bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein E Polymorphism and Stroke in a Population Sample Aged 75 Years or More
Authors: Basun H. , Corder E.H. , Guo Z. , Lannfelt L. , Corder L.S. , Manton K.G. , Winblad B. , Viitanen M.
Published: June 2011

Background and Purpose
We investigated apolipoprotein E polymorphism stroke risk in a population sample of 1810 persons aged 75 years or more in Stockholm (the Kungsholmen Project). Information on cognition at cohort inception (from 1987 to 1989) and on stroke occurrence (from 1969 to 1994) is available for the cohort. In the cohort, cognitive impairment is associated with the ε4 allele, and longer survival in subjects aged ≥85 years with good cognition is associated with the ε2 allele and the absence of ε4.

Methods
We compared stroke incidence in the 1077 of 1124 genotyped subjects who carried ε2/3, ε3/3, or ε3/4 and estimated the proportion of cognitive impairment attributable to stroke.

Results
Risk of stroke did not vary with apolipoprotein E polymorphism (
P
=.82): 24% of 87 incident stroke patients during follow-up compared with 25% of 827 subjects with normal cognition and no stroke diagnosis at baseline carried the ε3/4 genotype. An estimated 9% of cognitive impairment was attributable to stroke. Notably, a reduced ε3/4 frequency of 20% was found in subjects who survived a prior stroke and were included in the cohort, and risk of hemorrhagic stroke tended to be associated with the presence of the ε3/4 genotype and the absence of ε2/3.

Conclusions
This population-based study indicates that apolipoprotein E polymorphism is not a risk factor for ischemic stroke in subjects aged ≥75 years (although it might possibly influence survival after stroke occurrence and be a risk factor for infrequent hemorrhagic stroke) and that approximately 10% of cognitive impairment in this age group is attributable to stroke.
Apolipoprotein E
ε4
Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy
Authors: Greenberg Steven M. , Briggs Megan E. , Hyman Bradley T. , Kokoris George J. , Takis Constantino , Kanter Daniel S. , Kase Carlos S. , Pessin Michael S.
Published: June 2011

Background and Purpose
Cerebral amyloid angiopathy is an important cause of intracerebral hemorrhage in the elderly. The
ε4
allele of the apolipoprotein E gene, recently established as a genetic risk for Alzheimer's disease, has also been suggested as a possible risk factor for cerebral amyloid angiopathy. We sought to determine whether this allele is specifically associated with hemorrhages related to amyloid angiopathy and whether it correlates with the age at which first amyloid angiopathy-related hemorrhage occurs.

Methods
Forty-five consecutive patients presenting with lobar hemorrhage were prospectively classified according to clinical, radiological, and when available, pathological features and evaluated for apolipoprotein E genotype. They were compared with 1899 elderly patients from a population-based sample and with 18 consecutive patients with hemorrhages in deep regions typical of a hypertensive mechanism.

Results
Patients with multiple hemorrhages confined to the lobar territory demonstrated a greater than twofold overrepresentation (
P
<.001) in frequency of the apolipoprotein E
ε4
allele compared with the population-based sample. Apolipoprotein E genotypes of patients with hemorrhages in deep territories resembled the population sample. Among patients with strictly lobar hemorrhages, carriers of the
ε4
allele had their first hemorrhage more than 5 years earlier than noncarriers (mean age at first hemorrhage, 73.4±8.0 versus 78.9±7.4 years;
P
=.033). These effects were independent of the accompanying presence of Alzheimer's disease.

Conclusions
The data support a specific role for apolipoprotein E
ε4
in accelerating the process that leads to amyloid angiopathy-related hemorrhage.
Detection of Microembolic Signals in Patients With Middle Cerebral Artery Stenosis by Means of a Bigate Probe
Authors: Nabavi Darius G. , Georgiadis Dimitrios , Mumme Thorsten , Zunker Peter , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
Middle cerebral artery (MCA) stenosis is a relatively rare occlusive disease with an annual stroke risk of approximately 7% to 8%. However, the frequent coincidence of cardiac or ipsilateral carotid artery disease may lead to difficulties in identifying the relevant embolizing source in symptomatic patients. We undertook this study to evaluate the prevalence of microembolic signals (MES) as well as the potential and limitations of bigate monitoring in patients with MCA stenosis.

Methods
Fourteen patients aged 33 to 87 years with angiographically demonstrated symptomatic (acute, n=2; chronic, n=8) or asymptomatic (n=4) MCA stenosis were examined. Six patients (43%) had additional cardiac (n=3) or carotid artery (n=3) disease. By means of a bigate probe, simultaneous insonation of prestenotic and poststenotic vessel segments was attempted.

Results
In 10 patients (71%), MES detection could be performed sufficiently at target vessel sites. In the remaining patients, either prestenotic (n=3) or poststenotic (n=1) monitoring was not satisfactory due to insufficient transtemporal bone window or the great length or extent of MCA stenosis. Poststenotic MES were detectable in 2 acutely symptomatic and 1 asymptomatic patient (prevalence, 21%). In the latter case, the sequential appearance of MES in both prestenotic and poststenotic channels excluded MCA stenosis but strongly favored coexisting carotid artery stenosis as the active embolic source.

Conclusions
MES are detectable in patients with MCA stenosis. Bigate monitoring in this setting is feasible and allows identification of the active source among “competing” embolizing conditions.
A Transcranial Doppler Ultrasonography Study of Cerebrovascular CO
2
Reactivity in Mitochondrial Encephalomyopathy
Authors: Kodaka Ryuhei , Itagaki Yusuke , Matsumoto Masayasu , Nagai Toshisaburo , Okada Shintaro
Published: June 2011

Background and Purpose
To elucidate the pathogenic role of vascular involvement such as mitochondrial angiopathy in patients with mitochondrial encephalomyopathy (MEM), we used the transcranial Doppler sonography (TCD) method to detect impairment of cerebrovascular CO
2
reactivity.

Methods
The cerebral perfusion reserve in 13 MEM patients, including 6 with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) was studied by TCD for different CO
2
partial pressures. For the parameter of mean flow velocity, the mean spatial Doppler frequency (fm) was obtained from the right and left middle cerebral arteries and basilar artery under conditions of normocapnia, hypercapnia, and hypocapnia in cases in which hyperventilation was possible. By fitting the obtained fm and the end-tidal CO
2
partial pressure (P
etco
2
) to the exponential formula fm=a×e

(K×P
etco
2
)

, where a is the theoretical fm at a P
etco
2
of 0 mm Hg, the parameter K, an index of CO
2
reactivity, was calculated.

Results
The K value was lower than control values at at least one site of the middle cerebral arteries and basilar artery of all patients with MELAS as well as the other MEM patients except for one patient with myoclonic epilepsy with ragged-red fiber and one with Kearns-Sayer syndrome.

Conclusions
Our results suggest that there is a high incidence of impairment of cerebrovascular CO
2
reactivity in MEM patients. Moreover, the noninvasive TCD method was found useful for evaluation of cerebral hemodynamics in MEM patients.
Aneurysm of the Left Sinus of Valsalva
Authors: Stöllberger Claudia , Seitelberger Rainald , Fenninger Christof , Prainer Christian , Slany Jörg
Published: June 2011

Background
Aneurysm of the ascending aorta is rarely reported as the source of emboli. We report a patient with a minor stroke in whom a saccular aneurysm of the left sinus of Valsalva was diagnosed as the presumed source of cerebral embolism.

Case Description
A 49-year-old right-handed woman presented 10 days after sudden onset of right-sided hemiparesis. Her history was uneventful apart from an acute inflammation of the subcutaneous tissue in the right leg 20 years earlier. A diastolic murmur was heard best over the third left intercostal space. Results of duplex ultrasound investigation of the cerebral vessels, chest x-ray, and electrocardiography and biochemical and hematological variables were normal. CT of the brain showed a small hypodense area in the left frontal region. Transthoracic and transesophageal echocardiography detected moderate aortic regurgitation and a saccular aneurysm originating from the left sinus of Valsalva. The aneurysm had calcified walls and contained thrombotic material. Surgical closure of the aneurysm with a pericardial patch was performed to prevent recurrent embolism and rupture. Coaptation of the aortic valves was achieved, and no residual aortic regurgitation could be detected.

Conclusions
We conclude that an unruptured sinus of Valsalva aneurysm should be included in the list of sources of embolism. Transthoracic echocardiography establishes the diagnosis. Transesophageal echocardiography provides additional information about the origin and size of the aneurysm and presence of thrombotic material. Surgical closure of the aneurysm prevents rupture and recurrent embolism and possibly corrects aortic regurgitation.
Quality of Life After Stroke
Authors: King Rosemarie B.
Published: June 2011

Background and Purpose
The purposes of this study were to examine overall and domain-specific quality of life in long-term stroke survivors and to identify variables that predict quality of life after stroke.

Methods
The study used a cross-sectional, descriptive correlational design. Subjects were 86 stroke survivors who were interviewed 1 to 3 years after stroke. Quality of life was measured with the use of an instrument that assesses satisfaction and importance for four domains (health and functioning, socioeconomic, family, and psychological-spiritual). Independent variables were age, social class, aphasia, functional status, motor impairment, depression, comorbidity, and perceived social support. Multiple regression analysis was used to predict quality of life.

Results
Thirty percent of subjects scored in the depressed range. The mean overall quality of life score was relatively high and was comparable to that of a normative population. Quality of life was highest for the family domain and lowest for health and functioning. Depression, perceived social support, and functional status predicted quality of life (adjusted
R
2
=.38) and contributed to prediction of domain quality of life. Social support and three additional variables, social class, age, and cardiovascular disease, predicted socioeconomic quality of life.

Conclusions
The identification of depression, social support, and functional status as predictors of quality of life suggests the need to assist stroke survivors in coping and in maintaining and strengthening their support systems. (Stroke. 1996;27:1467-1472.)
Effect of BQ-123 and Tissue Plasminogen Activator on Vasospasm After Subarachnoid Hemorrhage in Monkeys
Authors: Kim Chul-Jin , Bassiouny Mohammed , Macdonald R. Loch , Weir Bryce , Johns Lydia M.
Published: June 2011

Background and Purpose
We aimed to determine the effect of intracisternal administration of an endothelin-A receptor antagonist (BQ-123) against vasospasm in a monkey model and to determine whether this drug would have adverse interactions with intracisternal tissue plasminogen activator (TPA).

Methods
Thirty-three monkeys were randomly allocated to undergo baseline cerebral angiography, creation of right subarachnoid hemorrhage (SAH), and intracisternal delivery of (1) placebo (n=10); (2) low-dose BQ-123 (5 mg/kg per day, n=7); (3) high-dose BQ-123 (10 mg/kg per day, n=9); or (4) BQ-123 10 mg/kg per day plus TPA 1 mg every 12 hours for three doses (n=7). Angiography was repeated after 7 days, and animals were killed. Vasospasm was assessed by comparisons of angiograms within groups across time by paired
t
test and by comparisons across groups at each time by ANOVA.

Results
Significant clot remained in the basal cisterns in all groups except those receiving TPA, in whom complete clot clearance was noted. Comparisons of angiograms at baseline and after 7 days showed significant vasospasm of the right middle cerebral artery in animals receiving placebo (mean±SEM reduction in diameter, 36±7%;
P
<.05) and low- and high-dose BQ-123 (16±4% and 18±7%, respectively). Animals that received TPA did not develop significant right cerebral artery vasospasm. Comparisons of arterial diameters at day 7 revealed significant variance in right middle cerebral artery diameter, with animals in the placebo group having significantly more and animals in the TPA group having significantly less vasospasm than the BQ-123 groups. Histopathological examination of the brains did not show inflammation or pathological change in animals that received BQ-123 or BQ-123 plus TPA.

Conclusions
Intracisternal TPA was efficacious against vasospasm in monkeys. Combination therapy with TPA and BQ-123 was not associated with reduction in efficacy of either drug or with evidence of toxicity.
Cerebral White Matter Is Highly Vulnerable to Ischemia
Authors: Pantoni Leonardo , Garcia Julio H. , Gutierrez Jorge A.
Published: June 2011

Background and Purpose
The effects of ischemia on the cerebral white matter structure seldom have been studied, possibly because white matter is generally considered less vulnerable to ischemia than gray matter. The objective of this study was to evaluate the early (≤24 hours) structural effects of experimental focal ischemia on the cerebral white matter of the rat as a preliminary step to investigating human conditions of unknown pathogenesis that are characterized by selective damage to the white matter.

Methods
Twenty-eight rats, including four controls, had a middle cerebral artery occluded with an intravascular filament for periods ranging between 0.5 and 24 hours. Brain samples from the subcortical white matter were examined with light and electron microscopic methods, and the abnormalities were quantified with an image-analysis system.

Results
As early as 30 minutes after the arterial occlusion, there was conspicuous swelling of oligodendrocytes and astrocytes; after 3 hours, large numbers of oligodendrocytes were lethally injured. These changes preceded by several hours the appearance of necrotic neurons in the cortex and basal ganglia. Vacuolation and pallor of the white matter were very marked after 24 hours and reflected the segmental swelling of myelinated axons, the formation of spaces between myelin sheaths and axolemma, and astrocyte swelling.

Conclusions
These results suggest that the cerebral white matter is highly vulnerable to the effects of focal ischemia. Pathological changes in oligodendrocytes and myelinated axons appear early and seem to be concomitant with, but independent of, neuronal perikaryal injury. Modifications of this experimental model of focal ischemia could provide the means to test the hypothesis that selected types of human leukoencephalopathies have an ischemic origin.
Severe Transient Hypoglycemia Causes Reversible Change in the Apparent Diffusion Coefficient of Water
Authors: Hasegawa Yasuhiro , Formato James E. , Latour Lawrence L. , Gutierrez Jorge A. , Liu Kai-Feng , Garcia Julio H. , Sotak Christopher H. , Fisher Marc
Published: June 2011

Background and Purpose
The aim of this study was to determine the effects of temporary severe hypoglycemia on the apparent diffusion coefficient (ADC) acquired by diffusion-weighted MRI of brain water with the use of serial multislice ADC mapping in rats. Severe hypoglycemia reduces the extracellular space volume, as does ischemia. Demonstrating a reduction of ADC with hypoglycemia should increase our understanding of the mechanisms underlying ADC changes in ischemia and other conditions.

Methods
Fasted rats were given regular insulin (15 IU/kg IP). Rats were subjected to 15 minutes (n=5) and 50 minutes (n=5) of temporary severe hypoglycemia, causing a transiently isoelectric electroencephalogram (EEG). ADC mapping was performed every 30 seconds beginning at the onset of isoelectricity for 8.5 minutes. ADC maps were also obtained later during the isoelectric EEG period and 10, 20, 30, and 40 minutes after glucose infusion. Control images were obtained from a separate group of animals suffering cardiac arrest (n=5).

Results
Abnormal ADC values were not observed before the onset of cerebral isoelectricity, except for isolated areas in the cortex and periventricular regions. Cortical ADC values globally declined at the onset of EEG isoelectricity. The ADC decline spread to subcortical regions within a few minutes. During the isoelectric period, significant declines of ADC values (27% to 45%) occurred in the entire brain. Glucose infusion normalized most of the ADC changes, even after a 50-minute period of isoelectricity.

Conclusions
ADC mapping during hypoglycemia clearly demonstrates changes likely related to energy depletion. Most of these ADC declines were reversible. Hypoglycemia is a condition known to be associated with shrinkage of the extracellular space. These observations support the hypothesis that ADC reductions observed in ischemia are also related to shifts of water from the extracellular to the intracellular compartment.
Automated Measurement of Infarct Size With Scanned Images of Triphenyltetrazolium Chloride–Stained Rat Brains
Authors: Goldlust Eric J. , Paczynski Richard P. , He Yong Y. , Hsu Chung Y. , Goldberg Mark P.
Published: June 2011

Background and Purpose
The extent of brain infarction after focal cerebral ischemia is frequently assessed with the mitochondrial activity indicator 2,3,5-triphenyltetrazolium chloride (TTC). We describe an automated procedure for analysis of infarct size in TTC-stained rat brains.

Methods
Rats were subjected to middle cerebral artery occlusion and killed after 24 to 36 hours, and their brains were processed for TTC staining. Digital images of coronal sections from these brains (n>50) were acquired with a desktop color scanner. The resulting images were divided into red, blue, and green component images. Total brain and infarct areas were automatically determined on the basis of total pixel intensity and area after segmentation of the red and green images, respectively. Automated measurements were compared with those made with a video camera–based image acquisition system that required manual tracing of lesion boundaries.

Results
The spatial resolution of scanned brain images (≈200 μm) was comparable to that of the camera-based system and provided sufficient detail to recognize infarct boundaries and neuroanatomical features. Scanner-based acquisition and analysis were faster than with the camera-based method. The green component image accurately distinguished infarcted from normal brain, and the red component image represented total brain dimensions. Infarct measurements obtained by the automated method correlated closely with those from conventional apparatus (
R
2
=.89,
P
<.001). Intraobserver reliability with the automated method (
R
2
=1.00) was higher than with the conventional method (
R
2
=.77).

Conclusions
Infarct size after middle cerebral artery occlusion in the rat can be rapidly and reproducibly assessed with inexpensive scanning equipment and automated image analysis of TTC-stained brains.
Human Cytomegalovirus and Restenosis of the Internal Carotid Artery
Authors: Pauletto Paolo , Pisoni Guglielmo , Boschetto Roberta , Zoleo Miranda , Pessina Achille C. , Palù Giorgio
Published: June 2011

Background
Although human cytomegalovirus (HCMV) has been implicated in coronary restenosis, data on the presence of HCMV in the restenosis lesion of the internal carotid artery (ICA) are lacking.

Summary of Report
We studied endarterectomy tissue from 5 ICA restenoses and 5 primary atherosclerotic lesions and tissue from 5 normal ICAs. The extracted DNA was tested for HCMV sequences with polymerase chain reaction by use of three primer pairs that amplify different genomic regions. The AD169 strain of HCMV served as the positive control. No trace of the HCMV genome was found in the intima or in the underlying media of endarterectomy specimens from restenosis and primary lesions. The media from control arteries was also HCMV negative.

Conclusions
At variance with previous studies carried out in coronary arteries, our results do not support the hypothesis that HCMV infection is implicated in restenosis of the ICA.
Immediate Early Gene Expression in Response to Cerebral Ischemia
Authors: Akins Paul T. , Liu Philip K. , Hsu Chung Y.
Published: June 2011

Background
Cerebral ischemia is a potent modulator of gene expression. Immediate early genes undergo rapid induction after both global and focal cerebral ischemia. Many immediate early genes code for transcription factors. Additional genes, including those encoding for neurotrophic factors and neurotransmitter systems, are induced in a delayed fashion after cerebral ischemia. The functional significance of early and late gene regulation after cerebral ischemia requires futher investivation. These changes may be beneficial (friend) or detrimental (foe). Many of the genes are likely neuroprotective and important for recovery, but others may be involved in ischemic cell death mediated by apoptosis.

Summary of Review
We review evidence that supports the hypothesis that cell death after cerebral ischemia occurs through the dual pathways of ischemic necrosis and apoptosis.

Conclusions
Gene regulation, including immediate early genes, is required for programmed neuronal death after trophic factor deprivation and is predicted to be involved in apoptosis triggered by cerebral ischemia. Novel therapies following cerebral ischemia may be directed at genes mediating either recovery or apoptosis.
Early Hemorrhage Growth in Patients With Intracerebral Hemorrhage
Authors: Brott Thomas , Broderick Joseph , Kothari Rashmi , Barsan William , Tomsick Thomas , Sauerbeck Laura , Spilker Judith , Duldner John , Khoury Jane
Published: June 2011

Background and Purpose
The goal of the present study was to prospectively determine how frequently early growth of intracerebral hemorrhage occurs and whether this early growth is related to early neurological deterioration.

Methods
We performed a prospective observational study of patients with intracerebral hemorrhage within 3 hours of onset. Patients had a neurological evaluation and CT scan performed at baseline, 1 hour after baseline, and 20 hours after baseline.

Results
Substantial growth in the volume of parenchymal hemorrhage occurred in 26% of the 103 study patients between the baseline and 1-hour CT scans. An additional 12% of patients had substantial growth between the 1- and 20-hour CT scans. Hemorrhage growth between the baseline and 1-hour CT scans was significantly associated with clinical deterioration, as measured by the change between the baseline and 1-hour Glasgow Coma Scale and National Institutes of Health Stroke Scale scores. No baseline clinical or CT prediction of hemorrhage growth was identified.

Conclusions
Substantial early hemorrhage growth in patients with intracerebral hemorrhage is common and is associated with neurological deterioration. Randomized treatment trials are needed to determine whether this early natural history of ongoing bleeding and frequent neurological deterioration can be improved.
Acute Ischemic Strokes Improving During the First 48 Hours of Onset: Predictability, Outcome, and Possible Mechanisms
Authors: Toni Danilo , Fiorelli Marco , Bastianello Stefano , Falcou Anne , Sette Giuliano , Ceschin Vanessa , Sacchetti Maria Luisa , Argentino Corrado
Published: June 2011

Background and Purpose
Our aims were to identify predictors of early neurological improvement in acute ischemic stroke patients, to evaluate its impact on clinical outcome, and to investigate possible mechanisms.

Methods
A consecutive series of 152 first-ever ischemic hemispheric stroke patients hospitalized within 5 hours of onset underwent a first CT scan within 1 hour of hospitalization, and the initial subset of 80 patients also underwent angiography. During the first 48 hours of hospital stay, an increase or a decrease of 1 or more points in the admission Canadian Neurological Scale (CNS) score was defined as early improvement or early deterioration, respectively. Repeated CT scan or autopsy was performed 5 to 9 days after stroke.

Results
Thirty-four patients (22%) improved, 84 (56%) remained stable, and 34 (22%) deteriorated. Logistic regression, which took into account vascular risk factors, baseline clinical and CT data, and therapies administered, selected younger age, lower admission CNS score, and absence of early hypodensity at first CT as independent predictors of early improvement. Among the patients who underwent angiography, logistic regression selected arterial patency and presence of collateral blood supply as independent predictors of early improvement. At the repeated CT scan or autopsy, improving patients presented the highest frequency of small infarcts. Thirty-day case-fatality rate and disability were lower in improving patients. Variables independently associated with outcome at logistic regression were admission CNS score, early deterioration, and early improvement.

Conclusions
Early improvement can be predicted by the absence of early CT hypodensity and is highly predictive of good outcome. Presence of collateral blood supply and presumably early spontaneous recanalization are likely to be the mechanisms underlying early improvement.
Cerebral Hemispheric Low-Flow Infarcts in Arterial Occlusive Disease
Authors: Mull Michael , Schwarz Michael , Thron Armin
Published: June 2011

Background and Purpose
Among the pathogenetic causes of subcortical hemispheric infarcts are small-vessel disease, thromboembolic occlusions of small arteries, and hemodynamic compromise in low-flow conditions. A topographic classification of these infarcts based on CT and MRI can be misleading.

Methods
We evaluated 30 consecutive patients with presumed supratentorial low-flow infarcts. CT was available in all cases, with additional MRI in 14 patients. In all cases the occlusion pattern of the extracranial and intracranial arterial system was studied in detail with angiography.

Results
The dominant lesion patterns seen on CT and MRI were multilocal chainlike lesions in 19 and confluent striated lesions in 8 cases located in the supraventricular and paraventricular deep white matter. In 8 patients subcortical lesions extended into the adjacent cortex. Angiography revealed that extracranial occlusive disease (n=24) or stenosis of the middle cerebral artery (n=6) was always accompanied by impairment of the circle of Willis, in either the anterior part (n=25) and/or the posterior part (n=16). Moreover, leptomeningeal pathways indicative of vascular hemispheric compromise were identified in 26 cases. In total, 29 of 30 patients displayed a noncompetent circle of Willis.

Conclusions
Low-flow infarcts show typical but not pathognomonic lesion patterns on CT and MRI. Definite diagnosis requires knowledge of the complex vascular compromise of the extracranial and/or intracranial arterial system. A noncompetent circle of Willis should be regarded as the additional predisposing condition in hemispheric low-flow infarcts.
Incomplete Brain Infarction of Reperfused Cortex May Be Quantitated With Iomazenil
Authors: Nakagawara Jyoji , Sperling Bjørn , Lassen Niels A.
Published: June 2011

Background and Purpose
[
123
I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies.

Methods
Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected as regions of interest to estimate receptor binding 5 days to 23 months after the stroke. A two-compartment model was used to compute the distribution volume (Vd) of iomazenil in relative units, with Vd proportional to benzodiazepine receptor concentration. The side-to-side asymmetry ratio of Vd was calculated.

Results
The mean asymmetry ratio was 0.89±0.11 (range, 0.64 to 1.05), 0.50±0.15 (range, 0.23 to 0.67), and 0.97±0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted cortex showed significant decrease of Vd (
P
<.00l). Contralateral cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6 months after the stroke, mild cortical atrophy was observed in two reperfused areas where the asymmetry ratio was moderately reduced (0.64 and 0.80).

Conclusions
The reduction of benzodiazepine receptor concentration in reperfused cortex that remained structurally intact is likely to be the result of injury involving only a limited number of neurons (ie, incomplete infarction). Our data suggest that the degree of viability of ischemic cortex apparently salvaged by early reperfusion can be quantified by iomazenil.
African Americans and Women Have the Highest Stroke Mortality in Texas
Authors: Morgenstern Lewis B. , Spears William D. , Goff David C. , Grotta James C. , Nichaman Milton Z.
Published: June 2011

Background and Purpose
Hispanic American (HA), African American (AA), and non-Hispanic white (NHW) populations are well represented in Texas. The Texas HA population is 95% Mexican American, affording comparison with other Hispanic populations. From risk factor profiles we expected stroke mortality to be highest in AAs and HAs. We also expected stroke mortality to be considerably higher for men than for women based on previous data.

Methods
We used
International Classification of Diseases, 9th Revision,
codes 430 to 438 to search Texas vital statistics data for the 5-year period from 1988 through 1992. Race/ethnic differences are presented in age- and sex-specific format to avoid masking the important interaction of age and sex with stroke mortality.

Results
Women constituted 61% of the 40 346 stroke deaths in Texas during this period. The ratio of stroke deaths for women versus men approximates the ratio of women to men in the population. AAs had a threefold to fourfold increased stroke mortality relative to NHWs at young ages. At older ages, when stroke mortality is the highest, the stroke mortality rate in NHWs approached the stroke mortality rate of AAs. HAs had a significantly higher rate of stroke mortality at younger ages relative to NHWs but a significantly lower rate at older ages.

Conclusions
Measures to prevent stroke mortality should emphasize its predilection for young AAs and women. A rigorous surveillance project is needed to determine whether stroke mortality is underestimated in the HA population.
Reperfusion Decreases Myogenic Reactivity and Alters Middle Cerebral Artery Function After Focal Cerebral Ischemia in Rats
Authors: Cipolla Marilyn J. , McCall Anthony L. , Lessov Nikola , Porter John M.
Published: June 2011

Background and Purpose
After focal cerebral ischemia, the function of cerebral arteries is critical to maintain cerebrovascular resistance and minimize damage to ischemic brain regions during reperfusion. In this study we examined the contractile function of isolated and pressurized middle cerebral arteries (MCAs) after 2 hours of occlusion with either 1 to 2 minutes or 24 hours of reperfusion using the intraluminal suture model of transient focal ischemia in rats.

Methods
MCAs were dissected after 2 hours of occlusion with either 1 to 2 minutes (OCC, n=8) or 24 hours (RPF, n=5) of reperfusion and compared with those of controls that did not have surgery (n=5). Isolated MCAs were mounted on two glass cannulas in an arteriograph chamber that allowed control over transmural pressure (TMP) and measurement of lumen diameter. Responses to changes in TMP (including myogenic reactivity, basal tone, and passive distensibility) and sensitivity to serotonin and acetylcholine were compared.

Results
Increasing TMP from 25 to 75 mm Hg caused vasoconstriction and development of tone that was similar in control and OCC arteries: percent tone was 33±5% versus 25±7% (
P
>.05). In contrast, tone was severely diminished in RPF MCAs after 24 hours of reperfusion: percent tone=8±4% (
P
<.01). Sensitivity to serotonin was reduced in OCC arteries, increasing the EC
50
value from 0.04±0.1 to 0.11±0.02 μmol/L (
P
<.05); after 24 hours of reperfusion, sensitivity of RPF MCAs was similar to control. Vasodilation to 10.0 μmol/L acetylcholine was significantly impaired only in RPF arteries: percent increased lumen diameter was 19±3% (control) and 13±4% (OCC,
P
>.05) versus 9±2% (RPF,
P
<.01). Passively, OCC MCAs were more distensible, which was reversed after 24 hours of reperfusion; RPF vessels had distensibility similar to that of control arteries but thicker arterial walls.

Conclusions
Abnormal structure and function of MCAs occur after 2 hours of ischemia, with diminished myogenic reactivity and tone associated with longer reperfusion.
Vascular Events During Follow-up in Patients With Aortic Arch Atherosclerosis
Authors: Mitusch Rolf , Doherty Christopher , Wucherpfennig Heiner , Memmesheimer Christian , Tepe Claudia , Stierle Ulrich , Kessler Christoph , Sheikhzadeh Abdolhamid
Published: June 2011

Background and Purpose
An association between aortic arch atherosclerosis and vascular events has been demonstrated. However, few data exist regarding follow-up evaluation of this disease.

Methods
In this study, 183 patients with the diagnosis of aortic arch atherosclerosis were prospectively followed up. This diagnosis was made during an echocardiographic cross-sectional study. In 136 patients, raised plaques with thickness <5 mm had been shown to exist, and in 47 patients complex plaques with thickness ≥5 mm or plaques with mobile components had been demonstrated on the initial transesophageal echocardiography.

Results
During a mean follow-up period of 16±7 months, vascular events with a presumed embolic origin occurred in 15 patients. The incidence was 4.1 per 100 person-years in patients with raised plaques compared with 13.7 per 100 person-years in the group with complex plaques. The Kaplan-Meier survival analysis revealed a significantly higher rate of vascular events in patients who were found to have complex plaques (
P
<.01). In the Cox proportional hazards analysis, the finding of complex plaques (relative risk [RR], 4.3; 95% confidence interval [CI], 1.5 to 12.0;
P
=.006), coronary artery disease (RR, 4.0; 95% CI, 1.2 to 13.1;
P
=.02), and a history of previous embolism (RR, 4.0; 95% CI, 1.1 to 14.4;
P
=.03) were independent predictors of vascular events.

Conclusions
Patients with the finding of protruding plaques or plaques with mobile components have a high risk of subsequent vascular events.
Prevalence and Risk Factors of Incontinence After Stroke
Authors: Nakayama H. , Jørgensen H.S. , Pedersen P.M. , Raaschou H.O. , Olsen T.S.
Published: June 2011

Background and Purpose
The purpose of this study was to investigate in a community-based population the prevalence of both urinary (UI) and fecal (FI) incontinence and to analyze risk factors by means of multivariate analysis.

Methods
Included were 935 acute stroke patients admitted consecutively during 19 months. We evaluated UI and FI using subscores of the Barthel Index during the hospital stay and at 6-month follow-up.

Results
On admission, the proportions of patients with full UI, partial UI, and no UI were 36%, 11%, and 53%, respectively (8%, 11%, and 81% at 6-month follow-up). The proportions of patients with full FI, partial FI, and no FI on admission were 34%, 6%, and 60%, respectively (5%, 4%, and 91% at 6-month follow-up). By multivariate analysis, significant risk factors for UI and FI were age, severity of stroke, diabetes, and comorbidity of other disabling diseases.

Conclusions
On admission in the acute state, almost half of an unselected stroke population have UI and/or FI. The proportion declines to one fifth (UI) and one tenth (FI) of the surviving patients at 6 months. Increasing age, stroke severity, diabetes, and other disabling diseases increase the risk of UI as well as FI.
Outcome of Aneurysmal Subarachnoid Hemorrhage in Patients on Anticoagulant Treatment
Authors: Rinkel Gabriel J.E. , Prins Nanine E.M. , Algra Ale
Published: June 2011

Background and Purpose
Intracranial hemorrhage is an important complication of treatment with anticoagulants. We studied outcome of aneurysmal subarachnoid hemorrhage (SAH) occurring in patients on anticoagulant drugs because this may influence management of patients needing anticoagulant treatment but with increased risk of aneurysmal hemorrhage.

Methods
From the prospective database of patients admitted with SAH to the Utrecht University Hospital, we compared 3-month outcome in patients with or without anticoagulant drugs by means of stratified analyses to adjust relative risks for biological and clinical differences between the two groups.

Results
Death or dependency after SAH occurred in 14 of 15 patients on anticoagulant treatment and in 62 of 126 patients not being treated with anticoagulants (relative risk, 1.9; 95% confidence interval, 1.5 to 2.4).The patients on treatment with anticoagulants were more often comatose on admission; the frequencies of rebleeding, secondary ischemia, and hydrocephalus were not higher in patients on anticoagulants. In the stratified analysis, the worse outcome in the group on anticoagulant drugs was not essentially influenced by differences in sex, age, cardiovascular history, site of aneurysm, amount of cisternal blood, or extension of hemorrhage into the ventricles.

Conclusions
The outcome of aneurysmal SAH in patients on anticoagulant drugs is extremely poor. The explanation for the worse prognosis in patients on anticoagulants lies in a worse clinical condition from the outset. The poor outcome urges a reconsideration of the balance of risks for anticoagulant treatment in patients with an unoperated intracranial aneurysm or with a family history of SAH and may lead to withholding treatment with anticoagulant drugs or to a preventive operation.
Stroke Unit Treatment
Authors: Indredavik B. , Slørdahl S. A. , Bakke F. , Rokseth R. , Håheim L. L.
Published: June 2011

Background and Purpose
We have previously shown that treatment in our combined acute and rehabilitation Stroke Unit improves outcome during the first year after onset of stroke compared with stroke patients treated in general wards. The aim of the present trial was to examine the long-term effects of the stroke unit care.

Methods
In a randomized controlled trial, 110 patients with symptoms and signs of an acute stroke were allocated to the Stroke Unit and 110 to general wards. No significant differences existed in baseline characteristics between the two groups. The outcome after 5 years was measured by the proportion of patients at home, the proportion of patients in an institution, the mortality, and the functional state assessed by Barthel Index.

Results
After 5 years, 38 (34.5%) of the patients randomized to the Stroke Unit and 20 (18.2%) of the patients randomized to the general wards were at home (
P
=.006). Sixty-five (59.1%) of the patients from the Stroke Unit and 78 (70.9%) of the patients from the general wards were dead (
P
=.041), while 7 (6.4%) and 12 (10.9%), respectively, were in an institution (eg, nursing home) (
P
=NS). Functional state was significantly better for patients treated in the Stroke Unit.

Conclusions
For the first time it is shown that stroke unit care improves long-term survival and functional state and increases the proportion of patients able to live at home 5 years after the stroke. Combined acute and rehabilitation stroke units appear to be an effective way of organizing treatment for acute stroke patients.
1
H-MRS Differentiates White Matter Hyperintensities in Subcortical Arteriosclerotic Encephalopathy From Those in Normal Elderly
Authors: Brooks William M. , Wesley Mary H. , Kodituwakku Piyadasa W. , Garry Philip J. , Rosenberg Gary A.
Published: June 2011

Background and Purpose
White matter hyperintensities in MRI of the brain are often seen in normal elderly subjects. Radiologically, these hyperintense regions are similar to those in symptomatic patients with subcortical arteriosclerotic encephalopathy (SAE). Our aim was to discriminate white matter hyperintensities (WMH) on MRI in patients with SAE from similar appearing changes in normal elderly.

Methods
Three groups of elderly patients were studied: symptomatic patients with WMH of SAE (n=5); asymptomatic subjects with diffuse, confluent WMH (n=4); and elderly control subjects (n=5). Proton density images revealed WMH in the occipital lobes. Proton magnetic resonance spectroscopy (
1
H-MRS) was used to acquire spectra in these hyperintensities. Metabolite concentrations were calculated from peak areas of
N
-acetylaspartate (NAA), creatine (Cre), and choline (Cho).

Results
The NAA/Cre and NAA/Cho ratios were reduced in the SAE group compared with the two asymptomatic groups (
P
<.05). NAA was decreased and Cho elevated in SAE compared with control subjects (
P
<.05). The average volumes of WMH in the SAE group (65.5 cm
3
) and in asymptomatic control subjects (59.4 cm
3
) were similar, and greater than those of the normal control group (4.0 cm
3
).

Conclusions
Proton MRS discriminates WMH in SAE patients from those in asymptomatic elderly, suggesting differing causes of the hyperintensities.
Acetylsalicylic Acid Increases Tolerance Against Hypoxic and Chemical Hypoxia
Authors: Riepe Matthias W. , Kasischke Karl , Raupach Anett
Published: June 2011

Background and Purpose
Treatment with acetylsalicylic acid (ASA) is established for secondary stroke prevention. Recent studies showed neuroprotection of ASA against glutamatergic excitants. The goal of this study was to investigate the time course of neuroprotection of ASA against indirect excitotoxicity by hypoxic hypoxia and chemical hypoxia.

Methods
Population spike amplitude (PSA) and ATP content were measured in hippocampal slices from untreated control animals (c-slices) and slices prepared from animals pretreated in vivo with a single intraperitoneal injection of 20 mg/kg body wt ASA 1 to 48 hours before slice preparation (p-slices).

Results
Posthypoxic recovery of PSA was 30% in c-slices (15 minutes of hypoxia, 45 minutes of recovery). When c-slices were treated in vitro for 15 minutes with 20 mg/L ASA 30 minutes before hypoxia, posthypoxic recovery improved to 82±4% (mean±SE,
P
<.01). In p-slices, posthypoxic recovery of PSA improved in a time-dependent manner. With a time interval of 1 hour between in vivo pretreatment with ASA and slice preparation, posthypoxic recovery of PSA was 64±16% (
P
<.05). With time intervals of 6 hours, 24 hours, and 48 hours, posthypoxic recovery of PSA was 87±19% (
P
<.01), 59±12%, and 40±9%, respectively. Pretreatment with ASA in vitro or in vivo decreased the decline of ATP content during hypoxic hypoxia and chemical hypoxia (inhibition of succinic dehydrogenase by 3-nitropropionic acid). When extracellular glucose was reduced to 4 mmol/L, no difference was observed between c-slices and p-slices.

Conclusions
We conclude that ASA is neuroprotective against hypoxic hypoxia and chemical hypoxia and delays the decline of intracellular ATP content.
Inhibition of Experimental Vasospasm With Anti–Intercellular Adhesion Molecule-1 Monoclonal Antibody in Rats
Authors: Oshiro Eric M. , Hoffman Patricia A. , Dietsch Gregory N. , Watts Mark C. , Pardoll Drew M. , Tamargo Rafael J.
Published: June 2011

Background and Purpose
Inflammation may play a role in delayed chronic vasospasm after aneurysmal subarachnoid hemorrhage. We investigated the role of intercellular adhesion molecule-1 (ICAM-1) and macrophage/granulocyte infiltration in the rat femoral artery model of vasospasm using systemic administration of a murine anti–ICAM-1 monoclonal antibody (MAb).

Methods
The femoral arteries (n=72) in Sprague-Dawley rats (n=36) were enclosed in latex pouches bilaterally. Autologous blood was injected into the pouch on one side, and saline was injected on the contralateral side. Chronic vessel narrowing was evaluated with the use of 29 rats, which were randomized into one of three groups for intraperitoneal injections: (1) anti–ICAM-1 MAb (2 mg/kg per dose, n=10), (2) isotype-matched MAb (2 mg/kg per dose, n=9), or (3) saline (n=10), given at 3 hours and 3, 6, and 9 days after blood exposure. These rats were killed 12 days after blood exposure, and femoral artery lumen cross-sectional areas were determined by computerized image analysis. Saturation of ICAM-1 binding sites with this dosing schedule was evaluated by fluorescence-activated cell sorter (FACS) analysis of splenocytes. Immunohistochemical studies with objective cell counts were performed to evaluate macrophage/granulocyte infiltration at 24 hours in 7 rats, comparing anti–ICAM-1 MAb treatment (n=4) with isotype-matched control MAb (n=3).

Results
Animals treated with anti–ICAM-1 MAb showed a significant inhibition of arterial narrowing at 12 days (
P
=.0081), with lumen patency of 96.5±5.3% (mean±SEM), compared with 77.3±5.6% for isotype-matched MAb and 72.2±5.3% for saline-treated controls. FACS analysis of splenocytes from animals treated with anti–ICAM-1 MAb confirmed saturation of ICAM-1 binding sites. Vessels treated with anti–ICAM-1 MAb showed a significant decrease in inflammatory cell infiltrates, with objective macrophage/granulocyte counts of 31.3±26.6 (mean±SEM) per high-powered field, compared with 171.4±30.7 for isotype-matched control MAb (
P
=.0027).

Conclusions
Anti–ICAM-1 MAb administered systemically starting 3 hours after blood exposure results in significant inhibition of chronic vasospasm in the rat femoral artery model and is correlated with a reduction in the number of infiltrating macrophages and granulocytes in the periadventitial region of blood-exposed arteries. We conclude that inflammatory changes associated with ICAM-1–mediated macrophage and granulocyte migration play an important role in the development of posthemorrhagic chronic vasospasm in this model.