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Background: We investigated the clinical effect of intravenous thrombolysis using a magnetic resonance imaging (MRI)-guided approach in cardioembolic stroke (CE) patients with unknown time of onset., Methods and results: This subanalysis of the THAWS trial assessed the efficacy and safety of alteplase 0.6 mg/kg in CE patients with unknown time of onset and showing diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch. Patients were classified as CE and non-CE using the SSS-TOAST classification system during the acute period. The efficacy outcome was a modified Rankin Scale score of 0-1 at 90 days. In all, 126 patients from the THAWS trial were included in this study, of whom 45 (35.7%) were diagnosed with CE. In the CE group, a favorable outcome was numerically more frequent in the alteplase than control group (52% vs. 35%; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 0.50-9.99). However, in the non-CE group, favorable outcomes were comparable between the alteplase and control groups (44% vs. 55%, respectively; aOR 0.39; 95% CI 0.12-1.21). Treatment-by-cohort interaction for a favorable outcome was modestly significant between the CE and non-CE groups (P=0.069). In the CE group, no patients experienced symptomatic intracranial hemorrhage (ICH) or parenchymal hematoma Type II following thrombolysis., Conclusions: When an MRI-guided approach is used, CE patients with unknown time of onset appear to be suitable candidates for thrombolysis.

Background and Objective: Whether asymptomatic intracranial hemorrhage (ICH) affects the clinical outcomes in patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains unclear. This study aimed to address this uncertainty., Methods: We retrospectively analyzed patients with acute ischemic stroke and internal carotid or middle cerebral (M1 segment) artery occlusion treated with MT between April 2011 and March 2021 at a single center. All patients had a premorbid modified Rankin scale (mRS) score ≤ 2 and an anterior circulation occlusion and underwent magnetic resonance imaging at admission. Asymptomatic ICH was defined as ICH without symptomatic ICH defined by the SITS-MOST criteria. A favorable outcome was defined as an mRS score ≤ 2 at 90 days after stroke onset., Results: Our study included 349 patients; 62% were men, the median age was 76 [67-83] years, and the median National Institutes of Health Stroke Scale (NIHSS) score was 15 [8-21]. As determined via computed tomography, 103 (30%) patients had ICH (20 symptomatic and 83 asymptomatic). The favorable outcome rate was significantly lower for asymptomatic vs. no ICH (30% vs. 67%, p < 0.01). In a multivariate regression analysis, a high NIHSS score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10; p < 0.01) and low Alberta Stroke Program Early CT Score (OR, 0.78; 95% CI, 0.65-0.92; p < 0.01) were independent risk factors for ICH., Conclusions: Asymptomatic ICH is associated with poor clinical outcome at 90 days after stroke onset., Competing Interests: Declaration of competing interest Kazumi Kimura received lecture fees from Bristol-Myers Squibb Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Bayer Healthcare Co. Ltd., and Daiichi Sankyo Co.; research funding from Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co., Pfizer Japan Inc., Medtronic Co. Ltd., and Teijin Pharma Ltd., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice., Methods: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time &gt;4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline., Results: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge., Conclusions: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them., (© 2023 S. Karger AG, Basel.)

Background: Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance., Aims: To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction., Methods: We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset., Results: Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P  < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P  < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P  < 0.01)., Conclusions: Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Kimura received lecture fees from Bristol-Myers Squibb Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Bayer Healthcare Co. Ltd., and Daiichi Sankyo Co.; research funding from Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co., Pfizer Japan Inc., Medtronic Co. Ltd., and Teijin Pharma Ltd.; and personal funding from the 38th Mihara Cerebrovascular Disorder Research Promotion Fund Ltd. Dr. Liebeskind receives support for acting as an imaging core laboratory for Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical. The other authors report no conflicts.

Aim: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke., Methods: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication., Results: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication., Conclusion: Alteplase appears more beneficial in patients with prior antithrombotic medication.

Background: There are a few accurate predictors of patient outcomes after mechanical thrombectomy (MT)., Objective: To investigate whether the National Institutes of Health Stroke Scale (NIHSS) score 24 hours after stroke onset could predict favorable outcomes at 90 days in patients with acute stroke treated with MT., Methods: Patients from the SKIP study were enrolled in this study. Using receiver operating characteristic curves, the optimal cut-off NIHSS score 24 hours after stroke onset was calculated to distinguish between favorable (modified Rankin Scale score 0-2) and unfavorable (modified Rankin Scale score 3-6) outcomes at 90 days. These receiver operating characteristic curves were compared with those of previously reported predictors of favorable outcomes, such as the ΔNIHSS score (baseline NIHSS score-NIHSS score at 24 h), percent delta (ΔNIHSS score × 100/baseline NIHSS score), and early neurological improvement indices., Results: A total of 177 patients (median age, 72 years; female, 65 [37%]) were enrolled, and 109 (61.9%) had favorable outcomes. The respective sensitivity, specificity, and area under the curve values for an NIHSS of 10 were 92.6%, 80.7%, and .906; a ΔNIHSS score of 7 were 70.6%, 76.1%, and .797; and percent delta of 48.3% were 85.3%, 80.7%, and .890., Conclusion: NIHSS score <10 at 24 hours after stroke onset is a strong predictor of favorable outcomes at 90 days in patients treated with MT., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Background and Aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke., Methods: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days., Results: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score ( p  = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group ( p interaction = 0.042)., Conclusion: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.

Objective: Several studies have investigated the predictors of functional outcome in patients with ischemic stroke after mechanical thrombectomy (MT). However, it is not clear whether pre-stroke cognitive (PSC) impairment is associated with the functional outcome of patients treated with MT., Methods: We enrolled 113 patients treated with MT from December 2016 to November 2018. PSC was evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Poor outcome was defined as a modified Rankin Scale score of 3-6. We compared the clinical characteristics between the groups with poor outcome (n = 61) and good outcome (n = 52) to determine if PSC could be a predictor of poor outcome., Results: IQCODE was significantly higher in the group with poor outcome than good outcome (3.34 vs. 3.13, P = 0.017). Moreover, the following metrics differed between those two groups: age (75.9 vs. 71.6 years old, P = 0.010), the percentage of females (39.9% vs. 17.3%, P = 0.009), the percentage with hypertension (72.1% vs. 44.2%, P = 0.003), National Institutes of Health Stroke Scale (NIHSS) score on admission (20 vs. 11, P < 0.001), and no successful recanalization (24.5% vs. 7.7%; P = 0.025). Multivariable logistic regression analysis demonstrated that PSC (OR: 5.59; 95% CI: 1.55-23.47), history of hypertension (OR: 3.33; 95% CI: 1.29-9.11), no successful recanalization (OR: 5.51; 95% CI: 1.49-25.03), and NIHSS score on admission (OR: 1.14; 95% CI: 1.07-1.22) were associated with poor outcome 3 months after stroke onset., Conclusions: PSC was significantly and independently associated with poor functional outcome in patients treated with MT., (© 2021. Fondazione Società Italiana di Neurologia.)

Background and Purpose: Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). The aim of this study was to investigate whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischaemic stroke., Methods: Acute ischaemic stroke patients hospitalized in the stroke care unit (SCU) within 24 h after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured on admission. We evaluated the associations among urinary L-FABP, incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria and other potentially predictive variables, using multivariable analysis., Results: In total, 527 acute ischaemic stroke patients (342 men, median age 74 years) were enrolled in the study. Twenty-seven patients (5.1%) experienced AKI within 7 days of admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI [53.8 μg/g creatinine (Cr) vs. 3.9 μg/g Cr; P < 0.001] and 90-day mortality (15.5 μg/g Cr vs. 4.0 μg/g Cr; P < 0.001). In the multivariate analysis, elevated urinary L-FABP level (per 10-μg/g Cr increase) was independently associated with AKI (odds ratio 1.225, 95% confidence interval (CI) 1.083-1.454; P = 0.003) and 90-day mortality (hazard ratio 1.091, 95% CI 1.045-1.138; P < 0.001)., Conclusion: Urinary biomarkers of kidney tubule injury are independently associated with the development of AKI and 90-day mortality in patients with acute ischaemic stroke treated at the SCU., (© 2020 European Academy of Neurology.)

Background: The long-term outcome in acute stroke patients with large vessel occlusion (LVO) treated with endovascular therapy (EVT) are unclear. We investigated functional outcomes one year after EVT in acute stroke patients with LVO., Methods: We retrospectively enrolled 149 stroke patients with LVO who underwent EVT from our prospective stroke registry. We assessed modified Rankin Scale (mRS) scores at one year from onset. The degree of recanalization was evaluated using modified thrombolysis in cerebral infarction (mTICI) grades. Good recanalization and a favorable outcome were defined as an mTICI grade ≥ 2b and mRS score ≤ 2, respectively., Results: Favorable outcomes were observed in 76 (51.0%) patients. The favorable outcome group was younger (median age: 72 [interquartile range, 63-79] years vs. 79 [70-84] years, P < .001) and had more male patients (79% vs. 60%, P = .013), lower National Institutes of Health Stroke Scale scores at admission (median 14 [7-18]) vs. 19 [15-25], P < .001), higher DWI-ASPECTS upon admission (median [6-9] vs. 6 [4-8], P = .022), more patients with mTICI ≥ 2b (93% vs. 64%, P < .001) and fewer post-therapy intracranial cerebral hemorrhages (13% vs. 29%, P = .019) than the poor outcome group. In our multivariate analysis, mTICI ≥ 2b were independently associated with favorable outcomes at one year from onset (odds ratio, 10.282; 95% confidence interval, 1.587-66.604; P = .015)., Conclusions: Good recanalization was associated with favorable functional outcomes one year after EVT in acute stroke patients with LVO., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: We investigated the impact of complete recanalization beyond partial recanalization in distal (M2) middle cerebral artery (MCA) occlusion., Methods: Data regarding M2 occlusion patients treated with endovascular thrombectomy (EVT) and/or intravenous thrombolysis (tPA) were reviewed from our prospective EVT registry and multicenter tPA (YAMATO study) data bank. Complete recanalization was modified thrombolysis with cerebral infarction score (TICI) of 3 at the end of EVT or similar appearances of both MCAs on magnetic resonance angiography (MRA) within 1.5 h after tPA. Partial recanalization was defined as TICI ≥2b or > 50% recanalization on MRA. At 3 months, favorable outcome was defined as a modified Rankin Scale score ≤ 2., Result: Data on 121 patients were analyzed. EVT-alone was in 38 patients; combined EVT and tPA in 28; and tPA-alone in 55. Complete recanalization was achieved in 27 (22%), partial recanalization in 48 (40%), and no-to-limited recanalization in 46 (38%). At 3 months, 51% of patients had favorable outcomes, and this rate was significantly higher in the complete recanalization group than in the partial and no-to-limited recanalization groups (75% vs. 41% vs. 49%, p = .043). Multivariate regression analysis showed that complete recanalization was an independent parameter related to favorable outcomes (odds ratio 4.78, 95% CI: 1.16-19.73, p = .030). However, combined complete and partial recanalization was not associated with favorable outcomes (odds ratio 1.49, 95% CI 0.53-4.22, p = .449)., Conclusion: Complete recanalization, but not partial recanalization, at the end of EVT and tPA therapy is associated with favorable outcomes in patients with M2 occlusion., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest. There is no funding sources., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Evaluation of cognitive status is not performed routinely in the acute stroke setting. This study aimed to evaluate the frequency of early cognitive impairment in patients with minor ischemic stroke, analyze the factors associated with early cognitive impairment, and assess functional outcomes., Methods: In this prospective study, 112 consecutive patients with acute minor ischemic stroke were enrolled. Neuroimages were assessed for semiquantitative evaluation of brain atrophy and small vessel disease (SVD) markers. Cognitive performance was measured within 5 days of onset using Montreal Cognitive Assessment (MoCA) scores. Functional outcome analyses were adjusted for demographic variables, premorbid cognitive status, education level, vascular risk factors, neuroimaging characteristics, stroke severity, and MoCA scores., Results: The median MoCA score was 22, and 63% of patients had cognitive impairment. Factors independently associated with cognitive impairment were education (odds ratios [OR], .79; confidence intervals [CI], .63-.99), smoking (OR, .26; 95%CI, .073-.89), and temporal horn atrophy (OR, 4.73; 95% CI, 1.66-13.49). Factors independently associated with poor functional outcome were total MoCA score (OR, .78; 95%CI, .62-.95) and the sum of 4 MoCA subscores (visuospatial/executive, attention, language, and orientation; OR, .72; 95%CI, .53-.92). The cutoff value of the sum of 4 MoCA subscores for predicting poor outcome was 13 points with 76.5% sensitivity and 81.1% specificity., Conclusions: Early cognitive impairment was common after minor ischemic stroke and was associated with preexisting temporal horn atrophy but not SVD markers. The sum of 4 MoCA subscores was useful in predicting the functional outcome., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: National institutes of Health Stroke Scale (NIHSS) score and the presence of successful recanalization are crucial determinants of clinical outcome in patients with major artery occlusion. However, it is unknown whether successful recanalization rate after endovascular therapy (EVT) depends on NIHSS score., Methods: From our prospective EVT registry, data on patients with an occlusion at the internal carotid artery or middle cerebral artery were analyzed. Successful recanalization was judged as positive when reperfusion of the thrombolysis in cerebral infarction (TICI) scale ≥2b was observed. Successful recanalization rate was also evaluated based on the NIHSS score subgroups: 0-8, 9-16, 17-24, and >24. Multivariate regression analysis was used to evaluate the impact of NIHSS score on successful recanalization., Results: We studied 183 patients (age 76 [68-83], male 110 [60%], NIHSS score 19 [14-24]). One hundred and forty-six (80%) patients had the successful recanalization. Patients achieved the recanalization had lower NIHSS score as 18 (12-23), contrary those failed it had higher NIHSS score as 24 (20-27) (p < .001). Successful recanalization rate was correlated to the NIHSS score grade; 100% in the NIHSS 0-8 group, 88% in 9-16, 81% in 17-24, and only 60% in >24 (p < .001). Multivariate regression analysis showed NIHSS score was an independent parameter of recanalization (odds ratio 0.905 [95%CI 0.837-0.979], p = .013)., Conclusion: NIHSS score may serve as a predictor of successful recanalization. Recanalization is relatively easier in mild stroke than in those with severe stroke., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Anticoagulant therapy often requires temporary interruption. Nevertheless, the frequency and clinical characteristics of stroke patients who develop stroke during anticoagulant interruption are not fully known., Methods: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF who were admitted to our stroke unit were retrospectively recruited. Patients who developed ischemic stroke during anticoagulant interruption were defined as those who developed ischemic stroke within 30 days from anticoagulant interruption. The frequency and clinical characteristics of patients during anticoagulant interruption were analyzed., Results: A total of 561 patients with AF and acute ischemic stroke (237 women; median age 78 [IQR 71-85] years) were admitted during the study period. Of these, 21 (3.7%, 12 patients discontinued vitamin K antagonist [VKA] and 9 discontinued direct oral anticoagulants [DOACs]) patients were admitted during the period of anticoagulant interruption. Severity and functional outcomes in stroke patients during anticoagulant interruption were not different from those without anticoagulant treatment. The number of days between anticoagulant interruption and stroke onset was shorter in patients who discontinued DOACs (3 [3-5] days) than in those who discontinuedVKAs (10 [7-20] days, p = .004). The major reason for interruption was planning of invasive procedures (52%). Guideline deviations were suspected in 82% of such cases., Conclusion: Patients developing stroke during anticoagulant interruption accounted for 3.7% of stroke patients with AF. Strokes occurred relatively early after interruption, especially in patients who discontinued DOACs. Guideline deviations was frequent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: This study investigated changes in anticoagulant use, treatment, and functional outcomes in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) over a 6-year period., Methods and results: Patients with AIS and NVAF admitted to our department from April 2011 to March 2017 were analyzed retrospectively. Patients were divided into 3 groups based on the time of the initial visit (Periods 1-3, corresponding to April 2011-March 2013, April 2013-March 2015, and April 2015-March 2017, respectively). Associations between prescribed medication prior to event and stroke severity, reperfusion therapy, and outcomes were assessed. There was no significant change in the rate of insufficient warfarin and inappropriately lowered doses of direct oral anticoagulant (DOAC) treatment over time. The number of patients receiving prior DOAC treatment increased, but neurological severity on admission was milder than in the other 2 groups. The rate of reperfusion therapy increased from 19.9% (Period 1) to 42.7% (Period 3) for moderate-to-severe stroke patients. Multivariate logistic regression analysis revealed that reperfusion therapy was independently positively associated with good functional outcomes, but negatively associated with mortality (odds ratios [95% confidence intervals] 7.14 [3.34-15.29] and 0.13 [0.008-0.69], respectively)., Conclusions: Inappropriate anticoagulant use for stroke patients with NVAF did not decrease over time. An increase in reperfusion therapy was a strong factor in improved functional outcomes and mortality.

Background and Purpose- The strong evidence of endovascular therapy in acute ischemic stroke patients with large vessel occlusion (LVO) is revealed. Such patients are required to direct transport to the hospital capable of endovascular therapy. There are several prehospital scales available for paramedics to predict LVO. However, they are time consuming, and several of them include factors caused by other types than LVO. Therefore, we need a fast, simple, and reliable prehospital scale for LVO. Methods- We developed a new prehospital stroke scale, emergent large vessel occlusion (ELVO) screen, for paramedics to predict LVO. The study was prospectively performed by multistroke centers. When paramedics referred to stroke center to accept suspected stroke patients, we obtain the following information over the telephone. ELVO screen was designed focusing on cortical symptoms: 1 observation; presence of eye deviation and 2 questions; paramedics show glasses, what is this? and paramedics show 4 fingers, how many fingers are there? If the presence of eye deviation or ≥1 of the 2 items were incorrect, ELVO screen was identified as positive. We evaluated between results of ELVO screen and presence of LVO on magnetic resonance angiography at hospital arrival. Results- A total of 413 patients (age, 74±13 years; men, 234 [57%]) were enrolled. Diagnosis was ischemic stroke, 271 (66%); brain hemorrhage 73 (18%); subarachnoid hemorrhage, 7 (2%); and not stroke, 62 (15%). One hundred fourteen patients had LVO (internal carotid artery, 33 [29%]; M1, 52 [46%]; M2, 21 [18%]; basilar artery, 5 [4%]; P1, 3 [3%]). Sensitively, specificity, positive predictive value, negative predictive value, and accuracy for ELVO screen to predict LVO were 85%, 72%, 54%, 93% and 76%, respectively. Among 233 patients with negative ELVO screen, only 17 (7%) had LVO, which indicated to be an ideal scale to avoid missing endovascular therapy. Conclusions- The ELVO screen is a simple, fast, and reliable prehospital scale for paramedics to identify stroke patients with LVO for whom endovascular therapy is an effective treatment.

Background and Purpose: Anticoagulant treatment with a vitamin K antagonist (VKA) has been reported to reduce stroke severity when patients with atrial fibrillation (AF) suffer acute ischaemic stroke (AIS). Direct oral anticoagulant (DOAC) therapy also has the potential to reduce the initial severity of AIS. However, the effect of DOAC therapy on the severity of AIS is not well known. The aim of the present study was to investigate the effect of DOACs on initial stroke severity in patients with AIS and non-valvular AF., Methods: From March 2011 to July 2016, consecutive patients with AIS having non-valvular AF were recruited. The effects of prior DOAC treatment on severity were assessed by multivariate logistic regression analyses., Results: A total of 484 patients [208 women; median age 79 (interquartile range, 71-85) years; National Institutes of Health Stroke Scale (NIHSS) score 9 (interquartile range, 3-20)] were enrolled. Of these, 352 (73%) were on no anticoagulant medication, 54 (11%) were undertreated with a VKA, 35 (7%) were sufficiently treated (admission prothrombin time-international normalized ratio: ≥2.0 for patients <70 years old and ≥1.6 for ≥70 years old) with a VKA and 43 (9%) were on a DOAC. The initial NIHSS score (median 10 in patients with no anticoagulation, 13 in undertreated VKA, 7 in sufficient VKA and 6 in DOAC, P = 0.018) was different among the groups. Multivariate analysis showed that DOAC was independently and negatively associated with severe (initial NIHSS score ≥ 10) stroke (odds ratio, 0.39; P = 0.041), compared with no anticoagulant therapy., Conclusions: Direct oral anticoagulant treatment prior to the event should reduce initial stroke severity in patients with AIS and non-valvular AF., (© 2017 EAN.)

Background and Purpose: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion., Methods: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization)., Results: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group ( P =1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P =0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group ( P =0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P =0.738)., Conclusions: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330., (© 2017 American Heart Association, Inc.)

Background: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke., Methods: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed., Results: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245)., Conclusion: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months., (© 2017 S. Karger AG, Basel.)

Objective: This study was performed to investigate whether the Penumbra 5MAX ACE is superior to other Penumbra systems., Materials and Methods: We performed a retrospective, single center analysis of patients with acute ischemic stroke with occlusion of the internal carotid artery or middle cerebral artery (M1 segment) who underwent endovascular therapy using a Penumbra system. The reperfusion success rate, puncture-to-revascularization time, and number of passes were assessed. Multivariate regression analysis was conducted to evaluate independent factors related to revascularization within 60 minutes. Successful revascularization was defined by a thrombolysis in cerebral infarction score ≥2b., Results: The Penumbra 5MAX ACE was used in 24 of the 40 patients (60%). Although the revascularization success rate was similar between patient groups (P = .229), the number of passes was significantly lower (1.5 ± .8 versus 2.6 ± 1.3, P = .006) and the puncture-to-revascularization time was shorter (50 ± 26 minutes versus 116 ± 69 minutes, P = .002) in patients treated with the Penumbra 5MAX ACE. The Penumbra 5MAX ACE was identified as an independent factor for early revascularization (odds ratio, 5.80; P = .041). Among patients with a premorbid modified Rankin Scale score of 0-1, a modified Rankin Scale score of 0-2 at 3 months was observed in 15 of the 19 patients (79%) treated with the Penumbra 5MAX ACE and in 8 of the 16 (50%) who were not (P = .072)., Conclusion: Acute revascularization therapy using the Penumbra 5MAX ACE can achieve rapid successful recanalization and tend to improve clinical outcomes., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke., Methods: We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration., Results: In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (<2.29pg/mL). In comparisons between FT3 quartiles (Q1 [≤2.11pg/mL], Q2 [2.12-2.45pg/mL], Q3 [2.46-2.77pg/mL], Q4 [≥2.78pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score., Conclusions: Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background and Purpose: Hyperintense vessels (HV) detected on fluid-attenuated inversion recovery (FLAIR) in patients with acute ischemic stroke (AIS) indicate cerebral hypoperfusion. However, the clinical meaning of changes in HV is yet to be clarified. Here, we investigated serial changes to HV in patients with AIS who received tissue plasminogen activator (t-PA) therapy., Methods: We studied t-PA patients presenting with HV on FLAIR in the middle cerebral artery territory. Patients underwent brain MRI 1 h before and after t-PA infusion. HV scores (range 1-7) were evaluated according to Alberta Stroke Program Early Computed Tomography Score territories, and then by subtracting HV scores at 1 h after t-PA infusion from those on admission, with a result of >1 defined as decrease in HV score (DHV). Patients were divided into 2 groups based on the presence or absence of DHV. Multivariate logistic regression analysis was conducted to identify variables independently associated with good outcome (modified Rankin Scale score at 90 days after stroke onset of 0-1)., Results: A total of 118 consecutive patients were enrolled (73 men; mean age 76 ± 9.7; median initial National Institutes of Health Stroke Scale (NIHSS) 13; median initial HV score 5), of whom 52 (44%) had DHV. Patients with DHV showed a significantly lower NIHSS time course (p < 0.001) and significantly smaller infarct volume time course (p < 0.001) compared to those without DHV. Multivariate analysis showed that DHV was independently associated with good outcome (OR 3.89; 95% CI 1.55-9.77; p < 0.01). The sensitivity and specificity of DHV for good outcome were 70 and 68%, respectively., Conclusion: A DHV on FLAIR predicts good outcome in patients receiving t-PA., (© 2016 S. Karger AG, Basel.)

Valproic acid (VPA) is widely used for the clinical treatment of epilepsy. Previous studies have demonstrated that VPA ameliorates brain injury following experimental stroke. However, the effect of VPA in stroke models featuring comorbid conditions has not been fully explored. In this study, we investigate the effects of VPA on permanent ischemic stroke with hyperglycemia. Hyperglycemia was induced by streptozotocin (STZ) injection 3 days before. Test animals received a single injection of VPA immediately after induction of ischemia. Control animals received occlusion and physiological saline injection, or STZ, occlusion, and saline. Magnetic resonance imaging of cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) was performed 60 min after ischemia. Infarct volume, neurological deficits, rotarod test performance, and immunohistological markers were assessed 3 days after ischemia. Hyperglycemia significantly expanded the area of decreased of CBF and ADC, and increased the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, inducible nitric oxide synthase-positive cells, von Willebrand factor-positive cells, and Fluoro-Jade C-positive cells in the ischemic boundary zone, which was accompanied by increased infarct volume and deteriorated neurological deficit and rotarod test compared with normoglycemia (P < 0.05). VPA significantly alleviated the aggravation of functional outcome accompanied by suppressing these inflammation, endothelial injury, and neuronal degeneration compared with saline-treated group (P < 0.05). A single injection of VPA following permanent ischemia in STZ-induced hyperglycemic rats ameliorates neurological deficits and reduces neuronal degeneration by inhibiting inflammation and endovascular injury. VPA may be promising as a candidate therapy for human stroke., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Intra-arterial (IA) thrombectomy for acute ischemic stroke has an excellent recanalization rate but variable outcomes. The core infarct also grows at a variable rate despite recanalization. We aim to study the factors that are associated with infarct growth after IA therapy., Methods: We reviewed the hyperacute ischemic stroke imaging database at Cleveland Clinic for those undergoing endovascular thrombectomy of anterior circulation from 2009 to 2012. Patients with both pretreatment and follow-up magnetic resonance imaging were included. Seventy-six patients were stratified into quartiles by infarct volume growth from initial to follow-up diffusion-weighted imaging (DWI) measure by a region of interest demarcation., Results: The median infarct growth of each quartile was .6 cm(3) (no-growth group), 13.8, 37, and 160.2 cm(3) (large-growth group). Pretreatment stroke severity was comparable among groups. Compared with the no-growth group, the large-growth group had larger initial infarct defined by computed tomography (CT) Alberta Stroke Program Early CT score (median 10 versus 8, P = .032) and DWI volume (mean 13.8 versus 29.2 cm(3), P = .034), lack of full collateral vessels on CT angiography (36.8% versus 0%, P = .003), and a lower recanalization rate (thrombolysis in cerebral infarction ≥2b, P = .044). The increase in infarct growth is associated with decrease in favorable outcomes defined by a modified Rankin Scale score of 0-2 at 30 days: 57.9%, 42.1%, 21.1%, and 5.3%, respectively (P < .001). DWI reversal was observed in 11 of 76 patients, translating to 82% favorable outcome., Conclusions: Infarct evolution after endovascular thrombectomy is associated with an outcome. DWI reversal or no growth translated to a favorable outcome. Small initial ischemic core, good collateral support, and better recanalization grades predict the smaller infarct growth and favorable outcome after endovascular thrombectomy., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: We investigated whether brain natriuretic peptide (BNP) levels could be used as a marker to predict recurrent stroke in ischemic stroke survivors., Methods: From April 2007 to March 2011, consecutive patients within 24h of onset of ischemic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up to 12 months after stroke onset. Patients were divided into two groups: the recurrence group and the non-recurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis., Results: A total of 793 patients who were alive at hospital discharge were included; 42 (5%) patients had recurrent stroke. There were no differences in BNP levels between groups. With respect to 257 patients with atrial fibrillation (AF), BNP levels were significantly higher in the recurrence group than in the non-recurrence group (426.0 vs. 192.0 pg/mL, P = 0.0007). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the non-recurrence group were 300.0 pg/mL, 80%, and 73%, respectively. After adjustment for age and sex, plasma BNP ≥ 300.0 pg/mL (OR, 9.2; 95% CI, 1.87-45.01, P = 0.0062) was found to be independently associated with recurrent stroke in stroke survivors with AF., Conclusion: Admission BNP levels can predict recurrent stroke in stroke survivors with AF., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This study compared the detection rate of ischemic lesions within 3 hours of onset by computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DWI). The study group comprised 130 patients (71 men; median age, 75 years) with an anterior territory stroke who underwent CT and DWI within 3 hours of onset. The lesions revealed on CT and DWI were assessed using the CT-Alberta Stroke Program Early CT Score (ASPECTS) and DWI-ASPECTS, and detection rates were compared for each ASPECTS region. The detection rate of ischemic lesions was higher on DWI than on CT (76.9% v 30.0%; P < .001). The DWI-ASPECTS score was not correlated with the CT-ASPECTS score (r = 0.51; P < .001). Ischemic lesions were detected in the insula (59.2% for DWI vs 15.4% for CT; P < .001), lentiform nucleus (43.8% v 20.0%; P < .001), and the M1 (30.8% v 6.9%, P < .001), M2 (50.8% v 6.2%; P = .006), M3 (28.5% v 3.1%; P = .006), M4 (32.3% v 6.9%; P < .001), M5 (48.5% v 10.8%; P < .001), and M6 (31.5% v 4.6%, P = .012) areas of the middle cerebral artery. DWI detected ischemic lesions significantly more frequently than CT in all ASPECTS regions except the caudate head and internal capsule., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

A diffusion-weighted imaging (DWI) lesion changed dramatically in a hyperacute stroke case treated with intravenous tissue-plasminogen activator (IV t-PA). The initial hyperintense lesion on DWI disappeared completely immediately after IV t-PA treatment without improvement of neurological symptoms. However, the lesion reappeared 24 hours later. Successful thrombolysis can resolve DWI lesions but does not always improve the neurological symptoms., (Copyright © 2011 by the American Society of Neuroimaging.)

Background and Purpose: The symptoms of about 30% of acute ischemic stroke patients progress, but the mechanism and predictors of the deterioration are not well known. The augmentation index (AIx), estimated with the arterial pulse waveform, is known to be pathophysiologically relevant to the pathogenesis of cardiovascular diseases. The aim of the present study was to investigate the prognostic value of the AIx for early symptom progression (ESP) in patients with acute ischemic stroke., Methods: Acute ischemic stroke patients admitted to our stroke center within 24h from onset were prospectively enrolled. The AIx was measured within 48 h from admission. ESP was defined as ≥ 2 increase in the NIHSS score during 7 days from admission. All patients were divided into 2 groups according to the ESP (the ESP group and the non-ESP group)., Results: A total of 147 patients (79 males, median age 74 [IQR 64-82]years, and NIHSS score 3 [1-7]) were enrolled. ESP was observed in 23 (16%) patients. There were no differences in clinical characteristics including the AIx between the two groups. However, when only cases with lacunar and atherothrombotic strokes were evaluated, the AIx was higher in the ESP group (37.0 [32.0-38.0]%) than in the non-ESP group (29.5 [21.8-33.3]%, p=0.003). With the optimal cut-off value of >36%, the AIx was independently associated with ESP (OR 37.3, 95% CI 1.71-811, p=0.021)., Conclusion: The AIx level was independently related to ESP in patients with acute lacunar and atherothrombotic strokes. The AIx may have a potential to predict ESP in these patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background and Purpose: The frequency of good outcome at 3 months after tissue plasminogen activator (t-PA) therapy is ∼35%. The present study aimed to devise a simple scale to predict good outcome using clinical factors and magnetic resonance imaging (MRI) findings before and immediately after t-PA infusion., Methods: Consecutive patients with acute ischemic stroke treated with t-PA within 3 hours of stroke onset were studied prospectively. We assessed clinical factors independently associated with good outcome [modified Rankin scale (mRS): 0-1] at 3 months after t-PA therapy. We created a simple scale to predict good outcome in t-PA patients using factors selected by multivariate logistic regression analysis., Results: Subjects comprised 105 patients (69 men; median age, 74 years). Multivariate logistic regression analysis revealed the following independent factors associated with good outcome: baseline National Institutes of Health Stroke Scale (NIHSS) <11 [odds ratio (OR), 13·64; 95% confidence interval (CI), 3·588-51·822; P = 0·0001], glucose <150 mg/dl (OR, 3·76; 95%CI, 1·014-13·963; P = 0·0475), and early recanalization within 1 hour after t-PA infusion (OR, 5·28; 95%CI, 1·179-23·656; P = 0·0296). Those three variables were selected for use in the good outcome scale, with NIHSS <11 as 2 points, glucose <150 mg/dl as 1 point, and early recanalization as 1 point. Frequencies of patients with good outcome for each score were as follows: score 0, 0·0%; score 1, 7·1%; score 2, 43·5%; score 3, 65·4%; and score 4, 71·4%. The C statistic for the score was 0·849 (95%CI, 0·776-0·922)., Conclusion: A simple clinical and MRI scale can predict good outcome in t-PA patients.

Background and Purpose: Detection rate of right-to-left shunt (RLS) may be lower in stroke patients with atrial fibrillation (AF) than in those without AF. This may be due to the mechanism of embolic stroke in AF patients that involves cardiac embolus rather than paradoxical embolism due to RLS. Patients with AF frequently have subclinical heart failure, resulting in elevated left atrial (LA) pressure, which may prevent opening of a patent foramen ovale (PFO). We aimed to investigate whether the detection rate of RLS in stroke patients with AF was affected by elevated LA pressure., Method: We enrolled consecutive acute stroke patients with AF and, as controls, consecutive acute stroke patients without AF. RLS was diagnosed using contrast transcranial Doppler. To assess LA pressure, the ratio of early mitral inflow velocity to diastolic mitral annular velocity (E/E') was measured using transthoracic echocardiography., Result: We enrolled 171 patients with AF (AF group, age, 78 years [IQR, 70-83]) and 171 patients without AF (control group, age, 73 years [IQR, 64-81]). RLS was observed less frequently in AF patients than in the control group (9% vs. 18%, p=0.024). E/E' ratio was higher in AF patients (13.1 [9.4-17.4] vs. 10.9 [8.2-13.7], p<0.001). Among controls, E/E' ratio did not differ between patients with and without RLS (11.8 [8.5-12.9] vs. 10.8 [8.0-13.9], p=0.884). Conversely, in AF patients, E/E' ratio was lower in patients with RLS than in those without RLS (9.0 [8.3-12.6] vs. 13.6 [10.2-18.1], p=0.008). Multivariate regression analysis demonstrated that E/E' ratio of <11.0 was an independently associated with RLS (OR 4.61, 95%CI 1.21-17.62, p=0.025)., Conclusion: RLS was detected less frequently in AF patients than in controls. Elevated LA pressure was associated with the absence of RLS in AF stroke patients and may prevent opening of a PFO., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Patients with atrial fibrillation (AF) and atrial thrombus are at high risk of thromboembolic events. We investigated whether BNP levels can serve as a biological marker of thrombus., Methods: We prospectively enrolled patients with AF within 7days of an ischemic stroke and transient ischemic attack (TIA). We measured BNP levels in all patients while they underwent transesophageal echocardiography (TEE) and then assigned them to groups based on the presence (positive group) or absence (negative group) of left atrial thrombus. Factors associated with atrial thrombus were investigated using multivariate logistic regression analysis., Results: Of the 67 (male, n = 40; mean age, 76.5 ± 11.1 years) enrolled patients, 17 (25.4%) had left atrial thrombus. The incidence of hypertension was significantly higher in the positive, than in the negative group (88.2% vs. 58.0%, p = 0.020). The BNP level was also significantly higher in the positive, than in the negative group (median (interquartile range) 189.8 (141.4-473.2) vs. 117.9 (70.3-187.1) pg/ml, p=0.012). The optimal cut-off value, sensitivity, and specificity of BNP levels to distinguish the positive, from the negative group were 140.0 pg/ml, 76.5%, and 62.0%, respectively. Multivariate logistic regression analysis demonstrated that a BNP concentration of>140.0 pg/ml (odds ratio, 5.62; 95% CI, 1.39-22.66, p = 0.015) was an independent factor associated with thrombus., Conclusion: Levels of BNP can serve as a marker of left atrial thrombus in acute ischemic stroke and TIA in patients with AF., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background and Purpose: atrial fibrillation (AF) is the most powerful predictor of early death in patients with acute ischaemic stroke. We investigated whether the plasma brain natriuretic peptide (BNP) level on admission can serve as a biological marker of in-hospital death in acute ischaemic stroke and transient ischaemic attack (TIA) patients with AF., Methods: we prospectively enrolled ischaemic stroke and TIA patients with AF within 24 h of onset and measured plasma BNP on admission. Patients were divided into two groups: the deceased group, who died during hospitalization, and the survival group. The factors associated with in-hospital death were investigated by multivariate logistic regression analysis., Results: a total of 221 patients with AF were enrolled. Death occurred in 24 (10.9%) patients. The mean ± SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group (714.1 ± 716.3 vs. 320.0 ± 380.7 pg/ml, P < 0.0001). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the deceased group from the survival group were 320 pg/ml, 79.2, and 69.0%, respectively. Multivariate logistic regression analysis demonstrated that age per 10 years increase (OR, 3.56; 95% CI, 1.728-7.346, P = 0.0006), internal carotid artery occlusion (OR, 10.20; 95% CI, 2.525-41.177, P = 0.0011), NIHSS score of >17 (OR, 4.68; 95% CI, 1.137-19.286, P = 0.0325), and plasma BNP level of > 320 pg/ml (OR, 4.74; 95% CI, 1.260-17.800, P = 0.0213) were independent factors associated with in-hospital death., Conclusion: the plasma BNP level on admission can predict in-hospital death in acute ischaemic stroke and TIA patients with AF.

Background and Purpose: In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization can improve patient outcome. Heart failure may result in reduction of brain perfusion, which limits the ability of the blood stream to wash out emboli. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. Most stroke patients with atrial fibrillation (AF) have elevated BNP levels. We investigated the relationships of plasma BNP levels before t-PA infusion and AF with early recanalization after t-PA infusion., Methods: Patients with a major brain artery occlusion were studied prospectively. MRAs were performed before and within 60 min after t-PA infusion. The relationship between BNP levels before t-PA infusion and the presence of AF with early recanalization was examined., Results: Seventy-nine patients (49 men; mean age, 75.5+/-10.4 years; ICA occlusion in 25 patients, M1 in 32, M2 in 13, PCA in 3, and BA in 6) were enrolled. Follow-up MRA within 60 min after t-PA infusion revealed recanalization in 35 (44.3%) patients and no recanalization in 44 (55.7%). Patients with AF (57.1% vs. 75.0%, P=0.0294) and BNP>150pg/dl (39.0% vs. 73.7%, P=0.0019) less frequently had early recanalization than those without AF and with BNP< or =150pg/dl. The combination of AF and BNP>150pg/ml was a useful predictor for no early recanalization (positive predictive value, 79.4%; negative predictive value, 62.2%; sensitivity, 61.4%; specificity, 80.0%)., Conclusion: The presence of AF and elevated BNP was associated with no early recanalization after IV-t-PA therapy. We should need further study to ascertain its predictive ability.

Background and Purpose: Congestive heart failure is a risk factor for ischemic stroke. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. We hypothesized that heart failure was associated with the onset of ischemic stroke patients with atrial fibrillation (AF)., Methods: Between June 2006 and December 2007, we prospectively enrolled consecutive acute ischemic stroke patients with AF within 24 h of onset. Plasma BNP was measured twice, on admission and on days 28 or at discharge. As a control, we measured plasma BNP of chronic phase of stroke outpatients with AF. We investigated whether plasma BNP was elevated in the acute phase of stroke., Results: One hundred and nine patients (58 females; mean age, 76.3 years) were enrolled in the present study. Mean+/-SD of NIHSS score on admission and mRS score at discharge were 12.6+/-8.3 and 3.7+/-1.8, respectively. The interval from stroke onset to plasma BNP measurement on admission was 6.8+/-6.3 h. Moreover, follow up BNP was measured at mean of 26+/-9 days after stroke onset. The plasma BNP level in the acute phase of stroke was significantly higher than that of the subacute phase of stroke (median (interquartile range, IQR) 299.0 (176.8-469.5) vs. 149.5 (68.1-347.0) pg/ml, p<0.001). There was no significant difference in plasma BNP level between the subacute phase of stroke and control group (median (IQR) 149.5 (68.1-347.0) vs. 165.0 (64.6-224.0) pg/ml, p=0.543)., Conclusion: Plasma BNP was elevated in the acute phase of stroke. Heart failure may be associated with the onset of ischemic stroke patients with AF.

Purpose: The present study investigated early recanalization rate of major occluded arteries after tissue plasminogen activator (t-PA) infusion using serial magnetic resonance angiography (MRA) studies., Methods: Consecutive stroke patients treated with t-PA within 3 h of onset were prospectively studied. Four serial MRA studies were conducted: before, immediately, 24 h and 5-7 days after t-PA infusion., Results: Initial MRA demonstrated occluded brain arteries in 64 patients: M1 occlusion, 30 patients; M2, 12, and internal carotid artery (ICA), 22. Combining M1 and M2 occlusion, the recanalization rates (complete and partial) were 52.3% (19.0 and 33.3%) within 1 h, 80.9% (47.6 and 33.3%) at 24 h and 87.8% (73.2 and 14.6%) 7 days after t-PA infusion. However, the recanalization rate of ICA occlusion was 31.8% (4.5 and 27.3%) within 1 h, 51.1% (14.3 and 47.6%) at 24 h and 66.7% (38.9 and 27.8%) 7 days after t-PA infusion. Complete recanalization rate at 24 h and 7 days was lower in ICA occlusion than M1 and M2 occlusion (p = 0.014 and p = 0.016)., Conclusion: Within 1 h after t-PA infusion, approximately half the patients with major arteries occlusion had early recanalization. ICA occlusion is resistant to intravenous t-PA therapy compared with middle cerebral artery occlusion., (Copyright 2009 S. Karger AG, Basel.)

We report a case of an acute stroke patient with pulmonary embolism (PE) caused by delayed-onset heparin-induced thrombocytopenia (HIT). She was treated with heparin to prevent neurological deterioration. However, 5 days after heparin had been given for 7 days, she developed PE. Heparin was re-started, but the platelet count decreased significantly, and a right ventricular thrombus appeared. She was finally diagnosed as having PE due to delayed-onset HIT because the HIT antibody was positive. When a patient develops thrombotic events during or after heparin therapy, the possibility of HIT should be considered.

Background and Purpose: Symptomatic intracranial hemorrhages are typically clinically catastrophic and occur more frequently with tissue plasminogen activator (t-PA) therapy compared to without t-PA therapy. However, it has been unclear whether asymptomatic intracranial hemorrhage has clinical implications., Methods: Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. Patients with symptomatic hemorrhages were excluded from the study. To identify the presence of early recanalization and intracranial hemorrhage, as well as to measure infarction volume, MRI examinations, including diffusion-weighted imaging, T2(), FLAIR, and MRA, were performed before and 1 h, 24 h, and 5-7 days after t-PA thrombolysis. At the same time, serial NIHSS scores were obtained. The independent predictors of dramatic recovery were determined using multivariate logistic regression analysis., Results: 51 patients were enrolled in the present study. 22 patients (H group) had an asymptomatic hemorrhage. The NIHSS score of the Non-H group decreased, but that of the H group did not (11.5+/-6.5 vs. 17.1+/-6.5 at baseline, and 4.5+/-6.8 vs. 14.3+/-7.6 at 7 days; P=0.0073 for ANOVA). Asymptomatic hemorrhage was more frequently seen in non-dramatic improvement group than in dramatic improvement group (65.5% vs. 13.6%, P=0.0002). On multivariate logistic regression analysis using the variables that had a P<0.1 on univariate analysis (AF, baseline NIHSS score, glucose, the presence of asymptomatic hemorrhage, ICA occlusion, early recanalization 1 h after t-PA infusion, and infarction volume 7 days after t-PA therapy), early recanalization (OR: 11.33; 95%CI: 1.064-120.704; P=0.044) and infarction volume <100 cm(3) (OR: 13.56; 95%CI: 1.020-180.125; P=0.048) were independent factors for dramatic improvement, while asymptomatic hemorrhage (OR: 0.03; 95%CI: 0.002-0.537; P=0.016) was an independent negative factor., Conclusion: Asymptomatic hemorrhage was an independent negative factor for dramatic improvement. Asymptomatic hemorrhage after t-PA thrombolysis may be associated with neurological recovery.

Background and Purpose: Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults., Methods: Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively., Results: Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (P<0.05) lower in transgenic mice (1.30+/-0.72, 1.12+/-0.04, and 14.0+/-7.7%, respectively) than in wild-type mice (2.56+/-0.93, 1.23+/-0.12, and 31.9+/-9.7%, respectively). Percentages of apoptotic cells were also significantly (P<0.001) lower in transgenic mice (cortex, 5.2+/-3.3%; hippocampus, 3.4+/-7.0%) than in wild-type mice (cortex, 41.1+/-16.9%; hippocampus, 58.9+/-15.3%)., Conclusions: These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia.