Background and Purpose-Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve as a noninvasive measure for brain water content? (2) Does morphometric assessment of brain swelling allow determination of true infarct size on MRI after correction for the space-occupying effect of edema? Methods-Thirty rats were subjected to permanent suture middle cerebral artery occlusion. MRI was performed after 6 or 24 hours, and hemispheric swelling was assessed morphometrically. Interobserver and intraobserver agreements were determined for MRI measurements. In study I, the space-occupying effect due to brain edema was correlated with the absolute brain water content by the wet/dry method. In study II, lesion volumes corrected and uncorrected for edema were calculated on MRI and on TTC staining and compared. Results-Interobserver and intraobserver agreements for MRI measurements were excellent (rՆ0.97). Brain water content and hemispheric swelling correlated well after 6 and 24 hours (rՆ0.95). Corrected lesion volumes correlated with rϭ0.78 between TTC staining and MRI. Without edema correction, lesion volumes were overestimated by 20.3% after 6 hours and by 29.6% after 24 hours of ischemia. Conclusions-Morphometric assessment of hemispheric swelling on MRI can determine the increase in absolute brain water content noninvasively and can also provide ischemic lesion volumes corrected for brain edema.

Cell injury leads to exposure of intracellular material and is associated with increased permeability of vessels in the vicinity of the damage. Here, we demonstrate that natural extracellular RNA as well as artificial RNA (poly- I IntroductionBrain homeostasis is maintained by the blood-brain barrier (BBB), which forms a mechanical and functional threshold between the central nervous system and the systemic circulation. The barrier is relatively impermeable to ions, many amino acids, small peptides, and proteins, and thus contributes to the maintenance of a specific neural tissue environment. In vertebrates, the BBB exists at the level of the endothelial cells that form brain capillaries 1 in order to regulate and limit the degree of trans-and paracellular flux. 2 The tight barrier properties of the BBB result from the absence of fenestrations, the low number of pinocytotic vesicles, and the presence of tight intercellular junctions between endothelial cells with extremely high electrical resistance. 3 Pathologic conditions associated with brain tumors, head injury, or ischemic stroke are accompanied by endothelial-cell dysfunction, leading to increased permeability across the BBB, which might lead to the development of vasogenic cerebral edema. 4,5 Vascular endothelial growth factor (VEGF) as a hypoxia/ischemia inducible protein in vitro and in vivo is one of the strongest natural permeability factors 6 and a likely candidate for the development of ischemia-and tumor-induced vasogenic brain edema. 7-9 VEGF stimulates endothelial-cell growth and migration in vitro 10,11 and angiogenesis in vivo. 6,12 VEGF was originally described as a potent vascular permeability factor responsible for the accumulation of plasma protein-rich fluid in the ascites of patients with tumors. 13 Structurally, VEGF exists as a dimeric glycoprotein of molecular weight (Mr) 34 000 to 42 000 and is related to the platelet-derived growth factor family of molecules. 14 Although VEGF is the product of a single gene, 6 differentially spliced isoforms between 121 and 206 amino acid residues exist in humans 15,16 that exhibit similar functional activities. Different isoforms are distinguished by their affinity for heparin: although VEGF 121 does not bind heparin, VEGF 165 has moderate affininity for heparin, whereas VEGF 189 and VEGF 206 bind heparin with high affinity. 17 VEGF exerts its multiple actions by ligation with tyrosine kinase receptors, VEGFreceptor 1 (VEGF-R1), as well as VEGF-R2, [18][19][20] which are expressed on vascular endothelial cells. A third member, VEGF-R3 is expressed on lymphatic endothelial cells. 21 During pathologic conditions of the brain associated with tumor burden, stroke, or head injury, nucleic acids might be released by damaged cells. RNA-proteolipid complexes were detected in the circulation of patients with cancer and were suggested to represent a specific secretory product of cancer cells. 22 Accordingly, circulating RNA is present in blood plasma of patients with tumors. 23 The presence of specific types ...

Background and Purpose-Transcranial color-coded duplex sonography has become a standard diagnostic technique to assess the intracranial arterial status in acute stroke. It is increasingly used for the evaluation of prognosis and the success of revascularization in multicenter trials. The aim of this international consensus procedure was to develop recommendations on the methodology and documentation to be used for assessment of intracranial occlusion and for monitoring of recanalization.

Background and Purpose-Transcranial color-coded duplex sonography (TCCS) of intracranial veins and sinuses in adults is a new, emerging application of ultrasonographic imaging. This study reports a standardized examination protocol for venous TCCS and provides reference data for clinical application. Methods-In 130 healthy volunteers (mean age, 45.9Ϯ16.9 years; range, 14 to 77 years) the intracranial venous system was examined using frequency-based transtemporal TCCS. Identification rate, blood flow velocity , resistance index, and systolic/diastolic ratio were recorded for each examined venous vessel. Results-Intracranial veins and sinuses show a low pulsatile forward flow with maximal systolic blood flow velocity up to 20 cm/s. Significant side differences of blood flow velocity in the paired venous structures could not be detected. Venous flow velocities decreased with age, whereas resistance indices and systolic/diastolic ratios increased. Women showed higher flow velocities than men. Mean identification rates for all age groups ranged from 70% to 90% for the deep middle cerebral vein, the basal cerebral vein, and the great cerebral vein of Galen. The straight sinus, the transverse sinus, and the rostral part of the superior sagittal sinus could be detected in 55% to 70% of cases. Detection rates were dependent on age and decreased as age increased. Conclusions-Venous TCCS can reliably image a significant part of the cerebral venous system. This method can provide information on venous hemodynamics in normal subjects and pathological cases.

This article represents the update of ‘European Stroke Initiative Recommendations for Stroke Management’, first published in this Journal in 2000. The recommendations are endorsed by the 3 European societies which are represented in the European Stroke Initiative: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.

Background and Purpose-Recanalization in dural sinus thrombosis (DST) has been observed previously; however, systematic prospective data are lacking. The influence of recanalization on DST outcome has not yet been thoroughly evaluated. Methods-Thirty-seven consecutive patients with DST were prospectively examined. Neurological deficits were graded with the National Institutes of Health Stroke Scale (NIHSS) on hospital admission and discharge. Functional outcome was assessed with the modified Rankin Scale (mRS) on hospital discharge and after 12 months. All patients were treated with intravenous heparin in the acute stage of illness, followed by oral anticoagulation for 12 months. Imaging follow-up with MR angiography and, in a few cases, with CT or conventional angiography was performed on hospital discharge and after 6 and 12 months. Results-Twelve-month functional outcome was excellent in 89% of patients with an mRS of 0 or 1. A recanalization rate of 60% was already observed on hospital discharge (22Ϯ6 days); thereafter, recanalization rates increased insignificantly. Early recanalization was not related to NIHSS score on hospital discharge or an mRS of 0 on discharge or after 12 months. Conclusions-We found a high frequency of early recanalization but without influence on clinical outcome parameters.Frequent imaging follow-ups in DST are not useful because they provide no information on patient outcome.

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Background and Purpose-Transcranial color-coded duplex sonography (TCCS) allows bedside imaging of intracranial hemodynamics and parenchymal structures. It provides reliable information regarding midline shift (MLS) in space-occupying hemispheric stroke. We studied the value of MLS measurement to predict fatal outcome at different time points after stroke onset. Methods-Forty-two patients with acute, severe hemispheric stroke were enrolled. Cranial computed tomography (CCT) and extracranial duplex sonography were performed on admission. TCCS was carried out 8Ϯ3, 16Ϯ3, 24Ϯ3, 32Ϯ3, and 40Ϯ3 hours after stroke onset. Lesion size was determined from follow-up CCT. Results-Twelve patients died as the result of cerebral herniation (group 1); 28 survived (group 2). Two patients received decompressive hemicraniectomy and were therefore excluded from further evaluation. MLS was significantly higher in group 1 as early as 16 hours after onset of stroke. Specificity and positive predictive values for death caused by cerebral herniation of MLS Ն2.5, 3.5, 4.0, and 5.0 mm after 16, 24, 32, and 40 hours were 1.0. Conclusions-TCCS