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Introduction: We investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan., Methods: This prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately., Results: The mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5-6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01-1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51-111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18-51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03-1.17), LVO (aOR: 14.88, 95%CI: 2.33-94.97), and log 10 D-dimer (aOR: 3.38, 95%CI: 1.01-11.26)., Conclusion: Upon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log 10 D-dimer., Registration: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age., Methods: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression., Results: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis., Conclusions: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine., 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: Y.Z. is an employee of Takeda Pharmaceutical Company Limited; however, Takeda Pharmaceutical Company Limited was not involved in this study. T.F. has been employed by the Department of Digital Health and Epidemiology, an Industry-Academia Collaboration Course supported by Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Real World Data Co., Ltd., and Mitsubishi Corporation; and has received consulting fees from Real World Data Co., Ltd. and speaker fees from Asahi Kasei Pharma Corporation and EPS Corporation. F.Y. declares no conflict of interest. M.T. received consulting fees from Eisai Co., Ltd. K.K. received research grants from Eisai Co., Ltd., Kyowa Kirin Co., Ltd., OMRON Corporation, and Toppan Inc.; consulting fees from Advanced Medical Care Inc., JMDC Inc., and Shin Nippon Biomedical Laboratories Ltd.; executive compensation from Cancer Intelligence Care Systems, Inc.; honoraria from Chugai Pharmaceutical Co., Ltd., and Pharma Business Academy.

Large-scaled post-marketing surveillance studies (PMSSs) of 4 direct oral anticoagulants (DOACs) for stroke prevention in non-valvular atrial fibrillation (AF) were conducted since 2011 in Japan, and the results of the last one have recently been published. Each reported a more than acceptable ischemic stroke prevention. The major bleeding rates were also acceptably low and comparable to each other in the PMSSs of dabigatran (J-dabigatran), rivaroxaban (XAPASS), and edoxaban (ETNA-AF-Japan). However, the incidence in PMSS of apixaban (STANDARD) was more than double the others. This finding appeared to contradict the globally accepted theory that apixaban is less likely than other DOACs to cause bleeding events. Possible responsible mechanisms included (1) the age and kidney function, (2) concomitant antiplatelet therapy, (3) drug actions, (4) follow-up duration, and (5) dose reduction criteria. Similarities in the clinical background shared by the 4 different PMSSs' participants and knowledge from previous studies did not support a dominant contribution of any of those former 4 factors to the increased major bleeding incidence in STANDARD. A possibility of the 5th factor was then examined. An estimated calculation we created showed that apixaban's dose reduction criteria was strict enough to considerably reduce the opportunity for participants to take its reduced rather than standard dose. We then successfully simulated how the "strict" dose reduction criteria would have increased the bleeding event rates under DOAC therapy. The discussion in this review may therefore raise a question about the validity of the current dose reduction criteria of apixaban for Japanese AF patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO., Methods: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days)., Results: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR., Discussion: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management., Classification of Evidence: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function., (© 2022 American Academy of Neurology.)

It has been reported that the incidence of epilepsy in individuals over the age of 75 years is similar to or higher than one year, suggesting that epilepsy is an important clinical condition in older people. The aging rate in Japan, which reached 27.3% in 2017, makes this an issue of increasing concern. Diagnosis begins with the collection of medical history and knowledge of seizure semiology. In the elderly, most seizures are of extratemporal origin with various seizure semiologies. Difficulties in diagnosis lie in the influence of the autonomic nervous system and nonconvulsive status epilepticus(NCSE). It is necessary to suspect "epilepsy" for any sudden-onset episodes of atypical symptoms and unusual behaviors. NCSE can be diagnosed by recording EEG for more than 6 hours. The narrow therapeutic window and pharmacokinetics complicated by aging make treatment much more difficult with anti-seizure medication(ASM). Comorbidities and drug interactions should also be considered. Stroke is the most common etiology of geriatric epilepsy. Despite several clinical reports on the risk factors of post-stroke epilepsy(PSE)on the preventive administration of enzyme-inducing ASM, a treatment protocol has not yet been established. Prophylactic administration is not recommended; however, ASM is often administered in the acute phase. Therefore, some guidelines for non-enzyme-inducing ASM are required for efficient control of PSE.

Background: The impact of prior antiplatelet therapy (APT) on clinical outcomes of endovascular therapy (EVT) for large vessel occlusion (LVO) on clinical outcomes is uncertain. We explored the associations between prior APT and in-hospital and 90-day outcomes in a real-world setting., Methods and Results: The RESCUE-Japan Registry 2 is a physician-initiated registry of 2408 consecutive patients with acute LVO admitted to hospital within 24 h of stroke onset. We compared 1281 patients who received EVT with and without APT before stroke onset (APT group and No-APT group) in terms of intracranial hemorrhage (ICH) within 72 h after the onset, successful recanalization after EVT, and the modified Rankin Scale (mRS) score 0-2 at 90 days were also evaluated. Among the 254 patients (19.8%) in the APT group, 68 (27%) patients presented any ICH and 265 (26%) patients in the No-APT group (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 0.71-1.53). The incidence of symptomatic ICH and successful recanalization were also similar between the APT and No-APT groups. The adjusted ORs of the APT group for mRS of 0-2 and death were 0.93 (95% CI, 0.62-1.41) and 0.59 (95% CI, 0.3-1.19), respectively. In patients with an onset to door time ≥ 180 min, any ICH tended to be more prevalent in the APT group than in their counterparts (P for interaction = 0.008)., Conclusions: The risk of ICH after EVT was not different between patients with and without APT before EVT for acute LVO., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: DS-1040 is a novel inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor that may have therapeutic potential in thromboembolic diseases, such as acute ischemic stroke (AIS) or pulmonary embolism. We undertook a Phase I clinical trial to investigate the safety, pharmacokinetics, and pharmacodynamics of DS-1040 in Japanese patients who were eligible for thrombectomy following AIS., Methods: The trial enrolled patients with AIS due to large vessel occlusion, who were planned for thrombectomy within 8 h of symptom onset. Subjects were randomized to receive a single intravenous infusion of placebo or DS-1040 (0.6, 1.2, 2.4 or 4.8 mg) in a sequential-cohort design. The primary endpoints were the incidence of intracranial hemorrhage (ICH) and major extracranial bleeding within 36 and 96 h, respectively, of treatment initiation. Treatment-emergent adverse events (TEAEs) and pharmacokinetic/pharmacodynamic parameters were also assessed., Results: Nine patients received placebo and 32 patients received DS-1040. There were no cases of symptomatic ICH or major extracranial bleeding with either placebo or DS-1040 after 36 and 96 h. One patient, who received DS-1040 0.6 mg, experienced a subarachnoid hemorrhage that was considered to be drug-related. Three patients died (2 placebo, 1 DS-1040), but no deaths were adjudicated as study drug-related. In vivo exposure to DS-1040 increased in proportion to dosage, but no clear dose-response relationship was seen for D-dimer levels and thrombin-activatable fibrinolysis inhibitor activity., Conclusions: Single doses of DS-1040 0.6-4.8 mg were well tolerated in Japanese patients with AIS undergoing thrombectomy., Clinical Trial Registration Number: NCT03198715; JapicCTI-163164., (© 2022. The Author(s).)

Limited information is available on anticoagulant-related nephropathy (ARN). We therefore reviewed the Japanese Adverse Drug Event Report database to investigate kidney injury (KI) in patients administered warfarin or direct oral anticoagulants (DOACs) and sought to clarify the risk factors for ARN. KI risk in warfarin users was associated with male sex (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.35-2.13; P < .01) and age ≥80 years (OR, 1.35; 95% CI, 1.07-1.72; P = .01). KI risk in DOAC users was associated with body weight ≥80 kg (OR, 1.60; 95% CI, 1.01-2.53; P = .04) and use of dabigatran (OR, 1.61; 95% CI, 1.09-2.37; P < .01). Our findings suggest that risk factors for ARN differ between warfarin and DOACs and that these risk factors may be associated with bleeding risk. Therefore, the risk of ARN may be decreased by better managing bleeding risk in patients taking anticoagulants., (© 2020 British Pharmacological Society.)

Background: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence., Methods: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined)., Results: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030)., Conclusions: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or funding sources to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We examined the impact of expansion of the time window (from 3 to 4.5 hours) in the labeled indication for recombinant tissue-plasminogen activator (rt-PA) in August 2012 on the use of rt-PA for patients with acute ischemic stroke (AIS) and the outcomes of patients treated with rt-PA., Materials and Methods: Using a Japanese nationwide inpatient claims database, we identified patients with AIS who admitted to hospitals that consecutively participated in the database from 2010 to 2014. We defined the pre-expansion period as before August 2012 and the post-expansion period as after August 2012. We conducted an interrupted time-series analysis using patient-level data to examine the association between the expansion and use of rt-PA. We also assessed the association of the expansion with outcomes in patients treated with rt-PA., Results: Among 257,778 patients with AIS, 4.5% patients (5,796/129,326) were treated with rt-PA in the pre-expansion period and 5.8% patients (7,483/128,452) were treated with rt-PA in the post-expansion period. The expansion was associated with greater use of rt-PA (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.24-1.48). Among patients treated with rt-PA, the expansion was associated with functional independence (modified Rankin scale of ≤2) at discharge (aOR, 1.26; 95% CI, 1.03-1.54), but not with in-hospital mortality (aOR, 0.92; 95% CI, 0.68-1.24)., Conclusions: This study showed that expansion of the time window for rt-PA was associated with increased use of rt-PA in patients with AIS, while the functional outcome at discharge was improved after the expansion in patients treated with rt-PA., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: There is scant data related to prehospital delay in cases of acute ischemic stroke from multicenter studies conducted after change of the therapeutic window of intravenous tissue plasminogen activator (iv-tPA) administration to within 4.5 h of onset. We investigated factors causing prehospital delay and their associations with clinical outcomes using data from a regional multicenter stroke registry., Methods: Data from the multicenter regional stroke registry were analyzed. Patients admitted within 24 h of the last known well time were categorized according to whether their admission was early (≤ 4 h; n = 2350) or delayed (> 4 h; n = 2752). We then compared patients' backgrounds and outcomes between the two groups., Results: Five-thousand, one-hundred two patients presented at hospitals within 24 h of onset. On multivariate analysis, atrial fibrillation, higher NIHSS score on admission, anterior circulation stroke, detection of symptoms immediately after onset, and emergency system use were positively associated with early admission, whereas modified Rankin Scale (mRS) score before onset, onset at home, diabetes, current smoking, dementia and symptom detection between 00:00 and 06:00 h were negatively associated. Early admission was associated with mRS scores of 0-2 at discharge independent of backgrounds, stroke severity, and thrombolytic therapy (odds ratio, 1.56; 95% confidence interval, 1.32-1.84)., Conclusions: Certain patient factors relating to prehospital delay, such as lack of awareness of onset or non-cardioembolic etiology, are crucial but often inevitable. However, earlier admission was associated mRS scores of 0-2 independent of other factors. This study may help to plan educational activities to general population or public awareness campaigns., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Although the number of seemingly healthy subjects who suffer a minor stroke increases, there are no data on how frequently they sustain another stroke while driving., Methods: A single-center, retrospective study was conducted to clarify the clinical characteristics of driving-related stroke occurring as a recurrent stroke by analyzing data prospectively acquired between January 2009 and June 2019 on 3452 acute stroke patients., Results: One hundred-thirty five patients (85 ischemic stroke [IS] and 50 hemorrhagic stroke [HS]) had suffered a driving-related stroke. Of them, 22 (16%) had suffered a prior stroke (recurrent stroke group), while 113 had never suffered a stroke before (first-time stroke group). While the use of anti-thrombotics was significantly more common in the RS group, other variables including the frequency of road traffic accidents, did not differ significantly. The first stroke-recurrent stroke interval ranged from 0.2 to 18 years. The stroke type at the time of recurrence was IS in the majority of patients with prior IS. When compared to 432 patients with recurrent IS unrelated to driving, patients with recurrent IS related to driving (n = 16) had significantly higher frequency of lacunar strokes (56% vs 27%, P = .02) and lower frequency of cardioembolic strokes (6% vs 29%, P = .04)., Conclusion: The current finding that 16% of patients who presented with driving-related stroke had previously suffered a stroke indicates that drivers with a prior stroke may be at increased risk for recurrent stroke while driving, and prolonged follow-up be necessary for minor stroke patients who resume driving., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The safety of prasugrel in elderly and/or low body weight Japanese patients with ischemic stroke who have a relatively high bleeding risk with antiplatelet therapy remains unknown., Objective: We aimed to investigate the safety and efficacy of long-term prasugrel monotherapy for stroke prevention compared with clopidogrel in elderly and/or low body weight Japanese patients with non-cardioembolic ischemic stroke., Methods: In this randomized, double-blind, comparative, phase III study, elderly (age ≥75 years) and/or low body weight (≤50 kg) Japanese patients with a previous history of non-cardioembolic ischemic stroke were assigned to a prasugrel 3.75 mg (PRA3.75) group, a prasugrel 2.5 mg (PRA2.5) group, or a clopidogrel 50 mg (CLO50) group and followed up for 48 weeks. The primary safety endpoint was the combined incidence of primary safety events, defined as life-threatening, major, and other clinically relevant bleeding. The efficacy endpoint was a composite of ischemic stroke, myocardial infarction, and death from other vascular causes., Results: A total of 654 patients (age 76.4 ± 7.3 years, body weight 55.6 ± 9.3 kg, women 43.9%) from 74 medical institutions within Japan were enrolled. The combined incidence (95% CI) of primary safety events was 4.2% (1.9-7.8%), 1.9% (0.5-4.7%), and 3.6% (1.6-6.9%) in the PRA3.75 group (n = 216), PRA2.5 group (n = 215), and CLO50 group (n = 223), respectively (hazard ratios [HR] PRA3.75/CLO50, 1.13 [0.44-2.93]; PRA2.5/CLO50, 0.51 [0.15-1.69]). The incidences of bleeding leading to treatment discontinuation (95% CI) were 2.3% (0.8-5.3%), 0.9% (0.1-3.3%), and 2.2% (0.7-5.2%) in the PRA3.75, PRA2.5, and CLO50 groups, respectively (HRs PRA3.75/CLO50, 1.01 [0.29-3.48]; PRA2.5/CLO50, 0.41 [0.08-2.12]). There was no significant difference in all bleeding events between groups. The incidence of ischemic stroke, myocardial infarction, and death from other vascular causes was lower, but not significantly so, in patients treated with prasugrel than in patients treated with clopidogrel: PRA3.75, 0.0% (0/216); PRA2.5, 3.3% (7/215); and CLO50, 3.6% (8/223; HRs PRA3.75/CLO50, 0.00 [0.00-0.00]; PRA2.5/CLO50, 0.90 [0.32-2.47])., Conclusions: Elderly and/or low body weight -Japanese patients with previous non-cardioembolic ischemic stroke who received PRA3.75 showed similar results in terms of primary safety endpoint, and a numerically lower incidence of ischemic stroke, myocardial infarction, and death from other vascular causes, compared with those who received CLO50., (© 2020 The Author(s)Published by S. Karger AG, Basel.)

Background: Previous small studies conducted around 2000 suggested an association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and a reduction in post-stroke aspiration pneumonia (AP) in Japan. However, it is unclear whether receiving ACEIs can reduce post-stroke AP in the current clinical environment, where stroke management has been improved. This study aimed to re-evaluate the preventive effect of ACEIs on post-stroke AP, compared with that of angiotensin II receptor blockers (ARBs)., Methods: Using the Japanese Diagnosis Procedure Combination database, we identified patients who were hospitalized for stroke and developed AP during hospitalization from July 2010 to December 2016. After applying the exclusion criteria, we performed 1:1 propensity score matching between patients receiving ACEIs and those receiving ARBs after discharge. The outcomes were 14-day, 30-day, and 90-day readmission for post-stroke AP among patients with stroke who had AP during their initial hospitalization. Cox regression was performed to analyze these readmissions., Results: In total, 35,586 eligible patients were identified. Of these patients, 5846 (16%) received ACEIs. Propensity score matching created 5789 pairs. No significant difference was seen in 14-day readmission (0.7% versus 0.8%), 30-day readmission (1.3% versus 1.3%), or 90-day readmission (2.4% versus 2.6%) between the ARB and ACEI groups. The hazard ratio of the ACEI group compared with the ARB group was not significant (1.21; 95% confidence interval: 0.98-1.48)., Conclusions: In this retrospective nationwide study, ACEIs could not be concluded to have a preventive effect on post-stroke AP in the current clinical environment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Guideline-adherent antithrombotic treatment (ATT) reduces the risk of stroke and death in patients with atrial fibrillation (AF). However, the effect of ATT adherence among different ethnicities remains uncertain. We compared the prognosis of AF patients in Japan and the UK according to guideline adherence status.Methods and Results:We compared the clinical characteristics and outcomes of AF patients from the Fushimi AF registry (Japan; n=4,239) and the Darlington AF registry (UK; n=2,259). ATT adherence was assessed against the Japanese Circulation Society Guidelines and UK National Institute for Health and Care Excellence guidelines. The rates of guideline-adherent ATT were 58.6% and 50.8% in the Fushimi and Darlington registries, respectively. There was no significant difference in 1-year stroke rates between Fushimi and Darlington (2.6% vs. 3.0%, P=0.342). On multivariate logistic regression analysis, non-guideline adherent-ATT was significantly associated with an increased risk of stroke (odds ratio [OR]: 1.69, 95% confidence interval [CI]: 1.21-2.34, P=0.002 for undertreatment, OR: 2.13, 95% CI: 1.19-3.80, P=0.010 for overtreatment). No significant interaction for ATT and the 2 populations was found in the incidence of stroke, all-cause death, and the composite outcome., Conclusions: Approximately half of the AF patients received optimal ATT according to guideline recommendations, which was associated with a lower risk of stroke. Furthermore, there was no interaction for the 2 populations and the influence of ATT adherence.

Background: Intravenous recombinant tissue plasminogen activator (rt-PA) has become a common treatment for acute ischemic stroke and has highly time-dependent benefits. We aimed to clarify temporal trends regarding the frequency and characteristics of patients receiving rt-PA and explore factors associated with door-to-needle time (DNT) in Japanese emergency hospitals., Methods: Consecutive patients who received intravenous rt-PA for acute ischemic stroke from October 2005 to December 2015 were retrospectively registered from 4 hospitals. Temporal trends in the frequency and characteristics of patients receiving rt-PA and factors associated with DNT were investigated., Results: A total of 750 patients, including 688 (420 men, median 75 years old) with out-of-hospital stroke, were registered. The frequency of patients receiving intravenous rt-PA for acute ischemic stroke continuously increased from 1.8% in 2005 to 9.5% in 2015. The proportion of patients who were elderly or had prestroke disability increased over time, while pretreatment stroke severity declined. The DNT gradually decreased (median 105 minutes in 2005, 61 minutes in 2015). According to multivariate regression analysis with correction for multiple comparisons, activation of a code stroke system (standardized partial regression coefficient (β) -.50, P < .001, q < .001), onset-to-door time (β -.15, P < .001, q < .001), pretreatment with antithrombotic agents (β .12, P < .001, q = .001), and year of treatment (β .11, P = .007, q = .011) were associated with DNT., Conclusions: Intravenous rt-PA was widely adopted in Japanese emergency hospitals. Characteristics of patients receiving intravenous rt-PA have changed over the past decade. Several factors, including the year of treatment, were associated with DNT, which has shortened over time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- Stroke is the most frequent severe clinical event in patients with Fabry disease. We aimed to evaluate the cerebral magnetic resonance imaging findings of patients with Fabry disease and assess their association with future stroke risk after enzyme replacement therapy (ERT) induction. Methods- We retrospectively reviewed the magnetic resonance imaging findings of 25 patients with Fabry disease. Of these, 12 adult patients without prior stroke or ERT were enrolled to evaluate the association between baseline magnetic resonance imaging findings and stroke occurrence after ERT initiation. We assessed white matter hyperintensities, periventricular hyperintensities, and basilar artery diameter as neuroimaging markers. Results- The mean age of participants was 38.8±16.8 years. Fourteen patients (56.0%) were women. White matter hyperintensities and periventricular hyperintensities were observed in 15 and 13 cases, respectively. The mean basilar artery diameter was 3.2±0.55 mm. Two patients demonstrated old infarct lesions. Three of 12 patients in whom ERT was initiated had symptomatic stroke after baseline magnetic resonance imaging. Of these, 2 developed stroke within 6-month post-ERT initiation. The baseline basilar artery diameter was larger in patients who developed stroke than in those who did not (4.0±0.40 versus 2.9±0.49 mm, P=0.02). Conclusions- Basilar artery diameter may be associated with stroke risk after ERT initiation among Japanese patients with Fabry disease.

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: The effect of prasugrel in terms of the prevention of recurrence of ischaemic stroke is unknown. We investigated the non-inferiority of prasugrel to clopidogrel for prevention of ischaemic stroke, myocardial infarction, and death from other vascular causes in Japanese patients with non-cardioembolic stroke., Methods: In this phase 3 randomised, double-blind, non-inferiority trial, patients aged 20-74 years who had had a non-cardioembolic stroke in the previous 1-26 weeks were recruited from 224 hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive prasugrel (3·75 mg/day) or clopidogrel (75 mg/day) orally for 96-104 weeks. Randomisation was stratified according to stroke subtype. The randomisation schedule was generated by an independent statistician who created a computer-generated random number sequence. Patients, investigators, and the funder were masked to treatment allocation. The primary endpoint was combined incidence of ischaemic stroke (fatal and non-fatal), myocardial infarction (fatal and non-fatal), and death from other vascular causes in the intention-to-treat population. The safety endpoint was incidence of bleeding events, comprising life-threatening bleeding, major bleeding, and clinically relevant bleeding. The safety analysis was done in the population excluding trial patients with serious Good Clinical Practice violations, and those who had not taken the trial drug. The predefined non-inferiority margin was an upper 95% CI limit for the risk ratio (RR) of 1·35. The trial was registered with the Japan Pharmaceutical Information Center (JapicCTI-111582)., Findings: Patients were recruited between Sept 1, 2011, and June 12, 2015. 3747 patients (797 [21%] women) were enrolled, with a mean age of 62·1 (SD 8·5) years. 3753 patients were randomly assigned to treatment and, of these patients, 1885 in the prasugrel group and 1862 in the clopidogrel group were confirmed to have taken the trial drug at least once, and six patients withdrew from the trial before administration of the trial drug. Thus, a total of 3747 patients were included in the full analysis set. 73 (4%) of 1885 patients in the prasugrel group and 69 (4%) of 1862 patients in the clopidogrel group reached the primary endpoint (RR 1·05, 95% CI 0·76-1·44). The incidence of bleeding events was not significantly different between treatment groups; life-threatening bleeding was observed in 18 (1%) patients in the prasugrel group and 23 (1%) patients in the clopidogrel group (RR 0·77, 0·41-1·42)., Interpretation: The non-inferiority of prasugrel to clopidogrel for the prevention of ischaemic stroke, myocardial infarction, and death from other vascular causes was not confirmed in Japanese patients with non-cardioembolic stroke. No safety concerns were identified., Funding: Daiichi Sankyo., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Purpose- Although several clinical studies suggested the beneficial effects of edaravone in acute ischemic stroke, most were performed under settings that differ from those in the current treatment strategy, which has dramatically changed with progress in reperfusion therapies. This study aimed to evaluate the efficacy of edaravone in patients with acute ischemic stroke treated by emergent endovascular reperfusion therapy. Methods- We conducted a retrospective observational study using a national administrative database. Patients with acute ischemic stroke treated by emergent endovascular reperfusion therapy were identified and dichotomized by whether edaravone was used within 2 days of admission. We compared the functional independence at hospital discharge, in-hospital mortality, and intracranial hemorrhage after admission between groups, adjusted by a well-validated case-mix adjustment model, in multivariate mixed-effect regression and propensity score matching analyses. Results- Of 11 508 patients eligible for analysis, 10 281 (89.3%) received edaravone therapy. The established risk adjustment model had good predictability for functional independence at hospital discharge, with an area under the receiver operating characteristic curve of 0.74. In the mixed-effect regression analysis, edaravone use was significantly associated with greater functional independence at hospital discharge (32.3% in the edaravone group versus 25.9% in the control group; adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.41), lower in-hospital mortality (9.9% in the edaravone group versus 17.4% in the control group; adjusted odds ratio, 0.52; 95% confidence interval, 0.43-0.62), and reduced intracranial hemorrhage after admission (1.4% in the edaravone group versus 2.7% in the control group; adjusted odds ratio, 0.55; 95% confidence interval, 0.37-0.82). Results of the propensity score matching analysis corroborated these results. Conclusions- This retrospective analysis of a Japanese nationwide administrative database suggested that combination therapy with edaravone and endovascular reperfusion therapy could be a promising therapeutic strategy in acute ischemic stroke. Further randomized control trials are warranted.

Importance: It is unknown whether poststroke outcome varies between different potential causes in patients with cryptogenic stroke., Objective: To investigate whether functional outcome differs according to potential embolic sources after cryptogenic stroke., Design, Setting, and Participants: This multicenter, hospital-based, prospective stroke registry cohort study investigated potential embolic sources on admission and assessed 3-month outcome in patients with ischemic stroke hospitalized at 7 stroke centers in the Fukuoka Stroke Registry. This registry enlisted 9866 consecutive patients with acute ischemic stroke who were enrolled from June 11, 2007, to May 31, 2016, in Fukuoka, Japan. Patients with small vessel occlusion (n = 3130), extracranial and intracranial atherosclerosis causing at least 50% luminal stenosis in arteries supplying the area of ischemia (n = 2011), and other specific uncommon causes of stroke identified (n = 301) were excluded. Potential embolic sources were diagnosed in patients with embolic stroke of undetermined source (ESUS) based on the following criteria proposed by the Cryptogenic Stroke/ESUS International Working Group: minor-risk potential cardioembolic sources (MCS) (n = 209), covert paroxysmal atrial fibrillation (CPAF) (n = 43), cancer associated (CA) (n = 79), arteriogenic emboli (AE) (n = 522), paradoxical embolism (PE) (n = 190), and undetermined embolism (unidentified or ≥2 potential embolic sources) (UE) (n = 1120)., Main Outcomes and Measures: The association between potential causes and functional outcome was evaluated in reference to cardioembolic stroke (CE) caused by major-risk cardioembolic sources after adjusting for age, sex, National Institutes of Health Stroke Scale score on admission, and reperfusion therapy using logistic regression analysis. Functional dependency (modified Rankin Scale score, 3-5) was evaluated at 3 months after onset., Results: The study enrolled 2261 patients with CE (mean [SD] age, 78.4 [10.7] years, 51.8% male) and 2163 patients with ESUS (mean [SD] age, 72.4 [12.6] years, 57.1% male). Compared with CE (median National Institutes of Health Stroke Scale score, 8 [interquartile range {IQR}, 3-17]), baseline neurological deficits did not differ in MCS (median, 7 [IQR, 2-18]), CPAF (median, 6 [IQR, 2-18]), and CA (median, 5 [IQR, 2-13]) but were less severe in AE (median, 2 [IQR, 1-4]), PE (median, 2 [IQR, 1-4]), and UE (median, 3 [IQR, 1-7]). Multivariable-adjusted odds ratios of functional dependency significantly increased in CA (3.61; 95% CI, 1.52-8.54 vs CE) but decreased in PE (0.33; 95% CI, 0.16-0.71 vs CE)., Conclusions and Relevance: Potential causes are associated with poststroke outcome in patients with cryptogenic stroke. Embolic sources potentially underlying cryptogenic stroke should be considered significant variables associated with outcome.

Background: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS 2 and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users., Conclusions: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

Background: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH., Methods: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg., Results: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032)., Conclusions: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH., (© 2018 S. Karger AG, Basel.)

Background and Purpose: The effect of statins on progression of carotid intima-media complex thickness (IMT) has been shown exclusively in nonstroke Western patients. This study aimed to determine the effect of low-dose pravastatin on carotid IMT in Japanese patients with noncardioembolic ischemic stroke., Methods: This is a substudy of the J-STARS trial (Japan Statin Treatment Against Recurrent Stroke), a multicenter, randomized, open-label, parallel-group trial to examine whether pravastatin reduces stroke recurrence. Patients were randomized to receive pravastatin (10 mg daily, usual dose in Japan; pravastatin group) or not to receive any statins (control group). The primary outcome was IMT change of the common carotid artery for a 5-year observation period. IMT change was compared using mixed-effects models for repeated measures., Results: Of 864 patients registered in this substudy, 71 without baseline ultrasonography were excluded, and 388 were randomly assigned to the pravastatin group and 405 to the control group. Baseline characteristics were not significantly different, except National Institutes of Health Stroke Scale scores (median, 0 [interquartile range, 0-2] versus 1 [interquartile range, 0-2]; P =0.019) between the 2 groups. Baseline IMT (mean±SD) was 0.887±0.155 mm in the pravastatin group and 0.887±0.152 mm in the control group ( P =0.99). The annual change in the IMT at 5-year visit was significantly reduced in the pravastatin group as compared with that in the control group (0.021±0.116 versus 0.040±0.118 mm; P =0.010)., Conclusions: The usual Japanese dose of pravastatin significantly reduced the progression of carotid IMT at 5 years in patients with noncardioembolic stroke., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00361530., (© 2017 The Authors.)

Although a wide range of strategies have been established to improve intravenous tissue plasminogen activator (IV-tPA) treatment rates, international benchmarking has not been regularly used as a systems improvement tool. We compared acute stroke codes (ASC) between two hospitals in Australia and Japan to study the activation process and potentially improve the implementation of thrombolysis. Consecutive patients who were admitted to each hospital via ASC were prospectively collected. We compared IV-tPA rates, factors contributing to exclusion from IV-tPA, and pre- and in-hospital process of care. IV-tPA treatment rates were significantly higher in the Australian hospital than in the Japanese (41% versus 25% of acute ischaemic stroke patients, p=0.0016). In both hospitals, reasons for exclusion from IV-tPA treatment were intracerebral haemorrhage, mild symptoms, and stroke mimic. Patients with baseline National Institutes of Health Stroke Scale score⩽5 were more likely to be excluded from IV-tPA in the Japanese hospital. Of patients treated with IV-tPA, the door-to-needle time (median, 63 versus 54minutes, p=0.0355) and imaging-to-needle time (34 versus 27minutes, p=0.0220) were longer in the Australian hospital. Through international benchmarking using cohorts captured under ASC, significant differences were noted in rates of IV-tPA treatment and workflow speed. This variation highlights opportunity to improve and areas to focus targeted practice improvement strategies., (Copyright © 2016. Published by Elsevier Ltd.)

Clinical data from Japan on the safety and real-world outcomes of alteplase (tPA) thrombolysis in the extended therapeutic window are lacking. The aim of this study was to assess the safety and real-world outcomes of tPA administered within 3-4.5 h of stroke onset. The study comprised consecutive acute ischemic stroke patients (n = 177) admitted across five hospitals between September 2012 and August 2014. Patients received intravenous tPA within <3 or 3-4.5 h of stroke onset. Endovascular therapy was used for tPA-refractory patients. In the 3-4.5 h subgroup (31.6 % of patients), tPA was started 85 min later than the <3 h group (220 vs. 135 min, respectively). However, outcome measures were not significantly different between the <3 and 3-4.5 h subgroups for recanalization rate (67.8 vs. 57.1 %), symptomatic intracerebral hemorrhage (2.5 vs. 3.6 %), modified Rankin Scale score of 0-1 at 3 months (36.0 vs. 23.4 %), and mortality (6.9 vs. 8.3 %). We present data from 2005 to 2012 using a therapeutic window <3 h showing comparable results. tPA following endovascular therapy with recanalization might be superior to tPA only with recanalization (81.0 vs. 59.1 %). Compared with administration within 3 h of ischemic stroke onset, tPA administration within 3-4.5 h of ischemic stroke onset in real-world stroke emergency settings at multiple sites in Japan is as safe and has the same outcomes.

Background and Purpose: Argatroban, a selective thrombin inhibitor, is recommended for the use in patients with atherothrombotic stroke by the Japanese Guidelines for the Management of Patients with Acute Ischemic Stroke. We performed a nationwide Japanese study to investigate whether argatroban improved early stroke outcomes in patients with acute atherothrombotic stroke., Methods: This retrospective observational study, using the Diagnosis Procedure Combination database in Japan, included patients who were hospitalized from July 1, 2010, to March 31, 2012, with a diagnosis of atherothrombotic stroke within 1 day of stroke onset. Patients were divided into 2 groups: those receiving argatroban on admission (argatroban group), and those who did not receive argatroban during hospitalization (control group). To balance the baseline characteristics and concomitant treatments during hospitalization between the 2 groups, one-to-one propensity-score matching analyses were performed. The main outcomes were the modified Rankin Scale score at discharge and the occurrence of hemorrhagic complications during hospitalization. An ordinal logistic regression analysis evaluated the association between argatroban use and modified Rankin Scale at discharge., Results: After propensity-score matching, 2289 pairs of patients were analyzed. There were no significant differences in modified Rankin Scale at discharge between the argatroban and the control groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.88-1.16). The occurrence of hemorrhagic complications did not differ significantly between the argatroban and the control groups (3.5% versus 3.8%; P=0.58)., Conclusions: The present study suggested that argatroban was safe, but had no added benefit in early outcomes after acute atherothrombotic stroke., (© 2015 American Heart Association, Inc.)

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: Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients., Methods: This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints., Finding: Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events., Interpretation: Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis., Funding: This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

Background: Large clinical trials are lack of data on non-vitamin K antagonist oral anticoagulants for acute stroke patients., Aim: To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry (ClinicalTrials.gov NCT01581502)., Method: The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23-day stay) was assessed., Results: Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10-month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS2 , CHA2 DS2 -VASc, and HAS-BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four-days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20-day or shorter hospitalization (OR 2·46, 95% CI 1·87-3·24)., Conclusions: Warfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia-risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe., (© 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.)

Background: Predicting a day that presents a high risk for the occurrence of ischemic stroke events may enable health professionals to prepare for emergency stroke therapy more properly. We evaluated the association between meteorological conditions and the frequency of ischemic stroke events in Japanese patients., Methods: Ischemic stroke patients (n = 299) who were treated with alteplase at 9 stroke hospitals in 3 restricted areas were examined. The daily rates of ischemic stroke events were compared with the daily mean thermo-hydrological index (THI), the atmospheric pressure, and the daily changes of these variables for the 6 days preceding an ischemic stroke event using Poisson regression analysis., Results: We trisected onset days based on the THI (low-temperature, intermediate-temperature, and high-temperature), atmospheric pressure (low-pressure, intermediate-pressure, and high-pressure), changes in THI for preceding 6 days from the previous day (cooler, unchanged-temperature, and warmer), and changes in atmospheric pressure (decreased-pressure, unchanged-pressure, and increased-pressure). The frequency of ischemic stroke was significantly higher on low-temperature or high-pressure days (risk ratio, 1.398, P = .022; risk ratio, 1.374, P = .039), on warmer-temperature days, and when atmospheric pressure varied from the day before (P < .05). There were significantly lower risks for ischemic stroke events on cooler-temperature days, and higher risks were associated with a variation in atmospheric pressure 3 days before the onset from 4 days before (P < .05)., Conclusions: There were higher risks for ischemic stroke events associated with low ambient temperature, high atmospheric pressure, increased temperature, and varied atmospheric pressure. Also, atmospheric pressure variation 3 days before may be associated., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Stroke-bypass transportation to the stroke center by paramedics is important to maximize the efficiency of intravenous tissue plasminogen activator (iv-tPA) therapy. To improve access to stroke thrombolysis, a citywide protocol was launched on January 2007 in Kawasaki City (population 1.4 million) using the Maria Prehospital Stroke Scale (MPSS), and quality assurance monitoring has been performed every 6 months. The aim was to identify whether the citywide quality assurance monitoring improves the process and outcome of iv-tPA therapy., Methods: All of the MPSS-based transportation data prospectively recorded by the Kawasaki City Fire Department and the associated clinical data in the 11 hospitals that accept stroke-bypass transfers were merged every 6 months for the quality assurance monitoring. Clinical indicators such as ambulance call-to-door time, onset-to-needle time, door-to-needle time, frequency of thrombolytic use, and outcome of thrombolytic therapy were analyzed. These clinical indicators were also compared between patients transferred on weekdays and on weekends., Results: A total of 2049 patients was registered from April 2009 to March 2013. Their mean age was 70.4 ± 13.2 (range, 24-98) years, and 64.3% were male. Ambulance call-to-door time decreased gradually from 37.5 ± 12.5 minutes to 33.9 ± 11.7 minutes over 4 years (P = .000, analysis of variance with the post hoc Dunnett test). Onset-to-needle time and door-to-needle time were similar over the 4 years. Good outcome (modified Rankin Scale score <2) after iv-tPA therapy increased from 24.1% to 35.3% (P = .045, 2010 vs. 2012). No deleterious effect of weekend admission was observed based on these clinical indicators., Conclusions: A citywide MPSS-based transportation protocol significantly decreased the delay in the ambulance call-to-door time. The implementation of standardized cross-institutional quality assurance programs for acute stroke therapy may improve the process and outcome of iv-tPA therapy in the community., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: There is controversy whether the annual number of acute ischemic stroke patients receiving stroke thrombolysis per hospital (hospital volume) is associated with outcomes in these patients., Aims: The study aims to assess the relationship between hospital volume and early outcomes in acute ischemic stroke patients treated with recombinant tissue plasminogen activator., Methods: Patients with acute ischemic stroke treated with recombinant tissue plasminogen activator from July 1, 2010 to March 31, 2012 were identified in the Japanese Diagnosis Procedure Combination database. Hospital volume was categorized into three levels (low, medium, and high volume) to obtain approximately equal numbers of patients in each group. Primary outcomes were seven-day mortality and functional independence (modified Rankin Scale score of 0 to 2) at discharge. Univariate analyses and multivariate logistic regression analyses fitted with generalized estimating equations were performed., Results: We identified 7476 eligible patients, including 2339 (31·3%) treated in low-volume hospitals (1-7 patients annually), 2670 (35·7%) in medium-volume hospitals (8-16 patients annually), and 2467 (33·0%) in high-volume hospitals (17-48 patients annually). Seven-day mortality and functional independence at discharge were comparable among the three hospital volume groups (P = 0·17 for seven-day mortality; P = 0·22 for functional independence at discharge). The comparability between groups persisted after multivariate adjustment., Conclusion: Hospital volume was not significantly associated with seven-day mortality or functional independence at discharge in acute ischemic stroke patients treated with recombinant tissue plasminogen activator in Japan., (© 2014 World Stroke Organization.)

Rationale: Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5 h from symptom onset., Aims: The THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg trial aims to determine the efficacy and safety of intravenous thrombolysis with alteplase at 0·6 mg/kg body weight, the approved dose for Japanese stroke patients, using magnetic resonance image-based selection in ischemic stroke patients with unclear time of symptom onset, and compare findings with standard treatment., Design: This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-end-point clinical trial. The design is similar to the Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke trial. Patients with unclear-onset time of stroke symptoms beyond 4·5 h and within 12 h after the time of the last-known-well period and within 4·5 h after symptom recognition, who showed a negative fluid-attenuated inversion recovery pattern, are randomized to either intravenous thrombolysis or standard treatment., Study Outcomes: The primary efficacy end-point is modified Rankin Scale 0-1 at 90 days. The safety outcome measures are symptomatic intracranial hemorrhage at 22-36 h, and major bleeding and mortality at 90 days., Discussion: This trial may help determine if low-dose alteplase at 0·6 mg/kg should be recommended as a routine clinical strategy for ischemic stroke patients with unclear-onset time., (© 2014 World Stroke Organization.)

Background: The presence or absence of the penumbra area is important when performing reperfusion therapy in patients with acute ischemic stroke. As a predictor of this penumbra area, magnetic resonance angiography (MRA)-diffusion-weighted imaging (DWI) mismatch is attracting attention. The usefulness of MRA-DWI mismatch (MDM) using the DWI-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) in endovascular treatment (EVT) of patients with cerebral large vessel occlusion was evaluated., Methods: Of 1442 patients registered in the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Registry between July 1, 2010 and June 30, 2011 who presented to the hospital within 24 hours of the onset of acute cerebral infarction because of cerebral large vessel occlusion, 188 patients who had internal carotid artery or middle cerebral artery occlusion and achieved recanalization with EVT were included. Of these, 71 patients underwent intracranial EVT because intravenous recombinant tissue plasminogen activator therapy was ineffective. The associations between the presence or absence of MDM (MDM-positive [MDM-P], DWI-ASPECTS≥6; MDM-negative [MDM-N], DWI-ASPECTS<6) and 90-day prognosis (modified Rankin Scale [mRS]) and symptomatic intracranial hemorrhage (sICH) were examined., Results: Of the 188 patients analyzed, the time from symptom onset to admission was within 3 hours in 143 patients, 3-8 hours in 36 patients, and 8 hours or more in 9 patients. The time from the onset was within 3 hours in 118 patients in the MDM-P and 25 patients in the MDM-N cases. Favorable outcomes (mRS score≤2 at 90 days) were seen in 63 patients (53.4%) in the MDM-P group and 7 patients (28.0%) in the MDM-N group, showing a significantly more favorable clinical outcome in the MDM-P group (P=.027). The incidence of sICH was significantly lower in the MDM-P group (MDM-P group 3.4%, MDM-P group 20.0%; P=.009). The time from the onset was 3-8 hours in 29 patients in the MDM-P group and in 7 patients in the MDM-N group. Favorable outcomes were seen in 12 patients (41.4%) in the MDM-P group and 2 patients (28.6%) in the MDM-N group, with no significant difference between the 2 groups. No patients had sICH. The patients admitted 8 hours or more after the onset were all MDM-P. Five patients (55.6%) had a favorable outcome., Conclusions: This study demonstrated the safety and efficacy of EVT in MDM-P patients within 3 hours of symptom onset. Although the ratio of patients who had a favorable outcome was high in the MDM-P patients admitted 3-8 hours after the onset, the difference was not significant., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The concept of telestroke networks has been proposed to overcome regional disparities in stroke treatment. Such networks do not yet operate in Japan. We aimed to determine the specific needs for telestroke networks and to estimate the effects on the number of thrombolytic therapies. Five of the 47 Japanese prefectures with various population densities to estimate the nationwide effect of telestroke networks were selected. The questionnaire survey was administered at hospitals in these prefectures that are authorized to admit patients with acute stroke. Low-volume hospitals that annually treated fewer than 12 patients with acute stroke had never used tissue plasminogen activator (tPA). The number of days when telestroke support might have been needed varied depending on the size of the population aged 65 years or older within a 30-minute-driving-time area of a hospital and the annual number of patients treated within 3 hours of onset. The geographic information system analysis showed that .6%-8.3% of the population lived in areas where they could not reach a hospital for acute stroke treatment within 60 minutes. If 24/7 full telestroke support was introduced to the existing hospitals, 6.8-69.3 more patients could be treated by intravenous (IV) tPA annually. These numbers exceeded the estimated annual increases of .8-13.7 more patients if a drip-and-ship telestroke network was introduced into an underserved area outside the 60-minute-driving-time area. This study uncovered that many Japanese stroke hospitals, especially low-volume facilities located in rural areas, do not perform IV tPA therapy in 24/7 fashion and telestroke support to these hospitals may be highly effective compared with the drip-and-ship network in an underserved area., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The use of intravenous tissue plasminogen activator (t-PA) can be an effective treatment for acute ischemic stroke if administered promptly. Despite its clinical effectiveness, overall use in Japan remains low, and regional variations have been reported. Factors such as ambulance utilization and geographical distance from patients' residences to hospitals may influence t-PA administration rates. The aim of this study is to identify factors associated with the administration of t-PA for acute ischemic stroke while adjusting for casemix using a large-scale administrative database in Japan., Methods: We analyzed acute ischemic stroke patients admitted to acute care hospitals between July 2010 and March 2011 using a nationwide database. A logistic regression model was used to analyze the factors influencing t-PA administration. Candidate factors included patient gender, age, stroke severity, direct distance between each patient's residence and admitting hospital, and ambulance utilization., Results: Of the 10,615 ischemic stroke patients from 89 hospitals analyzed, 557 (5.2%) received t-PA treatment. Patients aged 75 years and older were found to be associated with decreased t-PA administration. In contrast, severe stroke and ambulance utilization were associated with increased t-PA administration. Distance was not significantly associated with the use of t-PA., Conclusions: Our findings suggest that ambulance utilization is an important factor for improving the likelihood of t-PA administration in patients with stroke and may underline a need for educational programs to the general public that promote the use of ambulances for suspected stroke patients., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

We report two cases of stroke associated with the use of finasteride at 1 mg/day, which is approved in Japan for the treatment of male-pattern hair loss. The first case involved a 35-year-old male taking 1 mg of finasteride daily for 6 months to prevent male-pattern hair loss. He was taken to a hospital and later admitted to our hospital owing to headache and seizures. Brain computed tomography (CT) images showed a low-density area in the right frontal lobe. CT venography (CTV) revealed sinus thrombosis and he was treated with an anticoagulant. As the headache gradually subsided, medications were tapered and terminated 10 months later when venous flow to the sagittal sinus and left transverse sinus was confirmed to be recanalized. The second case involved a 41-year-old male taking 1 mg of finasteride and 6 mg of minoxidil daily for 1 year for male-pattern hair loss. He started having headaches and was admitted to our hospital when diffusion-weighted images of brain magnetic resonance imaging (MRI) showed a high-intensity area in the left parietotemporal lobe. He was treated with antiplatelet and anticoagulation medicines. The Japan Pharmaceutical and Medical Devices Agency (PMDA) has reported 14 cases of thrombosis in patients taking finasteride in Japan; 4 cases of stroke (our 2 cases and 2 reported by PMDA), 6 cases of myocardial infarction, and 4 cases of other thrombotic diseases. Increases in estrone and estradiol levels in prostate cancer patients and controls receiving 5 mg of finasteride have been reported. Gynecomastia has also been reported as one of the adverse effects of finasteride at 1 mg or 5 mg daily. Taken together, we assume that the increases in estrone and estradiol levels induced by finasteride lead to thrombosis development.

Background and Purpose: The findings of recent clinical trials suggest that treatment with high-dose statins reduces the risk of stroke recurrence. However, the doses approved in Japan are much lower than those in the previous studies. This study aimed to elucidate whether prescribed doses of statins reduce the risks of cerebrovascular events (CVEs: stroke recurrence or transient ischemic attack) and all-cause mortality in a cohort of Japanese patients with first-ever ischemic stroke., Methods: The 2822 eligible patients registered in the Fukuoka Stroke Registry with first-ever acute ischemic stroke from June 2007 to February 2011 were classified into statin users (n = 993) and non-users (n = 1829) at discharge, and followed up until March 2012. We assessed the cumulative risks of CVE and all-cause mortality by the Kaplan-Meier method, and calculated hazard ratios (HRs) and 95% confidential intervals (CIs) using the Cox proportional hazards model., Results: During the follow-up time (median, 2.0 years), 305 patients had CVEs and 345 died. The cumulative risks of CVE and death after 4 years were significantly lower in statin users than in non-users (13.8% versus 19.5%, P = 0.005 for CVE; 11.8% versus 21.7%, P < 0.001 for death). After adjusting for multiple confounding factors, statin treatment significantly reduced the risks of CVE (HR, 0.70; 95% CI, 0.53 to 0.92; P = 0.011) and all-cause mortality (HR, 0.67; 95% CI, 0.50 to 0.89; P = 0.006)., Conclusions: Our findings suggest that low-dose statin may reduce the risks of CVE and death in Japanese patients with acute ischemic stroke., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

To assess the predictive value of cerebral microbleeds (CMBs) on gradient-echo T2*-weighted magnetic resonance imaging for hemorrhagic transformation (HT) after antithrombotic therapy for an acute ischemic stroke, we prospectively examined the relationship between CMBs on T2*-weighted images before the start of therapy and the appearance of HT in a series of patients treated with antithrombotic therapies. The subjects were consecutive acute ischemic stroke patients admitted to Tokai University Hospital (187 subjects, mean age±SD: 74±11 years). The prevalence of CMBs was not significantly different between the subjects with and without HT on computed tomography (CT) (19% versus 36%, P=.081). In both the subgroup of patients treated with anticoagulants and the subgroup treated with antiplatelets, the prevalence of HT was not significantly different between the subjects with and without CMBs (anticoagulants, 9% versus 21%, P=.161; antiplatelets, 0% versus 9%, P=.542). The odds ratios (ORs) of increasing the National Institutes of Health Stroke Scale score (1.14, 95% confidence interval [CI]: 1.04-1.26, P=.005) and decreasing the Alberta Stroke Program Early CT Score on diffusion-weighted images (ASPECTS-DWI) (1.32, 95% CI: 1.10-1.59, P=.003) were significantly increased for the appearance of HT, but the OR of CMBs (.35, 95% CI: .09-1.41, P=.140) was not significantly increased for the appearance of HT. In conclusion, the severity of neurological deficits and the ASPECTS-DWI are closely correlated to the development of HT related to anticoagulants/antiplatelets but not to CMBs on T2*-weighted images., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

In Japan, stroke is a major cause of death and serious long-lasting neurological disabilities. Recently, the diagnosis and treatment of ischemic stroke has changed greatly. 1) Patients with TIA are more susceptible to ischemic stroke, and the susceptibility is predicted by the ABCD2score. 2) Brain natriuretic peptide (BNP) is a hormone released from the ventricular myocardium; BNP levels can predict new atrial fibrillation during hospitalization in patients with acute ischemic stroke. 3) In Japan, thrombolysis with intravenous recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke was approved in 2004, and the time window was extended up to 4.5 h in 2012. 4) Several novel oral anticoagulants (NOAC) have been developed over the last decade; the early initiation of NOACs in acute stroke and TIA patients with nonvalvular atrial fibrillation may be safe. More evidence-based treatment for stroke in Japanese people should be established.

Objective: Central post-stroke pain(CPSP)is the most difficult type of central neuropathic pain to control with medical treatment. Opioids are commonly used for chronic neuropathic pain, but their efficacy in treating central neuropathic pain, particularly CPSP, is not clear. Tramadol is an opioid analgesic that, in combination with acetaminophen, has been approved since 2011 for the treatment of non-cancer pain in Japan. In this study we evaluated the efficacy of tramadol/acetaminophen medication for CPSP., Methods: We retrospectively reviewed nine cases of CPSP that received oral tramadol/acetaminophen medication. All cases received tramadol/acetaminophen medication after first taking pregabalin then antidepressant medication. Pain levels were assessed before tramadol/acetaminophen medication began and one month after a maintenance dose was reached, using a visual analogue scale(VAS)and the McGill pain questionnaire(MPQ)., Results: The mean dose of tramadol was 121±61.6 mg/day. Tramadol/acetaminophen medication was effective in reducing pain in seven of nine cases(77.8%). The VAS improved 32.9±13.8% from pre-to post-medication, and the MPQ improved from 15.4±9.1 pre-medication to 8.1±4.7 post-medication(p<0.05). These effects continued 9.3±4.5 months during follow up periods. Side effects were observed in six cases(one severe, one moderate, two mild, two transient), but medication was continued in eight cases., Conclusion: Oral tramadol/acetaminophen medication was effective at reducing pain levels in patients with CPSP, and is a medication option for the treatment of CPSP.

Background: Various factors that have been implicated in recovery after the acute phase of stroke have not been well evaluated., Methods: To identify prognostic factors affecting outcomes at 90 days after stroke from the viewpoint of recovery patterns, we enrolled 660 patients from the Edaravone and Argatroban Stroke Therapy for Acute Ischemic Stroke study database. Fourteen groups of patients were identified based on an analysis of their recovery patterns according to changes in their National Institutes of Health Stroke Scale scores during the first 21 days. These groups were then divided into 2 groups: favorable recovery trend (patterns 1-3; n = 486) and poor recovery trend (patterns 4-14; n = 174). Patterns with >80% of the patients experiencing a favorable outcome (National Institutes of Health Stroke Scale score of ≤ 4 at 90 days) were defined as the favorable recovery trend group, whereas patterns that included ≤ 80% favorable outcomes were defined as the poor recovery trend group., Results: Using the poor recovery trend group, logistic regression analysis found that after controlling for covariates, lower scores at admission, fewer ischemic lesions, and nonsmoking were significant prognostic factors for a favorable outcome at 90 days., Conclusions: Based on a detailed analysis of the relationship between recovery patterns after stroke and clinical outcomes in the chronic stage of stroke, smoking cessation may improve the prognosis of patients after stroke., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: It has been suggested that antiplatelet or anticoagulant drugs elevate the rate of intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (MBs). To investigate the mechanism by which antiplatelet drugs or warfarin may contribute to deep ICH occurrences in patients with deep MBs, we prospectively analyzed deep ICH occurrences in 807 consecutive patients (351 females and 456 males; mean age ± standard deviation 69.8 ± 12.0 years) who were admitted to our hospital with strokes., Methods: Occurrence-free rate curves were generated using the Kaplan-Meier method; deep ICH occurrence-free rates were compared using the log-rank test. The follow-up period was 0.5 to 71 months (mean ± standard deviation 31.6 ± 22.2 months)., Results: In patients with deep MBs, the rates (1.0%/year; 6 ICHs in 180 patients) of deep ICH occurrence associated with antiplatelet drugs were not significantly greater than that without the drugs (1.0%/year; 6 ICHs in 167 patients; P = .977). The incidence of deep ICHs associated with warfarin use was not significantly greater than that without warfarin use., Conclusions: Multivariate analysis revealed that the use of antiplatelet drugs or warfarin did not significantly influence the occurrence of deep ICH in patients with deep MBs. Antiplatelet drugs or warfarin did not significantly elevate the rate of deep ICHs in stroke patients with pre-existing deep MBs., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

In Japan, intravenous alteplase, a recombinant tissue-type plasminogen activator (rt-PA), was approved for an indication of ischemic stroke in 2005 on the basis of the results of a clinical trial with a unique dose of the drug (0.6 mg/kg). The Japan Stroke Society published the guidelines for intravenous application of rt-PA and organized training sessions for proper use all over Japan in an effort to promote the safe, widespread use of intravenous alteplase. Seven years following its approval, clinical experience with intravenous alteplase has accumulated, additional evidence of intravenous alteplase has been found in Japan and overseas, and the medical environment has substantially changed, including approvals for new drugs and medical devices. Notably, the use of alteplase in the extended therapeutic time window (within 4.5 hours of symptom onset) became covered by insurance in Japan in August 2012. To address these changing situations, we have decided to prepare the revised guidelines. In preparing the second edition, we took care to make its contents more practical by emphasizing information needed in clinical practice. While the first edition was developed with emphasis on safety in light of limited clinical experience with intravenous alteplase in Japan in 2005, this second edition is a substantial revision of the first edition mainly in terms of eligibility criteria, on the basis of accumulated evidence and the clinical experience., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

There is no prehospital stratification tool specifically for predicting thrombolytic therapy after transportation. We developed a new prehospital scale named the Maria Prehospital Stroke Scale (MPSS) by modifying the Cincinnati Prehospital Stroke Scale. Our objective is to evaluate its utility in a citywide bypass transportation protocol for intravenous (IV) tissue plasminogen activator (tPA). In the MPSS, facial droop, arm drift, and speech disturbance are tested by emergency medical technicians (EMTs). Facial droop is graded as normal (0) or abnormal (1), and the other 2 items are graded in 3 levels as normal (0), not severe (1), and severe (2). Thus, the total MPSS score ranges from 0 to 5. The predictive value of MPSS for thrombolytic therapy after bypass transportation was evaluated in 1057 patients. The MPSS scored by EMTs was significantly correlated with the National Institutes of Health Stroke Scale score in the emergency room (Spearman rho = .67, P = .000). The onset-to-door time was significantly longer with a low MPSS score (analysis of variance, F5,4.21 = .001). The rate of thrombolytic therapy was increased when the MPSS score increased from 0 to 5: 0%, 4.1%, 8.8%, 13.0%, 20.3%, and 31.5%, respectively. The areas under the receiver operating characteristic curve for the correct diagnosis of stroke and prediction of IV tPA therapy were calculated as .737 (95% confidence interval [CI]: .688-.786) and .689 (95% CI: .645-.732), respectively. Multivariate logistic regression analysis showed that the MPSS score and the detection-to-door time were independent predictors of tPA use after transportation. The MPSS is a novel prehospital stratification tool for the prediction of thrombolytic therapy after transportation., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to devise a scale comprising a simple multiplication of initial National Institutes of Health Stroke Scale (NIHSS) score and onset-to-treatment time (OTT) as a scale for predicting outcomes after recombinant tissue plasminogen activator (rt-PA) therapy., Methods: Data from rt-PA patients in 10 stroke centers in Japan were investigated. NIHSS-time score was calculated as initial NIHSS score×OTT., Results: Subjects comprised 526 patients. Median NIHSS score was 12 (7-18), and median OTT was 2.42 h (2.00-2.75 h). Median NIHSS-time score was 27.7 (16.9-41.7). Good (modified Rankin Scale [mRS] 0-1) and poor (mRS 4-6) outcome rates at 3months for patients with NIHSS-time scores ≤ 10 were 71.1% and 7.8%, compared to 54.7% and 16.5% for scores >10 and ≤ 20, 38.9% and 31.9% for scores >20 and ≤ 30, 25.0% and 44.6% for scores >30 and ≤ 40, and 17.4% and 61.8% for scores >40, respectively. Cut-off NIHSS-time scores to predict good and poor outcomes with 50% probability were defined as 20 and 40, respectively. Multivariate logistic regression analysis revealed NIHSS-time score as an independent predictor of good (odds ratio [OR], 0.587; 95% confidence interval [CI], 0.422-0.818, p=0.002) and poor (OR, 1.756; 95%CI, 1.227-2.514, p=0.002) outcomes after adjusting for age, sex, NIHSS score, OTT, Alberta Stroke Program Early CT Score, internal carotid artery occlusion, and glucose level., Conclusions: NIHSS-time score predicts clinical outcomes in rt-PA patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In October 2005 in Japan, the recombinant tissue plasminogen activator (tPA) alteplase was approved for patients with acute ischemic stroke within 3 hours of onset at a dose of 0.6 mg/kg. The present study was undertaken to assess the safety and efficacy of alteplase in Japan. Between October 2005 and December 2009, a total of 114 consecutive patients admitted to 4 hospitals received intravenous tPA within 3 hours of stroke onset. Clinical backgrounds and outcomes were investigated. The patients were divided into 2 chronological groups: an early group, comprising 45 patients treated between October 2005 and December 2007, and a later group, comprising 69 patients treated between January 2008 and December 2009. The mean time from arrival at the hospital to the initiation of treatment was significantly reduced in the later group, from 82.6 minutes to 70.9 minutes. Intracerebral hemorrhage (ICH) occurred in 26 patients (22.8%); compared with patients without ICH, these patients had a significantly higher prevalence of cardiogenic embolism (88.5% vs 58.0%); greater warfarin use (26.8% vs 6.8%); higher mean National Institutes of Health Stroke Scale (NIHSS) scores on admission (16 vs 10), at 3 days after admission (14 vs 5), and at 7 days after admission (13.5 vs 3); and a lower Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score (7.8 vs 9.1). Patients who received edaravone had a higher prevalence of cardiogenic embolism (70.9% vs 36.4%), a higher recanalization rate (77.7% vs 36.4%), and lower NIHSS scores on admission and at 3 and 7 days after admission compared with those who did not receive edaravone. Our data suggest that administration of intravenous alteplase 0.6 mg/kg within 3 hours of stroke onset is safe and effective, that the NIHSS and Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score are useful predictors of ICH after tPA administration, and that warfarin-treated patients are more likely to develop symptomatic ICH despite an International Normalized Ratio <1.7., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)