bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Albumin Therapy of Acute Ischemic Stroke
Authors: Belayev Ludmila , Liu Yitao , Zhao Weizhao , Busto Raul , Ginsberg Myron D.
Published: June 2011

Background and Purpose
—We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection.

Methods
—Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-
l
-lysine–coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined.

Results
—Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67% and 58%, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68%), subcortical regions (by 52%), and total infarct (by 61%).

Conclusions
—Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.
Mild Hyperhomocyst(e)inemia
Authors: Gallai Virgilio , Caso Valeria , Paciaroni Maurizio , Cardaioli Gabriela , Arning Erland , Bottiglieri Teodoro , Parnetti Lucilla
Published: June 2011

Background and Purpose
—The pathogenesis of cervical artery dissection (CAD) remains unknown in most cases. Hyperhomocyst(e)inemia [hyperH(e)], an independent risk factor for cerebrovascular disease, induces damage in endothelial cells in animal cell culture. Consecutive patients with CAD and age-matched control subjects have been studied by serum levels of homocyst(e)ine and the genotype of 5,10-methylenetetrahydrofolate reductase (
MTHFR
).

Methods
—Twenty-six patients with CAD, admitted to our Stroke Unit (15 men and 11 women; 16 vertebral arteries, 10 internal carotid arteries), were compared with age-matched control subjects. All patients underwent duplex ultrasound, MR angiography, and/or conventional angiography.

Results
—Mean plasma homocyst(e)ine level was 17.88 μmol/L (range 5.95 to 40.0 μmol/L) for patients with CAD and 6.0±0.99 μmol/L for controls (
P
<0.001). The genetic analysis for the thermolabile form of
MTHFR
in CAD patients showed heterozygosity in 54% and homozygosity in 27%; comparable figures for controls were 40% (
P
=0.4) and 10% (
P
=0.1), respectively.

Conclusions
—Mild hyperH(e) might represent a risk factor for cervical artery dissection. The
MTHFR
mutation is not significantly associated with CAD. An interaction between different genetic and environmental factors probably takes place in the cascade of pathogenetic events leading to arterial wall damage.
111
In Platelet Scintigraphy for the Noninvasive Detection of Carotid Plaque Thrombosis
Authors: Manca Giampiero , Parenti Giuliano , Bellina Riccardo , Boni Giuseppe , Grosso Mariano , Bernini Walter , Palombo Carlo , Paterni Marco , Pelosi Gualtiero , Lanza Maria , Mazzuca Nicola , Bianchi Romano , De Caterina Raffaele
Published: June 2011

Background and Purpose
—Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect.

Methods
—We compared the performance of
111
In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%.

Results
—Positivity at
111
In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque.

Conclusions
—Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.
A Common Variant of Endothelial Nitric Oxide Synthase (Glu298Asp) Is an Independent Risk Factor for Carotid Atherosclerosis
Authors: Lembo G. , De Luca N. , Battagli C. , Iovino G. , Aretini A. , Musicco M. , Frati G. , Pompeo F. , Vecchione. C. , Trimarco B.
Published: June 2011

Background and Purpose
—Endothelium-derived NO is formed from
l
-arginine by endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because several studies have indicated that NO plays a key role in the development of the atherosclerotic process, we investigated whether common variants in the eNOS gene are associated with an increased risk of plaque on carotid arteries.

Methods
—We studied 375 subjects attending the hypertension center of our institution to be screened for arterial hypertension. The examined subjects were classified according to the presence of carotid plaques (intima-media thickness ≥1.5 mm), and 2 intronic (CA and 27-bp repeats) polymorphisms and 1 exonic (Glu298Asp) polymorphism of the eNOS gene were explored.

Results
—Only the Glu298Asp polymorphism of eNOS was associated with the presence of carotid plaques (
P
<0.05). In particular, there was an excess of homozygotes for the Asp298 variant among subjects with carotid plaques, whereas the number of subjects who had the Glu298 allele in exon 7 of the eNOS gene was equally distributed in both study groups. Interestingly, the risk of having carotid plaques was increased ≈3 times in subjects who were homozygotic for the Asp298 variant compared with subjects who were homozygotic for the Glu298 variant and was independent of the other common risk factors (age, blood pressure, and smoking).

Conclusions
—Homozygosity for Asp298, a common variant of the eNOS gene, is an independent risk factor for carotid atherosclerosis in this study population.
Expression of Tissue Factor in High-Grade Carotid Artery Stenosis
Authors: Jander Sebastian , Sitzer Matthias , Wendt Angélique , Schroeter Michael , Buchkremer Martin , Siebler Mario , Müller Wolfram , Sandmann Wilhelm , Stoll Guido
Published: June 2011

Background and Purpose
—The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation.

Methods
—In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration.

Results
—Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (
P
<0.0001) and T cells (
P
=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (
P
=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (
P
=0.008).

Conclusions
—Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.
Direct, Longitudinal Comparison of
1
H and
23
Na MRI After Transient Focal Cerebral Ischemia
Authors: Lin Shao-Pow , Song Sheng-Kwei , Miller J. Philip , Ackerman Joseph J.H. , Neil Jeffrey J.
Published: June 2011

Background and Purpose
—
23
Na MRI may offer new insight into the evaluation of tissue injury. We performed a direct, longitudinal, morphological comparison of
1
H T2 relaxation,
1
H apparent diffusion coefficient (ADC),
23
Na content, and histopathology after cerebral ischemia to address the hypotheses that (a)
23
Na MRI is unique in comparison to
1
H MRI, and (b) accumulation of
23
Na is an unambiguous marker for dead tissue.

Methods
—Rats underwent 30 minutes of focal ischemia. MRIs of
1
H T2,
1
H ADC, and
23
Na content were acquired from 12 hours up to 1, 2, or 14 days after reperfusion. On excision, brains were stained with triphenyltetrazolium chloride (TTC).

Results
—In all cases, the region of abnormality increased in size for 2 days. On day 5, both
1
H T2 and ADC temporarily appeared normal despite the presence of TTC-defined infarction. By comparison, the volume of tissue exhibiting abnormally intense
23
Na signal mirrored the TTC-defined infarct at all time points.

Conclusions
—Regions of high
23
Na content correlate well with the TTC-defined infarct and may be a quantitative in vivo marker for dead tissue. In contrast, the dynamics of the
1
H T2 and ADC make it difficult to interpret these images without additional information because they may appear normal despite infarction. Neither type of
1
H image delineates dead tissue, and none of these methods predicts the potential infarct size at early time points.
Predicting Tissue Outcome in Acute Human Cerebral Ischemia Using Combined Diffusion- and Perfusion-Weighted MR Imaging
Authors: Wu Ona , Koroshetz Walter J. , Østergaard Leif , Buonanno Ferdinando S. , Copen William A. , Gonzalez R. Gilberto , Rordorf Guy , Rosen Bruce R. , Schwamm Lee H. , Weisskoff Robert M. , Sorensen A. Gregory
Published: June 2011

Background and Purpose
—Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI.

Methods
—Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves.

Results
—At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (
P
=0.02) but no significant improvement over algorithms utilizing PWI alone (
P
=0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (
P
=0.02) or PWI (
P
=0.04). The performances of thresholding and GLM algorithms were comparable (
P
>0.2).

Conclusions
—Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.
Health-Related Quality of Life After Stroke A Comprehensive Review
Authors: Tengs Tammy O. , Yu Michelle , Luistro Elvina
Published: June 2011

Background and Purpose
—We performed a comprehensive review of all quality-of-life (QOL) estimates for stroke appearing in the peer-reviewed literature between 1985 and 2000. We examine variation in QOL weights and the rigor of methods used to assess QOL and discuss the implications for cost-utility assessment and resource allocation decisions.

Methods
—Through a systematic search, we identified 67 articles that met our inclusion criteria. A team of trained researchers read each article and followed detailed guidelines to extract QOL weights and other parameters. This effort yielded 161 QOL estimates for stroke-related health states. All estimates were measured on a 0 to 1 scale, with 0 representing the worst outcome and 1 representing the best.

Results
—QOL estimates range from −0.02 to 0.71 (n=67) for major stroke, from 0.12 to 0.81 (n=14) for moderate stroke, from 0.45 to 0.92 (n=38) for minor stroke, and from 0.29 to 0.903 (n=42) for general stroke. Although QOL should decrease with severity, there were many instances in which the QOL for major stroke as reported by one study exceeded the QOL for moderate stroke as reported by another. The same reversal was found for moderate and minor stroke, and it occurred even when both authors used similar assessment methods and subject populations. Authors of cost-utility and decision analyses rarely base their choice of QOL weights on their own primary data (19%). When obtaining weights from secondary sources, some authors (23%) chose QOL weights for a severity of stroke that did not match the severity for which they sought data.

Conclusions
—QOL estimates for stroke vary greatly and are not always estimated in sound fashion. This impedes the comparability and quality of the cost-effectiveness studies that use these QOL weights and hampers good resource allocation decisions.
Modified Emory Functional Ambulation Profile
Authors: Baer Heather R. , Wolf Steven L.
Published: June 2011

Background and Purpose
—The modified Emory Functional Ambulation Profile (mEFAP) is an easily administered test that measures the time to ambulate through 5 common environmental terrains with or without an assistive device or manual assistance. The mEFAP was evaluated for its interrater reliability, test-retest reliability, concurrent validity, and sensitivity to change during outpatient rehabilitation for poststroke gait dysfunction.

Methods
—Twenty-six poststroke patients were followed up prospectively in a rehabilitation day-treatment program. The mEFAP, Berg Balance Test (BBT), and 7-item mobility subsection of the Functional Independence Measure + Functional Assessment Measure (FAMm) were completed at admission and discharge.

Results
—mEFAP interrater reliability (intraclass coefficient [ICC] 0.999) and test-retest reliability (ICC 0.998) were high. The BBT demonstrated high interrater (ICC 0.992) but poor test-retest (ICC 0.605) reliability. Initial and final scores comparing the mEFAP with the BBT (
r
=−0.735,
r
=−0.703) and the mEFAP with the FAMm (
r
=0.685,
r
=−0.775) were strongly correlated. Improvement on the mEFAP correlated with improved BBT performance (
r
=−0.524). There was no correlation between overall change observed on the FAMm and change on the mEFAP (
r
=−0.145). Total mEFAP and all mEFAP subtask scores improved over time (
P
<0.0001).

Conclusions
—The mEFAP is a reliable gait-assessment tool for patients with stroke and is sensitive to change in ambulation speed.
Mevastatin, an HMG-CoA Reductase Inhibitor, Reduces Stroke Damage and Upregulates Endothelial Nitric Oxide Synthase in Mice
Authors: Amin-Hanjani Sepideh , Stagliano Nancy E. , Yamada Masaru , Huang Paul L. , Liao James K. , Moskowitz Michael A.
Published: June 2011

Background and Purpose
—The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) lower serum cholesterol and decrease the incidence of stroke and cardiovascular disease. There is growing evidence that statins exert some of their beneficial effects independent of cholesterol lowering. Indeed, we have previously demonstrated that chronic simvastatin administration upregulates endothelial nitric oxide synthase (eNOS), resulting in more functional protein, augmentation of cerebral blood flow, and neuroprotection in a murine model of cerebral ischemia. In this report we examined whether another member of the statin family shared these effects and whether eNOS upregulation is sustained with longer treatment.

Methods
—Mevastatin (2 mg/kg or 20 mg/kg per day) was administered to 18- to 22-g male mice for 7, 14, or 28 days before 2-hour middle cerebral artery occlusion with the use of the filament model (n=9 to 12). Neurological deficits and cerebral infarct volumes were assessed at 24 hours. Arterial blood pressure and gases, relative cerebral blood flow, and blood cholesterol levels were monitored in a subset of animals (n=5). Absolute cerebral blood flow was measured by the [
14
C]iodoamphetamine indicator fractionation technique (n=6). eNOS mRNA and protein levels were determined.

Results
—Mevastatin increased levels of eNOS mRNA and protein, reduced infarct size, and improved neurological deficits in a dose- and time-dependent manner. Greatest protection was seen with 14- and 28-day high-dose treatment (26% and 37% infarct reduction, respectively). Cholesterol levels were reduced only after 28 days of treatment and did not correlate with infarct reduction. Baseline absolute cerebral blood flow was 30% higher after 14-day high-dose treatment.

Conclusions
—Chronic prophylactic treatment with mevastatin upregulated eNOS and augmented cerebral blood flow. These changes occurred in the absence of changes in serum cholesterol levels, were sustained for up to 1 month of treatment, and resulted in neuroprotection after middle cerebral artery occlusion.
Chiropractic Manipulation and Stroke
Authors: Rothwell Deanna M. , Bondy Susan J. , Williams J. Ivan
Published: June 2011

Background and Purpose
—Several reports have linked chiropractic manipulation of the neck to dissection or occlusion of the vertebral artery. However, previous studies linking such strokes to neck manipulation consist primarily of uncontrolled case series. We designed a population-based nested case-control study to test the association.

Methods
—Hospitalization records were used to identify vertebrobasilar accidents (VBAs) in Ontario, Canada, during 1993–1998. Each of 582 cases was age and sex matched to 4 controls from the Ontario population with no history of stroke at the event date. Public health insurance billing records were used to document use of chiropractic services before the event date.

Results
—Results for those aged <45 years showed VBA cases to be 5 times more likely than controls to have visited a chiropractor within 1 week of the VBA (95% CI from bootstrapping, 1.32 to 43.87). Additionally, in the younger age group, cases were 5 times as likely to have had ≥3 visits with a cervical diagnosis in the month before the case’s VBA date (95% CI from bootstrapping, 1.34 to 18.57). No significant associations were found for those aged ≥45 years.

Conclusions
—While our analysis is consistent with a positive association in young adults, potential sources of bias are also discussed. The rarity of VBAs makes this association difficult to study despite high volumes of chiropractic treatment. Because of the popularity of spinal manipulation, high-quality research on both its risks and benefits is recommended.
Intravenous tPA for Ischemic Stroke Team Performance Over Time, Safety, and Efficacy in a Single-Center, 2-Year Experience
Authors: Koennecke Hans-Christian , Nohr Roland , Leistner Stefanie , Marx Peter
Published: June 2011

Background and Purpose
—Safety and efficacy concerns toward thrombolysis for ischemic stroke prevail among many neurologists because of the risks of hemorrhage and the small proportion of suitable patients. We therefore prospectively assessed feasibility, safety, efficacy, and team performance in a single center to prove whether thrombolytic treatment is practical in daily clinical routine.

Methods
—Patients were prospectively recruited over a 2-year period. Major inclusion and exclusion criteria from large, randomized controlled trials were combined. Prespecified outcome parameters were the modified Rankin scale (MRS) and the Barthel Index (BI) at 3 months and symptomatic hemorrhagic complications. In addition, certain time intervals during the diagnostic process preceding thrombolysis were prospectively recorded.

Results
—Within 2 years a total of 75 patients underwent intravenous thrombolysis, corresponding to 9.4% of all admitted patients with stroke and 14.9% of patients with ischemic stroke. Mean±SD age was 68±13 (range 34 to 90) years; median baseline National Institutes of Health Stroke Scale score was 13±6 (range 2 to 34). Thrombolysis was started at an average time of 144 minutes after symptom onset, and 13 patients (17.3%) were treated beyond 3 hours. Two cerebral hemorrhages (2.7%) occurred. Outcome according to the MRS was good (MRS 0 to 1) in 40%, moderate (MRS 2 to 3) in 32%, and poor (MRS 4 to 5) in 13%; the corresponding results, as measured by the BI, were 61% (BI 95 to 100, good), 16% (BI 55 to 90, moderate), and 8% (BI 0 to 50, poor). The mortality rate was 15%. Over 2 years the median door-to-CT time decreased from 30 to 22 minutes (27%), and the door-to-needle time was shortened from 96 to 73 minutes (14%). The mean number of patients treated per month increased from 2 to 4.

Conclusions
—Thrombolytic therapy can be performed safely and efficaciously in daily clinical routine. More than a minority of acute stroke patients might be eligible for intravenous thrombolysis. The performance of a stroke team can be improved over time, subsequently increasing the proportion of eligible patients and thereby the efficiency of the method.
Diagnosis and Initial Management of Stroke and Transient Ischemic Attack Across UK Health Regions From 1992 to 1996
Authors: Gibbs R. G. J. , Newson R. , Lawrenson R. , Greenhalgh R. M. , Davies A. H.
Published: June 2011

Background and Purpose
—The aim of this study was to establish the difference in burden of cerebrovascular disease across the different health regions of the United Kingdom and to determine whether the initial management of new cases of stroke and transient ischemic attack (TIA) was uniform across the United Kingdom.

Methods
—The General Practice Research Database (GPRD) is a national database used for epidemiological studies. This was a cohort study identifying incident cases of stroke and TIA over a 5-year study period between 1992 and 1996. The population studied was patients registered with general practitioners contributing to the GPRD across the different health regions of the United Kingdom. Outcome measures were new diagnoses of stroke and TIA, new prescriptions for antiplatelet and anticoagulant agents, and referrals made for specialist opinion.

Results
—The age-adjusted annual incidence rate across all regions was 151 per 100 000 for stroke and 190 per 100 000 for TIA. There was almost a 2-fold difference in the incidence of cerebrovascular disease between the regions. The management of stroke and TIA in terms of antiplatelet prescription and of referral onward for further opinion to hospital specialists varied significantly between regions.

Conclusions
—Reported stroke and TIA incidence on the GPRD was comparable to that of other European studies. There were striking regional differences in the incidence of disease. The primary care management, both in prescription and referral rates, varied significantly between the different regions. There was a marked underuse of antiplatelet and anticoagulant agents, and referral rates for specialists’ opinions were low.
Elevated Plasma Homocysteine Levels and Risk of Silent Brain Infarction in Elderly People
Authors: Matsui Toshifumi , Arai Hiroyuki , Yuzuriha Takefumi , Yao Hiroshi , Miura Masakazu , Hashimoto Setsuko , Higuchi Susumu , Matsushita Sachio , Morikawa Masatoshi , Kato Atsushi , Sasaki Hidetada
Published: June 2011

Background and Purpose
—Silent brain infarction (SBI) on MRI is common in elderly people, and recent studies have demonstrated that SBI increases the risk of progression to clinically apparent stroke and cognitive decline. Therefore, an early and accurate detection of SBI and a search for potential treatable risk factors may have a significant impact on public health.

Methods
—Community-dwelling elderly people aged ≥66 years who participated in the present study (n=153) underwent brain MRI and standardized physical and neuropsychological examinations as well as blood biochemistry determinations, including total plasma homocysteine (pHcy), renal function, vitamin status, and polymorphisms of the methylenetetrahydrofolate reductase gene.

Results
—SBI was found in 24.8% of the participants. In the univariate analysis, the pHcy levels in subjects with SBI (13.6±4.1 μmol/L) were significantly higher (
P
=0.0004) than those in subjects without SBI (11.0±3.3 μmol/L). When pHcy levels were stratified into high (≥15.1 mmol/L), moderate (11.6 to 15.0 mmol/L), and low (≤11.5 mmol/L) groups, age (
P
<0.0001), male sex (
P
<0.0001), the habits of cigarette smoking (
P
<0.0001) and of alcohol consumption (
P
=0.0002), and folate levels (
P
=0.01) were significantly associated with an elevation of pHcy levels. The elevated pHcy levels were significantly associated with SBI after individual adjustment for age, sex, hypertension, renal function, and the habits of smoking and alcohol consumption.

Conclusions
—pHcy level is associated with age and nutritional and other lifestyle factors, and it contributes to a risk for SBI.
Spontaneous Echo Contrast Caused by Platelet and Leukocyte Aggregates?
Authors: Zotz Rainer J. , Müller Matthias , Genth-Zotz Sabine , Darius Harald
Published: June 2011

Background and Purpose
—Spontaneous echocardiographic contrast (SEC) is correlated to clinical thromboembolic events. We sought to determine the origin of SEC by utilizing direct analysis of left atrial blood.

Methods
—We examined the blood of 13 patients with and 19 without SEC. Blood samples were taken from the femoral vein and artery and from the right and left atria after transseptal puncture. Samples were incubated with fluorescence-labeled antibodies directed against the platelet (CD41a-PE, CD42b-PE, and CD62p-FITC) and leukocyte membrane epitopes (CD45-APC and CD14-FITC). The expressed epitopes were analyzed by dual laser flow cytometry immediately after blood withdrawal.

Results
—In the peripheral blood of both groups, more activation and aggregation were found in the venous blood than in the arterial blood (CD41a,
P
=0.007; CD14neutro,
P
=0.017; and leukocyte-platelet aggregates [LTAg],
P
=0.002). In patients without SEC, the degree of activation and aggregation of the cardiac samples closely resembled the results of the peripheral samples. The degree of activation and aggregation was significantly higher in the right atrium than in the left atrium (LTAg,
P
<0.01; leukocyte activation,
P
<0.01; CD41a,
P
<0.01; CD62p,
P
<0.02). In contrast, in patients with SEC the parameters of platelet and leukocyte activation as well as LTAg was significantly higher in the left atrium than in the right atrium of the same patient (all
P
<0.01). A correlation between the amount of SEC and platelet-monocyte aggregates could be found (
r
=0.92,
P
<0.0001).

Conclusions
—The hypothesis that platelet aggregates are involved in the pathogenesis of SEC is supported by the fact that platelets in the left atrium of patients with SEC showed more activation.
Incidence and Significance of Early Aneurysmal Rebleeding Before Neurosurgical or Neurological Management
Authors: Ohkuma Hiroki , Tsurutani Hisanobu , Suzuki Shigeharu
Published: June 2011

Background and Purpose
—Rebleeding is a major cause of death and disability in aneurysmal subarachnoid hemorrhage (SAH); however, there has been no report focusing on rebleeding before hospitalization in neurosurgical or neurological institutions. The aim of this study was to clarify the incidence of prehospitalization rebleeding, its impact on the clinical course and prognosis in patients with aneurysmal SAH, and the possible factors inducing it.

Methods
—In 273 patients who were admitted to our institution within 24 hours after the initial SAH bleeding and whose clinical course before admission could be fully evaluated, the patients’ clinical conditions and CT findings on admission, operability, prognosis, and possible factors inducing rebleeding were comparatively evaluated between the patients with and without an episode of prehospitalization rebleeding.

Results
—Of the 273 patients, 37 (13.6%) patients suffered from 39 episodes of rebleeding in the ambulance or at the referring hospital before admission to our hospital. The peak time of rebleeding was within 2 hours (77%), in which the incidence was statistically significant compared with that occurring 2 to 8 hours after the initial SAH bleeding (
P
<0.01). The group experiencing rebleeding showed more severe Hunt and Hess grades on admission, higher rates of intracerebral hematoma, of intraventricular hematoma, and of subdural hematoma on CT scan on admission, less operability, and poorer prognoses with statistically significant differences compared with the group that did not experience rebleeding. Systolic arterial pressure >160 mm Hg was a possible risk factor of rebleeding (odds ratio 3.1, 95% CI 1.5 to 6.8).

Conclusions
—Rebleeding during transfer and at the referring hospital is not rare. To improve overall outcome of aneurysmal SAH, the results obtained in this study should be made available to general practitioners and the doctors devoted to emergency medicine.
Temporal Relationship Between Endothelin-1 Concentrations and Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Mascia L. , Fedorko L. , Stewart D. J. , Mohamed F. , terBrugge K. , Ranieri V. M. , Wallace M. C.
Published: June 2011

Background and Purpose
—Endothelin 1 (ET-1) is a potent vasoconstrictor that may play a role in cerebral vasospasm following subarachnoid hemorrhage (SAH). However, data regarding its pathogenic role in the development of vasospasm are controversial. We planned a prospective, observational clinical study to investigate the temporal relationship between increased ET-1 production and cerebral vasospasm or other neurological sequelae after SAH.

Methods
—ET-1 levels in cerebrospinal fluid (CSF) were measured in 20 SAH patients from admission (within 24 hours from the bleeding) until day 7. Patients received a daily transcranial Doppler study and a neurological evaluation. On day 7, angiography was performed to verify the degree and extent of vasospasm. Patients were then classified as having (1) clinical vasospasm, (2) angiographic vasospasm, (3) no vasospasm, or (4) poor neurological condition without significant vasospasm (low Glasgow Coma Scale score [GCS]).

Results
—On admission, ET-1 levels were increased in the low-GCS group compared with the other groups (
P
=0.04). On day 4 ET-1 levels were not significantly different among groups, whereas on day 7 ET-1 levels were significantly increased in both the clinical vasospasm and low-GCS groups compared with the angiographic vasospasm and no vasospasm groups (
P
<0.005). Moreover, when the low-GCS group was excluded, there was a significant relationship between vasospasm grade and CSF ET-1 levels (
R
2
=0.73).

Conclusions
—CSF ET-1 levels were markedly elevated in patients with clinical manifestations of vasospasm (day 7) and with a poor neurological condition not related to vasospasm. However, ET-1 levels were low in clinical vasospasm patients before clinical symptoms were evident (day 4) and remained low in angiographic vasospasm patients throughout the study period. Thus, our data suggest that CSF ET-1 levels are increased in conditions of severe neuronal damage regardless whether this was due to vasospasm or to the primary hemorrhagic event. In addition, CSF ET-1 levels paralleled the neurological deterioration but were not predictive of vasospasm.
Risk of Aneurysm Recurrence in Patients With Clipped Cerebral Aneurysms
Authors: Tsutsumi K. , Ueki Keisuke , Morita Akio , Usui Masaaki , Kirino Takaaki
Published: June 2011

Background and Purpose
—With many patients living long after microsurgical aneurysm clipping for subarachnoid hemorrhage (SAH) and with the evolution of intravascular procedures as less invasive alternatives, knowledge of the long-term results of clipping is becoming important.

Methods
—Of 412 patients who underwent clipping of ruptured or unruptured cerebral aneurysms at our institution between 1976 and 1994 and who survived >3 years after surgery, 225 patients who were in good general condition and younger than 80 years were offered follow-up angiography to detect newly formed aneurysms. Of the 225, 80 patients (35.6%) agreed to undergo angiography. In addition, 32 patients underwent angiography for new medical indications other than SAH. Therefore, 112 patients underwent angiography, representing a total of 140 clipped aneurysms.

Results
—The mean interval from surgery was 9.3 years for all patients and 9.0 years for the clipped aneurysms (range 3 to 21 years). Four aneurysm regrowths were detected of the 140 (2.9%) clipped aneurysms, representing 3 of 125 completely clipped aneurysms, 1 of 14 incompletely clipped aneurysms, and 0 of 1 aneurysm not studied with postoperative angiography. De novo aneurysms were detected in 9 of 112 (8.0%) patients. The annual rate of de novo aneurysm formation was 0.89%.

Conclusions
—This study shows that the annual rate of de novo aneurysm formation is relatively high (0.89%) and that the cumulative risk becomes significant after 9 years. In consideration of the fatality rate of SAH, follow-up angiography may be indicated for patients with clipped aneurysms 9 to 10 years after surgery.
Low Potentiality of Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism as a Useful Predictive Marker for Carotid Atherogenesis in a Large General Population of a Japanese City
Authors: Mannami Toshifumi , Katsuya Tomohiro , Baba Shunroku , Inamoto Nozomu , Ishikawa Kazuhiko , Higaki Jitsuo , Ogihara Toshio , Ogata Jun
Published: June 2011

Background and Purpose
—Some previous studies, almost all western, have investigated whether there is a relationship between the insertion/deletion (
I/D
) polymorphism of the angiotensin-converting enzyme (ACE) and carotid atherosclerosis. The results, however, have not been consistently positive. Further, there have been few investigations based on a large, general population. Therefore, the present study aimed to clarify whether ACE gene deletion polymorphism was associated with carotid atherosclerosis in a large Japanese general population with a more homogeneous genetic background than Caucasian populations.

Methods
—Subjects aged 30 to 86 years were randomly selected from Suita City, located in Osaka, the second largest urban area of Japan, and included 1894 men and 2137 women. With the aid of high-resolution ultrasonography, carotid atherosclerosis was evaluated using our atherosclerotic indexes of intimal-medial thickness (IMT), plaque number (PN), plaque score (PS), and percentage of stenosis of the carotid artery assessed using high-resolution B-mode ultrasonography. ACE gene
I/D
polymorphism was detected by polymerase chain reaction.

Results
—There were no significant differences among the ACE genotypes for age and conventional cardiovascular risk factors, except for systolic blood pressure (SBP) and the percentage of hypertension in men. The values of IMT, PN, and PS as carotid atherosclerotic indexes were not significantly different among genotypes for either sex. After adjusting for age, body mass index, smoking habit, high-density lipoprotein cholesterol, triglycerides, presence of hypertension, presence of diabetes mellitus, and presence of hyperlipidemia, the estimated ORs for the presence of IMT ≥1.10 mm (defined as thickened IMT), according to ACE genotype (
DD
versus
II
, DD+
ID
versus
II,
and
DD
versus
ID
+
II
), for men were 0.80 (95% CI 0.60 to 1.23), 0.89 (0.62 to 1.29), and 0.89 (0.70 to 1.28), respectively. On the other hand, the ORs for women after the same adjustment were 0.92 (95% CI 0.58 to 1.35), 0.93 (0.59 to 1.45), and 0.91 (0.59 to 1.27), respectively.

Conclusions
—Our present data suggest that ACE
I/D
polymorphism is not potentially a useful predictive marker for carotid atherogenesis when investigated in a large and homogeneous general Japanese population of 4031 subjects, a finding similar to that in a Caucasian population study, the Perth Carotid Ultrasound Disease Assessment Study, an Australian study based on a general population using 1111 subjects.
Estimates of the Prevalence of Acute Stroke Impairments and Disability in a Multiethnic Population
Authors: Lawrence Enas S. , Coshall Catherine , Dundas Ruth , Stewart Judy , Rudd Anthony G. , Howard Robin , Wolfe Charles D. A.
Published: June 2011

Background and Purpose
—The goals of the present study were to estimate the prevalence of acute impairments and disability in a multiethnic population of first-ever stroke and to identify differences in impairment and early disability between pathological and Bamford subtypes. Associations between impairments and death and disability at 3 months were identifed.

Methods
—Impairments that occur at the time of maximum neurological deficit were recorded, and disability according to the Barthel Index (BI) was assessed 1 week and 3 months after stroke in patients in the South London Stroke Register.

Results
—Of 1259 registered patients, 6% had 1 or 2, 31.1% had 3 to 5, 50.6% had 6 to 10, and 10.6% had >10 impairments. Common impairments were weakness (upper limb, 77.4%), urinary incontinence (48.2%), impaired consciousness (44.7%), dysphagia (44.7%), and impaired cognition (43.9%). Patients with total anterior circulation infarcts had the highest age-adjusted prevalence of weakness, dysphagia, urinary incontinence, cognitive impairment, and disability. Patients with subarachnoid hemorrhage had the highest rates of coma. Patients with lacunar stroke had the high prevalence of weakness but were least affected by disability, incontinence, and cognitive dysfunction. Blacks had higher age- and sex-adjusted rates of disability in ischemic stroke (BI <20, odds ratio 2.76, 95% CI 1.47 to 5.21,
P
=0.002; BI <15, odds ratio 1.8, 95% CI 1.45 to 2.81,
P
=0.01) but impairment rates similar to those of whites. On multivariable analysis, incontinence, coma, dysphagia, cognitive impairment, and gaze paresis were independently associated with severe disability (BI <10) and death at 3 months.

Conclusions
—The extent of these findings indicates that an acute assessment of impairments and disability is necessary to determine the appropriate nursing and rehabilitation needs of patients with stroke.
Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Kissela Brett , Broderick Joseph , Woo Daniel , Kothari Rashmi , Miller Rosie , Khoury Jane , Brott Thomas , Pancioli Arthur , Jauch Edward , Gebel James , Shukla Rakesh , Alwell Kathleen , Tomsick Thomas
Published: June 2011

Background and Purpose
—The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm
3
. The volume of first-ever ischemic stroke in the population is not known.

Methods
—The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured.

Results
—There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm
3
(interquartile range, 0.5 to 8.8 cm
3
). There was a significant relation between location of lesion and infarct size (
P
<0.001) and between volume and mechanism of stroke (
P
=0.001).

Conclusions
—The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.
Hemorrhagic Transformation After Fibrinolysis With Tissue Plasminogen Activator
Authors: Tejima Emiri , Katayama Yoichi , Suzuki Yasuyuki , Kano Tsuneo , Lo Eng H.
Published: June 2011

Background and Purpose
—We used a rat model of thromboembolic stroke to evaluate whether hypertension increases the incidence of hemorrhage after fibrinolysis with tissue plasminogen activator (tPA).

Methods
—In this model, a microclot suspension was injected into the middle cerebral artery territory to induce focal ischemia. Reperfusion was induced in spontaneously hypertensive rats (SHR) by administering tPA (10 mg/kg) intravenously at 2 hours or 6 hours after the onset of thromboembolic focal ischemia. In untreated control rats, saline was administered at 2 hours after ischemia.

Results
—Hemorrhagic transformation was observed only in rats that received tPA at 6 hours (6 of 8 rats [75%]). Reduction of mean arterial blood pressure from 122±3 to 99±2 mm Hg with hydralazine, given to SHR for 1 week before ischemia, significantly decreased the incidence of hemorrhage in 2 of 11 rats (18%). tPA reduced infarct volumes, but cotreatment with hydralazine did not result in further protection.

Conclusions
—This study demonstrates that in this rat thromboembolic model of stroke, tPA-induced hemorrhage is dependent on blood pressure and that pharmacological reduction of hypertension during fibrinolysis can reduce the risk of hemorrhagic transformation.
Role of Endothelium in Shear Stress–Induced Constrictions in Rat Middle Cerebral Artery
Authors: Bryan Robert M. , Steenberg Marie L. , Marrelli Sean P.
Published: June 2011

Background and Purpose
—Luminal shear stress has been reported to constrict cerebral arteries and arterioles of several species. Although the endothelium is not required for this response, it is not known whether the endothelium enhances or attenuates shear stress–induced constrictions.

Methods
—Middle cerebral arteries (MCAs) were isolated from male Long-Evans rats, mounted in a tissue bath, and pressurized to 80 mm Hg in the absence of luminal flow. In some MCAs, the endothelium was selectively loaded with fura 2 for the measurement of endothelial Ca
2+
concentration. Luminal shear stress was increased by adjusting luminal flow while maintaining a constant intraluminal pressure.

Results
—After the development of spontaneous tone in MCAs without luminal flow, inside diameters were ≈190 μm. MCAs constricted ≈15% when luminal flow was increased to produce a shear stress of 50 dyne/cm
2
. The shear stress–induced constrictions were more pronounced in vessels without intact endothelium. Scavenging reactive oxygen species with 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron) or superoxide dismutase/catalase significantly inhibited the shear stress–induced constrictions in vessels with intact endothelium and in vessels in which the endothelium had been removed. In intact vessels, endothelial Ca
2+
increased 33 nmol/L (from 133±11 to 166±12 nmol/L) when shear stress was increased to 50 dyne/cm
2
. The presence of
N
G
-nitro-
l
-arginine methyl ester (L-NAME), L-NAME+indomethacin, or L-NAME+indomethacin+charybdotoxin had no significant effect on the shear stress–induced constrictions in MCAs with intact endothelium.

Conclusions
—We conclude that the endothelium plays a role in attenuating the shear stress–induced constrictions in rat MCAs. The attenuation does not appear to be by release of NO, prostacyclin, or endothelium-derived hyperpolarizing factor. The endothelium apparently attenuates the constriction by an unknown dilating factor, by a dilating process, or simply by attenuating the mechanical force of the shear stress as it is transmitted to the abluminal side of the vessel.