bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Transcranial Doppler Ultrasound to Predict Outcome in Patients With Intracranial Large-Artery Occlusive Disease
Authors: Wong Ka Sing , Li Huan , Chan Yu Leung , Ahuja Anil , Lam Wynnie W.M. , Wong Agatha , Kay Richard
Published: June 2011

Background and Purpose
—Intracranial large-artery occlusive disease is the predominant vascular lesion found in stroke patients of Asian, African, and Hispanic ancestry, making it numerically perhaps the most common vascular cause of stroke in the world. Relatively little is known about the clinical significance of finding such lesions. We investigate whether the presence and the extent of these vascular lesions help predict outcome after stroke.

Methods
—On the basis of transcranial Doppler of the intracranial arteries with supplementary duplex ultrasound of the carotid arteries, we determined the number of occlusive arteries in the craniocervical circulation of consecutive patients who were hospitalized for acute cerebral ischemia. Patients were followed for 6 months for further vascular events (including transient ischemic attack, stroke, and acute coronary syndrome) or death.

Results
—Among 705 consecutive Chinese patients studied, occlusive arteries were found in 345 patients (49%): 258 patients (37%) had intracranial lesions only, 71 (10%) had both extracranial and intracranial lesions, and 16 (2.3%) had extracranial lesions only. Sixty-three (18%) of the 345 patients with occlusive arteries and 35 (9.7%) of the 360 patients without occlusive arteries had further vascular event or death within 6 months. The risk of vascular events or death increased rapidly with rising numbers of occlusive arteries, after adjustment for vascular risk factors and stroke severity (adjusted odds ratio [OR] 1.25 per occlusive artery, 95% CI 1.12 to 1.39). Other independent risk factors included age (OR 1.03 per year of age, 95% CI 1.01 to 1.05) and atrial fibrillation (OR 3.00, 95% CI 1.40 to 6.69).

Conclusions
—In patients with predominantly intracranial large-artery occlusive disease, the presence and the total number of occlusive arteries in the craniocervical circulation predict further vascular events or death within 6 months after stroke. Transcranial Doppler ultrasound is an important investigation for the evaluation of patients with stroke in populations at risk of intracranial atherosclerotic disease.
Polymorphism in the Promoter of Lipopolysaccharide Receptor CD14 and Ischemic Cerebrovascular Disease
Authors: Ito Daisuke , Murata Mitsuru , Tanahashi Norio , Sato Hideki , Sonoda Akira , Saito Ikuo , Watanabe Kiyoaki , Fukuuchi Yasuo
Published: June 2011

Background and Purpose
—A growing amount of evidence suggests that infectious and inflammatory processes may be involved in the initiation of arteriosclerosis, but the mechanisms are conceivably multifactorial and complex. Two European groups have recently demonstrated that a C(−260)→T polymorphism in the promoter of the CD14 lipopolysaccharide receptor may be a risk factor for coronary artery disease (CAD). The T allele of this polymorphism reportedly increases the expression of CD14 and may be involved in atherogenesis. In the present study we investigated a possible association between the C(−260)→T polymorphism in the CD14 promoter and the occurrence of symptomatic ischemic cerebrovascular disease (CVD).

Methods
—Genotype frequencies of the C(−260)→T polymorphism in the CD14 promoter were determined in 235 patients with CVD, as confirmed by brain CT and/or MRI, and 309 age- and sex-matched control subjects.

Results
—The distribution of genotypes was as follows: CVD patients,
T
/
T
24.3%,
C
/
T
53.2%, and
C
/
C
22.6%; controls,
T
/
T
26.9%,
C
/
T
50.2%, and
C
/
C
23.0%. There was no significant difference between the CD14 promoter genotypes of the CVD patients and the controls (χ
2
=0.601,
P
=0.741). We also measured the concentration of serum soluble CD14 and the density of membranous CD14 on monocytes in the CVD patients, but the polymorphism was not associated with either the concentration of soluble CD14 or the density of membranous CD14 (
P
=0.358,
P
=0.238, respectively).

Conclusions
—Our results indicate that the C(−260)→T polymorphism in the CD14 promoter is not associated with an increased risk for CVD.
Release of Glial Tissue–Specific Proteins After Acute Stroke
Authors: Herrmann Manfred , Vos Pieter , Wunderlich Michael T. , de Bruijn Chris H. M. M. , Lamers Karl J. B.
Published: June 2011

Background and Purpose
—This study was aimed at the comparative analysis of serum concentrations of glial fibrillary acidic protein (GFAP) and protein S-100B in patients with acute stroke.

Methods
—We investigated 32 patients with stroke symptoms consistent with cerebral ischemia in the anterior territory of vascular supply. Serial venous blood samples were taken after admission to the hospital and during the first 4 days after onset of stroke. Evaluation of lesion topography and volume of infarcted brain area was based on cranial CT data. The patients’ clinical status was consecutively evaluated by the National Institutes of Health Stroke Scale (NIHSS) and the Barthel Index score at discharge from the hospital.

Results
—Protein S-100B and GFAP release was found to be significantly correlated (
r
=0.96;
P
<0.001). The release of both biochemical markers was associated with the volume of brain lesions (S-100B:
r
=0.957,
P
<0.0001; GFAP:
r
=0.955,
P
<0.0001) and the neurological status at discharge from the hospital (S-100B:
r
=0.821,
P
=0.0002; GFAP:
r
=0.717,
P
=0.0003). The highest correlation between both S-100B and GFAP serum concentration and Barthel score was calculated at the last time of blood sampling, 4 days after stroke onset (S-100B:
r
=0.621,
P
<0.001; GFAP:
r
=0.655,
P
<0.001). The release of both astroglia derived proteins differed between different subtypes of stroke. GFAP was found to be a more sensitive marker of brain damage in patients with smaller lacunar lesions or minor strokes.

Conclusions
—Our results indicate that postischemic release patterns of GFAP and S-100B protein may allow insight into the underlying pathophysiology of acute cerebral infarcts and may be used as a valuable tool of clinical stroke treatment.
Differences in Vulnerability to Permanent Focal Cerebral Ischemia Among 3 Common Mouse Strains
Authors: Majid Arshad , He Yong Y. , Gidday Jeffrey M. , Kaplan Stuart S. , Gonzales Ernesto R. , Park T. S. , Fenstermacher Joseph D. , Wei Ling , Choi Dennis W. , Hsu Chung Y.
Published: June 2011

Background and Purpose
—Genetically engineered mice are used to study the role of single genes in cerebral ischemia, but inherent, strain-dependent differences in neuronal vulnerability may affect experimental end points. To examine this possibility, tissue injury resulting from focal ischemia and its relationship to cerebral hemodynamics were determined in 3 common mutant mouse strains.

Methods
—Permanent middle cerebral artery ligation was performed in male C57BL/6J, Balb/C, and 129X1/SvJ mice. Mean arterial blood pressure, blood gases, basal and postischemic cortical blood flow ([
14
C]iodoantipyrine autoradiography and laser-Doppler flowmetry), posterior communicating artery patency, and infarct size were determined.

Results
—Basal cortical blood flow did not differ among strains. Ten minutes after middle cerebral artery ligation, relative red cell flow in the ischemic cortex was 6% to 7% of preischemic flow in every strain. Despite similar hemodynamics, cortical infarcts in Balb/C mice were 3-fold larger than those in 129X1/SvJ and C57BL/6J mice; infarct size in the latter 2 strains was not significantly different. The posterior communicating artery was either poorly developed or absent in >90% of the Balb/C and C57BL/6J but in <50% of the 129X1/SvJ mice.

Conclusions
—The extent of ischemic injury differed markedly between the 3 strains. The presence and patency of posterior communicating arteries, although variable among strains, did not affect preischemic or postischemic cortical blood flow or bear any relationship to ischemic injury. Therefore, intrinsic factors, other than hemodynamic variability, may contribute to the differences in ischemic vulnerability among strains. These findings underscore the importance of selecting genetically matched wild-type controls.
Anticoagulant Patient Information Material Is Written at High Readability Levels
Authors: Estrada Carlos A. , Hryniewicz Mary Martin , Higgs Vetta Barnes , Collins Cathy , Byrd James C.
Published: June 2011

Background
—Warfarin therapy requires frequent monitoring and dose adjustment. Elderly patients with atrial fibrillation, prior stroke, and lower literacy skills may have difficulty reading brochures that explain dosing instructions, procedures to follow, and the risks and benefits of anticoagulants. In general, it is recommended that brochures be written at or below the 6th-grade level. We determined the readability of patient information material being offered to patients receiving anticoagulants.

Methods and Results
—We used the SMOG grade formula to measure readability of written patient materials. We obtained 50 brochures commonly used in anticoagulation management units from industry and health advocacy groups. Patient information was related to atrial fibrillation (16%, n=8), warfarin (44%, n=22), low-molecular-weight heparins (12%, n=6), or other related topics (28%, n=14). The mean readability was found to be grade 10.7 (95% CI 10.1 to 11.2); none had a readability score at the 6th-grade level or below, 12% of the brochures had readability scores at the 7th- to 8th-grade levels (n=6), 74% at the 9th- to 12th-grade levels (n=37), and 14% at higher than 12th-grade level (n=7). The readability grade level was similar for brochures produced by industry or health advocacy groups (
P
=0.9) but higher for information obtained from the Internet (12.2±1.3 grades) compared with other sources (10.3±2.1 grades;
P
=0.01).

Conclusions
—Patient education materials related to the use of anticoagulants are written at grade levels beyond the comprehension of most patients. Low-literacy brochures are needed for patients on anticoagulants.
Perimesencephalic Hemorrhage and CT Angiography
Authors: Ruigrok Ynte M. , Rinkel Gabriël J. E. , Buskens Erik , Velthuis Birgitta K. , van Gijn Jan
Published: June 2011

Background and Purpose
—The method of choice for detecting or excluding a vertebrobasilar aneurysm still is a matter of debate in patients with a characteristically perimesencephalic pattern of subarachnoid hemorrhage (SAH) on CT. We used decision analysis to compare possible diagnostic strategies in these patients.

Methods
—A decision analytic model was developed to evaluate the effect of 4 different diagnostic strategies following a perimesencephalic pattern of SAH on CT: 1, no further investigation; 2, digital subtraction angiography (DSA) by catheter; 3, CT angiography as initial modality, not followed by DSA if negative; and 4, CT angiography as initial modality, followed by DSA. We used a 4% prevalence of a vertebrobasilar aneurysm given a perimesencephalic pattern of hemorrhage, a 97% sensitivity and specificity of CT angiography, and a 99.5% sensitivity and 100% specificity of DSA. In a prospectively collected series, the complication rate from DSA in patients with a perimesencephalic pattern of hemorrhage was 2.6%. We calculated the expected utility of each of the 4 diagnostic options and used sensitivity analyses to examine the influence of the plausible ranges of the various estimates used.

Results
—The expected utilities were 99.09 for CT angiography only, 98.96 for no further investigation, 98.22 for DSA, and 96.34 for CT angiography plus DSA. The results of the sensitivity analysis indicate that over a wide range of assumptions, CT angiography only is the most beneficial option. Only when the complication rate of catheter angiography is <0.2% is DSA the preferred strategy.

Conclusions
—Our decision analysis shows that in patients with a perimesencephalic pattern of hemorrhage on CT, CT angiography only is the best diagnostic strategy. DSA can be omitted in patients with a perimesencephalic pattern of hemorrhage and a negative CT angiogram.
Quality of Life Among Stroke Survivors Evaluated 1 Year After Stroke
Authors: Carod-Artal Javier , Egido José Antonio , González José Luis , Varela de Seijas E.
Published: June 2011

Background and Purpose
—We sought to study overall and domain-specific quality of life in stroke survivors 1 year after stroke and to identify variables that could predict quality of life after stroke.

Methods
—We followed up for 1 year a cohort of 118 patients consecutively admitted to our stroke unit at San Carlos University Hospital in Madrid, Spain. The final series at 1-year follow-up consisted of 90 survivors (41 women and 49 men; mean age, 68 years; range, 32 to 90 years). A cross-sectional, descriptive design was developed. Patients completed a questionnaire that included socioeconomic variables, Hamilton Rating Scale for Depression, Sickness Impact Profile (SIP), Short Form 36, Frenchay Index, Barthel Index, Rankin Scale, and Scandinavian Stroke Scale. Independent variables were sex, age, functional status, motor impairment, and depression. We developed an ANOVA model for statistical analysis.

Results
—We interviewed 79 patients with ischemic and 11 with hemorrhagic stroke. Thirty-eight percent of patients scored in the depressed range. Variables related to depression were status as a housewife, female sex, inability to work because of disability, and diminished social activity (
P
<0.0001). Mean total SIP (24.3), SIP psychosocial dimension (27.5), and SIP physical dimension (21.2) were correlated with disability, female sex, motor impairment, and depression (
P
<0.0001).

Conclusions
—Functional status and depression were identified as predictors of quality of life. Patients independent in their activities of daily living suffered from a deterioration of the psychosocial dimension of the SIP.
N
-Acetylaspartate Distribution in Proton Spectroscopic Images of Ischemic Stroke
Authors: Wild J. M. , Wardlaw J. M. , Marshall I. , Warlow C. P.
Published: June 2011

Background and Purpose
—It is generally considered that tissue that appears abnormal on T2 MRI is already infarcted and that any penumbra lies outside the T2-visible lesion. We investigated the distribution of infarcted tissue using proton spectroscopic MRI.

Methods
—In patients with symptoms of acute hemispheric ischemic stroke, imaged within a maximum of 3 days of stroke, we explored the distribution of
N
-acetylaspartate (NAA), a marker of intact neurons, within and around the abnormal (hyperintense) areas on T2-weighted MR images, using proton spectroscopic MRI.

Results
—In 11 patients, imaged 24 to 72 hours after stroke onset, there was little evidence of damaged neurons (reduced NAA) beyond the margins of hyperintensity on the T2 image. However, within the abnormal T2 area, there were statistically significant differences in the amount of NAA (ie, the proportion of intact neurons) between areas that were obviously abnormal on T2 (very hyperintense) and those that were only slightly abnormal (slightly hyperintense).

Conclusions
—The extent and degree of hyperintensity of the T2-visible lesion directly reflect the amount of neuronal damage; lack of a T2-visible lesion would suggest predominantly intact neurons at the time of imaging. We hypothesize that once tissue damage has reached a critical (probably irreversible) level, the T2 image quickly becomes abnormal without any significant time lag between the pathological staging of the infarct and its visualization on T2. Further testing in a larger study with information on blood flow levels would be required to confirm this.
Serum Ferritin and C282Y Mutation of the Hemochromatosis Gene as Predictors of Asymptomatic Carotid Atherosclerosis in a Community Population
Authors: Rossi Enrico , McQuillan Brendan M. , Hung Joseph , Thompson Peter L. , Kuek Conchita , Beilby John P.
Published: June 2011

Background and Purpose
—Serum ferritin and heterozygosity for the C282Y mutation of the hemochromatosis gene have both been associated with an increased risk of cardiovascular events. The purpose of the study was to test whether either is a risk predictor for asymptomatic carotid atherosclerosis.

Methods
—We assessed carotid intima-media wall thickness (IMT) and focal plaque formation by high-resolution B-mode ultrasound, conventional risk factors, serum ferritin levels, and the C282Y mutation of the hemochromatosis gene in a randomly selected community population of 1098 subjects (545 women and 553 men) aged 27 to 77 years.

Results
—After adjustment for conventional risk factors, serum ferritin was not associated with carotid mean IMT. Women with ferritin values over the first quartile (>34 μg/L) had an adjusted odds ratio of 2.1 (95% CI, 1.3 to 3.4;
P
=0.0016) for carotid plaque compared with the first quartile. Ferritin was not associated with carotid plaque in men. Subjects who were heterozygous for the C282Y mutation constituted 11.4% of the population, and there was no independent association of this genotype with either carotid IMT or focal plaque formation.

Conclusions
—We conclude that in our community population, C282Y genotype status was not a risk predictor for either carotid mean IMT or plaque formation. Serum ferritin values in women were independently associated with carotid plaque.
Metalloproteinase Inhibition Reduces Thrombolytic (Tissue Plasminogen Activator)–Induced Hemorrhage After Thromboembolic Stroke
Authors: Lapchak Paul A. , Chapman Deborah F. , Zivin Justin A.
Published: June 2011

Background and Purpose
—A potentially dangerous side effect associated with tissue plasminogen activator (tPA) use is cerebral hemorrhage. We have focused on developing drugs that could be administered with tPA to reduce the rate of hemorrhage. Since recent studies suggest that various matrix metalloproteinases (MMPs) are important in tumor necrosis factor-α production and membrane and vessel remodeling after ischemia, we investigated whether MMP inhibition affected the rate of hemorrhage and infarct production in the absence or presence of tPA treatment.

Methods
—We occluded the middle cerebral artery of New Zealand White rabbits with radiolabeled blood clots. Five minutes after embolization, we administered either the MMP inhibitor BB-94 (30 mg/kg SC) or its vehicle. Additional groups received BB-94 or vehicle in combination with tPA, administered 60 minutes after embolization (3.3 mg/kg tPA). After 48 hours, the rabbits were killed and brains were removed, immersion fixed for 1 week in 4% paraformaldehyde, and then cut into 5-mm coronal sections that were examined for the presence of hemorrhage, infarcts, and recanalization.

Results
—Hemorrhage after embolic stroke was detected in 24% of the control group. tPA induced macroscopically visible hemorrhage in 77% of the tPA-treated group. The rabbits treated with BB-94 had an 18% incidence of hemorrhage (
P
>0.05 compared with control). However, when the combination of BB-94 and tPA was administered to rabbits, there was only a 41% incidence of hemorrhage (compared with 77% in the tPA group;
P
<0.05). Both tPA and BB-94/tPA were similarly effective at lysing clots, at 49% and 35% (
P
<0.05), respectively, compared with the 5% rate of lysis in the control group. There was a trend for a reduction in the number of infarcts, but it did not reach statistical significance.

Conclusions
—Our data suggest that MMP inhibition attenuates mechanisms involved in tPA-induced hemorrhage. This novel form of combination therapy may show promise as a treatment strategy for acute stroke.
Selfotel in Acute Ischemic Stroke
Authors: Davis Stephen M. , Lees Kennedy R. , Albers Gregory W. , Diener Hans Christoph , Markabi Sabri , Karlsson Goeril , Norris John
Published: June 2011

Background and Purpose
—Based on neuroprotective efficacy in animal models, we evaluated the
N
-methyl
d
-aspartate antagonist Selfotel in patients with ischemic stroke, after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies.

Methods
—Two pivotal phase 3 ischemic stroke trials tested the hypothesis, by double-blind, randomized, placebo-controlled parallel design, that a single intravenous 1.5 mg/kg dose of Selfotel, administered within 6 hours of stroke onset, would improve functional outcome at 90 days, defined as the proportion of patients achieving a Barthel Index score of ≥60. The trials were performed in patients aged 40 to 85 years with acute ischemic hemispheric stroke and a motor deficit.

Results
—The 2 trials were suspended on advice of the independent Data Safety Monitoring Board because of an imbalance in mortality after a total enrollment of 567 patients. The groups were well matched for initial stroke severity and time from stroke onset to therapy. There was no difference in the 90-day mortality rate, with 62 deaths (22%) in the Selfotel group and 49 (17%) in the placebo-treated group (RR=1.3; 95% CI 0.92 to 1.83;
P
=0.15). However, early mortality was higher in the Selfotel-treated patients (day 30: 54 of 280 versus 37 of 286;
P
=0.05). In patients with severe stroke, mortality imbalance was significant throughout the trial (
P
=0.05).

Conclusions
—Selfotel was not an effective treatment for acute ischemic stroke. Furthermore, a trend toward increased mortality, particularly within the first 30 days and in patients with severe stroke, suggests that the drug might have a neurotoxic effect in brain ischemia.
Effect of Hypervolemic Therapy on Cerebral Blood Flow After Subarachnoid Hemorrhage
Authors: Lennihan Laura , Mayer Stephan A. , Fink Matthew E. , Beckford Avis , Paik Myunghee C. , Zhang Haiying , Wu Ya-Chi , Klebanoff Louise M. , Raps Eric C. , Solomon Robert A.
Published: June 2011

Background and Purpose
—Cerebral blood flow (CBF) is reduced after subarachnoid hemorrhage (SAH), and symptomatic vasospasm is a major cause of morbidity and mortality. Volume expansion has been reported to increase CBF after SAH, but CBF values in hypervolemic (HV) and normovolemic (NV) subjects have never been directly compared.

Methods
—On the day after aneurysm clipping, we randomly assigned 82 patients to receive HV or NV fluid management until SAH day 14. In addition to 80 mL/h of isotonic crystalloid, 250 mL of 5% albumin solution was given every 2 hours to maintain normal (NV group, n=41) or elevated (HV group, n=41) cardiac filling pressures. CBF (
133
xenon clearance) was measured before randomization and approximately every 3 days thereafter (mean, 4.5 studies per patient).

Results
—HV patients received significantly more fluid and had higher pulmonary artery diastolic and central venous pressures than NV patients, but there was no effect on net fluid balance or on blood volume measured on the third postoperative day. There was no difference in mean global CBF during the treatment period between HV and NV patients (
P
=0.55, random-effects model). Symptomatic vasospasm occurred in 20% of patients in each group and was associated with reduced minimum regional CBF values (
P
=0.04). However, there was also no difference in minimum regional CBF between the 2 treatment groups.

Conclusions
—HV therapy resulted in increased cardiac filling pressures and fluid intake but did not increase CBF or blood volume compared with NV therapy. Although careful fluid management to avoid hypovolemia may reduce the risk of delayed cerebral ischemia after SAH, prophylactic HV therapy is unlikely to confer an additional benefit.
Effects of Poststroke Pyrexia on Stroke Outcome
Authors: Hajat Cother , Hajat Shakoor , Sharma Pankaj
Published: June 2011

Background and Purpose
—The effect of pyrexia on cerebral ischemia has been extensively studied in animals. In humans, however, such studies are small and the results conflicting. We undertook a meta-analysis using all such published studies on the effect of hyperthermia on stroke outcome.

Methods
—Three databases were searched for all published studies that examined the relationship of raised temperature after stroke onset and eventual outcome. Combined probability values and odds ratios were obtained. A heterogeneity test was performed to ensure that the data were suitable for such an analysis. Morbidity and mortality were used as outcome measures.

Results
—Nine studies were identified totaling 3790 patients, providing our study with 99% power to detect a 9% increase in morbidity and 84% power to detect a 1% increase in mortality for the pyrexial group. The combined odds ratio for mortality was 1.19 (95% CI, 0.99 to 1.43). A heterogeneity test was highly nonsignificant (
P
>0.05) for mortality, suggesting that the data were sufficiently similar to be meta-analyzed. Combined probability values were highly significant for both morbidity (
P
<0.0001) and mortality (
P
<0.00000001).

Conclusions
—The results from this meta-analysis suggest that pyrexia after stroke onset is associated with a marked increase in morbidity and mortality. Measures should be taken to combat fever in the clinical setting to prevent stroke progression. The possible benefit of therapeutic hypothermia in the management of acute stroke should be further investigated.
Health-Related Quality of Life Among Long-Term Survivors of Stroke
Authors: Hackett Maree L. , Duncan John R. , Anderson Craig S. , Broad Joanna B. , Bonita Ruth
Published: June 2011

Background and Purpose
—The consequences of stroke are a major health concern. This study was conducted to compare the health-related quality of life among long-term survivors of stroke with that of the general population.

Methods
—Our data are taken from a population-based case-control study of all 6-year survivors of stroke with an age- and sex-matched control population. SF-36 mean scores for cases were compared with raw and standardized control and New Zealand norm mean scores.

Results
—Of the original 1761 registered cases, 639 were still alive at 6-year follow-up, and all of these participated in the study. Case patients were more likely than control subjects to be dependent in all basic activities of daily living. Crude mean scores were lower for women; as age increased; for those living in institutions; when the SF-36 was completed by proxy; and when help was required with the activities of daily living. Cases had statistically lower mean scores than both the control group and New Zealand norms for physical functioning and general health. After standardization for age and sex, no differences were found between cases and controls in mental health and bodily pain.

Conclusions
—Health-related quality of life appears to be relatively good for the majority of patients 6 years after stroke. Despite significant ongoing physical disability, survivors of stroke appear to adjust well psychologically to their illness.
Genetic Predisposition to Stroke in Relatives of Hypertensives
Authors: Nicolaou M. , DeStefano A. L. , Gavras I. , Cupples L. A. , Manolis A. J. , Baldwin C. T. , Gavras H. , Farrer L. A.
Published: June 2011

Background and Purpose
—The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to test the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors.

Methods
—Genealogical and medical history information was obtained for a cohort of 354 hypertensive probands ascertained in a clinic-based setting, their 1427 first-degree relatives, and 239 of their spouses. Risks of stroke and hypertension in biological and nonbiological relatives were compared with the logistic model of the generalized estimating equations adjusted for age and sex.

Results
—The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio [OR]=2.4; 95% CI, 1.8 to 3.4; OR=2.2; 95% CI, 1.6 to 3.0, respectively). When the spouses were used as a reference group, the risk of stroke for parents of the hypertensive probands was 7.3 times higher (OR=7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings (OR=1.6; 95% CI, 0.8 to 3.3) was observed. Controlling for hypertension, obesity, smoking, coronary heart disease, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (OR
parents
=5.4; 95% CI, 2.6 to 11.2; OR
siblings
=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher for hypertensive parents and siblings than for nonhypertensive parents (OR=5.2; 95% CI, 2.8 to 9.7) and siblings (OR=5.8; 95% CI, 2.1 to 15.9). A history of hypertension was not associated with an increased risk for stroke in spouses (OR=0.7; 95% CI, 0.2 to 3.1). The risk of stroke in hypertensive relatives of probands with stroke was higher than that of the normotensive relatives (OR=13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (OR=4.0).

Conclusions
—Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that some of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not significant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treatment for hypertension. Although a history of hypertension increases the risk of stroke among parents and siblings, multivariate analyses revealed a familial component to stroke independent of hypertension.
Mechanism of Endothelin-1–Induced Contraction in Rabbit Basilar Artery
Authors: Zubkov Alexander Y. , Rollins K. Shadon , Parent Andrew D. , Zhang John
Published: June 2011

Background and Purpose
—Endothelin-1 (ET-1) is suggested to be a major cause of cerebral vasospasm after subarachnoid hemorrhage. However, the mechanism of ET-1–induced contraction in cerebral arteries remains unclear. This study was undertaken to demonstrate the possible role of protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC) in ET-1–induced contraction.

Methods
—PD-98059, damnacanthal, wortmannin, AG-490, genistein, calphostin C, and staurosporine were used to inhibit, or relax, the ET-1–induced contraction of basilar artery, studied with an isometric tension system. Immunoprecipitation of MAPK in ET-1–stimultated rings of basilar artery without or with the above inhibitors was studied with Western blot.

Results
—(1) ET-1 produced concentration-dependent contraction and MAPK immunoprecipitation in rabbit basilar artery by activation of ET
A
but not ET
B
receptors. (2) MAPK inhibitors PD-98059 and U-0126 produced dose-dependent inhibition of ET-1–induced contraction. (3) The Src tyrosine kinase inhibitor damnacanthal, the phosphatidylinositol-3 kinase inhibitor wortmannin, and the Janus tyrosine kinase
2
inhibitor AG-490 abolished ET-1–induced contraction. (4) The PKC inhibitor staurosporine but not calphostin C abolished ET-1–induced contraction, and the PTK inhibitor genistein partially reduced ET-1–induced contraction. (5) In arteries precontracted by ET-1, PD-98059, U-0126, wortmannin, AG-490, genistein, and staurosporine produced concentration-dependent relaxation. (6) ET-1 induced a biphasic and time-dependent MAPK immunoprecipitation. (7) PD-98059, U-0126, genistein, AG-490, and damnacanthal, but not staurosporine or wortmannin, abolished the effect of ET-1 on MAPK immunoreactivity.

Conclusions
—This study demonstrated that MAPK may be involved in ET-1–induced contraction in rabbit basilar artery. MAPK is downstream of PTK, Src, and Janus tyrosine kinase pathways but may not be downstream of phosphatidylinositol-3 kinase pathways. The possible involvement of PKC in ET-1–induced contraction requires further investigation. Inhibition of these pathways may offer alternative treatment for ET-1–induced contraction and cerebral vasospasm.
Racial Variation in Initial Stroke Severity
Authors: Jones Michael R. , Horner Ronnie D. , Edwards Lloyd J. , Hoff Jennifer , Armstrong S. Beth , Smith-Hammond Carol A. , Matchar David B. , Oddone Eugene Z.
Published: June 2011

Background and Purpose
—Blacks experience greater morbidity and mortality from stroke than do whites. The degree to which this is due to the severity of the initial stroke is not known. The objective of this study is to determine whether there is a racial difference in initial stroke severity.

Methods
—A secondary analysis of a prospective cohort of 984 veterans (29.7% black) admitted to any of 9 geographically diverse Veterans Administration Hospitals for acute stroke between April 1995 and March 1997 was performed. Initial stroke severity was ascertained by using the modified Canadian Neurological Scale (CNS) applied retrospectively to medical record data. Stroke severity, unadjusted and adjusted for covariates, was compared between black and white patients.

Results
—Blacks had greater initial stroke severity than did whites (mean CNS score 7.96 versus 8.32, respectively;
P
=0.039), with a 0.5-point difference on the scale corresponding to a single-level decrement in either speech or strength of half of an extremity. This difference persisted with adjustment for other important predictors of stroke severity (
P
=0.035). However, there was no significant racial difference in severity when CNS scores were collapsed into a priori clinically relevant categories.

Conclusions
—Compared with whites, blacks show greater severity of stroke at hospital admission. It remains uncertain whether the relatively small but significant difference at presentation fully explains the striking racial differences in morbidity and mortality from stroke.
Management Patterns and Costs of Acute Ischemic Stroke
Authors: Caro J. Jaime , Huybrechts Krista F. , Duchesne Inge
Published: June 2011

Background and Purpose
—With the ever-increasing pressure on healthcare budgets, we witness a growing demand for evidence of the economic implications of care across many therapeutic areas. Stroke is no exception.

Methods
—Detailed information on healthcare use was collected in conjunction with two 12-week international trials designed primarily to assess the safety and efficacy of a new potential neuroprotective agent. The information was gathered prospectively by means of a customized resource use instrument that included both acute and long-term inpatient management as well as community care. In this report, the results pertaining to the 1341 acute ischemic stroke patients are described.

Results
—More than 70% of the mean cost ($13 668) was explained by the initial hospitalization, which averaged 24 days. The total cost and its components varied according to patient age, the presence of comorbidities, and several indicators of disease severity. Pronounced country differences could be observed in the management of this fairly homogeneous patient group.

Conclusions
—This study provides a comprehensive picture of the healthcare services used for the treatment and rehabilitation of stroke victims, presented with respect to various patient and disease characteristics. It is expected that researchers evaluating the cost-efficiency of specific stroke treatments will benefit from the detailed information presented in this report.
Abciximab in Acute Ischemic Stroke
Authors: Investigators The Abciximab in Ischemic Stroke
Published: June 2011

Background and Purpose
—Abciximab is a potent parenterally administered platelet glycoprotein IIb/IIIa antagonist. Because this agent has been shown to improve outcomes in coronary artery disease, there is interest to evaluate whether it could improve cerebral perfusion and outcomes after ischemic stroke. This study was designed to evaluate the safety of abciximab in acute ischemic stroke and to obtain pilot efficacy data.

Methods
—We conducted a randomized, double-blind, placebo-controlled, dose-escalation trial. Seventy-four eligible and consenting patients presenting within 24 hours after ischemic stroke onset at 38 study sites were randomly allocated to receive either an escalating dose of abciximab (54 patients) or placebo (20 patients) in a ratio of 3:1. We studied 4 escalating doses of abciximab. Patients underwent a scheduled follow-up head CT scan 24 to 36 hours after the completion of study agent administration to monitor for bleeding complications and were evaluated through 3 months.

Results
—There were no cases of major intracranial hemorrhage. Asymptomatic parenchymal hemorrhages were detected on post–study agent CT in 4 of 54 abciximab patients (7%) and in 1 of 20 placebo patients (5%). Six additional abciximab patients had asymptomatic hemorrhagic lesions detected by unscheduled brain imaging during their follow-up period. Nine of 11 patients with asymptomatic hemorrhage had a baseline National Institutes of Health Stroke Scale score >14. At 3 months, there was a trend toward a higher rate of minimal residual disability (Barthel Index ≥95 or modified Rankin scale ≤1) among abciximab patients compared with those who received placebo.

Conclusions
—Abciximab appears to be safe when administered up to 24 hours after stroke onset, and it might improve functional outcome.
Internal Borderzone Infarction
Authors: Del Sette M. , Eliasziw M. , Streifler J. Y. , Hachinski V. C. , Fox A. J. , Barnett H. J. M.
Published: June 2011

Background and Purpose
—Among subcortical infarctions, internal borderzone infarcts (IBI) are considered to be separate entities from perforating artery infarcts (PAI). The purpose of the present study is to examine the relationship between the presence of IBI and the degree of angiographically defined internal carotid artery (ICA) stenosis in symptomatic patients.

Methods
—A review of 1253 brain CTs from patients recruited by the North American Symptomatic Carotid Endarterectomy Trial was performed, using templates for the identification of subcortical and cortical vascular territories.

Results
—A total of 413 patients had visible ischemic lesions on the side ipsilateral to their symptomatic ICA. Of these, 138 had PAI, 108 had IBI, 122 had cortical infarcts, and 45 had a combination of different lesions. Mean (±SD) lesion diameter was larger for IBI (11.0±5.9 mm) than for PAI (7.1±4.7 mm) (
P
<0.001 for comparing 2 means). IBI was associated with higher degrees of ICA stenosis (
P
<0.001). Sixty-three percent of the patients with IBI had severe (70% to 99%) ICA stenosis compared with 42% of patients with PAI; 18% of the IBI patients had stenosis of 90% or more compared with 8% of the patients with PAI. Multiple logistic regression did not identify any patient characteristics as confounders.

Conclusions
—Among subcortical infarctions, IBI are associated with higher degrees of ICA stenosis in symptomatic patients. Differentiating between internal borderzone and perforating artery infarcts is important, because each may arise from different mechanisms, namely, carotid disease and small-vessel disease, respectively.
Evolution of Cortical Activation During Recovery From Corticospinal Tract Infarction
Authors: Marshall Randolph S. , Perera Gerard M. , Lazar Ronald M. , Krakauer John W. , Constantine Robert C. , DeLaPaz Robert L.
Published: June 2011

Background and Purpose
—Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is known about the time course of cortical activation in these regions as recovery proceeds.

Methods
—Eight patients with first-ever corticospinal tract lacunes causing hemiparesis had serial fMRIs within the first few days after stroke and at 3 to 6 months. Six healthy subjects were used as controls. Statistically significant voxels during a finger-thumb opposition task were identified with an automated image processing program. An index of ipsilateral versus contralateral activity was used to compare relative contributions of the 2 hemispheres to motor function in the acute and chronic phases after stroke.

Results
—Controls showed expected activation in the contralateral sensorimotor cortex (SMC), premotor, and supplementary motor areas. Stroke patients differed from control patients in showing greater activation in the ipsilateral SMC, ipsilateral posterior parietal, and bilateral prefrontal regions. Compared with the nonparetic hand, the ratio of contralateral to ipsilateral SMC activity during movement of the paretic hand increased significantly over time as the paretic hand regained function.

Conclusions
—The evolution of activation in the SMC from early contralesional activity to late ipsilesional activity suggests that a dynamic bihemispheric reorganization of motor networks occurs during recovery from hemiparesis.
Significance of Acute Multiple Brain Infarction on Diffusion-Weighted Imaging
Authors: Roh Jae-Kyu , Kang Dong-Wha , Lee Seung-Hoon , Yoon Byung-Woo , Chang Kee-Hyun
Published: June 2011

Background and Purpose
—Diffusion-weighted imaging (DWI) is superior to conventional MRI in identification of small new ischemic lesions and discrimination of recent infarcts from old ones. Thus, this technique is useful in the detection of acute multiple brain infarcts (AMBI). We sought to determine the frequency and the topographical and etiologic patterns of AMBI detected on DWI.

Methods
—We studied 329 consecutive ischemic stroke patients who underwent DWI and MRI/MR angiography within 4 days of stroke onset. AMBI was defined as noncontiguous high signal intensities on DWI in >1 vascular territory. Stroke mechanism was determined according to the criteria of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

Results
—We detected AMBI in 95 patients (28.9%). AMBI in anterior circulation was found in 62 cases: in 1 hemisphere in 42 (group A) and in bilateral hemispheres in 20 (group B). Twenty-two patients had AMBI in the posterior circulation (group C) and 11 in both anterior and posterior circulations (group D). The most frequent cause of stroke was large-artery atherosclerosis in groups A (33/42), B (9/20), and C (15/22) (
P
=0.02) and cardioembolism in group D (6/11) (
P
=0.02). Elevated fibrinogen or hematocrit was significantly associated with group B (
P
=0.01). In 9 patients in groups B and D, anatomic variations of anterior or posterior cerebral arteries or patent posterior communicating artery contributed to AMBI.

Conclusions
—Different topographical patterns of AMBI are associated with different vascular pathologies and stroke mechanisms. Hemorheologic abnormality or vascular anatomic variations may be contributing factors in the pathogenesis of AMBI in bilateral cerebral hemispheres or in both anterior and posterior circulations.
Stroke in Estrogen Receptor-α–Deficient Mice
Authors: Sampei Kenji , Goto Shozo , Alkayed Nabil J. , Crain Barbara J. , Korach Kenneth S. , Traystman Richard J. , Demas Gregory E. , Nelson Randy J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
—Recent evidence suggests that endogenous estrogens or hormone replacement therapy can ameliorate brain damage from experimental stroke. Protective mechanisms involve enhanced cerebral vasodilation during ischemic stress as well as direct preservation of neuronal viability. We hypothesized that if the intracellular estrogen receptor subtype-α (ERα) is important to estrogen’s signaling in the ischemic brain, then ERα-deficient (knockout) (ERαKO) female mice would sustain exaggerated cerebral infarction damage after middle cerebral artery occlusion.

Methods
—The histopathology of cresyl violet–stained tissues was evaluated after reversible middle cerebral artery occlusion (2 hours, followed by 22 hours of reperfusion) in ERαKO transgenic and wild-type (WT) mice (C57BL/6J background strain). End-ischemic cerebral blood flow mapping was obtained from additional female murine cohorts by using [
14
C]iodoantipyrine autoradiography.

Results
—Total hemispheric tissue damage was not altered by ERα deficiency in female mice: 51.9±10.6 mm
3
in ERαKO versus 60.5±5.0 mm
3
in WT. Striatal infarction was equivalent, 12.2±1.7 mm
3
in ERαKO and 13.4±1.0 mm
3
in WT mice, but cortical infarction was paradoxically smaller relative to that of the WT (20.7±4.5 mm
3
in ERαKO versus 30.6±4.1 mm
3
in WT). Intraocclusion blood flow to the parietal cortex was higher in ERαKO than in WT mice, likely accounting for the reduced infarction in this anatomic area. There were no differences in stroke outcomes by region or genotype in male animals.

Conclusions
—Loss of ERα does not enhance tissue damage in the female animal, suggesting that estrogen inhibits brain injury by mechanisms that do not depend on activation of this receptor subtype.
Estradiol Exerts Neuroprotective Effects When Administered After Ischemic Insult
Authors: Yang Shao-Hua , Shi Jiong , Day Arthur L. , Simpkins James W.
Published: June 2011

Background and Purpose
—17β-Estradiol (E2) has been reported to exert neuroprotective effects when administered before an ischemic insult. This study was designed to determine whether E2 treatment after ischemia exerts the same effects and, if so, how long this therapeutic window remains open, and whether the effects are related to changes in cerebral blood flow (CBF).

Methods
—Female Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). In protocol 1, E2 was administered (100 μg/kg IV followed immediately by subcutaneous implantation of crystalline E2 in a silicone elastomer tube) to ovariectomized females (OVX+E2) at 0.5 (n=8), 1 (n=6), 2 (n=7), 3 (n=6), or 4 (n=9) hours after MCAO. Intact (INT; n=6) and ovariectomized females (OVX; n=12) were subjected to MCAO and received vehicle instead of E2. Two days after MCAO the animals were killed, and ischemic lesion volume was determined by 2,3,5-triphenyltetrazolium chloride staining. In protocol 2, CBF was monitored before and at 1, 24, and 48 hours in a group of animals receiving E2 or vehicle 0.5 hour after ischemia induction (INT, n=6; OVX, n=8; OVX+E2, n=6).

Results
—Lesion volume was 20.9±2.2% and 21.8±1.2% in the INT and OVX groups, respectively. E2 was found to decrease lesion volume significantly when administered within 3 hours after MCAO. The lesion volumes were 6.3±0.5%, 10.3±2.1%, 11.8±1.8%, 13.5±1.6%, and 17.9±2.8% when E2 was administered at 0.5, 1, 2, 3, or 4 hours after MCAO, respectively. CBF decreased to 43.1±2.2% and 25.4±1.0% in the INT and OVX animals, respectively, at 5 minutes after MCAO. In comparison to OVX rats, CBF was not different at 1 hour after E2 administration but was increased significantly in the OVX+E2 group 1 and 2 days after E2 administration.

Conclusions
—E2 exerts neuroprotective effects when administered after ischemia, with a therapeutic window in a permanent focal cerebral ischemia model of approximately 3 hours. This effect of estradiol was associated with no immediate change in blood flow but with a delayed increase in CBF.