bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital Charges for Stroke Patients
Authors: Alberts Mark J. , Bennett Cynthia A. , Rutledge Valinda R.
Published: June 2011

Background and Purpose
Stroke is a common disease with a yearly cost in the United States of approximately $30 billion. The increasing prevalence of managed care and cost-containment measures may affect the delivery of stroke care now and in the future. This study was performed to determine (1) hospital charges and test utilization for stroke patients and (2) the effectiveness of educational efforts in modifying test utilization and related hospital charges.

Methods
Patients with a diagnosis of stroke who were discharged from either the neurology service or another service of the Department of Medicine (DOM) were identified. Data on test utilization and hospital charges were collected and analyzed. Following this analysis, educational sessions were held in an effort to reduce the use of specific diagnostic tests. The effectiveness of these methods was studied in a second group of stroke patients.

Results
In the baseline period there were 303 stroke patients, of which 262 (86%) were discharged from the neurology service and 41 (14%) were discharged from other services of the DOM. Patients on the neurology service had a lower mean length of stay than patients on the other services of the DOM (9.2 days versus 10.5 days) and lower mean total charges per case ($13 149 versus $15 727), although the respective differences were not statistically significant. Patients on the neurology service were more likely to have both brain CT and MRI performed (82 of 262 patients, 31.3%) than patients on the other services of the DOM (4 of 41, 9.8%,
P
=.005). In addition, patients on the neurology service were more likely to undergo a transthoracic echocardiogram than patients on the other services of the DOM (71.8% versus 53.7%,
P
=.025). After educational sessions, the percentage of stroke patients on the neurology service having both CT and MRI fell from 31.3% to 17.7% (
P
=.005), and the number of stroke patients having a transthoracic echocardiogram fell from 71.8% to 60.3% (
P
=.025). However, the overall charges for stroke patients on the neurology service did not decrease.

Conclusions
Education can be successful in reducing the utilization of and associated charges for specific diagnostic tests for some stroke patients. A multidisciplinary approach to case management, using tools such as care maps, may be necessary to realize significant cost savings in certain groups of stroke patients.
Global Ischemia Impairs ATP-Sensitive K
+
Channel Function in Cerebral Arterioles in Piglets
Authors: Bari Ferenc , Louis Thomas M. , Meng Wei , Busija David W.
Published: June 2011

Background and Purpose
Indirect evidence from studies in which calcitonin gene–related peptide was used indicates that anoxic stress suppresses functioning of cerebral vascular ATP-sensitive K
+
channels. The purpose of this study was to directly examine effects of total global ischemia on cerebral arteriolar dilator responses to activators of ATP-sensitive K
+
channels.

Methods
We measured pial arteriolar diameters in anesthetized piglets using a closed cranial window and intravital microscopy. Baseline diameters were approximately 100 μm. Arteriolar responses to aprikalim (10
−8
and 10
−6
mol/L), a pharmacological activator of ATP-sensitive K
+
channels, and iloprost (0.1 and 1 μg/mL), a physiological activator of these channels, were determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure.

Results
Before ischemia, aprikalim dilated cerebral arterioles by 7±2% at 10
−8
mol/L and by 25±4% at 10
−6
mol/L (n=5). At 1 hour after ischemia, aprikalim did not cause significant dilation at either dose (3±2% at 10
−8
mol/L and 7±4% at 10
−6
mol/L;
P
<.05 compared with corresponding preischemic response). Arteriolar dilation returned toward normal values at 2 and 4 hours. Similar results were found with iloprost. Furthermore, prior treatment with indomethacin (5 mg/kg) preserved normal arteriolar dilation to aprikalim and iloprost after ischemia. In contrast, arteriolar dilator responses to prostaglandin E
2
were intact after ischemia.

Conclusions
Ischemia transiently eliminates cerebral arteriolar dilation to activation of ATP-sensitive K
+
channels; arteriolar responses are suppressed at 1 hour and return toward normal over 2 to 4 hours. In addition, reduced responsiveness can be prevented by prior treatment with indomethacin.
Flow-Related Anaerobic Metabolic Changes in Patients With Severe Stenosis of the Internal Carotid Artery
Authors: van der Grond J. , Eikelboom B.C. , Mali W.P.Th.M.
Published: June 2011

Background and Purpose
We sought to investigate whether the combination of blood flow measurements in the major cerebral arteries and measurements of cerebral metabolism can provide new insight into the hemodynamic effect of carotid lesions in patients with severe stenosis (>70% reduction in diameter) of the internal carotid artery (ICA).

Methods
Fifty-six patients with unilateral severe stenosis of the ICA and 14 control subjects underwent MR imaging,
1
H MR spectroscopy, and MR angiography. Anaerobic metabolic changes were studied by assessing
N
-acetyl aspartate/choline and lactate/
N
-acetyl aspartate ratios in the symptomatic and asymptomatic hemispheres. Quantitative flow was measured in the common carotid arteries (CCAs), the ICAs, the basilar artery, and the middle cerebral arteries (MCAs).

Results
Blood flow was significantly decreased in the CCA, ICA, and MCA on the ipsilateral side compared with the contralateral side. Flow in the basilar artery was increased, whereas flow in the contralateral MCA was decreased compared with control subjects. We found a significant correlation between anaerobic metabolic changes and the reduction in blood flow in the CCA, ICA, and MCA on the ipsilateral side.

Conclusions
This study shows that cerebral metabolism is less impaired in patients with relatively high flow in the major cerebral arteries on the ipsilateral side than in patients with relatively low flow on that side. The combination of MR spectroscopy and MR angiography can be of additional value in the understanding of cerebral hemodynamics and metabolism in patients with vascular disorders.
Magnetic Resonance Imaging White Matter Hyperintensities in Clinically Normal Elderly Individuals
Authors: Schmidt R. , Hayn M. , Fazekas F. , Kapeller P. , Esterbauer H.
Published: June 2011

Background and Purpose
White matter hyperintensities are a common magnetic resonance imaging (MRI) observation in the elderly. They are believed to represent a subclinical form of ischemic brain damage, but the underlying pathophysiological mechanisms are still incompletely understood. We postulated that oxidative mechanisms may favor the development of these changes and therefore correlated their presence and extent with the plasma concentrations of 10 naturally occurring antioxidants.

Methods
We studied 355 clinically normal volunteers 45 to 75 years of age who were randomly selected from the official community register. A 1.5-T MRI of the brain and measurements of the plasma concentrations of antioxidants including zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, alpha- and beta-carotene, retinol, gamma- and alpha-tocopherol, as well as ascorbate were performed in all study participants. White matter hyperintensities were graded as punctate, beginning confluent, and confluent abnormalities.

Results
Punctate, beginning confluent, and confluent white matter abnormalities occurred in 101 (28.5%), 44 (12.4%), and 14 (3.9%) individuals, respectively. Study participants with white matter damage were significantly older and had a higher frequency of arterial hypertension and cardiac disease but lower serum concentrations of total cholesterol. The plasma levels of lycopene and alpha-tocopherol were significantly lower in subjects with early confluent and confluent white matter hyperintensities, while individuals with punctate foci had an antioxidant status similar to those with normal MRI scans. Alpha-tocopherol was the only antioxidant that remained significantly and inversely related to the presence of beginning confluent and confluent white matter changes after adjustment for the between-group differences in age, arterial hypertension, cardiac disease, and cholesterol. The adjusted odds ratio for early confluent and confluent white matter abnormalities was 3.70 (95% CI, 1.69 to 8.10) in the lowest compared with the highest quartile of the alpha-tocopherol concentration. The odds ratio increased to 7.11 (95% CI, 1.63 to 22.84) when quintiles of the alpha-tocopherol level were compared.

Conclusions
These data do not prove a causal relation, but they provide evidence of an association between low plasma concentrations of vitamin E and a higher risk of cerebral white matter disease in elderly normal subjects.
Neurological Outcome in a Porcine Model of Descending Thoracic Aortic Surgery
Authors: Maharajh Gyaandeo S. , Pascoe Edward A. , Halliday William C. , Grocott Hilary P. , Thiessen Darren B. , Girling Linda G. , Cheang Mary S. , Mutch W. Alan C.
Published: June 2011

Background and Purpose
In a porcine model of thoracic aortic cross-clamping (AoXC), we compared the incidence and severity of paraplegia with two surgical techniques: left atrial–femoral artery (LA-FA) bypass (BP group; n=9) and clamp/repair (CR group; n=8). The descending thoracic aorta was clamped near its origin and distal to the third intercostal artery for 30 minutes. The intervening three intercostal arteries were ligated and divided.

Methods
All animals received methohexital anesthesia and were hyperventilated to a Pa
co
2
of 28 to 32 mm Hg. Animals in the CR group received mannitol, and after AoXC, proximal hypertension was controlled with phlebotomy. In the BP group, proximal hypertension was controlled with LA-FA bypass using a centrifugal pump (Biomedicus 520C). Proximal mean arterial pressure, distal mean arterial pressure, central venous pressure, and cerebrospinal fluid pressure were measured; radioactive microspheres were injected at baseline, at AoXC + 5 minutes, at AoXC + 20 minutes, at AoXC off + 5 minutes, and after resuscitation. Neurological function was assessed at 24 hours. The animals were killed, and the spinal cord was removed to determine spinal cord blood flow. Histological cross sections of the lumbar spinal cord were stained with cresyl violet/acid fuchsin and then examined with light microscopy to determine the ratio of altered to total spinal cord neurons.

Results
Fifteen animals survived (one death in each group) and were assessed neurologically at 24 hours after AoXC. Despite better distal perfusion and lumbar spinal cord blood flow in the BP group, during AoXC, and at AoXC off + 5 minutes, there was no significant difference in the severity of spinal cord ischemic injury between groups as assessed neurologically by Tarlov score (
P
=.90, Mann-Whitney
U
test). As well, the ratio of altered to total lumbar spinal cord neurons did not differ between groups (
P
=.24).

Conclusions
In this chronic porcine model, distal circulatory support with LA-FA bypass afforded better distal perfusion and improved lumbar spinal cord blood flow but did not influence the severity of spinal cord ischemic injury when compared with a clamp/repair technique.
Use of a Global Test for Multiple Outcomes in Stroke Trials With Application to the National Institute of Neurological Disorders and Stroke t-PA Stroke Trial
Authors: Tilley Barbara C. , Marler John , Geller Nancy L. , Lu Mei , Legler Julie , Brott Thomas , Lyden Patrick , Grotta James
Published: June 2011

Background
The National Institute of Neurological Disorders and Stroke (NINDS) held a workshop on statistical approaches to analysis of acute stroke trials that have multiple prespecified outcomes. An objective was to plan for statistical analysis of the NINDS t-PA Stroke Trial, a randomized, double-blind, placebo-controlled trial of recombinant tissue plasminogen activator (rt-PA) for patients with acute ischemic stroke. Treatment success was defined as a “consistent and persuasive difference” in the proportion of patients achieving favorable outcomes on the Barthel Index, Modified Rankin Scale, Glasgow Outcome Scale, and National Institutes of Health Stroke Scale. The Data and Safety Monitoring Committee for the trial recommended this outcome because the committee did not believe that a positive result for a single outcome would provide sufficient evidence of efficacy.

Summary of Comment
Workshop participants accepted the global test as a viable approach to testing the primary trial hypothesis. Clinician participants advocated categorizing outcomes as favorable/unfavorable, outcomes more clinically meaningful than continuous outcomes for evaluating a drug with potentially serious side effects. They agreed that a global test was appropriate for ischemic stroke when no single outcome is accepted. Hypothetical, special-case examples illustrate that highly correlated outcomes diminish the power of the global test. NINDS t-PA Stroke Trial data demonstrate the clinical interpretability of the global test.

Conclusions
Workshop participants concluded that a global statistic should be used to test the trial's primary hypothesis accompanied by secondary tests of individual outcomes. Workshop participants recommended familiarizing the clinical/scientific community with the global approach.
Echolucent Carotid Artery Plaques Are Associated With Elevated Levels of Fasting and Postprandial Triglyceride-Rich Lipoproteins
Authors: Grønholdt Marie-Louise Moes , Nordestgaard Børge G. , Nielsen Tina G. , Sillesen Henrik
Published: June 2011

Background and Purpose
Echolucent carotid atherosclerotic plaques are associated with an increased risk of neurological symptoms. Elevated plasma triglycerides is a risk factor for cerebral and coronary infarction. This study examined these individual pathogenetic risk factors to determine whether they were related.

Methods
We included 85 symptomatic patients with at least 40% carotid artery stenosis. Plaque morphology of the relevant artery was evaluated by high-resolution B-mode ultrasonography as echolucent, echo-rich, or intermediate. Fasting and postprandial lipids and lipoproteins were measured before and at hourly intervals for 4 hours after a fatty meal (1 g cream fat per kilogram body weight).

Results
When we compared patients with echolucent plaques to patients with echo-rich or intermediate plaques, the former had higher fasting and postprandial plasma triglycerides (
P
≤.006), higher chylomicron remnants/VLDL cholesterol (
P
=.02) and triglycerides (
P
≤.004), a larger area under the plasma triglyceride curve 0 to 4 hours after a fatty meal, with (AUC
TG−TG 0h
) or without (AUC
TG
) subtraction of fasting levels (
P
=.007 and
P
=.003), a larger body mass index (
P
=.03), and were younger (
P
=.01). Multiple logistic regression analysis found that when age and body mass index were taken into account, fasting plasma and VLDL triglycerides, postprandial chylomicron remnants/VLDL triglycerides, AUC
TG−TG 0h
and AUC
TG
with odds ratios of 4.1, 3.8, 3.0, 2.7, and 4.3, respectively, were independent predictors of an echolucent plaque.

Conclusions
Echolucent carotid artery plaques are associated with elevated levels of triglyceride-rich lipoproteins in the fasting or postprandial state.
Is Impaired Cerebral Vasomotor Reactivity a Predictive Factor of Stroke in Asymptomatic Patients?
Authors: Gur Alexander Y. , Bova Irena , Bornstein Natan M.
Published: June 2011

Background and Purpose
Identification of the subgroup of asymptomatic patients with severe internal carotid artery stenosis and high risk of stroke has important clinical implications. Cerebral vasomotor reactivity provides information regarding intracranial hemodynamic features and might have a prognostic value in predicting cerebrovascular ischemic events, especially in patients with carotid stenosis. The aim of our study was to assess the cerebral vasomotor reactivity in asymptomatic patients with carotid stenosis and evaluate its role in stroke occurrence.

Methods
Cerebral vasomotor reactivity was assessed using transcranial Doppler ultrasonology and the Diamox test (intravenous administration of 1.0 g acetazolamide) in 44 asymptomatic patients with severe (>70%) internal carotid artery stenosis. Patients were followed up prospectively (mean, 2 years).

Results
Cerebral vasomotor reactivity was estimated as good (>40% increase of blood flow velocity in the middle cerebral artery ipsilateral to the carotid stenosis after undergoing the Diamox test) in 23 patients; it was impaired in the other 21. During the follow-up period, the overall annual rate for ipsilateral stokes was 2.3%; it was 7.9% for all ischemic cerebral events. No strokes or transient ischemic attacks occurred in the former group, but there were 7 cerebral ischemic events (2 strokes [1 fatal] and 5 transient ischemic attacks) in the latter group. There was a statistically significant correlation between cerebral ischemic events and impaired cerebral vasomotor reactivity (
P
=.009).

Conclusions
The data of this preliminary study suggest an important role of impaired cerebral vasomotor reactivity in predicting ischemic cerebral events. Preventive vascular surgery might be considered in this high-risk subgroup of asymptomatic patients with severe carotid stenosis.
Assessment of Cerebral Autoregulation Using Carotid Artery Compression
Authors: Smielewski Peter , Czosnyka Marek , Kirkpatrick Peter , McEroy Helen , Rutkowska Helen , Pickard John D.
Published: June 2011

Background and Purpose
A simple method of testing cerebral autoregulation by observing transcranial Doppler changes in middle cerebral artery flow velocity (FV) during a brief ipsilateral carotid artery compression (the transient hyperemic response test) was studied in 11 normal healthy volunteers. The aim of this study was to assess the reliability of the method and to compare derived autoregulatory indices with those of a standard noninvasive test of autoregulation, Aaslid's leg-cuff test.

Methods
Volunteers were subjected to repeated carotid compressions and leg-cuff tests at different levels of CO
2
. Hypercapnia was induced using inhalation of a mixture of 5% CO
2
in air. Hypocapnia was induced by moderate hyperventilation. To assess the influence of the duration of carotid compression, a series of carotid compressions lasting 3, 4, 5, 7, and 9 seconds were performed in random sequence. Monitored parameters included ipsilateral FV, end-tidal CO
2
, and arterial blood pressure. The transient hyperemic response ratio (THRR), calculated as the maximum increase of FV divided by baseline values after release of the carotid compression, was taken as the autoregulation index. This index was compared with the rate of autoregulation index derived from the leg-cuff test.

Results
Both tests were significantly associated with end-tidal CO
2
(ANOVA,
P
<.000001 for both carotid compression and cuff test). There was a linear correlation between THRR and autoregulation index (
r
=.86). However, the reproducibility of the THRR was more consistent than for the autoregulation index from single tests (13% versus 46%, respectively;
P
<.0001). Although the influence of the duration of carotid compression on THRR values was significant for carotid compressions lasting up to 5 seconds, there was no relation to the relative magnitude of FV drop during the compression.

Conclusions
Brief (>5 seconds) carotid artery compression provides an index of cerebral autoregulation that is reproducible and is affected by CO
2
tension in a fashion similar to autoregulatory indices derived from a standard leg-cuff test. The simplicity of the method provides a potentially useful addition to other noninvasive autoregulation tests for clinical assessments, particularly when repeated measurements are required.
Acute Infection as a Risk Factor for Ischemic Stroke
Authors: Bova I.Y. , Bornstein N.M. , Korczyn A.D.
Published: June 2011

Background and Purpose
Prior studies have demonstrated that infections might precipitate ischemic strokes (IS), but the role of infection as a risk factor remains unclear. We conducted a case-control study to investigate this issue.

Methods
Consecutive patients (n=182) with acute IS were examined within 48 hours after admission to our center. A history of acute infections within 2 months before the IS was assessed by means of a specially designed questionnaire that was also given to a control group consisting of 194 consecutive patients who were seen in our outpatient clinic and had suffered IS at least 6 months previously.

Results
The prevalence of acute infection in the study group was significantly higher (44193/=24.2%) than in the control group (19193/=9.7%; odds ratio, 2.93; 95% confidence interval, 1.64 to 5.26;
P
=.0002) and infection occurred mostly within 1 week before the IS (41/44). Neither the severity of the IS nor the type of the infection was significantly different in patients and control subjects.

Conclusions
Acute infections of different types constitute a risk factor for IS, particularly within 1 week of the event. However, the severity of the stroke is not related to this factor.
Zinc Protoporphyrin, Zinc Ion, and Protoporphyrin Reduce Focal Cerebral Ischemia
Authors: Zhao Yong-Jie , Yang Guo-Yuan , Domino Edward F.
Published: June 2011

Background and Purpose
Zinc protoporphyrin pretreatment protects against temporary focal ischemic brain injury in rats. However, it is not known whether the zinc or the protoporphyrin portion of zinc protoporphyrin has effects on focal cerebral ischemia. Hence, all three agents were compared with regard to infarct size and edema in a rat model of middle cerebral artery occlusion.

Methods
Four groups of adult male Sprague-Dawley rats were subjected to 2 hours of temporary middle cerebral artery occlusion followed by 22 hours of reperfusion. Each group was pretreated 30 minutes before middle cerebral artery occlusion with 0.9% NaCl, and then three groups were given equimolar doses of zinc protoporphyrin, zinc chloride, or protoporphyrin, respectively. Regional cerebral blood flow in the ischemic cortex was monitored with a laser Doppler flowmeter. Cerebral infarct size, brain water content, and ion content were measured 24 hours after the onset of occlusion.

Results
Regional cerebral blood flow during middle cerebral artery occlusion was approximately 9.2% to 13% of baseline in all four groups. Brain water content in the infarcted zone after temporary focal ischemia in control, zinc protoporphyrin, zinc chloride, and protoporphyrin groups was 85.7%, 80.6%, 85.6%, and 81.4%, respectively. Brain sodium content in the same areas in all four groups paralleled the water content. Infarct size in the controls and groups treated with zinc protoporphyrin, zinc, and protoporphyrin was 25.6%, 7.2%, 7.6%, and 7.2%, respectively. Compared with the control group, the infarct volume in all three treated groups was significantly reduced (
P
<.05).

Conclusions
The present results indicate that zinc protoporphyrin, but also zinc and protoporphyrin, contribute to brain-protective effects when administered early in a temporary focal ischemia model. Zinc chloride reduced infarct size but not edema formation when compared with zinc protoporphyrin and protoporphyrin. Zinc ion in vivo has brain-protective effects, confirming in vitro studies previously reported by some but contrary to reports of others. Blood versus brain neuropil and cell body concentrations of zinc ion need to be studied in the future to define the precise role of zinc in the complex mechanisms involved in brain ischemia.
Regulation of Brain Capillary Endothelial Thrombomodulin mRNA Expression
Authors: Tran Nam D. , Wong Vicky L.Y. , Schreiber Steven S. , Bready James V. , Fisher Mark
Published: June 2011

Background and Purpose
Endothelial cells regulate hemostasis in part via expression of thrombomodulin, a potent anticoagulant protein. The purpose of this study was to analyze brain capillary endothelial cell expression of thrombomodulin mRNA.

Methods
Bovine brain capillary endothelial cells were grown in a blood-brain barrier model in which endothelial cells form capillary-like structures. In situ hybridization and polymerase chain reaction (PCR) were used to examine thrombomodulin expression. Endothelial cells were then cocultured with astrocytes. We examined both coculture and monoculture preparations for γ-glutamyl transpeptidase (GGTP), a marker of the blood-brain barrier. We then used quantitative-competitive PCR to compare thrombomodulin expression in endothelial monocultures and astrocyte-endothelial cocultures after 1 and 7 days of culture.

Results
Both in situ hybridization and PCR studies demonstrated thrombomodulin mRNA expression by endothelial cells. During 1 week of astrocyte-endothelial coculture, there was (1) progressive association of astrocytes with capillary-like structures and (2) expression of GGTP; endothelial monocultures did not express GGTP. There was no significant difference in thrombomodulin mRNA expression for cocultures versus monocultures after 1 day. After 1 week, however, astrocyte-endothelial cocultures had markedly decreased thrombomodulin mRNA compared with monocultures (9±2 versus 189±62 pg/mL;
P
<.025). This thrombomodulin mRNA decrease thus occurred when elements of the blood-brain barrier phenotype were demonstrable, ie, when astrocyte association with capillary-like structures was maximal and when GGTP was expressed in cocultures.

Conclusions
These findings indicate astrocyte regulation of thrombomodulin mRNA expression in vitro and suggest an important role for the blood-brain barrier in the regulation of thrombomodulin.
Thickening of the Carotid Wall
Authors: O’Leary Daniel H. , Polak Joseph F. , Kronmal Richard A. , Savage Peter J. , Borhani Nemat O. , Kittner Steven J. , Tracy Russell , Gardin Julius M. , Price Thomas R. , Furberg Curt D.
Published: June 2011

Background and Purpose
We investigated the relationships between prevalent coronary heart disease (CHD), clinically manifest atherosclerotic disease (ASD), and major established risk factors for atherosclerosis and intima-media thickness (IMT) in the common carotid arteries (CCA) and internal carotid arteries (ICA) separately and in combination in older adults. We wished to determine whether a noninvasive measurement can serve as an indicator of clinically manifest atherosclerotic disease and to determine which of the two variables, CCA IMT or ICA IMT, is a better correlate.

Methods
IMT of the CCA and ICA was measured with duplex ultrasound in 5117 of 5201 individuals enrolled in the Cardiovascular Health Study, a study of the risk factors and the natural history of cardiovascular disease in adults aged 65 years or more. Histories of CHD, peripheral arterial disease, and cerebrovascular disease were obtained during baseline examination. Risk factors included cholesterol levels, cigarette smoking, elevated blood pressure, diabetes, age, and sex. Relationships between risk factors and IMT were studied by multiple regression analysis and canonical variate analysis. Prediction of prevalent CHD and ASD by IMT measurements in CCAs and ICAs were made by logistic regression, adjusting for age and sex.

Results
IMT measurements of the CCAs and ICAs were greater in persons with CHD and ASD than those without, even after controlling for sex (
P
<.001). IMT measurements in the ICA were greater than those in the CCA. Risk factors for ASD accounted for 17% and 18% of the variability in IMT in the CCA and ICA, respectively. These same risk factors accounted for 25% of the variability of a composite measurement consisting of the sum of the ICA IMT and CCA IMT. The ability to predict CHD and ASD was greater for ICA IMT (odds ratio [confidence interval]: 1.36 [1.31 to 1.41] and 1.35 [1.25 to 1.44], respectively) than for CCA IMT (1.09 [1.05 to 1.13] and 1.17 [1.09 to 1.25]).

Conclusions
Whereas CCA IMT is associated with major risk factors for atherosclerosis and existing CHD and ASD in older adults, this association is not as strong as that for ICA IMT. The combination of these measures relates more strongly to existing CHD and ASD and cerebrovascular disease risk factors than either taken alone.
Reduced Heart Rate Variability After Right-Sided Stroke
Authors: Naver Hans K. , Blomstrand Christian , Wallin B. Gunnar
Published: June 2011

Background and Purpose
Recently, asymmetries have been demonstrated in skin sudomotor and vasomotor function after unilateral cerebral lesions. The present study was performed to determine whether other bedside tests reflecting sympathetic and parasympathetic cardiovascular functions would reveal differences with respect to the side of cerebrovascular lesions.

Methods
Heart rate variability during deep breathing as well as blood pressure and heart rate changes during tilt and isometric handgrip was measured in a group of patients with a monofocal stroke and compared with similar data from age-matched patients with transient ischemic attack and healthy control subjects.

Results
Compared with left-sided stroke and with the control subjects, stroke location on the right side was associated with a reduced respiratory heart rate variability (
P
>.01), a reflex mainly under parasympathetic control. In contrast, reflexes mainly reflecting peripheral sympathetic function were equal for right- and left-sided lesions.

Conclusions
Since an imbalance in cardiac autonomic innervation may be crucial for the generation of cardiac arrhythmias and since reduced heart rate variability has been associated with increased mortality, the findings suggest that the risk of sudden death may be correlated with lateralization and location of the brain infarct after stroke.
Generalized Anxiety Disorder in Stroke Patients
Authors: Åström Monica
Published: June 2011

Background and Purpose
This prospective study examined the prevalence and longitudinal course of generalized anxiety disorder (GAD) after stroke and its comorbidity with major depression over time. The contributions of lesion characteristics, functional impairment, and psychosocial factors to the development of GAD after stroke were studied.

Methods
In a population-based cohort of 80 patients with acute stroke, we assessed GAD and comorbid major depression, functional ability, and social network at regular time points over 3 years. Cerebral atrophy and brain lesion parameters were determined from CT scans performed at the acute stage and after 3 years.

Results
The prevalence of GAD after stroke was 28% in the acute stage, and there was no significant decrease through the 3 years of follow-up. At 1 year, only 23% of the patients with early GAD (0 to 3 months) had recovered; those not recovered at this follow-up had a high risk of a chronic development of the anxiety disorder. Comorbidity with major depression was high and seemed to impair the prognosis of depression. At the acute stage after stroke, GAD plus depression was associated with left hemispheric lesion, whereas anxiety alone was associated with right hemispheric lesion. Cerebral atrophy was associated with both depression and anxiety disorder late but not early after stroke. Dependence in activities of daily living and reduced social network were associated with GAD at all follow-up periods except at the acute stage.

Conclusions
GAD after stroke is a common and long-lasting affliction that interferes substantially with social life and functional recovery. There is a differentiation of factors implicated in its development based on the period of time since the stroke event.
Evaluation of Extracranial Vertebral Artery Dissection With Duplex Color-Flow Imaging
Authors: Bartels Eva , Flügel K.A.
Published: June 2011

Background and Purpose
We describe the diagnostic potential of duplex color-flow imaging in the evaluation of extracranial vertebral artery dissection.

Methods
Twenty patients with 24 extracranial vertebral artery dissections (four bilateral) were examined with duplex ultrasonography over a period of 6 years. Color-flow imaging was carried out in 16 of these patients. In 15 patients (75%), the dissection was temporally related to trauma. Angiography was available in 18 patients, confirming the diagnosis.

Results
In 15 patients, the diagnosis was primarily established with ultrasonography. Five patients with a dissection were referred for follow-up color-flow examinations. Six vertebral arteries were dissected at the origin or in the proximal V1 segment, one in the distal V2 segment, and one at the atlas loop. In contrast to other studies, the most frequent localization of the dissection in our patients was the region between the V1 and V2 segments (n=16), where the most typical dissection site was the entrance of the artery into the transverse foramen of the C6 vertebra (n=11). Typical ultrasonographic findings were irregular stenosis, dissecting membrane with true and false lumen, localized increase in diameter of the artery, pseudoaneurysm, intramural hematoma, and tapering stenosis with distal occlusion. In follow-up examination, a good regression of pathological findings was found in 17 dissections (70.8%). Two occlusions were completely recanalized.

Conclusions
Extracranial vertebral artery dissections can be diagnosed noninvasively with duplex color-flow imaging. It is therefore a useful method for early diagnosis and follow-up examination.
Heparin Reduces Neurological Impairment After Cerebral Arterial Air Embolism in the Rabbit
Authors: Ryu Keon Hee , Hindman Bradley J. , Reasoner Daniel K. , Dexter Franklin
Published: June 2011

Background and Purpose
Neurological injury after cerebral air embolism may be due to thromboinflammatory responses at sites of air-injured endothelium. Because heparin inhibits multiple thromboinflammatory processes, we hypothesized that heparin would decrease neurological impairment after cerebral air embolism.

Methods
To first establish a dose of air that would cause unequivocal neurological injury, anesthetized New Zealand White rabbits received either 0, 50, 100, or 150 μL/kg of air into the internal carotid artery (n=5 in each group). One hour later, anesthesia was discontinued. Animals were neurologically evaluated at 24 hours with the use of a scale ranging from 0 (normal) to 97 (coma) points. In a subsequent experiment, anesthetized rabbits received either heparin (n=17) or saline (n=15) 5 minutes before air injection (150 μL/kg). Heparin was given as a 200-IU/kg bolus and followed by a constant infusion of 75 IU · kg
−1
· h
−1
for 2 hours. Equal volumes of saline were given to control rabbits. Two hours later, anesthesia was discontinued. Animals were neurologically evaluated 24 hours after air embolism.

Results
There was a monotonic relationship between dose of air and severity of neurological impairment at 24 hours (
P
=1.1×10
−7
). Animals receiving 150 μL/kg of air were unequivocally injured (score, 60±16). In the second experiment, heparin animals had significantly less neurological impairment at 24 hours (34±14) than saline controls (52±8) (
P
=.0013).

Conclusions
When given prophylactically, heparin decreases neurological impairment caused by severe cerebral arterial air embolism.
Aminoguanidine Ameliorates and
l
-Arginine Worsens Brain Damage From Intraluminal Middle Cerebral Artery Occlusion
Authors: Zhang Fangyi , Casey Robyn M. , Ross M. Elizabeth , Iadecola Costantino
Published: June 2011

Background and Purpose
We studied whether the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine reduces focal cerebral ischemic damage in a relatively noninvasive stroke model in which the rat middle cerebral artery (MCA) is occluded using an intravascular filament.

Methods
In rats anesthetized with halothane, a nylon filament was advanced into the internal carotid artery until its tip occluded the origin of the MCA. The filament was left in place for 2 hours and then withdrawn. Twenty-four hours later, rats received intraperitoneal injections of aminoguanidine (100 mg/kg BID; n=7), aminoguanidine+
l
-arginine (300 mg/kg QID; n=7),
l
-arginine alone (n=6),
d
-arginine alone (n=6), or vehicle (n=10). Drugs were administered for 3 consecutive days. Infarct volume was determined by image analysis in thionin-stained brain sections 4 days after ischemia. iNOS mRNA was detected with the use of reverse transcription polymerase chain reaction.

Results
Cerebral ischemia led to iNOS mRNA expression in the affected brain 48 hours after induction of ischemia. Administration of aminoguanidine reduced neocortical infarct volume by 26% (
P
<.05 versus vehicle, ANOVA and Tukey’s test), a reduction that was antagonized by coadministration of
l
-arginine (
P
>.05 versus vehicle). Administration of
l
-arginine alone, but not
d
-arginine, enlarged the infarct by 29% (
P
<.05). Aminoguanidine or
l
-arginine did not influence the increase in water content in the postischemic brain, indicating that the effect on infarct volume is not related to modulation of ischemic edema.

Conclusions
These results demonstrate that cerebral ischemia is also associated with iNOS expression in a minimally invasive model of transient MCA occlusion and that iNOS inhibition reduces focal ischemic damage. The findings support the hypothesis that nitric oxide produced by iNOS contributes to ischemic brain damage and that inhibition of iNOS may be a valuable tool in the management of cerebral ischemia.
DNA Damage and Repair in Central Nervous System Injury
Authors: Chopp Michael , Chan Pak H. , Hsu Chung Y. , Ellen Cheung Mary , Jacobs Thomas P.
Published: June 2011

Background and Purpose
DNA damage and repair are areas of research with important implications for stroke and cerebral trauma. DNA damage is present in central nervous system (CNS) injury, and defects in repair mechanisms are associated with neurodegenerative disease.

Methods
A workshop,
DNA Damage and Repair in CNS Injury
, was organized by the National Institute of Neurological Disorders and Stroke in Bethesda, Md, on September 11, 1995. The objective of this workshop was to promote inquiry and to foster application of research in DNA damage and repair after stroke and trauma.

Results
The participants discussed the connection between the fields of DNA damage and repair and stroke and trauma and identified gaps in knowledge to be filled to expand research of DNA damage and repair in CNS injury. Specific recommendations were made targeting research opportunities in the areas of DNA repair and damage in stroke and trauma.

Conclusions
Research in the science of DNA injury and repair will likely provide new and important information on mechanisms of cell damage and provide opportunities for the development of novel and effective therapies to reduce CNS injury in stroke and trauma.
Investigating the Relationship Between Stroke and Obstructive Sleep Apnea
Authors: Dyken Mark E. , Somers Virend K. , Yamada Thoru , Ren Zong-Ying , Zimmerman M. Bridget
Published: June 2011

Background and Purpose
We aimed to prospectively determine whether the incidence of obstructive sleep apnea in patients with recent stroke was significantly different from that of a sex- and age-matched control group with no major medical problems.

Methods
We prospectively performed overnight polysomnography in 24 patients with a recent stroke (13 men and 11 women; mean age [±SD], 64.6±10.4 years) and 27 subjects without stroke (13 men and 14 women; mean age, 61.6±8.8 years). Patients with either ischemic or hemorrhagic stroke were entered into this study. Polysomnographic evaluations were performed within approximately 2 to 5 weeks after each patient’s stroke.

Results
Obstructive sleep apnea was found in 10 of 13 men with stroke (77%) and in only 3 of 13 male subjects without stroke (23%) (
P
=.0169). Seven of 11 women with stroke (64%) had obstructive sleep apnea, while only 2 of 14 female subjects without stroke (14%) had obstructive sleep apnea (
P
=.0168). For men with stroke, the mean apnea/hypopnea index (±SE) was 21.5±4.2 events per hour, while for male subjects without stroke it was 4.8±1.8 events per hour (
P
=.0014). For women with stroke the mean apnea/hypopnea index was 31.6±8.8 events per hour, while for female subjects without stroke it was 2.9±1.6 events per hour (
P
=.0024). The 4-year mortality for patients with stroke was 20.8%. All patients with stroke who died had obstructive sleep apnea.

Conclusions
Patients with stroke have an increased incidence of obstructive sleep apnea compared with normal sex- and age-matched control subjects. Hypoxia and hemodynamic responses to obstructive sleep apnea may have predisposed these patients to stroke.
Microthromboemboli in Acute Infarcts
Authors: Heye Norbert
Published: June 2011

Background and Purpose
We investigated the distribution and frequency of microthromboemboli (MTE) in acute infarcts in humans and determined whether MTE in the contralateral circulation resulted in histological changes.

Methods
Forty patients dying within the first month after unilateral infarct were investigated. Infarct etiology was determined mainly on the pathological findings. Whole brain sections from the region of maximal necrosis were stained for fibrin. Fibrin-containing MTE were transferred to a schematic drawing and counted. Sections from 20 patients without infarcts served as controls.

Results
Infarct sections had significantly more MTE than controls. Infarcts of thrombotic (n=6) and thromboembolic (n=21) origin had more MTE than infarcts of embolic origin (n=13). Thromboembolic infarcts had the highest number of MTE within the region assumed to be the ischemic penumbra, other arterial territories, and the contralateral hemisphere. Patients with large infarcts and those with short clinical courses had a higher number of MTE. Sixteen patients had recent micronecroses in the contralateral hemisphere.

Conclusions
There seems to be a pattern of MTE in acute infarcts that is dependent on cause, size, and clinical duration. Our findings of contralateral micronecroses emphasize that acute infarcts may result in more widespread cerebral injury than clinically expected. Given the many variables influencing stroke and death in humans, the results have to be interpreted with caution.
Variability in Measurement of Extracranial Internal Carotid Artery Stenosis as Displayed by Both Digital Subtraction and Magnetic Resonance Angiography
Authors: Young G.R. , Humphrey P.R.D. , Nixon T.E. , Smith E.T.S.
Published: June 2011

Background and Purpose
The degree of stenosis in the extracranial internal carotid artery helps predict the risk of an individual suffering subsequent cerebrovascular ischemic events. Different techniques have evolved to measure stenosis from angiograms, leading to some confusion and a call for the adoption of a single technique. To help choose the most reliable technique, this study assessed observer variability in reporting carotid stenosis for four different techniques, from both digital subtraction (DSA) and MR angiograms (MRA). Three of the techniques used caliper measurements; the fourth was the visual impression of stenosis.

Methods
From a total of 137 angiograms, caliper measurements were possible on 105 DSAs and 74 MRAs. Measurements from these angiograms were made by two independent observers on two separate occasions to assess interobserver and intraobserver variation in reporting.

Results
For DSA, the variability in reporting and the number of clinically significant differences arising as a result were similar for each of the four techniques. While the typical measurement errors for each of the techniques studied were on the order of ±5%, each technique produced some sizable individual differences for the same angiogram, with resultant wide 95% limits of agreement. Observer variability for reporting MRA was generally a little greater than for DSA. Compared with the caliper techniques, the visual impression of stenosis technique performed well, particularly for MRA.

Conclusions
Although observer variability in reporting can be considerable, no important differences were found among the different techniques widely used for measuring carotid stenosis.
Subarachnoid Injections of Lysed Blood Induce the
hsp70
Stress Gene and Produce DNA Fragmentation in Focal Areas of the Rat Brain
Authors: Matz Paul , Weinstein Philip , States Bradley , Honkaniemi Jari , Sharp Frank R.
Published: June 2011

Background and Purpose
Most experimental studies of subarachnoid hemorrhage have demonstrated little histological evidence of injury. In the present study we examined both the expression of the
hsp70
heat-shock gene, a molecular marker of reversible neuronal injury, and DNA fragmentation, a marker of irreversible cell injury and death.

Methods
Lysed blood, whole blood, oxyhemoglobin, bovine serum albumin, and saline were injected into the cisterna magna of adult rats. The induction of hsp70 mRNA and HSP70 heat-shock protein was assessed with the use of in situ hybridization and immunocytochemistry, respectively. Fragmentation of genomic DNA was studied by DNA nick end-labeling with the use of terminal deoxynucleotidyl transferase and biotinylated dATP.

Results
Expression of the
hsp70
gene was not induced in the brains of rats injected with whole blood, oxyhemoglobin, bovine serum albumin, or saline. Lysed blood injections, however, induced hsp70 mRNA at 6 and 24 hours in the cerebellar hemispheres and in focal regions of the basal forebrain. HSP70 protein was induced by 24 hours and persisted for at least 4 days in the same regions. HSP70 protein was localized to patches of glial cells and occasional neurons in the forebrain. In the cerebellum HSP70 was localized to Bergmann glial cells, granule cells, molecular layer stellate cells, and occasional Purkinje cells. DNA nick end-labeling showed patches of labeled cells in the basal forebrain that occurred in the same regions that hsp70 mRNA was induced.

Conclusions
The results demonstrate focal stress gene induction and DNA fragmentation after subarachnoid hemorrhage. It is hypothesized that the focal areas of hsp70 induction may reflect ischemic injury due to vasospasm produced by lysed blood and/or injury mediated by direct toxic effects of the lysed blood. The hsp70 induction and DNA nick end-labeling in the same regions suggests that lysed blood produces a spectrum of injury from HSP70 protein-labeled, reversibly injured cells to dead cells with fragmented DNA. Induction of the
hsp70
stress gene and DNA nick end-labeling may be useful for evaluating the causes of injury, the spectrum of injury, and potential pharmacological therapies in experimental models of subarachnoid hemorrhage.
Platelet-Activating Factor in Brain Regions After Transient Ischemia in Gerbils
Authors: Nishida Keiji , Markey S.P.
Published: June 2011

Background and Purpose
Platelet-activating factor (PAF) has been reported to be an active mediator in ischemic brain damage on the basis of indirect pharmacological data from PAF antagonists. The direct measurement of PAF in neuronal tissues has not been reported previously in analogous animal models. We have examined regional brain PAF concentration changes during the reperfusion period after ischemia in gerbils to obtain direct evidence for the involvement of PAF with ischemic brain damage and reported gas chromatography/mass spectrometry (GC/MS) methods of PAF quantitative analysis in brain tissues.

Methods
After transient (10 minutes) ischemia followed by controlled periods (0 to 96 hours) of reperfusion and recovery, regional PAF concentrations were determined in gerbil brain tissue. Quantitative analysis of PAF in brain regions is performed using an electron-capture negative chemical ionization GC/MS method, modified for brain tissue.

Results
The level of PAF was increased significantly and maximally in hippocampus (211%), cortex (168%), and thalamus (169%) after 1 hour of reperfusion. In contrast, there were no significant changes of PAF in any brain region from 6 hours to 96 hours after reperfusion.

Conclusions
PAF is increased in gerbil brain in response to ischemia at early stages of reperfusion. PAF increases could contribute to the onset and progress of ischemic neuropathology.