bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Ultrasound Observation of Carotid Artery Plaque Ulceration
Authors: Schminke Ulf , Motsch Lillian , Hilker Lutz , Kessler Christof
Published: June 2011

Background and Purpose
—Carotid artery plaque ulceration is associated with an increased risk of cerebral embolism. However, because of the rather poor diagnostic quality of conventional 2-D ultrasound and angiography compared with the evaluation of pathological specimens, little information exists on the natural course of carotid plaque ulceration. Recently, the introduction of 3-D ultrasound has made reproducible investigation of plaque morphology possible, providing a reliable plaque surface analysis.

Methods
—We performed 3-D ultrasound examinations of 17 carotid artery plaques with an ulcerated surface in a prospective study of 16 patients (10 men, 6 women; mean±SD age 68.9±7.1 years) over a mean observation period of 17.6±6.3 months. Exactly parallel B-mode ultrasound scans (slice distance 0.1 mm) were acquired with a 5-MHz linear array probe clamped in a carriage device and driven by a mechanical step motor. The recorded images were reconstructed into a volumetric data set in a Cartesian coordinate system.

Results
—At the end of the observation period, surface configuration had changed in 4 cases (23.5%). Plaque ulceration regressed in 3 cases, whereas ulcer progression occurred in 1 case. The remaining 13 plaques (76.5%) showed an unchanged surface configuration.

Conclusions
—Through the use of 3-D ultrasound, it is possible to noninvasively examine the regression and progression of carotid artery plaque ulceration.
Collateral Variations in Circle of Willis in Atherosclerotic Population Assessed by Means of Transcranial Color-Coded Duplex Ultrasonography
Authors: Hoksbergen A. W. J. , Legemate D. A. , Ubbink D. T. , Jacobs M. J. H. M.
Published: June 2011

Background and Purpose
—Transcranial color-coded duplex ultrasonography combined with common carotid artery (CCA) compression can be used to assess the collateral function of the circle of Willis. The aim of this study was to assess the unknown fraction of hemodynamic functional anterior and posterior communicating arteries (AcoA and PcoA, respectively) in an atherosclerotic population with no cerebrovascular symptoms.

Methods
—In 76 patients with a mean age of 61 (35 to 89) years, the blood flow velocity changes in the precommunicating parts (A1 and P1, respectively) of the anterior and posterior cerebral arteries were measured during CCA compression. The AcoA was defined as functional if blood flow was reversed in the ipsilateral A1 and enhanced in the contralateral A1 during CCA compression. The PcoA was defined as functional if the flow velocity in the P1 was enhanced >20% during ipsilateral CCA compression.

Results
—It was possible to assess cross flow through the anterior part of the circle of Willis in 95% of the subjects. Failure of this collateral pathway was caused by a hypofunctional AcoA in 4% and a hypofunctional A1 in 1% of the subjects. Anomalies in the posterior part of the circle of Willis hampering collateral flow from the basilar to the internal carotid artery were found in 45% of the hemispheres. Thirty-eight percent of PcoAs were hypofunctional, and 7% of the posterior cerebral arteries had a persistent fetal anatomy.

Conclusions
—We found that in subjects with no cerebrovascular symptoms, the anterior collateral pathway of the circle of Willis was nearly always functional. In contrast, the posterior collateral pathway was nonfunctional in almost half of the total number of hemispheres. Comparing these basic data with data from patients with cerebral ischemic disease might further help to elucidate the importance of the collateral capacity of the circle of Willis.
Effects of Fluid Management on Edema Volume and Midline Shift in a Rat Model of Ischemic Stroke
Authors: Paczynski Richard P. , Venkatesan Ramesh , Diringer Michael N. , He Yong Y. , Hsu Chung Y. , Lin Weili
Published: June 2011

Background and Purpose
—The purpose of this study was to investigate the effects of fluid management on brain water content (BW) and midline shift (MLS) after a focal cerebral ischemic insult.

Methods
—A suture model was used to induce focal cerebral ischemia for 90 minutes (n=44). The rats were randomly assigned to 3 groups 2.5 hours after reperfusion: dehydration (n=24), control (n=8), or hydration (n=12). BW was obtained with the wet-dry weight method 24 hours after middle cerebral artery (MCA) occlusion. In addition, MRI were obtained (n=31) 24 hours after the onset of ischemia so that the ratio of hemispheric volumes ipsilateral (IH) and contralateral (CH) to the infarct and the extent of MLS could be obtained.

Results
—Across the range from moderate dehydration to intravascular volume expansion with isotonic saline, BW of the IH increased linearly as a function of change in body weight (
r
2
=0.89), whereas few changes in relation to body weight were observed in CH, indicating a preferential effect of fluid management on the infarcted hemisphere. Furthermore, the hemispheric volume ratio (IH/CH) and MLS also increased in relation to changes in body weight. However, paradoxical increases in BW, IH/CH, and extent of MLS were observed in comparison with controls when severe dehydration was produced with high-dose mannitol.

Conclusions
—Changes in ischemic BW by fluid management correlated closely with changes in body weight except when high-dose mannitol was used. Mannitol, as a dehydrating agent, may be associated with bimodal effects, with a high dose aggravating ischemic BW.
Low-Molecular-Weight Heparins and Heparinoids in Acute Ischemic Stroke
Authors: Bath Philip M. W. , Iddenden Robert , Bath Fiona J.
Published: June 2011

Background and Purpose
—Low-molecular-weight heparins and heparinoids (LMWHs) are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism and acute coronary syndromes. We performed a systematic review of randomized controlled trials (RCTs) to examine the safety and efficacy of LMWH in acute ischemic stroke.

Methods
—Randomized, controlled, and nonconfounded trials of LMWH in acute ischemic stroke were identified from the Cochrane Library (version 2, 1999), previous systematic reviews, and a review of publication quality relating to acute stroke trials. The authors each independently extracted data by treatment group and assessed trial quality using Cochrane Collaboration criteria.

Results
—Eleven completed RCTs involving 3048 patients were identified; data were available from 10 of these. Four trials explicitly excluded patients with presumed cardioembolic stroke. Treatment with LMWH was associated with significant reductions in prospectively identified deep vein thrombosis (OR 0.27, 95% CI 0.08 to 0.96) and symptomatic pulmonary embolism (OR 0.34, 95% CI 0.17 to 0.69) and with increased major extracranial hemorrhage (OR 2.17, 95% 1.10 to 4.28). Nonsignificant increases in end-of-treatment (OR 1.20, 95% CI 0.86 to 1.69) and end-of-trial (OR 1.05, 95% CI 0.83 to 1.32) case fatality and symptomatic intracranial hemorrhage (OR 1.77, 95% CI 0.95 to 3.31) were observed. End-of-trial death and disability was nonsignificantly reduced (OR 0.87, 95% CI 0.72 to 1.06).

Conclusions
—LMWHs reduce venous thromboembolic events in patients with acute ischemic stroke and increase the risk of extracranial bleeding. A nonsignificant reduction in combined death and disability and nonsignificant increases in case fatality and symptomatic intracranial hemorrhage were also observed. On the basis of the current evidence, LMWH should not be used in the routine management of patients with ischemic stroke.
Timing of Recanalization After Tissue Plasminogen Activator Therapy Determined by Transcranial Doppler Correlates With Clinical Recovery From Ischemic Stroke
Authors: Christou Ioannis , Alexandrov Andrei V. , Burgin W. Scott , Wojner Anne W. , Felberg Robert A. , Malkoff Marc , Grotta James C.
Published: June 2011

Background
—The duration of cerebral blood flow impairment correlates with irreversibility of brain damage in animal models of cerebral ischemia. Our aim was to correlate clinical recovery from stroke with the timing of arterial recanalization after therapy with intravenous tissue plasminogen activator (tPA).

Methods
—Patients with symptoms of cerebral ischemia were treated with 0.9 mg/kg tPA IV within 3 hours after stroke onset (standard protocol) or with 0.6 mg/kg at 3 to 6 hours (an experimental institutional review board–approved protocol). National Institutes of Health Stroke Scale (NIHSS) scores were obtained before treatment, at the end of tPA infusion, and at 24 hours; Rankin Scores were obtained at long-term follow-up. Transcranial Doppler (TCD) was used to locate arterial occlusion before tPA and to monitor recanalization (Marc head frame, Spencer Technologies; Multigon 500M, DWL MultiDop-T). Recanalization on TCD was determined according to previously developed criteria.

Results
—Forty patients were studied (age 70±16 years, baseline NIHSS score 18.6±6.2). A tPA bolus was administered at 132±54 minutes from symptom onset. Recanalization on TCD was found at the mean time of 251±171 minutes after stroke onset: complete recanalization occurred in 12 (30%) patients and partial recanalization occurred in 16 (40%) patients (maximum observation time 360 minutes). Recanalization occurred within 60 minutes of tPA bolus in 75% of patients who recanalized. The timing of recanalization inversely correlated with early improvement in the NIHSS scores within the next hour (polynomial curve, third order
r
2
=0.429,
P
<0.01) as well as at 24 hours. Complete recanalization was common in patients who had follow-up Rankin Scores if 0 to 1 (
P
=0.006). No patients had early complete recovery if an occlusion persisted for >300 minutes.

Conclusions
—The timing of arterial recanalization after tPA therapy as determined with TCD correlates with clinical recovery from stroke and demonstrates a 300-minute window to achieve early complete recovery. These data parallel findings in animal models of cerebral ischemia and confirm the relevance of these models in the prediction of response to reperfusion therapy.
Cerebral Blood Flow and Blood Volume Measured by Magnetic Resonance Imaging Bolus Tracking After Acute Stroke in Pigs
Authors: Sakoh Masaharu , Røhl Lisbeth , Gyldensted Carsten , Gjedde Albert , Østergaard Leif
Published: June 2011

Background and Purpose
—Early and accurate assessments of cerebral ischemia allow therapy to be tailored to individual stroke patients. We examined the feasibility of using a novel method for measuring cerebral blood flow (CBF) of ischemic tissue based on MRI after middle cerebral artery occlusion (MCAO). Moreover, the regional correlations between CBF and cerebral blood volume (CBV) were investigated in the regions with acute ischemic stroke.

Methods
—CBF and CBV were measured before and after MCAO or reperfusion by positron emission tomography (PET) in 13 pigs. Just after the PET scans, CBF and CBV were measured by MR bolus tracking and were compared with results obtained by PET at 6 hours after permanent MCAO or reperfusion. The infarction was verified histologically.

Results
—The MR method yielded parametric CBF and CBV maps with tissue contrast in good agreement with parametric PET images, which demonstrated hypoperfused and hyperperfused areas after MCAO or reperfusion. Both MRI and PET technology showed that CBF values below 60% of the contralateral value induced a reduction of CBV, which committed the tissue to infarction.

Conclusions
—The novel MR method provides accurate measurement of CBF and CBV in acute stroke and hence gives useful information for planning the appropriate therapeutic intervention.
Superoxide Generation Links Nociceptin/Orphanin FQ (NOC/oFQ) Release to Impaired
N
-Methyl-
d
-Aspartate Cerebrovasodilation After Brain Injury
Authors: Kulkarni Miriam , Armstead William M.
Published: June 2011

Background and Purpose
—Although activation of the
N
-methyl-
d
-aspartate (NMDA) receptor is thought to contribute to altered cerebrovascular regulation after traumatic brain injury, the effects of such injury on the vascular response to NMDA itself has been less well appreciated. The newly described opioid nociceptin/orphanin FQ (NOC/oFQ) elicits pial artery dilation, at least in part, in a prostaglandin-dependent manner and is released into cerebrospinal fluid after fluid percussion brain injury (FPI). Generation of superoxide anion (O
2
−
) occurs after FPI, and a byproduct of cyclooxygenase metabolism is the generation of O
2
−
. This study was designed to determine whether NOC/oFQ generates O
2
−
, which in turn could link NOC/oFQ release to impaired NMDA-induced pial artery dilation after FPI.

Methods
—Injury of moderate severity (1.9 to 2.1 atm) was produced by the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase–inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O
2
−
generation.

Results
—Under non–brain injury conditions, topical NOC/oFQ (10
−
10
mol/L, the concentration present in cerebrospinal fluid after FPI) increased superoxide dismutase–inhibitable NBT reduction from 1±1 to 20±3 pmol/mm
2
but had no effect itself on pial artery diameter. Indomethacin (5 mg/kg IV) blunted such NBT reduction (1±1 to 6±2 pmol/mm
2
), whereas the NOC/oFQ receptor antagonist [F/G] NOC/oFQ (1-13) NH
2
(10
−
6
mol/L) blocked NBT reduction. [F/G] NOC/oFQ (1-13) NH
2
and indomethacin also blunted the NBT reduction observed after FPI (1±1 to 15±1 versus 1±1 to 4±1 versus 1±1 to 4±1 pmol/mm
2
for sham, NOC/oFQ antagonist, and indomethacin-treated animals, respectively). NMDA (10
−
8
and 10
−
6
mol/L)–induced pial artery dilation was reversed to vasoconstriction after FPI, and [F/G] NOC/oFQ (1-13) NH
2
attenuated such vasoconstriction (sham 9±1% and 16±1% versus FPI −7±1% and −12±1% versus FPI–[F/G] NOC/oFQ (1-13) NH
2
–pretreated animals −2±1% and −3±1%). Indomethacin and the free radical scavengers polyethylene glycol superoxide dismutase and catalase also partially restored NMDA-induced vasodilation.

Conclusions
—These data show that NOC/oFQ, in concentrations present in cerebrospinal fluid after FPI, increased O
2
−
production in a cyclooxygenase-dependent manner and contributes to such production after FPI. These data show that NOC/oFQ contributes to impaired NMDA-induced pial artery dilation after FPI. Therefore, these data suggest that cyclooxygenase-dependent O
2
−
generation links NOC/oFQ release to impaired NMDA-induced cerebrovasodilation after brain injury.
Neuroimaging in Deteriorating Patients With Cerebellar Infarcts and Mass Effect
Authors: Koh Merian G. , Phan Thanh G. , Atkinson John L. D. , Wijdicks Eelco F. M.
Published: June 2011

Background and Purpose
—The decision to proceed with surgery in cerebellar infarct with mass effect (CIMASS) in deteriorating patients is based on clinical features. The potential role of neuroimaging in predicting deterioration has not been systematically studied. In this study we determine the role of neuroimaging in predicting deterioration in CIMASS.

Methods
—We retrospectively reviewed the clinical and neuroimaging features in 90 patients with cerebellar infarcts. We selected for detailed analysis CIMASS in 35 patients.

Results
—Eighteen patients remained stable and 17 deteriorated. Of these 17 patients, 8 were treated conservatively and 9 had surgery. Radiological features indicative of progression were more common in deteriorating patients compared with stable patients: fourth ventricular shift (82.3% versus 50%,
P
=0.075, OR=4.67), hydrocephalus (76.5% versus 11.1%,
P
=0.0001, OR=26), brain stem deformity (47% versus 5.6%,
P
=0.0065, OR=15.1), and basal cistern compression (35.3% versus 0%,
P
=0.0076, OR=20.91). Differences in upward displacement of the aqueduct and pontomesencephalic junction from Twining’s line, tonsillar descent on sagittal MRI, and infarct volumes between stable and deteriorating patients were not statistically significant.

Conclusions
—Hydrocephalus, brain stem deformity, and basal cistern compression may herald deterioration in CIMASS. Admission to a neurological-neurosurgical intensive care unit and consideration of preemptive surgery are warranted in these patients. Vertical displacement of tonsils or aqueduct, demonstrated by MR imaging, did not predict deterioration.
Variations in Stroke Incidence and Survival in 3 Areas of Europe
Authors: Wolfe Charles D.A. , Giroud Maurice , Kolominsky-Rabas Peter , Dundas Ruth , Lemesle Martine , Heuschmann Peter , Rudd Anthony
Published: June 2011

Background and Purpose
—Comparison of incidence and case-fatality rates for stroke in different countries may increase our understanding of the etiology of the disease, its natural history, and management. Within the context of an aging population and the trend for governments to set targets to reduce stroke risk and death from stroke, prospective comparison of such data across countries may identify what drives the variation in risk and outcome.

Methods
—Population-based stroke registers, using multiple sources of notification, ascertained cases of first in a lifetime stroke between 1995 and 1997 for all age groups. The study populations were in Erlangen, Germany; Dijon, France; and London, UK. Crude incidence rates were age-standardized to the European population for comparative purposes. Case-fatality rates up to 1 year after the stroke were obtained, and logistic regression adjusting for age group, sex, and pathological subtype of stroke was used to compare survival in the 3 communities.

Results
—A total of 2074 strokes were registered over the 3 years. The age-standardized rate to the European population was 100.4 (95% CI 91.7 to 109.1) per 100 000 in Dijon, 123.9 (95% CI 115.6 to 132.2) in London, and 136.4 (95% CI 124.9 to 147.9) in Erlangen. Both crude and adjusted rates were lowest in Dijon, France. The incidence rate ratio, with Dijon as the baseline comparison (1), was 1.21 (95% CI 1.09 to 1.34) in London and 1.37 (95% CI 1.22 to 1.54) in Erlangen (
P
<0.0001). There were significant differences in the proportion of the subtypes of stroke between populations, with London having lower rates of cerebral infarction and higher rates of subarachnoid hemorrhage and unclassified stroke (
P
<0.001). Case-fatality rates varied significantly between centers at 1 year, after adjustment for age, sex, and subtype of stroke (35% overall, 34% Erlangen, 41% London, and 27% Dijon;
P
<0.001).

Conclusions
—The impact of stroke is considerable, and the risk of stroke varies significantly between populations in Europe as does the risk of death. The striking differences in survival require clarification but lend weight to the evidence that stroke management may differ between northern and central Europe and influence outcome.
Five-Year Survival After First-Ever Stroke and Related Prognostic Factors in the Perth Community Stroke Study
Authors: Hankey Graeme J. , Jamrozik Konrad , Broadhurst Robyn J. , Forbes Susanne , Burvill Peter W. , Anderson Craig S. , Stewart-Wynne Edward G.
Published: June 2011

Background and Purpose
—Few community-based studies have examined the long-term survival and prognostic factors for death within 5 years after an acute first-ever stroke. This study aimed to determine the absolute and relative survival and the independent baseline prognostic factors for death over the next 5 years among all individuals and among 30-day survivors after a first-ever stroke in a population of Perth, Western Australia.

Methods
—Between February 1989 and August 1990, all individuals with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event.

Results
—Three hundred seventy patients with first-ever stroke were registered, and 362 (98%) were followed up at 5 years, by which time 210 (58%) had died. In the first year after stroke the risk of death was 36.5% (95% CI, 31.5% to 41.4%), which was 10-fold (95% CI, 8.3% to 11.7%) higher than that expected among the general population of the same age and sex. The most common cause of death was the index stroke (64%). Between 1 and 5 years after stroke, the annual risk of death was approximately 10% per year, which was approximately 2-fold greater than expected, and the most common cause of death was cardiovascular disease (41%). The independent baseline factors among 30-day survivors that predicted death over 5 years were intermittent claudication (hazard ratio [HR], 1.9; 95% CI, 1.2 to 2.9), urinary incontinence (HR, 2.0; 95% CI, 1.3 to 3.0), previous transient ischemic attack (HR, 2.4; 95% CI, 1.4 to 4.1), and prestroke Barthel Index <20/20 (HR, 2.0; 95% CI, 1.2 to 3.2).

Conclusions
—One-year survivors of first-ever stroke continue to die over the next 4 years at a rate of approximately 10% per year, which is twice the rate expected among the general population of the same age and sex. The most common cause of death is cardiovascular disease. Long-term survival after stroke may be improved by early, active, and sustained implementation of effective strategies for preventing subsequent cardiovascular events.
α
1
-Antichymotrypsin Gene Polymorphism in Patients With Stroke
Authors: Vila Nicolás , Obach Victor , Revilla Marian , Oliva Rafael , Chamorro Angel
Published: June 2011

Background and Purpose
—A role for proteolytic enzymes has been suggested in the pathogenesis of stroke. In a search for new genetic factors, we investigated the gene polymorphism of the serine protease inhibitor α
1
-antichymotrypsin (ACT) in patients with stroke.

Methods
—Two hundred twenty patients with acute ischemic stroke (n=182) and primary intracerebral hemorrhage (n=38) and 70 control subjects without clinical cerebrovascular disease were genotyped for the ACT polymorphism.

Results
—The ACT-TT genotype was more frequent in patients with primary intracerebral hemorrhage than in patients with ischemic stroke (31.6% versus16.4%,
P
<0.05) or in control subjects (21.4%,
P
=0.1). After adjusting for age, gender, and vascular risk factors, the ACT-TT genotype was associated with primary intracerebral hemorrhage, with an OR of 2.3 (95% CI 1.0 to 5.2) compared with ischemic stroke and an OR of 1.8 (95% CI 0.85 to 9.65) compared with controls.

Conclusions
—Pending confirmation in a larger study, our results suggest that the ACT-TT genotype might be a risk factor for primary cerebral hemorrhage.
Does Feeding Alter Arterial Oxygen Saturation in Patients With Acute Stroke?
Authors: Rowat Anne M. , Wardlaw Joanna M. , Dennis Martin S. , Warlow Charles P.
Published: June 2011

Background and Purpose
—We measured arterial oxygen saturation (Sa
o
2
) during eating in acute stroke patients to establish the frequency of any meal-related hypoxemia, which could further damage already vulnerable brain tissue.

Methods
—Stroke patients (≤12 days from stroke onset) classified as “safe to feed orally” were compared with elderly hospitalized (for nonneurological causes) and young healthy controls. Sa
o
2
was measured noninvasively at the bedside by pulse oximetry continuously for 10 minutes before the patient ate a meal, during the meal, and for 10 minutes after completion of the meal.

Results
—The median baseline Sa
o
2
was significantly lower in stroke patients (n=106, 95.7%) than elderly (n=50, 96.7%) or young control subjects (n=20, 97.9%;
P
<0.001). There was a small decrease in the median Sa
o
2
during eating in stroke and elderly patients (95.6%,
P
=0.08, and 96.3%,
P
=0.004, respectively) but not in young controls. Only stroke patients had a significantly lower median Sa
o
2
after completion of the meal (95.4%,
P
<0.001). Sa
o
2
of ≤90% during and after eating occurred in 24% of stroke and 16% of elderly patients but not in young controls, and it was significantly more common in those who had Sa
o
2
of ≤90% during the baseline recordings (
P
≤0.003).

Conclusions
—Eating a meal was associated with a small fall in median Sa
o
2
among stroke and elderly patients, but only in stroke patients did this persist for at least 10 minutes after eating. A quarter of stroke patients had episodes in which the Sa
o
2
fell to ≤90% saturation (ie, hypoxemia) during or after eating, although this rarely coincided exactly with swallowing and was more common in patients who also experienced desaturation during the baseline recordings. Further studies are required to establish whether these changes are clinically important.
Prediction of Malignant Middle Cerebral Artery Infarction by Diffusion-Weighted Imaging
Authors: Oppenheim C. , Samson Y. , Manaï R. , Lalam T. , Vandamme X. , Crozier S. , Srour A. , Cornu P. , Dormont D. , Rancurel G. , Marsault C.
Published: June 2011

Background and Purpose
—This study was designed to analyze whether early diffusion-weighted imaging (DWI) provides reliable quantitative information for the prediction of stroke patients at risk of malignant brain infarct.

Methods
—We selected 28 patients with a middle cerebral artery (MCA) infarct and proven MCA or carotid T occlusion on DWI and MRI angiography performed within 14 hours after onset (mean 6.5±3.5 hours, median 5.2 hours). Of these, 10 patients developed malignant MCA infarct, whereas 18 did not. For the 2 groups, we compared the National Institutes of Health Stroke Scale (NIHSS) score at admission, site of arterial occlusion, standardized visual analysis of DWI abnormalities, quantitative volume measurement of DWI abnormalities (volume
DWI
), and apparent diffusion coefficient values. Univariate and multivariate discriminant analysis was used to determine the most accurate predictors of malignant MCA infarct.

Results
—Univariate analysis showed that an admission NIHSS score >20, total versus partial MCA infarct, and volume
DWI
>145 cm
3
were highly significant predictors of malignant infarct. The best predictor was volume
DWI
>145 cm
3
, which achieved 100% sensitivity and 94% specificity. Prediction was further improved by bivariate models combining volume
DWI
and apparent diffusion coefficient measurements, which reached 100% sensitivity and specificity in this series of patients.

Conclusions
—Quantitative measurement of infarct volume on DWI is an accurate method for the prediction of malignant MCA infarct in patients with persistent arterial occlusion imaged within 14 hours of onset. This may be of importance for early management of severe stroke patients.
Reproducibility of Computer-Quantified Carotid Plaque Echogenicity
Authors: Sabetai M.M. , Tegos T.J. , Nicolaides A.N. , Dhanjil S. , Pare G.J. , Stevens J.M.
Published: June 2011

Background and Purpose
—We sought to assess the reproducibility, interobserver variability, and application to clinical studies of a new method for the quantitative assessment of carotid plaque echogenicity.

Methods
—Carotid plaques were scanned with the use of ultrasound, and their images were stored in a computer. They were normalized by assigning certain gray values to blood and adventitia, and the gray scale median (GSM) was used to quantify their echogenicity. The variability between storage media, between degrees of magnification, and between probes was assessed. The method was applied to 232 asymptomatic carotid plaques causing 60% to 99% stenosis in relation to the presence of ipsilateral CT-demonstrated brain infarcts. In all parts of the study the plaque GSM was measured before and after normalization to evaluate its effect. Interobserver agreement for the scanning process was assessed.

Results
—The GSM mean difference before and after normalization for variability studies of storage media, degrees of magnification, and probes was −14.5 and −0.12, 2.24 and 1.68, and −8.3 and −0.7, respectively. The median GSM of plaques associated with ipsilateral nonlacunar silent CT-demonstrated brain infarcts was 14, and that of plaques that were not so associated was 30 (
P
=0.003). The interobserver GSM difference was −0.05 (95% CI, −1.7 to 1.6).

Conclusions
—Our method decreases the variability between storage media and between probes but not the variability between degrees of magnification. It separates echomorphologically the carotid plaques associated with silent nonlacunar CT-demonstrated brain infarcts from plaques that are not so associated.
Noninvasive Measurement of Cerebral Blood Flow With
99m
Tc-Hexamethylpropyleneamine Oxime Single-Photon Emission Computed Tomography and 1-Point Venous Blood Sampling
Authors: Isaka Yoshinari , Furukawa Satoshi , Etani Hideki , Nakanishi Etsuko , Ooe Yosuke , Imaizumi Masatoshi
Published: June 2011

Background and Purpose
—The arterial and venous blood concentration of technetium 99m–labeled hexamethylpropyleneamine oxime (
99m
Tc-HMPAO) reaches an equilibration more rapidly than other CBF tracers. We hypothesized that
99m
Tc radioactivity of a venous sample at equilibrium, which is similar to that of an arterial sample, would allow estimation of the integrated input function for the clinical measurement of CBF by use of single-photon emission CT.

Methods
—In 53 patients with stable cerebrovascular disease, the radioactivity of a venous sample 5 minutes after injection of
99m
Tc-HMPAO was correlated with 5-minute arterial blood radioactivity and the first 5 minutes of the integrated arterial curves of the lipophilic tracer. The measured CBF values were compared with those of xenon 133.

Results
—–The radioactivity of 5-minute venous blood was almost equivalent to that of 5-minute arterial blood (
r
2
=0.987;
y
=0.993
x
+1.63;
P
<0.0001). The correlation between the venous blood radioactivity and the integrated arterial lipophilic fraction was excellent (
r
2
=0.935,
P
<0.0001). A strong correlation was obtained between
99m
Tc-HMPAO and
133
Xe CBF values (
r
2
=0.825,
P
<0.0001). CBF values were reproducible (coefficient of variation, 8.6%).

Conclusions
—-This approach is fast, simple, and an alternative to continuous blood sampling in clinical quantitative
99m
Tc-HMPAO CBF studies.
Hydroxyethyl Starch Reduces Leukocyte Adherence and Vascular Injury in the Newborn Pig Cerebral Circulation After Asphyxia
Authors: Kaplan Stuart S. , Park T. S. , Gonzales Ernesto R. , Gidday Jeffrey M.
Published: June 2011

Background and Purpose
—Hydroxyethyl starch (HES) has beneficial effects on ischemic brain injury; however, its mechanism of action remains unclear. The present study was undertaken to test the hypothesis that HES can attenuate increases in leukocyte adherence and vascular permeability in the cerebral vasculature after global cerebral ischemia induced by asphyxia.

Methods
—Pial venular leukocyte adherence and permeability to sodium fluorescein were quantified in anesthetized newborn piglets by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2 hours of reperfusion after global ischemia induced by 9 minutes of asphyxia. Experimental animals received HES after the asphyxial insult (10% HES 257/0.47, 600 mg/kg IV bolus 5 minutes after asphyxia, followed by 600 mg/kg per hour IV drip during reperfusion; n=9).

Results
—A progressive and significant (
P
<0.05) increase in adherent leukocytes was observed during the initial 2 hours of reperfusion after asphyxia compared with nonasphyxial controls. In this model, vascular injury, as determined by significant (
P
<0.05) increases in fluorescein permeability at 2 hours of reperfusion, is largely dependent on adherent leukocytes. HES significantly reduced (
P
<0.05) leukocyte adherence at 1 hour and 2 hours of reperfusion and reduced fluorescein permeability at 2 hours. HES did not change hematocrit or alter pial arteriolar diameter.

Conclusions
—These findings indicate that a vascular anti-inflammatory action may underlie the beneficial effects of HES in global cerebral ischemia secondary to asphyxia. Since this compound is well tolerated by patients, future preclinical and clinical studies may reveal improvements in functional outcome with the early introduction of this or similar agents after perinatal asphyxia or global ischemia.
Effects of Estrogen on Leukocyte Adhesion After Transient Forebrain Ischemia
Authors: Santizo Roberto A. , Anderson Susan , Ye Shuhua , Koenig Heidi M. , Pelligrino Dale A.
Published: June 2011

Background and Purpose
—Recent findings indicate that estrogen (ie, 17β-estradiol [E
2
]) provides neuroprotection in models of transient global and focal ischemia. Enhanced postischemic leukocyte adhesion and infiltration have been linked to neuropathology in the brain as well as other tissues. We recently showed that estrogen reduces leukocyte adhesion in the cerebral circulation of female rats during resting conditions.

Methods
—We compared leukocyte adhesion in pial venules in vivo in intact, ovariectomized (OVX), and E
2
-treated OVX female rats subjected to transient forebrain ischemia (30-minute right common carotid artery occlusion and hemorrhagic hypotension) and reperfusion. Adherent rhodamine-6G–labeled leukocytes were viewed through a closed cranial window with the use of intravital microscopy. Leukocyte adhesion was measured before ischemia and at different times after reperfusion.

Results
—Before ischemia, leukocyte adhesion (measured as a percentage of venular area occupied by adherent leukocytes) was 2 to 3 times greater in OVX versus intact or E
2
-treated OVX rats (7.0%, 3.4%, and 2.2%, respectively). This difference disappeared at 120 minutes of reperfusion, when comparable levels of enhanced leukocyte adhesion were observed in all groups. In OVX rats, leukocyte adhesion remained elevated after 4 and 6 hours of reperfusion (11.6% and 12.9%, respectively), while the other 2 groups showed significantly lower levels (5.0% and 5.8% for intact rats and 7.0% and 7.2% for E
2
-treated OVX rats).

Conclusions
—Present results demonstrate that estrogen modulates leukocyte adhesion in the cerebral circulation after transient forebrain ischemia. This effect suggests that decreased leukocyte adhesion may be an important mechanism in estrogen-mediated neuroprotection.
CO
2
Reactivity Measured by Perfusion MRI During Transient Focal Cerebral Ischemia in Rats
Authors: Olah Laszlo , Franke Claudia , Schwindt Wolfram , Hoehn Mathias
Published: June 2011

Background and Purpose
—CO
2
response was examined in rats undergoing 60 minutes of middle cerebral artery occlusion (MCAO) and 4.5 hours of reperfusion. Because it is not clear whether the vasoreactivity improves during reperfusion in parallel with tissue recovery, CO
2
response was determined spatially resolved, sequentially in the initially ischemic but later recovered areas and in the permanently damaged areas.

Methods
—Apparent diffusion coefficient (ADC) maps were calculated from diffusion-weighted images, whereas CO
2
reactivity maps were determined from the difference in perfusion signal intensity before and after CO
2
stimulation. CO
2
reactivity (administration of 6% CO
2
for 5 minutes) was expressed in % change of perfusion signal intensity/mm Hg of P
co
2
increase. ATP levels of tissue were used as a measure of outcome. The recovered and permanently damaged tissues were differentiated by combined use of end-ischemic ADC map and ATP image at the end of the experiment.

Results
—The preischemic (control) CO
2
reactivity of 3.5±0.9%/mm Hg decreased dramatically during MCAO in the ischemic hemisphere. During reperfusion, it remained <1%/mm Hg in the region with end-ischemic ADC <80% of the preischemic control value, but showed gradual recovery in the region with end-ischemic ADC >80% of control. Although at the end of the experiment the CO
2
reactivity was significantly higher in the recovered tissue than in the permanently damaged tissue (1.15±0.44 and 0.13±0.47%/mm Hg, respectively;
P
<0.01), it still remained far below the normal control value (
P
<0.01).

Conclusions
—The noninvasive perfusion-weighted MR imaging in combination with a CO
2
challenge permits the investigation of the spatially resolved vascular reactivity during a longitudinal study of cerebral ischemia. Our data suggest that severe ischemia is followed by a prolonged disturbance of CO
2
reactivity, despite already normalized energy metabolism.
A New Model of Cerebral Microthrombosis in Rats and the Neuroprotective Effect of a Rho-Kinase Inhibitor
Authors: Toshima Yoshinori , Satoh Shin-ichi , Ikegaki Ichiro , Asano Toshio
Published: June 2011

Background and Purpose
—The aim of this study was to develop a new model of stroke based on endothelial damage and thrombotic occlusion in a perforating artery, leading to small cerebral infarcts and neurological deficits in rats. Moreover, the neuroprotective efficacy of fasudil, a rho-kinase inhibitor, was investigated in this model.

Methods
—Fifty-six male Sprague-Dawley rats were used in the present study. Rats were anesthetized with sodium pentobarbital, and 100 μg of sodium laurate was injected into the left internal carotid artery on days 1 and 3. The thrombus induction and consequent of ischemic brain damage were examined by histopathological analyses and neurological deficit scoring in a posture reflex test. To investigate the neuroprotective effects of fasudil, 1 or 10 mg/kg was administered intraperitoneally 5 minutes after the first injection of sodium laurate and once daily thereafter on the following 2 days.

Results
—One hour after the injection of sodium laurate, microscopic examination of phosphotungstic acid hematoxylin–stained sections (n=5) revealed that microthrombi containing fibrin strands obstructed the perforating arteries in the ipsilateral hemisphere. Under a transmission electron microscope (n=6), endothelial cells appeared exfoliated and the vascular lumen was obstructed by a thrombus composed of degranulated platelets, fibrin, leukocytes, and erythrocytes. No evidence of endothelial cell damage or thrombus could be found in the ipsilateral side of the pial artery (middle cerebral artery). Twenty-four hours after the second injection of sodium laurate (day 4), 13 of 15 rats (86.6%) showed mild to severe neurological deficits. Multiple small cerebral infarcts were observed in the hippocampus, cortex, and thalamus. Treatment with fasudil (1 and 10 mg/kg, n=15 each) resulted in a significant improvement in neurological deficits. Fasudil also significantly reduced the area of cerebral infarction.

Conclusions
—We present a new model of stroke in rats, in which the perforating arteries are selectively occluded by microthrombi. This model is useful to investigate the pathophysiology and treatment of small cerebral infarction, which is caused by perforating arterial occlusive diseases such as lacunar infarcts. Fasudil may be beneficial in the treatment of acute ischemic stroke.
Predicting Treatment Costs After Acute Ischemic Stroke on the Basis of Patient Characteristics at Presentation and Early Dysfunction
Authors: Caro J. Jaime , Huybrechts Krista F. , Kelley Heather E.
Published: June 2011

Background
—Given the pressure on healthcare budgets, assessing the cost of managing a disease has become a major research focus; yet collection of these data are labor intensive and difficult. Understanding the predictors of cost provides an efficient means of incorporating such information in decision-making concerning new therapies.

Methods
—Data from two 12-week multinational trials that collected information on a variety of neurological, functional, and cost parameters for 1341 ischemic stroke patients were examined by means of multiple linear regression. Because the intent is for the model to be predictive, only patient characteristics that can be known at the time of patient presentation or shortly thereafter were evaluated for inclusion in the model.

Results
—The Barthel Index was the strongest predictor of cost in all models evaluated. Other major predictors, either directly or through their impact on survival, were stroke subtype, neurological impairment, congestive heart failure, and country. A good model fit was obtained, judging by the model statistics (model
F
=84, 3
df
,
P
<0.0001) and the accuracy of the predictions (<3% difference between mean actual and predicted cost).

Conclusions
—Through the use of key patient characteristics, this regression model allows for prediction of the cost of stroke care, which may be helpful in the context of therapeutic decisions and budgetary planning purposes. It also provides insight into how specific treatments, through their impact on clinical characteristics, can modify the cost of stroke treatment.
Carotid Stenting for Radiation-Induced Stenoses
Authors: Houdart Emmanuel , Mounayer Charbel , Chapot René , Saint-Maurice Jean-Pierre , Merland Jean-Jacques
Published: June 2011

Background and Purpose
—Radiation-induced stenoses of the carotid artery are associated with fibrosis of the arterial layers and tissue planes that renders their surgical treatment difficult. We present our clinical experience in carotid angioplasty stenting (CAS) of patients harboring such stenoses.

Methods
—Seven patients underwent transfemoral CAS of 10 radiation-induced stenoses located on either the common or the internal carotid artery. Six patients presented neurological symptoms. Four patients had undergone previous radical neck dissection, and 3 had permanent tracheostomies. Stenoses were primarily covered with a self-expandable stent before carotid dilation.

Results
—All interventions were successful, with residual stenoses <20%. No permanent complication occurred. The mean follow-up was 8 months. Patients were symptom free at the last clinical examination, and Doppler control showed no evidence of restenosis.

Conclusions
—Carotid stenting appears very attractive for such “hostile neck” patients and seems a safe and efficient treatment for radiation-induced stenoses.
Protocol Violations in Community-Based rTPA Stroke Treatment Are Associated With Symptomatic Intracerebral Hemorrhage
Authors: Lopez-Yunez Alfredo M. , Bruno Askiel , Williams Linda S. , Yilmaz Engin , Zurrú Cristina , Biller José
Published: June 2011

Background
—Recombinant tissue plasminogen activator (rTPA) is an established treatment for acute ischemic stroke. The rate and type of protocol violations in rTPA use and their effect on patient outcomes in this setting are not well understood.

Objective
—The objective of this study was to examine associations between protocol violations and outcomes in community-based rTPA use.

Methods
—We reviewed medical records of stroke patients treated with rTPA in 10 acute-care hospitals in Indianapolis from July 1996 to February 1998 and assessed complications and outcome. Retrospective National Institute of Health Stroke Scale (on admission and discharge), Canadian Neurological Scale, and length of hospital stay were calculated. Appropriate use of rTPA was determined by the National Institute of Neurological Disorders and Stroke (NINDS) protocol.

Results
—Fifty patients (mean age, 66 years; 76% white; 56% men) were treated by general neurologists (70%), stroke neurologists (24%), or emergency physicians (6%). Mean times to hospital arrival, brain CT, and start of rTPA infusion were 44, 86, and 141 minutes, respectively. In-hospital mortality rate was 10% (4 intracerebral hemorrhage [ICH], 1 cardiogenic shock). Complications were more frequent among patients with protocol violations (n=8) compared with those without all hemorrhages (75% versus 10%,
P
<0.001), symptomatic ICH (38% versus 5%,
P
<0.02), and ICH attributable to rTPA, occurring within 36 hours (38% versus 2.4%,
P
<0.01), respectively.

Conclusions
—NINDS protocol violations are relatively common and are associated with symptomatic cerebral and systemic hemorrhages. When the NINDS protocol is strictly followed, hemorrhage rates in community-based rTPA use are similar to those in the NINDS trial.
Natural History and Effects on 2-Year Outcomes of Urinary Incontinence After Stroke
Authors: Patel Mehool , Coshall Catherine , Rudd Anthony G. , Wolfe Charles D.A.
Published: June 2011

Background and Purpose
—We sought to describe the natural history of poststroke incontinence and estimate its effect on survival and 2-year outcomes in stroke survivors.

Methods
—Two hundred thirty-five incident cases of stroke in 1995 were classified by continence status at 10 days after stroke. Age, sex, ethnicity, diabetes, hypertension, atrial fibrillation, premorbid disability, and Oxfordshire Community Stroke Project classification were recorded. Outcome data collected at 3 months and at 1 and 2 years included disability, case-fatality rates, and institutionalization rates. Disability was classified as severe, moderate, mild, or independent using the Barthel Index (without its “continence” component: 0–9, 10–14, 15–17, and 18, respectively) and Frenchay Activity Index (0–15, 16–30, and 31–45).

Results
—Of 235 cases, 95 were initially incontinent (group 1); 140 were continent (group 2). At the initial, 3-month, and 1- and 2-year assessments, incontinence was recorded in 95 patients (40%), 34 (19%), 23 (15%), and 12 (10%), respectively. In univariate analyses, the 2 groups were not different in terms of demographic factors and risk factors. Compared with group 2, group 1 patients were more likely to have atrial fibrillation (28% versus 16%;
P
=0.02). Multivariate analyses showed that age >75 years (OR 15.9; CI 2.2 to 116.2), dysphagia (OR 4.03; CI 1.85 to 8.73), motor weakness (OR 5.41; CI 1.38 to 21.1) and visual field defects (OR 4.78; CI 1.78 to 12.9) were all significantly associated with incontinence. Incontinence was less common in lacunar infarctions (OR 0.12; CI 0.02 to 0.62). At 2 years, compared with group 2, group 1 had higher case-fatality rates (67% versus 20%;
P
<0.001), higher institutionalization rates (39% versus 16%;
P
=0.007), and greater disability (Barthel [0–9]: 39% versus 5%;
P
<0.001; Frenchay [0–15]: 75% versus 37%;
P
=0.001). Death or disability at 2 years was worse in subjects with initial incontinence(OR 4.43; CI 1.76 to 11.2).

Conclusions
—Incontinence remains a prevalent condition 2 years after stroke. Initial incontinence was associated with age >75 years, dysphagia, visual field defect, and motor weakness. Poststroke incontinence adversely affected 2-year stroke survival, disability, and institutionalization rates.