Yuki Sakamoto

Intravenous Thrombolysis Based on Diffusion-Weighted Imaging and Fluid-Attenuated Inversion Recovery Mismatch in Acute Stroke Patients with Unknown Onset Time

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.

Administration of edaravone, a free radical scavenger, during t-PA infusion can enhance early recanalization in acute stroke patients — A preliminary study

BACKGROUND AND PURPOSE The aim of the present study was to investigate whether administration of edaravone during t-PA infusion can enhance early recanalization in acute stroke patients. METHODS This trial was undertaken as a multicenter, single blind, randomized, open-labeled study. Acute stroke patients with M1 or M2 occlusion within 3h of onset were studied prospectively. The subjects were randomly allocated to edaravone (Edaravone group: when t-PA was intravenously infused, intravenous edaravone (30 mg) was started at the same time) and no edaravone (Non-Edaravone group). Early recanalization within 1h after t-PA infusion and neurological recovery 24h after t-PA infusion were compared between the two groups. RESULTS 40 patients (23 men, 17 women; mean age, 76.4 ± 8.2 years, median 79 years) were enrolled; 23 patients were assigned to the Edaravone group and 17 to the Non-Edaravone group. Early recanalization was more frequently observed in the Edaravone group than in the Non-Edaravone group (56.5% vs. 11.8%, P=0.0072). Eight patients who underwent endovascular therapy immediately after t-PA infusion were excluded, and neurological recovery was analyzed. Remarkable and good recoveries were more frequently observed in the Edaravone group than in the Non-Edaravone group (80.1% vs. 45.5%, P=0.0396). CONCLUSION Early recanalization and good neurological recovery were more frequently observed in the Edaravone group than in the Non-Edaravone group. These results demonstrate that administration of edaravone during t-PA infusion should enhance early recanalization in acute stroke patients.

Clinical and MRI Predictors of No Early Recanalization Within 1 Hour After Tissue-Type Plasminogen Activator Administration

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<0.2, multivariate logistic regression analysis revealed that M1 susceptibility vessel sign was the only independent factor associated with no early recanalization (OR, 7.157; 95% CI, 1.756 to 29.172; 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.

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.

Annual Incidence of Atrial Fibrillation and Related Factors in Adults

The aim of this study was to investigate the annual incidence of atrial fibrillation (AF) and related factors from health surveys in 2006 and 2007. Participants (aged ≥ 40 years) were examined from annual health surveys provided by the Kurashiki Public Health Center twice, in 2006 and 2007. Participants were classified into 2 groups: a control group without AF in 2006 and 2007, and an AF group with documented AF in 2007 but not in 2006. Annual AF incidence (per 1,000 patient-years) was calculated, and baseline characteristics were compared between groups. Independent factors for new documented AF were analyzed using multivariate logistic regression modeling. Health surveys were performed for 30,449 participants in 2006 and 2007. Excluding 439 participants with AF in 2006, newly documented AF was observed in 278 participants (0.9%), while the control group comprised 29,732 participants. The overall incidence of newly documented AF was 9.3/1,000 patient-years. Newly documented AF was significantly associated with age ≥ 80 years (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.20 to 2.06, p = 0.001), history of cardiac disease (OR 7.47, 95% CI 5.79 to 9.63, p < 0.001), increasing estimated glomerular filtration rate of 10 ml/min/1.73 m(2) (OR 0.93, 95% CI 0.87 to 0.99, p = 0.025), and hypercholesterolemia (OR 0.75, 95% CI 0.58 to 0.96, p = 0.023).

DWI-ASPECTS as a Predictor of Dramatic Recovery After Intravenous Recombinant Tissue Plasminogen Activator Administration in Patients With Middle Cerebral Artery Occlusion

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 <7 with early recanalization than those without early recanalization (38% versus 0%; 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.

Early ischaemic diffusion lesion reduction in patients treated with intravenous tissue plasminogen activator: infrequent, but significantly associated with recanalization

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.

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%.

Spontaneous intra-cranial arterial dissection frequently causes anterior cerebral artery infarction.

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<0.001). 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.