Junya Aoki

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.

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.

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.

Hemorrhagic transformation of ischemic brain tissue after t-PA thrombolysis as detected by MRI may be asymptomatic, but impair neurological recovery

BACKGROUND AND PURPOSE Symptomatic intracranial hemorrhages are typically clinically catastrophic and occur more frequently with tissue plasminogen activator (t-PA) therapy compared to without t-PA therapy. However, it has been unclear whether asymptomatic intracranial hemorrhage has clinical implications. METHODS Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. Patients with symptomatic hemorrhages were excluded from the study. To identify the presence of early recanalization and intracranial hemorrhage, as well as to measure infarction volume, MRI examinations, including diffusion-weighted imaging, T2(), FLAIR, and MRA, were performed before and 1 h, 24 h, and 5-7 days after t-PA thrombolysis. At the same time, serial NIHSS scores were obtained. The independent predictors of dramatic recovery were determined using multivariate logistic regression analysis. RESULTS 51 patients were enrolled in the present study. 22 patients (H group) had an asymptomatic hemorrhage. The NIHSS score of the Non-H group decreased, but that of the H group did not (11.5+/-6.5 vs. 17.1+/-6.5 at baseline, and 4.5+/-6.8 vs. 14.3+/-7.6 at 7 days; P=0.0073 for ANOVA). Asymptomatic hemorrhage was more frequently seen in non-dramatic improvement group than in dramatic improvement group (65.5% vs. 13.6%, P=0.0002). On multivariate logistic regression analysis using the variables that had a P<0.1 on univariate analysis (AF, baseline NIHSS score, glucose, the presence of asymptomatic hemorrhage, ICA occlusion, early recanalization 1 h after t-PA infusion, and infarction volume 7 days after t-PA therapy), early recanalization (OR: 11.33; 95%CI: 1.064-120.704; P=0.044) and infarction volume <100 cm(3) (OR: 13.56; 95%CI: 1.020-180.125; P=0.048) were independent factors for dramatic improvement, while asymptomatic hemorrhage (OR: 0.03; 95%CI: 0.002-0.537; P=0.016) was an independent negative factor. CONCLUSION Asymptomatic hemorrhage was an independent negative factor for dramatic improvement. Asymptomatic hemorrhage after t-PA thrombolysis may be associated with neurological recovery.

IV t-PA therapy in acute stroke patients with atrial fibrillation.

BACKGROUND AND PURPOSE Atrial fibrillation (AF) is a predictor for severe stroke. Intravenous administration of tissue plasminogen activator (t-PA) can improve clinical outcomes in patients with acute ischemic stroke. We investigated clinical characteristics and patient outcome in patients with and without AF after t-PA therapy. METHODS Consecutive ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. MRI examinations, including diffusion weighted imaging and MRA, were performed before t-PA thrombolysis. NIHSS scores were obtained before and 7 days after t-PA infusion. The patients were divided into two groups (AF group and Non-AF group). Their clinical characteristics and outcome 7 days and 3 months after t-PA therapy were compared. RESULTS 85 patients (56 males, mean age, 73.4+/-11.5 years) were enrolled in the present study. The AF-group had 44 patients, and the Non-AF group had 41 patients. Fewer patients with AF had dramatic improvement at 7 days and favorable outcome (mRS 0-1) at 3 months after t-PA therapy than patients without AF (31.8% vs. 61.0%, P=0.007, and 15.9% vs. 46.3%, P=0.002). On the other hand, worsening at 7 days and poor outcome (mRS >3 and death) at 3 months after t-PA therapy were more frequently observed in AF group than Non-AF group (22.7% vs. 9.8%, P=0.107, and 70.5% vs. 41.5%, P=0.007). After adjusting age and gender, patients with AF more frequently had worsening and poor outcome than those without AF (adjusted OR; 4.54, 95% CI 1.04-19.75, P=0.044, and adjusted OR; 2.8, 95% CI 1.10-7.28, P=0.032). CONCLUSION The present study found that acute ischemic stroke patients with AF more frequently had poor outcome after IV-t-PA therapy compared with those without AF.

Addition of Hyperacute MRI Aids in Patient Selection, Decreasing the Use of Endovascular Stroke Therapy

Background and Purpose— The failure of recent trials to show the effectiveness of acute endovascular stroke therapy (EST) may be because of inadequate patient selection. We implemented a protocol to perform pretreatment MRI on patients with large-vessel occlusion eligible for EST to aid in patient selection. Methods— We retrospectively identified patients with large-vessel occlusion considered for EST from January 2008 to August 2012. Patients before April 30, 2010, were selected based on computed tomography/computed tomography angiography (prehyperacute protocol), whereas patients on or after April 30, 2010, were selected based on computed tomography/computed tomography angiography and MRI (hyperacute MRI protocol). Demographic, clinical features, and outcomes were collected. Univariate and multivariate analyses were performed. Results— We identified 267 patients: 88 patients in prehyperacute MRI period and 179 in hyperacute MRI period. Fewer patients evaluated in the hyperacute MRI period received EST (85 of 88, 96.6% versus 92 of 179, 51.7%; P<0.05). The hyperacute-MRI group had a more favorable outcome of a modified Rankin scale 0 to 2 at 30 days as a group (6 of 66, 9.1% versus 33 of 140, 23.6%; P=0.01), and when taken for EST (6 of 63, 9.5% versus 17 of 71, 23.9%; P=0.03). On adjusted multivariate analysis, the EST in the hyperacute MRI period was associated with a more favorable outcome (odds ratio, 3.4; 95% confidence interval, 1.1–10.6; P=0.03) and reduced mortality rate (odds ratio, 0.16; 95% confidence interval, 0.03–0.37; P<0.001). Conclusions— Implementation of hyperacute MRI protocol decreases the number of endovascular stroke interventions by half. Further investigation of MRI use for patient selection is warranted.