Junichi Uemura

Large Ischemic Lesions on Diffusion-Weighted Imaging Done Before Intravenous Tissue Plasminogen Activator Thrombolysis Predicts a Poor Outcome in Patients With Acute Stroke

Background and Purpose— MRI is useful for detecting early ischemic lesions before administration of tissue plasminogen activator in patients with hyperacute ischemic stroke. However, it is unclear whether early ischemic change seen on diffusion-weighted imaging (DWI) can be used to predict patient outcomes. Methods— Consecutive patients with anterior circulation ischemic stroke treated with tissue plasminogen activator within 3 hours of stroke onset were prospectively studied. The National Institutes of Health Stroke Scale score was obtained before and 7 days after tissue plasminogen activator administration. MRI, including DWI, was done before tissue plasminogen activator thrombolysis. The relationship between the DWI Alberta Stroke Programme Early CT Score (ASPECTS) and patients’ outcomes was assessed. Results— The subjects consisted of 49 consecutive patients with stroke (27 males; mean age, 72.9±10.3 years). The median (range) of the baseline DWI ASPECTS value was 9 (3–10). Dramatic improvement was seen in one of 8 patients with an ASPECTS ≤5 compared with 21 of 41 patients with a DWI ASPECTS >5 (P=0.0592). On the other hand, worsening was noted more frequently in patients with a DWI ASPECTS ≤5 (3 of 8 patients) than in patients with an ASPECTS >5 (4 of 41 patients; P=0.0753). Bad outcome was seen more frequently in patients with a DWI ASPECTS ≤5 (6 of 8 patients) than in patients with a DWI ASPECTS >5 (2 of 41 patients; P<0.0001). Multivariate logistic regression analysis demonstrated that a DWI ASPECTS ≤5 was the only independent predictor of a bad outcome (OR, 33.4; 95% CI, 2.7 to 410.8; P=0.0062). Conclusion— DWI ASPECTS appears to be a reliable tool for predicting bad outcome. Patients with a DWI ASPECTS >5 should be considered eligible for tissue plasminogen activator therapy.

Relation of Atrial Fibrillation to Glomerular Filtration Rate

Although both atrial fibrillation (AF) and decreasing glomerular filtration rate (GFR) are strongly related to advanced age and share common associated vascular risk factors, few studies have explored the relation between AF and GFR. From residents (age >or=40 years) in Kurashiki City, a total of 41,417 subjects (median age 72 years; 13,956 men) were enrolled in the Kurashiki City Annual Medical Survey from May to December 2006. The estimated overall prevalence of AF was 1.6% (2.8% in the low-GFR tertile, 1.2% in the middle tertile, and 0.9% in the high tertile, p <0.001). After all subjects were categorized into age tertiles (age thresholds 68 and 76 years), AF was identified in 0.9% in the low-GFR tertile, 0.6% in the middle tertile, and 0.5% in the high tertile in the low-age tertile (p = 0.018); 2.6% in the low-GFR tertile, 1.2% in the middle tertile, and 1.1% in the high tertile in the middle-age tertile (p <0.001); and 3.9% in the low-GFR tertile, 2.4% in the middle tertile, and 1.7% in the high tertile in the high-age tertile (p <0.001). The odds ratio for AF adjusted for age, gender, vascular risk factors, cardiac disease, and hemoglobin was 1.91 (95% confidence interval 1.54 to 2.38, p <0.001) for the low-GFR tertile versus the high tertile and 1.12 (95% confidence interval 0.88 to 1.42, p = 0.364) for the middle-GFR tertile versus the high tertile. The prevalence of AF gradually increased with decreasing GFR. In conclusion, AF appears to be associated with decreasing GFR.

New Appearance of Extraischemic Microbleeds on T2*-Weighted Magnetic Resonance Imaging 24 Hours After Tissue-type Plasminogen Activator Administration

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.

Early recanalization rate of major occluded brain arteries after intravenous tissue plasminogen activator therapy using serial magnetic resonance angiography studies.

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

Intracranial Hemorrhage Caused by Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) – Multicenter Retrospective Cohort Study in Japan –

BACKGROUND We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs). METHOD AND RESULTS We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3±8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively). CONCLUSIONS More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH.

Recanalization between 1 and 24 hours after t-PA therapy is a strong predictor of cerebral hemorrhage in acute ischemic stroke patients

BACKGROUND AND PURPOSE Intravenous administration of tissue plasminogen activator (t-PA) can improve clinical outcomes in patients with acute ischemic stroke. The most important complication of t-PA therapy is intracerebral hemorrhage (ICH). The aim of this study was to use serial MRI studies to identify independent predictors of symptomatic and asymptomatic ICH after t-PA therapy. METHODS Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. To identify the presence of recanalization in the occluded arteries and the presence of ICH, MRI, including diffusion weighted imaging (DWI), T2*, and magnetic resonance angiography (MRA), was performed before and 1 h, 24 h, and 5-7 days after t-PA thrombolysis. The independent predictors of ICH were determined using multivariate logistic regression analysis. RESULTS 41 patients (21 males, 20 females; mean age, 73.2+/-10.7 years) were enrolled, and 19 ICHs (1 symptomatic, 18 asymptomatic) were observed on T2*. The initial MRA demonstrated occluded brain arteries in 31 patients (75.6%), of which follow-up MRA at 1 h, 24 h, and 5-7 days after t-PA therapy revealed recanalization in 48.4%, 80.0%, and 90.0% of patients, respectively. The frequency of recanalization within 1 h after t-PA therapy did not differ between ICH and No-ICH groups, but the ICH group had more frequent recanalization between 1 h and 24 h after t-PA than the No-ICH group (50.0% vs. 4.5%, P=0.001). The ICH group had arterial fibrillation (AF) more frequently than the No-ICH group (78.9% vs. 27.3%, P=0.001). Compared to the No-ICH group, the NIHSS score was higher (16.4+/-5.7 vs. 11.5+/-6.5, P=0.011) and the ASPECTS-DWI value (a normal DWI has an ASPECTS-DWI value of 11 points) was lower (7.3+/-2.4 vs. 8.9+/-1.9, P=0.019) in the ICH group. Multivariate logistic regression analysis demonstrated that the presence of recanalization between 1 and 24 h after the end of t-PA infusion (OR: 20.2; CI: 1.0-340.9; P=0.037) was the only independent predictor of ICH. CONCLUSION Recanalization of occluded arteries between 1 and 24 h but not within 1 h after t-PA infusion should be independently associated with symptomatic and asymptomatic ICH after t-PA therapy.

Admission hyperglycemia and serial infarct volume after t-PA therapy in patients with and without early recanalization.

BACKGROUND AND PURPOSE The present study examined the effects of admission hyperglycemia and early recanalization (ER) after t-PA administration on infarct volume and patient outcome. METHODS Acute ischemic stroke patients with major artery occlusion treated with t-PA within 3h of onset were studied prospectively. Hyperglycemia was identified as admitting blood glucose value≥130 mg/dl. We compared serial infarct volume and patient outcome between normoglycemic and hyperglycemic groups, and assessed correlation between admitting blood glucose value and △infarct volume (7 days-baseline) between patients with and without ER. RESULTS 97 patients (ICA occlusion in 30, M1 in 44, and M2 in 23 patients) were enrolled in the present study; 52 had hyperglycemia, and 40 had ER. The initial infarct volume did not differ between the normoglycemic and hyperglycemic groups. However, infarct volume at 7 days was larger in the hyperglycemic group than in the normoglycemic group (156.2±157.1cm(3), vs. 85.4±140.7 cm(3), P=0.0061) and the baseline admitting blood glucose value was correlated with Δinfarct volume (7 days-baseline) (r=0.340, P=0.0014). Regarding ER, Δinfarct volume (7 days-baseline) in patients without ER was correlated with admitting blood glucose value(r=0.372, P=0.0078). However, in patients with ER, Δinfarct volume was not associated with admitting blood glucose value (r=0.225, P=0.1173). Good outcome (mRS 0-2) at 3 months was more frequent in normoglycemic patients than hyperglycemic patients (43.2% vs. 22.2%, P=0.0418). CONCLUSION Admission hyperglycemia was associated with infarct volume expansion and patient outcome in t-PA patients. However, if ER occurs, hyperglycemia should not adversely affect infarct volume.

HbA1c and atrial fibrillation: A cross-sectional study in Japan

BACKGROUND 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. METHODS 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 (HbA1c <6.5% 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. RESULTS 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; p<0.001), elevating HbA1c (OR, 1.57; 95%CI, 1.33-1.84; p<0.001), increasing age (OR, 1.40; 95%CI, 1.30-1.51; p<0.001), 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; p<0.001) 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; p<0.001) was the factor in association with AF. CONCLUSIONS The presence of AF appears to be associated with the level of HbA1c, especially in patients with HbA1c <6.5%.

The DASH score: a simple score to assess risk for development of malignant middle cerebral artery infarction.

BACKGROUND AND PURPOSE The aim of the present study was to devise a simple grading scale for assessing the risk of development of malignant MCA infarction (MMI). METHODS Using MRI, patients with MCA infarction and proximal vessel occlusion (ICA or M1) within 24h of onset were retrospectively studied. MMI was defined as clinical deterioration, midline shift ≥ 5 mm, or brain herniation within 48 h of admission. We evaluated clinical factors independently associated with MMI and created a simple score according to the multivariate logistic regression analysis. RESULTS Subjects comprised 119 patients, 57 of which (47.9%) developed MMI. Multivariate logistic regression analysis revealed the following independent factors associated with MMI: DWI ASPECTS ≤ 3 [odds ratio (OR), 4.16; 95% CI, 1.36-12.66, P=0.012], ACA territory involvement [OR, 6.90; 95% confidence interval [CI], 2.06-23.10, P=0.002], M1 susceptibility vessel sign (SVS) on T2*-gradient echo [OR, 4.55; 95% CI, 1.38-14.98, P=0.013], and hyperglycemia (glucose value ≥ 145 mg/dl) [OR, 5.31; 95% CI, 1.80-15.68, P=0.002]. These four variables were selected for use in the DASH score, with DWI ASPECTS ≤ 3 as 1 point, ACA territory involvement as 1 point, M1 SVS as 1 point, and hyperglycemia as 1 point. The likelihood of developing MMI for each score was as follows: score 0, 9.1%; score 1, 20.5%; score 2, 63.0%; score 3-4, 96.8%. The C statistic for the score was 0.88 (95% CI, 0.82-0.94, P<0.001). CONCLUSION Our DASH score reliably assessed a risk for development of MMI in large MCA infarctions.

Chronic kidney disease is an independent predictor of adverse clinical outcomes in patients with recent small subcortical infarcts.

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 <60 ml/min/1.73 m2 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. Coxs 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.