bluuebunny/crossref_metadata_2025 huggingface dataset:
The Epidemiology of Stroke in Native Americans
Authors: Gillum Richard F.
Published: June 2011

Background and Purpose
Because of the paucity of published information, this report seeks to better characterize the pattern of stroke occurrence and risk factors among Native Americans in the United States.

Methods
Data from the US Vital Statistics System and two National Health and Nutrition Examination Surveys were analyzed.

Results
Stroke was a leading cause of death among US Native Americans in 1990. In persons aged 45 and over, stroke was the cause of 6% of deaths in Native Americans and 7% of deaths in whites. The percentage of stroke deaths due to hemorrhagic stroke was higher in Native Americans than whites. In 1988 through 1990, stroke death rates were similar in Native Americans and whites under age 65 but lower in Native Americans at ages 65 years and over. High prevalence of diabetes, smoking, and obesity may contribute to stroke mortality in Native Americans.

Conclusions
Targeted research, innovative analyses of existing data, and use of ongoing surveys and the Census should be considered in the study of the epidemiology of stroke, other leading causes of death, and risk factors in Native Americans. Continued hypertension detection and treatment efforts are needed for Native Americans as for other groups. Smoking cessation and prevention should receive high priority in Native American populations.
Early Determination of Neurological Outcome After Prehospital Cardiopulmonary Resuscitation
Authors: Berek Klaus , Lechleitner Peter , Luef Gerhard , Felber Stephan , Saltuari Leopold , Schinnerl Adolf , Traweger Christian , Dienstl Franz , Aichner Franz
Published: June 2011

Background and Purpose
Although there are various methods of determining neurological prognosis after cardiopulmonary resuscitation, the final outcome of patients often remains unclear for quite a long time.

Methods
We investigated 30 consecutively admitted patients who had been successfully resuscitated by the team of the local mobile intensive care unit after cardiac arrest. Determinations of the period of anoxia and of the cardiopulmonary resuscitation time, clinical investigation, echocardiography, electroencephalography, evoked potentials, magnetic resonance imaging, and magnetic resonance spectroscopy were performed.

Results
Demonstration of brain lactate in proton magnetic resonance spectroscopy (
P
<.01) and absent N20 waves in short-latency somatosensory evoked potentials (
P
<.01) proved to be significant in terms of a poor prognosis. Correlations between both duration of anoxia and cardiopulmonary resuscitation time and neurological outcome could be shown as well (both
P
<.05).

Conclusions
Proton magnetic resonance spectroscopy and short-latency evoked potentials are of great benefit in the prognostic evaluation after cardiopulmonary resuscitation.
Effects of Interstate Migration on the Geographic Distribution of Stroke Mortality in the United States
Authors: Lanska Douglas J. , Peterson Patrick M.
Published: June 2011

Background and Purpose
This study examines the effects of lifetime net interstate migration on the geographic distribution of stroke mortality in the United States.

Methods
National Center for Health Statistics and Bureau of the Census data were used to map the geographic distribution of age-adjusted, race-, and race/sex-specific stroke mortality rates by interstate migration status for natives, outmigrants, nonmigrants, inmigrants, and residents in the United States for 1979 to 1981.

Results
High age-adjusted stroke mortality rates were significantly clustered in the southeastern United States for both whites and blacks; in addition, for whites, low-rate states were concentrated in some Mountain and northeastern states. Migrant status did not change this large-scale pattern, but individual states showed significant migration effects, which varied in magnitude and direction. Among whites, states that benefited from migration, with markedly lower stroke mortality rates among residents than natives, included Arizona, Colorado, District of Columbia, and Florida, whereas states that suffered from migration included California, Idaho, Montana, North Dakota, Nevada, and Oklahoma. Among blacks, only Colorado showed an apparent large benefit from migration, whereas 21 states suffered from migration.

Conclusions
Although the overall large-scale spatial distribution of resident stroke mortality rates cannot be explained by migration effects, some individual states had rates that were strongly influenced by migration. Patterns of mortality among migrant groups in Sun Belt retirement destination states probably result from differential selection effects for retirement migration in older adults. Patterns of mortality for black migrants to the North are probably influenced by “carryover” effects from their origin states.
Does Arterial Recanalization Improve Outcome in Carotid Territory Stroke?
Authors: von Kummer Rüdiger , Holle Rolf , Rosin Ludger , Forsting Michael , Hacke Werner
Published: June 2011

Background and Purpose
We sought to determine whether early (<8 hours) or delayed (8 to 24 hours) recanalization after stroke may be an independent variable in the improvement of clinical outcome in patients with occlusion of the middle cerebral artery.

Methods
We prospectively studied 77 patients by combined Scandinavian Stroke Scale score at admission, repeated computed tomography and angiography before and after thrombolytic treatment at <8 hours after stroke onset, and transcranial Doppler ultrasound 24 hours later. We tested an association between clinical and neuroradiological baseline characteristics, recanalization, and outcome as assessed by the modified Rankin Scale 4 weeks after stroke and determined the effect of recanalization on mortality and good outcome (Rankin Scale grades 0 to 3) by multiple logistic regression analyses.

Results
Recanalization rates at 8 and 24 hours after stroke correlated with sites of occlusion (middle cerebral artery branch, 73% and 73%; trunk, 27% and 38%, respectively; intracranial internal carotid artery bifurcation, 14% and 14%;
P
=.002), collaterals (good, 43% and 51%, respectively; scarce, 17% and 19%, respectively;
P
=.01), and Scandinavian Stroke Scale score at admission (
P
=.002). Six of 7 patients with delayed recanalization had good outcomes. Recanalization at <8 hours after symptom onset had no independent predictive value for good outcome (
P
=.69). Recanalization at 24 hours increased the proportion of good outcomes from 23% to 75% in a subgroup of patients. Recanalization did not independently affect mortality (
P
>.15).

Conclusions
Even if delayed, arterial recanalization may improve clinical outcome in a subgroup of patients with middle cerebral artery occlusion.
Safety and Tolerability of the Glutamate Antagonist CGS 19755 (Selfotel) in Patients With Acute Ischemic Stroke
Authors: Grotta James , Clark Wayne , Coull Bruce , Pettigrew L. Creed , Mackay Bruce , Goldstein Larry B. , Meissner Irene , Murphy Deborah , LaRue Linda
Published: June 2011

Background and Purpose
CGS 19755 is a competitive
N
-methyl-
d
-aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke.

Methods
At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg.

Results
Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of ≥70 at the terminal visit.

Conclusions
We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.
Impact of Thalamic Hematoma on Six-Month Mortality and Motor and Cognitive Functional Outcome
Authors: Mori Sakan , Sadoshima Seizo , Ibayashi Setsuro , Fujishima Masatoshi , Iino Kozo
Published: June 2011

Background and Purpose
In this study we examined the functional outcome of thalamic hemorrhage after 6 months as it related to neurological and computed tomographic (CT) findings in 104 patients.

Methods
Level of consciousness was determined on admission. Extension and volume of hematoma were examined with CT within 3 days. After 6 months, motor function was evaluated using hemiplegic staging by the scale of Brunnström, and cognition was assessed by the Hasegawa dementia rating scale administered in Japanese.

Results
Twelve patients (12%) died from stroke after 6±6 days (mean±SD), which correlated with volume of hematomas (
P
<.001), levels of consciousness (
P
<.005), and miosis (
P
<.01). Six patients (6%) died from systemic complications after 23±18 days, which correlated with age (
P
<.05). Initially, 88 patients (85%) had hemiparesis, which persisted in 78 (75%) patients (18 deaths and 60 survivors). After 6 months, the Brunnström scale scores were lower in patients with hematomas extending to the internal capsule (
P
<.01) than in those with hematomas localized within the thalamus, and scores were lowest in patients with hematomas extending to the midbrain or putamen (
P
<.01). Motor function was well correlated with the extension and volume of hematomas (
P
<.001) and with the consciousness level (
P
<.001). Activities of daily living were correlated with hematoma extension and advanced age. Cognitive impairment was correlated with disturbance of consciousness (
P
<.01) and ventricular extension of the hematoma (
P
<.05) in 80 nonaphasic patients.

Conclusions
The extension and volume of hematomas, indicating direct cerebral damage, are useful indicators of mortality from thalamic hemorrhage, motor functional outcome, and level of activities of daily living after 6 months. The disturbance of consciousness and ventricular extension of the hematoma, suggesting diffuse brain damage, could be predictors of cognitive function.
Temporal Thresholds for Hyperglycemia-Augmented Ischemic Brain Damage in Rats
Authors: Warner David S. , Todd Michael M. , Dexter Franklin , Ludwig Paula , McAllister Alice M.
Published: June 2011

Background and Purpose
Although acute hyperglycemia is known to increase global ischemic brain damage, the duration of ischemia necessary to elicit such an effect is unknown. Accordingly, an experiment was performed to determine the duration of forebrain ischemia at which hyperglycemia becomes a factor in histological and behavioral outcome in rats.

Methods
Fasted rats were anesthetized and prepared for forebrain ischemia. Before ischemia, rats received either intravenous saline (plasma glucose, 112±18 mg/dL) or glucose (plasma glucose, 343±50 mg/dL). After 4, 8, 12, or 15 minutes of ischemia (n=12), recovery was allowed. Rats surviving 7 days underwent evaluation of motor function and then histological analysis of damage in the caudate putamen, hippocampal CA1, and substantia nigra pars reticulata.

Results
After 4 minutes of ischemia, damage was present in all structures. Only in the caudate putamen was hyperglycemia associated with worsened damage, but this did not result in seizures or death. After 8 minutes of ischemia, seizures occurred in 33% of hyperglycemic rats, and a hyperglycemic effect on damage in the CA1 and substantia nigra pars reticulata was observed. No seizures or mortality occurred in normoglycemic rats regardless of duration of ischemia. Longer durations of ischemia resulted in an increased incidence of seizures and mortality in hyperglycemic rats only. Among surviving rats, motor function was worsened in hyperglycemic rats after 12 minutes of ischemia.

Conclusions
Hyperglycemia-augmented brain damage is evident after global ischemic insults as brief as 4 minutes and becomes critical to survival after 8 minutes of ischemia.
Monocyte Chemoattractant Protein–1 Messenger RNA Expression in Rat Ischemic Cortex
Authors: Wang Xinkang , Yue Tian-Li , Barone Frank C. , Feuerstein Giora Z.
Published: June 2011

Background and Purpose
Previously we demonstrated that focal cerebral ischemia results in an increased expression of several cytokines/chemokines that precede the infiltration of leukocytes into the ischemic cortex after focal stroke induced by occlusion of the middle cerebral artery (MCAO). Monocyte chemoattractant protein–1 (MCP-1) is a potent chemoattractant specific for monocytes. The aim of the present study was to examine whether MCP-1 messenger RNA (mRNA) is expressed in ischemic brain tissue after MCAO.

Methods
The expression of MCP-1 mRNA in the ischemic cortex was first identified by means of a sensitive reverse transcription and polymerase chain reaction technique. The time course of expression of MCP-1 mRNA in the ischemic and nonischemic cerebral cortex after both permanent MCAO and temporary MCAO (160 minutes) with reperfusion was then examined by means of Northern blot analysis.

Results
Almost no expression of MCP-1 mRNA was found in the sham-operated or nonischemic (contralateral) cortex. A significant increase in MCP-1 mRNA expression in the ischemic cortex was observed after either permanent or temporary MCAO. MCP-1 mRNA was elevated at 6 hours (4.4-fold increase over sham; n=4), reached its highest expression from 12 hours to 2 days (22.7-fold at the peak level;
P
<.01), and remained elevated up to 5 days (5.6-fold;
P
<.01) after permanent MCAO. The profile of MCP-1 mRNA expression in the ischemic cortex after MCAO with reperfusion was similar to that of permanent MCAO except that MCP-1 mRNA was increased earlier (ie, 12.5-fold increase at 3 hours; n=4;
P
<.01). Also, MCP-1 mRNA expression in the ischemic cortex after permanent MCAO was significantly greater in hypertensive rats than in two normotensive rats (n=4;
P
<.05).

Conclusions
The demonstration of induced MCP-1 mRNA expression early after focal ischemia suggests that MCP-1 may represent a locally expressed monocyte chemoattractant that plays an important role in monocyte infiltration into ischemic tissue and therefore may contribute to the tissue injury in ischemic stroke. Further studies must concentrate on identifying the induced expression of MCP-1 and its cellular localization in the ischemic brain when the appropriate antibodies become available.
Sensitivity of Magnetic Resonance Diffusion-Weighted Imaging and Regional Relationship Between the Apparent Diffusion Coefficient and Cerebral Blood Flow in Rat Focal Cerebral Ischemia
Authors: Perez-Trepichio Alejandro D. , Xue Min , Ng Thian C. , Majors Anthony W. , Furlan Anthony J. , Awad Issam A. , Jones Stephen C.
Published: June 2011

Background and Purpose
Magnetic resonance (MR) diffusion-weighted imaging (DWI), a noninvasive procedure, may play an important role in detecting and accurately localizing the extent of evolving infarction within the period immediately following stroke. We evaluated the sensitivity and specificity of DWI in detecting ischemia and compared a quantitative measure derived from the DWI, the apparent diffusion coefficient (ADC), with autoradiographic cerebral blood flow (CBF) in an experimental model of focal cerebral ischemia in rats.

Methods
MR imaging data were obtained with a General Electric 4.7-T horizontal bore magnet CSI II system with self-shielded gradients. DWI was acquired within 41±6 minutes (mean±SD) after onset of ischemia and repeated at 169±14 minutes, followed by CBF determination at 237±21 minutes. DWI, ADC, and CBF images from each animal were then compared.

Results
The sensitivities for detecting an abnormality at 1 and 3 hours for DWI were significantly different, and the sensitivity of 3-hour DWI did not differ from the CBF sensitivity of 99%. A mean±SD ADC threshold of 460±95 μm
2
/s was defined as 45% higher than the low ADC in the ischemic core compared with the contralateral ADC. Subthreshold ADC area and ischemic area were significantly correlated (
r
2
=.69,
P
<.05). In 19 of 48 regions of interest classified as ischemic (<35 mL · 100 g
−1
· min
−1
) from both the 3-hour ADC and CBF images, 3-hour ADC correlated significantly with CBF (
r
2
=.27, n=19,
P
<.05), whereas in the nonischemic regions ADC was inversely correlated with CBF. Several ischemic regions showed a sharp drop in ADC to 37% (
P
<.001, n=5) compared with all other regions (n=43) from 1 to 3 hours.

Conclusions
Because of the change in the sensitivity of detecting ischemia with DWI, the difference in correlation of CBF with ADC between ischemic and nonischemic cortex, and the presence of several regions in which ADC dropped to 37% from 1 to 3 hours, our data suggest that ADC values potentially can be used to monitor evolving infarction.
Relation of Coronary Atherosclerosis and Apolipoprotein E Genotypes in Alzheimer Patients
Authors: Kosunen O. , Talasniemi S. , Lehtovirta M. , Heinonen O. , Helisalmi S. , Mannermaa A. , Paljärvi L. , Ryynänen M. , Riekkinen P.J. , Soininen H.
Published: June 2011

Background and Purpose
Apolipoprotein E (apoE) ε4 allele has been associated with a high risk for coronary heart disease. Increased frequency of the ε4 allele has also been reported in patients with late-onset familial and sporadic Alzheimer’s disease (AD). The aim of this study was to investigate the degree of coronary and cerebral atherosclerosis in a neuropathologically verified series of AD patients with different apoE genotypes. In addition, we studied the relationship between the degree of coronary and cerebral atherosclerosis and the extent of β-amyloid (Aβ) accumulation.

Methods
We studied 38 subjects (32 patients with definite AD and 6 age-matched control subjects) for whom postmortem autopsy delay was less than 8 hours. ApoE genotypes were identified through
Hha
I digestion of the polymerase chain reaction–amplified samples. We used Aβ immunohistochemistry to detect diffuse and neuritic plaques as well as cerebrovascular amyloid. The degree of coronary and cerebral atherosclerosis was rated as none, mild, moderate, or severe.

Results
The apoE genotypes of the AD patients were ε4/4 2, ε3/4 19, ε3/3 9, and ε3/2 2. We found more severe atherosclerosis of the coronary vessels among AD patients with the apoE ε4 allele compared with those AD patients without the ε4 allele (χ
2
=4.1,
df
=1,
P
<.05). The extent of cerebral atherosclerosis did not differ among AD subgroups with and without the ε4 allele. The degree of coronary or cerebral atherosclerosis was not related to the amount of amyloid accumulation in the frontal and temporal cortices or in the hippocampal structures.

Conclusions
This study confirms the association of apoE ε4 allele with coronary atherosclerosis in AD patients.
Anticardiolipin Antibodies in Normal Subjects
Authors: Schmidt R. , Auer-Grumbach P. , Fazekas F. , Offenbacher H. , Kapeller P.
Published: June 2011

Background and Purpose
Our aim was to assess the association of elevated anticardiolipin antibody (aCL) titers with silent brain damage and cognitive functioning in middle-aged and elderly normal subjects.

Methods
We determined the IgM and IgG aCL titers from 233 randomly selected clinically normal participants of a population-based stroke prevention study (age range, 44 to 82 years). aCL titers were categorized into negative (0 to 10 U/L), low positive (10 to 20 U/L), and moderately high positive (>20 U/L). All participants underwent 1.5-T MRI and demanding neuropsychological testing. Semiautomated measurements of the total white matter hyperintensity area and the size of ventricles and cortical sulci were conducted.

Results
There were 180 subjects (77.3%) with negative, 35 (15.0%) with low positive, and 18 (7.7%) with moderately high positive aCL titers. The frequency and extent of focal and diffuse brain abnormalities were not related to the aCL status of those examined. However, subjects with positive aCL results performed worse than those with negative findings on almost all tests administered, and this effect was mainly IgG titer related. When an ANCOVA test and partial correlations to correct for slight group differences in age and for the presence of major vascular risk factors were used, values of
P
<.05 were noted on tests assessing mnemonic and visuopractical abilities.

Conclusions
Increased aCL titers in normal elderly persons may be associated with subtle neuropsychological dysfunction, but they do not appear to cause any morphological changes as demonstrated by MRI.
Serum Fatty Acids and the Risk of Stroke
Authors: Simon Joel A. , Fong Josephine , Bernert John T. , Browner Warren S.
Published: June 2011

Background and Purpose
To examine the relationship between serum fatty acids, which reflect dietary intake, and stroke, we conducted a nested case-control study of 96 men with incident stroke and 96 control subjects matched by age, clinical center, treatment group, and date of randomization who were enrolled in the Multiple Risk Factor Intervention Trial.

Methods
After confirming the stability of the stored serum samples, we measured serum cholesterol ester and phospholipid fatty acid levels as the percentage of total fatty acids by gas-liquid chromatography and examined their association with incident stroke. Using stepwise conditional logistic regression that controlled for risk factors for stroke, we determined which fatty acids were independent correlates of stroke.

Results
In univariate models, a standard deviation (SD) increase (1.37%) in phospholipid stearic acid (18:0) was associated with a 37% increase in the risk of stroke, whereas an SD increase (0.06%) in phospholipid ω-3 α-linolenic acid (18:3) was associated with a 28% decrease in the risk of stroke (all
P
<.05). Only α-linolenic acid in the cholesterol ester fraction was associated with the risk of stroke in multivariate models: an SD increase (0.13%) in the serum level of α-linolenic acid was associated with a 37% decrease in the risk of stroke (
P
<.05). Systolic blood pressure and cigarette smoking were also independently associated with stroke risk.

Conclusions
Our findings suggest that higher serum levels of the essential fatty acid α-linolenic acid are independently associated with a lower risk of stroke in middle-aged men at high risk for cardiovascular disease.
Cerebral Metabolism of Patients With Stenosis or Occlusion of the Internal Carotid Artery
Authors: van der Grond J. , Balm R. , Kappelle L.J. , Eikelboom B.C. , Mali W.P.T.M.
Published: June 2011

Background and Purpose
Occlusion or severe stenosis of extracranial vessels may lead to hypoperfusion without overt infarction of brain tissue. The aim of this study was to investigate whether occlusion of the internal carotid artery or stenosis with reduction in diameter of more than 70% leads to altered cerebral metabolism in regions in which no infarcts are visible with magnetic resonance imaging.

Methods
We studied 10 control subjects and 55 patients with transient or nondisabling cerebral ischemia (25 patients with severe unilateral stenosis, 15 patients with unilateral occlusion, and 15 patients with bilateral severe stenosis or occlusion of the internal carotid artery). All subjects underwent magnetic resonance imaging and
1
H magnetic resonance spectroscopic imaging. Cerebral metabolism was studied by assessing ratios of
N
-acetyl aspartate (NAA) to choline and to creatine as well as lactate from noninfarcted frontal, mesial, and parietal regions in the centrum semiovale in both hemispheres.

Results
All patients with unilateral stenosis or occlusion of the internal carotid artery had decreased NAA/choline ratios in noninfarcted areas in the hemisphere on the side of the stenosis or occlusion and normal NAA/choline ratios in the contralateral hemisphere. Patients with bilateral stenosis or occlusion had decreased NAA/choline ratios in both hemispheres. In one third of all patients, cerebral lactate was found in regions without abnormalities on magnetic resonance imaging.

Conclusions
A severe reduction in the diameter of the internal carotid artery affects cerebral metabolism in regions that are not infarcted. These changes are reflected in a decreased NAA/choline ratio and a high incidence of cerebral lactate. These regions are probably at risk for infarction in the long term or if cerebral perfusion decreases further.
A Population-Based Assessment of the Impact and Burden of Caregiving for Long-term Stroke Survivors
Authors: Anderson Craig S. , Linto Jennie , Stewart-Wynne Edward G.
Published: June 2011

Background and Purpose
Little attention has been focused on the demands on caregivers in stroke outcome research. A major aim of this study was to identify factors in patients associated with emotional distress in caregivers 1 year after stroke.

Methods
One-year stroke survivors with residual handicap (defined by the Oxford Handicap Scale) and their chief caregivers were interviewed as part of the follow-up activities for patients (n=492) registered with the Perth Community Stroke Study. We assessed emotional distress in caregivers using the Hospital Anxiety and Depression Scale and the 28-item General Health Questionnaire. Appropriate sections of the Social Behaviour Assessment Schedule were used to assess the patient’s behavior and the impact on the caregiver’s life. Other aspects of the patient’s functional state were assessed with the Barthel Index, the Mini-Mental State Examination, the Frenchay Activities Index, and the Psychiatric Assessment Schedule (at 4 months after stroke).

Results
Of 241 patients who survived to 1 year after stroke and were living outside of an institution, 103 patients (43%; 95% confidence interval, 37% to 49%) were handicapped. Eighty-four patient/caregiver units were assessed from this latter group. Almost all caregivers reported adverse effects on their emotional health, social activities, and leisure time, and more than half reported adverse effects on family relationships. Forty-six caregivers (55%) showed evidence of emotional distress on either of the two screening instruments, particularly if they were caregiving for patients with dementia and/or abnormal behavior. There was no significant relationship between emotional illness among caregivers and the degree of patients’ physical disability.

Conclusions
In this population, the high level of emotional distress among caregivers of stroke patients suggests that many caregivers have unmet needs. Community services need to focus attention on the neuropsychological aspects of stroke patients and the social functioning of caregivers who support them.
Poststroke Depression
Authors: Herrmann Manfred , Bartels Claudius , Schumacher Martin , Wallesch Claus-W.
Published: June 2011

Background and Purpose
This study is aimed at the pathoanatomic correlates of depression in the postacute stage of patients with stroke.

Methods
Of a consecutive series of 104 stroke patients, a subgroup of 47 patients with single demarcated unilateral lesions was selected. Clinical examination, neuroradiological CT scan examination, and psychiatric assessment were performed within a 2-month period after the acute stroke. Depression was assessed with the Cornell Depression Scale, the Montgomery-Åsberg Depression Rating Scale, and according to modified DSM-III-R criteria. The neuroradiological examination of all patients was performed on the same scanner, and lesion location, lesion volume, and ventricle-to-brain ratio were analyzed.

Results
We found no significant differences in depression scores between patients with left and right hemisphere lesions and no correlation between the severity of depression and the anteriority and the volume of lesion or brain atrophy. Major depressive disorders were only found in nine patients with left hemisphere lesions, all involving the basal ganglia, whereas none of the patients with right hemisphere stroke exhibited major depression.

Conclusions
Lesions in the vicinity of the left hemisphere basal ganglia tend to play a crucial role in the development of major depression after the acute stage of stroke. The pathophysiological implications of this finding are discussed.
Nitro
-l-
Arginine Analogues
Authors: Traystman Richard J. , Moore Laurel E. , Helfaer Mark A. , Davis Stephen , Banasiak Kenneth , Williams Meagan , Hurn Patricia D.
Published: June 2011

Background and Purpose
The purpose of the present study was to measure cortical nitric oxide synthase (NOS) activity and determine the appropriate doses of
N
ω
-nitro
-l-
arginine methyl ester (L-NAME) or
N
ω
-nitro
-l-
arginine (L-NNA) for near-complete enzyme inhibition in dogs, cats, and pigs. We anticipated that NOS inhibition was dose- and time-dependent and questioned if the dose-response relationship was related to the specific drug or animal species.

Methods
Saline or L-NAME or L-NNA in escalating doses was administered to pentobarbital-anesthetized pigs, dogs, and cats. Brain temperature and arterial blood gas, hemoglobin, and blood pressure levels were maintained within the physiological range. Cortical tissue was biopsied at baseline and 30, 120, and 360 minutes after agent administration for measurement of NOS activity by isotopic assay of the conversion of [
14
C]arginine to [
14
C]citrulline.

Results
L-NAME produced >70% enzyme inhibition at a dose of 20 mg/kg across the species tested. Arterial blood pressure was elevated at 30 minutes after L-NAME treatment. However, consistent decreases in brain NOS activity required a longer period of time. Near-complete inhibition was apparent in most animals by 120 minutes and persisted for 6 hours after administration. A smaller dose of L-NNA was required for >70% enzyme inhibition in the cats and dogs (10 mg/kg). Near-complete NOS inhibition was evident in most animals at 30 minutes after L-NNA administration, which also persisted for 6 hours. In pigs, this same level of inhibition required 20 mg/kg.

Conclusions
These results suggest that administration of L-NAME and L-NNA diminishes brain NOS activity in a dose- and time-dependent manner and that the duration of effect is at least 6 hours.
Atrial Natriuretic Peptide Blocks Hemorrhagic Brain Edema After 4-Hour Delay in Rats
Authors: Rosenberg Gary A. , Estrada Edward Y.
Published: June 2011

Background and Purpose
Atrial natriuretic peptide (ANP) and arginine vasopressin regulate brain water and electrolytes. Treatment with ANP at the onset of a hemorrhagic injury reduces edema. Clinically, however, hemorrhagic masses form too rapidly for preventive treatment. Therefore, we measured the effect of ANP on brain edema after the hemorrhagic mass was formed.

Methods
Adult rats had hemorrhagic lesions produced by the intracerebral injection of 0.4 U bacterial collagenase. Four hours later, an infusion of ANP (120 or 700 ng/kg per 20 hours) was begun into the peritoneum using an implanted miniosmotic pump. Twenty-four hours after the injury, brain water and electrolyte values were measured. The mechanism of ANP action was explored in other groups of rats that either had osmolality increased with mannitol or were injected with the cyclic GMP analogue, 8-bromo-cGMP.

Results
Atrial natriuretic peptide given after a 4-hour delay significantly reduced brain water and sodium 24 hours after the injury (
P
<.05). However, neither mannitol nor 8-bromo-cGMP affected brain edema.

Conclusions
Delayed administration of ANP reduces brain edema secondary to a hemorrhagic mass. Because it is effective after the mass has formed, ANP may be useful in treatment of edema secondary to intracranial bleeding.
Contralateral Hyperhidrosis After Cerebral Infarction
Authors: Kim Beum-Saeng , Kim Yeong-In , Lee Kwang-Soo
Published: June 2011

Background
Excessive sweating from cerebral infarction has been reported rarely in the available stroke literature, and its pathophysiological mechanisms and clinical significance have remained obscure. In addition, there have been no reports that medullary infarction results in only contralateral hemihyperhidrosis without ipsilateral Horner’s syndrome. In the hope of increasing recognition of this phenomenon, we describe five patients with hyperhidrosis, including two patients with medullary infarction, and discuss the clinicoanatomic correlations.

Case Descriptions
Contralateral hyperhidrosis occurred in two patients with large strokes involving both superficial cortical and deep subcortical structures of the middle cerebral artery territory and in two patients with medullary infarctions. Bilateral hyperhidrosis of the face was noted in one patient with basilar artery thrombosis and bilateral cerebellar and pontine infarctions. The hyperhidrosis typically involved the face and arm and was transient, lasting from 2 days to 2 months. No associated Horner’s syndrome, hypothalamic dysfunction, or other autonomic dysfunction was observed.

Conclusions
The phenomenon of hyperhidrosis might be attributed to a lesion of a putative sympathoinhibitory pathway that controls sweating. This pathway might originate in the cortex, possibly in the operculum, and make terminal connections with the contralateral thoracic spinal cord. Our observations suggest that the fibers of this putative pathway may be very close to the corticospinal tract.
Comparison of Static and Dynamic Cerebral Autoregulation Measurements
Authors: Tiecks Frank P. , Lam Arthur M. , Aaslid Rune , Newell David W.
Published: June 2011

Background and Purpose
Cerebral autoregulation can be evaluated by measuring relative blood flow changes in response to a steady-state change in the blood pressure (static method) or during the response to a rapid change in blood pressure (dynamic method). The purpose of this study was to compare the results of the two methods in humans with both intact and impaired autoregulatory capacity.

Methods
Using intraoperative transcranial Doppler sonography recordings from both middle cerebral arteries, we determined static and dynamic autoregulatory responses in 10 normal subjects undergoing elective surgical procedures. The changes in cerebrovascular resistance were estimated from the changes in cerebral blood flow velocity and arterial blood pressure in response to manipulations of blood pressure. Static autoregulation was determined by analyzing the response to a phenylephrine-induced rise in blood pressure, whereas rapid deflation of a blood pressure cuff around one thigh served as a stimulus for testing dynamic autoregulation. Both measurements were performed in patients with intact autoregulation during propofol anesthesia and again in the same patients after autoregulation had been impaired by administration of high-dose isoflurane.

Results
There was a significant reduction in autoregulatory capacity after the administration of high-dose isoflurane, which could be demonstrated using static (
P
<.0001) and dynamic (
P
<.0001) methods. The correlation between static or steady-state and dynamic autoregulation measurements was highly significant (
r
=.93,
P
<.0001).

Conclusions
These data show that in normal human subjects measurement of dynamic autoregulation yields similar results as static testing of intact and pharmacologically impaired autoregulation.
Cerebral Blood Flow During Inhibition of Brain Nitric Oxide Synthase Activity in Normal, Hypertensive, and Stroke-Prone Rats
Authors: Izuta Makoto , Clavier Nathalie , Kirsch Jeffrey R. , Traystman Richard J.
Published: June 2011

Background and Purpose
Because tonic production of nitric oxide (NO) is important in regulating cerebrovascular tone and NO may be important in the mechanism of brain injury from focal ischemia, we speculated that stroke predisposition in spontaneously hypertensive stroke-prone rats (SHR-SP) may be related to impaired tonic production of NO. This study was designed to test the hypothesis that the cerebral blood flow (CBF) response to inhibition of NO synthase in SHR-SP would be different than that observed in normal Wistar-Kyoto (WKY) rats and non–stroke-prone spontaneously hypertensive rats (SHR).

Methods
Pentobarbital-anesthetized, mechanically ventilated rats were tested for CBF response to saline, 5 or 20 mg/kg IV of
N
G
-monomethyl-
l
-arginine (L-NMMA), or 20 mg/kg IV of
N
ω
-nitro-
l
-arginine (L-NA). In addition, specificity for an NO-dependent mechanism was assessed by determining the ability to reverse any alteration in CBF with
l
-arginine. Hemorrhage was used to minimize any increase in mean arterial blood pressure (MABP) from NO synthase inhibition. In a separate cohort of rats, differential sensitivity of NO synthase for inhibition by nitro-arginine analogues was determined.

Results
Baseline MABP was greater in SHR-SP (185±3, n=38) and SHR (169±3, n=38) compared with WKY rats (101±2 mm Hg, n=38,
P
<.05). Baseline CBF was similar between strains; however, cerebrovascular resistance was higher in SHR-SP (2.16±0.09, n=27) and SHR (1.94±0.07, n=27) compared with WKY rats (1.23±0.06 mm Hg/mL per minute per 100 g, n=27,
P
<.05). CBF was unchanged with 5 mg/kg L-NMMA or with
l
-arginine in the absence of L-NMMA in each strain. CBF decreased similarly in SHR and SHR-SP (n=9 each) in response to 20 mg/kg L-NMMA (SHR, 85±6 to 67±6; SHR-SP, 87±7 to 69±5 mL/min per 100 g) and was completely reversed by
l
-arginine. CBF did not decrease with 20 mg/kg L-NMMA in WKY rats. Administration of L-NA (n=5 each) produced similar reduction of CBF (WKY rats, 67±6%; SHR, 49±9%; SHR-SP, 61±6% of baseline) and inhibition of NO synthase in each strain (≈80% inhibition).

Conclusions
There was no difference in the cerebrovascular response to NO synthase inhibition in SHR-SP and non–stroke-prone SHR. Therefore, it is unlikely that an altered sensitivity of NO synthase to inhibition can explain predisposition to stroke in SHR-SP.
Changes in Striatal Dopamine Metabolism After Microsphere Embolism in Rats
Authors: Takagi Norio , Tsuru Hironobu , Yamamura Motoko , Takeo Satoshi
Published: June 2011

Background and Purpose
Dopamine plays an important role in striatal function. The present study was undertaken to elucidate the pathophysiological changes in striatal dopamine metabolism after microsphere embolism.

Methods
Microspheres (48 μm) were injected into the right internal carotid artery of rats. Extracellular levels of dopamine and its metabolites were measured by in vivo microdialysis with the aid of high-performance liquid chromatography. In vivo striatal tyrosine hydroxylation and turnover (catabolism) rate of dopamine were estimated on the first and third days after the embolism. These were estimated by measuring tissue dopa or dopamine content in the presence of either an aromatic
l
-amino acid decarboxylase inhibitor or a tyrosine hydroxylase inhibitor, respectively.

Results
In the microdialysis study, a 190-fold increase in the release of dopamine from the right striatum was observed 40 minutes after microsphere embolism, whereas the striatal dopamine metabolites decreased during the first 180 minutes after the embolism. Microsphere embolism decreased the striatal dopamine content throughout the experiment (28 days), whereas it increased tissue dopamine metabolites on the first day, followed by a decline in the metabolites on the third day or later. The in vivo turnover rate of dopamine decreased both on the first and third days, whereas the in vivo tyrosine hydroxylation decreased only on the third day after the embolism.

Conclusions
The results suggest that microsphere embolism induces severe damage to striatal dopaminergic metabolism 3 to 28 days after the embolism. Dopamine synthesis may be more resistant to the embolism-induced ischemic insults than its catabolism.
Vasospasm and Thrombus Formation as Possible Mechanisms of Stroke Related to Alkaloidal Cocaine
Authors: Konzen Jon P. , Levine Steven R. , Garcia Julio H.
Published: June 2011

Background
“Crack” cocaine (alkaloidal cocaine) induces ischemic stroke. However, the mechanisms by which this occurs are not well documented in humans. We present pertinent information on three patients whose ischemic strokes involved the territory of the internal carotid artery and were associated with crack use.

Case Descriptions
These patients were investigated clinically, radiologically, intraoperatively, and/or histopathologically at the same institution, and the diagnostic evaluations did not reveal a definite cardiac or hematologic cause for stroke. Large filling defects were noted on conventional carotid angiography in two of these patients; in the third patient, the histopathological changes were compatible with vasospasm. To our knowledge, these changes have not been previously documented in human arteries.

Conclusions
We suggest that some brain infarcts among crack cocaine users may result from vasospasm of large arteries and secondary intravascular thrombosis.
Frequency and Accuracy of Prehospital Diagnosis of Acute Stroke
Authors: Kothari Rashmi , Barsan William , Brott Thomas , Broderick Joseph , Ashbrock Stephen
Published: June 2011

Background and Purpose
This pilot study evaluated the frequency and accuracy of diagnosis of stroke made by prehospital care system dispatchers, emergency medical technicians (EMTs), and paramedics in one emergency medical services (EMS) system. In addition, the study determined patient prehospital triage and time intervals in the transport and evaluation of patients given a diagnosis of stroke by this EMS system.

Methods
We reviewed records of 4413 consecutive prehospital records of a two-tiered EMS system for patients with potential stroke. Hospital records were obtained for patients given a diagnosis of stroke or transient ischemic attack (TIA) by an EMS dispatcher, EMT, or paramedic. The EMS system studied serves a community of 13 000 within the greater Cincinnati area.

Results
Of 4413 EMS on-scene evaluations, the diagnosis of stroke or TIA was made by an EMT or paramedic for 96 patients (2%). Of the study population (n=86), a final hospital discharge diagnosis of stroke or TIA was made for 62 patients (72%). EMS dispatchers correctly identified 52% and paramedics 72% of these 86 patients as having sustained a stroke or TIA. Twenty-two of the 86 patients required paramedic-level interventions, which included three intubations. Of the 24 patients whose symptoms were misdiagnosed as stroke or TIA by the paramedics, 16 (19%) had acute conditions for which effective therapies are available. Prehospital personnel arrived at the scene to examine potential stroke patients in a mean of 3 minutes after the emergency 911 call was received by the dispatcher. Patients transported by basic life support units (EMTs) arrived earlier at the hospital than did those transported by advanced life support units (paramedics) (40±1 versus 45±1 minutes,
P
=.004). However, patients transported by advanced life support units were seen by a physician sooner after arrival at the emergency department (10±2 versus 20±4 minutes,
P
=.02) and underwent computed tomography of the brain sooner (47±5 versus 69±10 minutes,
P
=.04).

Conclusions
Prehospital evaluation of potential stroke patients can be accomplished promptly after the EMS system is activated. Urgent evaluation and transport of potential stroke patients is justified because paramedic-level interventions are frequently required and because almost 20% of patients with potential stroke have acute medical conditions for which effective specific therapies are available.
Variability of Vascular Territory in Stroke
Authors: Lang Erhard W. , Daffertshofer Michael , Daffertshofer Andreas , Wirth Steffen B. , Chesnut Randall M. , Hennerici Michael
Published: June 2011

Background and Purpose
We investigated the efficacy and feasibility of determining infarction mechanisms and underlying embolic or hemodynamic pathologies from topographical patterns of ischemic damage seen on computed tomography or magnetic resonance imaging.

Methods
Infarction patterns from 22 patients with ipsilateral severe, hemodynamically relevant carotid stenosis (n=6) or occlusions (n=16) were superimposed, using two matching algorithms, onto maps showing the variability of the cerebral vascular territories as determined from recent cadaver studies. These images were used to classify the infarctions as border-zone or territorial for the two conditions of minimal and maximal middle cerebral artery distribution.

Results
Classification of infarction patterns resulting from carotid stenosis was independent of the territorial extension map chosen: 83% were classified as territorial. Classification of patterns due to carotid occlusion, however, varied highly; 81% of infarctions were considered territorial when the maximal middle cerebral artery distribution map was used, whereas only 19% were when the minimal territorial extension map was used.

Conclusions
The current concept that stroke mechanisms can be inferred from the interpretation of stroke patterns seen on computed tomography scans or magnetic resonance imaging is significantly confounded by the demonstrated variability in intracranial vascular distributions. Stroke pattern interpretation appears to be highly dependent on the in vivo vascular tree of the individual, which is unknown to the examiner. This calls into question the reliability of classifying infarction patterns as border-zone or territorial. Determination of true underlying stroke mechanisms requires a comprehensive approach and cannot be based solely on stroke pattern interpretation.
Geographic Variation in the Decline of Stroke Mortality in the United States
Authors: Lanska Douglas J. , Peterson Patrick M.
Published: June 2011

Background and Purpose
This study examines the geographic variation in the decline of stroke mortality rates in the United States.

Methods
National Center for Health Statistics and Bureau of the Census data were used to assess regional and state level temporal trends of stroke mortality in the United States for 1970 to 1989.

Results
Underlying- and multiple-cause stroke mortality rates have declined fairly steadily in all regions of the United States and for all race/sex groups, although the rates of decline were greater during 1970 to 1978 than during 1979 to 1989. The declines in underlying-cause rates could not be attributed to a shift toward reporting stroke as a contributing rather than underlying cause of death, since both underlying- and multiple-cause rates declined similarly. There was significant regional variation in the rate of decline, particularly during 1979 to 1989. The South initially had the highest rates, but it experienced the most rapid decline, so that by 1989 the South no longer had the highest rates. States with the most rapid rates of decline were significantly clustered in the South and particularly the Southeast. Most of the decline in overall stroke mortality was due to declines in ischemic stroke mortality.

Conclusions
During 1970 to 1989 there was significant geographic variation in the rate of decline of stroke mortality rates, with the most rapid rates of decline concentrated in the high-rate areas of the South and particularly the Southeast. As a result, there has been a decrease in interregional and interstate variation in stroke mortality rates, which is apparently not due to an artifact of changing reporting patterns.