Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

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.

Mortality and cause of death after hospital discharge in 10,981 patients with ischemic stroke and transient ischemic attack.

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.

Variation in ischemic stroke frequency in Japan by season and by other variables.

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.

Analysis of 16,922 patients with acute ischemic stroke and transient ischemic attack in Japan. A hospital-based prospective registration study.

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.

Penumbral topography in human stroke: methodology and validation of the 'Penumbragram'.

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.

Hospital-based prospective registration of acute ischemic stroke and transient ischemic attack in Japan.

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.

Clinical and radiographic features of lobar cerebral hemorrhage: hypertensive versus non-hypertensive cases.

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.

[Multicenter survey on clinical features and regional variations in acute brain infarction].

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.