bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracerebral Hemorrhage in Young People
Authors: Ruíz-Sandoval José Luis , Cantú Carlos , Barinagarrementeria Fernando
Published: June 2011

Background and Purpose
—The frequency of intracerebral hemorrhages (ICHs) in people aged ≤40 years has been poorly studied. We investigated the incidence, causes, locations, and prognosis of ICH in young patients.

Methods
—We evaluated all consecutive patients with neuroimaging evidence or pathological confirmation of symptomatic ICH. We excluded patients with primary subarachnoid or traumatic hemorrhage, past evidence of vascular malformation, or brain tumor. We analyzed the risk factors, number, locations, and causes of ICH, and final outcome measured by the modified Glasgow Outcome Scale.

Results
—We retrospectively evaluated 200 patients (mean age, 27 years; range, 15 to 40 years). The most frequent risk factors were tobacco use (20%), hypocholesterolemia (35%), hypertension, (13%), and alcohol use (10%). The locations of ICH were lobar (55%), basal ganglia/internal capsule (22%), and others (24%). The most common causes of ICH were vascular malformations (49%), including cavernous angioma, and hypertension (11%). Cryptogenic ICH was considered in 15%. Other causes included cerebral venous thrombosis (5%) and sympathomimetic drug use (4%). The majority of patients with ICH that resulted from hypertension were aged >31 years (odds ratio, 3.48), and those with ICH that resulted from arteriovenous malformations were aged <20 years (odds ratio, 2.80). The final outcome was considered favorable in 60%.

Conclusions
—ICHs in young people are mainly lobar in location and result from vascular malformation. Hypertension causes most cases in which the ICH is located in the basal ganglia. Mortality and morbidity in the acute phase are low and are related to hypertension as the cause of ICH.
CT Angiography and Doppler Sonography for Emergency Assessment in Acute Basilar Artery Ischemia
Authors: Brandt Tobias , Knauth Michael , Wildermuth Susanne , Winter Ralph , von Kummer Rüdiger , Sartor Klaus , Hacke Werner
Published: June 2011

Background and Purpose
—Both Doppler sonography (DS) and spiral CT angiography (CTA) are noninvasive vascular assessment tools with a high potential for application in acute cerebral ischemia. The usefulness of CTA for vascular diagnosis in acute basilar artery (BA) ischemia has not yet been studied.

Methods
—We prospectively studied 19 patients (mean±SD age, 58±11 years) with clinically suspected acute BA occlusion by DS and CTA. Prior extracranial and transcranial DS was performed in all but 1 patient, with DS 4 hours after CTA. In 6 of 19 patients, we performed digital subtraction angiography.

Results
—CTA was diagnostic in all but 1 patient. CTA revealed complete BA occlusion in 9 patients and incomplete BA occlusion with some residual flow in 2 patients. A patent BA was shown in 7 patients. Because of severe BA calcification, CTA results were inconclusive in 1 patient. DS was diagnostic in only 7 of 19 patients, indicating certain BA occlusion in 3 patients and BA patency in 4 patients. In an additional 9 patients, the results of DS were inconclusive. DS was false-negative in 2 patients with distal BA occlusion shown by CTA and digital subtraction angiography. In 1 patient with DS performed after CTA, recanalization was demonstrated. In addition to the diagnosis or exclusion of BA occlusion, CTA provided information on the exact site and length of BA occlusion and collateral pathways. In our series, CTA results prompted indication for intra-arterial thrombolysis in 5 patients.

Conclusions
—CTA was superior to DS in the assessment of BA patency in patients with the syndrome of acute BA ischemia in terms of feasibility and conclusiveness, particularly in cases with distal BA occlusion. Our study confirmed the usefulness of combined extracranial and transcranial DS in the diagnosis and exclusion of proximal BA occlusion.
Thrombolysis With Tissue Plasminogen Activator Alters Adhesion Molecule Expression in the Ischemic Rat Brain
Authors: Zhang Rui Lan , Zhang Zheng Gang , Chopp Michael
Published: June 2011

Background and Purpose
—We tested the hypothesis that treatment of embolic stroke with recombinant human tissue plasminogen activator (rhtPA) alters cerebral expression of adhesion molecules.

Methods
—Male Wistar rats were subjected to middle cerebral artery occlusion by a single fibrin-rich clot. P-selectin, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) immunoreactivity was measured at 6 or 24 hours after embolic stroke in control rats and in rats treated with rhtPA at 1 or 4 hours after stroke. To examine the therapeutic efficacy of combined rhtPA and anti–ICAM-1 antibody treatment at 4 hours after embolization, ischemic lesion volumes were measured in rats treated with rhtPA alone, rats treated with rhtPA and anti–ICAM-1 antibody, and nontreated rats.

Results
—Administration of rhtPA at 1 hour after embolization resulted in a significant reduction of adhesion molecule vascular immunoreactivity after embolization in the ipsilateral hemisphere compared with corresponding control rats. However, when rhtPA was administered to rats at 4 hours after embolization, significant increases of adhesion molecule immunoreactivity in the ipsilateral hemisphere were detected. A significant increase of ICAM-1 immunoreactivity was also detected in the contralateral hemisphere at 24 hours after ischemia. A significant reduction in lesion volume was found in rats treated with the combination of rhtPA and anti–ICAM-1 antibody compared with rats treated only with rhtPA.

Conclusions
—The present study suggests that the time of initiation of thrombolytic therapy alters vascular immunoreactivity of inflammatory adhesion molecules in the ischemic brain and that therapeutic benefit can be obtained by combining rhtPA and anti–ICAM-1 antibody treatment 4 hours after stroke.
Estrogen Provides Neuroprotection in Transient Forebrain Ischemia Through Perfusion-Independent Mechanisms in Rats
Authors: Wang Qiong , Santizo Roberto , Baughman Verna L. , Pelligrino Dale A.
Published: June 2011

Background and Purpose
—Estrogen-related neuroprotection in association with animal models of transient forebrain and focal ischemia has been documented in several recent reports. Some of those studies indicated that part of that benefit was a function of improved intraischemic vasodilating capacity. In the present study we examined whether chronic estrogen depletion and repletion affected ischemic neuropathology through perfusion-independent mechanisms.

Methods
—Normal, ovariectomized (OVX), and OVX female rats treated with 17β-estradiol (E
2
) were subjected to 30 minutes of transient forebrain ischemia (right common carotid occlusion plus hemorrhagic hypotension) and reperfusion. Neurological function and brain histopathology were assessed over the 72-hour recovery period. In all rats, preischemic and intraischemic cortical cerebral blood flow (CBF) levels were monitored with laser-Doppler flowmetry. In additional rats, CBF changes in the striatum and hippocampus were also monitored with laser-Doppler flowmetry probes and radiolabeled microspheres. In each experiment, the level of ischemia was targeted to a 75% to 80% reduction in cortical CBF.

Results
—The similarity in ischemic severity among groups was supported by measurements of comparable patterns of electroencephalographic power changes during the ischemic period. Compared with normal females, OVX rats showed diminished neurological outcomes and more severe histopathology in the hippocampus and striatum. Two-week treatment of OVX rats with E
2
was accompanied by postischemic neuropathological changes similar to those seen in normal females. Intraischemic CBF reductions in the hippocampus and striatum were similar in all groups (to 35% to 50% of the preischemic value) but significantly less than the cortical CBF reductions.

Conclusions
—These findings indicate that estrogen provides ischemic neuroprotection through mechanisms unrelated to improvement of intraischemic cerebral perfusion.
Cerebrovascular Alterations in Protein Kinase C–Mediated Constriction in Stroke-Prone Rats
Authors: Smeda John S. , King Shelley
Published: June 2011

Background and Purpose
—Cerebrovascular pressure-dependent constriction may involve the smooth muscle production of diacylglycerol, which could facilitate constriction by activating protein kinase C (PKC). A dysfunctional PKC system could promote the loss of pressure-dependent constriction. We attempted to determine whether the alterations in pressure-dependent constriction in the middle cerebral arteries (MCAs) observed in relation to stroke development in Wistar-Kyoto stroke-prone spontaneously hypertensive rats (SHRsp) were associated with defects in the ability of the arteries to constrict in response to PKC activation.

Methods
—MCAs were sampled from SHRsp before and after stroke development and in stroke-resistant Wistar-Kyoto spontaneously hypertensive rats. A pressure myograph was used to test the ability of the arteries to constrict in response to a 100 mm Hg pressure step and subsequently to contract in response to phorbol 12,13-dibutyrate in the presence of nifedipine (3 μmol/L).

Results
—Pressure-dependent constriction and constriction in response to phorbol dibutyrate in the MCAs were inhibited by PKC inhibitors (staurosporine [40 nmol/L], chelerythrine [12 μmol/L], bisindolylmaleimide [5 μmol/L]), declined with age before stroke development in SHRsp, and were absent after stroke. There was a significant relationship between pressure- and phorbol dibutyrate–induced constriction (
r
=0.815,
P
<0.05).

Conclusions
—Phorbol esters interact with the same activation site as diacylglycerol to stimulate PKC. An inability to constrict in response to phorbol dibutyrate may reflect unresponsiveness to diacylglycerol and may contribute to the loss of pressure-dependent constriction associated with stroke in the MCAs of SHRsp. The loss of this autoregulatory function before stroke could increase the risk of cerebral hemorrhage.
Facial Diplegia Complicating a Bilateral Internal Carotid Artery Dissection
Authors: Gout O. , Bonnaud I. , Weill A. , Moulignier A. , Quenet J. J. , Moret J. , Bakouche P.
Published: June 2011

Background and Purpose
—We report a case of facial diplegia complicating a bilateral internal carotid artery dissection.

Case Description
—A 49-year-old patient presented with unilateral headache and oculosympathetic paresis. Cerebral angiography revealed a bilateral internal carotid artery dissection. A few days later, the patient developed a facial diplegia that regressed after arterial recanalization. An arterial anatomic variation may explain this ischemic complication of carotid dissection.

Conclusions
—Double carotid dissection should be included among the causes of bilateral seventh nerve palsy.
Stroke Units in Their Natural Habitat
Authors: Stegmayr Birgitta , Asplund Kjell , Hulter-Åsberg Kerstin , Norrving Bo , Peltonen Markku , Terént Andreas , Wester P. O.
Published: June 2011

Background and Purpose
—Meta-analyses of randomized controlled trials of acute stroke care have shown care in stroke units (SUs) to be superior to that in conventional general medical, neurological, or geriatric wards, with reductions in early case fatality, functional outcome, and the need for long-term institutionalization. This study examined whether these results can be reproduced in clinical practice.

Methods
—A multicenter observational study of procedures and outcomes in acute stroke patients admitted to designated SUs or general medical or neurological wards (GWs), the study included patients of all ages with acute stroke excluding those with subarachnoid hemorrhage, who were entered into the Riks-Stroke (Swedish national quality assessment) database during 1996 (14 308 patients in 80 hospitals).

Results
—Patients admitted to SUs who had lived independently and who were fully conscious on admission to the hospital had a lower case fatality than those cared for in GWs (relative risk [RR] for death, 0.87; 95% confidence interval [CI], 0.79 to 0.96) and at 3 months (RR, 0.91; 95% CI, 0.85 to 0.98). A greater proportion of patients cared for in an SU could be discharged home (RR, 1.06; 95% CI, 1.03 to 1.10), and fewer were in long-term institutional care 3 months after the stroke (RR, 0.94; 95% CI, 0.89 to 0.99). No difference was seen in outcome in patients cared for in SUs or GWs if they had impaired consciousness on admission.

Conclusions
—The improvement in outcomes after stroke care in SUs compared with care in GWs can be reproduced in the routine clinical setting, but the magnitude of the benefit appears smaller than that reported from meta-analyses.
Hemiosteoporosis After Severe Stroke, Independent of Changes in Body Composition and Weight
Authors: Ramnemark A. , Nyberg L. , Lorentzon R. , Olsson T. , Gustafson Y.
Published: June 2011

Background and Purpose
—Fractures are a serious complication after stroke, and the risk of hip fractures among stroke patients is increased 2 to 4 times versus a reference population. Fractures after stroke are probably caused by the development of hemiosteoporosis and the high incidence of accidental falls. The aim of this study was to investigate the development of hemiosteoporosis in relation to other changes in body composition during the first year after severe stroke.

Methods
—The study included 24 patients with extensive paresis after stroke. Bone mineral content (BMC) and fat and lean mass were assessed 1, 4, 7, and 12 months after stroke onset by a dual-energy x-ray absorptiometer.

Results
—The loss of total body BMC was significant during the first year after stroke (–1.6%;
P
<0.05), but there were no significant changes in total lean or fat mass. At inclusion, there were no significant differences between sides in lean or fat mass or BMC, but during follow-up, BMC of the affected side decreased significantly compared with the same side at inclusion (–7.5%;
P
<0.01). Side differences in fat mass became significant between legs (9.3%;
P
<0.001) and whole sides (4.8%;
P
<0.01). There were only minor side changes in lean mass. Loss of BMC was independent of weight changes.

Conclusions
—During the first year after severe stroke, patients developed pronounced hemiosteoporosis. This was not associated with general changes in lean or fat mass. The development of hemiosteoporosis was independent of weight changes after stroke.
Frontal Bone Windows for Transcranial Color-Coded Duplex Sonography
Authors: Stolz Erwin , Kaps Manfred , Kern Andeas , Dorndorf Wolfgang
Published: June 2011

Background and Purpose
—The use of the conventional temporal bone window for transcranial color-coded duplex sonography (TCCS) often results in difficulties in obtaining angle-corrected flow velocity measurements of the A2 segment of the anterior cerebral artery, the posterior communicating artery, and the midline venous vasculature because of the unfavorable insonation angle. The same applies to B-mode imaging of the frontal parenchyma. However, transorbital TCCS raises problems with the insonation of the orbital lens. To overcome these drawbacks, we studied the feasibility of frontal bone windows for TCCS examinations.

Methods
—In 75 healthy volunteers (mean age, 45.3±17.0 years; age range, 17 to 77 years), the circle of Willis and the venous midline vasculature were insonated through a lateral and paramedian frontal bone window. Insonation quality of parenchymal structures (B-mode) was graded on a 3-point scale depending on the visibility of typical parenchymal landmarks. In a similar manner, the quality of the color-/Doppler-mode imaging of the arteries of the circle of Willis and the internal cerebral veins was assessed. In 15 patients (mean age, 62.7±13.7 years; age range, 33 to 83 years), the color-/Doppler-mode imaging quality of the intracranial vessels before and after application of an ultrasound contrast-enhancing agent was compared.

Results
—B-mode insonation quality was optimal to fair in 73.3% of cases using the lateral and in 52.0% of cases using the paramedian frontal bone window, with defined parenchymal structures used as reference. Insonation quality decreased in those older than 60 years. In those younger than 60 years, angle-corrected flow velocity measurements of the A2 segment of the anterior cerebral artery and the internal cerebral vein were possible in 73.6% and 60.0%, respectively. Contrast enhancement resulted in a highly significant improvement in the imaging quality of the intracranial vessels.

Conclusions
—The transfrontal bone windows offer new possibilities for TCCS examinations, although the insonation quality is inferior to the conventional temporal bone window in terms of failure of an acoustic window. This can be compensated for by application of an ultrasound contrast-enhancing agent.
Mild Carotid Artery Atherosclerosis
Authors: Räsänen Heikki T. , Manninen Hannu I. , Vanninen Ritva L. , Vainio Pauli , Berg Marja , Saari Tapani
Published: June 2011

Background and Purpose
—Our aim was to evaluate the usefulness of 3-dimensional time-of-flight magnetic resonance angiography (3-D TOF MRA) in detection and quantification of mild atherosclerotic changes of carotid arteries with reference to intravascular ultrasound (IVUS) and contrast angiography.

Methods
—TOF MRA at 1.5 T, IVUS, and selective digital subtraction angiography were performed on 31 extracranial carotid arteries of 27 patients (mean age, 52 years; age range, 17 to 75 years) undergoing neuroendovascular interventions. The atherosclerotic lesions were registered, and quantitative measurements of plaque thickness, luminal diameters, and diameter stenosis were independently performed for the imaging modalities.

Results
—Among 170 arterial segments analyzed, IVUS revealed a total of 48 atherosclerotic lesions (mean diameter stenosis, 17%; range, 4% to 40%), only 25 of which were depicted on digital subtraction angiography. Analysis of the axial source images of TOF MRA resulted in sensitivity of 77% to 83% and specificity of 71% to 80% in lesion depiction for the 2 readers with reference to IVUS. The values of diameter stenosis measured from MRA and IVUS were closely interrelated (
r
=0.53 to 0.61,
P
<0.001).

Conclusions
—Three-dimensional TOF MRA is feasible and moderately accurate for evaluation of mild atherosclerotic changes of carotid arteries.
Influence of Platelet-Activating Factor on Cerebral Microcirculation in Rats
Authors: Uhl Eberhard , Pickelmann Sven , Röhrich Frank , Baethmann Alexander , Schürer Ludwig
Published: June 2011

Background and Purpose
—Platelet-activating factor (PAF) is involved in the development of secondary brain damage after ischemic and traumatic brain injury. On the basis of data from studies in peripheral organs, we hypothesized that PAF-mediated effects after cerebral injury could be secondary to alterations in cerebral microcirculation.

Methods
—Changes in cerebral microcirculation focusing on leukocyte-endothelium interactions were quantified with the use of a closed cranial window model in Sprague-Dawley rats (n=33) by means of intravital fluorescence microscopy. The brain surface was superfused with PAF in concentrations from 10
−3
(n=3) to 10
−12
mol/L (n=6) for 20 minutes (5 mL/h).

Results
—PAF 10
−4
mol/L (n=4) increased the number of rolling and adherent leukocytes in venules from 9.7±0.4 to 19.7±2.3 cells/100 mm · min (
P
=NS versus control) and from 2.2±0.5 to 4.3±0.7 cells/100 mm · min (
P
<0.05 versus control), respectively. Lower concentrations did not elicit leukocyte-endothelium interactions. Vessel diameters remained unchanged except for a transient increase of arteriolar diameters during superfusion with PAF 10
−4
and 10
−6
mol/L (n=6). Although only a limited area of the brain surface was exposed to PAF, the mediator induced a significant dose-dependent transitory arterial hypotension and caused irreversible circulatory shock at the high concentration (PAF 10
−3
mol/L). Arterial hypotension after administration of PAF 10
−3
mol/L could be attenuated by the intravenous pretreatment with the PAF antagonist WEB 2170BS.

Conclusions
—PAF, when locally released after brain injury, can penetrate the blood-brain barrier and induce systemic effects, including arterial hypotension. Its role as a mediator in the development of secondary brain damage seems, at least in the initial phase, not to be associated with disturbances of cerebral microcirculation or activation of leukocytes.
Antiplatelet Therapy in Acute Cerebral Ischemia
Authors: Bednar Martin M. , Gross Cordell E.
Published: June 2011

Background
—Improved recognition of stroke signs and symptoms has paralleled the development of pharmacological strategies that may be examined to reduce stroke mortality and morbidity. Presently, tissue plasminogen activator is the only therapy that significantly improves outcome in acute stroke, with no agent demonstrating a significant reduction in mortality.

Summary of Review
—Antiplatelet agents are a heterogenous class of drugs that have been successfully used for more than 2 decades in secondary stroke prevention. These agents include aspirin, with or without dipyridamole, and more recently, the adenosine antagonists ticlopidine and clopidogrel. However, studies of the use of antiplatelet agents within 48 hours of the ictus have examined only aspirin. Only 1 study, the Multicentre Acute Stroke Trial–Italy (MAST-I), entered patients within 6 hours of the ictus. These data suggest that an improvement in mortality may be related to the speed of administration. No significant adverse events were noted with early antiplatelet monotherapy. However, MAST-I did note a significant increase in early mortality in patients receiving aspirin plus streptokinase, a finding not adequately explained by an increase in the intracranial hemorrhage rate.

Conclusions
—The use of antiplatelet therapy in acute stroke, clinical or experimental, has only recently received attention. It is likely that the use of antiplatelet agents for acute stroke therapy will be less restrictive than that currently seen for thrombolytics. Future studies should include an examination of those agents that have previously demonstrated efficacy in secondary stroke prevention, most notably, aspirin. The recognition that all platelet stimuli share a final common pathway that is dependent on the surface glycoprotein IIb/IIIa (fibrinogen) receptor has resulted in the development of various agents which block this receptor and are currently the focus for clinical trials. The role of nitric oxide in stroke therapy will depend on minimizing the hypotensive side effects of this agent. Stroke models are needed to provide preliminary data on the efficacy of antiplatelet therapy, especially as relates to the interaction of antiplatelet agents with thrombolytics.
Dynamic Behavior of Heart Rate in Ischemic Stroke
Authors: Korpelainen Juha T. , Sotaniemi Kyösti A. , Mäkikallio Anne , Huikuri Heikki V. , Myllylä Vilho V.
Published: June 2011

Background and Purpose
—Traditional spectral and nonspectral methods have shown that heart rate (HR) variability is reduced after stroke. Some patients with poor outcome, however, show randomlike, complex patterns of HR behavior that traditional analysis techniques are unable to quantify. Therefore, we designed the present study to evaluate the complexity and correlation properties of HR dynamics after stroke by using new analysis methods based on nonlinear dynamics and fractals (“chaos theory”).

Methods
—In addition to the traditional spectral components of HR variability, we measured instantaneous beat-to-beat variability and long-term continuous variability analyzed from Poincaré plots, fractal correlation properties, and approximate entropy of R-R interval dynamics from 24-hour ambulatory ECG recordings in 30 healthy control subjects, 31 hemispheric stroke patients, and 15 brain stem stroke patients (8 medullary, 7 pontine) in the acute phase of stroke and 6 months after stroke.

Results
—In the acute phase, the traditional spectral components of HR variability and the long-term continuous variability from Poincaré plots were impaired (
P
<0.01) in patients with hemispheric and medullary brain stem stroke, but not in patients with pontine brain stem stroke, in comparison with control subjects. At 6 months after stroke, measures of HR variability in hemispheric stroke patients were still lower (
P
<0.05) than those of the control subjects. Various complexity and fractal measures of HR variability were similar in patients and control subjects. The conventional frequency domain measures of HR variability as well as the Poincaré measures showed strong correlations (Pearson correlation coefficient,
r
=0.68 to
r
=0.90) with each other but only weak correlations (
r
=0.09 to
r
=0.56) with the complexity and fractal measures of HR variability.

Conclusions
—Hemispheric and medullary brain stem infarctions seem to damage the cardiovascular autonomic regulatory system and appear as abnormalities in the magnitude of HR variability. These abnormalities can be more easily detected with the use of analysis methods of HR variability, which are based on moment statistics, than by methods based on nonlinear dynamics. Abnormal HR variability may be involved in prognostically unfavorable cardiac complications and other known manifestations of autonomic failure associated with stroke.
Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts
Authors: Droste Dirk W. , Reisener Martina , Kemény Vendel , Dittrich Ralf , Schulte-Altedorneburg Gernot , Stypmann Jörg , Wichter Thomas , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Cardiac right-to-left shunts can be identified by transcranial Doppler ultrasound (TCD) with the use of different contrast agents and by transesophageal echocardiography (TEE). Systematic data are available on neither the reproducibility of contrast TCD, the comparison of different contrast agents, nor the comparison of simultaneous bilateral to unilateral recordings. Furthermore, we assessed the side distribution of thus provoked artificial cardiac emboli.

Methods
—Fifty-four patients were investigated by TEE and by bilateral TCD of the middle cerebral artery. The following protocol was performed twice: injection of 9 mL of agitated saline without Valsalva maneuver, injection of 9 mL of agitated saline with Valsalva maneuver, injection of 5 mL of a commercial galactose-based contrast agent without Valsalva maneuver, and injection of 5 mL of the galactose-based contrast agent with Valsalva maneuver.

Results
—In 18 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-nine patients were negative in both investigations, 1 was positive on TEE and negative on TCD, and 6 patients were only positive on TCD. Both bilateral and repeated recordings increased the sensitivity of contrast TCD. There was a symmetrical distribution of microembolic signals in the right and left middle cerebral artery.

Conclusions
—TCD performed twice and with the use of saline or a galactose-based contrast agent is a sensitive method in the identification of cardiac right-to-left shunts also identified by TEE. The cardiac microemboli in this study did not show any side preference for one of the middle cerebral arteries.
Lack of Correlation Between Pattern of Collateralization and Misery Perfusion in Patients With Carotid Occlusion
Authors: Derdeyn Colin P. , Shaibani Ali , Moran Christopher J. , Cross DeWitte T. , Grubb Robert L. , Powers William J.
Published: June 2011

Background and Purpose
—Misery perfusion, identified by increased oxygen extraction fraction (OEF), predicts subsequent stroke in patients with carotid occlusion. The purpose of this investigation was to determine the relationship of angiographic findings to increased OEF in these patients.

Methods
—Forty-seven patients with carotid occlusion were studied with cerebral angiography and positron emission tomography (PET). The following angiographic data were collected blind to PET results: (1) pial collateralization, defined as retrograde filling of the MCA branches to the level of the insula; (2) presence of border zone shift; (3) presence of delayed venous phase; and (4) measurement of posterior communicating artery size. Patients were divided into 2 groups based on the PET measurement of normal or increased OEF.

Results
—Seventeen of 47 patients had increased OEF distal to the occluded carotid artery. No significant relationship between increased OEF and any angiographic finding was found. Pial collateralization was present in only 2 patients, both with increased OEF (
P
=0.105). Border zone shift was equally distributed between the 2 groups (12 of 30 with normal OEF and 6 of 15 with increased OEF). Delayed venous phase was present in 4 patients, 3 of whom had increased OEF (
P
=0.073). The relationship between the size of the posterior communicating artery and OEF was not significant by linear regression analysis (
P
=0.242).

Conclusions
—With the possible but infrequent exceptions of delayed venous phase and pial collateralization, anatomic findings made on routine angiographic studies of patients with carotid occlusion do not correlate with increased OEF.
Outcome of Angioplasty for Atherosclerotic Intracranial Stenosis
Authors: Marks Michael P. , Marcellus Mary , Norbash Alexander M. , Steinberg Gary K. , Tong David , Albers Gregory W.
Published: June 2011

Background and Purpose
—We sought to assess the long-term outcome and efficacy of percutaneous transluminal angioplasty in the treatment of symptomatic intracranial atherosclerotic stenoses.

Methods
—Twenty-three patients with fixed symptomatic intracranial stenoses were treated over a 5-year period with percutaneous transluminal angioplasty. Patients who underwent successful angioplasty were followed up for 16 to 74 months (mean, 35.4 months).

Results
—An angioplasty that resulted in decreased stenosis was performed in 21 of 23 patients (91.3%). In 1 case a stenosis could not be safely crossed, and in another balloon dilatation resulted in vessel rupture. This vessel rupture resulted in the 1 periprocedural death in the series. In follow-up there was 1 stroke in the same vascular territory as the angioplasty and 2 strokes in the series overall. This yielded an annual stroke rate of 3.2% for strokes in the territory appropriate to the site of angioplasty.

Conclusions
—Intracranial angioplasty can be performed with a high degree of technical success. The long-term clinical follow-up available in this series suggests that it may reduce the risk of future stroke in patients with symptomatic intracranial stenoses.
Attenuated Corticomedullary Contrast: An Early Cerebral Computed Tomography Sign Indicating Malignant Middle Cerebral Artery Infarction
Authors: Haring Hans-Peter , Dilitz Erika , Pallua Anton , Hessenberger Gerald , Kampfl Andreas , Pfausler Bettina , Schmutzhard Erich
Published: June 2011

Background and Purpose
—No neuroradiological markers have been characterized that support a timely decision for decompressive surgery in malignant middle cerebral artery (MCA) infarction (mMCAI). This case-control study was designed to analyze whether early cerebral CT (CCT) scanning provides reliable information for the prospective selection of stroke patients at risk of developing mMCAI.

Methods
—Thirty-one pairs (n=62) were formed with cases (mMCAI) and controls (acute but not malignant MCA infarction) closely matched in terms of age, sex, and stroke etiology. CCT was performed within 18 hours of stroke onset and analyzed by a blinded neuroradiologist according to a defined panel of 12 CCT criteria.

Results
—In terms of predicting mMCAI, the criteria of extended MCA territory hypodensities >67% and >50%, hemispheric brain swelling, midline shift, and hyperdense MCA sign exhibited high specificity (100%, 93.5%, 100%, 96.7%, and 83.9%, respectively) but low sensitivity (45.2%, 58.1%, 12.9%, 19.4%, and 70.9%, respectively). Two criteria yielded high sensitivity (subarachnoid space compressed, 100%; cella media compressed, 80.6%) but low specificity (29% and 74.2%, respectively). The criterion of attenuated corticomedullary contrast yielded both high specificity (96.8%) and sensitivity (87.1%). The latter remained as the crucial criterion [Exp(B)=90.8; 95% CI, 5.8 to 1427.5] in a 2-tailed logistic regression analysis with the strongest correlating parameters (Spearman correlation factor ≥0.6 or ≤−0.6).

Conclusions
—The analysis of CCT scans within 18 hours of stroke onset revealed an attenuated corticomedullary contrast as the crucial CCT criterion, which, with both sufficient sensitivity and specificity, predicted mMCAI with 95% certainty.
Clinical and Neuroradiological Features of Intracranial Vertebrobasilar Artery Dissection
Authors: Hosoya Takaaki , Adachi Michito , Yamaguchi Koichi , Haku Tamami , Kayama Takamasa , Kato Takeo
Published: June 2011

Background and Purpose
—We sought to determine the clinical and neuroradiological features of intracranial vertebrobasilar artery dissection.

Methods
—The clinical features and MR findings of 31 patients (20 men and 11 women) with intracranial vertebrobasilar artery dissections confirmed by vertebral angiography were analyzed retrospectively. The vertebral angiography revealed the double lumen sign in 11 patients (13 arteries) and the pearl and string sign in 20 patients (28 arteries).

Results
—The patients ranged in age from 25 to 82 years (mean, 54.8 years). Clinical symptoms due to ischemic cerebellar and/or brain stem lesions were common, but in 3 cases the dissections were discovered incidentally while an unrelated disorder was investigated. Headache, which has been emphasized as the only specific clinical sign of vertebrobasilar artery dissection, was found in 55% of the patients. Intramural hematoma on T1-weighted images has been emphasized as a specific MR finding. The positive rate of intramural hematoma was 32%. Double lumen on 3-dimensional (3-D) spoiled gradient-recalled acquisition (SPGR) images after the injection of contrast medium was identified in 87% of the patients. The 3-D SPGR imaging method is considered useful for the screening of vertebrobasilar artery dissection.

Conclusions
—Intracranial vertebrobasilar artery dissection is probably much more frequent than previously considered. Such patients may present no or only minor symptoms. Neuroradiological screening for posterior circulation requires MR examinations, including contrast-enhanced 3-D SPGR. Angiography may be necessary for the definite diagnosis of intracranial vertebrobasilar artery dissection because the sensitivity of the finding of intramural hematoma is not satisfactory.
CD18-Mediated Neutrophil Recruitment Contributes to the Pathogenesis of Reperfused but Not Nonreperfused Stroke
Authors: Prestigiacomo Charles J. , Kim Samuel C. , Connolly E. Sander , Liao Hui , Yan Shi-Fang , Pinsky David J.
Published: June 2011

Background and Purpose
—Neutrophil (PMN) recruitment mediated by increased expression of intercellular adhesion molecule-1 expression (ICAM-1, CD54) in the cerebral microvasculature contributes to the pathogenesis of tissue injury in stroke. However, studies using blocking antibodies against the common β
2
-integrin subunit on the PMN, the counterligand for ICAM-1 (CD18), have demonstrated equivocal efficacy. The current study tested the hypothesis that mice deficient in CD18 would be protected in the setting of reperfused but not nonreperfused stroke.

Methods
—Two groups of mice were studied, those whose PMNs could express CD18 (CD18 +/+) and those mice hypomorphic for the CD-18 gene (CD18 −/−). PMNs obtained from CD18 −/− or CD18 +/+ mice were fluorescently labeled and tested for binding to murine brain endothelial monolayers. Using a murine model of focal cerebral ischemia in which an occluding suture placed in the middle cerebral artery (MCA) is removed after 45 minutes (transient ischemia, reperfused stroke) or left in place (permanent ischemia, nonreperfused stroke), cerebral infarct volumes (% ipsilateral hemisphere by TTC staining), cerebral blood flow (CBF, % contralateral hemisphere by laser-Doppler flowmetry), and survival (%) were examined 24 hours after the initial ischemic event. Adoptive transfer studies used
111
In-labeled PMNs (from either CD18 +/+ or CD18 −/− mice) to examine the relative accumulation of PMNs in the ischemic region.

Results
—PMNs obtained from CD18 −/− mice exhibit reduced adhesivity (compared with CD18 +/+ PMNs) for both quiescent and cytokine-activated endothelial monolayers. CD18 −/− mice (n=14) subjected to transient focal cerebral ischemia demonstrated a 53% decrease in infarct volumes versus CD18 +/+ mice (n=26,
P
<0.05), improved penumbral CBF at 24 hours (1.8-fold,
P
=0.02), and a 3.7-fold decrease in mortality (
P
=0.02). However, when CD18 −/− mice (n=12) were subjected to permanent focal cerebral ischemia, no differences were noted in infarct volume, mortality, or CBF versus similarly treated CD18 +/+ mice (n=10). There was a greater accumulation of CD18 +/+ PMNs in the ischemic zone of CD18 +/+ animals than CD18 −/− animals subjected to reperfused stroke (82% increase,
P
=0.02), although there was no difference between groups when subjected to permanent MCA occlusion.

Conclusions
—Deficiency for the CD18 gene confers cerebral protection in a murine model of reperfused stroke, but this benefit does not extend to CD18-deficient animals subjected to permanent MCA occlusion. These data suggest that anti-PMN strategies should be targeted to reperfused stroke and may perhaps be used in conjunction with thrombolytic therapy that establishes reperfusion.
Early Delineation of Ischemic Tissue in Rat Brain Cryosections by High-Contrast Staining
Authors: Vogel Johannes , Möbius Christian , Kuschinsky Wolfgang
Published: June 2011

Background and Purpose
—After short periods of ischemia, commonly used staining methods yield only moderate differences in optical contrast between normal and damaged brain tissue when gray-scale images are used for computer-assisted image analysis. We describe a high-contrast silver infarct staining (SIS) method that allows an early delineation of ischemic tissue as soon as 2 hours after middle cerebral artery occlusion (MCAO) in rat brain cryosections.

Methods
—Rats were subjected to permanent MCAO for 2, 4, 6, and 48 hours. The optical densities were quantified in nonischemic white and gray matter and in damaged tissue from gray-scale images of serial sections with the use of a video camera–based image analyzing system. SIS, hematoxylin-eosin, Nissl, and nitroblue tetrazolium stainings were performed in cryosections, and 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining was performed in unfrozen vibratome sections. In addition, the range of reduced cerebral blood flow (CBF) in areas demarcated by SIS was determined in iodo[
14
C]antipyrine autoradiograms of adjacent cryosections.

Results
—At all times after MCAO, only SIS showed significantly (
P
<0.01) lower optical densities in damaged than in normal brain tissue for both white and gray matter. TTC staining was as effective as SIS 6 and 48 hours after MCAO. The tightest correlation between areas of reduced SIS and of reduced CBF was found at a mean ischemic CBF of 22.3 mL/100 g per minute. This corresponds to a CBF range of 0 to 44 mL/100 g per minute in areas of reduced SIS.

Conclusions
—In contrast to other staining methods, SIS allows a reliable delineation of ischemic brain tissue (core plus penumbra) from nonischemic white and gray matter of rat brain cryosections as soon as 2 hours after MCAO.
Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in Deep Cerebral Venous Thrombosis
Authors: Keller Ewald , Flacke Sebastian , Urbach Horst , Schild Hans H.
Published: June 2011

Background
—Diffusion-weighted (DWI) and perfusion-weighted (PI) MRI are highly sensitive techniques for early diagnosis of arterial infarction, but little data on venous cerebral ischemia are available. We describe a case in which DWI, PI, and fast T2–weighted sequences were performed in the acute phase of deep cerebral venous thrombosis (CVT).

Case Description
—An 11-year-old girl with Crohn’s disease developed deep CVT in which extensive edema was shown in the deep gray matter on T2-weighted sequence images. Isotropic echo-planar DWI demonstrated a local augmentation of the apparent diffusion coefficient (1.1 to 1.6×10
−3
mm
2
/s), consistent with vasogenic edema. In dynamic contrast–enhanced PI, the regional cerebral blood volume was increased and the passage time of the contrast bolus was markedly prolonged. Clinically, the patient recovered totally after intravenous full-dose heparinization. T2 abnormalities, apparent diffusion coefficient values (0.8 to 0.92×10
−3
mm
2
/s), and brain perfusion alterations resolved without damage to brain tissue.

Conclusions
—Unlike arterial infarction, DWI demonstrated vasogenic edema in a patient with deep CVT, which proved to be reversible in follow-up magnetic resonance imaging. PI showed areas with extensive venous congestion, but perfusion deficits were missing. Therefore, we believe that DWI and PI may play a role in detecting venous congestion in CVT and in prospective differentiation of vasogenic edema and venous infarction.
Risk of Subarachnoid Hemorrhage After Surgical Treatment of Unruptured Cerebral Aneurysms
Authors: Tsutsumi K. , Ueki K. , Usui M. , Kwak S. , Kirino T.
Published: June 2011

Background and Purpose
—Recent progress in noninvasive imaging techniques has resulted in increased detection of unruptured aneurysms. Although many neurosurgeons advocate surgical intervention for such unruptured aneurysms, the long-term results of surgery for unruptured aneurysms have not been carefully investigated.

Methods
—We analyzed 173 consecutive patients who had unruptured intracranial saccular aneurysm(s) detected by angiography that was performed for reasons other than subarachnoid hemorrhage (SAH). Of those, 115 cases were surgically treated and studied. All patients were followed up for either SAH, repeat treatment of aneurysms, or death. The median follow-up period was 8.8 years.

Results
—Four of the 115 patients suffered SAH either from a de novo aneurysm (2) or from regrowth of clipped aneurysm (1), or from regrowth after wrapping (1). Additionally, 1 patient also suffered SAH from an unstudied basilar aneurysm. One patient was incidentally found to have de novo aneurysm and underwent reoperation 14 years after the first operation. The cumulative risk for SAH for the 114 cases excluding the basilar aneurysm case was 1.4% in 10 years and 12.4% in 20 years.

Conclusions
—Although this study confirmed the long-term efficacy of clipping unruptured aneurysms, the risk of SAH was high compared with that in the general population, even after treatment. Considering the high mortality rate of SAH, long-term follow-up by angiography may be warranted for patients with surgically treated unruptured aneurysms.
Methodological Parameters Influence the Detection of Right-to-Left Shunts by Contrast Transcranial Doppler Ultrasonography
Authors: Schwarze J. J. , Sander D. , Kukla C. , Wittich I. , Babikian V. L. , Klingelhöfer J.
Published: June 2011

Background and Purpose
—Contrast transcranial Doppler ultrasonography is a new method to detect intracardiac right-to-left shunts, such as the patent foramen ovale. However, the methodology of the procedure varies considerably among investigators. This study was undertaken to assess the influence of methodological parameters on the results of the contrast transcranial Doppler examination in the detection of right-to-left shunts.

Methods
—A total of 72 patients (mean age, 58.2±14.7 years) had a contrast transcranial Doppler ultrasonography examination. To study the influence of methodological factors, patients with evidence of a right-to-left shunt underwent repeated examinations with modified procedures. Parameters under investigation were the timing of the Valsalva maneuver, the dose of the contrast medium, and the patient’s posture during the examination.

Results
—The median contrast signal count was 58.5 and 48.0 (
P
<0.001) and the median latency of the first intracranially detected contrast signal was 12.5 and 8.5 seconds (
P
=0.05) when the Valsalva maneuver was performed 5 and 0 seconds after the start of the injection, respectively. Reducing the contrast medium dose from 10 to 5, 2.5, and 1.2 mL resulted in a decline of the median signal count from 54.5 to 28.5, 20.5, and 12.0 (
P
<0.01), respectively, while the latency of the first contrast signal increased from 13.3 to 14.0, 14.6, and 15.0 seconds (
P
<0.05). The sitting position also produced a lower signal count than the supine position (
P
<0.02).

Conclusions
—This study demonstrates that several essential methodological parameters influence the results of the contrast transcranial Doppler ultrasonography examination. Therefore, it is necessary to standardize the procedure to permit comparable quantitative assessments of the shunt volume. The findings of the present study suggest that 10 mL of contrast medium be injected with the patient in the supine position and that the Valsalva maneuver be performed 5 seconds after the start of the injection.
Attenuation of Thrombin-Induced Brain Edema by Cerebral Thrombin Preconditioning
Authors: Xi Guohua , Keep Richard F. , Hua Ya , Xiang Jianming , Hoff Julian T.
Published: June 2011

Background and Purpose
—Edema formation after intracerebral hemorrhage has been linked to thrombin toxicity induced by the clot. However, thrombin at low concentrations actually protects neurons and astrocytes in culture from hypoglycemic and ischemic cell death. It is also known that a brief episode of brain ischemia increases neuronal tolerance to a subsequent severe ischemic episode. The objective of this study was to investigate whether pretreatment of the brain with low-dose thrombin induces tolerance to a subsequent large dose of thrombin injected into brain parenchyma.

Methods
—The rat brain was preconditioned with 1 U thrombin by direct infusion into the right caudate nucleus. After thrombin pretreatment, the effects of a large dose (5 U) of thrombin on brain edema formation were studied at different intervals. We examined whether heat-shock protein (HSP) 27, HSP32, and HSP70 were induced by Western blot analysis, immunocytochemistry, and immunofluorescent double staining.

Results
—Thrombin pretreatment significantly attenuated the brain edema that normally follows the infusion of a large dose of thrombin (79.2±0.4 versus 84.0±0.3;
P
<0.01). This effect was abolished by the thrombin inhibitor hirudin. Time course studies showed that the maximal effect of thrombin preconditioning (TPC) on brain edema formation was 7 days after pretreatment. This time course corresponded to marked upregulation of HSP27 in the ipsilateral brain. TPC also induced HSP32, but this effect occurred earlier than the effect on edema formation. TPC had no effect on HSP70. Immunocytochemistry and immunofluorescent double labeling showed that HSP27 and HSP32 were expressed in astrocytes after TPC.

Conclusions
—The phenomenon of thrombin-induced tolerance of the brain to edema formation may be related to HSP27 induction.