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We describe a patient with a cerebral infarction localized mainly in the left posterior frontal and anterior parietal subcortices who experienced a Broca's aphasia which evolved into a conduction aphasia. Such a rare recovery pattern of aphasia appeared to result from amelioration of the damage to the left precentral gyrus.

Objective: The purpose of the present study was to clarify the present status of stroke medicine in Japan using a hospital-based, prospective registration study of 156 hospitals from all over Japan. Methods: Consecutive patients with acute ischemic stroke and transient ischemic attack (TIA) who presented to hospital within 7 days of onset from May 1999 to April 2000 were enrolled in this study. A common protocol was applied in every participating hospital. Results: A total of 16,922 patients (TIA, 6.4%) with a mean age of 70.6 ± 11.5 years (median 71 years, range 18–107 years) were enrolled in the study. Lacunar stroke was the most frequent stroke subtype (38.8%), followed by atherothrombotic (33.3%), cardioembolic (21.8%) and other stroke (6.1%). NIHstroke scale score on admission was 8.0 ± 7.9 (median 5; 25th to 75th percentile, 2–11). 36.8% arrived at hospital within 3 h of symptom onset, and 49.5% within 6 h. The ambulance was used for 70.2% of patients arriving within 3 h after onset, but in only 29.9% of patients visiting the hospital later than 3 h after onset (p < 0.0001). 60.8% displayed good outcome (modified Rankin Scale score of 0–2 at discharge), while 32.3% displayed poor outcome (score 3–5), and mortality rate was 6.9%. Conclusions: More than half of the acute stroke patients arrived at hospital later than 6 h after onset. Establishment of ideal emergency systems is needed for better management of stroke and for improvement of patient outcome, in particular, in the future after approval of intravenous recombinant tissue plasminogen activator for acute ischemic stroke by the Japanese government.Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, unexpected activity patterns emerged among Yucatan mini-swine models for heart failure and atrial fibrillation. As part of our laboratory research, we tracked activity data by FitBark™ collars that the Yucatan mini-swine wore. Previously, staff engaged with the swine daily, such as applying lotion and conducting 6-min treadmill runs. However, pandemic restrictions reduced interaction to 1 or 2 times a week, often for less than 10 min each session. Contrary to expectations, there was a significant increase in the swine's activity levels during these minimal interaction periods. After cleaning, moisturizing, weighing, and FitBark data collection, staff engaged with the swine through feeding and play. Three time frames were analyzed: prepandemic, pandemic, and reentry. Prepandemic and reentry periods involved daily 15-min interactions with 2 staff members per swine to maintain cleanliness and health. During the pandemic, interaction was reduced to 1 or 2 times weekly. The hours between 1000 and 1400 were designated as 'passive activity', representing the swines' isolated behavior, unaffected by staff interaction. The chronic heart failure swine ( n = 3) had an average passive activity area under the curve prepandemic value of 47.23 ± 2.52 compared with pandemic 57.09 ± 2.90, pandemic 57.09 ± 2.90 compared with reentry 50.44 ± 1.61, and prepandemic compared with reentry. The atrial fibrillation swine ( n = 3) had an average passive activity area under the curve minimal interaction (mimicking pandemic) value of 59.27 ± 6.67 compared with interaction (mimicking prepandemic or reentry) 37.63 ± 1.74. The heightened activity levels during minimal interaction suggest physiologic and psychologic changes in the animals due to reduced socialization. This highlights the importance of enrichment and interaction in research animals and underscores the broader impact of the COVID-19 pandemic on research outcomes. These findings could also shed light on the effects of the pandemic on human behavior.

Aim: The present study aimed to investigate the impact of mild tricuspid regurgitation (TR) on the exercise capacity or clinical outcomes in patients with chronic heart failure (CHF)., Methods and Results: The study enrolled 511 patients with CHF who underwent cardiopulmonary exercise testing (CPET) between 2013 and 2018. The primary outcome was a composite of heart failure hospitalization and death. Patients with mild TR ( n = 324) or significant TR (moderate or greater; n = 60) displayed worse NHYA class and reduced exercise capacity on CPET than those with non-TR ( n = 127), but these were more severely impaired in patients with significant TR. A total of 90 patients experienced events over a median follow-up period of 3.3 (interquartile range 0.8-5.5) years. Patients with significant TR displayed a higher risk of events, while patients with mild TR had a 3.0-fold higher risk of events than patients with non-TR (hazard ratio (HR) 3.01; 95% confidence interval (CI), 1.50-6.07). Multivariate Cox regression analysis showed that, compared with non-TR, mild TR was associated with increased adverse events, even after adjustment for co-variates (HR 2.97; 95% CI, 1.35-6.55)., Conclusions: TR severity was associated with worse symptoms, reduced exercise capacity, and poor clinical outcomes. Even patients with mild TR had worse clinical characteristics than those with non-TR.

Background: The differences in pre- and early post-procedural blood flow dynamics between the two major types of bioprosthetic valves, the balloon-expandable valve (BEV) and self-expandable valve (SEV), in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), have not been investigated. We aimed to investigate the differences in blood flow dynamics between the BEV and SEV using four-dimensional flow cardiovascular magnetic resonance (4D flow CMR)., Methods: We prospectively examined 98 consecutive patients with severe AS who underwent TAVR between May 2018 and November 2021 (58 BEV and 40 SEV) after excluding those without CMR because of a contraindication, inadequate imaging from the analyses, or patients' refusal. CMR was performed in all participants before (median interval, 22 [interquartile range (IQR) 4-39] days) and after (median interval, 6 [IQR 3-6] days) TAVR. We compared the changes in blood flow patterns, wall shear stress (WSS), and energy loss (EL) in the ascending aorta (AAo) between the BEV and SEV using 4D flow CMR., Results: The absolute reductions in helical flow and flow eccentricity were significantly higher in the SEV group compared in the BEV group after TAVR (BEV: - 0.22 ± 0.86 vs. SEV: - 0.85 ± 0.80, P < 0.001 and BEV: - 0.11 ± 0.79 vs. SEV: - 0.50 ± 0.88, P = 0.037, respectively); there were no significant differences in vortical flow between the groups. The absolute reduction of average WSS was significantly higher in the SEV group compared to the BEV group after TAVR (BEV: - 0.6 [- 2.1 to 0.5] Pa vs. SEV: - 1.8 [- 3.5 to - 0.8] Pa, P = 0.006). The systolic EL in the AAo significantly decreased after TAVR in both the groups, while the absolute reduction was comparable between the groups., Conclusions: Helical flow, flow eccentricity, and average WSS in the AAo were significantly decreased after SEV implantation compared to BEV implantation, providing functional insights for valve selection in patients with AS undergoing TAVR. Our findings offer valuable insights into blood flow dynamics, aiding in the selection of valves for patients with AS undergoing TAVR. Further larger-scale studies are warranted to confirm the prognostic significance of hemodynamic changes in these patients., (© 2023. Society for Cardiovascular Magnetic Resonance.)

Background: The characteristics of high-risk coronary atherosclerosis evaluated using optical coherence tomography (OCT) can have a prognostic role. Inflammatory biomarkers may be related to the severity of coronary artery disease. This study investigated the association of high-risk morphological features of coronary plaques on OCT with circulating levels of inflammatory biomarkers and target lesion revascularization (TLR)., Materials and Methods: We prospectively analyzed the data of 30 consecutive patients with chronic coronary syndrome who underwent percutaneous coronary intervention (PCI) using OCT. The levels of interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein, pentraxin 3, vascular endothelial growth factor, and monocyte chemoattractant protein-1 (MCP-1) were measured in plasma samples. Coronary plaque characteristics were scored quantitatively in the form of coronary plaque risk score (CPRS). The estimated high-risk plaque characteristics for TLR were plaque rupture, plaque erosion, calcified nodule, lipid-rich plaque, thin-cap fibroatheroma, cholesterol crystals, macrophage infiltration, microchannels, calcification angle >90°, and microcalcifications. Each high-risk feature carries 1 point. Patients were defined as having a low CPRS (CPRS ≤3) or a high CPRS (CPRS ≥4)., Results: The primary outcome was TLR. TLR occurred in 6 (20%) patients within 15 months of PCI. High CPRS on OCT was directly correlated with TLR (P=0.029). In logistic regression analysis, CPRS was associated with TLR (odds ratio, 10.0; 95% confidence interval, 1.34-74.5). Serum MCP-1 level was significantly correlated with the CPRS (P=0.020)., Conclusions: In patients with chronic coronary syndrome, CPRS may be a surrogate predictor of TLR. Serum MCP-1 may aid in the detection of high-risk coronary atherosclerosis., Competing Interests: None., (AJCD Copyright © 2023.)

Background: Although high-sensitivity cardiac troponins may be sensitive and easily repeatable markers of disease activity in patients with cardiac sarcoidosis (CS), the association between longitudinal cardiac troponin trajectory and adverse events remains unclear. This study aimed to clarify whether longitudinal cardiac troponin levels were associated with adverse events in patients with CS., Methods: We examined 63 consecutive CS-initiated prednisolone (PSL) patients with available longitudinal high-sensitivity cardiac troponin T (cTnT) data between December 2013 and March 2023. The area under the cTnT trajectory, which reflected cumulative cTnT release, was calculated to assess the association between longitudinal cTnT levels and adverse events. Patients were divided into two groups according to the median area under the cTnT trajectory per month. The primary outcome was a composite of sustained ventricular tachycardia or fibrillation, worsening heart failure, and sudden cardiac death (SCD)., Results: In total, 463 cTnT measurements were collected over a median follow-up period of 30.4 (interquartile range [IQR] 15.6-34.2) months. The primary outcome was observed in 12 (19%) patients. A higher area under the cTnT trajectory was significantly associated with an increased incidence of the primary outcome (P = 0.027), while cTnT levels before and one month after initiation of PSL, and these changes were not related to adverse events (P = 0.179, 0.096, and 0.95, respectively)., Conclusions: Longitudinal cTnT trajectory following PSL initiation was associated with adverse cardiac events in patients with CS, suggesting that longitudinal measurement of cTnT would be useful for the early identification of high-risk patients., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Several liver fibrotic markers are associated with prognosis in patients with heart failure (HF). However, the optimal markers for outcome prediction remain unclear. This study aimed to simultaneously investigate the prognostic value of liver fibrotic markers and the associations between these markers and clinical parameters in patients with HF without organic liver disease. We prospectively examined 211 consecutive patients with chronic HF between April 2018 and August 2021, excluding those with organic liver disease, using liver magnetic resonance imaging and ultrasound. A total of 7 representative liver fibrotic markers were measured in all patients. The primary outcome of interest was the composite of all-cause death and hospitalization for worsening HF. During a median follow-up period of 747 (interquartile range 465 to 1,042) days, the primary outcome occurred in 45 patients. Patients with higher hyaluronic acid and type III procollagen N-terminal peptide (P-III-P) levels showed a significantly higher incidence of the primary outcome than those without (p <0.001 and p = 0.005, respectively). The multivariable Cox regression analysis revealed that hyaluronic acid and P-III-P levels were independently associated with the risk of adverse events (hazard ratio 1.84, 95% confidence interval 1.18 to 2.87 and hazard ratio 2.89, 95% confidence interval 1.32 to 6.34, respectively) even after adjustment for a mortality prediction model, whereas the other 5 markers were not associated with the primary outcome. In conclusion, among the representative liver fibrotic markers, hyaluronic acid and P-III-P might be the optimal markers for outcome prediction in patients with HF., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The prognostic impact of peak workload-to-weight ratio (PWR) during cardiopulmonary exercise testing (CPET) and its determinants in patients with chronic heart failure (CHF) are not well understood. Consecutive 514 patients with CHF referred for CPET at the Hokkaido University Hospital between 2013 and 2018 were identified. The primary outcome was a composite of hospitalization because of worsening heart failure and death. PWR was calculated as peak workload normalized to body weight (W/kg) by CPET. Patients with low PWR (cut-off median 1.38 [W/kg], n = 257) were older and more anemic than those with high PWR (n = 257). In CPET, patients with low PWR displayed reduced peak oxygen consumption and impaired ventilatory efficiency compared with those with high PWR, whereas the peak respiratory exchange ratio was not significantly different between the 2 groups. There were 89 patients with events over a median follow-up period of 3.3 (interquartile range 0.8 to 5.5) years. The incidence of composite events was significantly higher in patients with low PWR than in those with high PWR (log-rank p <0.0001). In the multivariable Cox regression, lower PWR was associated with adverse events (hazard ratio 0.31, 95% confidence interval 0.13 to 0.73, p = 0.008). Low hemoglobin concentration was strongly related to impaired PWR (β coefficient = 0.43, per 1 g/100 ml increased, p <0.0001). In conclusion, PWR was associated with worse clinical outcomes, where blood hemoglobin was strongly related to PWR. Further study is required to identify therapies targeting peak workload achievements in exercise stress tests to improve the outcome in patients with CHF., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography., Methods: In a systematic review of OVID MEDLINE-with additional hand-searching of relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5-24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known., Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36-0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46-11·60; p<0·0001), antiplatelet use (1·68, 1·06-2·66; p=0·026), and anticoagulant use (3·48, 1·96-6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75-0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95-6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03-0·07)., Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials., Funding: UK Medical Research Council and British Heart Foundation., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of this study was to examine the 1-year cumulative mortality rate and cause of death, and to identify the predictive factors for death after hospital discharge following ischemic stroke and transient ischemic attack (TIA) using data from the Japan Multicenter Stroke Investigators' Collaboration study., Methods: We prospectively registered 16,922 consecutive patients with acute ischemic stroke or TIA from May 1999 to April 2000 in 156 Japanese hospitals. We mailed a questionnaire to the 15,322 patients who were alive at hospital discharge., Results: 10,981 patients (6,945 men, 4,036 women, age 70 +/- 11 years, median 71, range 19-100 years) were enrolled in the follow-up study. The mean follow-up period was 271 +/- 110 days (median 272 days; range 1-487 days). The 1-year cumulative mortality was 6.8% (7.0% for 10,234 stroke patients and 3.5% for 747 TIA patients). The causes of death were: cerebrovascular disease, 24.1%; pneumonia, 22.6%; heart disease, 18.1%; cancer, 11.0%, and miscellaneous causes, 24.1%. Multivariate analysis suggested that male gender, age, diabetes mellitus, atrial fibrillation, history of stroke, nonlacunar stroke, functional disability and transfer to another hospital or nursing home on discharge were significant independent predictors of death during the follow-up period., Conclusions: The major causes of death after hospital discharge were found to be cerebrovascular diseases, pneumonia and heart diseases. Thus, in order to improve survival after hospital discharge, in addition to appropriate management of vascular risk factors following stroke, it appears to be important to take measures to prevent pneumonia and to discharge patients to their own home, if possible., (Copyright 2005 S. Karger AG, Basel)

Background and Purpose: It is unclear whether acute ischemic stroke exhibits a seasonal pattern in Japan. The aim of the present study was to elucidate seasonal differences in acute ischemic stroke., Methods: Our study enrolled 12,660 patients with ischemic stroke (7943 men, 4717 women; mean age, 70.1 years, S.D. 11.5; median 70; range 18-107). We divided the year into four parts: spring (March-May); summer (June-August); fall (September-November); and winter (December-February). Time of stroke onset was divided into three subgroups: daytime (08:00-16:00), evening (16:00-24:00), and night (24:00-08:00). We examined the association between clinical characteristics, season, and time of stroke onset., Results: Stroke occurred least frequently in spring (22.9%), followed by winter (25.3%), fall (25.8%), and summer (26.0%) (P<0.001). No differences in age, National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (m-RS) score, history of stroke/transient ischemic attack (TIA), or risk factors for stroke were observed among the four seasons. Stroke in men (63.8% vs. 62.4%; P<0.01), lacunar stroke (LS) (41.2% vs. 39.4%, P<0.01), atherothrombotic stroke (ATS) (34.0% vs. 32.3%; P<0.01), and nighttime stroke (26.5% vs. 24.8%; P<0.05) were observed more frequently in summer compared to other seasons. This contrasts with the findings for stroke in women (39.0% vs. 36.7%; P<0.05), cardioembolic stroke (CES) (23.4% vs. 20.6%; P<0.05), and daytime stroke (47.4% vs. 45.0%; P<0.05), which were more frequent in winter., Conclusions: Acute ischemic stroke displays seasonal characteristics according to gender, stroke subtype, and time of stroke onset. These results may have important clinical implications in ischemic stroke prevention.

In ischaemic stroke, expansion of the infarct core occurs at the expense of surrounding hypoxic, metabolically compromised tissue over a period of 24 h or more in a considerable proportion of patients. It is uncertain whether hypoxic tissue observed at later times after stroke onset retains the potential for survival or whether such survival has an impact on functional outcome. These factors may determine the effectiveness of therapeutic strategies aimed at salvaging this tissue. We tested the hypotheses that metabolically compromised hypoxic tissue observed within 48 h after onset of ischaemic stroke retains the potential for spontaneous survival and that the impact of such survival on functional outcome is time dependent. Consecutive patients presenting within 48 h of ischaemic stroke were studied with [(18)F]fluoromisonidazole, a ligand binding to hypoxic but viable tissue, and PET. Subjects were grouped into two time epochs, 12 h, based on the interval from stroke onset to the time of tracer injection, and had infarct volumes measured on CT/MRI at 7 days (n = 60). The total ischaemic volume (TIV) and the proportion of the TIV that spontaneously survived (surviving hypoxic volume ratio, SHVR) were defined from the co-registered CT/MRI images. These volumetric measures were correlated with neurological outcome assessed at day 7-10 by percentage change in the National Institutes of Health Stroke Scale (DeltaNIHSS), and at 3 months by Barthel Index (BI) and modified Rankin Score (mRS). Of 66 patients investigated, hypoxic tissue occurred in 33 and outcome data was available in 27. Hypoxic tissue constituted >20% of the TIV in 60% of studies 12 h. The spontaneously surviving proportion of the TIV (median 6.9%) or hypoxic tissue (median 45.9%) was not significantly different in patient subgroups studied 12 h after stroke onset. Spontaneous survival of hypoxic tissue (surviving hypoxic volume ratio) was associated with improved neurological outcome in both time epochs: 12 h, DeltaNIHSS (r = 0.59, P < 0.01) and day 90 mRS (r = -0.46, P < 0.05). The finding that similar proportions of hypoxic tissue survived spontaneously within each time epoch suggests that its fate is not predetermined. The favourable neurological outcome associated with spontaneous survival of hypoxic tissue, even 12-48 h after stroke onset, suggests that the volume of hypoxic tissue that progressed to infarction may represent a valuable target for therapeutic intervention.

The location as well as the volume of the ischemic penumbra in human stroke is likely to influence the outcome of therapeutic intervention but its spatial extent is poorly characterized. Based on the observation that infarct expansion progresses from the center to the periphery of the penumbra in animal stroke models, we describe a method of mapping the three-dimensional spatial extent of the penumbra relative to the infarct in a 'Penumbragram'. Central, peripheral and external zones of the final infarct were defined according to median voxel distance from the infarct center (IC) and were further subdivided by coronal, sagittal and axial planes through the IC. In 10 patients with hypoxic, viable (penumbral) tissue identified by (18)F-Fluoromisonidazole positron emission tomography within 48 h of stroke onset, 'Penumbragrams' displaying the percentage of penumbra in each region were generated using anatomically co-registered data sets. The correlation between penumbral percentage and time from stroke onset was negative in the central (P < 0.05) and peripheral (P > 0.05) zones of the infarct and positive in external zones (P < 0.05). The validity of infarct segmentation was assessed by factor analysis with no a priori grouping of regions. Negative and positive correlations of penumbra volume and time from stroke onset were observed in seven (five corresponding to central zone of the infarct) and four (all in external zone) infarct regions and were measured reliably (Cronbach's alpha 0.84 and 0.9, respectively). The 'Penumbragram' is a valid method for objectively mapping the spatial extent of the penumbra, which is applicable to other imaging modalities.

The purpose of this study was to obtain fundamental information on patients with acute ischemic stroke and transient ischemic attack (TIA) in Japan. We prospectively registered consecutive stroke and TIA patients who visited 156 participating hospitals within 7 days of onset between May 1, 1999 and April 30, 2000. A total of 16,922 patients with 70.6 +/- 11.5 years old (median 71, range 18-107) were enrolled in the study. TIA was seen in 7% of registered patients, lacunar stroke in 36%, atherothrombotic in 31%, cardioembolic stroke in 20%, and other in 6%. Hypertension was present in 61%, diabetes mellitus in 24%, atrial fibrillation (AF) in 21%, smoking in 18%, and hypercholesterolemia in 17%. Overall, 37% of patients arrived at hospital within 3 hours of symptom onset, and 50% within 6 hours. Among those who visited the hospital within 6 hours, 64% used an ambulance service. Mean NIHSS score was 8.0 +/- 7.9 (median, 5). Only 3% were treated with thrombolytic agents in acute phase of stroke. Only 19% of all patients were treated in stroke care unit or intensive care unit. The modified Rankin Scale score of 0 to 2 at discharge was observed in 61% of the patients, 3 to 5 in 32%, and the mortality rate was 7%. More than half of the acute stroke patients arrived at the hospital after 6 hours of onset, and the stroke care unit was used only in one fifth of all patients. Establishment of ideal emergency system and arrangement of stroke units are also awaited for better management and improvement of patients' outcome.

Objective: The purpose of the present study was to clarify the present status of stroke medicine in Japan using a hospital-based, prospective registration study of 156 hospitals from all over Japan., Methods: Consecutive patients with acute ischemic stroke and transient ischemic attack (TIA) who presented to hospital within 7 days of onset from May 1999 to April 2000 were enrolled in this study. A common protocol was applied in every participating hospital., Results: A total of 16,922 patients (TIA, 6.4%) with a mean age of 70.6 +/- 11.5 years (median 71 years, range 18-107 years) were enrolled in the study. Lacunar stroke was the most frequent stroke subtype (38.8%), followed by atherothrombotic (33.3%), cardioembolic (21.8%) and other stroke (6.1%). NIH stroke scale score on admission was 8.0 +/- 7.9 (median 5; 25th to 75th percentile, 2-11). 36.8% arrived at hospital within 3 h of symptom onset, and 49.5% within 6 h. The ambulance was used for 70.2% of patients arriving within 3 h after onset, but in only 29.9% of patients visiting the hospital later than 3 h after onset (p < 0.0001). 60.8% displayed good outcome (modified Rankin Scale score of 0-2 at discharge), while 32.3% displayed poor outcome (score 3-5), and mortality rate was 6.9%., Conclusions: More than half of the acute stroke patients arrived at hospital later than 6 h after onset. Establishment of ideal emergency systems is needed for better management of stroke and for improvement of patient outcome, in particular, in the future after approval of intravenous recombinant tissue plasminogen activator for acute ischemic stroke by the Japanese government., (Copyright 2004 S. Karger AG, Basel)

Background and Purpose: We sought to characterize the spatial and temporal evolution of human cerebral infarction. Using a novel method of quantitatively mapping the distribution of hypoxic viable tissue identified by 18F-fluoromisonidazole (18F-FMISO) PET relative to the final infarct, we determined its evolution and spatial topography in human stroke., Methods: Patients with acute middle cerebral artery territory stroke were imaged with 18F-FMISO PET (n=19; <6 hours, 4; 6 to 16 hours, 4; 16 to 24 hours, 5; 24 to 48 hours, 6). The hypoxic volume (HV) comprised voxels with significant (P<0.05; >1 mL) uptake on statistical parametric mapping compared with 15 age-matched controls. Central, peripheral, and external zones of the corresponding infarct on the anatomically coregistered delayed CT were defined according to voxel distance from the infarct center and subdivided into 24 regions by coronal, sagittal, and axial planes. Maps ("penumbragrams") displaying the percentage of HV in each region were generated for each time epoch., Results: Higher HV was observed in the central region of the infarct in patients studied within 6 hours of onset (analysis of covariance [ANCOVA]; P<0.05) compared with those studied later, in whom the HV was mainly in the periphery or external to the infarct. HV was maximal in the superior, mesial, and posterior regions of the infarct (ANCOVA; P<0.05)., Conclusions: These observations suggest that infarct expansion occurs at the expense of hypoxic tissue from the center to the periphery of the ischemic region in humans, similar to that seen in experimental animal models. These findings have important pathophysiological and therapeutic implications.

Objectives: The underlying cause of lobar intracerebral hemorrhage (ICH) is often difficult to determine, since these vascular abnormalities are not necessarily visualized in radiographic studies. We sought to determine the clinical features of hypertensive and nonhypertensive lobar ICH, and further predict the presence or absence of vascular abnormalities in terms of clinical features and radiographic abnormalities., Patients and Methods: Eighty-one patients with lobar ICH were retrospectively assigned to either hypertensive or non-hypertensive groups based on their blood pressure levels during the chronic phase or a history of antihypertensive medication. The clinical and radiographic features of these two groups were compared., Results: Forty-nine patients (60%) were hypertensive, and the other thirty-two (40%) were non-hypertensive. In the non-hypertensive group, amyloid angiopathy (n = 6), aneurysms (n = 5), arteriovenous malformation (n = 4), use of anticoagulants (n = 2), liver cirrhosis (n = 2) and thrombasthenia (n = 1) were found as underlying causes. There were no significant differences between these two groups in the frequencies of stroke risk factors except for hypertension, clinical features and initial neurological findings. On the contrary, subarachnoid extension of the hematoma on CT was significantly more frequent in the non-hypertensive lobar ICH group than in the hypertensive group (p < 0.001). The patients with subarachnoid extension were more likely to have vascular abnormality than those without subarachnoid extension (p < 0.01)., Conclusion: Subarachnoid extension of the hematoma on CT strongly indicates a non-hypertensive cause, and more specifically, it suggests lobar ICH caused by vascular abnormalities.

To assess the clinical features and regional variations in clinical profile of and managements for acute ischemic stroke patients, 14,864 patients with 3 major clinical categories of brain infarction (lacunar, atherothrombotic and cardioembolic stroke), among the acute ischemic stroke patients registered by 156 representative hospitals all over Japan (Japan Multicenter Stroke Investigators' Collaboration: J-MUSIC) during a period of one year from May 1999 to April 2000, were subjected to the study. Data were analyzed in each 7 geographic district (Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku/Shikoku and Kyushu). As for overall proportions of 3 major categories, lacunar stroke was the most common type (41.3%), followed by atherothrombotic (35.4%) and cardioembolic stroke (23.3%). In Kanto, Kinki and Chugoku/Shikoku Districts, however, proportion of atherothrombotic stroke was larger than that of lacunar stroke, which seemed to correspond to the higher frequency of patients with diabetes mellitus and hyperlipidemia in these 3 districts. Drug treatments, care and hospital facilities varied among districts considerably. Nation-wide consensus for ideal treatments by each stroke category is therefore needed.

Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects.

Objective: Since little is known concerning factors which may influence long-term prognosis of patients presenting with lacunar stroke, we conducted a longitudinal study of this stroke subtype. Variables likely to affect outcome were assessed at baseline, including those from transoesophageal echocardiographic studies., Methods: Consecutive patients presenting with first-ever lacunar stroke underwent diagnostic workup that included brain CT or MRI, carotid duplex, and transthoracic and transoesophageal echocardiography. An assessment of patients was planned at entry (baseline), and thereafter every 12 months (clinic visit or telephone call), drop-out, or endpoint. The primary endpoint was nonfatal or fatal stroke. Secondary endpoint was death due to any cause., Results: Among 60 consecutive lacunar patients with the mean follow-up period of 3.9 years, 12 patients (20%) had stroke recurrence. The mean annual rate for stroke was 5.2%, and for death 2.8%. For multivariate Cox proportional hazards analysis, the following three variables with the values of p < 0.1 after univariate testing were chosen: age (p = 0.095); aortic atheroma (p = 0.066); and any source of embolism from heart (p = 0.007). Any source of embolism from heart was the only factor which significantly enhanced the risk of stroke recurrence (p = 0.015). Using Kaplan-Meier life table analysis, the curves of percent free of recurrent stroke were significantly different (log rank test p = 0.002)., Conclusions: Until the mechanism of lacunar stroke is better understood, it is reasonable to suggest that its investigation and prevention should be directed at all potential causes of future strokes including cardioembolism., (Copyright 2001 S. Karger AG, Basel)

To reassess the independent risk factors for lacunar stroke and to clarify the role of potential embolic sources, we conducted a case-control study using transesophageal echocardiography and duplex ultrasonography. Among 62 consecutive patients with their first lacunar stroke and 202 normal controls, we found that hypertension (p < 0.001), smoking (p = 0.001), and aortic arch atheroma (p = 0.006) were independently associated with an increased risk of lacunar stroke. Whether proximal aortic arch atheroma is mechanistically associated with lacunar stroke or merely coexistent is uncertain.

Homolateral ataxia and crural paresis (HACP) is defined as predominantly crural paresis with ipsilateral ataxia, a variant of ataxic hemiparesis (AH), by Fisher and his colleagues. HACP usually resulted from lacunar infarction in the basis pontis at the junction of the upper one-third and inferior two-third of the pons, or in the posterior limb of the internal capsule. We reported a patient with HACP which was caused by an infarct in the paracentral gyrus irrigated by the anterior cerebral artery (ACA). He had had no cerebellar signs before the onset of HACP, although he had old small infarcts in the right pons, right thalamus and left cerebellar hemisphere. Neuroimaging and other clinical studies suggested that the mechanism of the present infarction was the most-likely embolic, but not lacunar. As far as we know, there has been only one abstract presentation of a patient with HACP due to ACA territory infarction in Japan, although five such cases were recently reported by Bogousslavsky and others.

A 58-year-old man with a intravascular malignant lymphomatosis initially developed myeloradiculopathy without cerebral symptoms. His MRI, however, demonstrated solid, wedge-shaped, and well-demarcated lesions in the deep white matter and a string-shaped lesion along with nerve fibers in the splenium of corpus callosum. A variety of cerebral symptoms manifested a month afterward. The possibility of this disease should be considered in cases of undiagnosed myeloradiculopathy with such silent brain lesions.

Background and Purpose: Enlargement of intracerebral hemorrhage is a major cause of clinical deterioration. Identification of factors that predispose to hematoma enlargement is important in managing patients., Methods: We selected 186 patients (71 women and 115 men; mean age, 64.8 +/- 12.5 years) with spontaneous intracerebral hemorrhage who had undergone an initial CT within 24 hours and a second scan within 120 hours of symptom onset. We compared patients with (n = 41) and without (n = 145) hematoma enlargement according to clinical characteristics and laboratory data., Results: By multiple logistic regression analysis (n = 139), interaction of long interval (> 6 hours) from onset to first CT and small hematoma (< 25 cm3) strongly reduced risk of enlargement. The analysis also demonstrated that the following factors independently predisposed to enlargement: history of brain infarction; liver disease; interaction of fasting plasma glucose > or = 141 mg/dL and systolic blood pressure on admission > or = 200 mm Hg; and interaction of glycosylated hemoglobin A1c > or = 5.1% and systolic blood pressure on admission > or = 200 mm Hg., Conclusions: A patient examined > 6 hours after ictus who has a hematoma volume < 25 cm3 is unlikely to experience further hematoma growth. Prevention of brain infarction and premorbid management of liver disease may serve to lower the risk of hematoma enlargement. Although it remains controversial whether antihypertensive drugs should be used in the acute phase of intracerebral hemorrhage, poorly controlled diabetics with high systolic blood pressure (> or = 200 mm Hg) on admission also were at high risk of hematoma enlargement.

We report a 49-year-old man who had right hemiparesis and motor aphasia. A computed tomography revealed hypodense areas in the left frontal subcortex. A cerebral angiography demonstrated occlusion of the left distal internal carotid artery and both anterior cerebral arteries, as well as stenosis of the left internal carotid artery at the cervical portion. The second angiogram obtained a month later showed no changes. The diagnosis of atherothrombotic cerebral infarction was established on the basis of clinical profile and angiographic findings. Protein C activity and antigen levels were reduced to approximately one half of the normal level in the patient and his brother. The patient had no other risk factors for stroke. Protein C deficiency has been considered one of the risk factors for thrombotic diseases. Venous thrombosis is the most common clinical manifestation, whereas arterial thrombosis is relatively rare. It is generally believed that arterial ischemic stroke associated with protein C deficiency occurs with embolic mechanism, and atherothrombotic infarction is extremely rare. This is the first report suggesting the possibility that protein C deficiency can cause cerebral thrombosis.

Background and Purpose: Standard radiographic criteria for hematoma enlargement have not been established. We undertook this investigation to assess the incidence and time course of hematoma growth using objective cutoff values., Methods: We reviewed the clinical records of 204 patients with spontaneous intracerebral hemorrhage treated nonsurgically who underwent initial computed tomography (CT) within 48 hours and repeat CT within 120 hours of the onset of symptoms. The consensus of five observers reading the CT films was considered the "gold standard" for hematoma enlargement. The discriminant values of the difference (V2-V1) or the ratio (V2/V1) of the hematoma volume on the initial (V1) and second (V2) CT scans were determined by use of receiver operating characteristic curves. We chose the cutpoint that had the highest sensitivity and specificity for identifying hematoma expansion., Results: The cutpoint for hematoma enlargement was determined as V2-V1 = 12.5 cm3 or V2/V1 = 1.4 (sensitivity = 94.4%, specificity = 95.8%). Forty-one patients (20%) had changes that exceeded these criteria. Frequency of hematoma expansion was greatest among those who underwent the initial CT scan early (27 [36%] of 74 patients at < or = 3 hours) and progressively declined as the time to initial scan was prolonged (7 [16%] of 45 patients at 3 to 6 hours; 5 [15%] of 33 patients at 6 to 12 hours; 2 [6%] of 34 patients at 12 to 24 hours; and 0 [0%] of 18 patients at 24 to 48 hours)., Conclusions: The enlargement of hematoma was defined radiographically as the increase of its volume by > or = 12.5 cm3 or by > or = 1.4 times. Although expansion of intracerebral hemorrhage on CT scan was common in the hyperacute stage, 17% of hematoma expansion occurred even after 6 hours of onset. Enlargement after 24 hours of onset seems extremely rare. Early CT scanning appears to increase the rate of detection of enlarging hematomas.

Background: While magnetic resonance imaging has revealed progressive changes in the pyramidal tract in accordance with histopathologic stages of wallerian degeneration secondary to a supratentorial lesion, computed tomography (CT) has only demonstrated a shrinkage of the pyramidal tract in the midbrain or pons during the chronic stage. We present a patient with frontoparietal subcortical hemorrhage in whom serial CT scans clearly demonstrated wallerian degeneration along the axis of the pyramidal tract early in the acute stage., Case Description: A 63-year-old man with a history of hypertension suddenly developed a deterioration of consciousness, transcortical mixed aphasia, and dense hemiplegia on the right side. CT scans revealed a massive intracerebral hematoma in the frontoparietal subcortices of the left hemisphere. Although initial CT did not detect any hypodense areas along the left pyramidal tract below the hematoma, ill-defined areas of decreased density appeared in the posterior limb of the internal capsule, cerebral peduncle of the midbrain, and pontine base of the left side on day 13 after the stroke. These areas became well demarcated on day 22 and persisted thereafter., Conclusions: An extensive hematoma can interrupt the pyramidal tract fibers that arise not only from the motor cortex and caudal premotor cortex but also from the somatosensory and parietal cortices, allowing very early CT demonstration of wallerian degeneration of the pyramidal tract.

Background: Protein C deficiency leads to reduced inhibition of coagulation and an increased likelihood of thrombosis. It is widely accepted that the most common syndromes associated with protein C deficiency are venous thrombosis and pulmonary thromboembolism, whereas arterial thrombosis is rare. Here we describe two patients with hypertension and hereditary heterozygous protein C deficiency who developed multiple lacunar infarcts., Case Descriptions: Patient 1 was a 46-year-old man with a history of hypertension who developed a right upper quadrantanopia and gradually progressive intellectual and behavioral deterioration. Patient 2 was a 61-year-old man with history of hypertension and two episodes of right-sided motor weakness who developed left sixth and seventh cranial-nerve palsies and reduced pinprick sensation in the right extremities. In both patients, magnetic resonance imaging revealed multiple small lesions in the pons as well as the bilateral basal ganglia, thalamus, corona radiata, and other subcortical structures, which are consistent with lacunar infarcts. Protein C activity and antigen levels were reduced to approximately one half of normal in these two patients, as well as in some of their family members who had no other serological or coagulation abnormalities. A diagnosis of heterozygous protein C deficiency type 1 was thus established., Conclusions: Although it remains uncertain whether protein C deficiency itself increases the risk of cerebral artery thrombosis, it may predispose a patient to develop multiple brain infarctions in association with hypertension.

We describe a patient with left unilateral ideomotor apraxia without left-sided agraphia caused by a callosal lesion that was demonstrated by magnetic resonance imaging. The clinical features, together with data in the literature, suggest that the callosal fibers for writing are concentrated in the posterior corpus callosum, while those for praxis cross in the more rostral part of the posterior half of the callosum.

Background and Purpose: Brain infarction localized in the anterior cerebral artery territory is rather uncommon, and its etiology has not yet been fully elucidated., Methods: Based on computed tomographic findings, 17 patients with solitary anterior cerebral artery territory infarction were selected from among 3,619 patients admitted consecutively to our institute. Patients without angiographic examinations were excluded. The angiographic findings and clinical category of stroke were analyzed in each patient., Results: Angiographic abnormalities were revealed in all patients. These consisted of occlusive changes (n = 10) or reversible segmental dilatation (n = 3) of the anterior cerebral artery, A1 hypoplasia (n = 5), and occlusive changes of the carotid artery (n = 3). In one patient with anterior cerebral artery occlusion, the occluded artery was reopened and subsequently became reoccluded. The clinical category of stroke was classified as atherothrombotic in 10 patients, cardioembolic in three, and undetermined in the remaining four. In eight of the 10 patients with atherothrombotic infarction, the anterior cerebral artery was narrowed or occluded. In all patients with cardioembolic infarction, the A1 segment contralateral to the infarction was hypoplastic., Conclusions: In our series, solitary anterior cerebral artery territory infarction was attributable most commonly to local atherothrombosis and occasionally to cardiogenic embolism. A hypoplastic A1 segment may facilitate the occurrence of embolism in the anterior cerebral artery. Reversible dilatatory and occlusive changes of this artery may be another important cause of infarction.

We describe a patient with a cerebral infarction localized mainly in the left posterior frontal and anterior parietal subcortices who experienced a Broca's aphasia which evolved into a conduction aphasia. Such a rare recovery pattern of aphasia appeared to result from amelioration of the damage to the left precentral gyrus.

Sequential gadolinium-DTPA (Gd-DTPA) enhanced MR images were obtained before and after steroid therapy in a case of neuro-Behçet's disease. Multiple scattered lesions, which could not be detected on pre- and post-contrast CT, were demonstrated mainly in the white matter of the pons and/or the cerebrum with both T1- and T2-weighted images. Some of these lesions, however, were not enhanced at all by infusion of Gd-DTPA. The Gd-DTPA infusion study demonstrated marked enhancement in the white matter of the pons and cerebrum. Some lesions not seen with T2-weighted images were also strongly enhanced by Gd-DTPA infusion at the acute stage. After steroid therapy, the symptoms and abnormal laboratory findings were resolved. The pontine and cerebral lesions on plain MR images remained unchanged even after resolution of the symptoms, suggesting that they were inactive old foci. On the other hand, the lesions detected in the enhancement study before steroid therapy disappeared with the repeat Gd-DTPA enhanced MR images hich were performed after resolution of the symptoms. Some active inflammatory lesions in neuro-Behçet's disease may be demonstrated only on Gd-DTPA enhanced MR images. Gd-DTPA enhanced MR imaging appears to be potentially useful for detecting active inflammatory lesions in neuro-Behçet's disease and for evaluating the efficacy of treatment.

A case of generalized auditory agnosia without aphasia secondary to cardiogenic cerebral embolism is reported. The infarcts in this patient were localized within the bitemporal subcortices as confirmed by computerized axial tomography and magnetic resonance imaging. The findings suggested that interruption of both auditory radiations by bilateral subcortical lesions may play an important role in the occurrence of "cerebral auditory disorders."

In 80 patients with no stenotic lesions in the vertebrobasilar arterial system, a study was made of the relationship between the deviation of the basilar artery (BA) from the midline on computed tomography (CT) and the right-to-left vertebral arterial caliber difference on angiograms. In 66 patients (83%), the BA was visible on plain CT films, and 55 of them showed deviation of the BA to either side. In 44 of these patients (80%), the vertebral artery (VA) contralateral to the side of BA deviation had a larger caliber compared with the ipsilateral one on angiograms. In 6 patients whose unilateral VA terminated in the posterior inferior cerebellar artery (PICA) and showed an extremely small caliber compared to the contralateral one, the BA was always deviated to the side of the smaller VA. Our data suggest that the deviation of the BA on plain CT films may represent a good indicator for estimating the right-to-left VA caliber difference. At the time of vertebral angiography, injection of contrast medium should preferably be made from the larger VA in order to avoid laminar flow in the BA and to shorten the procedure. Prior estimation of the right-to-left VA caliber difference by CT may be of great benefit to the angiographic procedure.