.0% of the completers., Discussion: Low-dose and slow-dose escalation of TPM in add-on therapy for patients with refractory partial epilepsy is effective and well tolerated in long-term, individualized clinical practice.

Background: The prevalence of extracranial (EC) and intracranial (IC) atherosclerosis varies among races. Although several studies have sought to identify specific vascular risk factors that are associated with EC or IC atherosclerosis, the exact relationships are uncertain. This study aimed to determine if there are any specific risk factors for EC or IC atherosclerosis., Methods: For this study, we considered 3,349 consecutive patients who had been entered into a stroke registry between January 1999 and June 2007. After the exclusion of patients who had not undergone angiography, patients with cardiac sources of embolism or other causes of stroke, and non-Koreans, we had a total of 2,169 patients of single ethnicity with an angiographic analysis. Patients with atherosclerosis in both the IC and EC arteries (856 patients) were excluded. Finally, we identified 1,313 patients who had EC atherosclerosis (EC group, n = 256), IC atherosclerosis (IC group, n = 566) or normal angiographic findings (no-lesion group, n = 488). The frequency of risk factors and the demographic parameters were compared among these groups., Results: When compared to the normal group, the IC group was associated with older age and hypertension, and the EC group was associated with older age, higher initial blood sugar and low-density lipoprotein cholesterol levels. However, in a direct comparison between the IC and EC groups, we did not observe any significant risk factors or variables except for a higher frequency of males and higher total cholesterol levels in the EC group., Conclusions: Vascular risk factors may not be major determinants of location for atherosclerosis in the EC or IC arteries., (2009 S. Karger AG, Basel.)