Ischemic brain and peripheral white blood cells release cytokines, chemokines and other molecules that activate the peripheral white blood cells after stroke. To assess gene expression in these peripheral white blood cells, whole blood was examined using oligonucleotide microarrays in 15 patients at 2.4 ± 0.5, 5 and 24 h after onset of ischemic stroke and compared with control blood samples. The 2.4 h blood samples were drawn before patients were treated either with tissue-type plasminogen activator (tPA) alone or with tPA plus Eptifibatide (the Combination approach to Lysis utilizing Eptifibatide And Recombinant tPA trial). Most genes induced in whole blood at 2 to 3 h were also induced at 5 and 24 h. Separate studies showed that the genes induced at 2 to 24 h after stroke were expressed mainly by polymorphonuclear leukocytes and to a lesser degree by monocytes. These genes included: matrix metalloproteinase 9; S100 calcium-binding proteins P, A12 and A9; coagulation factor V; arginase I; carbonic anhydrase IV; lymphocyte antigen 96 (cluster of differentiation (CD)96); monocarboxylic acid transporter (6); ets-2 (erythroblastosis virus E26 oncogene homolog 2); homeobox gene Hox 1.11; cytoskeleton-associated protein 4; N-formylpeptide receptor; ribonuclease-2; N-acetylneuraminate pyruvate lyase; BCL6; glycogen phosphorylase. The fold change of these genes varied from 1.6 to 6.8 and these 18 genes correctly classified 10/15 patients at 2.4 h, 13/15 patients at 5h and 15/15 patients at 24 h after stroke. These data provide insights into the inflammatory responses after stroke in humans, and should be helpful in diagnosis, understanding etiology and pathogenesis, and guiding acute treatment and development of new treatments for stroke.

Background and Purpose-Early identification of stroke patients at risk for fatal brain edema may be useful in selecting patients for aggressive interventions. Prior studies suggested that early nausea/vomiting and major hypodensity on baseline computed tomography (CT) were predictive of herniation. Methods-This study was a retrospective multicenter case-control study of patients with large middle cerebral artery (MCA) strokes admitted within 48 hours of symptom onset. Medical records, laboratory data, and CT scans were analyzed. Cases, defined as patients who died of massive brain swelling, were compared with all remaining patients as controls. Results-Two hundred one patients with large MCA strokes were identified: 94 (47%) died of brain swelling, 12 (6%) died of non-neurological causes, and 95 (47%) survived at day 30. Multivariable analysis, adjusted for age and clustered by center, identified the following predictors of fatal brain edema: history of hypertension (OR 3.0, 95% CI 1.2 to 7.6, Pϭ0.02), history of heart failure (OR 2.1, 95% CI 1.5 to 3.0, PϽ0.001), elevated white blood cell count (OR 1.08 per 1000 white blood cells/L, 95% CI 1.01 to 1.14, Pϭ0.02), Ͼ50% MCA hypodensity (OR 6.3, 95% CI 3.5 to 11.6, PϽ0.001), and involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery, or anterior choroidal artery; OR 3.3, 95% CI 1.2 to 9.4, Pϭ0.02). Initial level of consciousness, National Institutes of Health Stroke Scale score, early nausea/vomiting, and serum glucose were associated with neurological death in bivariable but not multivariable analyses. Conclusions-Among patients with large MCA infarctions, an increased risk of fatal brain edema is associated with history of hypertension or heart failure, increased baseline white blood cell count, major early CT hypodensity involving Ͼ50% of the MCA territory, and involvement of additional vascular territories. These data confirm and expand on prior research with a broad-based patient population. The presence of these risk factors identifies those stroke patients who may require aggressive therapeutic approaches. (Stroke. 2001;32:2117-2123.)

the tPA Stroke Survey Group Background and Purpose-Intravenous tissue plasminogen activator (tPA) administered within 3 hours of symptom onset is the first available effective therapy for acute ischemic stroke (AIS). Few data exist, however, on its use in very elderly patients. We examined the characteristics, complications, and short-term outcome of AIS patients aged Ն80 years treated with tPA. Methods-Patients aged Ն80 years (nϭ30) were compared with counterparts aged Ͻ80 years (nϭ159) included in the tPA Stroke Survey, a US retrospective survey of 189 consecutive AIS patients treated with intravenous tPA at 13 hospitals. Results-Risk of intracerebral hemorrhage (fatal, symptomatic, and total) was 3%, 3%, and 7% in the elderly age group and 2%, 6%, and 9%, respectively, in their younger counterparts (PϭNS for all comparisons). Likelihood of favorable outcome, defined as modified Rankin score 0 to 1, National Institutes of Health Stroke Scale score Յ5, or marked improvement by hospital discharge, was comparable between groups (37%, 54%, and 43% versus 30%, 54%, and 43%, respectively; PϭNS for all comparisons). Elderly patients were more likely to be treated by stroke specialists (87% versus 60%; Pϭ0.005) and less likely to have an identified protocol deviation (13% versus 33%; Pϭ0.03). Elderly patients were discharged more often to nursing care facilities (17% versus 5%; Pϭ0.003). In logistic regression models there were no differences in odds ratio for favorable or poor outcome, other than tendency for higher in-hospital mortality in elderly patients (odds ratio, 2.8; 95% CI, 0.81 to 9.62; Pϭ0.10). Conclusions-Among AIS patients treated with intravenous tPA, age-related differences in characteristics and disposition were identified. No evidence for withholding tPA treatment for AIS in appropriately selected patients aged Ն80 years was identified. (Stroke. 2000;31:370-375.)