bluuebunny/crossref_metadata_2025 huggingface dataset:
Compensatory Mechanisms for Chronic Cerebral Hypoperfusion in Patients With Carotid Occlusion
Authors: Derdeyn Colin P. , Videen Tom O. , Fritsch Susanne M. , Carpenter David A. , Grubb Robert L. , Powers William J.
Published: June 2011

Background and Purpose
—The purpose of this experiment was to assess long-term cerebral hemodynamic and metabolic changes in patients with increased oxygen extraction fraction (OEF) in the hemisphere distal to an occluded carotid artery who remain free of stroke.

Methods
—Ten patients with increased OEF and no interval stroke underwent repeated positron emission tomography examinations 12 to 59 months after the initial examination. Quantitative regional measurements of cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism (CMRO
2
), and OEF were obtained. Regional measurements of the cerebral rate of glucose metabolism (CMRGlc) were made on follow-up in 5 patients. Statistical significance (
P
<0.05) was measured with
t
tests and linear regression analysis.

Results
—The ipsilateral/contralateral OEF ratio declined from a mean of 1.16 to 1.08 (
P
=0.022). Greater reductions were seen with longer duration of follow-up (
P
=0.023,
r
=0.707). The cerebral blood flow ratio improved from 0.81 to 0.85 (
P
=0.021). No change in cerebral blood volume or CMRO
2
was observed. CMRGlc was reduced in the ipsilateral hemisphere (
P
=0.001 compared with normal), but the CMRO
2
/CMRGlc ratio was normal.

Conclusions
—Increased OEF improves in patients with carotid occlusion and no interval stroke. This improvement in OEF is due to an improvement in collateral blood flow.
Plasma Homocyst(e)ine Concentration, But Not
MTHFR
Genotype, Is Associated With Variation in Carotid Plaque Area
Authors: Spence J. David , Malinow M. Rene , Barnett Peter A. , Marian Ali J. , Freeman David , Hegele Robert A.
Published: June 2011

Background and Purpose
—Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis. A common cause of elevated plasma H(e) concentration is a thermolabile mutation (677T) in the gene encoding methylenetetrahydrofolate reductase (
MTHFR
). We sought to determine whether plasma H(e) concentration or
MTHFR
genotype would be more strongly associated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis.

Methods
—In 307 subjects who were ascertained through a premature atherosclerosis clinic, we measured CPA with 2-dimensional ultrasound and also determined traditional atherosclerosis risk factors, in addition to plasma H(e) concentration and
MTHFR
genotypes.

Results
—We found that the frequency of the
MTHFR
677T allele was 0.363 in this sample. Mean plasma H(e) concentration was significantly higher in 677T/T homozygotes than in 677T/C heterozygotes and 677C/C homozygotes (17.1±13.7 versus 13.5±6.1 versus 12.6±5.9 μmol/L, respectively,
P
<0.001). Analysis of variance showed that CPA was significantly associated with age, sex, smoking, diabetes, hypertension, and hyperlipidemia (each
P
<0.05). When plasma H(e) concentration was included in the model, it was significantly associated with CPA (
P
<0.05). However, when the
MTHFR
genotype was included in the model, it was not associated with CPA (
P
=0.50). Furthermore, there was a significant correlation of CPA with plasma H(e) (
r
=0.23,
P
<0.0001). However, the mean CPA did not differ between subjects according to genotype.

Conclusions
—Thus, plasma H(e), but not
MTHFR
genotype, is significantly associated with carotid atherosclerosis, suggesting that the biochemical test may be sufficient to identify patients who may be at increased risk of atherosclerosis through this mechanism.
Hyperhomocysteinemia and Hypofibrinolysis in Young Adults With Ischemic Stroke
Authors: Kristensen Bo , Malm Jan , Nilsson Torbjörn K. , Hultdin Johan , Carlberg Bo , Dahlén Gösta , Olsson Tommy
Published: June 2011

Background and Purpose
—Data from epidemiological and case-control studies suggest that increased total homocysteine (tHcy) levels are associated with increased risk for thromboembolic disease. The mechanisms by which hyperhomocysteinemia contributes to thrombogenesis are incompletely understood. The main objectives of this study of young ischemic stroke patients were (1) to examine fasting and post–methionine load levels of tHcy, (2) to ascertain the genotype frequency of the C677CT mutation in the methylenetetrahydrofolate reductase gene (TT genotype), and (3) to study the possible interaction between plasma tHcy levels and fibrinolytic factors.

Methods
—This case-control study was based on 80 consecutive patients aged 18 to 44 years admitted between January 1992 and May 1996 as a result of a first-ever ischemic stroke. Forty-one healthy control subjects were recruited. Measurement of fasting tHcy and post–methionine load levels and evaluation of the fibrinolytic system were undertaken at least 3 months (mean, 5.1±1.9 months) after admission. Genotyping of the methylenetetrahydrofolate reductase gene was performed.

Results
—Although the increase after methionine loading (ie, postload tHcy minus fasting-level tHcy) was significantly higher among patients, there was no difference in fasting and postload tHcy levels. After adjustment for conventional risk factors, elevated postload increase tHcy levels were associated with a 4.8-fold increased risk of ischemic stroke. There was no difference between patients and control subjects in either TT genotype frequency or T allele frequency. Abnormal response to methionine loading was associated with higher tissue plasminogen activator (tPA) mass concentration, higher plasminogen activator inhibitor-1 levels, and lower tPA activity. After adjustment for age, sex, body mass index, serum cholesterol, and triglycerides, an abnormal increase in postload tHcy levels remained significantly associated with tPA mass concentration levels (
P
=0.03).

Conclusions
—A moderately elevated increase in tHcy levels after methionine loading was associated with an increased risk for ischemic stroke in young adults. In contrast, fasting tHcy levels did not differ between patients and controls. A moderately elevated increase in tHcy after methionine loading may provide a additional thrombogenic risk mediated in part by interactions with the fibrinolytic system. In young stroke patients, a methionine loading test to detect hyperhomocysteinemia should always be considered in the convalescent phase of the disease.
Risk Assessment and Anticoagulation for Primary Stroke Prevention in Atrial Fibrillation
Authors: Kalra L. , Perez I. , Melbourn A.
Published: June 2011

Background and Purpose
—Risk assessment before anticoagulation is important for effective stroke prevention in atrial fibrillation (AF).

Methods
—A study was undertaken in patients with AF to investigate the contribution of clinical and echocardiography (ECHO) criteria to treatment decisions on anticoagulation. Patients were stratified by age and stroke risk; contraindications to anticoagulation and warfarin use were assessed. The value of ECHO in treatment decisions, effect of age, and existing anticoagulation practice were evaluated.

Results
—The mean±SD age of 234 patients was 67.1±11.8 years, and 122 (52%) were women. Clinical risk factors were present in 74 of 80 patients (92%) aged >75 years compared with 99 of 154 patients (64%) ≤75 years (
P
<0.01). ECHO risk was identified in 94 of 154 patients (61%) ≤75 years, 16 (17%) of whom had no clinical risk factors. ECHO risk was present in 71 patients (88%) >75 years of age, and was associated with clinical risk factors in all patients. Eligibility for anticoagulation was seen in 72 of 154 (47%) to 105 of 154 (68%) patients aged ≤75 years, depending on the criteria used, and in 66 of 80 patients (83%) >75 years, regardless of criteria used (
P
<0.01). Warfarin was being used in 55 of 105 patients (51%) ≤75 years and 8 of 66 patients (12%) >75 years (
P
<0.001). Anticoagulation was being undertaken in 7 of 49 patients (14%) ≤75 years despite no clinical or ECHO risks.

Conclusions
—Accurate assessments of eligibility and appropriateness of anticoagulation in AF can be made on clinical criteria alone, especially in older people. The value of ECHO in treatment decisions is limited to patients ≤75 years of age with no clinical risk factors.
Factors Associated With Ischemic Stroke During Aspirin Therapy in Atrial Fibrillation
Authors: Hart Robert G. , Pearce Lesly A. , McBride Ruth , Rothbart Robert M. , Asinger Richard W.
Published: June 2011

Background and Purpose
—Nonvalvular atrial fibrillation (AF) is a strong, independent risk factor for stroke, but the absolute rate of stroke varies widely among AF patients, importantly influencing the potential benefit of antithrombotic prophylaxis. We explore factors associated with ischemic stroke in AF patients taking aspirin.

Methods
—We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low, inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I–III trials followed for a mean of 2.0 years, during which 130 ischemic strokes were observed.

Results
—Age (relative risk [RR]=1.8 per decade,
P
<0.001), female sex (RR=1.6,
P
=0.01), history of hypertension (RR=2.0,
P
<0.001), systolic blood pressure >160 mm Hg (RR=2.3,
P
<0.001), and prior stroke or transient ischemic attack (RR=2.9,
P
<0.001) were independently associated with increased stroke risk. Regular consumption of ≥14 alcohol-containing drinks per week was associated with reduced stroke risk (adjusted RR=0.4,
P
=0.04). Among SPAF III participants, estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke (adjusted RR=3.2,
P
=0.007). With the use of these variables, a risk stratification scheme for primary prevention separated participants into those with high (7.1%/y, 22% of the cohort), moderate (2.6%/y, 37% of the cohort), and low (0.9%/y, 41% of the cohort) rates of stroke. Ischemic strokes in low-risk participants were less often disabling (
P
<0.001).

Conclusions
—Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified. However, validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management. Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF, but these findings require confirmation.
Cerebral Hemodynamics in Relation to Patterns of Collateral Flow
Authors: Kluytmans M. , van der Grond J. , van Everdingen K. J. , Klijn C. J. M. , Kappelle L. J. , Viergever M. A.
Published: June 2011

Background and Purpose
—We sought to investigate the relation between collateral flow via different pathways and hemodynamic parameters measured by dynamic susceptibility contrast–enhanced MRI in patients with severe carotid artery disease.

Methods
—Dynamic susceptibility contrast–enhanced MRI was performed in 66 patients and 33 control subjects. Patients had severe stenosis (>70%, n=12), unilateral occlusion (n=38), or bilateral occlusion (n=16) of the internal carotid artery (ICA). Cerebripetal flow and collateral flow via the circle of Willis were investigated with MR angiography. Collateral flow via the ophthalmic artery was investigated with transcranial Doppler sonography.

Results
—Patients with ICA stenosis had well-preserved cerebral perfusion and were in general not dependent on collateral supply. Patients with unilateral ICA occlusion had impaired cerebral perfusion. However, appearance time, peak time, and mean transit time in white matter were less increased in patients with than in patients without collateral flow via the circle of Willis (
P
<0.05). Furthermore, patients with collateral flow via both anterior and posterior communicating arteries had less increased regional cerebral blood volume than patients with collateral flow via the posterior communicating artery only (
P
<0.05). Patients with bilateral ICA occlusion had severely compromised hemodynamic status despite recruitment of collateral supply.

Conclusions
—In patients with unilateral ICA occlusion, the pattern of collateral supply has significant influence on hemodynamic status. Collateral flow via the anterior communicating artery is a sign of well-preserved hemodynamic status, whereas no collateral flow via the circle of Willis or flow via only the posterior communicating artery is a sign of deteriorated cerebral perfusion.
Which Targets Are Relevant for Therapy of Acute Ischemic Stroke?
Authors: Heiss Wolf-Dieter , Thiel Alexander , Grond Martin , Graf Rudolf
Published: June 2011

Background
—The efficiency of various strategies of neuroprotection is well documented in animal experiments but is thus far disappointing in ischemic stroke, for which only early reperfusion induced by thrombolysis has improved clinical outcome. This discrepancy between expectation from experimental research and clinical reality may be related to differences in the pathogenetic factors contributing to infarction.

Summary of Comment
—Positron emission tomography cerebral blood flow studies within 3 hours of onset were used to identify the various compartments of the infarct outlined on MRI 2 to 3 weeks after a hemispheric stroke in 10 patients. Critical hypoperfusion below the viability threshold accounted for the largest proportion (mean, 70%) of the final infarct, whereas penumbral tissue (18%) and initially sufficiently perfused tissue (12%) were responsible for considerably smaller portions of the final infarct.

Conclusions
—These results indicate that early critical flow disturbance leading to rapid cell damage is the predominant cause of infarction, while secondary and delayed pathobiochemical processes in borderline or initially sufficiently perfused regions contribute only little to the final infarct. Therefore, emerging therapeutic strategies should be targeted to the initially critically perfused tissue subcompartments. Clinical drug trials might benefit from stratification of patients for target tissue compartments applying functional imaging.
Race/Ethnicity and Location of Stroke Mortality
Authors: Wein Theodore H. , Smith Melinda A. , Morgenstern Lewis B.
Published: June 2011

Background and Purpose
—Stroke community surveillance projects often focus on hospital data rates. We hypothesized that not including strokes which occurred in nursing homes or at home would differentially affect race/ethnic stroke rates.

Methods
—Texas vital statistics data were studied to compare age-specific (45 to 59, 60 to 74, and ≥75 years) location of stroke death for African Americans (AAs), Hispanic Americans (HAs), and non-Hispanic whites (NHWs). Rate ratios are reported with 95% CIs; NHW is used as the referent group.

Results
—During 1991 to 1996, there were 52 996 stroke deaths in Texas for individuals aged 45 years and older. HAs in the oldest age group (≥75 years) were 33% more likely than NHWs to die in the hospital, and HAs aged 45 to 59 and 60 to 74 years were 4% and 10%, respectively, more likely to die in the hospital. AAs aged ≥75 years were 19% more likely to die in the hospital. HAs aged 60 to 74 years were 35% less likely to die in a nursing home, whereas HAs aged ≥75 years were 43% less likely than NHWs to die in a nursing home. AAs aged ≥75 were 33% less likely to die in a nursing home. Death at home was 19% more likely in HAs aged 60 to 74 years. Significant gender differences are also reported.

Conclusions
—Using hospital data alone would overestimate stroke mortality in the HA and AA groups. Stroke community surveillance projects should account for ethnic and gender differences in location of death to avoid bias in race/ethnic and gender comparisons.
Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion
Authors: Ishikawa Mami , Sekizuka Eliichi , Sato Shuzo , Yamaguchi Noriyuki , Inamasu Joji , Bertalanffy Helmut , Kawase Takeshi
Published: June 2011

Background and Purpose
—It has been demonstrated that moderate hypothermia attenuates brain damage, but the mechanism whereby this is achieved has not been clearly shown. Recently, the role of leukocytes as mediators of secondary brain damage after brain ischemia has been discussed. The aim of this study is to examine the effects of moderate hypothermia on leukocyte-endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO).

Methods
—Rhodamine 6G–labeled leukocytes in brain surface were visualized with intravital fluorescence videomicroscopy through a closed cranial window. We analyzed the number of leukocytes adhering to the venular and arteriolar endothelium before ischemic insult and up to 3 hours after reperfusion. Rats were divided into 4 experimental groups. Group I (n=6) consisted of sham-operated animals. Groups II (n=6) and III (n=6) received left MCAO for 1 hour under normothermia (36°C to 37°C, group II) and under moderate hypothermia (30°C to 32°C, group III). Group IV (n=4) received left common carotid artery occlusion for 1 hour under normothermia.

Results
—The number of adhering leukocytes in venules in groups II and IV increased significantly (
P
<0.001) after reperfusion compared with the group I, but that in group III did not increase significantly (
P
>0.05). The number of adhering leukocytes in arterioles in group II increased significantly (
P
<0.01) compared with the other groups, although the adhering leukocytes were not as numerous as those seen in venules.

Conclusions
—It is demonstrated that hypothermia attenuates adhering leukocytes in venules and arterioles after reperfusion of MCAO. The inhibition of the leukocyte function may be an important factor in the neuroprotective effect of hypothermia.
Local Treatments of Dorsal Raphe Nucleus Induce Changes in Serotonergic Activity in Rat Major Cerebral Arteries
Authors: Marco Emilio J. , Moreno María Jesús , de Pablo Angel Luis López
Published: June 2011

Background and Purpose
—Rat major cerebral arteries seem to receive serotonergic fibers originating from the dorsal raphe nucleus (DRN), but little is known about their function. The aim of our present work was to establish a functional relationship between this brain stem nucleus and the cerebral blood vessels by studying the effects of several treatments in the DRN on cerebrovascular serotonergic activity.

Methods
—Serotonin, clomipramine, 8-OH-DPAT, and WAY-100635 were administered in DRN. A stereotaxically localized electrode allowed the electrical stimulation of this brain stem nucleus. Serotonergic activity was appraised in major cerebral arteries, striatum, and hippocampus from 5-hydroxytryptophan accumulation after aromatic
l
-amino acid decarboxylase inhibition with NSD-1015.

Results
—Serotonin significantly decreased serotonergic activity in major cerebral arteries and striatum without affecting it in hippocampus. This reduction was blocked by previous injection of WAY-100635 in DRN. Local administration of 8-OH-DPAT or clomipramine elicited an effect similar to that of serotonin, whereas that of WAY-100635 did not modify serotonergic activity in either of the tissues. Electrical stimulation of DRN significantly increased serotonergic activity in major cerebral arteries and striatum but not in hippocampus.

Conclusions
—These results confirm the presence of a serotonergic innervation in rat major cerebral arteries functionally related to DRN. 5-HT
1A
receptor activation partly mediates the action of serotonin in DRN. A serotonergic tone acting on these somatodendritic receptors was not clearly found.
Circadian Variation in Ischemic Stroke Subtypes
Authors: Chaturvedi Seemant , Adams Harold P. , Woolson Robert F.
Published: June 2011

Background and Purpose
—While previous studies suggest that the peak time period for the occurrence of ischemic stroke is in the mid- to late-morning hours, detailed information pertaining to circadian variations among the various stroke subtypes has been limited. The purpose of our study was to define the circadian patterns of symptom onset in an acute stroke trial with an established system for stroke subtype classification.

Methods
—An analysis was conducted on 1272 patients enrolled in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) study. All patients had a documented time of stroke symptom onset, and all stroke subtype determinations were made by a single rater.

Results
—The greatest portion of atherothrombotic strokes (25.7%), cardioembolic strokes (30.5%), and strokes of other/unknown mechanism (27.1%) occurred between 6:01
am
and 12:00 noon. The greatest portion of lacunar strokes (31.6%) were present on awakening. More than one half of the infarcts in this series were either present on awakening or occurred in the mid- to late-morning hours. The correlation between stroke subtype and time of symptom onset did not reach statistical significance (
P
=0.07, Pearson’s χ
2
method).

Conclusions
—Although there is a trend for clustering of ischemic stroke in the morning hours, there is insufficient specificity to predict with any reasonable likelihood the stroke subtype according to the circadian pattern of symptom onset.
Combination Drug Therapy and Mild Hypothermia
Authors: Schmid-Elsaesser Robert , Hungerhuber Edwin , Zausinger Stefan , Baethmann Alexander , Reulen Hanns-Juergen
Published: June 2011

Background and Purpose
—Hypothermia has been suggested to be the most potent therapeutic approach to reduce experimental ischemic brain injury identified to date, and mild hypothermia is increasingly used for neuroprotection during neurovascular surgery. We have recently demonstrated that combined administration of tirilazad mesylate and magnesium provides for an overall enhanced neuroprotective effect. The present study was designed to determine whether the efficacy of mild hypothermia (33°C) can be increased by combination pharmacotherapy with tirilazad and magnesium (MgCl
2
).

Methods
—Forty Sprague-Dawley rats were subjected to transient, middle cerebral artery occlusion and were randomly assigned to 1 of 4 treatment arms (n=10 each): (1) normothermia+vehicle, (2) normothermia+tirilazad+MgCl
2
, (3) hypothermia+vehicle, or (4) hypothermia+tirilazad+MgCl
2
. Cortical blood flow was monitored by a bilateral laser-Doppler flowmeter, and the electroencephalogram was continuously recorded. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days.

Result
s

—Tirilazad+MgCl
2
, hypothermia, and hypothermia+tirilazad+MgCl
2
reduced total infarct volume by 56%, 63%, and 77%, respectively, relative to controls. In animals treated with both hypothermia and combination pharmacotherapy, cortical infarction was almost completely abolished (−99%), and infarct volume in the basal ganglia was significantly reduced by 55%. In addition, this treatment provided for the best electrophysiological recovery and functional outcome.

Conclusions
—The neuroprotective efficacy of hypothermia can be increased by pharmacological antagonism of excitatory amino acids and free radicals by using clinically available drugs. This treatment strategy could be of great benefit when applied during temporary artery occlusion in cerebrovascular surgery.
Effect of Ganaxolone in a Rodent Model of Cerebral Hematoma
Authors: Lyden Patrick , Shin Caroline , Jackson-Friedman Catherine , Hassid Steven , Chong Anthony
Published: June 2011

Background and Purpose
—Therapy with γ-aminobutyric acid (GABA) agonists appears to improve outcome after experimental hematoma but with unacceptable side effects. We looked to synthetic GABA agonists, or positive GABA modulators, widely developed as anticonvulsants and anxiolytics, to find compounds that may be effective. Ganaxolone is a synthetic neuroactive steroid that positively modulates GABA. We sought to determine whether ganaxolone was beneficial using a model of intracerebral hematoma.

Methods
—We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats to induce blood-brain barrier failure and hematoma formation. Four hours later, we administered intravenously 15 or 30 mg/kg ganaxolone (n=23 each group), 20 mg/kg pregnanolone (n=21), or vehicle (n=30). Forty-eight hours after collagenase injection, we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase using the quantal bioassay procedure. Other sets of animals were tested later for visuospatial learning. Brains were then prepared for histomorphometry, and brain volumes were estimated.

Results
—We found that ganaxolone 30 mg/kg significantly increased the ED
50
in the bioassay, for a potency ratio of 1.8±0.41 compared with vehicle (
P
<0.05). Ganaxolone 15 mg/kg and pregnanolone did not affect neurological outcome. Ganaxolone 30 mg/kg did not clearly improve visuospatial learning several weeks after hemorrhage. Ganaxolone exhibited a weak effect on cerebral volumes 48 hours after stroke, but 3 months after hemorrhage no such effect could be detected.

Conclusions
—Ganaxolone improves neurological outcome 48 hours after intracerebral hematoma but not visuospatial learning several weeks after intracerebral hematoma. Histological evidence of damage was reduced at 48 hours but not at 3 months.
Widening Gap of Stroke Between East and West
Authors: Stegmayr Birgitta , Vinogradova Tatyana , Malyutina Sofia , Peltonen Markku , Nikitin Yuri , Asplund Kjell
Published: June 2011

Background and Purpose
—Stroke is declining in most of the western and northern European countries, whereas no such decline is seen in eastern Europe. The aim of this study was to investigate trends in stroke attack rates and 28-day case fatality and risk factor levels in Novosibirsk, Siberia, and northern Sweden during 1987–1994.

Methods
—Within the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project, acute stroke events and 28-day case fatality were registered in a standardized way in men and women aged 35 to 69 years. Cardiovascular risk factors were monitored in randomly selected men and women in the group aged 35 to 64 years in 1985–1986 and 1994–1995.

Results
—Stroke attack rates increased significantly from 430 per 100 000 to 660 (
P
=0.005) in men in Novosibirsk and from 298 to 500 (
P
=0.02) in women. In northern Sweden, stroke attack rates varied between 244 and 303 per 100 000 in men and from 117 to 157 in women, with a small increasing trend in women (
P
=0.03). The mortality rates were 5 times higher in Novosibirsk, and the case fatality was significantly lower in northern Sweden (
P
=0.0001). The risk factor surveys showed significantly higher blood pressure, overweight, and more smoking men in Novosibirsk, while northern Sweden had higher cholesterol levels and more smoking women. Most risk factors showed stable or improving patterns over time.

Conclusions
—Large differences in both attack rates and case fatality account for the large and widening gap in stroke mortality between Russia and Sweden. A higher prevalence of hypertension in Russia may explain much of the differences in stroke occurrence. In Russia, a marked increase in attack rates has occurred despite stable or improving patterns of conventional cardiovascular risk factors.
Association Between Risk Factors for Atherosclerosis and Mechanical Forces in Carotid Artery
Authors: Jiang Yinong , Kohara Katsuhiko , Hiwada Kunio
Published: June 2011

Background and Purpose
—Mechanical stresses on the arterial wall participate in the pathogenesis of atherosclerosis as local factors. The relationships between local mechanical forces and risk factors for atherosclerosis were investigated.

Methods
—Mechanical forces on the arterial wall were evaluated in the carotid artery in 117 patients with risk factors for atherosclerosis including hypertension, dyslipidemia, diabetes mellitus, and smoking, as well as in 20 age- and sex-matched normal controls. Circumferential wall tension and shear stress were evaluated with Laplace’s law and a poiseuillean parabolic model of velocity distribution. Circumferential wall strain was also evaluated as carotid mechanical force.

Results
—Mechanical forces in subjects with risk factors were characterized by low wall shear stress, high circumferential wall tension, and reduced strain. Systolic blood pressure was significantly negatively associated with shear stress and circumferential wall strain. HDL cholesterol showed a significant positive correlation with shear stress and a negative correlation with wall tension. Fasting blood glucose was significantly associated with shear stress, while smoking showed a negative correlation with shear stress and a positive correlation with wall tension. Accumulation of risk factors was associated with further deterioration of mechanical forces. Furthermore, stepwise regression analysis showed that the number of risk factors was significantly associated with mechanical forces independently of carotid intima-media thickness.

Conclusions
—These findings suggest that risk factors for atherosclerosis were associated with alteration of mechanical forces. Consequent alteration in mechanical forces could be an underlying local mechanism for the progression of atherosclerosis.
Predictors of Survival Among Elders Suffering Strokes in Taiwan
Authors: Wang Shu-Li , Pan Wen-Harn , Lee Meng-Chih , Cheng Shu-Ping , Chang Ming-Cheng
Published: June 2011

Background and Purpose
—Cerebrovascular disease was the leading cause of death in Taiwan from 1963 to 1982. Deaths due to stroke now rank second only to cancer, with more deaths resulting from strokes than from any other single pathology. It is important to understand stroke prognosis among elderly stroke survivors, with respect to survival and attendant predictive factors, because aged population in Taiwan is growing rapidly. The aim of the present study was to discern factors affecting survival in stroke patients from a nationally representative elderly sample.

Methods
—A total of 99 stroke survivors, from a representative national sample of elders aged ≥65 years on December 31, 1988, whose strokes occurred in the period 1989–1993, were followed for mortality until July 1, 1995. Personal data were gathered through home interviews conducted by well-trained community nurses, and mortality data were obtained from the national census office by using identification card numbers. Cox proportional hazards regression analysis and the stepwise technique were used to search for important prognostic factors of survival.

Results
—Women experienced a higher mortality rate (139.8 per 1000 person-years) than men (126.4 per 1000 person-years), as age-adjusted for World Health Organization world-population figures. Stroke patients who received continuous treatment for diabetes experienced mortality risks similar to those of patients without diabetes and much lower risks than those with discontinuous diabetes treatment. Cognitive impairment was also an independent predictor of survival (relative risk 2.69,
P
<0.05). In addition, patients with both cognitive and mobility impairments had a 2- to 3-fold greater risk of mortality than those with only a single abnormality.

Conclusions
—This first report on the various prognostic factors related to survival of elderly stroke patients in Taiwan’s Chinese population emphasized the benefit of continuous diabetes treatment in improving survival chances. These stroke patients should also be monitored for cognitive and mobility impairments and undergo rehabilitation.
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Compare the Efficacy and Safety of Three Doses of Botulinum Toxin Type A (Dysport) With Placebo in Upper Limb Spasticity After Stroke
Authors: Bakheit A. M. O. , Thilmann A. F. , Ward A. B. , Poewe W. , Wissel J. , Muller J. , Benecke R. , Collin C. , Muller F. , Ward C. D. , Neumann C.
Published: June 2011

Background and Purpose
—We sought to define an effective and safe dose of botulinum toxin type A (Dysport) for the treatment of upper limb muscle spasticity due to stroke.

Methods
—This was a prospective, randomized, double-blind, placebo-controlled, dose-ranging study. Patients received either a placebo or 1 of 3 doses of Dysport (500, 1000, 1500 U) into 5 muscles of the affected arm. Efficacy was assessed periodically by the Modified Ashworth Scale and a battery of functional outcome measures.

Results
—Eighty-three patients were recruited, and 82 completed the study. The 4 study groups were comparable at baseline with respect to their demographic characteristics and severity of spasticity. All doses of Dysport studied showed a significant reduction from baseline of muscle tone compared with placebo. However, the effect on functional disability was not statistically significant and was best at a dose of 1000 U. There were no statistically significant differences between the groups in the incidence of adverse events.

Conclusions
—The present study suggests that treatment with Dysport reduces muscle tone in patients with poststroke upper limb spasticity. Treatment was effective at doses of Dysport of 500, 1000, and 1500 U. The optimal dose for treatment of patients with residual voluntary movements in the upper limb appears to be 1000 U. Dysport is safe in the doses used in this study.
Effect of Contralateral Carotid Artery Stenosis on Carotid Ultrasound Velocity Measurements
Authors: Henderson Robert D. , Steinman David A. , Eliasziw Michael , Barnett Henry J. M.
Published: June 2011

Background and Purpose
—Carotid ultrasonography is being increasingly performed as the sole investigation to assess internal carotid artery (ICA) stenosis. A potential source of error in using ultrasound peak systolic velocity (PSV) measurements is that the redistribution of blood flow due to severe stenosis in a contralateral carotid artery may lead to artificially elevated values.

Methods
—Ultrasonography was performed before and after carotid endarterectomy in symptomatic patients who participated in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). The mean change in PSV in the unoperated artery was assessed across all degrees of angiographically defined stenosis. A simple theoretical resistance model of the cerebral circulation was also derived.

Results
—Complete bilateral ultrasound examinations were performed within 90 days of the initial scan in 386 patients. In the presence of a contralateral severe (70% to 99%) ICA stenosis, the PSV in the unoperated artery was artificially elevated by a mean of 84 cm/s (
P
=0.03; 95% CI, 10 to 159 cm/s). The mean elevation was less pronounced for lesser degrees of stenosis (11 to 21 cm/s). Small elevations (3 to 12 cm/s) were observed when the contralateral artery had <70% stenosis. The patterns of observed results were congruent with those from the theoretical model.

Conclusions
—The present study showed that a severely stenosed contralateral ICA can artificially elevate ultrasound PSV. Since the effect was greatest when bilaterally severe stenoses were present, caution must be exercised when assessing the degree of ICA stenosis on the basis of ultrasonography PSV measurements alone.
Late Resolution of Diffusion-Weighted MRI Changes in a Patient With Prolonged Reversible Ischemic Neurological Deficit After Thrombolytic Therapy
Authors: Krueger Karsten , Kugel Harald , Grond Martin , Thiel Alexander , Maintz David , Lackner Klaus
Published: June 2011

Background
—Reduced apparent diffusion coefficients (ADCs) correlate with cerebral ischemia. The combination of ADC with techniques to measure cerebral perfusion may help to assess the effect of treatment.

Case Description
—The authors describe a patient who experienced an acute stroke with hemianopia, consequently treated with intravenous recombinant tissue plasminogen activator. Positron emission tomographic imaging and MRI, including diffusion-weighted MRI, were performed during and shortly after treatment with recombinant tissue plasminogen activator and 34 to 35 hours later. Cerebral perfusion of the left occipital region was reduced to 74%. Diffusion-weighted MRI detected a territory of restricted water movement in the corresponding area. Further magnetic resonance sequences did not show any pathologies. In follow-up, positron emission tomography demonstrated reperfusion. The volume of diffusion and ADC abnormalities detected by MRI decreased markedly. A few hours later, the patient recovered completely. A third MRI examination 10 days later showed normal findings.

Conclusions
—In a patient with prolonged reversible ischemic neurological deficit, resolution of early diffusion changes corresponded to cerebral reperfusion and to the recovery of clinical symptoms.
Cochrane Report
Authors: Bereczki Dániel , Liu Ming , Prado Gilmar Fernandes do , Fekete István
Published: June 2011

Background
—Mannitol was reported to decrease cerebral edema associated with tissue damage and is used to treat acute stroke in many countries.

Summary of Review
—We tested whether there is any evidence from unconfounded randomized clinical trials that treatment with mannitol reduces short- and long-term case fatality and dependency if administered after ischemic stroke or cerebral parenchymal hemorrhage. Trials were identified by the standard search strategy of the Cochrane Collaboration Stroke Review Group. A supplementary MEDLINE search was performed, and the Chinese Stroke Trials Register and the Latin-American databank LILACS were checked. A search was performed of master’s and PhD degree theses in the databank of Sao Paulo University and in abstracts of medical congresses on neurology and neurosurgery during 1965–1997 in Brazil. Investigators were contacted for unpublished information. Only truly randomized unconfounded clinical trials were eligible for inclusion. Two of the reviewers independently extracted data from the trials. Data synthesis and analysis was performed with the use of the Cochrane Review Manager software (RevMan version 4.0.4).

Conclusions
—Only 1 trial fulfilled the inclusion criteria. The number of included patients was small, and the follow-up was short. Case fatality, the proportion of dependent patients, and side effects were not reported and were not available from the investigators. As a result of lack of appropriate randomized trials, currently no conclusion can be drawn on the effects of mannitol in acute stroke. The routine use of mannitol in all patients with acute stroke is not supported by evidence from randomized controlled clinical trials.
Impairment of Cerebrovascular Reactivity by Methionine-Induced Hyperhomocysteinemia and Amelioration by Quinapril Treatment
Authors: Chao Chia-Lun , Lee Yuan-Teh
Published: June 2011

Background and Purpose
—Human studies have shown that methionine-induced hyperhomocysteinemia impairs brachial artery endothelial function via decreasing nitric oxide activity. However, the effect of homocysteine on cerebrovascular reactivity (CVR), which has been reported to be nitric oxide related in experimental and animal studies, remains unclear in humans. Inhibition of angiotensin-converting enzyme may improve nitric oxide–mediated cerebral as well as peripheral endothelial function. The aim of the present study was to investigate the effect of methionine-induced hyperhomocysteinemia on CVR before and after treatment with quinapril, an angiotensin-converting enzyme inhibitor, in healthy adults.

Methods
—Plasma homocysteine and CVR were measured at baseline and 4 hours after methionine load (0.1 g/kg body wt) before and after quinapril treatment (10 mg/d for 1 week) in both younger and older groups. CVR was assessed by transcranial Doppler ultrasonography, measuring the percent increase of flow velocity in the middle cerebral artery after brief carotid compression (expressed as transient hyperemic response ratio [THRR]).

Results
—Homocysteine levels were significantly increased after methionine load either before or after quinapril treatment in both groups. Before quinapril treatment, postmethionine THRR was preserved in younger adults (24.2±5.3% versus 23.8±6.3% at baseline,
P
=0.73) and decreased in older adults (12.9±2.2% versus 21.8±4.0% at baseline,
P
<0.001). After quinapril treatment, postmethionine THRR was preserved in both groups (24.5±5.9% versus 24.0±5.0% at baseline,
P
=0.42 in younger adults; 20.4±3.9% versus 21.3±3.3% at baseline,
P
=0.35 in older adults).

Conclusions
—Our study suggests that methionine-induced hyperhomocysteinemia may be causally associated with impairment of CVR in older normal subjects.
Endothelin-1 in Subarachnoid Hemorrhage
Authors: Faßbender Klaus , Hodapp Britta , Rossol Siegbert , Bertsch Thomas , Schmeck Joachim , Schütt Sandra , Fritzinger Michael , Horn Peter , Vajkoczy Peter , Wendel-Wellner Martina , Ragoschke Andreas , Kuehl Sandra , Brunner Jürgen , Schürer Ludwig , Schmiedeck Peter , Hennerici Michael
Published: June 2011

Background and Purpose
—The most potent vasoconstrictor known, endothelin-1, is currently considered to mediate cerebral vasospasm in subarachnoid hemorrhage (SAH), which can cause delayed cerebral ischemia. In our study, we performed clinical and in vitro experiments to investigate the origin and the mechanisms of the secretion of endothelin-1 in SAH.

Methods
—Endothelin-1 and markers of inflammatory host response (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) were comparatively quantified in the cerebrospinal fluid (CSF) of SAH patients and control subjects, and concentrations were related to clinical characteristics. Furthermore, mononuclear leukocytes isolated from the CSF of SAH patients and control subjects were analyzed regarding their mRNA expression of endothelin-1 and inflammatory cytokines. Finally, complementary in vitro experiments were performed to investigate whether coincubation of blood and CSF can trigger leukocytic mRNA expression and release of these factors.

Results
—Activated mononuclear leukocytes in the CSF of SAH patients synthesize and release endothelin-1 in parallel with known acute-phase reactants (IL-1β, IL-6, and tumor necrosis factor-α). Complementary in vitro experiments not only further confirmed this leukocytic origin of endothelin-1 but also showed that aging and subsequent hemolysis of blood is sufficient to induce such endothelin-1 production.

Conclusions
—The demonstration that endothelin-1 is produced by activated CSF mononuclear leukocytes suggests that subarachnoid inflammation may represent a therapeutic target to prevent vasospasm and delayed cerebral ischemia after SAH.
Stent Angioplasty for Cervical Carotid Artery Stenosis in High-Risk Symptomatic NASCET-Ineligible Patients
Authors: Malek Adel M. , Higashida Randall T. , Phatouros Constantine C. , Lempert Todd E. , Meyers Philip M. , Smith Wade S. , Dowd Christopher F. , Halbach Van V.
Published: June 2011

Background and Purpose
—Although the North American Symptomatic Carotid Endarterectomy Trial (NASCET) has shown carotid endarterectomy (CEA) to be protective compared with medical therapy alone, its stringent eligibility criteria excluded patients with severe medical, angiographic, and neurological risk factors. We sought to determine the safety and efficacy of stent angioplasty in this high-risk subset for whom the perioperative morbidity and mortality of surgery are elevated.

Methods
—Twenty-eight consecutive symptomatic NASCET-ineligible patients (10 female; median age, 72.2 years) underwent microcatheter-based carotid stent angioplasty. Half of the patients had sustained a previous stroke. Classification of surgical risk by Sundt criteria yielded no patients in grade 1, 3 patients in grade 2 (10.7%), 8 in grade 3 (28.6%), and 17 (60.7%) in grade 4. Stratification of stroke risk for medical therapy according to the European Carotid Surgery Trial (ECST) 5-point score showed 8 patients with a score of 3 (28.6%), 12 with 4 (42.8%), and 8 with 5 (28.6%). Follow-up was obtained in all patients at a median of 14 months.

Results
—The procedure was technically successful in all cases (100%), with immediate stenosis reduction from a mean of 80.3% to 2.7%. There were no periprocedural deaths, 1 major stroke (3.6%), no minor strokes, and 3 transient ischemic attacks (10.7%). In-hospital complications included 2 nonfatal myocardial infarctions, 1 case of acute renal failure, and 1 groin hematoma requiring transfusion. There were 5 deaths during the follow-up period, all beyond 30 days after the procedure: 3 from cardiac causes, 1 from lung cancer, and 1 following unrelated surgery. The patient with major stroke died at 7.8 months during rehabilitation. No surviving patients had further strokes, and all except 1 (95.5%) remained asymptomatic. Anatomic follow-up in 20 patients showed occlusion in 2 (10%) (1 symptomatic, 1 asymptomatic) and intimal hyperplasia in 3 asymptomatic patients (15%).

Conclusions
—The clinical results and sustained freedom from symptoms and stroke during the short available follow-up period suggest that stent angioplasty may be useful in the treatment of symptomatic cervical carotid stenosis in high-risk patients despite a notable incidence of restenosis.
LY353381.HCl, a Selective Estrogen Receptor Modulator, and Experimental Stroke
Authors: Rossberg Mark I. , Murphy Stephanie J. , Traystman Richard J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
—The impact of postmenopausal estrogen replacement therapy on stroke prevention and stroke severity remains controversial. Previously we have shown that cerebral tissue infarction volume sustained after middle cerebral artery (MCA) occlusion is smaller in female than in male animals. This protection is lost after ovariectomy but is restored by 17β-estradiol replacement. However, the therapeutic range for estradiol is suboptimal, since only doses resulting in a narrow range of plasma levels are protective in brain. The present study tested the hypothesis that a benzothiophene analogue and selective estrogen receptor modulator, LY353381.HCl (LY), reduces tissue infarction after MCA occlusion in estrogen-deficient, ovariectomized female rats.

Methods
—Ovariectomized female Wistar rats received LY 10 mg/kg (n=16) or an equivalent volume of vehicle (n=14) by gavage for 5 to 8 days. Subsequently, each animal was anesthetized with halothane (1.2%) and treated with 2 hours of MCA occlusion by the intraluminal filament technique and 22 hours of recovery. Infarction volumes in the cerebral cortex and caudoputamen were determined by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis. End-ischemic regional cerebral blood flow (CBF) was measured in separate animal cohorts by quantitative [
14
C]iodoantipyrine autoradiography.

Results
—Caudoputamen infarction was reduced by LY treatment (49±6% versus 64±4% of ipsilateral caudoputamen in LY and vehicle groups, respectively;
P
<0.05). Cerebral cortical infarction was not different in the LY compared with vehicle group (7±3% versus 13±4% of ipsilateral cerebral cortex, respectively). Intra-ischemic blood pressure, arterial blood gases, and temporalis muscle temperature were controlled and equivalent between treatment groups. Averaged laser-Doppler flow during MCA occlusion was 36±3% of baseline in the LY group versus 29%±2% in the vehicle group. However, end-ischemic CBF or blood flow distribution within the MCA territory was not altered by LY treatment. Cortical or caudoputamen tissue volumes with end-ischemic CBF <20 mL/100 g per minute were similar in both groups.

Conclusions
—We conclude that LY confers neuroprotection from focal cerebral ischemia in caudoputamen in ovariectomized female rats. The mechanism of protection is not linked to preservation of ischemic cerebral blood flow, as determined by end-occlusion quantitative autoradiography.