bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Platelet Glycoprotein Ibα Genotype and Ischemic Cerebrovascular Disease
Authors: Sonoda Akira , Murata Mitsuru , Ito Daisuke , Tanahashi Norio , Ohta Atsumi , Tada Yoko , Takeshita Eiko , Yoshida Tadashi , Saito Ikuo , Yamamoto Masatoshi , Ikeda Yasuo , Fukuuchi Yasuo , Watanabe Kiyoaki
Published: June 2011

Background and Purpose
—Platelets play pivotal roles in the development of ischemic cerebrovascular disease (CVD). The platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor, which plays a major role in the initial phase of platelet activation under high shear stress conditions. This study was designed to investigate the association between a genetic variation of this receptor and the prevalence of CVD.

Methods
—Two hundred patients with ischemic CVD, as confirmed by brain CT and/or MRI, and 317 age- and sex-matched control subjects without clinical evidence of CVD or cardiovascular disease were analyzed for their genotype frequencies of the
145
Thr/Met dimorphism of the α-chain of GPIb (GPIbα).

Results
—Genotypes with
145
Met (
T/M
and
M/M
) were more frequently found in the CVD patients (26.5%) than in control subjects (14.2%,
P
=0.0005). The genotype effect was more obvious in those <60 years of age or without acquired cardiovascular risk factors. The odds ratio for nonsmoking women <60 years of age was 10.6 (95% confidence intervals, 2.2 to 51.7). Although the number of patients studied was small (n=24), transient ischemic attack showed the highest odds ratio (4.3,
P
=0.0004), followed by lacunar infarction (OR=2.2,
P
=0.0024) and atherothrombotic infarction (OR=1.5,
P
=0.3143). Logistic regression analysis revealed that the presence of Met-allele was independently associated with CVD.

Conclusions
—Our study suggests that the platelet GPIbα genotype is a genetic risk factor for ischemic CVD.
Interrelation Between Plaque Surface Morphology and Degree of Stenosis on Carotid Angiograms and the Risk of Ischemic Stroke in Patients With Symptomatic Carotid Stenosis
Authors: Rothwell P. M. , Gibson R. , Warlow C. P.
Published: June 2011

Background and Purpose
—The risk of ischemic stroke distal to an atherothrombotic carotid stenosis increases with the degree of stenosis. The main mechanism of stroke is thought to be embolism from fissured or ruptured plaque, but there are few published data on the relationship between plaque morphology and severity of stenosis and their independent effects on the risk of ischemic stroke. We sought to determine the interrelation between plaque surface morphology, degree of carotid stenosis, and the risk of ipsilateral ischemic stroke.

Methods
—Severity of stenosis and plaque surface morphology were assessed on angiograms of the symptomatic carotid artery in 3007 patients in the European Carotid Surgery Trial and were related to baseline clinical characteristics, pathological characteristics of plaques examined at endarterectomy, and the risks of carotid territory ipsilateral ischemic stroke and other vascular events on follow-up.

Results
—The early risk of ipsilateral ischemic stroke on medical treatment was closely related to the degree of carotid stenosis. However, the initial degree of carotid stenosis was not predictive of strokes occurring >2 years after randomization. Angiographic plaque surface irregularity and plaque surface thrombus at endarterectomy increased in frequency as the degree of stenosis increased (both
P
<0.0001). However, the degree of stenosis was still predictive of the 2-year risk of stroke on medical treatment after correction for plaque surface irregularity. Angiographic plaque surface irregularity was an independent predictor of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis (hazard ratio=1.80; 95% CI, 1.14 to 2.83;
P
=0.01). This relationship was maintained when the analysis was confined to strokes occurring >2 years after randomization (hazard ratio=2.75; 95% CI, 1.30 to 5.80;
P
=0.01). Neither the degree of stenosis nor plaque surface irregularity was predictive of the “background” stroke risk after endarterectomy or the risk of nonstroke vascular events.

Conclusions
—Angiographic plaque surface irregularity is associated with an increased risk of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis. The increase in stroke risk with degree of stenosis is partly accounted for by the parallel increase in plaque surface irregularity and thrombus formation, but the degree of narrowing of the vessel lumen is still an independent predictor of ischemic stroke within 2 years of presentation.
The Symptomatic Carotid Plaque
Authors: Golledge Jonathan , Greenhalgh Roger M. , Davies Alun H.
Published: June 2011

Background
—The natural histories of equally severe symptomatic and asymptomatic carotid stenoses are very different, which suggests dichotomy in plaque behavior. The vascular biology of the symptomatic carotid plaque is presented in this review.

Summary of Review
—Histology studies comparing asymptomatic and symptomatic plaques were identified from MEDLINE. Reports in which stenosis severity was not stated or not similar for symptomatic and asymptomatic patients were excluded. In vitro studies and reports from the coronary circulation were reviewed with regard to the vascular biology of the plaque. Histology studies comparing carotid plaques removed from symptomatic and asymptomatic patients reveal characteristic features of unstable plaques: surface ulceration and plaque rupture (48% of symptomatic compared with 31% of asymptomatic,
P
<0.001), thinning of the fibrous cap, and infiltration of the cap by greater numbers of macrophages and T cells. In vitro studies suggest that macrophages and T cells release cytokines and proteinase, which stimulate breakdown of cap collagen and smooth muscle cell apoptosis and thereby promote plaque rupture.

Conclusions
—Infiltration of inflammatory cells to the surface of carotid plaques may be a critical step in promoting plaque rupture and resultant embolization or carotid occlusion. Further understanding of cell recruitment and behavior in carotid atherosclerosis may allow better detection of unstable plaques and therapeutic methods of plaque stabilization.
Early Growth, Adult Income, and Risk of Stroke
Authors: Eriksson J. G. , Forsén T. , Tuomilehto J. , Osmond C. , Barker D. J. P.
Published: June 2011

Background and Purpose
—A number of studies have shown that reduced intrauterine growth and low birth weight are associated with raised rates of fatal and nonfatal stroke in adult life. Whether this increased risk of stroke is modified by growth in childhood or by socioeconomic status in adult life is not known.

Methods
—We studied hospital admissions and deaths from stroke among 3639 men who were born in Helsinki University Central Hospital during 1924 to 1933. They had detailed records of their body size at birth, their growth through childhood, and their social circumstances as adults. Three hundred thirty-one of the men had had a stroke.

Results
—Hazard ratios for stroke were related to low birth weight in relation to head circumference (
P
=0.005) and to short length in relation to head circumference (
P
=0.02). These associations were stronger for hemorrhagic than for thrombotic stroke. Men who developed stroke still had below-average stature at 7 years (
P
=0.05), but after 7 years their height “caught up” through accelerated growth. As adults they had low incomes and low social class (
P
<0.0001).

Conclusions
—Stroke may originate through reduced fetal growth, with low body weight and short body length at birth but “sparing” of head growth. Other studies suggest that this pattern of growth is associated with persisting elevation of blood pressure and raised plasma fibrinogen concentrations, 2 known risk factors for stroke. The risk of stroke is increased by accelerated growth in height during childhood. Accelerated growth has previously been linked to the development of hypertension in adult life. Stroke risk is further increased by adverse influences linked to low income.
Identification Of Echocardiographic “Smoke” in a Bench Model With Transcranial Doppler Ultrasound
Authors: Yang Yi , Grosset Donald G. , Li Qiu , Lees Kennedy R.
Published: June 2011

Background and Purpose
—Spontaneous echo contrast in cardiac chamber has been indicated as a source of cerebral embolism. The nature of the echocardiographic smokelike signal is still not fully understood. This study was designed to regenerate spontaneous echo contrast and verify its thromboembolic characters in an in vitro model.

Methods
—Spontaneous echo contrast was reproduced in an expansion chamber under low flow conditions in a close circulation system. The spontaneous echo contrast was monitored and recorded with a 2-dimensional cardiosonography system and a transcranial Doppler device. Meanwhile, clinically commonly encountered embolic materials such as whole-blood clots, platelet aggregate–rich plasma, air bubbles, and 100-mL normal saline were injected into this monitored circuit. The differentiation of spontaneous echo contrast from emboli was performed by both visual observations of the echo images and offline Doppler signal intensity analysis. Average signal intensities produced by spontaneous contrast and injection of embolic materials and saline were compared. Furthermore, the effect of Doppler-detected flow velocity on generation of spontaneous contrast was also evaluated.

Results
—Spontaneous echo contrast was reproduced at low flow settings (90 to 120 mL/min) in this model. There was no significant difference in average signal intensity between the flow with spontaneous echo contrast and that without the echo (
P
=0.71). However, injection of embolic materials or normal saline did not generate smokelike image but caused much higher average signal intensity than the flow with spontaneous contrast (
P
<0.001). Injection of normal saline also increased average signal intensity.

Conclusions
—Our results suggest that smokelike echo is a special echo phenomenon occurring at low flow situations and does not itself produce material capable of embolizing into the systemic circulation.
Association Between High Homocyst(e)ine and Ischemic Stroke due to Large- and Small-Artery Disease but Not Other Etiologic Subtypes of Ischemic Stroke
Authors: Eikelboom John W. , Hankey Graeme J. , Anand Sonia S. , Lofthouse Elizabeth , Staples Nicole , Baker Ross I.
Published: June 2011

Background and Purpose
—Elevated plasma homocyst(e)ine may be a causal and modifiable risk factor for ischemic stroke, but the results of previous studies have been conflicting. One possible explanation is that homocyst(e)ine may only be associated with certain pathophysiological subtypes of ischemic stroke.

Methods
—We conducted a case-control study of 219 hospital cases with a first-ever ischemic stroke and 205 randomly selected community control subjects stratified by age, sex, and postal code. With the use of established criteria, cases of stroke were classified by etiologic subtype in a blinded fashion. The prevalence of conventional vascular risk factors, fasting plasma homocyst(e)ine levels, vitamin levels, and nucleotide 677 methylene tetrahydrofolate reductase
(MTHFR)
genotypes were determined in cases and controls.

Results
—Increasing homocyst(e)ine was a strong and independent risk factor for ischemic stroke (adjusted OR 2.7, 95% CI 1.4 to 5.1 for a 5-μmol/L increase in fasting plasma homocyst(e)ine from 10 to 15 μmol/L). Compared with the lowest quartile, the highest quartile of homocyst(e)ine was associated with an adjusted OR of ischemic stroke of 2.2 (95% CI 1.1 to 4.2). Mean plasma homocyst(e)ine was significantly higher in cases of ischemic stroke due to large-artery disease (14.1 μmol/L, 95% CI 12.5 to 15.9,
P
<0.001) and small-artery disease (12.7 μmol/L, 95% CI 11.4 to 14.1,
P
=0.004) compared with control subjects (10.5 μmol/L; 95% CI 10.0 to 11.0) but not in cardioembolic or other etiologic subtypes of ischemic stroke. Compared with the lowest quartile of homocyst(e)ine, the upper 3 quartiles were associated with an adjusted OR of ischemic stroke due to large-artery disease of 3.0 (95% CI 0.8 to 10.8) for the second quartile, 5.6 (95% CI 1.6 to 20) for the third quartile, and 8.7 (95% CI 2.4 to 32) for the fourth quartile (
P
for trend=0.0005). However, despite a clear association between the
TT MTHFR
genotype and elevated fasting plasma homocyst(e)ine, there was no association between
MTHFR
genotype and ischemic stroke or subtype of ischemic stroke.

Conclusions
—There is a strong, graded association between increasing plasma homocyst(e)ine and ischemic stroke caused by large-artery atherosclerosis and, to a much lesser extent, small-artery disease, but not cardioembolic or other etiologic subtypes of ischemic stroke. Our results are consistent with the hypothesis that the deleterious effect of high homocyst(e)ine is mediated primarily via a proatherogenic effect.
Diffusion- and Perfusion-Weighted MRI Patterns in Borderzone Infarcts
Authors: Chaves Claudia J. , Silver Brian , Schlaug Gottfried , Dashe John , Caplan Louis R. , Warach Steve
Published: June 2011

Background and Purpose
—The pathophysiology of borderzone infarcts is not well understood. We investigated whether combined diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) could identify pathophysiologically meaningful categories of borderzone infarcts.

Methods
—Seventeen patients with borderzone infarcts were identified from the Beth Israel Deaconess Medical Center Stroke Database. All patients had DWI and PWI, the majority of them within the first 24 hours of symptom onset.

Results
—Three patterns of perfusion abnormalities were associated with the diffusion lesions: 1, normal perfusion (5 patients); 2, localized perfusion deficits matching the area of restricted diffusion (5 patients); and 3, extensive perfusion deficits involving 1 or more vascular territories (7 patients). All but 1 patient with pattern 1 had transient peri-infarct hypotension as the presumed stroke mechanism. Two patients with pattern 2 had cardiac or aortic embolic sources; none had large-artery disease or arterial hypotension. Reperfusion was detected in all patients with this pattern who submitted to a follow-up study. All patients with pattern 3 had severe stenosis or occlusion of a large artery: the internal carotid, anterior cerebral, or middle cerebral.

Conclusions
—We postulate that the perfusion abnormality varies according to the mechanism of the borderzone infarction. Transient perfusion deficits occurring with hypotension in the absence of significant large-artery disease may not be revealed by PWI. Embolism may cause some cases of small borderzone perfusion deficits. Critical large-artery disease may cause large territorial perfusion deficits and predispose to borderzone infarction.
Visualization of the Basilar Artery By Transcranial Color-Coded Duplex Sonography
Authors: Schulte-Altedorneburg Gernot , Droste Dirk W. , Popa Vasile , Wohlgemuth Walter A. , Kellermann Mónika , Nabavi Darius G. , Csiba László , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Transcranial color-coded sonography (TCCS) via the suboccipital approach allows direct and continuous visualization of the basilar artery (BA). In this study, we intended to evaluate the ability of native TCCS in visualizing the length of the BA by means of a comparison with postmortem measurements.

Methods
—The BA was prospectively studied by TCCS shortly before death (median 3 days) in 46 moribund neurological patients (mean±SD age 71.1±13.1 years). The length of the BA was determined by measuring the distance between the vertebrobasilar junction and the deepest available flow signal in the top of the BA. During autopsy, photos of the vertebrobasilar system were taken to evaluate the true anatomic length and variations of the course of BA in situ, eg, straight, curved, or S-shaped.

Results
—Comparison of the in vivo ultrasound measurements of BA length and postmortem data was possible in 44 of 46 cases. In the 2 remaining patients, the BA was occluded. The mean insonation depth of the vertebrobasilar junction was found at 66.9±7.1 mm. The mean BA length was 21.5±6.8 mm by color-coded duplex and 32.9±6 mm anatomically (
P
<0.0001). The mean difference between color mode and anatomic findings was 11.3±6.4 mm in the case of a straight BA (35 cases) and 16.3±4.8 mm in an anatomically tortuous course of the BA (9 cases).

Conclusions
—Color duplex imaging enables correct visualization of the proximal two thirds of the BA, but only exceptionally of its distal one third. A tortuous course of the BA leads to an underestimation of its anatomic length.
Stroke Knowledge Among Stroke Support Group Members
Authors: Weltermann B. M. , Homann J. , Rogalewski A. , Brach S. , Voss S. , Ringelstein E. B.
Published: June 2011

Background and Purpose
—Community stroke education is needed to improve early stroke recognition and reduce delays in the referral of stroke patients. In some regions, stroke support groups are important promoters of regional stroke education. However, there are no data about the level of stroke knowledge among support group members that support this promotional role.

Methods
—We performed a cross-sectional questionnaire survey among 11 German stroke support groups. The questionnaire asked for stroke knowledge and sociodemographic and medical data. Stroke knowledge was excellent if a participant knew (1) at least 2 stroke symptoms (good symptom knowledge) and (2) at least 2 stroke risk factors (good risk factor knowledge), as well as knowing (3) that immediate hospital admission or an emergency call is necessary in case of stroke (good action knowledge).

Results
—A total of 133 members (96.2%) of 11 stroke support groups took part in the study. Mean age was 65.3 years (SD 11.2 years). Fifty-four percent of subjects were female, 72.8% were retired, and 69.8% were stroke patients. Of the participants, 80.3% had good symptom knowledge, 64.7% had good risk factor knowledge, and 79.7% had good action knowledge. Stroke knowledge was excellent in 44.0% of subjects. Logistic regression analysis showed that age <70 years and not having had a stroke were significant predictors for excellent stroke knowledge.

Conclusions
—Overall, members of stroke support groups are well informed about all aspects of modern stroke care. Because of their knowledge and personal experience, support groups should be viewed as important partners in community stroke education.
Collateral Configuration of the Circle of Willis
Authors: Hoksbergen A. W. J. , Fülesdi B. , Legemate D. A. , Csiba L.
Published: June 2011

Background and Purpose
—The anterior communicating artery (AcoA) and posterior communicating arteries (PcoA) of the circle of Willis provide the main route for collateral blood flow in cases of carotid artery obstruction. Transcranial color-coded duplex ultrasonography (TCCD) allows real-time measurement of the collateral function of the AcoA and PcoA. The primary objective of this study was to determine the collateral artery threshold diameters for supplying collateral flow.

Methods
—In 12 acute stroke patients with a median age of 75 years (51 to 91 years), the collateral integrity of the circle of Willis as assessed by TCCD and carotid compression tests was compared with their postmortem anatomy. The lengths and diameters of the collateral arteries were measured.

Results
—TCCD demonstrated absent anterior collateral flow in 3 patients. In 1 of these patients, absence of anterior cross-flow was due to an occluded anterior cerebral artery, which was revealed at autopsy. Absent posterior collateral flow was found in 14 hemispheres. In 2 of these hemispheres, autopsy revealed a fetal configuration of the posterior cerebral artery hampering posterior collateral flow. The median (range) diameters as found at autopsy of the functional (n=19) and nonfunctional (n=16) collateral arteries of the circle of Willis were 1.1 (0.4 to 2.0) and 0.5 (0.3 to 0.7) mm, respectively (
P
=0.003). PcoA diameters were found to correlate negatively (ρ=−0.50,
P
=0.01) to the diameters of their accessory P1 segments.

Conclusions
—The threshold diameter allowing for cross-flow through the primary collateral arteries of the circle of Willis is between 0.4 and 0.6 mm.
Stroke Patients in South Madrid
Authors: Muro M. Jiménez , de Pedro-Cuesta J. , Almazán J. , Holmqvist L. Widén
Published: June 2011

Background and Purpose
—The purpose of the present study was to describe the epidemiology of stroke disability and the use of health resources in South Madrid.

Methods
—Among a population of 665 168 residents in South Madrid, patients with an acute stroke of clinical onset during March to July 1996 who were seen at a general hospital or at 1 of 3 primary care centers were evaluated at baseline (n=147) and at 3 months (n=110) and 6 months (n=112) after stroke. We assessed the frequencies of stroke and stroke-related residual disability per population unit, as well as the impairment, disability, secondary complications, use of health resources, and impact on quality of life.

Results
—In patients ≥60 years old, the incidence of stroke with severe residual disability after 6 months was 75 per 10 000, was higher in men, and increased with age; the proportion of survivors among those examined at baseline was 20%. The use of hospital days per population unit was similar to that of reported European data, but the use of other health care resources was less. Patients frequently used bladder and nasal catheters and presented with shoulder pain. Social activities were infrequent and decreased after stroke. Access to technical aids was limited, and home adaptations were exceptional. The impact of stroke on health-related quality of life among patients and main caregivers was modest.

Conclusions
—The study shows that in South Madrid, (1) the use of health resources after stroke is low; (2) patients with stroke register low activities of daily living scores with a comparatively small impact on quality of life; and (3) relative to need, the use of rehabilitation, aids, and home adaptations and services was low.
Systematic Comparison of the Early Outcome of Angioplasty and Endarterectomy for Symptomatic Carotid Artery Disease
Authors: Golledge Jonathan , Mitchell Adam , Greenhalgh Roger M. , Davies Alun H.
Published: June 2011

Background and Purpose
—Endoluminal treatment is being increasingly used for carotid artery disease. The aim of this study was to compare the stroke and death risk within 30 days of endovascular treatment or endarterectomy for symptomatic carotid artery disease.

Methods
—A systematic comparison of the 30-day outcome of angioplasty with or without stenting and endarterectomy for symptomatic carotid artery disease reported in single-center studies, published since 1990, was performed.

Results
—Thirty-three studies (13 angioplasty and 20 carotid endarterectomy) were included in this analysis. Carotid stents were deployed in 44% of angioplasty patients. Mortality within 30 days of angioplasty was 0.8% compared with 1.2% after endarterectomy (OR 0.68, 95% CI 0.43 to 1.05;
P
=0.6). The stroke rate was 7.1% for angioplasty and 3.3% for endarterectomy (OR 2.22, CI 1.62 to 3.04;
P
<0.001), while the risk of fatal or disabling stroke was 3.2% and 1.6%, respectively (OR 2.09, CI 1.3 to 3.33;
P
<0.01). The risk of stroke or death was 7.8% for angioplasty and 4% for endarterectomy (OR 2.02, CI 1.49 to 2.75;
P
<0.001), while disabling stroke or death was 3.9% after angioplasty and 2.2% after endarterectomy (OR 1.86, CI 1.22 to 2.84;
P
<0.01).

Conclusions
—In the treatment of symptomatic carotid artery disease, the risk of stroke is significantly greater with angioplasty than carotid endarterectomy. At present, carotid angioplasty is not recommended for the majority of patients with symptomatic carotid artery disease.
Poststroke Dementia
Authors: Barba Raquel , Martínez-Espinosa Susana , Rodríguez-García Elena , Pondal Margarita , Vivancos José , Del Ser Teodoro
Published: June 2011

Background and Purpose
—The goal of the present study was to examine a series of putative risk factors of poststroke dementia (PSD), especially those factors usually associated with cerebrovascular disease and degenerative dementia, in a series of 251 consecutive unselected stroke patients.

Methods
—A standard protocol was prospectively applied at admission and 3 months after stroke; this protocol included clinical, functional, and cognitive assessments, hemogram and serum biochemistry, ECG and CT exams, apolipoprotein E and angiotensin-converting enzyme genotype, and neuropsychological examination. After a neuropsychological examination and an interview with a relative, the following diagnostic criteria were used: the
Diagnostic and Statistical Manual of Mental Disorders
(DSM)-IV for dementia after stroke, DSM-III-R for previous dementia and dementia stage, and Association Internationale pour la Recherche et l’Enseignement en Neurologie (NINDS-AIREN) for vascular dementia.

Results
—Seventy-five cases (30%) demonstrated dementia at 3-month follow up; 25 of them (10%) had demonstrated dementia before the stroke. Dementia was unrelated to type (ischemic/hemorrhagic) or location of stroke, vascular factors (hypertension, diabetes, ischemic heart disease, or hypercholesterolemia), apolipoprotein E or angiotensin-converting enzyme genotype, and serum homocysteine. Age (odds ratio [OR] 1.1, 95% CI 1.03 to 1.2), previous nephropathy (OR 6.1, 95% CI 1.5 to 24.3), atrial fibrillation (OR 4.4, 95% CI 1.4 to 13.9), low Canadian Neurological Scale score at discharge (OR 0.5, 95% CI 0.4 to 0.6), and previous mental decline assessed by the shortened Spanish version of the Informant Questionnaire on Cognitive Decline in the Elderly (SS-IQCODE; OR 1.2, 95% CI 1.1 to 1.4) were the correlates of dementia in logistic regression analyses. The same risks factors were found when cases with previous dementia and with hemorrhagic stroke were excluded.

Conclusions
—Dementia is frequent after ischemic or hemorrhagic stroke. Age, nephropathy, atrial fibrillation, previous mental decline, and stroke severity independently contribute to the risk.
Memory Impairment in Out-of-Hospital Cardiac Arrest Survivors Is Associated With Global Reduction in Brain Volume, Not Focal Hippocampal Injury
Authors: Grubb Neil R. , Fox Keith A. A. , Smith Karen , Best Jonathan , Blane Annette , Ebmeier Klaus P. , Glabus Michael F. , O’Carroll Ronan E.
Published: June 2011

Background and Purpose
—More than 30% of out-of-hospital cardiac arrest (OHCA) survivors suffer significant memory impairment. The hippocampus may be vulnerable to hypoxic injury during cardiac arrest. The purpose of this study was to determine whether selective hippocampal injury is the substrate for this memory impairment.

Methods
—Seventeen OHCA survivors and 12 patients with uncomplicated myocardial infarction were studied. OHCA survivors were divided into those with impaired and intact memory. Memory was assessed by use of the Rivermead Behavioural Memory Test and Doors and People Test. MRI was used to determine intracranial, whole-brain, amygdala-hippocampal complex, and temporal lobe volumes. Brain structure was also examined by statistical parametric mapping.

Results
—Left amygdala-hippocampal volume was reduced in memory-impaired OHCA victims compared with control subjects (mean 3.93 cm
3
and 95% CI 3.50 to 4.36 cm
3
versus mean 4.65 cm
3
and 95% CI 4.37 to 4.93 cm
3
;
P
=0.002). Left temporal lobe and whole-brain volumes were also reduced. There were no differences in amygdala-hippocampal volume indexed against ipsilateral temporal lobe volume. Significant correlations were observed between total brain volume and Rivermead Behavioural Memory Test (
r
=0.56,
P
<0.05) and Doors and People Test (
r
=0.67,
P
<0.01) scores in OHCA survivors. Both recall and recognition were compromised in memory-impaired subjects. Statistical parametric mapping did not detect focal brain abnormalities in these subjects. Global cerebral atrophy was confirmed by qualitative assessment.

Conclusions
—Memory impairment in OHCA survivors is associated with global cerebral atrophy, not selective hippocampal damage. Rehabilitation protocols need to account for the global nature of the brain injury.
Chlamydia pneumoniae
Seropositivity Is Associated With Carotid Artery Intima-Media Thickness
Authors: Schmidt Caroline , Hulthe Johannes , Wikstrand John , Gnarpe Håkan , Gnarpe Judy , Agewall Stefan , Fagerberg Björn
Published: June 2011

Background and Purpose
—Infection may both augment the atherosclerotic process and contribute to later manifestations of overt clinical disease.
Chlamydia pneumoniae
elementary bodies have been detected in atherosclerotic lesions. The aim of the present study was to investigate whether elevated titers of antibodies and circulating immune complexes to
C pneumoniae
were associated with ultrasound findings indicating presence of atherosclerosis in the carotid artery.

Methods
—Serum titers of antibodies to
C pneumoniae
(IgM, IgA, IgG, and circulating immune complex) were related to intima-media thickness (IMT) and plaque status measured by B-mode ultrasound in the carotid artery in 113 men with treated hypertension and at least 1 of the following risk factors: hypercholesterolemia, smoking, or diabetes.

Results
—Any of the titers was elevated in 56 (50%) men, and common carotid artery IMT was thicker in this group compared with the 57 men without any elevated titers (1.00 versus 0.92 mm,
P
<0.05). There were no accompanying differences in blood pressure, lipid levels, blood glucose, or smoking. Elevation of separate antibody types and circulation immune complex were also associated with increased IMT. In the latter group, systolic blood pressure was higher among seropositive patients compared with those who had no circulating immune complex. Seropositivity was not related to plaque status.

Conclusions
—Seropositivity for
C pneumoniae
was associated with an increased intima-media thickness in the common carotid artery but not plaque status in hypertensive men at high risk for cardiovascular disease.
Cerebral Oxygenation Declines in Healthy Elderly Subjects in Response to Assuming the Upright Position
Authors: Mehagnoul-Schipper D. Jannet , Vloet Lilian C. M. , Colier Willy N. J. M. , Hoefnagels Willibrord H. L. , Jansen René W. M. M.
Published: June 2011

Background and Purpose
—With increasing age, assuming the upright position is more often accompanied by symptoms such as dizziness and lightheadedness, possibly as a result of a diminished oxygen supply to the brain due to impaired cerebral autoregulation. We aimed to quantify postural changes in cerebral oxygenation and systemic hemodynamics in healthy elderly and young subjects.

Methods
—In 18 healthy elderly subjects (aged 70 to 83 years) and 10 healthy young subjects (aged 22 to 45 years), frontal cortical oxygenation and hemodynamic responses were continuously monitored by near infrared spectroscopy and Finapres, respectively, before and during 10 minutes of active standing.

Results
—Cortical oxyhemoglobin concentration [O
2
Hb] decreased by −4.6±2.2 μmol/L (
P
<0.001) and cortical deoxyhemoglobin concentration increased by 1.5±2.4 μmol/L (
P
<0.05) in the elderly subjects after posture change, whereas these variables did not change significantly in the young subjects. The postural hemodynamic changes tended to be attenuated in the elderly subjects, except for the increases in systolic blood pressure (BP). Smaller postural increases in diastolic BP were related to larger [O
2
Hb] decreases
(r
=0.53,
P
<0.01, corrected for the age effect).

Conclusions
—Assuming the upright position evokes an asymptomatic decrease in frontal cortical oxygenation in healthy elderly subjects but not in healthy young subjects. Cortical [O
2
Hb] changes are affected by diastolic BP changes. These findings may indicate that regulation of cerebral oxygenation alters with increasing age.
Visualization of Brain Perfusion With Harmonic Gray Scale and Power Doppler Technology
Authors: Seidel Günter , Algermissen Christian , Christoph Arnd , Katzer Tobias , Kaps Manfred
Published: June 2011

Background and Purpose
—It is unclear which harmonic imaging mode (power Doppler or gray-scale imaging) is superior and which measuring method is the most robust for the description of brain perfusion.

Methods
—We performed an animal study on 6 beagles through the intact skull using a SONOS 5500 device and Optison injected intravenously in 3 different doses (0.15, 0.3, and 0.6 mL). Intensity versus heart-cycle plots for the brain parenchyma and the basal cerebral arteries were generated to evaluate the peak increase (PI) from baseline and the area under the curve (AUC).

Results
—With harmonic gray-scale imaging, a homogeneous increase in echo contrast of the brain parenchyma was observed. The effect was dose dependent, resulting in a significant increase in PI as well as an insignificant increase of the AUC with 0.3 mL versus 0.15 mL contrast agent (
P
=0.03 and
P
=0.65, respectively; n=5). With harmonic power Doppler, injection of the 3 different doses resulted in a nonsignificant increase in PI and AUC
P
=0.17, n=6 for both). After normalization of the brain signal to the peak arterial signal in individual dogs, a significant increase could be demonstrated (
P
=0.03 and
P
=0.01, respectively; n=6). The signal pattern of harmonic power Doppler was inhomogeneous, with stronger signal increases in the anterior part of the brain.

Conclusions
—Gray-scale imaging leads to a more homogeneous increase in echo contrast of the brain tissue and may be more suitable for displaying brain perfusion. The PI of the signal intensity seems the most robust parameter for the description of cerebral perfusion with both imaging modes under investigation.
Prediction of Mortality by Ultrasound Screening of a General Population for Carotid Stenosis
Authors: Joakimsen Oddmund , Bønaa Kaare H. , Mathiesen Ellisiv B. , Stensland-Bugge Eva , Arnesen Egil
Published: June 2011

Background and Purpose
—The extensive use of ultrasound examination of carotid arteries has revealed stenosis in many asymptomatic subjects, and clinical studies have shown that carotid stenosis is a risk factor for cardiovascular disease and death. However, information on stenosis as detected in a general population and its relation to mortality is scarce. The purpose of this population-based study was to assess whether carotid stenosis is a predictor of death.

Methods
—In 1994 to 1995, 248 subjects with suspected carotid stenosis were identified among 6727 men and women 25 to 84 years of age who were examined with ultrasound. These subjects and 496 age- and sex-matched control subjects were followed up for 4.2 years, and the number and causes of deaths were registered.

Results
—The unadjusted relative risk for death was 2.72 (95% CI, 1.57 to 4.75) for subjects with stenosis compared with control subjects. Adjusting for cardiovascular risk factors increased the relative risk to 3.47 (95% CI, 1.47 to 8.19). The adjusted relative risk in persons with stenosis and no cardiovascular disease or diabetes was 5.66 (95% CI, 1.53 to 20.90), which was higher than in subjects with stenosis and self-reported disease (1.79; 95% CI, 0.75 to 4.27). There was a dose-response relationship between degree of stenosis and risk of death (
P
=0.002 for linear trend). Carotid stenosis was a stronger predictor of death than self-reported cardiovascular disease or diabetes.

Conclusions
—Carotid stenosis is a strong and independent predictor of death.
Effects of Delayed Intraischemic and Postischemic Hypothermia on a Focal Model of Transient Cerebral Ischemia in Rats
Authors: Kawai Nobuyuki , Okauchi Masanobu , Morisaki Kuniaki , Nagao Seigo
Published: June 2011

Background and Purpose
—Intraischemic mild hypothermia has been shown to be neuroprotective in reducing cerebral infarction in transient focal ischemia. As a more clinical relevant issue, we investigated the effect of delayed intraischemic and postischemic hypothermia on cerebral infarction in a rat model of reversible focal ischemia. We also examined the effect of hypothermia on the inflammatory response after ischemia-reperfusion to assess the neuroprotective mechanism of brain hypothermia.

Methods
—Rats were subjected to 2 hours of middle cerebral artery occlusion followed by 22 hours of reperfusion under the following protocols: (1) rats were treated with normothermia (37.0°C, 4 hours) and then housed in room temperature (25°C, 18 hours) and (2) rats were treated with hypothermia (33.0°C, 4 hours, brain temperature modulation was started 30 minutes before the reperfusion) and then housed in cold temperature (5°C, 18 hours). Animals were killed 24 hours after the onset of ischemia. The infarct volume was examined with 2,3,5-triphenyl-tetrazolium chloride staining. The accumulation of polymorphonuclear leukocytes (PMNLs) and the expression of intercellular adhesion molecule-1 mRNA were evaluated in both groups.

Results
—A significant reduction (
P
<0.05) in infarct volume was found in the hypothermia group compared with the normothermia group. Compared with the normothermia group, hypothermic treatment also significantly reduced the accumulation of PMNLs (
P
<0.01) and inhibited the overexpression of intercellular adhesion molecule-1 mRNA at 22 hours of reperfusion after 2 hours of ischemia.

Conclusions
—Ischemic brain damage can be reduced with delayed intraischemic and prolonged postischemic hypothermia in a focal model of transient cerebral ischemia in rats. The neuroprotective mechanism of hypothermia may be mediated by suppression of PMNL-mediated inflammatory response after ischemia-reperfusion in this model.
Piracetam Improves Activated Blood Flow and Facilitates Rehabilitation of Poststroke Aphasic Patients
Authors: Kessler J. , Thiel A. , Karbe H. , Heiss W. D.
Published: June 2011

Background and Purpose
—In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow.

Methods
—Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H
2
15
O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images.

Results
—Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (
P
<0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests.

Conclusions
—Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and this effect is accompanied by a significant increase of task-related flow activation in eloquent areas of the left hemisphere.
Are Morphological or Functional Changes in the Carotid Artery Wall Associated With
Chlamydia pneumoniae, Helicobacter pylori,
Cytomegalovirus, or Herpes Simplex Virus Infection?
Authors: Espinola-Klein Christine , Rupprecht Hans-Jürgen , Blankenberg Stefan , Bickel Christoph , Kopp Helmuth , Rippin Gerd , Hafner Gerd , Pfeifer Ulf , Meyer Jürgen
Published: June 2011

Background and Purpose
—Chronic infection with
Chlamydia pneumoniae
,
Helicobacter pylori
, cytomegalovirus (CMV), and herpes simplex virus (HSV) has been implicated in the pathogenesis of atherosclerosis. The carotid intima-media thickness (IMT) can be taken to indicate early atherosclerosis, the presence of a carotid stenosis is a marker of a manifest carotid atherosclerosis, and an increase in arterial stiffness is used as marker of structural and functional changes in an atherosclerotic vessel wall.

Methods
—In 504 patients (75% men; mean age 62.9 [SD 10] years), we measured the IMT and the elastic pressure modulus (EP; n=445) of the common carotid artery and the prevalence of a internal or external carotid artery stenosis. Blood samples were taken, and antibodies against
C pneumoniae, H pylori
, CMV, and HSV types 1 and 2 were evaluated. Statistical evaluation was performed with regression procedures and multivariate logistic regression analyses.

Results
—Seropositivity for
C pneumoniae
was an independent predictor for a combined end point of highest category of IMT and carotid artery stenosis (OR 1.8, 95% CI 1.1 to 3.1; adjusted) for IgG titers. Independently, CMV increased the risk for the combined end point (OR 1.7, 95% CI 1.1 to 2.8; adjusted) for IgG titers and for IgA titers (OR 2.3, 95% CI 1.1 to 4.9; adjusted). We found a significant correlation between IgG antibodies against CMV and EP; HSV type 2 IgG titers were associated with IMT and carotid stenosis, but the latter results were no longer significant after adjustment. There was no association with
H pylori
or HSV type 1.

Conclusions
—We found a significant association of IgG antibodies against
C pneumoniae
and CMV with early and advanced carotid atherosclerosis. CMV was also correlated to functional changes of the carotid artery, but this could not be confirmed after adjustment.
Intravenous Brain-Derived Neurotrophic Factor Reduces Infarct Size and Counterregulates Bax and Bcl-2 Expression After Temporary Focal Cerebral Ischemia
Authors: Schäbitz Wolf-R. , Sommer Clemens , Zoder Werner , Kiessling Marika , Schwaninger Markus , Schwab Stefan
Published: June 2011

Background and Purpose
—Pretreatment with intraventricular brain-derived neurotrophic factor (BDNF) reduces ischemic damage after focal cerebral ischemia. In this experiment we studied the effect of intravenous BDNF delivered after focal cerebral ischemia on neurological outcome, infarct size, and expression of proapoptotic and antiapoptotic proteins Bax and Bcl-2, respectively.

Methods
—With the use of the suture occlusion technique, the right middle cerebral artery in rats was temporarily occluded for 2 hours. Thirty minutes after vessel occlusion, BDNF (300 μg/kg per hour in vehicle; n=12) or vehicle alone (n=13) was continuously infused intravenously for 3 hours. After 24 hours the animals were weighed and neurologically assessed on a 5-point scale. The animals were then killed, and brains underwent either 2,3,5-triphenyltetrazolium chloride staining for assessment of infarct volume or paraffin embedding for morphology and immunohistochemistry (Bax, Bcl-2).

Results
—Physiological parameters (mean arterial blood pressure, P
o
2
, P
co
2
, pH, body temperature, glucose) and weight revealed no difference between groups. Neurological deficit was improved in BDNF-treated animals versus controls (
P
<0.05, unpaired, 2-tailed
t
test). Mean±SD infarct volume was 229.7±97.7 mm
3
in controls and 121.3±80.2 mm
3
in BDNF-treated animals (
P
<0.05, unpaired, 2-tailed
t
test). Cortical infarct volume was 155.5±78.5 mm
3
in the placebo group and 69.9±50.2 mm
3
in the BDNF-treated group (
P
<0.05, unpaired, 2-tailed
t
test). Subcortical infarct volume was 74.1±30.6 mm
3
in the placebo group and 51.1±26.8 mm
3
in the BDNF-treated group (
P
=NS). Bax-positive neurons were significantly reduced in the ischemic penumbra in BDNF-treated animals (
P
<0.05, unpaired, 2-tailed
t
test), whereas Bcl-2–positive neurons were significantly increased in this area (
P
<0.001, unpaired, 2-tailed
t
test).

Conclusions
—This study demonstrates a neuroprotective effect of BDNF when delivered intravenously after onset of focal cerebral ischemia. As shown here, one possible mechanism of action of neuroprotection of BDNF after focal ischemia appears to be counterregulation of Bax/Bcl-2 proteins within the ischemic penumbra.
Improved Recovery in Activities of Daily Living Associated With Remission of Poststroke Depression
Authors: Chemerinski Eran , Robinson Robert G. , Kosier James T.
Published: June 2011

Background and Purpose
—Poststroke depression is associated with impaired recovery of activities of daily living (ADL) function compared with similar nondepressed patients. We examined the differences on recovery of ADL functions among poststroke depressed patients with remission of their depression compared with poststroke depressed patients without mood recovery over the first 3 to 6 months after stroke.

Methods
—On the basis of a semistructured psychiatric examination and DSM-IV diagnostic criteria, a consecutive series of patients with poststroke major or minor depression (n=55) were selected. Their impairment in ADL function was assessed by means of the Johns Hopkins Functioning Examination during acute hospitalization and either 3 or 6 months later.

Results
—Patients whose mood improved at follow-up (n=21) had significantly greater recovery in ADL functions at follow-up than patients whose mood did not improve (n=34). There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups. Furthermore, patients with either major or minor depression at the initial evaluation showed the same amount of recovery in ADL function if they improved at follow-up.

Conclusions
—Our findings suggest that remission of poststroke depression over the first few months after stroke is associated with greater recovery in ADL function than continued depression. Early effective treatment of depression may have a positive effect on the rehabilitation outcome of stroke patients.
Relaxant Effect of U0126 in Hemolysate-, Oxyhemoglobin-, and Bloody Cerebrospinal Fluid–Induced Contraction in Rabbit Basilar Artery
Authors: Zubkov Alexander Y. , Rollins K. Shadon , McGehee Bennett , Parent Andrew D. , Zhang John H.
Published: June 2011

Background and Purpose
—It has been suggested that mitogen-activated protein kinase (MAPK) is involved in cerebral vasospasm after subarachnoid hemorrhage. The present study was undertaken to explore the inhibitory effect of U0126, a novel MAPK inhibitor, in the contraction of the rabbit basilar artery by 3 spasmogens: hemolysate, oxyhemoglobin, and bloody cerebrospinal fluid (CSF) from patients with vasospasm.

Methods
—The contraction and relaxation of rabbit basilar arteries were measured by isometric tension. MAPK immunoprecipitation was assessed by Western blot analysis.

Results
—(1) Pretreatment of the rabbit basilar arteries with U0126 reduced contractions to hemolysate, oxyhemoglobin, or bloody CSF applied subsequently. (2) In the absence of endothelial cells, U0126 produced an inhibitory effect similar to the contractions induced by hemolysate, oxyhemoglobin, or bloody CSF. (3) U0126 relaxed the sustained contraction induced by hemolysate, oxyhemoglobin, or bloody CSF. (4) Hemolysate, oxyhemoglobin, and bloody CSF enhanced MAPK immunoprecipitation. (5) U0126 reduced MAPK immunoprecipitation induced by hemolysate, oxyhemoglobin, and bloody CSF. (6) Hemolysate, oxyhemoglobin, and bloody CSF significantly increased MAPK activity in the rabbit basilar artery. (7) U0126 abolished the effect of hemolysate, oxyhemoglobin, or bloody CSF on MAPK activation.

Conclusions
—This study demonstrated a role of MAPK in the contraction of rabbit basilar arteries by hemolysate, oxyhemoglobin, and bloody CSF. MAPK inhibitor U0126 may be useful in the treatment of cerebral vasospasm.