bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Blood Pressure and Subcortical Lesions in Healthy Elderly People
Authors: Goldstein Iris B. , Bartzokis George , Hance Darwood B. , Shapiro David
Published: June 2011

Background and Purpose
—The relationship between blood pressure (BP) and heart rate (HR) and MRI assessments of subcortical T2 hyperintensities was evaluated in healthy elderly men and women.

Methods
—Casual and 24-hour ambulatory BPs and HR measurements were taken of 144 elderly individuals, aged 55 to 79 years. Subjects had no evidence of previous health disorders. MRI scans of white matter, subcortical gray matter, and insular subcortex were coded for severity of hyperintensities.

Results
—Mean casual BP for the group was 120/72 mm Hg. With age and sex accounted for, individuals with the highest severity rating of white matter hyperintensities had higher casual, awake, and sleep systolic BPs; higher awake diastolic BPs; greater awake systolic BP variability; and a smaller nocturnal fall in systolic and diastolic BPs than individuals with less severe ratings. Higher severity ratings for subcortical gray matter hyperintensities were associated with elevations in casual, awake, and asleep systolic BPs and a smaller HR drop during sleep. Subjects with higher ratings for the insular subcortex had higher systolic and diastolic BPs (casual, awake, and asleep), greater HR variability during sleep, and a smaller nocturnal fall in HR.

Conclusions
—Casual and 24-hour ambulatory BPs and some ambulatory HR measures are associated with subcortical lesions of the brain. Longitudinal studies are needed to further explore the relationship between white matter lesions and cardiovascular measures, as well as the significance of these lesions for cerebrovascular disease in healthy elderly subjects.
Apoptosis of Motor Neurons With Induction of Caspases in the Spinal Cord After Ischemia
Authors: Hayashi T. , Sakurai M. , Abe K. , Sadahiro M. , Tabayashi K. , Itoyama Y.
Published: June 2011

Background and Purpose
—Some neuronal subpopulations are especially vulnerable to ischemic injury. In the spinal cord, large motor neurons are vulnerable to ischemia and are selectively lost after transient ischemia. However, the mechanisms of the neuronal loss have been uncertain. We hypothesized that spinal motor neurons might be lost by apoptosis and investigated a possible mechanism of neuronal death by detection of double-strand breaks in genomic DNA and immunohistochemical analysis for caspases, ie, interleukin-1β converting enzyme (ICE),
Nedd-2
, and CPP32.

Methods
—We used a rabbit spinal cord ischemia model created with a balloon catheter. The spinal cord was removed at 8 hours, 1, 2, or 7 days after 15 minutes of transient ischemia, and histological changes were studied with hematoxylin-eosin staining. To detect double-strand breaks in DNA, a staining with terminal deoxynucleotidyl transferase–mediated dUTP-biotin in situ nick end labeling (TUNEL) was performed. Furthermore, expression of ICE,
Nedd-2
, and CPP32 was investigated by Western blotting and immunohistochemical analysis.

Results
—Motor neurons were selectively lost at 7 days after transient ischemia. TUNEL study demonstrated that no cells were positively labeled until 1 day after ischemia, but nuclei of some motor neurons were positively labeled at 2 days. Western blot analysis revealed no immunoreactivity for ICE and slight immunoreactivities for
Nedd-2
and CPP32 in the sham-operated spinal cords. However, immunoreactivity became apparent at 8 hours after transient ischemia, decreased at 1 day, and returned to baseline level at 2 days. Immunohistochemical analysis demonstrated that motor neurons were responsible for induction of those caspases.

Conclusions
—Double-strand breaks in genomic DNA and induction of three caspases were demonstrated. These results indicate that motor neuron death in the spinal cord after transient ischemia is profoundly associated with activation of apoptotic processes.
Cigarette Smoking as a Determinant of High-Grade Carotid Artery Stenosis in Hispanic, Black, and White Patients With Stroke or Transient Ischemic Attack
Authors: Mast Henning , Thompson John L.P. , Lin I-Feng , Hofmeister Christoph , Hartmann Andreas , Marx Peter , Mohr Jay P. , Sacco Ralph L.
Published: June 2011

Background and Purpose
—We sought to investigate the association of cigarette smoking with high-grade carotid artery stenosis in Hispanic, black, and white patients with cerebral ischemia in two independent samples.

Methods
—Prospectively collected data from the Northern Manhattan Stroke Study (NOMASS) (n=431) and the Berlin Cerebral Ischemia Databank (BCID) (n=483) were used separately for a cross-sectional study estimating the association between cigarette smoking and high-grade carotid stenosis (defined as a luminal narrowing of ≥60%, diagnosed by duplex and/or Doppler ultrasound). In both studies, cerebral ischemia patients with normal sonographic findings or nonstenosing plaques of their carotid arteries served as a comparison group. Multivariate logistic regression models were used for statistical tests to determine the association between smoking and the dependent variable for high-grade carotid stenosis. Age, sex, hypertension, diabetes, hypercholesterolemia, and race/ethnicity were considered potential confounders. Further analyses of the NOMASS data estimated the effect of the amount of cigarette use and the impact of race/ethnicity.

Results
—High-grade carotid stenoses were found in 14% of the NOMASS and in 21% of the Berlin patients. In Berlin the entire sample was white, whereas in New York only 19% of the cohort were white. In both samples, smoking was independently associated with severe carotid stenosis (NOMASS: odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0; BCID: OR, 3.9; 95% CI, 2.4 to 6.4). Patients smoking 20 pack-years or more showed a significant association (OR, 2.0; 95% CI, 1.1 to 3.9), whereas no significant effect was found for lower amounts of cigarette use. In NOMASS, white smokers displayed a significant (OR, 3.2; 95% CI, 1.1 to 8.9) association with high-grade carotid stenosis, the association for black smokers was less strong, and no association was found among Hispanics.

Conclusions
—Smoking is an independent determinant of severe carotid artery stenosis in patients with focal cerebral ischemia. The association differs by race/ethnicity, with the greatest effect observed among whites.
Potential and Limitations of Echocontrast-Enhanced Ultrasonography in Acute Stroke Patients
Authors: Nabavi Darius G. , Droste Dirk W. , Kemény Vendel , Schulte-Altedorneburg Gernot , Weber Sepp , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Ultrasonography (US) is a well-established method used to assess the brain-supplying arteries in the acute stroke setting. However, several technical and anatomic limitations are known to reduce its diagnostic accuracy and confidence level. Echocontrast agents (ECA) are known to improve the signal-to-noise ratio by enhancing the intensity of the reflecting Doppler signal. We undertook this prospective study to evaluate the diagnostic value of ECA in a consecutive, nonselected cohort of acute stroke patients with insufficient native US investigations.

Methods
—During a 1-year period, 25 patients were examined within 48 hours of the onset of stroke. The need for ECA was due to an insufficient transtemporal (n=18), transforaminal (n=4), or extracranial (n=3) imaging of arteries potentially involved in the ischemic event. In 12 patients, a diagnostic suspicion could natively be raised, whereas in the other 13 patients, the strongly reduced image quality did not allow for any neurovascular conclusions. Four grams of Levovist was injected at a concentration of 200 mg/mL and 400 mg/mL for the extracranial and transcranial insonations, respectively. The effect of the echocontrast enhancement was assessed with respect to (1) signal enhancement, (2) image quality, (3) final diagnostic confidence, and (4) the need for additional neurovascular imaging methods.

Results
—In all but one patient (96%), a strong signal enhancement was noted, leading to a moderate (n=11) or strong improvement (n=10) of the transcranial image quality. Thus in a total of 18 patients (72%), the echoenhancement provided a neurovascular diagnosis of sufficient confidence. This led to the confirmation of the previously suspected findings and disclosed three further occlusions and four stenoses of the intracranial arteries. In contrast, for the three extracranial examinations the image quality was not sufficiently improved because of persistent color artifacts derived from adjacent neck vessels. Besides the seven patients with inconclusive examinations, five patients with conclusive echoenhanced US studies (48% in total) demanded additive neurovascular imaging studies, based on the clinical decision of the attending physicians. This led to confirmation of all high-confident sonographic diagnoses.

Conclusions
—In summary, in approximately three fourths of our acute stroke patients with insufficient native US investigations, echocontrast enhancement enabled a reliable neurovascular diagnosis, allowing the cancellation of additive neurovascular imaging procedures in half of our cohort. Our preliminary results suggest that ECA can reasonably support the early cerebrovascular workup in the acute stroke setting.
Clinical Efficiency Tools Improve Stroke Management in a Rural Southern Health System
Authors: Newell Samuel D. , Englert Janet , Box-Taylor Anita , Davis Kenneth M. , Koch Karen E.
Published: June 2011

Background and Purpose
—Ischemic stroke is a high-volume and financially draining diagnosis at this rural health system. The purpose of this clinical practice analysis was to identify resource utilization and clinical process inefficiencies and to promote clinically efficient, evidence-based improvements.

Methods
—A retrospective analysis of medical record and financial databases of 356 patients with ischemic stroke was performed. The medical record data were adjusted for severity, and outliers were eliminated. The resources utilized by each physician were determined. Comparative graphs were prepared, presented, and discussed. The physicians implemented two types of changes: (1) alteration of resource utilization and consultation patterns and (2) support of clinical process improvement. In 1997, a follow-up analysis of 399 patients was performed.

Results
—The initial comparison of internists’ to neurologists’ patient populations found the following: patient age (75 versus 65 years), patient severity ratings (2.8 versus 2.5), length of stay (10.7 versus 8.8 days), costs ($7360 versus $6862), mortality rates (12.5% versus 8.9%), and aspiration pneumonia rate (8.5% versus 3.8%). A comparison of the 1995 analysis to the 1997 analysis revealed the following per patient resource utilization decreases (all
P
<0.05): chemistry laboratory, 2.65 to 1.95 studies; intravenous fluids, 2.85 to 1.85 L; oxygen use, 6.06 to 2.75 U; and nifedipine use, 1.62 to 0.33 capsules. The clinical process improvements resulted in the following overall outcomes (all
P
<0.05 except mortality): length of stay (7.2 days), nonadjusted costs ($6246), mortality (6.5%), and rates of pneumonia (2.7%).

Conclusions
—Objective analysis of resource utilization resulted in physicians changing their individual management of stroke and collectively supporting clinical process changes that improved clinical and financial outcomes.
Diagnosis of Stroke by the Nonneurologist
Authors: Ferro J. M. , Pinto A. N. , Falcão I. , Rodrigues G. , Ferreira J. , Falcão F. , Azevedo E. , Canhão P. , Melo T. P. , Rosas M. J. , Oliveira V. , Salgado A. V.
Published: June 2011

Background and Purpose
—The first medical contact of an acute stroke victim is often a nonneurologist. Validation of stroke diagnosis made by these medical doctors is poorly known. The present study seeks to validate the stroke diagnoses made by general practitioners (GPs) and hospital emergency service physicians (ESPs).

Methods
—Validation through direct interview and examination by a neurologist was performed for diagnoses of stroke made by GPs in patients under their care and doctors working at the emergency departments of 3 hospitals.

Results
—Validation of the GP diagnosis was confirmed in 44 cases (85%); 3 patients (6%) had transient ischemic attacks and 5 (9%) suffered from noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in 169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most frequent conditions misdiagnosed as stroke were neurological in nature (cerebral tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo, 1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical disorders, 7).

Conclusions
—In the majority of cases, nonneurologists (either GPs or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke with drugs that do not cause serious side effects can be started before evaluation by a neurologist and CT scan.
Carotid Atherosclerosis in Premenopausal and Postmenopausal Women and Its Association With Risk Factors Measured After Menopause
Authors: Sutton-Tyrrell Kim , Lassila Holly C. , Meilahn Elaine , Bunker Clareann , Matthews Karen A. , Kuller Lewis H.
Published: June 2011

Background and Purpose
—In women, symptoms of coronary artery disease are delayed by 10 to 15 years in comparison with men, most likely because of the protective effect of ovarian hormones. This report compares the prevalence and degree of carotid atherosclerosis between 292 premenopausal women and 294 women at 5 to 8 years after menopause.

Methods
—Scans were performed in the same laboratory over the same time period for both groups. Intima-media thickness (IMT) was averaged across the common, bulb, and internal carotids. The plaque index summarized degree of focal plaque based on the size and number of plaques throughout both carotid systems.

Results
—Mean IMT was 0.69 mm for premenopausal women and 0.77 mm for postmenopausal women (
P
<0.001). Prevalence of plaque was 25% among premenopausal women and 54% among postmenopausal women (
P
<0.001). In both premenopausal and postmenopausal women, risk factors measured before menopause were associated with carotid atherosclerosis. Premenopausal risk factors independently associated with IMT were higher pulse pressure (
P
<0.001), triglycerides (
P
=0.002), body mass index (
P
<0.001), and study group (a surrogate for both age and menopausal status;
P
<0.001). Premenopausal risk factors independently associated with focal plaque were ever smoking (
P
=0.002), higher pulse pressure (
P
=0.028), higher LDL (
P
=0.003), age at baseline (
P
=0.050), and study group (
P
<0.001).

Conclusions
—Subclinical carotid atherosclerosis can be observed in middle-aged women. Risk factors measured before menopause are clearly associated with subclinical disease measured both concurrently and at 5 to 8 years after menopause.
Feeding Artery Pressure and Venous Drainage Pattern Are Primary Determinants of Hemorrhage From Cerebral Arteriovenous Malformations
Authors: Duong D. Hoang , Young William L. , Vang Meng C. , Sciacca Robert R. , Mast Henning , Koennecke Hans-Christian , Hartmann Andreas , Joshi Shailendra , Mohr J. P. , Pile-Spellman John
Published: June 2011

Purpose
—The purpose of this study was to define the influence of feeding mean arterial pressure (FMAP) in conjunction with other morphological or clinical risk factors in determining the probability of hemorrhagic presentation in patients with cerebral arteriovenous malformations (AVMs).

Methods
—Clinical and angiographic data from 340 patients with cerebral AVMs from a prospective database were reviewed. Patients were identified in whom FMAP was measured during superselective angiography. Additional variables analyzed included AVM size, location, nidus border, presence of aneurysms, and arterial supply and venous drainage patterns. The presence of arterial aneurysms was also correlated with site of bleeding on imaging studies.

Results
—By univariate analysis, exclusively deep venous drainage, periventricular venous drainage, posterior fossa location, and FMAP predicted hemorrhagic presentation. When we used stepwise multiple logistic regression analysis in the cohort that had FMAP measurements (n=129), only exclusively deep venous drainage (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.4 to 9.8) and FMAP (OR, 1.4 per 10 mm Hg increase; 95% CI, 1.1 to 1.8) were independent predictors (
P
<0.01) of hemorrhagic presentation; size, location, and the presence of aneurysms were not independent predictors. There was also no association (
P
=0.23) between the presence of arterial aneurysms and subarachnoid hemorrhage.

Conclusions
—High arterial input pressure (FMAP) and venous outflow restriction (exclusively deep venous drainage) were the most powerful risk predictors for hemorrhagic AVM presentation. Our findings suggest that high intranidal pressure is more important than factors such as size, location, and the presence of arterial aneurysms in the pathophysiology of AVM hemorrhage.
Differences in Cellular Responses to Mitogens in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease
Authors: Yamamoto Mari , Aoyagi Masaru , Fukai Naomi , Matsushima Yoshiharu , Yamamoto Kiyotaka
Published: June 2011

Background and Purpose
—Moyamoya disease is a progressive cerebrovascular occlusive disease affecting primarily children. The etiology remains unknown. We examined the chemotactic and proliferative activities of inflammatory cell products from arterial smooth muscle cells (SMCs) derived from moyamoya patients and compared them with those from control subjects.

Methods
—We used 12 SMC strains from moyamoya patients and eight from control subjects. SMC migration was examined in a micro chemotaxis chamber. DNA synthesis was measured by an immunoperoxidase technique.

Results
—Platelet-derived growth factor (PDGF)-BB markedly stimulated cell migration and DNA synthesis in control SMCs. PDGF-AA stimulated only DNA synthesis in control SMCs. In moyamoya SMCs, PDGF-AA and PDGF-BB stimulated cell migration but not DNA synthesis. Basic fibroblast growth factor had little migratory activity but stimulated DNA synthesis in moyamoya SMCs and control SMCs. Conversely, hepatocyte growth factor stimulated cell migration but not DNA synthesis in moyamoya SMCs and control SMCs. In contrast, interleukin-1β (IL-1β) significantly stimulated the migration and DNA synthesis of control SMCs, while it inhibited moyamoya SMC migration. The levels of IL-1β–induced nitric oxide production did not differ between moyamoya SMCs and control SMCs, suggesting that IL-1β inhibits the migration of moyamoya SMCs through a nitric oxide–independent pathway.

Conclusions
—The differences in responses to PDGF and IL-1 in moyamoya SMCs are involved in the mechanism by which intimal thickening develops in moyamoya disease.
High Levels of Myogenic Tone Antagonize the Dilator Response to Flow of Small Rabbit Cerebral Arteries
Authors: Thorin-Trescases Nathalie , Bevan John A.
Published: June 2011

Background and Purpose
—Pressure and shear stress exerted by flowing blood are two mechanical forces that play a major role in the regulation of vascular tone. We sought to evaluate the interaction between pressure and flow in isolated rabbit cerebral arteries.

Methods
—Responses to intraluminal flow of isolated pressurized rabbit posterior cerebral arteries were investigated at low, medium, and high levels of myogenic tone by setting the luminal pressure at 40, 60, and 80 mm Hg, respectively.

Results
—At both low and medium levels of myogenic tone, flow induced dilation. The response was significantly larger at 40 than at 60 mm Hg. At the high level of myogenic tone, the response to flow consisted of a combination of an initial transient dilation followed by sustained constriction. Flow-induced dilation but not flow-induced constriction response was endothelium dependent. Removal of the endothelium inhibited the dilator response by ≈80%. Flow-induced dilation was inhibited (≈40%) by
N
ω
-nitro-
l
-arginine (100 μmol/L) but not by indomethacin (10 μmol/L). Endothelium removal not only decreased the amplitude of flow-induced dilation but also promoted the appearance of flow-induced constriction at low and medium levels of myogenic tone.

Conclusions
—The intraluminal pressure and in consequence the level of myogenic tone at which flow is applied determine the nature of the response of the smooth muscle cells of the blood vessel wall.
Vascular Smooth Muscle Actin Cytoskeleton in Cerebral Artery Forced Dilatation
Authors: Cipolla Marilyn J. , Osol George
Published: June 2011

Background and Purpose
—We investigated the role of actin polymerization in regulating arterial diameter in response to increasing pressure and modulating forced dilatation of cerebral arteries at pressures above the upper limit of autoregulation.

Methods
—Posterior cerebral arteries (n=12) were isolated and pressurized in a special arteriograph that allowed control of intravascular pressure and measurement of lumen diameter. Intact arteries in the absence (control) or presence of 3.0 μmol/L cytochalasin B (CB), an inhibitor of actin polymerization, were subjected to stepwise increases in pressure from 75 to 200 mm Hg. Lumen diameter was continuously recorded, as was the pressure at which forced dilatation (loss of tone) occurred. After a period of time at 200 mm Hg, pressure was returned to 75 mm Hg and the extent of tone recovery was evaluated.

Results
—Arteries with and without CB developed a similar amount of tone during equilibration at 75 mm Hg: percent tone=27±3% for control versus 29±4% for CB arteries (
P
>0.05). However, arteries in the presence of CB could not withstand pressure as well and underwent FD at significantly lower pressures: 168±5 mm Hg for control versus 142±5 mm Hg for CB arteries (
P
<0.01). The amount of tone that arteries regained after FD when pressure was returned to 75 mm Hg was also less in CB arteries: percent tone=34±3% for control versus 11±2% for CB arteries (
P
<0.01).

Conclusions
—Cytoskeletal integrity appears important for maintaining cerebral arterial diameter during changing intravascular pressure. In addition, the process of actin polymerization may be a significant contributor to development of myogenic tone after forced dilatation.
Bilateral Hemispheric Activation in the Early Recovery of Motor Function After Stroke
Authors: Silvestrini Mauro , Cupini Letizia M. , Placidi Fabio , Diomedi Marina , Bernardi Giorgio
Published: June 2011

Background and Purpose
—Functional recovery after cerebral infarction is a complex phenomenon that depends on various factors. The aim of this study was to investigate changes in cerebral perfusion during motor activity in stroke patients with very early recovery of motor function.

Methods
—We included 9 consecutive patients hospitalized for acute-onset hemiparesis who showed complete functional recovery within 24 hours. CT of the brain showed an ischemic or hemorrhagic cerebral lesion in areas compatible with the symptomatology. Within 36 hours (range, 28 to 36) all patients were examined for the effects of a thumb-to-finger opposition task on cerebral blood flow in the middle cerebral arteries, evaluated by means of bilateral transcranial Doppler ultrasonography. Data were compared with those of 9 healthy subjects matched for age and sex. In patients, the evaluation was repeated 2 to 4 months later.

Results
—A comparable increase in flow velocity (% mean±SD) was observed with respect to baseline in the contralateral middle cerebral artery during motor activity with patients’ normal (8.8±2.0%) and recovered hand (9.7±4.1%) and with both hands of control subjects (10.6±1.4%). In the middle cerebral artery ipsilateral to the hand performing the motor task, the increase in flow velocity was significantly higher (
P
<0.0001) during movement of the recovered hand in patients (8.6±2.7%) than during movement of the normal hand in both patients (2.6±1.6%) and control subjects (1.4±0.7%). In patients, pattern of changes in flow velocity during motor performance remained the same in the second evaluation.

Conclusions
—These observations suggest that areas of the healthy hemisphere can be activated soon after a focal injury and contribute to the positive evolution of a functional deficit in some patients. This phenomenon of ipsilateral activation cannot be considered transient because it is evident months after stroke onset.
Clinical Features of Moyamoya Disease in the United States
Authors: Chiu David , Shedden Peter , Bratina Patti , Grotta James C.
Published: June 2011

Background and Purpose
—We report the clinical features and longitudinal outcome of the largest cohort of patients with moyamoya disease described from a single institution in the western hemisphere. Moyamoya disease in Asia usually presents with ischemic stroke in children and intracranial hemorrhage in adults.

Methods
—Our study population included all patients with moyamoya disease evaluated at a university hospital in Houston, Texas from 1985 through 1995 (n=35). We used Kaplan-Meier methods to estimate individual and hemispheric stroke risk by treatment status (medical versus surgical). Predictors of neurological outcome were assessed.

Results
—The ethnic background of our patients was representative of the general population in Texas. The mean age at diagnosis was 32 years (range, 6 to 59 years). Ischemic stroke or transient ischemic attack was the predominant initial symptom in both adults and children. Of the 6 patients with intracranial hemorrhage, 5 had an intraventricular site of hemorrhage. The crude stroke recurrence rate was 10.3% per year in 116 patient-years of follow-up. Twenty patients underwent surgical revascularization, the most common procedure being encephaloduroarteriosynangiosis. The 5-year risk of ipsilateral stroke after synangiosis was 15%, compared with 20% for medical treatment and 22% overall for surgery.

Conclusions
—Our observations indicate that moyamoya disease may have a different clinical expression in the United States than in Asia, and may demonstrate a trend toward a lower stroke recurrence rate and better functional outcome after synangiosis.
Time Trends in Long-term Survival After Stroke
Authors: Peltonen Markku , Stegmayr Birgitta , Asplund Kjell
Published: June 2011

Background and Purpose
—Stroke mortality rates and case fatality of stroke have declined since the beginning of the 1970s in Sweden, but the incidence of stroke has been stable. The aim of this study was to analyze trends in long-term survival after stroke.

Methods
—Within the framework of the population-based WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project, all acute stroke events were recorded in the age group 25 to 74 years in northern Sweden during the period 1985 to 1994. All first-ever stroke patients were followed for information on vital status (minimum follow-up time was 1 year). Survival time was related to time period of stroke onset, stroke diagnosis, and concomitant diseases.

Results
—Survival times for a total of 6819 first-ever stroke patients (4057 men and 2762 women) were analyzed. Age-adjusted odds ratio for death within 1 year after stroke was 0.70 (95% confidence interval [CI], 0.55 to 0.88) in the period 1993 to 1994 as compared with the period 1985 to 1986 in men and 0.69 (95% CI, 0.53 to 0.90) in women. Corresponding odds ratios were 0.73 in men and 0.70 in women among those who survived the first 28 days. Similar improvements were seen for 3- and 5-year survival. Improvements in survival over time were most marked among patients with ischemic stroke. There was no improvement in survival over time among patients with the most severe deficits at onset.

Conclusions
—Gradually improved survival, both short and long term, was observed during the 10-year study period. The improvements are not explained by changes in known confounding prognostic factors.
An Electrocardiographic Criterion for Diagnosis of Patent Foramen Ovale Associated With Ischemic Stroke
Authors: Ay Hakan , Buonanno Ferdinando S. , Abraham Stephen A. , Kistler J. Philip , Koroshetz Walter J.
Published: June 2011

Background and Purpose
—An M-shaped bifid notch on the ascending branch, or on the zenith, of the R wave in inferior ECG leads (II, III, aVF), so called “crochetage,” is an indicator of ostium secundum atrial septal defects. The pathophysiology underlying this finding remains unknown. A crochetage pattern has not been previously reported in patients with patent foramen ovale (PFO); however, the location of this defect and the secundum atrial septum are similar. The purpose of this study was to determine the prevalence of crochetage in cryptogenic stroke patients with or without PFO.

Methods
—A conservative selection scheme was used to identify patients likely to have had PFO-associated strokes (ie, cryptogenic) and to exclude any structural, functional, or vascular heart disease responsible for ECG changes. All patients had a standard 12-lead ECG. The prevalence of crochetage in each group was determined.

Results
—Sixty consecutive patients were studied (28 with echo-documented PFO and 32 echo-negative control subjects). The crochetage pattern was present in at least 1 inferior limb lead in 10 of 28 PFO patients (36%) and 3 of 32 control subjects (9%) (
P
<0.05). The sensitivity and specificity of the crochetage pattern for diagnosis of PFO in cryptogenic stroke cases were 36% and 91%, respectively; positive predictive value was 77%.

Conclusions
—The finding of an ECG crochetage pattern may help to identify stroke patients with PFO, may help to streamline their diagnostic workup, and may warrant future studies to determine its value in stratifying stroke risk in patients with PFO.
Increased Endothelial Expression of Intercellular Adhesion Molecule-1 in Symptomatic Versus Asymptomatic Human Carotid Atherosclerotic Plaque
Authors: DeGraba Thomas J. , Sirén Anna-Leena , Penix LaRoy , McCarron Richard M. , Hargraves Ronald , Sood Suman , Pettigrew Karen D. , Hallenbeck John M.
Published: June 2011

Background and Purpose
—The mechanisms that cause carotid atherosclerotic plaque to become symptomatic remain unclear. Evidence suggests that mediators of inflammation are not only instrumental in the formation of plaque but may also be involved in the rapid progression of atheromatous lesions leading to plaque fissuring, endothelial injury, and intraluminal thrombosis. Our goal is to determine whether intercellular adhesion molecule-1 (ICAM-1), a known component of the inflammatory pathway, is preferentially expressed on symptomatic versus asymptomatic carotid plaques.

Methods
—Carotid plaques from symptomatic (n=25) and asymptomatic (n=17) patients undergoing carotid endarterectomy with lesions involving >60% stenosis were snap-frozen at the time of surgery. Immunofluorescence studies were performed to measure the percentage of luminal endothelial surface that expressed ICAM-1. The relationships of stroke risk factors, white blood cell count, percent stenosis, and soluble ICAM-1 (sICAM-1) plasma levels to endothelial ICAM-1 expression were investigated.

Results
—An increased expression of ICAM-1 was found in the high-grade regions of symptomatic (29.5%±2.4%, mean±SEM) versus asymptomatic (15.7%±2.7%, mean±SEM) plaques (
P
=0.002) and in the high-grade versus the low-grade region of symptomatic plaques (29.5±2.4, mean±SEM, versus 8.9±1.6;
P
<0.001). Plasma sICAM-1 levels were not predictive of symptomatic disease, and no significant correlation between risk factor exposure and endothelial ICAM-1 expression was found.

Conclusions
—An elevation in ICAM-1 expression in symptomatic versus asymptomatic plaque suggests that mediators of inflammation are involved in the conversion of carotid plaque to a symptomatic state. The data also suggest a differential expression of ICAM-1, with a greater expression found in the high-grade region than in the low-grade region of the plaque specimen.
Reduction of Ischemic Brain Injury by Topical Application of Glial Cell Line–Derived Neurotrophic Factor After Permanent Middle Cerebral Artery Occlusion in Rats
Authors: Kitagawa H. , Hayashi T. , Mitsumoto Y. , Koga N. , Itoyama Y. , Abe K.
Published: June 2011

Background and Purpose
—Glial cell line–derived neurotrophic factor (GDNF) plays important roles in the survival and recovery of some mature neurons under pathological conditions. However, the effect of GDNF in ameliorating ischemic brain injury has not been well documented. Therefore, we investigated a possible effect of GDNF on the changes of infarct size, brain edema, DNA fragmentation, and immunoreactivities for caspases after permanent middle cerebral artery occlusion (MCAO) in rats.

Methods
—For the estimation of ischemic brain injury, we calculated the infarct size of MCA region and also measured the brain water content as edema formation at 24 hours after the MCAO. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin in situ nick labeling (TUNEL) staining was performed for the detection of DNA fragmentation. Immunoreactivities for caspase-1 (ICE), caspase-2 (Nedd-2), and caspase-3 (CPP32) were stained.

Results
—Both infarct size and brain edema after permanent MCAO were significantly reduced by topical application of GDNF (48% and 30% decreases,
P
=0.01). TUNEL staining and immunoreactivities for caspases were markedly induced at 12 hours after permanent MCAO in the vehicle-treated animals. However, the spatial distribution of those immunohistochemically positive cells was dissociative in each caspase. Induction of TUNEL staining and immunoreactivities for caspases-1 and -3 was greatly reduced with GDNF treatment, whereas the reduction of caspase-2 staining was only minimum.

Conclusions
—These data suggest that the reduction of infarct size and brain edema by GDNF was greatly associated with the reduction of DNA fragmentation and apoptotic signals predominantly through caspases-1 and -3 cascades.
Modulation of Basal and Postischemic Leukocyte-Endothelial Adherence by Nitric Oxide
Authors: Gidday Jeffrey M. , Park T.S. , Shah Aarti R. , Gonzales Ernesto R.
Published: June 2011

Background and Purpose
—Recent studies indicate that leukocytes are important contributors to secondary vascular and parenchymal injury after cerebral ischemia. The present study was undertaken to define nitric oxide (NO)−based mechanisms that regulate leukocyte-endothelial interactions in the cerebral vasculature, how these mechanisms are affected by cerebral ischemia, and whether NO-based therapies can affect postischemic leukocyte dynamics.

Methods
—Leukocyte adherence to pial venules of anesthetized newborn piglets was quantified by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during reperfusion after 9 minutes of asphyxia. Nitric oxide synthase (NOS) was inhibited by local window superfusion of
l
-nitroarginine; superfusion of sodium nitroprusside was used to donate NO.

Results
—Local inhibition of NOS under resting conditions increased leukocyte-endothelial adherence 2.2-fold and 3.9-fold over baseline values after 1 hour and 2 hours, respectively; this response was completely blocked by cosuperfusion with
l
-arginine. Cosuperfusion of superoxide dismutase reversed
l
-nitroarginine−induced leukocyte adherence by 89% and 63% at these respective time points. The extent of acute leukocyte adherence elicited by NOS inhibition was similar in magnitude to that observed during the initial 2 hours of reperfusion after asphyxia. Leukocyte adherence was not additionally increased in asphyxic animals treated with
l
-nitroarginine. Sodium nitroprusside robustly inhibited asphyxia-induced leukocyte adherence back to control levels.

Conclusions
—NO exerts a tonic antiadherent effect in the cerebral microcirculation by inactivation of adherence-promoting superoxide radical formation. Cerebral ischemia is associated with an inhibition of NOS or lower levels of NO, which results in leukocyte-endothelial adherence that can be prevented by NO donors. The latter may be useful therapeutically to prevent the purported vascular and parenchymal dysfunction and injury caused by activated leukocytes in ischemic brain.
Protein Kinase C Expression and Activity After Global Incomplete Cerebral Ischemia in Dogs
Authors: Sieber Frederick E. , Traystman Richard J. , Brown Phillip R. , Martin Lee J.
Published: June 2011

Background and Purpose
—Studies suggest that protein kinase C (PKC) activation during ischemia plays an important role in glutamate neurotoxicity and that PKC inhibition may be neuroprotective. We tested the hypothesis that elevations in the biochemical activity and protein expression of Ca
2+
-dependent PKC isoforms occur in hippocampus and cerebellum during the period of delayed neurodegeneration after mild brain ischemia.

Methods
—We used a dog model of 20 minutes of global incomplete ischemia followed by either 6 hours, 1 day, or 7 days of recovery. Changes in PKC expression (Western blotting and immunocytochemistry) and biochemical activity were compared with neuropathology (percent ischemically damaged neurons) by means of hematoxylin and eosin staining.

Results
—The percentage of ischemically damaged neurons increased from 13±4% to 52±10% in CA1 and 24±11% to 69±6% in cerebellar Purkinje cells from 1 to 7 days, respectively. The occurrence of neuronal injury was accompanied by sustained increases in PKC activity (240% and 211% of control in hippocampus and cerebellum, respectively) and increased protein phosphorylation as detected by proteins containing phosphoserine residues. By Western blotting, the membrane-enriched fraction showed postischemic changes in protein expression with increases of 146±64% of control in hippocampal PKCα and increases of 138±38% of control in cerebellar PKCα, but no changes in PKCβ and PKCγ were observed. By immunocytochemistry, the neuropil of CA1 and CA4 in hippocampus and the radial glia in the molecular layer of cerebellum showed increased PKCα expression after ischemia.

Conclusions
—This study shows that during the period of progressive ischemic neurodegeneration there are regionally specific increases in PKC activity, isoform-specific increases in membrane-associated PKC, and elevated protein phosphorylation at serine sites.
Vasopressin Combined With Epinephrine Decreases Cerebral Perfusion Compared With Vasopressin Alone During Cardiopulmonary Resuscitation in Pigs
Authors: Wenzel Volker , Lindner Karl H. , Augenstein Sven , Prengel Andreas W. , Strohmenger Hans U.
Published: June 2011

Background and Purpose
—It is unknown whether a combination of vasopressin and epinephrine may be superior to vasopressin alone by targeting both nonadrenergic and adrenergic receptors.

Methods
—After 15 minutes of cardiac arrest (13 minutes of ventricular fibrillation and 2 minutes of pulseless electrical activity) and 3 minutes of chest compressions, 16 animals were randomly treated with either 0.8 U/kg vasopressin (n=8) or 0.8 U/kg vasopressin combined with 200 μg/kg epinephrine (n=8).

Results
—Comparison of vasopressin with vasopressin and epinephrine at 90 seconds and 5 minutes after drug administration resulted in comparable mean (±SEM) coronary perfusion pressure (54±3 versus 57±5 and 36±4 versus 35±4 mm Hg, respectively), cerebral perfusion pressure (59±6 versus 65±8 and 40±6 versus 39±6 mm Hg, respectively), and median (25th to 75th percentiles) left ventricular myocardial blood flow [116 (81 to 143) versus 108 (97 to 125) and 44 (35 to 81) versus 62 (42 to 74) mL · min
−1
· 100 g
−1
, respectively], but significantly increased (
P
<0.05) total cerebral blood flow [81 (77 to 95) versus 39 (34 to 58) and 50 (43 to 52) versus 28 (16 to 35) mL · min
−1
· 100 g
−1
, respectively]. Return of spontaneous circulation rates in both groups were comparable (vasopressin, 7 of 8; vasopressin and epinephrine, 6 of 8).

Conclusions
—Comparison of vasopressin with vasopressin and epinephrine resulted in comparable left ventricular myocardial blood flow but significantly increased cerebral perfusion.
Effects of a Long-term Hypertension Control Program on Stroke Incidence and Prevalence in a Rural Community in Northeastern Japan
Authors: Iso Hiroyasu , Shimamoto Takashi , Naito Yoshihiko , Sato Shinichi , Kitamura Akihiko , Iida Minoru , Konishi Masamitsu , Jacobs David R. , Komachi Yoshio
Published: June 2011

Background and Purpose
—Although randomized clinical trials have demonstrated the benefit of antihypertensive treatment in preventing stroke, the effectiveness of community-based programs is largely unknown. We investigated long-term community-based prevention activities.

Methods
—In rural northeastern Japan, people aged ≥30 years numbered 3219 in the full intervention community and 1468 in the minimal intervention community in 1965. Systematic blood pressure screening and health education began in 1963. Stroke was registered through 1987.

Results
—More than 80% of people aged 40 to 69 years were screened in both communities in the 1960s. One community charged for screening services after 1968, whereas the other community intensified intervention; subsequently, screening rates and the follow-up of hypertensive individuals declined in the minimal intervention community, especially in men. In men, stroke incidence declined more (
P
<0.001) in the full intervention (42% in the period 1970 to 1975, 53% in the period 1976 to 1981, and 75% in the period 1982 to 1987) than in the minimal intervention community (5% increase, 20% decrease, and 29% decrease, respectively); in women, the stroke incidence declined about 45% to 65% in both communities. Changes in stroke prevalence paralleled those in stroke incidence. Trends in systolic blood pressure levels tend to explain the differential stroke rates in men.

Conclusions
—Delivery of hypertension control services through intensive, free, community-wide screening and health education was effective in prevention of stroke for men in a community.
Migrainous Visual Accompaniments Are Not Rare in Late Life
Authors: Wijman Christine A. C. , Wolf Philip A. , Kase Carlos S. , Kelly-Hayes Margaret , Beiser Alexa S.
Published: June 2011

Background and Purpose
—Questionnaires to elicit symptoms of transient ischemic attacks (TIAs) may detect late-life transient visual symptoms similar to the visual aura of migraine, often without headache. We determined the frequency, characteristics, and stroke outcome of these symptoms in the Framingham Study.

Methods
—During 1971–1989, at biennial examinations, 2110 subjects of the Framingham cohort were systematically queried about the occurrence of sudden visual symptoms.

Results
—Visual migrainous symptoms were reported by 1.23% (26/2110) of subjects (1.33% of women and 1.08% of men). In 65% of subjects the episodes were stereotyped, and they began after age 50 years in 77%. Mean±SD age at onset of the episodes was 56.2±18.7 years. In 58% of subjects the episodes were never accompanied by headaches, and 42% had no headache history. The number of episodes ranged from 1 to 500 and was 10 or more in 69% of subjects. The episodes lasted 15 to 60 minutes in 50% of subjects. Sixty-five percent of the subjects were examined by a study neurologist, and only 19% of them met the criteria of the International Headache Society. Twelve percent of subjects sustained a stroke after the onset of migrainous visual symptoms: a subarachnoid hemorrhage 1 year later, an atherothrombotic brain stem infarct 3 years later, and a cardioembolic stroke 27 years later. In contrast, of 87 subjects with TIAs in the same cohort, 33% developed a stroke (
P
=0.030), two thirds within 6 months of TIA onset.

Conclusions
—Late-life-onset transient visual phenomena similar to the visual aura of migraine are not rare and often occur in the absence of headache. These symptoms appear not to be associated with an increased risk of stroke, and invasive diagnostic procedures or therapeutic measures are generally not indicated.
Plasma Concentrations of Brain Natriuretic Peptide in Patients With Subarachnoid Hemorrhage
Authors: Tomida Mamoru , Muraki Masaaki , Uemura Kenichi , Yamasaki Kenji
Published: June 2011

Background and Purpose
—Hyponatremia after subarachnoid hemorrhage (SAH) is commonly associated with diuresis and natriuresis, but the causes are still controversial. We investigated whether brain natriuretic peptide (BNP) was related to such hyponatremia.

Methods
—Plasma BNP concentrations were measured by immunoradiometric assay in 18 patients at 0 to 2 days (period 1), 7 to 9 days (period 2), and >14 days (period 3) after SAH. Plasma concentrations of antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), and noradrenaline were also measured during period 2.

Results
—The 11 patients with hyponatremia (serum sodium concentration of <135 mEq/L) had much higher plasma BNP concentrations during each period than did healthy controls (
P
<0.05), whereas the 7 patients with normonatremia did not show statistically higher values. In the patients with hyponatremia, the plasma BNP concentration during period 2 was statistically higher than that during periods 1 and 3 (
P
<0.05). The plasma noradrenaline concentration during period 2 was higher in patients with hyponatremia than in those with normonatremia (
P
<0.05), whereas the plasma concentrations of ADH and ANP during period 2 were not statistically different between the hyponatremic and normonatremic patients.

Conclusions
—We conclude that BNP may be related to hyponatremia associated with natriuresis following SAH. The increase of noradrenaline may promote the secretion of BNP.
The Burden of Caregiving in Partners of Long-Term Stroke Survivors
Authors: Reimer W. J. M. Scholte op , de Haan R. J. , Rijnders P. T. , Limburg M. , van den Bos G. A. M.
Published: June 2011

Background and Purpose
—Few data are available on the specific caregiving-related problems of stroke patients’ caregivers and factors that influence the burden of these caregivers. The aim of this study was to describe the level and specific nature of the burden of caregiving as experienced by stroke patients’ partners and to estimate the relative contribution of patient and partner characteristics to the presence of partners’ burden.

Methods
—As part of a multicenter study on quality of care, burden of caregiving was assessed in 115 partners at 3 years after stroke. Explanatory factors of burden were studied in terms of (1) characteristics of patients (sociodemographic status, severity, type, and localization of stroke, disability, handicap, and unmet care demands) and (2) characteristics of partners (age, sex, disability, quality of life, loneliness, amount of care provided, and unmet care demands).

Results
—Partners of stroke patients perceived most caregiving burden in terms of feelings of heavy responsibility, uncertainty about patients’ care needs, constant worries, restraints in social life, and feelings that patients rely on only their care. Multiple regression analysis revealed that a higher level of burden could partly be explained by patients’ disability (
R
2
=14%), but primarily by partners’ characteristics in terms of emotional distress (
R
2
=16%), loneliness (
R
2
=6%), disability (
R
2
=3%), amount of informal care provided (
R
2
=2%), unmet demands for psychosocial care (
R
2
=4%), and unmet demands for assistance in activities of daily living (
R
2
=2%).

Conclusions
—Higher levels of burden are primarily related to partners’ emotional distress and less to the amount of care they provided, or to patients’ characteristics. Sharing responsibilities, helping to clarify the patients’ needs, and getting occasional relief of caregiving may be important in the support of caregivers.