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Background and Purpose: IV alteplase at 0.6 mg/kg for acute wake-up and unclear onset strokes was recommended in Japanese stroke guidelines in March 2019. We determined the safety and effectiveness of this newly recommended thrombolysis in clinical practice. Methods: This is a multicenter observational study, enrolling acute ischemic stroke patients with a time last-known-well >4.5 h who have a mismatch between DWI and FLAIR treated with intravenous alteplase. The safety outcomes are intracranial hemorrhage (ICH) with neurological deterioration within 36 h after thrombolysis, all cause deaths within 90 days, and adverse events. The efficacy outcomes are functionally independence defined as a mRS score of 0-1 at 90 days, and NIHSS change at 24h from baseline. Results: Between 2019 March and 2020 March, 63 patients (33 females; age, 74±11y; premorbid functionally independence, 50 (82%); median NIHSS on admission, 11) were enrolled at 14 hospitals. Of them, 40 patients (63%) recognized stroke symptoms at wake-up time, and median time between last-known-well and admission was 6.5 h. Baseline MRA showed any vessel occlusion in 52 patients (88%). IV alteplase was disrupted in one patient. Two patients (3%) had symptomatic ICH (≥4 increase in NIHSS) within 36 h. NIHSS change was -5.1±8.1. Twenty-one patients (36%) had functionally independence at discharge and there was no death during acute hospitalization. Of the overall 63 patients, 22 also underwent mechanical thrombectomy (36%, 72±9y, median NIHSS 16), showing no symptomatic ICH, mean NIHSS change of -8.9±7.5, and 8 patients (42%) had functionally independence at discharge. Conclusions: In clinical practice, IV alteplase for wake-up and unclear onset stroke patients with DWI-FLAIR mismatch seemed to be safe and effective compared with previous randomized control trials. Mechanical thrombectomy could be combined with alteplase safely and effectively.

Background & Purpose: Both atrial fibrillation (AF) and carotid stenosis (CS) can be associated with acute stroke recurrence and consequent bad outcome even in minor stroke. We investigated stroke recurrence and outcome in Japanese minor stroke patients with AF and/or CS. Subjects & Methods: Among the consecutive 6246 stroke patients who were admitted to the 7 stroke centers within 7 days after the onset, 634 patients with acute ischemic stroke with AF, the initial NIH stroke scale score of 7 or less, and prior modified Rankin scale (mRS) of 0 or 1 were included in the present study. We observed an acute stroke recurrence during 3 weeks. Results: Acute stroke recurrence was observed in 27 (4.3%) patients. Major cerebral artery stenosis of 50% or more in diameter was observed in 159 (25.1%) patients, and among them 43 (6.8%) had carotid stenosis. Any major artery stenosis was more frequent in patients with than without stroke recurrence (55.6% vs 23.7%, p=0.0002). Carotid stenosis was more frequent in patients with than without stroke recurrence (25.9% vs 5.9%, p<0.0001). The initial NIHSS score was not different between patients with and without an acute stroke recurrence. Dyslipidemia, diabetes mellitus, and history of brain hemorrhage were more frequent, and HDL cholesterol and estimated GFR values were lower, and HbA1c, fasting glucose, BUN, and D-dimer values were higher, intima-media thickness 0f the common carotid artery was thicker in patients with than without an acute stroke recurrence. On the multivariate analysis, carotid stenosis (OR 4.93, 95%CI 1.60~15.2) and D-dimer value (OR 1.13, 95%CI 1.00~1.28) had a positive association with an acute stroke recurrence. Among 43 patients with both AF and CS, 7 had an acute stroke recurrence. With regard to the acute antithrombotic treatment, 5 patients were treated with only anticoagulant agents and other 2 patients were treated with both anticoagulant and antiplatelet agents. Conclusions: Carotid stenosis was a significant predictor for an acute stroke recurrence in patients with atrial fibrillation. Optimal antithrombotic treatment in the acute phase in stroke patients with both AF and CS should be investigated.

Background & Purpose: Atrial fibrillation (AF) and large artery atherosclerosis (LAA) can be associated with a bad outcome even in minor stroke. We investigated stroke recurrence and outcome in Japanese minor stroke patients with AF and/or LAA. Subjects & Methods: Among the consecutive 6246 stroke patients who were admitted to the 7 stroke centers within 7 days after the onset, 3725 patients with acute ischemic stroke with the initial NIH stroke scale score of 7 or less and prior modified Rankin scale (mRS) of 0 or 1 were included in the present study. In accordance with AF and intracranial or extracranial LAA (stenosis of 50% or more in diameter), they were classified into 4 subgroups: patients without both AF and LAA (Group A, n=2154), patients with only AF (Group B, n=475), patients with only LAA (Group C, n=937), and patients with both AF and LAA (Group D, n=159). We observed stroke recurrence and outcome during one year. Results: On the multivariate analysis, age (OR, 0.94; 95%CI 0.93~0.95), initial NIH stroke scale score (OR, 0.70; 95%CI, 0.67~0.74), chronic kidney disease (OR, 0.72; 95%CI, 0.55~0.95), initial HbA1c value (OR 0.87, 95%CI 0.79~0.95), and LAA (OR 0.70, 95%CI 0.55~0.88) had a negative association with a good outcome. Acute stroke recurrences within 3 weeks after the onset were observed in 2.0%, 2.5%, 6.1%, and 9.4% in Group A-D patients respectively (p<0.0001). Stroke recurrences during 1 year were observed 7.0%, 10.7%, 11.6%, and 13.8% in Group A-D patients respectively (p<0.0001). A good outcome (mRS of 0-1) 1 year after the onset was observed in 77.0%, 6.4%, 67.9%, and 65.8% in Group A-D patients respectively (p<0.0001). With regard to the Kaplan-Meier method, there was a significant difference in stroke recurrence among the 4 subgroups, and stroke recurrences were most frequent in Group D (p<0.0001, Log-rank test). Conclusions: In Japanese minor stroke, age, NIH stroke scale score, chronic kidney disease, HbA1c, and LAA were significant predictors for the long-term outcome. In patients with both AF and LAA, stroke recurrences were most frequent, especially in the acute phase, and a long-term good outcome was least frequent consequently.