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Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion.We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes.322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186).Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non‐Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator‐initiated, prospective, multicenter (34 hospitals in Japan), randomized, open‐label, and aspirin‐controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61–77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1–4) in both groups ( P =0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group ( P =0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group ( P =0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short‐term neurological worsening. Clinical Trial Registration URL : umin.ac.jp/ctr/index/htm. Unique identifier: UMIN 000004950.

Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group.

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

Objectives The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. Design The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. Conclusions The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Background and Purpose— Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants’ data meta-analysis. Methods— We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants’ data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index. Results— From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up. Conclusions— Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification.

We herein report a case of ischemic stroke in a 69-year-old man with unilateral moyamoya vessels originating from the proximal portion of the left middle cerebral artery. In addition, digital-subtraction angiography demonstrated a string-of-beads-like appearance in the cavernous portion of the left internal carotid artery. A genetic analysis revealed a heterozygous c.14576G>A variant in ring finger protein 213. The patient's younger brother had a history of hemorrhagic stroke and had been diagnosed with moyamoya disease. We finally considered that the unilateral moyamoya vessel and string-of-beads appearance observed in the current case were not simply caused by atherosclerosis, but rather represented symptoms within the moyamoya spectrum.

Background Half of acute stroke patients have poor outcomes at 3 months even when treated with intravenous thrombolysis using tissue-plasminogen activator (t-PA) therapy. The aim of the present study was to evaluate the impact of the susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) T2* at the proximal portion of the middle cerebral artery (M1 proximal SVS) on clinical outcome in anterior circulation stroke patients treated with t-PA. Methods The presence of the M1 proximal SVS was assessed before t-PA therapy. Good outcome and poor outcome at 3 months were defined as a modified Rankin Scale score of 0 to 2 and 4 to 6, respectively. The predictive values of the M1 proximal SVS for a good and poor outcome were calculated. Results 161 patients (median age [interquartile], 76 [67–83] years; male, 91 [57%]) were enrolled. At 3 months after stroke, 68 (42%) patients achieved a good outcome, and 75 (47%) had a poor outcome. The M1 proximal SVS was found in 17 (11%) patients, of whom none (0%) achieved a good outcome, and 16 (94%) had a poor outcome. The sensitivity and positive predictive value of the M1 proximal SVS for good outcome were very low (0.000 and 0.000, respectively). Furthermore, the specificity and positive predictive value of the M1 proximal SVS for poor outcome were very high (0.988 and 0.941, respectively). Conclusion The M1 proximal SVS appears to be a strong predictor for poor outcome after t-PA therapy.

Background: Chronic kidney disease (CKD) is associated with cerebral small vessel diseases (SVD) and predicts stroke, cardiovascular events and mortality. However, its association with recent small subcortical infarcts (RSSI), a novel subtype of cerebral SVD, has not yet been established in stroke patients. The aim of this longitudinal study was to clarify whether CKD can predict clinical outcome in patients with RSSI. Methods: We enrolled patients with first-ever RSSI (formerly categorized as acute lacunar stroke). CKD was defined as an estimated glomerular filtration rate of 2 on admission. The patients were divided into two groups according to the presence or absence of CKD. The endpoints were recurrent stroke, cardiovascular events or all-cause mortality. The patients were followed up at 3, 6 and 12 months after stroke onset and yearly thereafter. Event-free survival analysis was undertaken using Kaplan-Meier plots and the log-rank test. Cox's proportional-hazards analysis was conducted regarding age, sex and the presence of any cerebral SVD. Results: A total of 152 patients (66% males; mean age: 67.6 years) were consecutively enrolled, and 44 (29%) had CKD. During the follow-up period (median: 3 years; interquartile range: 1-4), 27 patients (18%) reached endpoints. The numbers of patients per endpoint were as follows: all-cause mortality 14, ischemic stroke 9, hemorrhagic stroke 2 and aortic dissection 2. Patients with CKD were significantly older (77 vs. 64 years; p < 0.001), had higher serum creatinine (0.96 vs. 0.65 mg/dl; p < 0.001), higher brain natriuretic peptide (51.1 vs. 18.5 pg/ml; p < 0.001) and a higher National Institutes of Health Stroke Scale score on admission (3 vs. 2; p < 0.001), and were less likely to have modified Rankin Scale scores of 0-2 after stroke onset (52 vs. 77%; p = 0.003). Patients with white matter hyperintensity [odds ratio (OR) 3.0; 95% confidence interval (CI): 1.5-6.2; p = 0.003] and those with microbleeds (OR 2.5; 95% CI: 1.2-5.1; p = 0.015) had more pronounced CKD than the remaining patients. A Kaplan-Meier curve analysis showed that patients with CKD had a less favorable outcome than those without CKD (p < 0.001). The multivariate Cox proportional-hazards analysis revealed that CKD was associated with recurrent stroke, cardiovascular events or all-cause mortality (hazard ratio 2.22; 95% CI: 1.12-4.25; p = 0.02). Conclusions: CKD was found to be independently associated with recurrent stroke, cardiovascular events or all-cause mortality in patients with RSSI.

The frequency and clinical characteristics of intractable hiccups due to the medullary infarction is unknown. The aim of this study was to identify the lesions of hiccups using by brain MRI. Ninety acute medullary patients admitted to our stroke center within 14 days of stroke onset between April 2004 and August 2012 were retrospectively studied. We evaluated clinical characteristics and the frequency of the patients causing intractable hiccups among acute medullary stroke patients. We divided the patients into two groups, intractable hiccups group, and not hiccups group. Of 90 patients, five (5.5%) had intractable hiccups. Hiccups group had more frequently involved right middle medullary lesion than not hiccups group (hiccups group vs. not hiccups group; (60% vs. 4%, p < 0.001). In 16 cases reported the lesion of intractable hiccups, the right middle medullary lesion was 11 cases. We suspected that the lesion of the intractable hiccups was associated with the right middle medullary.

Background and Purpose: The purpose of the present study was to test the hypothesis that plasma brain natriuretic peptide (BNP) is associated with short-term mortality after intracerebral hemorrhage (ICH). Methods: We prospectively enrolled 271 patients (median age 72 years; 109 females) who were admitted within 24 h of ICH onset between April 2007 and July 2011 and in whom plasma BNP levels were measured upon admission. The patients were assigned to two groups according to survival within 1 month of ICH. Factors associated with mortality were determined by multivariate logistic regression analysis. Results: Within 1 month of ICH, 48 (17.7%) of the 271 enrolled patients died. The median (interquartile range) level of plasma BNP was significantly higher in the group of non-survivors than in the group of survivors [102.5 (48.7-205.0) vs. 32.4 (17.3-85.0) pg/ml; p < 0.001]. A cutoff BNP level of 60.0 pg/ml could predict death within 1 month of ICH. Multivariate logistic regression analysis showed that a plasma BNP of >60.0 pg/ml (OR 4.7; 95% CI 1.43-15.63; p = 0.011) was independently associated with mortality within 1 month after ICH. Conclusions: A high BNP level upon admission is associated with mortality within 1 month after ICH.

The purpose of this study was to examine the frequency and characteristics of re-exacerbation of stroke symptoms within 24 hours after tissue plasminogen activator (t-PA) infusion.We studied consecutive stroke patients treated with t-PA within 3 hours of onset of symptoms admitted between October 2005 and March 2010. We divided patients into 4 groups: improvement (IM; improvement in National Institutes of Health Stroke Scale [NIHSS] ≥4 points), unchanged (UN; no change or decline in NIHSS4 points), exacerbation (EX; decline in NIHSS ≥4 points), and re-exacerbation (RE-EX; decline of NIHSS ≥4 points accompanied by re-exacerbation of neurologic symptoms in NIHSS ≥4 points). We compared clinical characteristics among the 4 groups.Two hundred twenty-two patients (135 men; median age 76 years) were enrolled. Sixteen of the 222 (7%) were in the RE-EX group. Small vessel disease (SVD), hemorrhagic cerebral infarction, and reocclusion were significantly more common among patients in the RE-EX group. SVD, hemorrhagic cerebral infarction, and reocclusion occurred in 44%, 25%, and 13% of patients in the RE-EX group, in 9%, 22%, and 0% of patients in the EX group, in 5%, 6%, and 0% of patients in the IM group, and in 17%, 14%, and 1% of patients in the UN group, respectively (P .001, P = .041, and P .001). Multivariate logistic regression analysis revealed that SVD was the only independent factor associated with re-exacerbation within 24 hours after t-PA infusion (odds ratio 3.52; 95% confidence interval [CI] 1.19-10.40; P = .023).Seven percent of patients re-exacerbated within 24 hours after intravenous infusion of t-PA. Re-exacerbation within 24 hours after t-PA infusion was strongly associated with SVD.

Transient neurological attacks (TNAs) are attacks with temporary (< 24 h) neurological symptoms, and reported in 1975. Ischemic cerebral infarction often occurres after transient neurological symptoms which are not sometimes involved in transient ischemic attack (TIA) criteria. The purpose of this study was to clarity transient neurological symptoms before the onset of ischemic stroke. Consecutive acute stroke and TIA patients within 7 days of onset between July 2011 and December 2012 were studied. Questionnaire survey of transient neurological symptoms was done and we investigated the history of transient neurological symptoms and divided the patients into three groups, TIA group (history of TIA), TNAs group (history of TNAs), and no past history group. We compared clinical characteristics, the rate of posterior circulation lesions, and number of attacks among three groups. 184 patients (male 112 patients, mean 73 years old) were enrolled into the present study. TNAs group had 13 (7%) patients, and TIA had 20 (11%). Neurological symptoms of TNAs group were 5 (38%) transient dizziness, 3 (23%) disturbance of consciousness, 2 (23%) weakness of legs, 1 (8%) sensory disturbance of legs, 1 (8%) gait disturbance, and 1 (8%) sensory disturbance of lips. Five (38%) TNAs group had multiple attacks. In 33 transient neurological symptom patients, 17 (52%) patients did not have hospital visit, and 7 (21%) patient did not have antiplatelet and anticoagulant drug. TNAs group more frequently had hyperlipidemia, diabetes mellitus, and posterior circulation lesions among three groups. 20% posterior circulation lesion patients had TNAs history, and posterior circulation might be examined in TNAs patients.

Background and purpose Sleep-disordered breathing (SDB) is a risk factor for stroke. The frequency of SDB in Japanese patients with acute intracerebral hemorrhage (ICH) was investigated, as well as factors associated with SDB severity. Methods Between April 2010 and April 2013, patients with ICH within 24 h of onset were prospectively enrolled to participate in a sleep study within 7 days of admission. SDB was defined as a respiratory disturbance index (RDI: apnea or hypopnea events per hour) of ≥5. Patients were assigned to groups based on RDI values of ≥30 (severe SDB) and

Background and Purpose— It is unknown whether new-extraischemic microbleeds (new-EMBs) develop rapidly after tissue-type plasminogen activator (tPA) infusion. We hypothesized that new-EMBs may develop rapidly after tPA infusion using T2*-weighted MRI (T2*) and investigated the frequency and clinical factors associated with new-EMBs. Methods— Patients with acute stroke within 3 hours of onset who were treated with tissue-type plasminogen activator (tPA) were studied prospectively. T2* was performed before and 24 hours after tPA therapy. Independent clinical factors associated with new-EMBs development were examined using multivariate logistic regression analysis. Results— A total of 224 patients (121 men; mean age, 76.2±10.6 years) were enrolled in the present study. MBs before tPA infusion were observed in 72 (32.1%) patients. Within 24 hours after tPA infusion, 6 (2.7%) patients had symptomatic intracranial hemorrhage (extraischemic [n=4], and hemorrhagic transformation [n=2]). Follow-up T2* revealed asymptomatic new-EMBs in 11 (4.9%) patients and hemorrhagic transformation in the infarcted area in 65 (29.0%). The total and mean number of new-EMBs were 23 and 1.6±1.3, respectively. Patients with new-EMBs more frequently had symptomatic extraischemic hemorrhage than those without new-EMBs (27.3% [3/11] versus 0.5% [1/213]; P =0.0003). However, the frequency of hemorrhagic transformation was not different between patients with and without new-EMBs (27.3% versus 29.1%; P =0.9999). Multivariate logistic regression demonstrated that the presence of MBs before tPA infusion was the only independent factor associated with new-EMBs (odds ratio, 10.6; 95% confidence interval, 20.68–54.279; P =0.0046). Conclusions— New-EMBs occurred rapidly after tPA infusion in 4.9% of patients. The presence of MBs before tPA therapy was associated with new-EMBs. Patients with new-EMBs are likely to have symptomatic extraischemic hemorrhage.

Background and purpose The aim of this study was to investigate whether early initiation of new oral anticoagulants (NOAC) for acute stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF) are safe. Methods Between March 2011 and September 2012, stroke or TIA patients with NVAF who started NOAC within 2 weeks were enrolled retrospectively. Symptomatic intracerebral hemorrhage (ICH), hemorrhagic transformation (HT) on T2⁎-weighted MRI, recurrence of stroke or TIA, systemic embolism and any bleeding complications after initiation of NOAC were evaluated. Results 41 patients (25 males; mean age 76.2 years) started NOAC; of which, 39 (95%) patients had stroke, and 2 (5%) had TIA. The median (interquartile range) interval from onset to treatment with NOAC was 2 (1–6) days. Symptomatic ICH was not observed. HT on initial T2⁎ and new HT on follow-up T2⁎ were 5 (12%) and 11 (31%), but it was asymptomatic. Of 5 patients who had HT on the initial T2⁎, enlargement of hemorrhage on follow-up T2⁎ (hemorrhagic infarction (HI) Type 1 → HI Type 2) was observed in 1 patient, but it was asymptomatic. None of the patients had recurrent stroke or TIA, systemic embolism, and any bleeding complications. Conclusions The NOAC may be safe in acute stroke or TIA patients with NVAF. A large, prospective study is needed to confirm this.

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 3 months 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.

Background and Purpose— In patients with middle cerebral artery trunk occlusion we investigated whether the diffusion-weighted imaging- the Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) predicts short-term neurological recovery after intravenous recombinant tissue plasminogen activator administration, and investigated how DWI-ASPECTS relates to clinical outcome. Methods— Dramatic recovery was defined as a ≥10-point reduction or a total National Institutes of Health Stroke Scale score of 0 to 1 at 24 hours and 7 days. Early recanalization was defined as recanalization within 1 hours after intravenous recombinant tissue plasminogen activator. Favorable outcome at 3 months was defined as a modified Rankin Scale score of 0 to 2. Results— Sixty-six patients (median age [interquartile], 79 [70–85] years, male; 34 [52%]) were enrolled. DWI-ASPECTS was 6 (5–9). Dramatic recovery was seen in 16 (24%) and 26 (39%) patients at 24 hours and on day 7, respectively. Early recanalization occurred in 22 (33%) patients. DWI-ASPECTS ≥7 was an independent predictor of dramatic recovery at 24 hours (odds ratio, 100.85; 95% confidence interval, 4.29–2371.40; P =0.004) and 7 days (odds ratio, 14.15; 95% confidence interval, 2.21–90.48; P =0.005). Although the favorable outcome rate was not significantly different between patients with DWI-ASPECTS ≥7 with and without early recanalization (60% versus 31%; P =0.228), it was statistically more frequent in patients with DWI-ASPECTS P =0.017). Conclusions— DWI-ASPECTS predicted short-term recovery in patients with middle cerebral artery trunk occlusion receiving intravenous recombinant tissue plasminogen activator. In patients with lower DWI-ASPECTS, there may still be benefit from early recanalization.

Background and Purpose: We investigated whether brain natriuretic peptide (BNP) can serve as a biological marker of long-term mortality in ischemic stroke survivors. Methods: Consecutive patients with ischemic stroke within 24 h of onset from April 2007 to December 2010 were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up until 1 year after stroke onset. Patients were divided into two groups: the deceased group and the surviving group. The factors associated with long-term mortality were investigated by multiple logistic regression analysis. Results: A total of 736 patients who were alive at hospital discharge were included; 130 (17.7%) patients died. On multivariate analysis, age >75 years (odds ratio, OR, 2.83; 95% CI, 1.74-4.60, p = 0.0001), dialysis-dependent chronic renal failure (OR, 5.99; 95% CI, 2.18-16.47, p = 0.0005), modified Rankin Scale score >3 at discharge (OR, 4.41; 95% CI, 2.76-7.05, p < 0.0001), and plasma BNP >100.0 pg/ml (OR, 3.94; 95% CI, 2.31-6.73, p < 0.0001) were found to be independently associated with long-term mortality. We developed a risk score from 4 variables (each variable: 1 point, total score: 0-4 points). The mortality rates were 2% with a score of 0, 9% with a score of 1, 27% with a score of 2 and 50% with a score ≥3. Conclusions: The risk score, composed of clinical parameters and BNP, may predict long-term mortality in ischemic stroke survivors.

A 46-year-old man with a history of the left retinal central artery obstruction and old cerebral infarction in the right middle cerebral artery region presented with right total blindness due to the right retinal central artery occlusion accompanied by a cherry red spot. He had been found to have a giant, 17 mm-in-diameter aneurysm of the right internal carotid artery and a right vertebral arterial aneurysm. The intra-arterial thrombolysis was performed with urokinase injection for the right eye artery origin, and the right eyesight has improved. Cranial and pelvic angiography showed multiple stenosis and dilatation of external carotid and internal iliac arteries. The right superficial temporal artery biopsy revealed the arteritis with fibrinoid necrosis. He was diagnosed as having polyarteritis nodosa (PAN) by clinical course, angiography, and the superficial temporal artery biopsy. Several studies have reported that PAN had less intracranial aneurysm and the diameter of the aneurysm was less than 5 mm. Our case is the first report that PAN had giant aneurysm of 17 mm, diagnosed by temporal artery biopsy. The temporal artery biopsy should be considered to diagnose PAN.

Background and Purpose: Our previous retrospective study demonstrated that a brain natriuretic peptide (BNP) level of >140 pg/ml on admission was useful to distinguish cardioembolism (CE) from non-CE. The aim of the present study was to prospectively investigate the utility of this predefined threshold. Method: Two hundred and twenty-one consecutive patients were prospectively enrolled. On admission, the BNP levels of the patients were measured and classified according to low BNP (≤140.0 pg/ml) or high BNP (>140.0 pg/ml) levels. Final diagnosis of stroke subtype on discharge was made using the TOAST criteria. Measured parameters included the sensitivity, specificity, positive predictive value, and negative predictive value for CE in the high BNP group. Results: There were 81 patients in the high BNP group and 140 patients in the low BNP group. A total of 76 (34.4%) patients were diagnosed with CE, including 59 (72.8%) patients in the high BNP group and 17 (12.1%) patients in the low BNP group (p < 0.001). A BNP level >140.0 pg/ml corresponded to a sensitivity of 77.6%, specificity of 84.8%, positive predictive value of 72.8%, and negative predictive value of 87.9% for a diagnosis of CE. Conclusion: A BNP level of >140.0 pg/ml on admission in patients with acute ischemic stroke is a strong biochemical predictor for CE.

Background: The aim of the present study was to clarify the effect of glucose profiles after stroke, which was assessed by a continuous glucose monitoring (CGM) device. Methods: Acute ischemic stroke patients within 24 h of onset were prospectively studied. CGM was performed for 72 h after admission. CGM parameters were evaluated as follows: (1) mean glucose level, (2) area under the curve (AUC) for glucose level >140 mg/dl and (3) SD of the glucose level. Infarct volume was measured at admission and 24 and 72 h after admission using diffusion-weighted imaging. CGM data and infarct volume growth were compared at 24 and 72 h. Results: Seventy-eight patients were enrolled in the present study. Spearman's rank correlation coefficients showed that both the mean glucose level (r = 0.433, p < 0.001 for 24 h; r = 0.308, p = 0.006 for 72 h) and AUC >140 mg/dl (r = 0.417, p < 0.001 for 24 h; r = 0.277, p = 0.014 for 72 h) were significantly correlated with acute infarct volume growth. The SD of the glucose level was associated with infarct volume growth at 24 h (r = 0.303, p = 0.007), but not 72 h (r = 0.195, p = 0.088). Conclusion: Post-stroke hyperglycemia was associated with infarct volume growth during the acute phase of ischemic stroke.

A 64-year-old man developed right arm weakness and dysarthria, and was admitted to our hospital. Diffusion-weighted magnetic resonance imaging of the brain showed a high intensity area in the frontal lobe. T2*-weighted images showed multiple spotty low intensity lesions in bilateral cerebral hemispheres, mimicking cerebral microbleeds. Cerebral angiography showed multiple aneurysms in the anterior, middle, posterior cerebral arteries and cerebellar arteries. Transthoracic echocardiography revealed a floating structure in the left atrial chamber, indicating cardiac myxoma. We diagnosed cardioembolic ischemic stroke due to left atrial myxoma. Cardiac surgery for excision of a left atrial myxoma was performed on the 3rd hospital day. Multiple aneurysms should be taken into account for differential diagnosis in patients with cardiac myxoma and with atypical spotty low intensity on T2*-weighted images.

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 24 h 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.

Background and purpose Recent studies have shown that thrombolysis could decrease or eliminate ischaemic diffusion-weighted imaging lesions. However, the features of such diffusion-weighted imaging lesion reduction are not well known. Aims To clarify, the frequency of and factors associated with lesion reduction were investigated. Methods Patients given intravenous tissue plasminogen activator therapy within three-hours of onset were prospectively enrolled. Magnetic resonance imaging including diffusion-weighted imaging and magnetic resonance angiography was performed four times: on admission, just after intravenous tissue plasminogen activator, 24 h from intravenous tissue plasminogen activator, and seven-days after intravenous tissue plasminogen activator. The diffusion-weighted imaging lesion volume was measured by manual trace using National Institutes of Health imaging software. All patients were divided into three groups according to the early diffusion-weighted imaging lesion volume change from admission to just after intravenous tissue plasminogen activator: the lesion reduction group (>20% decrease); the lesion growth group (>20% increase); and the lesion unchanged group. Results In total, 105 patients [56 males, median age 77 (interquartile range 70–83) years, and National Institutes of Health Stroke Scale score 16 ( 10 – 22 )] were enrolled. Early diffusion-weighted imaging lesion reduction was observed in seven (7%) patients. The decreased lesion increased subsequently. On multivariate analysis, the glucose level on admission (odds ratio 0·95, 95% confidence interval 0·91 to 0·99, P = 0·045) and early recanalization (odds ratio 15·7, 95% confidence interval 1·61 to 153, P = 0·018) were independently related to early lesion reduction. Conclusion Early diffusion-weighted imaging lesion reduction was observed in 7% of patients treated with intravenous tissue plasminogen activator. The decreased lesion increased subsequently. Initial glucose level and early recanalization were independently associated with early diffusion-weighted imaging lesion reduction.

Sleep-disordered breathing (SDB) is a risk factor for cerebrovascular disease. We investigated the frequency of SDB in Japanese patients with acute ischaemic stroke and transient ischaemic attack (TIA), as well as factors associated with SDB severity.Between April 2010 and March 2011, we prospectively enrolled patients with ischaemic stroke and TIA within 24 h of onset to participate in a sleep study within 7 days of admission. We defined SDB as a respiratory disturbance index (RDI) (number of apnoeas or hypopnoeas per hour) of ≥ 5. Patients were assigned to groups based on RDI values of ≥ 30 (severe) and30 (absent or not severe). The frequency of SDB and factors associated with severity were investigated using multivariate regression analysis.We enrolled 150 patients amongst whom 126 (84%) had SDB. The frequencies of SDB were 21 (75%) patients with TIA, 105 (86%) with ischaemic stroke, 8/10 (80%) with large artery atherosclerosis, 14/14 (100%) with small vessel occlusion, 37/41 (90%) with cardioembolism and 46/57 (81%) with other causes of stroke/undetermined. Severe SDB was evident in 44 (29%) patients. The frequency of males (75% vs. 56%, P = 0.027), atrial fibrillation (AF) (39% vs. 23%, P = 0.045), higher body mass index (23.8 ± 3.8 vs. 22.3 ± 3.8, P = 0.043) and a larger neck circumference (37.8 ± 4.3 vs. 35.8 ± 4.2, P = 0.012) was significantly higher in the group with severe SDB. Multivariate regression analysis found that AF (OR 2.4; 95% CI 1.079-5.836, P = 0.0359) was independently associated with severe SDB.Most Japanese patients with acute ischaemic stroke and TIA had SDB, and AF was associated with SDB.

Background and purpose Hyperglycemia (HG) is associated with infarct volume expansion in acute ischaemic stroke patients. However, collateral circulation can sustain the ischaemic penumbra and limit the growth of infarct volume. The aim of this study was to determine whether the association between HG and infarct volume expansion is dependent on collateral circulation. Methods We performed a retrospective analysis of 93 acute ischaemic stroke patients with internal carotid artery or middle cerebral artery occlusion within 24 h of onset were retrospectively studied. HG was diagnosed in patients with an admitting blood glucose value ≥140 mg/dl. Angiographic collateral grade 0–1 was designated as poor collateral circulation and grade 2–4 as good collateral circulation. Infarct volume was measured at admission and at again within 7 days using diffusion-weighted magnetic resonance images. Results Among 34 patients with poor collateral grade, the change in infarct volume was significantly greater in the HG group than in the non-HG group (106.0 ml vs. 22.7 ml, P = 0.002). Among the 59 patients with good collateral circulation, the change in infarct volume was greater in the HG group than in the non-HG group (53.3 ml vs. 10.9 ml, P = 0.047). Multiple regression analysis indicated that admission HG (P = 0.004), baseline National Institutes of Health Stroke Scale score (P = 0.018), and poor collateral circulation (P = 0.040) were independently associated with infarct volume expansion. Conclusions Infarct volume expansion was greater in individuals with HG on admission regardless of collateral circulation status.

The aim of the present study was to investigate whether the prevalence of atrial fibrillation (AF) is associated with the level of glycated hemoglobin (HbA1c) in Japanese adults in Kurashiki-city.Adult residents (≧ 40 years old) were examined twice, in 2006 and 2007. Electrocardiography was conducted to determine the presence of AF. After categorizing all participants into two groups (HbA1c6.5% as low group and ≧ 6.5% as high group), factors independently associated with the prevalence of AF were investigated in total cohort, low and high groups using multivariate logistic regression analysis.Of the total 52,448 participants (median age, 72 years; range, 65-78 years; 17,980 men), AF prevalence was 2.2% (1161/52,448). After classifying all participants by HbA1c level, the proportion of participants with AF was 2.2% (1073/49,498) in the low group and 3.0% (88/2950) in high group (p=0.005). AF was significantly associated with cardiac disease (OR, 5.78; 95%CI, 5.07-6.58; p0.001), elevating HbA1c (OR, 1.57; 95%CI, 1.33-1.84; p0.001), increasing age (OR, 1.40; 95%CI, 1.30-1.51; p0.001), and male sex (OR, 1.27; 95%CI, 1.10-1.47; p=0.001) in low group and was related to cardiac disease (OR, 4.85; 95%CI, 3.08-7.62; p0.001) and age (OR, 1.45; 95%CI, 1.09-1.93; p=0.010) in high group. After adjusted age, gender, vascular risk factors, cardiac disease, and eGFR, elevating HbA1c (OR, 1.18; 95%CI, 1.09-1.28; p0.001) was the factor in association with AF.The presence of AF appears to be associated with the level of HbA1c, especially in patients with HbA1c6.5%.

A 94-year-old woman was admitted to our hospital because of altered mental status and cerebellar ataxia of left upper and lower extremities. A brain CT scan revealed a right cerebellar hemorrhage approximately 15 cc. Plasma brain natriuretic peptide (BNP) value on admission was 1,064.6 pg/ml. Twelve-lead ECG revealed negative T-wave in V3-V5. Transthoracic echocardiology confirmed an ejection fraction of 35%, and left ventricular apical akinesia and basal hyperkinesis were seen. Plasma BNP value was dramatically declined in the subacute phase of cerebellar hemorrhage. On the 14th day, echocardiography showed completely improvement of the left ventricular wall abnormalities. Therefore, we diagnosed having as a Tako-tsubo cardiomyopathy. Tako-tsubo cardiomyopathy is a rare complication of acute intracerebral hemorrhage. In the present case, plasma BNP was effective as a screening marker of Tako-tsubo cardiomyopathy and serial measurement of BNP was made helpful to know cardiac status.

約25％の急性期脳梗塞例は発症時間が不明であるためt-PA静注療法の対象から除外される．頭部MRI DWIで高信号を呈していてFLAIRで信号変化がない場合（DWI/FLAIRミスマッチ），発症3時間以内と推定できる．我々は発症時間不明の脳梗塞例に対しDWI/FLAIRミスマッチに基づいたt-PA静注療法を行った．2009年6月から2011年10月までに13例［83 （67-90）歳，NIHSSスコア16 （11-20）点］が登録された．最終無事確認時間からt-PA静注療法まで5.6 （5.0-11.6）時間であった．24時間以内の再開通は10例（完全再開通：5例），症候性頭蓋内出血は0例であった．発症7日後の著明改善例は7例で，3カ月後の転帰良好例（mRS 0-2）は5例であった．発症時間が不明であってもDWI/FLAIRミスマッチがあればt-PA静注療法の対象になる可能性がある．

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.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.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], glucose150 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 NIHSS11 as 2 points, glucose150 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).A simple clinical and MRI scale can predict good outcome in t-PA patients.

Background and Purpose— The aim of the present study was to investigate independent clinical and MRI factors associated with no early recanalization within 1 hour after tissue-type plasminogen activator (tPA) administration. Methods— Patients with acute stroke within 3 hours of onset who were treated with tPA were studied prospectively. Patients with internal carotid artery, M1, and M2 occlusion were enrolled, and independent clinical and MRI factors associated with no early recanalization within 1 hour after tPA administration were examined using multivariate logistic regression analysis. Results— One hundred thirty-two patients (63 men; mean age, 76.4±10.2 years; internal carotid artery occlusion in 37 patients, M1 occlusion in 58, and M2 occlusion in 37) were enrolled. Follow-up MR angiography within 60 minutes after tPA infusion revealed early recanalization in 49 (37.1%) patients (complete in 16 patients, partial in 33) and no recanalization in 83 (62.9%). Using 8 variables (atrial fibrillation, time from stroke onset to treatment ≥140 minutes, use of warfarin, glucose ≥135 mg/dL, large artery diseases, internal carotid artery occlusion, M1 occlusion, and M1 susceptibility vessel sign on T2*) identified on univariate analysis at P P =0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of M1 susceptibility vessel sign for predicting no early recanalization were 31.3%, 93.9%, 89.7%, and 44.7%, respectively. Conclusions— Of clinical and MRI factors before tPA infusion, M1 susceptibility vessel sign on T* is the only independent factor associated with no early recanalization within 1 hour after tPA administration.

Background and purpose Spontaneous intra-cranial arterial dissection (SICAD) without history of head and neck injury is now recognized as an important cause of stroke. However, the frequency of SICAD involving the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories remains unclear. This study therefore investigated the distribution of SICAD. Methods Subjects comprised 194 patients (126 men, 68 women; median age, 68.0 years) with infarct isolated to the ACA, MCA or PCA territories who underwent conventional angiography. Diagnosis of SICAD was based on clinical and neuroradiological findings. Frequency of SICAD was compared among ACA, MCA, and PCA infarcts. All patients were divided into SICAD and non-SICAD groups, and clinical characteristics were compared between groups. Results Infarcts involved the ACA in 14 cases (7.2%), MCA in 165 cases (85.1%), and PCA in 15 cases (7.7%). SICAD was diagnosed in 17 of 194 cases (8.8%), with cerebral angiography showing main findings of the string sign in 11 patients (64.7%), the pearl and string sign in 6 patients (35.3%), and pseudoaneurysm formation in 2 patients (11.7%). SICAD most frequently involved the ACA (ACA, 64.3%; MCA, 4.2%; PCA, 6.7%; P Conclusion SICAD was seen in 64.3% of patients with ACA infarct. The mechanisms of ACA infarction may thus differ from those of MCA and PCA infarction.

Purpose Our aim was to investigate the relationship between number of stroke physicians (SPs) and number of patients treated with intravenous thrombolysis (IV rt-PA) per year. Methods Questionnaires about the infrastructure of acute stroke care including number of SPs and patients given IV rt-PA from October 2008 to September 2009 were sent to 3877 hospitals in Japan. We compared the number of SPs between: 1) hospitals not giving IV rt-PA for a year vs. hospitals giving IV rt-PA for ≥ 1 patient; 2) ≤ 5 vs. > 5 patients; 3) ≤ 10 vs. > 10 patients; and 4) ≤ 25 vs. > 25 patients. We established cut-off numbers of SPs administering IV rt-PA for ≥ 1, > 5, > 10, and > 25 patients/hospital/year using a sensitivity–specificity curve. Results Responses were received from 2488 of the 3877 hospitals (64.2%), and 919 hospitals admitted acute stroke patients. Of these, 385 hospitals were not administering IV rt-PA in that year, 250 hospitals gave IV rt-PA for 1–4 patients, 131 hospitals for 5–9 patients, 102 hospitals for 10–25 patients, and 30 hospitals for > 25 patients. Cut-off numbers of SPs per hospital were 1 doctor administering IV rt-PA for ≥ 1 patient/year (sensitivity, 83.8%; specificity, 84.5%), 2 doctors for > 5 patients (sensitivity, 85.9%; specificity, 74.1%), 3 doctors for > 10 patients (sensitivity, 76.3%; specificity, 75.5%), and 4 doctors for > 25 patients (sensitivity, 86.2%; specificity, 78.5%). An independent factor for IV rt-PA with > 25 patients was ≥ 4 SPs (odds ratio, 3.83; 95% confidence interval, 1.17–12.63; p = 0.027). Conclusions Higher numbers of SPs should be associated with higher numbers of patients getting IV rt-PA.

Background and Purpose: Patients with unknown onset time would be able to receive intravenous thrombolysis when showing diffusion-weighted imaging (DWI)/fluid-attenuated inversion recovery (FLAIR) mismatch. Methods: Consecutive acute stroke patients with unknown onset time were prospectively enrolled. We defined patients as having unknown onset time when the last known normal time (LNT) was not consistent with the first found abnormal time (FAT). Only patients with anterior-circulation stroke and presence of arterial lesion were enrolled. Intravenous thrombolysis was conducted within 3 h from FAT if the patient showed DWI/FLAIR mismatch. Results: From June 2009 to May 2010, 10 patients [median age, 84 years (interquartile range, IQR, 64–90); National Institutes of Health Stroke Scale (NIHSS) score, 14 (IQR, 9–19)] were enrolled. Subjects included 4 patients who developed stroke during sleep, 5 with disturbance of consciousness, and 1 with aphasia. Median interval between LNT and thrombolysis was 5.6 h (IQR, 4.5–9.8) and median interval between FAT and thrombolysis was 2.5 h (IQR, 2.1–2.8). Three patients had internal carotid artery occlusion, 5 had M1 occlusion, and 2 had M2 occlusion. Early recanalization within 24 h was seen in 7 patients (complete recanalization, n = 4; partial recanalization, n = 3). No patients experienced symptomatic cerebral hemorrhage within 48 h. At day 7, 5 patients showed dramatic recovery (defined as ≧10-point reduction in total NIHSS score or score of 0 or 1). At 3 months, favorable outcome (modified Rankin scale score, 0–2) was seen in 4 patients. Conclusion: Acute stroke patients with DWI/FLAIR mismatch may be able to safely receive intravenous thrombolysis.