Takeshi Iwanaga

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.

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.

Clinical–Diffusion Mismatch and Benefit From Thrombolysis 3 to 6 Hours After Acute Stroke

Background and Purpose— The clinical-diffusion mismatch (CDM) model has been proposed as a simpler tool than perfusion-diffusion mismatch (PDM) to select acute ischemic stroke patients for thrombolytic therapy. We hypothesized that in the 3- to 6-hour time window, the effect of tPA was significantly greater in patients with CDM than in patients without CDM. Methods— This is a substudy of EPITHET, a double-blind multi-center study of 100 patients randomized to tPA or placebo 3 to 6 hours after stroke onset. MRI was obtained before treatment, and at 3 to 5 days and 90 days after treatment. Presence of PDM (perfusion deficit/DWIvolume >1.2 and perfusion deficit at least 10 mL>DWIvolume) and CDM (NIHSS ≥8 and DWIvolume ≤25 mL) was determined for each patient. We assessed lesion growth and neurological improvement (decrease in NIHSS ≥8 points between baseline and 90 days, or a 90-day NIHSS ≤1). Results— 86% of the patients had PDM, but only 41% had CDM. CDM detected PDM with a sensitivity of 46% and a specificity of 86%. We found statistically significant effects of reperfusion on the rate of neurological improvement (OR 9.92, 95% CI 1.91 to 51.64; P<0.01) and on absolute growth (difference: −59.60 mL, 95% CI −95.40 mL to −23.81 mL; P<0.01). Neither treatment with tPA nor reperfusion had a significantly different impact on lesion growth or clinical course in CDM patients compared to patients without CDM. Conclusions— There was no increased benefit from tPA in patients with CDM. The beneficial effects of reperfusion were similar in patients with and without CDM.

Transcranial Doppler and Carotid Duplex Ultrasonography Findings in Bow Hunter's Syndrome

Bow hunters syndrome (BHS) is caused by transient vertebro‐basilar ischemia on head rotation. We report a patient with BHS who was identified from dynamic changes to blood flow velocities in the posterior cerebral, basilar and vertebral arteries using carotid duplex ultrasonography and transcranial Doppler, simultaneously. Neurosonology appears to be useful for diagnosing and evaluating BHS.

Increasing number of stroke specialists should contribute to utilization of IV rt-PA: Results of questionnaires from 1466 hospitals in Japan

PURPOSE To determine the present status of intravenous recombinant tissue plasminogen activator (IV rt-PA) administration in Japan, we investigated the components of stroke case related to IV rt-PA utilization using a questionnaire sent to hospitals. METHODS Questionnaires about the infrastructure of acute stroke care were sent to 8,589 hospitals between August and October 2007. Responses were categorized as follows: 1) stroke service run by stroke physicians (SPs) 24 h/day, 7 days/week (24/7); 2) IV rt-PA utilizable 24/7 (rt-PA hospitals); 3) the total number of SPs. The components related to rt-PA hospitals were analyzed and the significance of the number in SPs to the rt-PA hospital was investigated. RESULTS Responses were received from 4,690 (54.7%) of 8,569 hospitals. Of these, 1,466 hospitals were admitting acute stroke patients. 519 of those hospitals were rt-PA hospitals. Of the 1,466 (35.4%), 48.4% were serviced 24/7 by SPs, with 75.2% having <5 SPs. Multivariate analysis revealed administration of rt-PA was significantly associated with >4 SPs (odds ratios (OR), 2.8; 95% confidence interval (95%CI), 1.9-4.1; p<0.001). Compared to hospitals with 0-1 SPs as a reference, the OR for rt-PA utilization was 5.6 (95%CI, 2.5-12.9; p<0.001) with 5 SPs, 10.8 (95%CI, 5.0-23.6; p<0.001) with 6-10 SPs, and 37.3 (95%CI, 6.5-213.1; p<0.001) with >10 SPs. CONCLUSIONS An increased number of SPs was associated with increased IV rt-PA utilization. Development of stroke centers with larger numbers of SPs is therefore urgently needed.

Diameter of the Basilar Artery May Be Associated with Neurological Deterioration in Acute Pontine Infarction

Purpose: The present study investigated the factors related to neurological deterioration in pontine infarction. Methods: Consecutive patients with acute pontine infarction without basilar artery (BA) occlusion were enrolled. Patients were classified into two groups (D, group with neurological deterioration; ND, group without neurological deterioration). After magnetic resonance angiography was performed to identify the diameters of internal carotid artery (ICA) and BA, the BA diameter/ICA diameter (BA/ICA) ratio was calculated. When the ischemic lesion on diffusion-weighted magnetic resonance imaging extended to the ventral basal pial surface, it was diagnosed as branch atheromatous disease (BAD). Results: Neurological deterioration occurred in 16 (31%) of 51 patients. BAD was found in 13 (81%) of 16 patients of the D group and 14 (40%) of 35 in the ND group (p = 0.008). The BA/ICA ratio was 0.73 (0.59–0.84) in the D group and 0.64 (0.55–0.71) in the ND group (p = 0.049). Multivariate regression analysis demonstrated that BAD (OR 15.62, 95% CI 2.37–103.13, p = 0.004) and a BA/ICA ratio of ≧0.70 (OR 7.76, 95% CI 1.55–38.88, p = 0.013) were independent factors associated with neurological deterioration. Conclusion: The BA diameter may be associated with neurological deterioration in acute pontine infarction.

Microembolic signals are associated with progression of arterial lesion in Moyamoya disease: A case report

Transcranial Doppler ultrasonography (TCD) and magnetic resonance angiography (MRA) confirmed a rapid progression of arterial lesion in Moyamoya disease after the patient gave birth. TCD could initially detect a large number of microembolic signals (MES) at the distal portion of stenotic lesions. After MRA showed the development of stenotic lesions 10 days after first TCD monitoring, MES were absent. MES may be related to the clinical activity of Moyamoya disease.

In-hospital onset ischemic stroke may be associated with atrial fibrillation and right-to-left shunt

BACKGROUND AND PURPOSE Ischemic stroke during hospitalization can occasionally be found, but the mechanisms and causes underlying stroke have not been investigated in detail. The present study aimed to identify differences in stroke etiology between in-hospital and out-of-hospital onset. METHODS Subjects comprised 357 consecutive patients (221 men, 136 women) with ischemic stroke prospectively enrolled within 24 h of onset. Contrast saline transcranial Doppler ultrasonography (c-TCD) or transesophageal echocardiography (TEE) was performed in all participants to identify right-to-left shunts (RLS). Patients were divided into 2 groups: in-hospital onset (IHO group, n=49); and out-of-hospital onset (OHO group, n=308). Clinical characteristics were compared between groups. RESULTS Mean age was 71.5+/-12.3 years. Mean National Institute of Health stroke scale score was 6.9+/-7.2. RLS, atrial fibrillation (AF) and malignancy were more frequent in the IHO group than in the OHO group (39% vs. 20%, p=0.006; 45% vs. 16%, p<0.001; 18% vs. 4%, p<0.001, respectively). AF and/or RLS was more frequent in the IHO group (61%) than in the OHO group (30%, p<0.001). CONCLUSION Ischemic stroke with in-hospital onset may be associated with AF and RLS.