Yasuyuki Iguchi

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.

Hyperglycemia independently increases the risk of early death in acute spontaneous intracerebral hemorrhage

BACKGROUND It is unclear whether hyperglycemia on admission in patients with acute intracerebral hemorrhage (ICH) increases the risk of early death. METHODS 100 consecutive patients (median age, 67.8 years) with acute supratentorial ICH within 24 h of onset were prospectively enrolled. Clinical characteristics and plasma glucose were assessed in all patients. ICH volume was measured on admission CT (<24 h) and follow-up CT (<48 h) scans. Patients were divided into two groups: the death group, who died within 14 days of onset, and the survival group. The association between early death and clinical characteristics were investigated by multivariate logistic regression analysis. RESULTS The death group consisted of 11 patients (median age, 77 years), while the survival group consisted of 89 patients (median age, 67 years). The admission plasma glucose level and the ICH volume were higher in the death group than in the survival group (glucose: death, 205 mg/dl vs. survival, 131 mg/dl, p<0.0001; and ICH volume: survival, 13.6+/-15.3 ml vs. death 101.1+/-48.7 ml, p<0.0001). Using receiver operating characteristic (ROC) curve, cut-off values that predicted early death were 150 mg/dl for the glucose level and >20 ml for the initial IVH volume. On multivariate logistic regression analysis, admission plasma glucose level>150 mg/dl (OR 37.5, CI 1.4-992.7, p=0.03) and IVH volume>20 ml (OR 64.6, CI 1.3-3173.5, p=0.04) were independent factors associated with early death. CONCLUSION Admission hyperglycemia may independently increase the risk of early death in acute spontaneous intracerebral hemorrhage.

FLAIR can estimate the onset time in acute ischemic stroke patients

BACKGROUND AND PURPOSE Although thrombolysis can be performed for acute ischemic stroke (AIS) within 6h of onset, patients with an unknown onset time cannot receive this treatment. The aim of the present study is to investigate a method for determining the onset time of stroke in AIS patients within 24 hours (h) of onset. METHODS AIS patients with onset time clearly defined within 24h were enrolled. All patients were examined using diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR). We investigated the utility of FLAIR in estimating the onset time of stroke. RESULTS We enrolled 333 consecutive patients (median age, 74 years [interquartile range, 63-81]; males, 207 [62%]). Fifty-three patients underwent multiple MRI examinations; thus, a total of 389 MRI studies were analyzed. When the MRI findings were DWI-positive and FLAIR-negative (DWI+/FLAIR-), the interval between onset and imaging time was estimated to be within 3h with sensitivity of 0.83, specificity of 0.71, positive predictive value (PPV) of 0.64, and negative predictive value (NPV) of 0.87; to be within 4.5h with sensitivity of 0.74, specificity of 0.85, PPV of 0.87, and NPV of 0.70; and to be within 6h with sensitivity of 0.69, specificity of 0.91, PPV of 0.94, and NPV of 0.59. When patients with infra-tentorial lesions, lacunar stroke on imaging, and mild neurological deficit were excluded, DWI+/FLAIR- estimated that the onset time was within 3h with sensitivity of 0.93 and PPV of 0.77; within 4.5h with sensitivity of 0.77 and PPV of 0.96; and within 6h with sensitivity of 0.74 and PPV of 1.00. CONCLUSION FLAIR can estimate the onset time of stroke in AIS within 24h of onset.

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.

M1 Susceptibility Vessel Sign on T2* as a Strong Predictor for No Early Recanalization After IV-t-PA in Acute Ischemic Stroke

Background and Purpose— In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization of occluded arteries can improve the clinical outcome. The magnetic susceptibility effect of deoxygenated hemoglobin in red thrombi can present as hypointense signals on T2*-weighted gradient echo imaging. We investigated whether the gradient echo imaging M1 susceptibility vessel sign (M1 SVS) can predict no early recanalization after t-PA infusion. Methods— Patients with internal carotid artery and M1 occlusion were prospectively studied. MRI studies, including DWI, T2*, and MRA, were performed before and within 30 minutes and 24 hours after t-PA infusion. The NIHSS score was obtained before and 7 days after t-PA administration. The relationship between the presence of the M1 SVS and no early recanalization and patient outcome was examined. Results— A total of 48 patients (29 men; mean age, 74.6±11.2 years) were enrolled. M1 SVS was present in 13 (27.1%) patients and absent in 35 (72.9%) patients. There were no significant differences in clinical characteristics between the 2 groups. Follow-up MRA within 30 minutes after t-PA infusion revealed that 20 (57.1%) of the 35 patients without the M1 SVS had early recanalization, but that none of the 13 patients with the M1 SVS had early recanalization (P=0.0002). Seven days after t-PA infusion, dramatic improvement was more frequently observed in patients without the M1 SVS (51.4%) than in those with the M1 SVS (0%, P=0.0007). Conclusion— The M1 SVS on T2* appears to be a strong predictor for no early recanalization after t-PA therapy.

Atrial fibrillation as an independent predictor for no early recanalization after IV-t-PA in acute ischemic stroke

BACKGROUND AND PURPOSE Intravenous administration of tissue plasminogen activator (t-PA) dissolves the clot and can improve clinical outcome in patients with acute ischemic stroke. However, lack of early recanalization frequently does not result in good outcome. METHODS We prospectively studied acute stroke patients treated with t-PA and examined clinical factors associated with no early recanalization of occluded arteries after t-PA administration using serial magnetic resonance angiography (MRA). NIHSS score was obtained before and at 24h after t-PA administration. RESULTS Subjects comprised 49 consecutive stroke patients treated with t-PA. Initial MRA before t-PA infusion demonstrated occluded arteries in 37 patients. Of the 37 occluded arteries, follow-up MRA within 30min after t-PA administration revealed complete recanalization in 6 patients, partial recanalization in 12, and no early recanalization in 19. Neurological worsening (total NIHSS score increased by > or =4) occurred in 0 of 18 patients with recanalization and 4 of 19 patients with no recanalization (P=0.039). Atrial fibrillation (AF) and hypertension were more frequent in patients with non-early recanalization than in patients with recanalization (73.7% vs. 38.9%, P=0.03; 73.6% vs. 38.9%, P=0.03, respectively). However, no differences were observed in other clinical factors between groups. Multivariate logistic regression analysis demonstrated AF (OR: 9.3; CI: 1.5-55.8, P=0.015) as the only independent factor associated with no recanalization. CONCLUSION No early recanalization after t-PA administration was observed in 51.4% of acute stroke patients with occluded arteries and was significantly associated with neurological worsening. AF was independently associated with no recanalization after t-PA administration.

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.

Effects of Public Education by Television on Knowledge of Early Stroke Symptoms Among a Japanese Population Aged 40 to 74 Years A Controlled Study

Background and Purpose— An educational campaign by mass media has been associated with great increases in the knowledge about early symptoms of stroke. However, few studies were conducted with a controlled community intervention study. Methods— To clarify the effects of a 1-year television campaign for the whole population on improvement of knowledge about stroke symptoms in 2 cities, a campaign area and a control area in Japan were selected. Before and after the campaign, 1960 randomly selected residents aged 40 to 74 years answered a telephone survey regarding knowledge of early stroke symptoms. We calculated the percentage and 95% CIs of participants who correctly chose all 5 early symptoms of stroke in each area and in each year. Results— Before the campaign, 53% of participants (95% CI, 50%–55%) in the campaign area and 46% (95% CI, 44%–49%) in the control area correctly chose 5 early symptoms. After the 1-year television campaign, knowledge was significantly improved only in the campaign area (campaign area, 63%; 95% CI, 60%–66%; control area, 51%; 95% CI, 48%–54%). After sex stratification, only women showed improved knowledge of early symptoms. The audience rate for the campaign television programs was found to be higher in women than in men. Conclusions– A 1-year stroke educational television campaign effectively improved knowledge about early stroke symptoms among Japanese women aged 40 to 74 years. No impact was found among men in this age group. Future studies should examine the impact of this approach on stroke knowledge among younger individuals and whether there are any behavioral changes that contribute to earlier presentation for treatment.

Brain Natriuretic Peptide Levels as a Predictor for New Atrial Fibrillation During Hospitalization in Patients With Acute Ischemic Stroke

The aim of this study was to investigate the relation between brain natriuretic peptide (BNP) levels and the detection rate of new documented atrial fibrillation (AF) after ischemic stroke. Consecutive patients with ischemic stroke prospectively enrolled within 24 hours of onset. Patients with AF on admission electrocardiography or with histories of AF were excluded. The plasma BNP level was measured on admission, and the factors associated with new documented AF were investigated by multivariate logistic regression analysis. Furthermore, the detection rates of AF according to BNP level were evaluated. A total of 584 patients were enrolled. AF was detected in 40 patients (new AF group; 6.8%). The median BNP level of the new AF group was significantly higher than for the non-AF group (186.6 pg/ml [interquartile range 68.7 to 386.3] vs 35.2 pg/ml [interquartile range 15.9 to 80.1], p <0.0001). The cut-off level, sensitivity, and specificity of BNP levels to distinguish the new AF group from the non-AF group were 65.0 pg/ml, 80%, and 70%, respectively. Multivariate logistic regression analysis demonstrated that National Institutes of Health Stroke Scale score >7 (odds ratio 3.4, 95% confidence interval 1.685 to 7.006, p = 0.0007) and a plasma BNP level >65.0 pg/ml (odds ratio 6.8, 95% confidence interval 2.975 to 15.359, p <0.0001) were independently associated with new AF. The detection rates of AF according to BNP level were as follows: 2% of patients with <50 pg/ml, 4% of those with 50 to <100 pg/ml, 12% of those with 100 to <200 pg/ml, 26% of those with 200 to <400 pg/ml, and 38% of those with ≥400 pg/ml. In conclusion, BNP levels can predict new AF in patients with acute ischemic stroke. Elevated BNP levels result in an increase in the frequency of detection of new AF.