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Background: The clinical benefits of faster recanalization in acute large vessel occlusion are well recognized, but the optimal procedure time remains uncertain. The aim of this study was to identify patient characteristics that necessitate puncture-to-recanalization (P-R) time within 30 min to achieve favorable outcome., Methods: We evaluated the patients from a prospective, multicenter, observational registry of acute ischemic stroke patients. The study included patients who underwent endovascular therapy for ICA or MCA M1 occlusion and achieved successful recanalization. Patients were categorized into subgroups based on pre-treatment characteristics and the frequency of favorable outcomes was compared between P-R time < 30 min and ≥ 30 min. Interaction terms were incorporated into the models to assess the correlation between each patient characteristic and P-R time., Results: A total of 1053 patients were included in the study. Univariate analysis within each subgroup revealed a significant association between P-R < 30 min and favorable outcomes in patients with DWI ASPECTS ≤6, age > 85 and NIHSS ≥16. In the multivariable analysis, NIHSS, age, time from symptom recognition to puncture, and DWI ASPECTS were significant independent predictors of favorable outcomes. Notably, only DWI ASPECTS exhibited interaction terms with P-R < 30 min. The multivariable analysis indicated that P-R < 30 min was an independent predictor for favorable outcome in DWI ASPECTS ≤6 group, whereas not in DWI ≥7., Conclusions: P-R time < 30 min is predictive of favorable outcomes; however, the effect depends on DWI ASPECTS. Target P-R time < 30 min is appropriate for patients with DWI ASPECTS ≤6., Competing Interests: Declaration of Competing Interest The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. T.U. reports consulting fees from Kaneka Medix. Dr. Y.H. reports consulting fees from Bayer Pharmaceutical and Nippon Boehringer Ingelheim. Dr. M.T. reports consulting and lecture fees from Johnson and Johnson and Stryker., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Endovascular treatment (EVT) for acute large vessel occlusion has proven to be effective in randomized controlled trials. We conducted a prospective cohort study to evaluate the real-world efficacy of EVT in a metropolitan area with a large number of comprehensive stroke centers and to compare it with the results of other registries and randomized controlled trials (RCTs)., Methods: We analyzed the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry, a prospective, multicenter observational study of patients treated by EVT and/or intravenous tissue-type plasminogen activator (tPA). Of the 2488 patients enrolled from January 2018 to June 2020, 1764 patients treated with EVT were included. The primary outcome was a good outcome, which was defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Secondary analysis included predicting a good outcome using multivariate logistic regression analysis., Results: The median age was 77 years, and the median National Institute of Health Stroke Scale (NIHSS) score was 18. Pretreatment mRS score 0-2 was 87%, and direct transport was 92%. The rate of occlusion in anterior circulation was 90.3%. Successful recanalization was observed in 88.7%. The median time from onset to recanalization was 193 min. Good outcomes at 90 days were 43.3% in anterior circulation and 41.9% in posterior circulation. Overall mortality was 12.6%. Significant predictors for a good outcome were as follows: age, male, direct transfer, NIHSS score, Alberta Stroke Program Early Computed Tomography Score, intravenous tPA, and successful recanalization., Conclusion: EVT in routine clinical use in a metropolitan area showed comparable good outcomes and lower mortality compared to previous studies, despite the high proportion of patients with older age, pretreatment mRS score of >2, posterior circulation occlusion, and higher NIHSS. Those results may have been associated with more direct transport and faster onset-to-recanalization times.

Purpose: Endovascular therapy (EVT) preceded by intravenous thrombolysis with recombinant tissue plasminogen activator (iv-rtPA) has been established as a standard treatment in patients with stroke caused by large-vessel occlusion (LVO). Primary stroke centers without EVT competence need to identify patients with residual LVO after iv-rtPA therapy and transport them to an EVT-capable facility. Carotid ultrasonography (CUS) is easily applicable at bed side and useful for detecting extra- and intracranial LVO. This study aimed to determine whether CUS findings at admission are useful to predict patients with residual LVO after iv-rtPA., Methods: Patients scheduled to undergo iv-rtPA for acute cerebral infarction were registered. Before iv-rtPA, they underwent CUS, followed by CTA or MRA evaluation within 6 h after iv-rtPA. A model that can achieve 100% sensitivity for detecting residual LVO after iv-rtPA was studied., Results: This study included 68 of 116 patients treated with iv-rtPA during the study period. National Institutes of Health Stroke Scale (NIHSS) score (cutoff value = 10) on arrival, hyperdense MCA sign on non-contrast CT, end-diastolic (ED) ratio on CUS, and eye deviation were significantly different between patients with residual LVO after iv-rtPA and those without. If any of these clinical features are positive in the screening test, residual LVO could be predicted with 100% sensitivity, 50% specificity, 64% positive predictive value, and 100% negative predictive value., Conclusion: Prediction of residual LVO with 100% sensitivity may be feasible by adding CUS to NIHSS score > 10, the presence of eye deviation, and hyperdense MCA sign., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Objectives: While the intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke patients with cancer is recommended when survival of ≥ 6 months is expected, the risk factors for death and stroke recurrence within 6 months after stroke are not well known. Thus, we aimed to identify markers for death and recurrence risks within six months from stroke onset in patients with cancer., Materials and Methods: In a retrospective cohort study, the subjects comprised acute ischemic stroke patients with cancer hospitalized at St. Marianna University hospital from 2008 through 2019. To evaluate the associations between the clinical factors within 24 h of the initial stroke and death or stroke recurrence events within 6 months from stroke onset, Logistic analysis and Cox proportional hazards regression analysis was used respectively. Next, the optimal cutoff point of markers for different mortality groups was determined using the receiver operating characteristic curve analysis and cumulative outcome rate of each group was compared using the Kaplan-Meier method., Results: Among 194 patients with cancer who developed acute stroke, 167 were ultimately selected for analysis. 47 subjects (28.14%) passed away within 6 months following stroke onset, and 20 subjects (11.98%) had stroke recurrence. High D-dimer levels, low fibrinogen levels, high Glasgow prognostic scores (GPS), and multiple vascular territory infarctions was independently associated with death, where higher death rate was significantly confirmed in the group with D-dimer levels of ≥3.95 mg/dl, fibrinogen levels <277.5 mg/dl and GPS scores of 2. Low fibrinogen level, lack of antithrombotic therapy, and the presence of metastasis were associated with stroke recurrence., Conclusions: When patients with cancer suffer stroke, D-dimer levels, fibrinogen levels, GPS, and multiple vascular territory infarctions would be associated with the risk of death within 6 months. Low fibrinogen levels, lack of antithrombotic therapy, and the presence of metastasis correlated with high risk of stroke recurrence., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Various pathogenesis are presumed to be involved in the etiology of embolic stroke of undetermined source (ESUS), which has a high recurrence rate, and much remains unknown about the clinical subtype of recurrent stroke. The purpose of this study was to clarify the pathogenesis of ESUS using the ASCOD classification for ESUS patients and to examine the factors involved in the recurrence of ischemic stroke., Methods: The subjects of this study were 236 of these patients who fulfilled the criteria for ESUS. The rate of stroke recurrent, subtype of recurrent ischemic stroke, and new-onset atrial fibrillation (AF) in these patients were surveyed retrospectively, and each patient was graded for the A, S, and C categories of the ASCOD classification., Results: Ischemic stroke recurred in 32 patients during the follow-up period (7 days to 12.9 years [median 54.3 months]), and new-onset AF was seen in 44 (18.6%) patients. The most subtype of recurrent ischemic stroke was ESUS again (19 patients). Multivariate analysis with a Cox proportional hazards model, the S score (hazard ratio 5.21; 95% confidence interval (CI) 2.38-11.42; P < .001) and the number of A, S, C categories (hazard ratio 1.90; 95% CI 1.14-3.10; P = .013) were factors significantly related to recurrent ischemic stroke., Conclusions: Assessment of comorbid conditions in ESUS patients based on the ASCOD classification may be useful in predicting the likelihood of recurrence of ischemic stroke., (Copyright © 2019. Published by Elsevier Inc.)

Background: In patients with acute ischemic stroke, current guidelines recommend maintaining blood glucose levels in a range of 140-180 mg/dL and closely monitoring to prevent hypoglycemia (<60 mg/dL). We aimed to assess glucose variability by continuous glucose monitoring (CGM) and to demonstrate the risk of acute ischemic stroke patients with glucose levels outside of the glucose management recommendations., Methods: Patients with ischemic stroke admitted within 7 days after onset were prospectively enrolled, and their blood glucose levels were monitored every 15 minutes for 72-hour period using the FreeStyle Libre Pro. Multivariate logistic regression analyses were used to analyze potential predictors for hyperglycemic (>180 mg/dL) and hypoglycemic (<60 mg/dL) events., Results: A total of 39 acute ischemic stroke patients (mean age 75.9 ± 11.5 years) were enrolled, and CGM was started from 58.6 ± 41.9 hours after stroke onset. CGM showed hypoglycemic events in 19 patients and hyperglycemic events in 21 patients, and the frequencies of hypo- and hyperglycemic events during CGM were 10.1 ± 15.7% and 11.9 ± 22.5%, respectively. Hypoglycemic events were mainly observed in the night-time in patients with normoglycemia at admission. Logistic regression analyses demonstrated significant associations between the blood glucose level at admission and hypo- and hyperglycemic events on CGM., Conclusions: This study of CGM found that many stroke patients have blood glucose levels outside the recommended guideline range in the acute phase. Blood glucose level on admission may be used as a predictor for hypo- and hyperglycemic events after admission., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months., Methods: This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups., Results: The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs., Discussion: This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background We aimed to clarify associations between prior anticoagulation and short- or long-term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42-0.81; P=0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16-0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20-6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

Background: Faster time to recanalization leads to better clinical outcomes in patients treated with endovascular thrombectomy. Whether the association between time to recanalization and clinical outcomes depends on cerebral blood volume (CBV) obtained from pretreatment computed tomography (CT) perfusion (CTP) imaging was investigated., Methods: In consecutive patients with acute ischemic stroke who achieved recanalization by endovascular thrombectomy for intracranial internal carotid artery or M1 occlusion, the effects on clinical outcome of time to recanalization and the relative CBV value (rCBV) assessed by pretreatment CTP were evaluated. The patient population was divided into 2 groups according to rCBV: normal rCBV group (rCBV ≥ .9) and low rCBV group (rCBV < .9). In each group, time to recanalization was compared between the good and the poor clinical outcome groups., Results: Sixty-four patients were eligible for this study. Twenty-six patients (40.6%) achieved good clinical outcomes. In the normal rCBV group, no association was found between clinical outcome and time to recanalization. In the low rCBV group, time to recanalization from CTP (101 minutes versus 136 minutes, P = .040) was significantly shorter in the good clinical outcome group. On binary logistic regression modeling, CTP to recanalization time (odds ratio 1.035 [1.004-1.067], P = .025) was an independent predictor of good clinical outcome only in the low rCBV group., Conclusions: The association between time to recanalization and clinical outcomes depends on rCBV obtained from pretreatment CTP. Time to recanalization is more important for good clinical outcomes in patients with low rCBV than in patients with normal rCBV., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry., Methods: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years., Results: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001; 1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p = 0.008; respectively) scores were independently associated with all outcome measures., Conclusions: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years., (© 2018 S. Karger AG, Basel.)

Rationale: Subcutaneous implantable electrocardiographs are highly effective in detecting covert atrial fibrillation (AF) in cryptogenic stroke. However, these invasive devices are not indicated for all cryptogenic stroke patients, and noninvasive improvements over conventional Holter-type ambulatory electrocardiography are needed. We evaluated the clinical application and effectiveness of Duranta (ImageONE Co., Ltd.), a wireless patch-type electrocardiographic monitoring system developed in Japan for chronically ill patients or home-based patients at the end of life. A Duranta device was used to detect covert AF in patients with acute ischemic stroke of undetermined source with no sign of AF during cardiographic monitoring ≥24 hours postadmission., Patient Concerns: A 72-year-old man with severe aortic stenosis was admitted to our hospital with dysarthria and right upper limb weakness. Diffusion-weighted plain head magnetic resonance imaging (MRI) showed acute cerebral infarctions across the left middle cerebral artery territory. Twelve-lead electrocardiography, Holter-type ambulatory electrocardiography, and cardiographic monitoring for ≥24 hours revealed no AF, indicating a probable diagnosis of artery-to-artery embolism following left common carotid artery stenosis detected by carotid ultrasound imaging and cerebral angiography., Interventions: However, because of high blood brain natriuretic peptide (BNP) and valvular heart disease, continuous monitoring using Duranta was performed from the 2nd to 13th days after onset to exclude possible cardioembolic stroke. Waveform and heart rate trend graph analysis showed paroxysmal AF (PAF) occurred on the 5th and 9th days after onset. PAF did not occur at any other time during the observation period. The quality of the cardiograms sufficed for analysis and diagnosis of AF. The lightweight compact device can be placed quickly with no movement restriction. These features and our findings show the usefulness of the Duranta device for long-term continuous monitoring., Lessons: A noninvasive wireless patch-type electrocardiographic monitoring system, Duranta, placed at the precordium, was useful in detecting covert AF in cryptogenic stroke patients, warranting further investigation.

Background and Purpose: The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack., Methods: Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups., Results: The median follow-up period was 1.8 (interquartile range, 0.93-2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43-0.87; P=0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26-3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63-2.08)., Conclusions: Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01581502., (© 2016 American Heart Association, Inc.)

Aims: This study was performed to determine the short-term risk-benefit profiles of patients treated with oral anticoagulation for acute ischemic stroke or transient ischemic attack using a multicenter, prospective registry., Methods: A total of 1137 patients (645 men, 77 ± 10 years old) with acute ischemic stroke/transient ischemic attack taking warfarin (662 patients) or non-vitamin K antagonist oral anticoagulants (dabigatran in 205, rivaroxaban in 245, apixaban in 25 patients) for nonvalvular atrial fibrillation who completed a three-month follow-up survey were studied. Choice of anticoagulants was not randomized. Primary outcome measures were stroke/systemic embolism and major bleeding., Results: Both warfarin and non-vitamin K antagonist oral anticoagulants were initiated within four days after stroke/transient ischemic attack onset in the majority of cases. Non-vitamin K antagonist oral anticoagulant users had lower ischemia- and bleeding-risk indices (CHADS2, CHA2DS2-VASc, HAS-BLED) and milder strokes than warfarin users. The three-month cumulative rate of stroke/systemic embolism was 3.06% (95% CI 1.96%-4.74%) in warfarin users and 2.84% (1.65%-4.83%) in non-vitamin K antagonist oral anticoagulant users (adjusted HR 0.96, 95% CI 0.44-2.04). The rate of major bleeding was 2.61% (1.60%-4.22%) and 1.11% (0.14%-1.08%), respectively (HR 0.63, 0.19-1.78); that for intracranial hemorrhage was marginally significantly lower in non-vitamin K antagonist oral anticoagulant users (HR 0.17, 0.01-1.15). Major bleeding did not occur in non-vitamin K antagonist oral anticoagulant users with a CHADS2 score <4 or those with a discharge modified Rankin Scale score ≤2., Conclusions: Stroke or systemic embolism during the initial three-month anticoagulation period after stroke/transient ischemic attack was not frequent as compared to previous findings regardless of warfarin or non-vitamin K antagonist oral anticoagulants were used. Intracranial hemorrhage was relatively uncommon in non-vitamin K antagonist oral anticoagulant users, although treatment assignment was not randomized. Early initiation of non-vitamin K antagonist oral anticoagulants during the acute stage of stroke/transient ischemic attack in real-world clinical settings seems safe in bleeding-susceptible Japanese population., (© 2016 World Stroke Organization.)

Background and Purpose: This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke., Methods: Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 μg/kg and then 90 μg/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography. The incidence of symptomatic intracranial hemorrhage (≤72 hours) was defined as the primary end point. The occurrence of asymptomatic ICH, symptomatic cerebral edemas, and adverse events were other safety outcomes of special interest., Results: Symptomatic intracranial hemorrhage was observed within 72 hours in 2 patients treated with placebo and in 1 patient treated with 70 μg/kg desmoteplase. Any ICH (symptomatic or asymptomatic ICH) within 72 hours were observed in 7 (43.8%) patients treated with placebo, in 8 (50%) patients treated with 70 μg/kg desmoteplase, and in 9 (56.3%) patients treated with 90 μg/kg desmoteplase. Desmoteplase treatment with 70 or 90 μg/kg was not associated with an increased risk of symptomatic cerebral edema compared with placebo. There were no other serious safety concerns associated with desmoteplase., Conclusions: Desmoteplase in both 70 and 90 μg/kg doses had a favorable safety profile and was well tolerated in Japanese patients with acute ischemic stroke when administered 3 to 9 hours after stroke symptoms onset., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01104467., (© 2015 American Heart Association, Inc.)

Background: Proinflammatory state has been implicated as a pathogenetic mechanism in the progression of intracranial large artery atherosclerosis (ILA). High levels of inflammatory biomarkers in healthy populations and in patients with acute stroke or acute coronary syndrome are known to be associated with subsequent stroke events. This study investigated the relationship between circulating biomarkers measured early after stroke onset and future ILA progression., Methods: In 48 patients with acute ischemic stroke, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2 and MMP-9 were measured within 48 hours after onset. Baseline severity and ILA progression were assessed by serial magnetic resonance angiography (MRA). The median follow-up period for MRA was 3.1 years. Hazard ratio (HR) was calculated using the Cox proportional hazard model adjusted for traditional risk factors, and accuracy of predicted ILA progression was analyzed by receiver operating characteristic (ROC) curve analysis., Results: ILA progression was observed in 6 of 48 patients (12.5%). After adjusting for age, sex, and presence of hypertension, baseline ILA severity score (HR 2.814; 95% confidence interval [CI] 1.172-6.754) and IL-6 (HR 1.215; 95% CI 1.002-1.473) were significantly associated with ILA progression. Area under the ROC curve (AUC) for prediction of ILA progression by traditional risks, baseline ILA severity score and IL-6, was 0.647. When IL-6 was removed from this model, AUC remained at 0.631., Conclusions: In addition to traditional risk factors and baseline radiologic findings, circulating levels of IL-6 measured soon after stroke onset are associated with future ILA progression., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The purpose of this study was to determine the safety and efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg alteplase) within 3 hours of stroke onset in Japanese patients outside the indications in the European license., Methods: Of the 600 patients who were treated with recombinant tissue-type plasminogen activator, 422 met the inclusion criteria of the European license (IN group) and 178 did not (OUT group)., Results: The OUT group was inversely associated with any intracerebral hemorrhage (adjusted OR, 0.50; 95% CI, 0.29-0.84), positively associated with an unfavorable outcome (2.48; 1.55-3.94) and mortality (2.04; 1.02-4.04), and not associated with symptomatic intracerebral hemorrhage (0.53; 0.11-1.79) or complete independency (0.65; 0.40-1.03) after multivariate adjustment., Conclusions: Functional and vital outcomes 3 months after low-dose recombinant tissue-type plasminogen activator in patients outside the European indications were less favorable compared with those included in the indications; however, the risk of intracerebral hemorrhage was not.

Background and Purpose: Alberta Stroke Programme Early CT Score (ASPECTS) is a quantitative topographical score to evaluate early ischemic change in the middle cerebral arterial territory on CT as well as on diffusion-weighted imaging (DWI). The aim of the present study was to elucidate the relationship between CT-ASPECTS and DWI-ASPECTS for patients with hyperacute stroke and their associations with outcomes after recombinant tissue-type plasminogen activator therapy based on a multicenter registry., Methods: ASPECTS was assessed on both CT and DWI before intravenous 0.6 mg/kg alteplase in 360 patients with stroke (119 women, 71 ± 11 years old). The outcomes were symptomatic intracerebral hemorrhage within 36 hours and independence at 3 months defined by a modified Rankin Scale score of 0 to 2., Results: DWI-ASPECTS was positively correlated with CT-ASPECTS (ρ=0.511, P<0.001) and was lower than CT-ASPECTS (median 8 [interquartile range, 6 to 9] versus 9 [8 to 10], P<0.001). Higher baseline National Institutes of Health Stroke Scale score (standardized partial regression coefficient [β] 0.061, P<0.001) and cardioembolic stroke (β 0.35, P<0.001) were related to this discrepancy. The area under the receiver operating characteristic curve for predicting sICH (12 patients) using ASPECTS was 0.673 (95% CI, 0.503 to 0.807) by CT and 0.764 (95% CI, 0.635 to 0.858) by DWI (P=0.275). The area for predicting independence at 3 months (192 patients) was 0.621 (0.564 to 0.674) by CT and 0.639 (0.580 to 0.694) by DWI (P=0.535)., Conclusions: For patients with hyperacute stroke, DWI-ASPECTS scored approximately 1 point lower than CT-ASPECTS. Both CT-ASPECTS and DWI-ASPECTS were useful predictors of symptomatic intracerebral hemorrhage and independence at 3 months after recombinant tissue-type plasminogen activator.

Background and Purpose: This study aimed to identify the recurrence rate and risk factors or clinical variables predictive of vascular events after mild ischemic stroke (IS)., Methods: From December 2006 to September 2007, patients with acute IS with a modified Rankin Scale of 0∼1 were consecutively enrolled in this study. Variables including sex, family history of vascular disease, age, height, weight, stroke subtype, blood pressure, lipid profile, fasting glucose, HbA1c, smoking, alcohol consumption, exercise habits, waist circumference, ankle-brachial pressure index, salt intake and physical activity were assessed. The primary outcome was stroke recurrence or other vascular events such as myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models., Results: A total of 102 mild IS patients (78 men and 24 women, mean age 64 years) were successfully followed for 3 years. Of those 102 patients, 25 (24.5%) had stroke recurrence, and 4 (3.9%) had a coronary event. Among the variables studied, abnormal ankle-brachial pressure index, metabolic syndrome, stroke subtypes, salt intake and poor lifestyle management were significant independent predictors of stroke recurrence or cardiovascular events., Conclusions: In mild IS patients within 3 years after onset, not only pathophysiological factors but also lifestyle factors can aid in the identification of patients at high risk for recurrence., (Copyright © 2011 S. Karger AG, Basel.)

Antiplatelet effects of angiotensin II receptor blocker have been suggested, but satisfactory results in clinical settings are lacking. We investigated spontaneous platelet aggregation (SPA) and CD62P levels in patients with hypertension and chronic-stage ischemic stroke. The study comprised 35 patients assigned to losartan (50 mg/day) or telmisartan (40 mg/day) for 4 weeks randomly. SPA was evaluated using laser-scattered light aggregometry and CD62P levels using whole blood flow cytometry before and after treatment. SPA was not significantly reduced after losartan or telmisartan treatment. CD62P was significantly reduced after losartan treatment (P = .016), but no significant differences were noted with telmisartan. These findings suggest that standard doses of losartan display antiplatelet effect as measured by CD62P levels.

Background: In Japan, the healthcare expenditure has increased to 8.0% of the gross domestic products in 2001. Stroke care is costly., Objective: To examine hospital costs and clinical outcomes of ischemic stroke (IS) and intracerebral hemorrhage (ICH) in Japanese stroke centers., Design: A prospective non-interventional multi-center study., Setting: Ten Japanese stroke centers., Study Period: Fourteen months between October 2000 and December 2001., Patients: Patients were those who were consecutively hospitalized with acute IS or ICH within 72 h of onset, excluding subarachnoid hemorrhage. Stroke was defined as focal neurological deficits lasting more than 24 h and the relevant lesions were to be confirmed by brain CT and/or MRI., Methods: We examined demography, in-hospital cares, length of hospital stay, clinical outcomes at discharge, and direct hospital medical costs including physician's fees. The hospital medical cost data were collected from official hospital medical cost charts for reimbursement to the healthcare insurance systems., Results: There were a total of 1113 patients with a mean age of 70 years, of whom 913 (82%) patients had an IS and 200 (18%) patients had an ICH. The 317 patients (28%) experienced a recurrent stroke. Patients with ICH had the higher baseline stroke severity, resulting in longer hospitalization (39 days for IS and 46 days for ICH; P<0.001), lower independence rate at discharge (55 and 40%; P<0.001), higher mortality rate (5 and 10%; P=0.03), and higher medical costs (US dollar 8662 and US dollar 10,260; P<0.001) than those with IS. Patients with recurrent stroke had significantly older age, higher stroke severity, and lower independence rate at discharge than those with first-ever stroke. The length of stay, in-hospital mortality, and hospital medical costs were similar among first-ever and recurrent strokes. In subtype of IS, patients with cardioembolic stroke had the worst neurological deficits, poorest outcomes, and highest medical costs. The hospital costs had a greatest association with length of stay., Conclusions: Stroke care is costly in Japan. ICH is more likely to impose substantial physical and economic burden than IS. Because the cares of both first-ever and recurrent stroke were costly, primary and secondary prevention of stroke is important on the healthcare aspects.

Background and Purpose: Whether misery perfusion (MP) commonly accompanies brain borderzones (BZs) in patients with major cerebral artery occlusion remains unclear. We elucidated topographic patterns of chronic hemodynamic failure in such patients., Methods: Twenty-four patients with unilateral occlusion or severe stenosis (>75% in diameter) of the internal carotid artery (ICA) or middle cerebral arterial (MCA) trunk with minimal or no infarct underwent PET with (15)O-labeled gas inhalation. Mean cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen, oxygen extraction fraction (OEF), and CBV/CBF ratio were determined in the superficial BZs, internal BZ, and MCA territory excluding BZs. Values in BZs were standardized and compared with those in controls. Topographic distributions of regions with OEF greater than that in controls were determined., Results: Values in patients and controls were not significantly different. Topographic distributions included matched perfusion in 10 patients, MP in only the ipsilateral internal BZ in four, MP in both ipsilateral internal and superficial BZs in two, MP in the ipsilateral MCA territory including BZs in one, MP in the ipsilateral MCA territory including BZs and contralateral BZs in two, and MP in the ipsilateral MCA territories including BZs in five., Conclusion: Only 25% of the patients had MP localized in affected BZs Although localized MP more frequently accompanied the internal BZ than other regions, no patient had elevated OEF in the superficial BZ alone. These results are inconsistent with clinical observations that 80% of BZ infarctions develop superficially. Thus, hemodynamic mechanisms may not cause most superficial BZ infarctions.