bluuebunny/crossref_metadata_2025 huggingface dataset:
Is It Clinically Possible to Distinguish Nonhemorrhagic Infarct From Hemorrhagic Stroke?
Authors: Besson Gérard , Robert Claudine , Hommel Marc , Perret Jean
Published: June 2011

Background and Purpose
Diagnosis of the nonhemorrhagic ischemic type of stroke by analysis of patients’ clinical features is considered unreliable because no clinical feature is specific. The diagnosis is so difficult to establish that we cannot hope to use the same method to make a reliable diagnosis in all stroke cases. In this study, we propose a simple scoring system with a positive predictive value of close to 100% to distinguish nonhemorrhagic infarct from hemorrhagic stroke. This scoring is available for all physicians in bedside diagnosis even if this score can be applied to a subgroup of patients.

Methods
Twenty-six clinical variables that might potentially distinguish cerebral hemorrhage from infarction were recorded in patients consecutively admitted to our stroke unit for stroke lasting more than 24 hours with at least unilateral motor weakness affecting face and/or arm and/or leg (internal validity study). Patients previously receiving anticoagulant therapy were excluded. We used CT scan as the gold standard. We used multivariate logistic regression to establish a clinical score from which we derived the classification rule. This rule was validated with data from the next 200 consecutive patients hospitalized in the stroke unit (external validity study).

Results
Three hundred sixty-eight patients were enrolled in the internal study. The obtained score was (2×alcohol consumption)+(1.5×plantar response)+(3×headache)+(3×history of hypertension)−(5×history of transient neurological deficit)−(2×peripheral arterial disease)−(1.5×history of hyperlipidemia)−(2.5×atrial fibrillation on admission). All patients with a score less than 1 (n=123) had a nonhemorrhagic infarct (ie, 40% of the 305 patients with a nonhemorrhagic infarct). No threshold was found to diagnose cerebral hemorrhage with a sufficiently high positive predictive value. Among the 200 patients enrolled in the external validity study, 72 patients with a score below 1 had a nonhemorrhagic infarct (ie, 43% of patients with a nonhemorrhagic infarct).

Conclusions
Diagnosis of nonhemorrhagic infarct can be made in 36% (95% confidence interval [CI], 29 to 43) of patients with a high level of accuracy (100% in the external validity study, which gives a 95% CI of 93 to 100). Thus, 43% (95% CI, 36 to 50) of patients with a nonhemorrhagic infarct could receive a bedside diagnosis. The score is simple and can be calculated from information available to all physicians.
Preoperative Cerebrovascular Symptoms and Electroencephalographic Abnormalities Do Not Predict Cerebral Ischemia During Carotid Endarterectomy
Authors: Kearse Lee A. , Lopez-Bresnahan Maria , McPeck Kathleen , Zaslavsky Alan
Published: June 2011

Background and Purpose
The purpose of this prospective study was to establish (1) whether patients with neurological symptoms scheduled for carotid endarterectomy had an increased incidence of electroencephalographic (EEG) abnormalities during awake baseline recordings, (2) whether these symptoms and EEG abnormalities predicted ischemic EEG pattern changes at carotid artery cross-clamp, and (3) whether there was an association between age, presence of EEG baseline abnormalities, and ischemic pattern changes at carotid artery cross-clamp.

Methods
We reviewed the medical record of each patient scheduled to undergo carotid endarterectomy and recorded the patient’s age and history of previous neurological symptoms. We then continuously monitored and analyzed 16 channels of anteroposterior bipolar EEG and two of referential derivations from at least 5 minutes before induction of anesthesia and throughout the operation.

Results
We completed 394 consecutive studies. Preoperative neurological symptoms were related to EEG abnormalities in awake patients (
P
<.001) and to EEG asymmetries in anesthetized patients (
P
<.001). Abnormal awake EEG findings were associated with asymmetries after anesthesia (
P
<.0001). Twenty-eight percent of both symptomatic (70/249) and asymptomatic (41/145) patients had EEG ischemic pattern changes at carotid artery cross-clamp. Neither neurological symptoms nor EEG abnormalities were associated with age or the development of EEG ischemic pattern changes at carotid artery cross-clamp.

Conclusions
Despite the strong association between a history of cerebral ischemic symptoms and preoperative EEG abnormalities in patients undergoing carotid endarterectomy, patients who have suffered strokes or transient ischemic events are at no greater risk of having EEG evidence of cerebral ischemia during carotid artery cross-clamp than patients without symptoms and with normal baseline EEGs. We conclude that preoperative EEG abnormalities in symptomatic patients are not due to age or to insufficiency of regional cerebral blood flow.
Plaque Ulceration and Lumen Thrombus Are the Main Sources of Cerebral Microemboli in High-grade Internal Carotid Artery Stenosis
Authors: Sitzer M. , Müller W. , Siebler M. , Hort W. , Kniemeyer H.-W. , Jäncke L. , Steinmetz H.
Published: June 2011

Background and Purpose
Previous work has shown that rates of cerebral microemboli downstream of high-grade internal carotid artery stenosis are higher in recently symptomatic compared with asymptomatic patients. In addition, microembolic rates decline after carotid endarterectomy. We conducted a prospective investigation of 40 consecutive asymptomatic or recently symptomatic patients undergoing carotid endarterectomy for 70% to 95% internal carotid artery stenosis to determine the relationship between microembolic rate and pathoanatomic features of the carotid plaque.

Methods
Transcranial Doppler monitoring including automated emboli detection was performed preoperatively to assess the rate of cerebral microemboli of the ipsilateral middle cerebral artery. The corresponding endarterectomy specimens were evaluated histologically with respect to the occurrence of plaque fissuring, intraplaque hemorrhage, plaque ulceration, or intraluminal thrombosis.

Results
There were strong associations between plaque ulceration, intraluminal thrombosis, and downstream cerebral microemboli (
P
≤.005, respectively). There were no correlations of microembolism with plaque fissuring or intraplaque hemorrhage (
P
=.82 and
P
=.28, respectively).

Conclusions
We conclude that ulceration and luminal thrombosis of the atheromatous plaque are the main sources of downstream cerebral microemboli in patients with high-grade internal carotid artery stenosis. Our data support the view that these pathoanatomic features may also play a key role in symptom development.
Induction of DNA Fragmentation After 10 to 120 Minutes of Focal Cerebral Ischemia in Rats
Authors: Li Yi , Chopp Michael , Jiang Ning , Zhang Zheng Gang , Zaloga Cecylia
Published: June 2011

Background and Purpose
The induction of neuronal necrosis has been studied after various durations of transient middle cerebral artery (MCA) occlusion in the rat. The objective of the present study was to measure the numbers and anatomic distribution of cells exhibiting apoptotic bodies as an indication of DNA fragmentation and apoptotic cell death as a function of duration of transient MCA occlusion in the rat.

Methods
The MCA of male Wistar rats (n=24) was occluded for 10, 20, 30, 60, 90, and 120 minutes (n=4 per group) with the use of an intraluminal monofilament, and reperfusion was instituted for 48 hours. DNA fragmentation was measured in paraffin sections with the use of a terminal deoxynucleotidyl- transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) method. Adjacent sections were stained with hematoxylin and eosin for analysis of ischemic cell damage, and immunohistochemical double staining methods were used for cell identification. Sham-operated rats (n=4) and normal rats not subjected to any surgical procedure (n=4) were used as controls for apoptosis detection.

Results
Within 5-μm-thick coronal sections, DNA fragmentation was present in 0 to 3 apoptotic cells in each hemisphere of normal, sham-operated rats as well as in the contralateral hemisphere of ischemic rats. After 10 to 20 minutes of MCA occlusion, apoptotic cells exhibiting DNA fragmentation (10 to 20) increased in the regions of selective neuronal necrosis in the preoptic area and in the striatum. After 30 to 60 minutes of ischemia, scattered apoptotic cells (30 to 60) exhibited DNA fragmentation and expanded into areas of selective neuronal necrosis in the cortex. After 90 to 120 minutes of occlusion, groups of apoptotic cells (70 to 200, >95% neurons) were primarily localized to the inner boundary zone of the infarct.

Conclusions
A range of mild to severe ischemia-reperfusion stimuli induce internucleosomal DNA cleavage. The presence and anatomic location of apoptotic cells exhibiting DNA fragmentation after transient cerebral occlusion indicate that apoptosis accompanies neuronal necrosis.
Morbidity, Mortality, and Antihypertensive Treatment Effects by Extent of Atherosclerosis in Older Adults With Isolated Systolic Hypertension
Authors: Sutton-Tyrrell Kim , Alcorn Hope G. , Herzog Holly , Kelsey Sheryl F. , Kuller Lewis H.
Published: June 2011

Background and Purpose
The Systolic Hypertension in the Elderly Program (SHEP) demonstrated a significant reduction in stroke and coronary event rates among participants randomly assigned to active blood pressure treatment. Selected participants were evaluated for peripheral atherosclerosis and followed up for cardiovascular events beyond the end of the SHEP trial. Antihypertensive treatment effects were evaluated based on the presence or absence of clinical or subclinical atherosclerosis.

Methods
As an ancillary study to SHEP, 190 participants at the Pittsburgh center were evaluated for peripheral atherosclerosis, defined as either an internal carotid stenosis (by duplex scan) or lower extremity arterial disease (identified by ankle blood pressure). Participants were subsequently followed up for cardiovascular events.

Results
Estimates of 4-year mortality rates were 4.8% for participants with no atherosclerosis, 16.7% for those with subclinical atherosclerosis, and 23% among those with clinical evidence of atherosclerosis (
P
<.001). Fatal plus nonfatal cardiovascular event rates were 10.9%, 29.8%, and 58.3% for the three groups, respectively (
P
<.001). Differences remained significant after adjustment for age, sex, treatment assignment, smoking, and high-density lipoprotein cholesterol. Individuals assigned to placebo at the beginning of SHEP had higher cardiovascular event rates than individuals assigned to active treatment (
P
=.011), with the most striking difference 3 or more years after the end of the SHEP trial. When this analysis was stratified by the presence or absence of detectable atherosclerosis, the absolute treatment effect was largest among those with evidence of disease.

Conclusions
Individuals with systolic hypertension and evidence of peripheral atherosclerosis are at high risk for cardiovascular events. Targeting this group for antihypertensive therapy would result in the prevention of a large number of cardiovascular events.
Validation of a Population Screening Questionnaire to Assess Prevalence of Stroke
Authors: O’Mahony Paul G. , Dobson Ruth , Rodgers Helen , James Oliver F. W. , Thomson Richard G.
Published: June 2011

Background and Purpose
A cross-sectional survey is the best method for determining the prevalence of a chronic condition such as stroke. Before embarking on a large population study, a valid screening instrument is necessary. This study aimed to validate a self-completion postal screening questionnaire for assessing lifetime history of stroke.

Methods
A random sample of 2000 people aged 45 years and over was selected from the Family Health Services Authority register. A brief self-completion questionnaire requesting self-reported history of stroke was mailed to each individual. Responders reporting a history of stroke received a request for a standardized home assessment visit. Confirmation of the diagnosis of stroke was made based on information from the home visit together with multiple sources of case ascertainment. False-negative responses and assessment of nonresponse bias were documented.

Results
The response rate for the questionnaire was 88%. Of the sample, 120 (6%) who were wrongly registered were excluded; 173 (10%) of the 1663 responders reported a history of stroke. The question “Have you ever had a stroke?” had a sensitivity of 95% and a specificity of 96%.

Conclusions
This simple self-completion questionnaire is a valid means of screening for cases of stroke in the community and could form the basis for subsequent studies of prevalence and health needs.
Silent Brain Infarcts and Transient Ischemic Attacks
Authors: Brainin Michael , McShane Lisa M. , Steiner Michaela , Dachenhausen Alexandra , Seiser Andreas
Published: June 2011

Background and Purpose
We undertook to study the clinical relevance of silent strokes and history of transient ischemic attacks (TIAs) and their individual and combined effects on outcome variables of neurological and epidemiological interest in first-ever stroke patients.

Methods
We performed univariate and multivariate analyses of data prospectively collected in the Klosterneuburg Stroke Data Bank, a hospital-based registry in Austria that includes a 3-year follow-up program.

Results
Of 728 patients (mean age, 68±10 years) with a first-ever ischemic stroke, 110 (15%) had had a previous TIA, and 66/618 (11%) patients did not have a history of TIA but showed evidence of silent brain infarct on CT. Outcome variables of neurological interest were not significantly different between groups, including time between stroke and study entry, activities of daily living status at first presentation, median time of hospitalization, 30-day mortality, or 3-year mortality. Univariate analyses of epidemiologically important risk factors showed either history of TIA or evidence of silent infarct to be more frequently associated with hypertension (
P
=.007). Cox models of survival showed that neither history of TIA nor evidence of silent infarct were significantly associated with an increase in 3-year mortality.

Conclusions
Over a period of 3 years, neither history of TIA nor evidence of silent infarct diagnosed at the time of the presenting major stroke in first-ever ischemic stroke patients exert an important influence on neurological or epidemiological outcome variables.
Spontaneous Early Improvement Following Ischemic Stroke
Authors: Rothrock John F. , Clark Wayne M. , Lyden Patrick D.
Published: June 2011

Background and Purpose
Recognizing that early spontaneous neurological improvement not uncommonly follows acute ischemic stroke, we conducted this study to determine the incidence of such improvement and its potential relation to stroke etiology.

Methods
We prospectively evaluated 68 patients who presented within 12 hours after ischemic stroke, exhibited moderate or severe new functional neurological deficit acutely, and received either no stroke-specific therapy or only antiplatelet therapy over the ensuing week. We reexamined all patients 1 week after stroke onset.

Results
Sixteen (24%) of the 68 patients improved to the point of having no or mild functional neurological deficit at 1 week. Patients with lacunar stroke were more likely to enjoy early spontaneous improvement (8/22=36% versus 8/46=17%), but this difference did not reach statistical significance (
P
=.15).

Conclusions
Early spontaneous improvement after ischemic stroke may occur in a substantial proportion of patients and more commonly after lacunar stroke. Even so, the majority of patients with acutely disabling stroke will remain significantly impaired 1 week after stroke onset.
Cigarette Smoking Accelerates Carotid Artery Intimal Hyperplasia in a Dose-Dependent Manner
Authors: Petrik Pavel V. , Gelabert Hugh A. , Moore Wesley S. , Quinones-Baldrich William , Law Michael M.
Published: June 2011

Background and Purpose
Intimal hyperplasia is the single most important cause of early restenosis after carotid endarterectomy. Cigarette smoking is an independent risk factor associated with peripheral vascular disease and cerebrovascular accidents. We undertook a dose-response experiment to determine the effect of cigarette smoke on development of intimal hyperplasia in a rat carotid artery intimal injury model.

Methods
Seventy-two rats were divided into six equal groups and underwent standardized balloon injury to the carotid artery. Each group received 0 (controls), 1, 2, 3, 6, or 8 cigarettes per day for 4 weeks. Resultant intimal hyperplasia was expressed as a percentage of original lumen replaced by intimal hyperplasia.

Results
Percent intimal hyperplasia development (±SD) was as follows: controls (0 cigarettes per day), 17.7±13.2; 1 cigarette per day, 22.8±15.0; 2 cigarettes per day, 20.0±14.7; 3 cigarettes per day, 19.2±12.1; 6 cigarettes per day, 43.5±15.5; and 8 cigarettes per day, 36.7±9.8. Six and 8 cigarettes per day significantly increased the development of intimal hyperplasia after intimal injury (
P
<.01).

Conclusions
High-dose cigarette smoke accelerates development of intimal hyperplasia and may pose a significant risk factor in developing carotid restenosis.
Cerebral Protection Against Ischemia by Locomotor Activity in Gerbils
Authors: Stummer Walter , Baethmann Alexander , Murr Reinhard , Schürer Ludwig , Kempski Oliver S.
Published: June 2011

Background and Purpose
A previous communication of this laboratory demonstrated reduced mortality and neuronal damage by spontaneous locomotor activity preceding forebrain ischemia in Mongolian gerbils. The present experiments seek to elucidate potential mechanisms of protection by measurement of cerebral blood flow, cerebral tissue conductance as an indicator of ischemic cell swelling, and the cerebral release of eicosanoids.

Methods
Gerbils were maintained either in conventional cages (nonrunners) or with free access to running wheels (runners) for 2 weeks preceding 15 minutes of forebrain ischemia. During ischemia and 2.5 hours of reperfusion, cerebral tissue conductance was determined with a two-electrode system. Simultaneously, prostaglandin D
2
, prostaglandin F
2α
, and thromboxane B
2
were measured in ventriculocisternal perfusate. In additional animals cerebral blood flow was assessed by hydrogen clearance.

Results
Decreases in tissue conductance during ischemia were similar in nonrunners (56±3%) and runners (62±3%) but normalized more rapidly in runners during reperfusion. In both groups reperfusion was accompanied by marked increases of perfusate prostaglandin D
2
, prostaglandin F
2α
, and thromboxane B
2
. In nonrunners, however, thromboxane B
2
was already elevated during ischemia (147±9%,
P
<.01) and remained elevated longer during recirculation (
P
<.05). Postischemic perfusion maxima were higher in runners (70.8±7.4 versus 47.0±5.0 mL/100 g per minute,
P
<.05) and were observed sooner (27.4±6.9 versus 62.2±12.3 minutes,
P
<.05). Both groups displayed delayed hypoperfusion of a similar magnitude (runners, 29.0±2.4 mL/100 g per minute; nonrunners, 30.1±2.4 mL/100 g per minute).

Conclusions
Protection by preischemic locomotor activity may involve enhanced postischemic reperfusion, leading to more rapid normalization of conductance and thus of cell volume. Enhanced reperfusion may be the consequence of attenuated thromboxane liberation during and after ischemia.
Perfusion and Diffusion-Weighted MR Imaging for In Vivo Evaluation of Treatment With U74389G in a Rat Stroke Model
Authors: Müller Tomm B. , Haraldseth Olav , Jones Richard A. , Sebastiani Giovanni , Lindboe Christian F. , Unsgård Geirmund , Øksendal Audun N.
Published: June 2011

Background and Purpose
The present study was performed to examine the potential of diffusion-weighted (DW) imaging and dynamic first-passage bolus tracking of susceptibility contrast agents (perfusion imaging) for early in vivo evaluation of the effects of treatment with the free radical scavenger U74389G in a rat model of temporary focal ischemia.

Methods
After 45 minutes of middle cerebral artery occlusion, the treatment group (n=9) received an infusion of U74389G, and the control group (n=9) received the identical volume of the vehicle. Reperfusion was instituted in both groups after 120 minutes of middle cerebral artery occlusion. The DW images were collected during middle cerebral artery occlusion and reperfusion and were compared with histologically assessed areas of tissue injury after 2 hours of reperfusion. The dynamic perfusion series were processed on a pixel-to-pixel basis to produce parametric maps reflecting the maximum reduction in the signal obtained during the first passage of the contrast agent and the time delay between the arrival of the bolus and the point of maximum contrast-agent effect.

Results
The area of ischemic injury, as assessed from the DW imaging at 60 minutes of reperfusion, was significantly smaller in the treatment group: 9±8% of ipsilateral hemisphere compared with 19±8% in the control group. The histological examination after 2 hours of reperfusion demonstrated an area of ischemic injury of 10±8% for the treatment group compared to 25±10% in the control group. In the treatment group, the perfusion imaging showed a reduction in time delay to maximum effect of the contrast agent in the ischemic hemisphere compared with the control group.

Conclusions
The DW imaging during early reperfusion showed a protective effect of postocclusion treatment with the free radical scavenger U74389G. The improvement of time delay to maximum effect of the contrast agent observed in the perfusion imaging of the treatment group may reflect an improvement in the collateral flow to the ischemic tissue.
Ischemic Delayed Neuronal Death
Authors: Abe K. , Aoki M. , Kawagoe J. , Yoshida T. , Hattori A. , Kogure K. , Itoyama Y.
Published: June 2011

Background
A brief period of global brain ischemia causes cell death in hippocampal CA1 pyramidal neurons days after reperfusion in rodents and humans. Other neurons are much less vulnerable. This phenomenon is commonly referred to as delayed neuronal death, but the cause has not been fully understood although many mechanisms have been proposed.

Summary of Review
Hippocampal CA1 neuronal death usually occurs 3 to 4 days after an initial ischemic insult. Such a delay is essential for the mechanism of this type of cell death. Previous hypotheses have not well explained the reason for the delay and the exact mechanism of the cell death, but a disturbance of mitochondrial gene expression could be a possibility. Reductions of mitochondrial RNA level and the activity of a mitochondrial protein, encoded partly by mitochondrial DNA, occurred exclusively in CA1 neurons at the early stage of reperfusion and were aggravated over time. In contrast, the activity of a nuclear DNA–encoded mitochondrial enzyme and the level of mitochondrial DNA remained intact in CA1 cells until death. Immunohistochemical staining for cytoplasmic dynein and kinesin, which are involved in the shuttle movement of mitochondria between cell body and the periphery, also showed early and progressive decreases after ischemia, and the decreases were found exclusively in the vulnerable CA1 subfield.

Conclusions
A disturbance of mitochondrial DNA expression may be caused by dysfunction of the mitochondrial shuttle system and could cause progressive failure of energy production of CA1 neurons that eventually results in cell death. Thus, the mitochondrial hypothesis could provide a new and exciting potential for elucidating the mechanism of the delayed neuronal death of hippocampal CA1 neurons.
Lipoprotein(a) and Asymptomatic Carotid Artery Disease
Authors: Willeit Johann , Kiechl Stefan , Santer Peter , Oberhollenzer Friedrich , Egger Georg , Jarosch Elmar , Mair Agnes
Published: June 2011

Background and Purpose
Elevated levels of lipoprotein(a) [Lp(a)] have been reported in association with symptomatic coronary and carotid artery disease. Relevancy of Lp(a) as a risk predictor of presymptomatic atherosclerosis in general populations is not well established.

Methods
Serum Lp(a) distribution and its relation to sonographically assessed carotid atherosclerosis were examined in a random sample of 885 men and women aged 40 to 79 years (Bruneck Study).

Results
Logistic regression analysis revealed a binary-type association between Lp(a) and carotid artery disease, with the threshold level of Lp(a) for an enhanced atherosclerosis risk defined at 32 mg/dL. The strength of relation increased with advancing severity of carotid atherosclerosis (odds ratios for Lp(a), 1.8 for nonstenotic and 4.7 for stenotic carotid artery disease;
P
<.001). Lp(a) was unaffected by environmental factors except for a significant decrease in women taking hormone replacement therapy (
P
<.05). In a multivariate approach, Lp(a) turned out to be an independently significant predictor of carotid atherosclerosis (
P
<.001). No differential effect of Lp(a) on atherosclerosis (effect modification) was observed for sex, age, low-density lipoprotein cholesterol, apolipoprotein A-I and B, fasting glucose, diabetes, or hypertension. However, the Lp(a)-atherosclerosis relation was significantly modified by fibrinogen (
P
<.01) and antithrombin III (
P
<.05).

Conclusions
The present study demonstrates a strong and independent association between elevated Lp(a) levels and carotid atherosclerosis in a large randomized population and provides evidence of a potential role of Lp(a) in the evolution of carotid stenosis. Apart from atherogenicity of Lp(a) cholesterol, interference with fibrinolysis of atheroma-associated clots and fibrin deposits in the arterial wall may achieve pathophysiological significance.
Immunohistochemical Alterations of Fibronectin During the Formation and Proliferative Repair of Experimental Cerebral Aneurysms in Rats
Authors: Futami Kazuya , Yamashita Junkoh , Tachibana Osamu , Higashi Sotaro , Ikeda Kiyonobu , Yamashima Tetsumori
Published: June 2011

Background and Purpose
To determine whether distributional changes of fibronectin, a factor promoting wound healing, occur during the formation and repair of cerebral saccular aneurysms, we performed immunohistochemical analyses in experimental aneurysms.

Methods
Cerebral aneurysms were induced in rats by both the ligation of the unilateral common carotid artery and induced hypertension. Intimal proliferation in aneurysmal walls was induced by the ligation of the preserved common carotid artery 3 months after the first operation. The distribution of fibronectin was examined by immunohistochemistry in anterior cerebral artery–olfactory artery bifurcations under the following three conditions: normal bifurcations in control rats, early aneurysmal lesions during the aneurysm induction, and aneurysmal lesions with intimal proliferation. Furthermore, the immunohistochemical distributions of type I and IV collagens were examined to evaluate the specificity of fibronectin immunoreactivity.

Results
In the normal bifurcations, fibronectin was positive in the subintimal space, the surrounding area of the medial smooth muscle cells, and the adventitial fibrous tissue. In early aneurysmal lesions, linear staining of fibronectin and type I and IV collagens in the subendothelial space disappeared with the loss of the internal elastic lamina. In the intimal proliferation of early aneurysmal lesions, fibronectin was strongly immunostained in the subendothelial space and diffusely immunostained in the widened extracellular space surrounding proliferated cells. In contrast, the stainings of type I and IV collagens were sparse or negative.

Conclusions
Although the present findings regarding dynamic changes of fibronectin distribution do not prove any causality in the process of aneurysm formation and repair, these immunohistochemical changes may constitute the crucial sequela of intimal endothelial damage and its subsequent recovery in cerebral aneurysms.
Expression of bcl-2 From a Defective Herpes Simplex Virus–1 Vector Limits Neuronal Death in Focal Cerebral Ischemia
Authors: Linnik Matthew D. , Zahos Peter , Geschwind Michael D. , Federoff Howard J.
Published: June 2011

Background and Purpose
A process resembling programmed cell death appears to contribute to postischemic neuronal loss in several models of stroke. Because the expression of the bcl-2 gene has been shown to rescue neurons from programmed cell death due to other causes, we determined whether it would be similarly neuroprotective in stroke.

Methods
Replication defective herpes viral vectors that transduce bcl-2 (HSVbcl2) or
Escherichia coli
lacZ (HSVlac) were injected into two sites in the rat cerebral cortex 24 hours before induction of neocortical focal ischemia by tandem permanent occlusion of the right middle cerebral artery and ipsilateral common carotid artery. Local ischemic damage was determined 24 hours after occlusion by staining with 2% 2,3,5-triphenyltetrazolium chloride.

Results
Expression of bcl-2 in cerebral cortex was confirmed by immunohistochemistry in animals injected with the HSVbcl2 expression vector. Viable tissue was significantly increased at the injection sites in HSVbcl2- but not HSVlac-injected animals. The protection observed in the HSVbcl2 animals was localized to the injection sites.

Conclusions
These data indicate that bcl-2 expression protects neurons in vivo from ischemic injury and suggest the feasibility of gene therapy for stroke and perhaps other neurological diseases in which programmed cell death is involved.
Thrombus Associated With Mitral Valve Calcification
Authors: Stein James H. , Soble Jeffrey S.
Published: June 2011

Background
Several studies have demonstrated an association between mitral annular calcification and stroke; however, the pathophysiological explanation remains speculative.

Case Descriptions
We describe two patients with cerebral embolism in whom mitral valve calcification was demonstrated by transthoracic echocardiography. In both patients, transesophageal echocardiography identified a mass that appeared to be thrombus on the calcified portion of the mitral apparatus. There was no evidence of a hypercoagulable state or endocarditis in either case. Repeated transesophageal echocardiography after anticoagulation demonstrated resolution of the masses in both patients.

Conclusions
These cases support the hypothesis that thrombus formation may be a pathophysiological link between ischemic cerebral events and mitral annular calcification in some patients.
Epidemiology of Stroke in Hispanic Americans
Authors: Gillum Richard F.
Published: June 2011

Background and Purpose
In 1990 cerebrovascular disease was the fourth leading cause of death in Hispanics in the United States. However, little information has been published about the epidemiology of stroke in US Hispanic populations.

Methods
Data from the National Center for Health Statistics were examined to characterize the pattern of stroke occurrence and risk factors among Hispanics in the United States.

Results
In 1989 through 1991, stroke death rates were similar in Hispanics and whites aged 45 to 64 years; at ages 65 and over, Hispanics had rates that were substantially lower than those of whites. Data from national surveys suggest that the ethnic differences in stroke mortality may be due in part to lower blood pressure in Hispanics than non-Hispanics.

Conclusions
Cohort studies, well-designed case-control studies, and continued oversampling of Hispanics in national surveys are needed to further define the epidemiological patterns of stroke in US Hispanics and to guide stroke prevention efforts.
Epidemiology of Carotid Endarterectomy and Cerebral Arteriography in the United States
Authors: Gillum Richard F.
Published: June 2011

Background and Purpose
Results of North American and European trials of carotid endarterectomy published in 1991 may have affected the frequency of the procedure in the United States. Therefore, data from a national survey of hospital discharges were examined to determine whether rates of carotid endarterectomy and arteriography increased after 1991 and whether race and sex variations in rates have persisted.

Methods
Data from the National Hospital Discharge Survey were examined for the years 1980 through 1993. Estimated numbers of procedures performed in nonfederal US hospitals were used to compute rates per 100 000 population by year, age, race, and sex.

Results
In persons aged 65 years and over, the rate of carotid endarterectomy increased rapidly between 1980 and 1983 with a slight further increase through 1985. A marked fall in the rate occurred between 1985 and 1988, followed by a plateau and a sharp upturn in 1992. After 1985, there was a steady decline in the rate of cerebral arteriography procedures in hospital. No reliable data were available on outpatient cerebral arteriography. Throughout the period, whites had estimated rates of carotid endarterectomy procedures over four times higher than blacks. Whites also had higher rates of cerebral arteriography, but the disparity was not as great as for endarterectomy. Rates of carotid endarterectomy were 60% higher in men than women, but rates of cerebral arteriography were only 9% higher in men than women.

Conclusions
Rates of carotid endarterectomy increased sharply after the 1991 publication of trial results. Marked racial disparities in the use of this procedure persist and require further evaluation.
Improved Cerebral Resuscitation From Cardiac Arrest in Dogs With Mild Hypothermia Plus Blood Flow Promotion
Authors: Safar Peter , Xiao Feng , Radovsky Ann , Tanigawa Koichi , Ebmeyer Uwe , Bircher Nicholas , Alexander Henry , Stezoski S. William
Published: June 2011

Background and Purpose
In past studies, cerebral outcome after normothermic cardiac arrest of 10 or 12.5 minutes in dogs was improved but not normalized by resuscitative (postarrest) treatment with either mild hypothermia or hypertension plus hemodilution. We hypothesized that a multifaceted combination treatment would achieve complete cerebral recovery.

Methods
With our established dog outcome model, normothermic ventricular fibrillation of 11 minutes (without blood flow) was followed by controlled reperfusion (with brief normothermic cardiopulmonary bypass simulating low flow and low Pa
o
2
of external cardiopulmonary resuscitation) and defibrillation at <2 minutes. Controlled ventilation was provided to 20 hours and intensive care to 96 hours. Control group 1 (n=8) was kept normothermic (37.5°C), normotensive, and hypocapnic throughout. Experimental group 2 (n=8) received mild resuscitative hypothermia (34°C) from about 10 minutes to 12 hours (by external and peritoneal cooling) plus cerebral blood flow promotion with induced moderate hypertension, mild hemodilution, and normocapnia.

Results
All 16 dogs in the protocol survived. At 96 hours, all 8 dogs in control group 1 achieved overall performance categories 3 (severe disability) or 4 (coma). In group 2, 6 of 8 dogs achieved overall performance category 1 (normal); 1 dog achieved category 2 (moderate disability), and 1 dog achieved category 3 (
P
<.001). Final neurological deficit scores (0% [normal] to 100% [brain death]) at 96 hours were 38±10% (22% to 45%) in group 1 versus 8±9% (0% to 27%) in group 2 (
P
<.001). Total brain histopathologic damage scores were 138±22 (110 to 176) in group 1 versus 43±9 (32 to 56) in group 2 (
P
<.001). Regional scores showed similar group differences.

Conclusions
After normothermic cardiac arrest of 11 minutes in dogs, resuscitative mild hypothermia plus cerebral blood flow promotion can achieve functional recovery with the least histological brain damage yet observed with the same model and comparable insults.
Effects of Cerebral Ischemia on

N

-Methyl-
d
-Aspartate and Dihydropyridine-Sensitive Calcium Currents
Authors: Dalkara Turgay , Ayata Cenk , Demirci Mehmet , Erdemli Gül , Onur Rüstü
Published: June 2011

Background and Purpose
During cerebral ischemia, both promoting and limiting factors are present for activation of the
N
-methyl-
d
-aspartate (NMDA) receptor ion channel and the dihydropyridine (DHP)-sensitive Ca
2+
channels. We investigated the activity of these channels during ischemia and reperfusion in the rat hippocampus in situ.

Methods
Reversible ischemia was induced by bilateral carotid artery ligation. NMDA and BAY K8644 were applied by iontophoresis or pneumatic ejection, and extracellular field potential and resistance changes were recorded from the CA1 region of the rat hippocampus. Resting membrane potentials of the CA1 neurons were also recorded.

Results
DC potential shifts produced by NMDA and BAY K8644 were reduced when ischemia depressed the evoked activity more than 50%. They disappeared on total failure of synaptic transmission and recovered during reperfusion. When the evoked activity was depressed less than 50%, DC shifts were greater than their preischemic values; however, BAY K8644-induced potentiation did not reach statistical significance. CA1 neurons were depolarized during ischemia.

Conclusions
These data suggest that ischemia severe enough to cause transmission failure inactivates NMDA and DHP-sensitive Ca
2+
currents. During less intense ischemia and reperfusion, NMDA and DHP-sensitive Ca
2+
channels are functional, and their overactivation may lead to neurotoxicity.
Comparison of Rehabilitation Practice on Hospital Wards for Stroke Patients
Authors: Lincoln N.B. , Willis D. , Philips S.A. , Juby L.C. , Berman P.
Published: June 2011

Background and Purpose
The aim of the study was to observe patients on a stroke unit and to compare their activity with that of patients on conventional hospital wards to identify aspects of rehabilitation practice that might account for differences in outcome.

Methods
Stroke patients admitted to the hospital were observed on three 8-hour shifts over 3 consecutive days. An observer recorded, at 10-minute intervals, where patients were, what they were doing, and whether their positioning was as recommended by rehabilitation therapists. Patients on a stroke unit were compared with those on conventional wards.

Results
Stroke unit patients spent less time by their beds and more time in other locations on the ward (
P
<.001). There were significant differences in the frequency of behaviors observed in the two types of ward (
P
<.001). Stroke unit patients had significantly more interaction with nurses and therapists (
P
<.001). They were also more often in the recommended position (
P
<.001).

Conclusions
The proportion of time in therapeutic activity was low in all locations, with patients spending many hours sitting and doing nothing. Despite this, stroke unit patients had more therapeutic contact with staff and were more often in the recommended position. These two features may account for some of the differences in outcome.
Lubeluzole in Acute Ischemic Stroke
Authors: Diener H.C. , Hacke W. , Hennerici M. , Rådberg J. , Hantson L. , De Keyser J.
Published: June 2011

Background and Purpose
We aimed to assess the safety and efficacy of lubeluzole in patients with a clinical diagnosis of acute (<6 hours) ischemic stroke in the carotid artery territory.

Methods
A randomized, double-blind, placebo-controlled multicenter trial was conducted in 232 patients. Because treatment was administered within 6 hours and a CT scan was not mandatory before the start of treatment, 39 patients with either an intracerebral hemorrhage or ischemic stroke in the vertebrobasilar circulation were excluded from the primary efficacy analysis as prespecified in the protocol. Of the 193 patients with acute ischemic stroke in the carotid artery territory (target population), 61 received placebo, 66 lubeluzole 7.5 mg over 1 hour followed by 10 mg/d for 5 days, and 66 lubeluzole 15 mg over 1 hour followed by 20 mg/d for 5 days.

Results
The trial, initially aimed at a patient inclusion of 270, was terminated prematurely according to the advice of the Safety Committee because of an imbalance in mortality between the treatment groups. Mortality rates at the final follow-up of 28 days for placebo, lubeluzole 10 mg/d, and lubeluzole 20 mg/d were, respectively, 18%, 6%, and 35% in the target population, results that were confirmed in the intent-to-treat population. Multivariate logistic regression analysis showed that the lower mortality in the lubeluzole 10 mg/d group was significantly in favor of the 10 mg/d treatment (
P
=.019). The higher mortality rate in the 20 mg/d group could be explained, at least in part, by an imbalance at randomization that led to a higher number of patients in that group with severe ischemic stroke. A total of 26 of 66 patients (39%) who received lubeluzole 10 mg/d had a score on the Barthel Index of >70 at day 28, indicating no or mild disability, compared with 21 of 61 (34%) in the placebo group and 19 of 66 (29%) in the lubeluzole 20 mg/d group (
P
=NS).

Conclusions
In patients with acute ischemic stroke, the dosage regimen of 7.5 mg over 1 hour followed by 10 mg/d of intravenous lubeluzole is safe and statistically significantly reduced mortality. Further clinical trials in a larger number of patients are ongoing to confirm efficacy.
Single-Photon Emission Computed Tomography Using Hexamethylpropyleneamine Oxime in the Prognosis of Acute Cerebral Infarction
Authors: Bowler J.V. , Wade J.P.H. , Jones B.E. , Nijran K. , Steiner T.J.
Published: June 2011

Background and Purpose
The role of single-photon emission CT (SPECT) in the prognosis of cerebral infarction is controversial, but most studies report that SPECT using a variety of radiopharmaceutical agents gives useful prognostic information. Only one study has questioned whether acute perfusion deficits independently add to a valid clinical prognostic score. This study was limited to middle cerebral artery territory infarcts and was negative. We present data on the prognostic utility of SPECT using
99m
Tc–hexamethylpropyleneamine oxime (HMPAO) in cerebral infarction, unselected by site.

Methods
Fifty consecutive unselected patients admitted to the hospital with acute cerebral infarction, of whom 10 died and 7 withdrew, had SPECT performed serially at onset and at 1 week and 3 months after stroke onset using
99m
Tc-HMPAO and the NOVO 810 dedicated high-resolution head tomograph. Clinical severity at presentation and outcome was measured with the Canadian Neurological Scale and the Barthel Index. Infarct volumes were measured from both the SPECT and CT scans. The data for the 43 subjects who completed the study or died were evaluated to determine the most powerful prognostic measures. Predictors were the Canadian Neurological Scale score at onset and 1 week, the Barthel Index at 1 week, the CT infarct volume typically done between 3 and 7 days after stroke onset, and the infarct volumes at the first and second SPECT. Outcome measures were the Canadian Neurological Scale score and Barthel Index score at 3 months, scored as zero for those patients who died.

Results
The clinical prognostic indicators correlated with the outcome measures, with coefficients between .617 and .821 (
P
<.0006 in all cases). The Canadian Neurological Scale score measured at 1 week was the best of these. Infarct volumes measured from SPECT correlated less well (coefficients between −.518 and −.683,
P
<.0019 in all cases). CT infarct volume was the poorest predictor. Although SPECT infarct volumes predicted outcome, they did so less well than clinical examination. Spontaneous infarct reperfusion did not affect outcome.

Conclusions
Although the measurement of infarct volume on SPECT using
99m
Tc-HMPAO provides a predictor of stroke outcome, it is not a better predictor than the Canadian Neurological Scale score.
Recovery of Cognitive Function After Stroke
Authors: Desmond David W. , Moroney Joan T. , Sano Mary , Stern Yaakov
Published: June 2011

Background and Purpose
Previous studies have suggested that recovery of cognitive function after stroke is maximal within the first 3 months after onset. We performed the present study to investigate the long-term course and clinical correlates of improvement in generalized cognitive function after ischemic stroke.

Methods
We administered a battery of neuropsychological tests to 151 patients (age, 70.4±7.7 years; education, 10.4±4.6 years) at 3 months and then annually after stroke. We transformed their test results into
z
scores based on the performance of a stroke-free normative group, averaged those scores to create a summary score, and defined improvement in annual examinations as an increase in that summary score greater than two standard deviations above the mean first annual change of the normative group. We then used logistic regression to determine whether stroke location, syndrome, or recurrence; vascular risk factors; dementia status; depression; or demographic variables were associated with improvement.

Results
We found that 19 of the 151 patients exhibited improvement, which was evident only at the first annual examination in most cases. Logistic regression determined that improvement was significantly related to left hemisphere infarction relative to brain stem/cerebellar infarction (odds ratio [OR], 5.57), while the presence of a major hemispheral stroke syndrome showed a trend toward significance (OR, 3.32). Diabetes mellitus was significantly associated with a failure to exhibit improvement (OR, 0.12). Based on the logistic model, the probability of long-term improvement would be 54.0% for a patient with a left hemisphere infarct and a major hemispheral syndrome but only 11.9% if diabetes was also present.

Conclusions
Long-term improvement in generalized cognitive function may be evident after stroke in association with left hemisphere infarction and severe hemispheral syndromes, while it may be compromised by diabetes, possibly because of an increased burden of cerebrovascular disease.
Plasma Antioxidant Consumption Associated With Ischemia/Reperfusion During Carotid Endarterectomy
Authors: Bacon Pamela J. , Love Shirley A. , Gupta Arun K. , Kirkpatrick Peter J. , Menon David K.
Published: June 2011

Background and Purpose
Thirteen patients undergoing carotid endarterectomy were studied to correlate changes in jugular bulb venous oxygen saturation (S
j
o
2
) with indices of free radical production during cerebral ischemia/reperfusion. Levels of oxidant species were also monitored in arterial samples to determine any change across the cerebral circulation.

Methods
Blood was sampled from a venous catheter inserted in the ipsilateral jugular bulb and from an arterial catheter. Co-oximetry measurements were made to determine jugular bulb venous oxygenation saturation. To monitor changes in oxidant stress, a colorimetric assay was used to determine plasma antioxidant potential, and electron paramagnetic resonance spectroscopy was used to quantify free radical–spin trap adducts formed in a blood sample treated with the spin trap α-tert-butyl phenyl nitrone (PBN).

Results
S
j
o
2
decreased significantly from 68±11% to 61±10% (
P
<.05) during clamping of the internal carotid artery and returned to baseline (65±11%) when the carotid clamp was removed. Jugular venous plasma antioxidant potential decreased significantly from 32.76±5.42% inhibition to 28.02±6.77% inhibition (
P
<.05). There was no concomitant change in arterial plasma antioxidant potential values, indicating a decrease in antioxidant capacity across the cerebral circulation. However, analysis of spin trap–free radical adducts did not provide conclusive evidence for free radical production.

Conclusions
These results provide supportive evidence for oxidant production during cerebral ischemia/reperfusion in a clinical setting.