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Abstract This study aimed to investigate the relationship between complex aortic plaque (CAP) and short-term as well as long-term outcomes following cardioembolic stroke. CAP is a known risk factor for occurrence and recurrence of ischemic stroke. However, the association of CAP on cardioembolic stroke remains unclear. This was retrospective study using prospective cohort of consecutive patients with cardioembolic stroke who underwent transesophageal echocardiography. The functional outcome was evaluated using the modified Rankin Scale score at 3 months, and long-term outcomes were assessed by recurrence of ischemic stroke and occurrence of major adverse cardiovascular events (MACE). Among 759 patients with cardioembolic stroke, 91 (12.0%) had CAP. Early ischemic stroke recurrence within 3 months was associated with CAP (p = 0.025), whereas CAP was not associated with functional outcome at 3 months (odd ratio 1.01, 95% confidence interval [CI] 0.57–1.84, p = 0.973). During a median follow-up of 3.02 years, CAP was significantly associated with ischemic stroke recurrence (hazard ratio = 2.68, 95% CI 1.48–4.88, p = 0.001) and MACE occurrence (hazard ratio = 1.61, 95% CI 1.03–2.51, p = 0.039). In conclusion, CAP was associated with early ischemic stroke recurrence and poor long-term outcomes in patients with cardioembolic stroke. It might be helpful to consider transesophageal echocardiography for patients with cardioembolic stroke to identify CAP.

Cancer can induce hypercoagulability, which may lead to stroke. This occurs when tumor cells activate platelets as part of their growth and metastasis. Tumor cells activate platelets by generating thrombin and expressing tissue factor, resulting in tumor cell-induced platelet aggregation. Histopathological studies of thrombi obtained during endovascular thrombectomy in patients with acute stroke and active cancer have shown a high proportion of platelets and thrombin. This underscores the crucial roles of platelets and thrombin in cancer-associated thrombosis. Cancer-associated stroke typically occurs in patients with active cancer and is characterized by distinctive features. These features include multiple infarctions across multiple vascular territories, markedly elevated blood D-dimer levels, and metastasis. The presence of cardiac vegetations on echocardiography is a robust indicator of cancer-associated stroke. Suspicion of cancer-associated stroke during endovascular thrombectomy arises when white thrombi are detected, particularly in patients with active cancer. Cancer-associated stroke is almost certain when histopathological examination of thrombi shows a very high platelet and a very low erythrocyte composition. Patients with cancer-associated stroke have high risks of mortality and recurrent stroke. However, limited data are available on the optimal treatment regimen for stroke prevention in these patients. Thrombosis mechanism in cancer is well understood, and distinct therapeutic targets involving thrombin and platelets have been identified. Therefore, direct thrombin inhibitors and/or antiplatelet agents may effectively prevent stroke recurrence. Additionally, this strategy has potential benefits in cancer treatment as accumulating evidence suggests that aspirin use reduces cancer progression, metastasis, and cancer-related mortality. However, clinical trials are necessary to assess the efficacy of this strategy involving the use of direct thrombin inhibitors and/or antiplatelet therapies.

Background: Protease-activated receptor 1 (PAR1) is expressed in human platelets and can be activated by low concentrations of thrombin. Vorapaxar, a selective antagonist of PAR1, inhibits thrombin-induced calcium mobilization in human platelet, which is associated with an increased risk of bleeding. Conversely, the administration of a positive allosteric modulator (PAM) of PAR1 may pose a substantial risk of thrombosis due to inducing excessive platelet activation. In this study, we discovered a novel PAM of PAR1 and investigated the effect of enhanced PAR1 activation by PAM of PAR1 on platelet activation.Methods: To find PAMs of PAR1, a cell-based screen was performed in HT29 cells, and finally, gestodene, an oral contraceptive drug (OC), was identified as a novel PAM of PAR1. The mechanism of action of gestodene and its effects on platelet activation were investigated in human megakaryocytic leukemia cell line MEG-01 cells and human platelet.Results: Gestodene enhanced both thrombin- and PAR1-activating peptide (AP)-induced intracellular calcium levels in a dose-dependent manner without altering PAR2 and PAR4 activity. Gestodene significantly increased PAR1-AP-induced internalization of PAR1 and phosphorylation of ERK1/2, and the enhancing effects were significantly blocked by vorapaxar. Furthermore, gestodene potently increased PAR1-AP induced morphological changes in MEG-01 cells. Remarkably, in human blood, gestodene exerted a robust augmentation of PAR1-AP-induced platelet aggregation, and vorapaxar effectively attenuated the gestodene-induced enhancement of platelet aggregation mediated by PAR1.Conclusion: Gestodene is a selective PAM of PAR1 and suggest one possible mechanism for the increased risk of venous thromboembolism associated with OCs containing gestodene.

Abstract This study aimed to investigate the association between muscle mass deficit and the initial severity of ischemic stroke. The impact of muscle mass deficit on the discharge outcome was also evaluated. This retrospective study included 660 patients with acute ischemic stroke who underwent bioelectrical impedance analyses. We compared the National Institute of Health Stroke Scale (NIHSS) score, occurrence of moderate stroke (NIHSSS ≥ 5) at admission, and unfavorable functional outcome (modified Rankin Scale score ≥ 2) at discharge between patients with and without muscle mass deficit using Poisson and logistic regression analyses. The mean age of the study patients was 65.6 ± 13.0, and 63.3% were males. Muscle mass deficit was present in 24.4% of patients. Muscle mass deficit was significantly and independently associated with NIHSS score or moderate stroke (all p

Abstract Clot perviousness on computerized tomography (CT) is predictive of response to reperfusion therapy. This study aimed to determine the association of clot perviousness with ultrastructural features of clot in stroke patients undergoing endovascular thrombectomy. We quantitatively analyzed the ultrastructural components identified using scanning electron microscopy. The clot components were determined in the inner portions of the clots. Clot perviousness was assessed as thrombus attenuation increase (TAI) using noncontrast CT and CT angiography. We compared the association between the identified ultrastructural components and clot perviousness. The proportion of pores consisted of 3.5% on scanning electron microscopy images. The proportion of porosity in the inner portion was 2.5%. Among the ultrastructural components, polyhedrocytes were most commonly observed. The mean TAI was 9.3 ± 10.0 (median 5.6, interquartile range 1.1–14.3) Hounsfield units. TAI correlated positively with inner porosity (r = 0.422, p = 0.020). Among the ultrastructural clot components, TAI was independently associated with polyhedrocytes (B = − 0.134, SE = 0.051, p = 0.008). Clot perviousness is associated with porosity and the proportion of polyhdrocytes of clots.

Background d‐Dimer level is a marker of hypercoagulability, which is associated with thrombus formation and resolution. We investigated the value of d‐dimer levels in predicting outcomes of acute ischemic stroke in patients who underwent endovascular treatment (EVT). Methods We analyzed data of patients who underwent only EVT from the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) registry. d‐Dimer levels were routinely measured in 10 of 15 participating hospitals. Patients were grouped into tertiles (tertile 1, tertile 2, and tertile 3) according to d‐dimer levels (lowest, moderate, and highest, respectively). We compared serial scores on the National Institutes of Health Stroke Scale at baseline, on day 1 of hospitalization, and at discharge; functional outcome 3 months after EVT; and rate of mortality within 6 months after EVT. Results In the 170 patients, the median d‐dimer level was 477 ng/mL (interquartile range, 249–988 ng/mL). In tertile 3, the National Institutes of Health Stroke Scale score was higher at discharge than on day 1 of hospitalization. Poor outcome 3 months after EVT (modified Rankin Scale score, ≥3) was more common with high d‐dimer levels (26.3% of tertile 1, 57.1% of tertile 2, and 76.4% of tertile 3; P

Clinical benefit can be time-dependent even after first-pass recanalization (FPR) in endovascular treatment of acute stroke. This study aimed to evaluate the association between favorable outcome and FPR under a specific time frame. Patients who underwent mechanical thrombectomy were retrospectively reviewed. Recanalization status was categorized into four groups based on FPR and dichotomized time from groin puncture to recanalization (P-to-R time). Favorable outcomes were compared between groups. A total of 458 patients were included. As the cutoff of P-to-R time for favorable outcome was 30 min, recanalization status was categorized into FPR (+) with a P-to-R time ≤ 30 min (Group 1), FPR (–) with a P-to-R time ≤ 30 min (Group 2), FPR (+) with a P-to-R time > 30 min (Group 3), and FPR (–) with a P-to-R time > 30 min (Group 4). Favorable outcomes in Group 3 (37.5%) were significantly less frequent than those in Group 1 (60.4%, p = 0.029) and Group 2 (59.5%, p = 0.033) but were not significantly different from those in Group 4 (35.7%, p = 0.903). Compared to Group 1, Group 3 (adjusted odds ratio, 0.30 [95% confidence interval, 0.12–0.76]; p = 0.011) and Group 4 (0.25 [0.14–0.48]; p < 0.001) were adversely associated with favorable outcomes. FPR was associated with functional outcome in a time-dependent manner. Even for patients who have achieved FPR, their functional outcome might not be favorable if the P-to-R time is >30 min.

Antithrombotic therapy is a cornerstone of acute ischemic stroke (AIS) management and secondary stroke prevention. Since the first version of the Korean Clinical Practice Guideline (CPG) for stroke was issued in 2009, significant progress has been made in antithrombotic therapy for patients with AIS, including dual antiplatelet therapy in acute minor ischemic stroke or high-risk transient ischemic stroke and early oral anticoagulation in AIS with atrial fibrillation. The evidence is widely accepted by stroke experts and has changed clinical practice. Accordingly, the CPG Committee of the Korean Stroke Society (KSS) decided to update the Korean Stroke CPG for antithrombotic therapy for AIS. The writing members of the CPG committee of the KSS reviewed recent evidence, including clinical trials and relevant literature, and revised recommendations. A total of 35 experts were invited from the KSS to reach a consensus on the revised recommendations. The current guideline update aims to assist healthcare providers in making well-informed decisions and improving the quality of acute stroke care. However, the ultimate treatment decision should be made using a holistic approach, considering the specific medical conditions of individual patients.

We aimed to evaluate the association between preprocedural D-dimer levels and endovascular and clinical outcomes. We retrospectively reviewed patients with acute intracranial large-vessel occlusion who underwent mechanical thrombectomy. Plasma D-dimer levels were measured immediately before the endovascular procedure. Endovascular outcomes included successful recanalization, first-pass recanalization (first-pass effect (FPE) and modified FPE (mFPE)), thrombus fragmentation, and the number of passes of the thrombectomy device. Clinical outcomes were assessed at 3 months using the modified Rankin Scale. A total of 215 patients were included. Preprocedural D-dimer levels were lower in patients with FPE (606.0 ng/mL [interquartile range, 268.0–1062.0]) than in those without (879.0 ng/mL [437.0–2748.0]; p = 0.002). Preprocedural D-dimer level was the only factor affecting FPE (odds ratio, 0.92 [95% confidence interval, 0.85–0.98] per 500 ng/mL; p = 0.022). D-dimer levels did not differ significantly based on successful recanalization and thrombus fragmentation. The number of passes of the thrombectomy device was higher (p = 0.002 for trend) and the puncture-to-recanalization time was longer (p = 0.044 for trend) as the D-dimer levels increased. Patients with favorable outcome had significantly lower D-dimer levels (495.0 ng/mL [290.0–856.0]) than those without (1189.0 ng/mL [526.0–3208.0]; p < 0.001). Preprocedural D-dimer level was an independent factor for favorable outcome (adjusted odds ratio, 0.88 [0.81–0.97] per 500 ng/mL; p = 0.008). In conclusion, higher preprocedural D-dimer levels were significantly associated with poor endovascular and unfavorable functional outcomes.

Background and objectiveInflammation is an important factor in the development of aneurysm, and has been identified as a key characteristic predictive of rupture of intracranial aneurysm (IA). However, the role of inflammatory peripheral blood cell ratios in patients with IA has not been well delineated.MethodsA total of 1,209 patients, including 1,001 with unruptured IA and 208 with ruptured IA, were enrolled in this study. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white-blood-cell ratio (PWR) were compared between ruptured and unruptured IA.ResultsCompared with the ruptured IA group, the unruptured IA group had higher PNR {median, 65.96 [interquartile range (IQR) 48.95–85.05] vs. 37.78 (IQR, 23.17–54.05); p < 0.001} and PWR [median, 36.89 (IQR 29.38–44.56) vs. 22.39 (IQR, 16.72–29.29); p < 0.001]. In multivariate analysis, PNR and PWR were independently associated with ruptured IA (p = 0.001 and p < 0.001, respectively). Unruptured IA subgroup analyses according to the PHASES scores showed that a higher PHASES score was associated with significantly higher NLR and erythrocyte sedimentation rate (p < 0.001 and p = 0.025) and lower PNR and PWR (p < 0.001 and p = 0.007).ConclusionsWe demonstrated that lower PNR and PWR levels are associated with ruptured IA and a higher PHASES score. Unlike many other inflammatory markers and bioassays, peripheral blood cell ratios are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with cerebral aneurysm. However, a long-term prospective study is needed to clarify this matter.

Background and Purpose Long-term changes in post-stroke depression (PSD), post-stroke emotional incontinence (PSEI), and post-stroke anger (PSA) have rarely been studied. Methods This is a sub-study of EMOTION, a randomized, placebo-controlled trial, that examined the efficacy of escitalopram on PSD, PSEI, and PSA in patients with stroke. We interviewed patients at the long-term period (LTP) using predefined questionnaires: Montgomery-Åsberg depression rating scale (MADRS) for PSD, modified Kim’s criteria for PSEI, and Spielberger trait anger scale for PSA. Additionally, the ENRICHD Social Support Instrument (ESSI) for the social support state and the modified Rankin Scale (mRS) were measured. We investigated the changes in and factors behind PSD, PSEI, and PSA at LTP. Results A total of 222 patients were included, and the median follow-up duration was 59.5 months (interquartile range, 50 to 70). Compared to the data at 6 months post-stroke, the prevalence of PSEI (11.7% at 6 months, 6.3% at LTP; P=0.05) and mean anger score (21.62, 16.24; P

BackgroundAlthough many electrocardiography wearable devices have been released recently for the detection of atrial fibrillation (AF), there are few studies reporting prospective data for wearable devices compared to the strategy of the existing guidelines in the detection of atrial fibrillation (AF) after cryptogenic stroke. A tiny single-patch monitor is more convenient than a conventional Holter monitor recording device and, therefore, longer duration of monitoring may be acceptable.Methods and DesignThe CANDLE-AF study is a multicenter, prospective, randomized controlled trial. Patients with transient ischemic attack or ischemic stroke without any history of AF will be enrolled. The superiority of the 72-h single-patch monitor to standard strategy and non-inferiority of the 72-h single-patch monitor to an event-recorder-type device will be investigated. Single-patch monitor arm will repeat monitoring at 1, 3, 6, and 12 months, event-recorder-type arm will repeat monitoring twice daily for 12 months. The enrollment goal is a total of 600 patients, and the primary outcome is the detection of AF which continues at least 30 s during study period. The secondary outcome is the rate of changes from antiplatelet to anticoagulant and major adverse cardiac and cerebrovascular events within 1 year.ConclusionsThe results of CANDLE-AF will clarify the role of a single-lead patch ECG for the early detection of AF in patients with acute ischemic stroke. In addition, the secondary outcome will be analyzed to determine whether more sensitive AF detection can affect the prognosis and if further device development is meaningful. (cris.nih.go.kr KCT0005592).

Abstract 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

Abstract Background Sex hormones may be associated with a higher incidence of ischemic stroke or stroke-related events. In observational studies, lower testosterone concentrations are associated with infirmity, vascular disease, and adverse cardiovascular risk factors. Currently, female sexual hormones are considered neuroprotective agents. The purpose of this study was to assess the role of sex hormones and the ratio of estradiol/testosterone (E/T) in patients with acute ischemic stroke (AIS). Methods Between January 2011 and December 2016, 146 male patients with AIS and 152 age- and sex-matched control subjects were included in this study. Sex hormones, including estradiol, progesterone, and testosterone, were evaluated in the AIS patient and control groups. We analyzed the clinical and physiological levels of sex hormones and hormone ratios in these patients. Results The E/T ratio was significantly elevated among patients in the stroke group compared to those in the control group (P = 0.001). Categorization of data into tertiles revealed that patients with the highest E/T ratio were more likely to have AIS [odds ratio (OR) 3.084; 95% Confidence interval (CI): 1.616-5.886; P < 0.001) compared with those in the first tertile. The E/T ratio was also an independent unfavorable outcome predictor with an adjusted OR of 1.167 (95% CI: 1.053-1.294; P = 0.003). Conclusions These findings support the hypothesis that increased estradiol and reduced testosterone levels are associated with AIS in men.

Background The purpose of the RAFAS (Risk and Benefits of Urgent Rhythm Control of Atrial Fibrillation in Patients With Acute Stroke) trial was to explore the risks and benefits of early rhythm control in patients with newly documented atrial fibrillation (AF) during an acute ischemic stroke (IS). Method and Results An open‐label, randomized, multicenter trial design was used. If AF was diagnosed, the patients in the early rhythm control group started rhythm control within 2 months after the occurrence of an IS, unlikely the usual care. The primary end points were recurrent IS within 3 and 12 months. The secondary end points were a composite of all deaths, unplanned hospitalizations from any cause, and adverse arrhythmia events. Patients (n=300) with AF and an acute IS (63.0% men, aged 69.6±8.5 years; 51.2% with paroxysmal AF) were randomized 2:1 to early rhythm control (n=194) or usual care (n=106). A total of 273 patients excluding those lost to follow‐up (n=27) were analyzed. The IS recurrences did not differ between the groups within 3 months of the index stroke (2 [1.1%] versus 4 [4.2%]; hazard ratio [HR], 0.257 [log‐rank P=0.091]) but were significantly lower in the early rhythm control group at 12 months (3 [1.7%] versus 6 [6.3%]; HR, 0.251 [log‐rank P=0.034]). Although the rates of overall mortality, any cause of hospitalizations (25 [14.0%] versus 16 [16.8%]; HR, 0.808 [log‐rank P=0.504]), and arrhythmia‐related adverse events (5 [2.8%] versus 1 [1.1%]; HR, 2.565 [log‐rank P=0.372]) did not differ, the proportion of sustained AF was lower in the early rhythm control group than the usual care group (60 [34.1%] versus 59 [62.8%], P

BackgroundIschemic strokes (ISs) can appear even in non-gender-related CHA2DS2-VA scores 0~1 patients with atrial fibrillation (AF). We explored the determinants associated with IS development among the patients with non-gender-related CHA2DS2-VA score 0~1 AF.Methods and ResultsIn this single-center retrospective registry data for AF catheter ablation (AFCA), we included 1,353 patients with AF (24.7% female, median age 56 years, and paroxysmal AF 72.6%) who had non-gender-related CHA2DS2-VA score 0~1, normal left ventricular (LV) systolic function, and available H2FPEF score. Among those patients, 113 experienced IS despite a non-gender-related CHA2DS2-VA score of 0~1. All included patients underwent AFCA, and we evaluated the associated factors with IS in non-gender-related CHA2DS2-VA score 0~1 AF. Patients with ISs in this study had a lower estimated glomerular filtration rate (eGFR) (p < 0.001) and LV ejection fraction (LVEF; p = 0.017), larger LA diameter (p < 0.001), reduced LA appendage peak velocity (p < 0.001), and a higher baseline H2FPEF score (p = 0.018) relative to those without ISs. Age [odds ratio (OR) 1.11 (1.07–1.17), p < 0.001, Model 1] and H2FPEF score as continuous [OR 1.31 (1.03–1.67), p = 0.028, Model 2] variable were independently associated with ISs by multivariate analysis. Moreover, the eGFR was independently associated with IS at low CHA2DS2-VA scores in both Models 1 and 2. AF recurrence was significantly higher in patients with IS (log-rank p < 0.001) but not in those with high H2FPEF scores (log-rank p = 0.079), respectively.ConclusionsAmong the patients with normal LVEF and non-gender-related CHA2DS2-VA score 0~1 AF, the high H2FPEF score, and increasing age were independently associated with IS development (ClinicalTrials.gov Identifier: NCT02138695).

Background and Purpose Nonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known. Methods We included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up. Results Among the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P

Recent advances in endovascular thrombectomy have enabled the histopathologic analysis of fresh thrombi in patients with acute stroke. Histologic analysis has shown that the thrombus composition is very heterogeneous between patients. However, the distribution pattern of each thrombus component often differs between patients with cardiac thrombi and those with arterial thrombi, and the efficacy of endovascular thrombectomy is different according to the thrombus composition. Furthermore, the thrombus age is related to the efficacy of reperfusion therapy. Recent studies have shown that neutrophils and neutrophil extracellular traps contribute to thrombus formation and resistance to reperfusion therapy. Histologic features of thrombi in patients with stroke may provide some clues to stroke etiology, which is helpful for determining the strategy of stroke prevention. Research on thrombus may also be helpful for improving reperfusion therapy, including the development of new thrombolytic agents.

Background and Purpose: Successful reperfusion therapy is supposed to be comprehensive and validated beyond the grade of recanalization. This study aimed to develop a novel scoring system for defining the successful recanalization after endovascular thrombectomy.Methods: We analyzed the data of consecutive acute stroke patients who were eligible to undergo reperfusion therapy within 24 h of onset and who underwent mechanical thrombectomy using a nationwide multicenter stroke registry. A new score was produced using the predictors which were directly linked to the procedure to evaluate the performance of the thrombectomy procedure.Results: In total, 446 patients in the training population and 222 patients in the validation population were analyzed. From the potential components of the score, four items were selected: Emergency Room-to-puncture time (T), adjuvant devices used (A), procedural intracranial bleeding (B), and post-thrombectomy reperfusion status [Thrombolysis in Cerebral Infarction (TICI)]. Using these items, the TAB-TICI score was developed, which showed good performance in terms of discriminating early neurological aggravation [AUC 0.73, 95% confidence interval (CI) 0.67–0.78, P < 0.01] and favorable outcomes (AUC 0.69, 95% CI 0.64–0.75, P < 0.01) in the training population. The stability of the TAB-TICI score was confirmed by external validation and sensitivity analyses. The TAB-TICI score and its derived grade of successful recanalization were significantly associated with the volume of thrombectomy cases at each site and in each admission year.Conclusion: The TAB-TICI score is a valid and easy-to-use tool to more comprehensively define successful recanalization after endovascular thrombectomy in acute stroke patients with large vessel occlusion.

Introduction: Cardioembolic stroke (CE) has poor outcomes and high recurrence rates. A low ankle-brachial index (ABI

Background and Purpose: Intracranial atherosclerosis-related large-vessel occlusion caused by in situ thrombo-occlusion (ICAS-LVO) has been regarded an important reason for refractoriness to mechanical thrombectomy (MT). To achieve better outcomes for ICAS-LVO, different endovascular strategies should be explored. We aimed to investigate an optimal endovascular strategy for ICAS-LVO.Methods: We retrospectively reviewed three prospective registries of acute stroke underwent endovascular treatment. Among them, patients with ICAS-LVO were assigned to four groups based on their endovascular strategy: (1) MT alone, (2) rescue intracranial stenting after MT failure (MT-RS), (3) glycoprotein IIb/IIIa inhibitor infusion after MT failure (MT-GPI), and (4) a combination of MT-RS and MT-GPI (MT-RS+GPI). Baseline characteristics and outcomes were compared among the groups. To evaluate whether the endovascular strategy resulted in favorable outcome, multivariable analysis was also performed.Results: A total of 184 patients with ICAS-LVO were included. Twenty-four patients (13.0%) were treated with MT alone, 25 (13.6%) with MT-RS, 84 (45.7%) with MT-GPI, and 51 (27.7%) with MT-RS+GPI. The MT-RS+GPI group showed the highest recanalization efficiency (98.0%). Frequency of patent arteries on follow-up (98.0%, p < 0.001) and favorable outcome (84.3%, p < 0.001) were higher in the MT-RS+GPI group than other groups. The MT-RS+GPI strategy remained an independent factor for favorable outcome (odds ratio, 20.4; 95% confidence interval, 1.97–211.4; p = 0.012).Conclusion: Endovascular strategy was significantly associated with procedural and clinical outcomes in acute stroke by ICAS-LVO. A combination of RS and GPI infusion might be an optimal rescue modality when frontline MT fails.

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.

Introduction: High resolution vessel wall MRI (VW-MRI) has enabled to characterize intracranial atherosclerosis (ICAS). We studied to identify the factors for enhancement of ICAS in VW-MRI in patients with acute ischemic stroke.Methods: Consecutive patients with acute ischemic stroke or TIA who underwent VW-MRI between January 2017 and December 2017 were included. Enhancement on VW-MRI was defined as an increase in intensity on contrast-enhanced T1-weighted sequence. We compared the clinical and the radiologic findings between patients with wall enhancement and those without wall enhancement.Results: Of the 48 patients with ICAS, 28 patients revealed enhancement on VW-MRI. Patients with enhancement were more likely to have severe stenotic lesions and higher levels of total cholesterol, triglycerides, low-density cholesterol, Apo (b), and Apo (b)/Apo (a) lipoprotein ratio (p < 0.05). Multivariable analysis demonstrated that total cholesterol (OR: 5.378, 95% CI, 1.779–16.263), triglycerides (OR: 3.362, 95% CI, 1.008–11.209), low density lipoprotein cholesterol (OR: 4.226, 95% CI, 1.264–14.126), Apo (b) lipoprotein (OR: 3639.641, 95% CI, 17.854–741954.943) levels, and Apo (b)/Apo (a) lipoprotein ratio (OR, 65.514; 95% CI, 1.131–3680.239) were independently associated with enhancement of ICAS. High-density lipoprotein cholesterol and Apo (a) lipoprotein levels were not significantly different between the patients with wall enhancement and those without wall enhancement.Conclusions: The presence and severity of enhancement of ICAS was significantly associated with dyslipidemic conditions. These results suggest that strict lipid modification should be achieved for the management of ICAS.

Purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). However, it remains unclear which stroke patients should undergo evaluation for asymptomatic CAD, and which screening tools are appropriate. We investigated the role of coronary artery calcium (CAC) score as a screening tool for asymptomatic but severe CAD in acute stroke patients. We determined the selection criteria for CAC screening based on risk factors and cerebral atherosclerosis.Materials and Methods: The present study included consecutive patients with acute stroke who had undergone cerebral angiography and multi-detector computed tomography coronary angiography. Severe CAD was defined as left main artery disease or three-vessel disease. Enrolled patients were randomly assigned to two sets; a set for developing selection criteria and a set for validation. To develop selection criteria, we identified associated factors with severe CAD regarding clinical factors and cerebral atherosclerosis. CAD predictability of selection criteria with the CAC score was calculated.Results: Overall, 2,658 patients were included. Severe CAD was present in 360 patients (13.5%). CAC score was associated with CAD severity (P < 0.001). In the development set (N = 1,860), severe CAD was associated with age >65 years [odds ratio (95% confidence interval), 2.62 (1.93–3.55)], male sex (1.81 [1.33–2.46]), dyslipidemia (1.77 [1.25–2.61]), peripheral artery disease (2.64 [1.37–5.06]) and stenosis in the cervicocephalic branches, including the internal carotid (2.79 [2.06–3.78]) and vertebrobasilar arteries (2.08 [1.57–2.76]). We determined the combination of clinical and arterial factors as the selection criteria for CAC evaluation. The cut-off criterion was two or more elements of the selection criteria. The area under the curve (AUC) of the selection criteria was 0.701. The AUC significantly improved to 0.836 when the CAC score was added (P < 0.001). In the validation set (N = 798), the AUC of the selection criteria only was 0.661, and that of the CAC score was 0.833. The AUC of the selection criteria + CAC score significantly improved to 0.861(P < 0.001).Conclusion: The necessity for CAC evaluation could be determined based on the presence of risk factors and significant stenosis of the cervicocephalic arteries. CAC evaluation may be useful for screening for severe CAD in stroke patients.

Background Stent‐retriever thrombectomy is the first‐line therapy in acute stroke with intracranial large vessel occlusion. In case of failure of stent‐retriever thrombectomy, rescue stent angioplasty might be the only treatment option to achieve permanent recanalization. This study aims at identifying predictors for poor outcome and complications in a large, multicenter cohort receiving rescue stent angioplasty. Methods and Results We performed a retrospective analysis of patients with large vessel occlusion who were treated with rescue stent angioplasty after stent‐retriever thrombectomy between 2012 and 2018 in 7 neurovascular centers. We defined 2 binary outcomes: (1) functional clinical outcome (good modified Rankin Scale, 0–2; and poor modified Rankin Scale, 4–6) and (2) early symptomatic intracerebral hemorrhage. Impacts of clinical, radiological, and interventional parameters on outcomewere assessed in uni‐ and multivariable logistic regression models. Two hundred ten patients were included with target vessels located within the anterior circulation (136 of 210; 64.8%) and posterior circulation (74 of 210; 35.2%). Symptomatic intracerebral hemorrhage occured in 22 patients, 86.4% (19 of 22) after anterior and 13.6% (3 of 22) after posterior circulation large vessel occlusion. Good functional outcome was observed in 44.8% (73 of 163). A higher National Institutes of Health Stroke Scale on admission (adjusted odds ratio, 1.10; P=0.002), a higher premorbid modified Rankin Scale (adjusted odds ratio, 2.02; P=0.049), and a modified Thrombolysis in Cerebral Infarction score of 0 to 2a after stenting (adjusted odds ratio, 23.24; P

Background and Purpose: Recently, acute intracranial stenting (ICS) has gained more interest as a potential bailout strategy for large vessel occlusions (LVO) that are refractory to thrombectomy. However, there are currently no reports on ICS in patients with moderately severe stroke discussing the question if implementing a permanent stent is feasible and leads to improved recanalization after failed thrombectomy.Methods: We analyzed a large multicenter database of patients receiving ICS for anterior circulation LVO after failed thrombectomy. Inclusion criteria were defined as: Moderately severe stroke (National Institute Health Stroke Scale (NIHSS) ≤9 on admission), anterior circulation LVO, acute ICS after failed stent retriever MT. Primary endpoint was the rate of improved successful recanalization after ICS defined as a modified Thrombolysis In cerebral Infarction (mTICI) score≥2b. Favorable neurological outcome was defined as an early neurological improvement (ENI) of 4 points or reaching 0 with respect to baseline NIHSS.Results: Forty-one patients met the inclusion criteria. A median of 2 retrievals were performed (IQR 1–4) prior decision-making for ICS. ICS led in 90.2% (37/41) of cases to a final mTICI≥2b with significant improvement (p < 0.001) after the last retrieval attempt. The median NIHSS decreased (p = 0.178) from 7 (IQR 3.5–8) on admission to 2.5 (IQR 0–8.25) at discharge. ENI was observed in 47.4% (18/38). sICH occurred in 4.8% (2/41).Conclusion: ICS after failed thrombectomy appears to effectively improve recanalization rates in patients with moderately severe strokes. Thus, ICS should be considered also for patients with baseline NIHSS ≤9 if thrombectomy fails.

IntroductionPrior 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 methodsWe 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.ResultsOf 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.ConclusionsIn patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity.

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 a post hoc analysis 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 (p for interaction=0.058). Several risk factors differentially affected PSD development based on the presence of baseline depression (p for interaction

In ischemic brain tissue, hypoperfusion severity can be assessed using the hypoperfusion intensity ratio (HIR). We evaluated the link between HIR and clinical outcomes after successful recanalization by endovascular treatment. We retrospectively reviewed 162 consecutive patients who underwent endovascular treatment for intracranial large vessel occlusion. The HIR was calculated using an automated software program, with initial computed tomography perfusion images. The HIR was compared between patients with and without favorable outcomes. To observe the modifying effect of the HIR on the well-known major outcome determinants, regression analyses were performed in the low and high HIR groups. The median HIR value was significantly lower in patients with a favorable outcome, with an optimal cut-off point of 0.54. The HIR was an independent factor for a favorable outcome in a specific multivariable model and was significantly correlated with the Alberta Stroke Program Early Computed Tomography Score (ASPECTS). In contrast to the high HIR group, the low HIR group showed that ASPECTS and onset-to-recanalization time were not independently associated with a favorable outcome. Finally, the low HIR group had a more favorable outcome even in cases with an unfavorable ASPECTS and onset-to-recanalization time. The HIR could be useful in predicting outcomes after successful recanalization.

Abstract Background Accurate evaluation of diplopia during bedside physical examination is challenging. We developed a new computerized red glass test (CRT) to detect, localize, and quantify diplopia and investigated whether the CRT is useful and feasible. Methods During the CRT, a white dot randomly appears on a monitor. Because a red glass is applied on the right eye, a patient can see one white dot and one red dot when diplopia is present. We defined the degree of diplopia as the direct distance of the two points with the largest deviation and compared the degree with the Hess score and Hess area ratio. Results We prospectively enrolled 14 patients with binocular diplopia. Test–retest reliability of the CRT was excellent (overall intraclass correlation coefficient = 0.948, 95% CI 0.939–0.956). The degree of diplopia in the CRT was well correlated with both the Hess score (r = 0.719, p = 0.005) and the Hess area ratio (r = −0.620, p = 0.018). Conclusions The CRT can easily detect the presence of diplopia and provided the quantitative values of the degree of diplopia. The CRT was useful and feasible for improving routine bedside examination.

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.

Study Objectives: Coronary artery disease is considered to be the major cause of death amongst patients with ischemic stroke. The coronary artery calcium (CAC) score is related not only to sleep-disordered breathing, but also with future risk of cardiovascular mortality. We investigated the association between the severity of sleep-disordered breathing and CAC score in patients with ischemic stroke.Methods: We included 32 patients who underwent coronary multichannel computed tomography and polysomnography (within 2 years of the stroke event) amongst the patients admitted to our clinic due to acute ischemic stroke. We investigated vascular risk factors, polysomnography findings, and sleep questionnaire scores, and their relationships with the CAC score.Results: All patients were found to have sleep apnea of any degree, and 23 (72%) had severe sleep apnea. Twenty-three (72%) patients had a positive CAC score. Higher CAC scores were associated with elevated respiratory disturbance index (RDI), apnea index, oxygen desaturation index, and STOP-BANG test scores. Multivariate analysis after adjusting for potential confounding factors revealed independent relationships between the CAC score and the RDI (ß [SE] = 5.3 [2.1], p = 0.01), oxygen desaturation index (ß [SE] = 6.8 [2.8], p = 0.02), and STOP-BANG test score (ß [SE] = 90.3 [37.7], p = 0.02).Conclusion: Our findings indicate a relationship between coronary atherosclerotic burden measured by the CAC score and the severity of sleep apnea. Performing polysomnography could be useful for investigating the severity of hidden coronary artery disease among these patients.Brief SummaryCurrent Knowledge/Study Rationale: The effect of sleep apnea on coronary artery disease in patients with ischemic stroke has not been explored. We investigated the relationship between sleep apnea, its related characteristics and the coronary artery calcium score in patients with stroke.Study Impact: Our findings reveal a close relationship between the atherosclerosis-related burden measured by the coronary artery calcium score and the severity of sleep apnea that persisted after adjusting for confounding variables related to the risk of coronary artery disease. Proper detection and treatment of sleep apnea might mitigate the risk of future coronary events in patients with ischemic stroke.

Background: Overweight contributes to type 2 diabetes mellitus (T2DM) development. Although the obesity paradox has been suggested in many vascular diseases, little information is available about stroke patients with T2DM. We investigated whether body mass index (BMI) has a differential impact on the incidence of major adverse cardiovascular events (MACE) in patients with ischemic stroke and T2DM.Methods: This retrospective study used a prospective cohort of patients with acute ischemic stroke and included consecutive patients with T2DM after excluding those with active cancer or who died within 1 month of an index stroke. We investigated the long-term risk of MACE (stroke, myocardial infarction, unstable angina, coronary revascularization procedure, and death) according to BMI.Results: Among the 1,338 patients, MACE occurred in 415 patients (31.1%) during a median follow-up of 3.6 years. Compared to the normal weight group, MACE occurred more frequently in the underweight group [adjusted hazard ratio (HR) 1.55, 95% confidence interval (CI): 1.01–2.38], but less frequently in the overweight group (adjusted HR: 0.87, 95% CI: 0.70–1.08) and obese group (adjusted HR: 0.58, 95% CI: 0.41–0.86) group. In analyses of association between BMI and each component of MACE, stroke and cardiovascular mortality indicated an L- and a U-shaped pattern, respectively. However, fatal or non-fatal stroke showed an inverse pattern, and fatal or non-fatal cardiovascular events showed a reversed J-shaped pattern.Discussions: This study showed the overall presence of the obesity paradox in stroke patients with T2DM. However, obese patients had different risks of cardiovascular events and stroke.

Background: There is very limited information on the relationship between non-alcoholic fatty liver disease (NAFLD) and the severity or functional outcomes of ischemic stroke or transient ischemic stroke (TIA). We investigated the correlation between NAFLD and stroke outcomes.Methods: NAFLD was assessed in 321 patients with first-ever acute ischemic stroke or TIA, who underwent transient elastography from January 2014 to December 2014. The association of liver steatosis with stroke severity, assessed using the National Institute of Health Stroke Scale (NIHSS), was investigated using robust regression analysis. We also compared the functional outcome at 90 days according to the presence or burden of liver steatosis.Results: NAFLD was observed in 206 (64.2%) patients. Patients with NAFLD had less severe stroke (median NIHSS score 2 vs. 3, P = 0.012) and more favorable functional outcome at 90 days (85.3 vs. 70.5, P = 0.004). Patients with NAFLD were likely to have a 23.3% lower [95% confidence interval (CI), −39.2 to −3.2%, P = 0.026] NIHSS score and a 2.5-fold higher (95% CI, 1.08–5.67, P = 0.033) possibility of favorable functional outcome in multivariate analysis.Conclusions: Our study shows that a higher burden of liver steatosis seems to be associated with less severe stroke and better functional outcome after ischemic stroke or TIA.

Background and Purpose: Endovascular treatment (EVT) for acute vertebrobasilar intracranial atherosclerosis-related large vessel occlusion (ICAS-LVO) and its outcomes are not well known. We aimed to evaluate endovascular and clinical outcomes of vertebrobasilar ICAS-LVO patients who underwent EVT.Methods: Consecutive acute stroke patients who underwent EVT for vertebrobasilar LVO were retrospectively reviewed. Patients were assigned to the ICAS (+) or the ICAS (–) group based on angiographical findings. Procedural details and clinical outcomes were compared between the ICAS (+) and ICAS (–) groups.Results: This study included 77 patients with acute vertebrobasilar LVO who underwent EVT. Among the study subjects, 24 (31.2%) had an ICAS-LVO. Recanalization was achieved in 19 patients in the ICAS (+) group (79.2%), which was comparable with the ICAS (–) group (84.9%; p = 0.529). However, recanalization using conventional endovascular modalities (stent retriever thrombectomy, contact aspiration thrombectomy, or intra-arterial urokinase infusion) was less successful in the ICAS (+) group (36.8%) than the ICAS (–) group (100.0%; p < 0.001). All the remaining patients in the ICAS (+) group required specific rescue treatments appropriate for ICAS, including balloon angioplasty, stenting, or intra-arterial glycoprotein IIb/IIIa inhibitor infusion to obtain a successful recanalization. Procedural time was not significantly longer in the ICAS (+) group. The rates of favorable outcomes (37.5% vs. 41.5%; p = 0.740), death, and symptomatic intracerebral hemorrhage were not significantly different between the groups.Conclusion: ICAS-LVO was common in patients who underwent EVT for acute vertebrobasilar LVO. Although conventional modalities were often ineffective for vertebrobasilar ICAS-LVO, a comparable recanalization rate could be obtained with ICAS-specific modalities. Recanalization rate and procedural time were comparable, and clinical outcomes did not differ between patients with or without ICAS-LVO.

BackgroundEtiology is unknown in approximately one-quarter of stroke patients after evaluation, which is termed cryptogenic stroke (CS). The prognosis of CS patients is largely undetermined. We created a novel index from transcranial Doppler parameters including mean flow velocity (MV) and pulsatility index (PI) and investigated whether the calculation of asymmetry in the novel parameter can predict functional outcomes in CS patients.MethodsWe made the middle cerebral artery (MCA) index (%) as a novel parameter, which was calculated as 100 X (MCA MV + MCA PI X 10) / (MCA MV-MCA PI X 10). The MCA asymmetry index (%) was also calculated as 100 X (|Rt MCA index-Lt MCA index|) / (Rt MCA index + Lt MCA index) / 2. Poor functional outcomes were defined as modified Rankin Scale score (mRS) ≥3 at 3 months after stroke onset.ResultsA total of 377 CS patients were included. Among them, 52 (13.8%) patients had a poor outcome. The overall MCA asymmetry index was two-fold higher in CS patients with a poor outcome (10.26%) compared to those with a good outcome (5.41%, p = 0.002). In multivariable analysis, the overall MCA asymmetry index (OR, 1.054, 95% CI, 1.013-1.096, p = 0.009) and the cutoff value of the overall MCA asymmetry index >9 were associated with poor outcomes at 3 months (OR, 3.737, 95% CI, 1.530-9.128, p = 0.004).ConclusionWe demonstrated that the novel asymmetric MCA index can predict short-term functional outcomes in CS patients.

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 groupsResults: 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 and Purpose Cerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke. Methods We included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated. Results AA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75). Conclusions In this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients.

After recent randomized control trials (RCTs), non-vitamin K oral anticoagulants (NAOAs) are now widely being used in patients with atrial fibrillation (AF) worldwide. However, current guidelines for the use of NOACs in patients with AF are derived mostly using a Caucasian population and non-stroke patients. Relatively few Asian patients with AF and stroke are included in the recent RCTs. As a result, the optimal use of NOACs in this particular group of patients is remains to be settled. The optimal dose of NOACs and response to current dose of NOACs of Asian patients with AF and stroke may differ from those of westerners and patients without stroke. We reviewed available research on NOACs by searching PubMed and ClinicalTrials.gov published in English up to December 2015. In this review, the characteristics of Asian AF patients with prior stroke/transient ischemic attack, which might influence the efficacy and safety profiles of NOACs, are discussed. In addition, we summarize the risk factors for bleeding complications on NOACs, which are related or unrelated with the blood level of NOACs. Lastly, we provide recent data of reduced dose of NOACs from RCTs or large cohorts. The results reviewed herein call for clinical trials to test whether a reduced dose of NOACs is beneficial in Asian patients with AF and stroke. In the meantime, further researches are needed to establish the safety and efficacy of dose-adjusted NOACs considering both blood levels of NOACs and fragility of patients in Asian patients with AF and stroke.

Background and Purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

Background and Purpose We developed a novel method named Gray-matter Volume Estimate Score (GRAVES), measuring early ischemic changes on Computed Tomography (CT) semi-automatically by computer software. This study aimed to compare GRAVES and Alberta Stroke Program Early CT Score (ASPECTS) with regards to outcome prediction and inter-rater agreement. Methods This was a retrospective cohort study. Among consecutive patients with ischemic stroke in the anterior circulation who received intra-arterial therapy (IAT), those with a readable pretreatment CT were included. Two stroke neurologists independently measured both the GRAVES and ASPECTS. GRAVES was defined as the percentage of estimated hypodense lesion in the gray matter of the ipsilateral hemisphere. Spearman correlation analysis, receiver operating characteristic (ROC) comparison test, and intra-class correlation coefficient (ICC) comparison tests were performed between GRAVES and ASPECTS. Results Ninety-four subjects (age: 68.7±10.3; male: 54 [54.9%]) were enrolled. The mean GRAVES was 9.0±8.9 and the median ASPECTS was 8 (interquartile range, 6-9). Correlation between ASPECTS and GRAVES was good (Spearman’s rank correlation coefficient, 0.642; P

Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or dead without timely reperfusion. Previously, intravenous tissue plasminogen activator (IV-TPA) within 4.5 hours after stroke onset was the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy, which enables more fast and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of endovascular recanalization therapy (ERT) when added to IV-TPA. Accordingly, to update the recommendations, we assembled members of the writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. Reviewing the evidences that have been accumulated, the writing members revised recommendations, for which formal consensus was achieved by convening a panel composed of 34 experts from the participating academic societies. The current guideline provides the evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization.