bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin Use and Incident Stroke in the Cardiovascular Health Study
Authors: Kronmal R. A. , Hart R. G. , Manolio T.A. , Talbert R.L. , Beauchamp N.J. , Newman A.
Published: June 2011

Background and Purpose
—Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study.

Methods
—We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years.

Results
—Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk=1.6; 95% confidence interval [CI], 1.2 to 2.2;
P
=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (
P
<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (
P
=0.003).

Conclusions
—Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.
Stroke Unit Treatment Improves Long-term Quality of Life
Authors: Indredavik B. , Bakke F. , Slørdahl S. A. , Rokseth R. , Håheim L. L.
Published: June 2011

Background and Purpose
—We have previously shown that treatment of acute stroke patients in the combined acute and rehabilitation stroke unit in our hospital improves survival and functional outcome compared with treatment in general wards. The primary aim of the present trial was to examine whether the treatment in our stroke unit had an effect on different aspects of quality of life (QoL) for stroke patients 5 years after the onset of stroke.

Methods
—In a randomized controlled trial, 110 patients with symptoms and signs of an acute stroke were allocated to the stroke unit and 110 to general wards. No significant differences existed in baseline characteristics between the two groups. The patients alive after 5 years were assessed by the Nottingham Health Profile (NHP) and the Frenchay Activities Index (FAI), which were the scales used as primary outcome measures for QoL. As secondary outcome measures we used a global score for the NHP and a simple visual analogue scale (VAS).

Results
—After 5 years, 45 of the patients treated in the stroke unit and 32 of those treated in general wards were alive. All surviving patients were assessed by the FAI. Thirty-seven (82.2%) of the stroke unit patients and 25 (78.1%) of the general wards patients were assessed by the NHP; 38 (84.4%) and 28 (87.5%), respectively, were assessed by the VAS. Patients treated in the stroke unit had a higher score on the FAI (
P
=0.0142). Assessment with the NHP showed better results in the stroke unit group for the dimensions of energy (
P
=0.0323), physical mobility (
P
=0.0415), emotional reactions (
P
=0.0290), social isolation (
P
=0.0089), and sleep (
P
=0.0436), although there was no difference in pain (
P
=0.3186). The global NHP score and VAS score also showed significantly better results in the stroke unit group (NHP,
P
<0.01; VAS,
P
<0.001). Patients who were independent in activities of daily living had significantly better QoL assessed by these scales than patients who were dependent.

Conclusions
—Our study shows for the first time that stroke unit care improves different aspects of long-term QoL for stroke patients.
Alcohol Consumption and Atherosclerosis: What Is the Relation?
Authors: Kiechl Stefan , Willeit Johann , Rungger Gregor , Egger Georg , Oberhollenzer Friedrich , Bonora Enzo
Published: June 2011

Background and Purpose
—Potential effects of regular alcohol consumption on atherogenesis are still controversial mainly due to the lack of prospective population-based studies.

Methods
—The Bruneck Study is a prospective population-based survey of atherosclerosis and its risk factors. The study population comprises a sex- and age-stratified random sample of men and women aged 40 to 79 years. Participation and follow-up were more than 90% complete. Changes in carotid atherosclerosis between the 1990 baseline and the first follow-up in 1995 were monitored by high-resolution duplex ultrasonography. Alcohol intake was quantified with a standardized questionnaire and prospective diet records.

Results
—Alcohol consumption less than once a week (occasional drinking) had no effect on atherogenesis. The association between regular alcohol intake and incident carotid atherosclerosis (early atherogenesis) was J-shaped, with light drinkers facing a lower risk than either heavy drinkers or abstainers. Protection offered by alcohol consumption of <50 g/d appeared to act through inhibition of the injurious action of high levels of low-density lipoprotein (LDL) cholesterol. Excess risk of incident atherosclerosis observed among heavy alcohol consumers (≥100 g/d) clearly surpassed the risk burden afforded by heavy smoking. The association between regular alcohol intake and incident carotid stenosis (advanced atherogenesis) was U-shaped. Odds ratios were generally shifted toward protection and did not rely on LDL cholesterol levels. We failed to find any differential effects of alcohol from various sources. All associations remained independently significant when we adjusted for lifestyle, coincidental smoking, and the metabolic complex associated with drinking.

Conclusions
—Our findings support the view that adverse and beneficial effects of alcohol on arterial disease are mediated in part by a dose-dependent promotion or deceleration of atherogenesis. The protection afforded by light drinking may possibly be attributed to antithrombotic effects and inhibition of the atherogenic action of high levels of LDL cholesterol.
Can Cerebrovascular Reactivity Be Assessed Without Measuring Blood Pressure in Patients With Carotid Artery Disease?
Authors: Dumville J. , Panerai R. B. , Lennard N. S. , Naylor A. R. , Evans D. H.
Published: June 2011

Background and Purpose
—Conventional methods of assessing cerebrovascular reactivity (CVR) omit the influence of blood pressure (BP). This study demonstrates the significant influence of BP during the assessment of CVR in patients with carotid artery disease.

Methods
—In 56 subjects the CVR was bilaterally assessed by measurement of cerebral blood flow velocity change in response to inhalation of 5% CO
2
in air while BP was continuously monitored. Three methods of calculating the CVR were used: the conventional ratio between relative cerebral blood flow velocity and end-tidal CO
2
, simple linear regression, and multiple linear regression analysis (MLRA). The clinical significance of the difference in CVR indices was evaluated. The Bland-Altman test was applied to quantify the comparability and bias between measurements. The magnitude and significance of a change in BP during the CVR assessment were calculated in conjunction with an estimate of the velocity change attributed to the BP. The statistical significance of the data segment length on the variability and magnitude of the CVR index was computed.

Results
—The value of the CVR index was reduced by 20% and 6% in comparison to the conventional ratio approach when MLRA and linear regression were applied, respectively. With the use of MLRA, in 96% of cases the value of the BP coefficient was statistically significant, and in four patients the increase in velocity was primarily attributed to the increase in BP.

Conclusions
—The influence of BP is significant and requires consideration when the CVR index is calculated in patients with carotid artery disease.
Assessment of Clinical Outcomes in Acute Stroke Trials
Authors: Roberts Lucy , Counsell Carl
Published: June 2011

Background and Purpose
—Adequate outcome assessment is crucial to randomized trials. We wished to assess the types of outcomes used in acute stroke trials and the appropriateness of these outcomes and their analyses.

Methods
—Acute stroke trials from the Cochrane Stroke Group’s database were included from 1955 to 1995 if they were published in full text in English. For each trial we collected year of publication, number of patients randomized, blinding of outcome assessment, the specific outcome instruments used, the statistical methods used for analysis, and the significance of the results. The validity and reliability of each outcome measure were assessed by review of the literature.

Results
—Our study included 174 trials. Outcomes were assessed blindly in 69%. Death was recorded in only 76% of trials, impairment in 76%, disability in 42%, and handicap or quality of life in only 2%. Of the trials that measured impairment, 35% used a measure of established validity or reliability. For disability and handicap, the proportions with valid or reliable measures were 70% and 25%, respectively. Impairment and handicap measures were primarily analyzed as continuous variables, while disability was mainly analyzed as a dichotomous variable. Continuous data were usually analyzed with inappropriate parametric statistics. There was no relationship between the method of analysis, the type of outcome, and the statistical significance of results.

Conclusions
—Most acute stroke trials up to 1995 have used clinical outcome measures that were inadequate in terms of their content, reliability, validity, blinded assessment, and statistical analysis. This has important implications for future stroke research.
Circadian Variation in the Timing of Stroke Onset
Authors: Elliott William J.
Published: June 2011

Background and Purpose
—Acute myocardial infarction and sudden death display a circadian rhythm, with a higher risk between 6
am
and noon. Some reports suggest that stroke does not follow such a circadian variation and that hemorrhagic stroke occurs more often during the evening.

Methods
—A meta-analysis of 31 publications reporting the circadian timing of 11 816 strokes was performed, subdividing (when possible) by the type of stroke, according to the time of onset of symptoms. When precise timing was not given, strokes were distributed evenly (that is, biasing toward the null hypothesis of lack of circadian variation).

Results
—All subtypes of strokes displayed a significant (
P
<0.001) circadian variation in time of onset, whether divided into 3-, 4-, or 6-hour time periods. There was a 49% increase (95% confidence interval, 44% to 55%) in stroke of all types between 6
am
and noon (compared with expectations if no circadian variation was present), which is a 79% (95% confidence interval, 72% to 87%) increase over the normalized risk of the other 18 hours of the day. There were 29% fewer strokes between midnight and 6
am
, a 35% decrease compared with the other 18 hours of the day. All three subtypes of stroke had a significantly higher risk between 6
am
and noon (55% for 8250 ischemic strokes; 34% for 1801 hemorrhagic strokes, and 50% for 405 transient ischemic attacks).

Conclusions
—These data support the presence of a circadian pattern in the onset of stroke, with a significantly higher risk in the morning.
A Reproducible Model of Circulatory Arrest and Remote Resuscitation in Rats for NMR Investigation
Authors: Liachenko Serguei , Tang Pei , Hamilton Ronald L. , Xu Yan
Published: June 2011

Background and Purpose
—Because noninvasive physiological monitoring of cerebral blood flow, metabolic integrity, and brain ion and water homeostasis can now be accomplished with new, state-of-the-art MR spectroscopy and imaging techniques, it is appropriate to develop controllable and reproducible animal models that permit prolonged circulatory arrest and resuscitation in the magnet and also allow for studies of long-term survival and outcome. We have developed such a model in rats that involves minimal surgical preparations and can achieve resuscitation remotely within precisely controlled time.

Methods
—Cardiac arrest was induced by asphyxiation, the duration of which ranged from 8 to 24 minutes. Resuscitation was achieved remotely by a slow, intra-aortic infusion of oxygenated blood (withdrawn either from the same rat before asphyxia or from a healthy donor rat) along with a resuscitation cocktail containing heparin (50 U/100 g), sodium bicarbonate (0.1 mEq/100 g), and epinephrine (4 μg/100 g). The body temperature was measured by a tympanic thermocouple probe and was controlled either by a heating pad (constant tympanic temperature=37°C) or by warm ambient air (constant air temperature=37°C). Interleaved
31
P/
1
H nuclear magnetic resonance (NMR) spectroscopy was used in a selected group of rats to measure the cerebral metabolism before and during approximately 20 minutes of circulatory arrest and after resuscitation.

Results
—The overall success rate of resuscitation, irrespective of the duration of cardiac arrest, was 82% (51 of 62). With a programmed infusion pump, the success rate was even higher (95%). The survival time for rats subjected to 15 and 19 minutes of asphyxia with core temperature tightly controlled was significantly lower than that with ambient temperature control (
P
<0.001 and
P
<0.04, respectively). High-quality NMR spectra can be obtained continuously without interference from the resuscitation effort. Final histological examinations taken 5 days after resuscitation showed typical neuronal damages, similar to those found in other global ischemia models.

Conclusions
—Because the no-flow time and resuscitation time can be precisely controlled, this outcome model is ideally suited for studies of ischemic and reperfusion injuries in the brain and possibly in other critical organs, permitting continuous assessment of long-term recovery and follow-up in the same animals.
Changes of Cerebrovascular CO
2
Reactivity During Normal Aging
Authors: Kastrup Andreas , Dichgans Johannes , Niemeier Matthias , Schabet Martin
Published: June 2011

Background and Purpose
—During the past decade, transcranial Doppler sonography has widely been used to assess blood flow velocities in the basal intracranial arteries and cerebrovascular reactivity (CR) to various stimuli. Although numerous studies have shown a decline of cerebral blood flow velocity with age, the age dependency of CR, including cerebrovascular CO
2
reactivity, however, is controversial. Recently, we have reported a significant sex-related difference in CR, stressing the need to study the relation between normal aging and CR in both sexes separately.

Methods
—By means of transcranial Doppler sonography, CR was determined in 100 healthy, nonsmoking volunteers (age 20 to 70 years, 10 men and 10 women per decade).

Results
—In men, no change of CR with increasing age could be observed (
P
=0.98). In contrast, CR in women declined significantly, with a step decrease from the 4th to the 5th decades (F=4.413;
P
<0.01) and was significantly higher in the 3rd and 4th compared with the 5th, 6th, and 7th decades (
P
<0.05). Information on hormone replacement therapy (HRT) in women of the 6th and 7th decades was obtained retrospectively. HRT was associated with enhanced CR (HRT, n=7 versus non-HRT, n=13;
P
<0.001), with values similar to those found in premenopausal women.

Conclusions
—There are no changes of CR during normal aging in men, whereas CR declines significantly from the 4th to the 5th decades in women. HRT in postmenopausal women appears to enhance CR.
Adenovirus-Mediated Gene Transfer In Vivo to Cerebral Blood Vessels and Perivascular Tissue in Mice
Authors: Christenson Stuart D. , Lake Kristy D. , Ooboshi Hiroaki , Faraci Frank M. , Davidson Beverly L. , Heistad Donald D.
Published: June 2011

Background and Purpose
—Gene transfer to cerebral blood vessels has been accomplished in rats and dogs by injection of replication-deficient adenovirus into cerebrospinal fluid. In this study we examined transgene expression after injection of adenovirus into the cerebrospinal fluid of mice. Responses were observed in ICR mice and C57BL/6 mice, which are outbred and inbred strains, respectively.

Methods
—We injected replication-deficient recombinant adenovirus expressing nuclear targeted β-galactosidase, driven by either the Rous sarcoma virus promoter (AdRSV-βGal) or the cytomegalovirus promoter (AdCMV-βGal), into the cisterna magna of anesthetized ICR and C57BL/6 strains of mice. The brains were examined from 1 to 21 days after injection by chemiluminescent enzyme activity assay or histochemical staining.

Results
—After injection of AdRSV-βGal, expression of β-galactosidase in ICR mice peaked on day 7 and returned to basal by day 14. Expression of β-galactosidase in C57BL/6 mice was maximal on days 7 to 14 and was minimal by day 21 after injection of AdRSV-βGal. After injection of AdCMV-βGal in C57BL/6 mice, peak expression of transgene occurred on day 1 and was greatly diminished by day 3. Transgene expression was observed primarily on the ventral surface of the brain, with preferential expression in leptomeninges and adventitia along the major cerebral arteries of that region.

Conclusions
—Injection of recombinant adenovirus in the cisterna magna resulted in transgene expression in leptomeninges and perivascular tissue of cerebral blood vessels in two strains of mice. The CMV promoter elicited rapid but short-lived expression of the transgene, while the RSV promoter elicited slower, more sustained transgene expression. Expression of AdRSV transgene was prolonged in C57BL/6 mice compared with ICR mice. This approach for gene transfer may be useful to study cerebral vascular biology in genetically altered strains of mice.
Mortality and Morbidity of Surgery for Unruptured Intracranial Aneurysms
Authors: Raaymakers Theodora W. M. , Rinkel Gabriel J. E. , Limburg Martien , Algra Ale
Published: June 2011

Background and Purpose
—Greater availability and improvement of neuroradiological techniques have resulted in more frequent detection of unruptured aneurysms. Because prognosis of subarachnoid hemorrhage is still poor, preventive surgery is increasingly considered as a therapeutic option. Elective surgery requires reliable data on its risks. Therefore, we performed a meta-analysis on the mortality and morbidity of surgery for unruptured intracranial aneurysms.

Methods
—Through Medline and additional searches by hand, we retrieved studies on clipping of unruptured (additional, symptomatic, or incidental) aneurysms published from 1966 through June 1996. Two authors independently extracted data. We used weighted linear regression for data analysis.

Results
—We included 61 studies that involved 2460 patients (57% female; mean age, 50 years) and at least 2568 unruptured aneurysms (27% >25 mm, 30% located in the posterior circulation). Mortality was 2.6% (95% confidence interval [CI], 2.0% to 3.3%). Permanent morbidity occurred in 10.9% (95% CI, 9.6% to 12.2%) of patients. Postoperative mortality was significantly lower in more recent years for nongiant aneurysms and aneurysms with an anterior location; the last 2 characteristics were also associated with a significantly lower morbidity.

Conclusions
—In studies published between 1966 and 1996 on clipping of unruptured aneurysms, mortality was 2.6% and morbidity was 10.9%. In calculating the pros and cons of preventive surgery, these proportions should be taken into account.
A Cohort Study of the Safety and Feasibility of Intraventricular Urokinase for Nonaneurysmal Spontaneous Intraventricular Hemorrhage
Authors: Coplin William M. , Vinas Federico C. , Agris Jacob M. , Buciuc Razvan , Michael Daniel B. , Diaz Fernando G. , Muizelaar J. Paul
Published: June 2011

Background and Purpose
—Small case series have reported potential benefit from thrombolysis after spontaneous intraventricular hemorrhage (IVH). Our objective was to review our experience using intraventricular urokinase (UK) in treating selected patients with IVH.

Methods
—Using medical records, we identified all patients who received ventriculostomies for CT-confirmed nonaneurysmal nontraumatic spontaneous IVH from December 1992 through November 1996. We reviewed charts and CT images and examined the data for associations with specific outcomes.

Results
—We identified 40 patients, 18 treated with ventriculostomy alone and 22 receiving adjunctive intraventricular UK. The initial Glasgow Coma Scale (GCS) scores of the two groups were similar (
P
=0.5). While there was a trend for patients with any intraparenchymal hemorrhage (IPH) to receive UK (
P
=0.07), the mean size of IPH in those who received ventriculostomy alone was larger than in those who received adjunctive UK (
P
=0.002). There was lower mortality in the group treated with UK (31.8 versus 66.7%;
P
=0.03), but there was only a trend toward an increase in favorable outcome (22.2% versus 36.4%;
P
=0.3). Overall, the most significant association with outcome was neurological condition at presentation (GCS >5 versus ≤5;
P
=0.003). Receiving UK did not increase the occurrence of complications or hospital length of stay for survivors (
P
=0.5).

Conclusions
—Intraventricular UK remains a safe and potentially beneficial intervention. While it appeared to lower mortality, a randomized, placebo-controlled trial is needed to explore whether the therapy can increase the incidence of favorable outcomes.
Collagen Organization in the Branching Region of Human Brain Arteries
Authors: Finlay Helen M. , Whittaker Peter , Canham Peter B.
Published: June 2011

Background and Purpose
—Unruptured saccular aneurysms are relatively common, occurring in 4% to 9% of autopsies. Their development at the apex region of brain artery bifurcations is attributed to a combination of structural factors and the effect of blood pressure. Collagen is a primary tension-bearing fabric of the vessel wall, and our purpose was to examine its 3-dimensional alignment at arterial branches.

Methods
—Sixteen segments of arteries from the circle of Willis, including bifurcations, were pressure distended, fixed, and sectioned in 1 of 3 orthogonal planes. We measured the 3-dimensional organization of collagen at the flow divider by using the polarized light microscope. An electron microscopy study performed in tandem provided measurements on the collagen fibril diameters and packing density.

Results
—Orientation data of the collagen fabric were obtained from sections from 3 different cutting planes. The tunica media of all bifurcations had an alignment that was primarily circumferential, and the medial gap (medial defect) was distinguishable at the apex of all bifurcations. The subendothelial layer was thin at the apex but thicker and more disorganized distally. Adventitial collagen showed little organization except for a high degree of alignment along the apex. Results from the electron microscopy study showed densely packed collagen fibrils of uniform diameter at the apex, compared with slightly smaller and less densely packed fibrils nearby.

Conclusions
—In the region of the medial gap, a narrow band of highly aligned tendonlike collagen running in the direction of the ridge of the flow divider was a consistent finding. This structure would provide strength and stability to the vessel and is inconsistent with the concept of an inherent defect in the structure of bifurcations.
Cerebral Hemodynamic Changes Induced by Simulated Tracheal Intubation: A Possible Role in Perioperative Stroke?
Authors: Weintraub Michael I. , Khoury Andre
Published: June 2011

Background and Purpose
—Perioperative stroke is a rare complication of generalized surgery (1% to 6%). Unexpected difficulties with tracheal intubation (TI), as well as the hyperextended position, may predispose a patient to or play a role in stroke. We sought to identify blood flow changes in carotid and vertebral arterial circulation during simulated TI and develop profile models for stroke risk before possible generalized surgery.

Methods
—One hundred sixty consecutive patients with suspected cerebral vascular disease or pending surgery underwent MR angiography with flow analysis. Simulated TI position was maintained for 3 to 4 minutes per acquisition.

Results
—The cohort consisted of 89 females (56%) and 71 males (44%) with a mean age of 66 years (range, 17 to 89 years). Hypoplastic vertebral arteries with flow less than 50 mL/s were present in 40 patients (25%). Profound alteration in basilar artery flow was noted in this group with increased frequency of microinfarctions on MRI (77% versus 38%). Unsuspected carotid occlusion (n=6) and vertebral artery occlusion (n=2) were associated with significant basilar artery flow changes. Flow reversal was present in five cases. Carotid arterial changes were not significant with simulated TI. No overt ischemic symptoms developed during these maneuvers.

Conclusions
—Simulated TI is safe yet induces distinct and potentially detrimental flow abnormalities. Individuals identified with the biological markers of hypoplasia, carotid and vertebral occlusion, severe stenosis, or prior ischemic vascular disease should receive special attention to neck position not only during surgery but also in the postoperative period. Sustained neck hyperextension greater than 12 minutes appears to be a neglected potential hemodynamic factor that may play a pivotal role in the pathogenesis of perioperative stroke.
High Prevalence of Antiphosphatidylinositol Antibodies in Young Patients With Cerebral Ischemia of Undetermined Cause
Authors: Toschi Vincenzo , Motta Adele , Castelli Carlo , Paracchini Maria Luisa , Zerbi David , Gibelli Andrea
Published: June 2011

Background and Purpose
—Anticardiolipin antibodies (aCL) are associated with thrombotic phenomena including cerebral ischemia in young adults. Although aCL are directed to a neoepitope formed by phospholipid and β2-glycoprotein I (β2-GPI), immunoassays based on cardiolipin as target antigen are widely used. We previously demonstrated that 47% of aCL-negative systemic lupus erythematosus (SLE) patients had antiphospholipid antibodies (aPL) to epitopes other than cardiolipin, and we found an association between aPL to noncardiolipin antigens and thrombosis. We now assess the prevalence and clinical significance of noncardiolipin aPL in young adults with cerebrovascular disease of undetermined etiology.

Methods
—Seventy-seven non-SLE patients, aged <51 years, with cerebral ischemia were studied. Specificity of aPL were characterized by ELISAs using 7 different phospholipids: cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylcholine, and phosphatidylethanolamine.

Results
—Thirty-four patients (44.1%), had aPL to 1 or more of the following antigens: 23.4% to CL, 18.2% to PS, 15.6% to PG, 14.3% to PA, and 28.6% to PI. Fifty-nine patients (76.6%) were aCL negative. Of these subjects 23.4% showed aPL to noncardiolipin epitopes. PI was the specificity with highest prevalence in all subgroups, and in 6 patients anti-PI antibodies were the only detectable aPL. The binding of aPL to the different antigens was β2-GPI dependent.

Conclusions
—Our data demonstrate a high prevalence of aPL in young adults with cerebral ischemia of undetermined cause. PI was the specificity with highest prevalence, suggesting that anti-PI antibodies may be an immunological marker in young patients with cerebrovascular disease.
Early Hemicraniectomy in Patients With Complete Middle Cerebral Artery Infarction
Authors: Schwab S. , Steiner T. , Aschoff A. , Schwarz S. , Steiner H. H. , Jansen O. , Hacke W.
Published: June 2011

Background and Purpose
—Malignant, space-occupying supratentorial ischemic stroke is characterized by a mortality rate of up to 80%. Several reports indicate a beneficial effect of hemicraniectomy in this situation. However, whether and when decompressive surgery is indicated in these patients is still a matter of debate.

Methods
—In an open, prospective trial we performed hemicraniectomy in 63 patients with acute complete middle cerebral artery infarction. Initial clinical presentation was assessed by the Scandinavian Stroke Scale (SSS) and the Glasgow Coma Scale (GCS). All survivors were reexamined 3 months after surgical decompression, with the clinical evaluation graded according to the Rankin Scale (RS) and Barthel Index (BI). We analyzed the influence of early decompressive surgery (<24 hours after symptom onset, based on clinical status at admission and initial CT findings) versus late surgery (>24 hours after first reversible signs of herniation) on mortality, functional outcome, and the length of time of critical care therapy was needed.

Results
—In total, 46 patients (73%) survived. Despite complete hemispheric infarction, no survivor suffered from complete hemiplegia or was permanently wheelchair bound. In patients with speech-dominant hemispheric infarction (n=11), only mild to moderate aphasia was present. The mean BI score was 65, and RS score revealed severe handicap in 13% of the patients. In 31 patients with early decompressive surgery, mortality was 16% and BI score 68.8. Early hemicraniectomy led to a significant reduction in the length of time critical care therapy was needed (7.4 versus 13.3 days,
P
<0.05).

Conclusions
—In general, the outcome of patients treated with craniectomy in severe ischemic hemispheric infarction was surprisingly good. In addition, early decompressive surgery may further improve outcome in these patients.
Delayed Treatment With an Adenosine Kinase Inhibitor, GP683, Attenuates Infarct Size in Rats With Temporary Middle Cerebral Artery Occlusion
Authors: Tatlisumak Turgut , Takano Kentaro , Carano Richard A. D. , Miller Leonard P. , Foster Alan C. , Fisher Marc
Published: June 2011

Background and Purpose
—Brain ischemia is associated with a marked increase in extracellular adenosine levels. This results in activation of cell surface adenosine receptors and some degree of neuroprotection. Adenosine kinase is a key enzyme controlling adenosine metabolism. Inhibition of this enzyme enhances the levels of endogenous brain adenosine already elevated as a result of the ischemic episode. We studied a novel adenosine kinase inhibitor (AKI), GP683, in a rat focal ischemia model.

Methods
—Four groups of 10 adult Sprague-Dawley rats were exposed to 90 minutes of temporary middle cerebral artery (MCA) occlusion. Animals were injected intraperitoneally with vehicle, 0.5 mg/kg, 1.0 mg/kg, or 2.0 mg/kg of GP683 30, 150, and 270 minutes after the induction of ischemia by a researcher blinded to treatment group. The animals were euthanatized 24 hours after MCA occlusion, and brains were stained with 2,3,5-triphenyltetrazolium chloride. We measured brain temperatures in a separate group of 6 rats before and after administration of 1.0 mg/kg GP683.

Results
—All treated groups showed a reduction in infarct volumes, but a significant effect was observed only in the 1.0 mg/kg–dose group (44% reduction,
P
=0.0077). Body weight, physiological parameters, neurological scores, and mortality did not differ among the 4 groups. No apparent behavioral side effects were observed. Brain temperatures did not change after drug injection.

Conclusions
—Our results indicate that the use of AKIs offers therapeutic potential and may represent a novel approach to the treatment of acute brain ischemia. The therapeutic effect observed was not caused by a decrease in brain temperature.
The Effect of Hyperbaric Oxygen on the Mental and Verbal Ability of Stroke Patients
Authors: Sarno John E. , Rusk Howard A. , Diller Leonard , Sarno Martha T.
Published: June 2011

Based upon the assumption that oxygen under increased atmospheric pressure (OHP) might improve the verbal and mental function of patients who had suffered vascular infarcts, 32 stroke patients were exposed to such an ambient atmosphere and tested under controlled conditions. The results make it clear that a single exposure to 100% oxygen under two atmospheres of pressure, which is productive of high blood oxygen levels, does not improve the communication and cognitive-perceptual function of these patients.
Opacity Pulse Propagation Measurement and Thermometry in the Evaluation of Carotid Occlusive Vascular Disease: Correlations With Angiography
Authors: PRICE THOMAS R. , HECK ALBERT F.
Published: June 2011

A correlative study of four-vessel angiography with measurements of opacity pulse propagation times and skin temperatures over the medial supraorbital areas of the forehead was carried out in 46 patients. Differences in propagation times of greater than 12 milliseconds and/or in thermometric measurements of 1 °F or more were always associated with angiographically demonstrable carotid occlusive disease. In patients with positive angiographical findings, prolongation of pulse propagation time was associated with lower skin temperature when the latter occurred. Test results indicated abnormality in six of seven patients with bilateral carotid occlusive disease. By these methods, unilateral occlusive lesions of 30% to 50% of the vascular lumen were detected in three of five instances where such lesions occurred; occlusive lesions greater than this degree were detected in 15 of 18 patients. The tests identified as "normal" 18 of 23 patients whose four-vessel angiograms were either totally unremarkable or showed lesions compromising less than 30% of the carotid lumen. Combination of these screening tests is more useful than either test employed alone and may be helpful in clinical evaluation of patients with cerebrovascular disease.
The Outcome for patients With Cerebrovascular Disease in University and Community Hospitals
Authors: CARPENTER ROBERT R. , REED DAVID E.
Published: June 2011

Medical records form 1,117 cases of cerebrovascular disese from a university and four community hospitals contained data adequate to define the care process, case severity and rates of death and disability (outcome) for patients with certain stroke syndromes. Outcome for patients with "acute stroke" and "vague syndrome" attributed to stroke was different according to the patient's hospital and attending physician.

The more frequent case fatality among generalists' patients with vague syndrome was related to case severity; generalists' patients were older and more severely obtunded. Different fatality rates for acute stroke according to the patients's attending physician and hospital, and for vague syndrome according to hospital, were not explained by differences in case severity. Instead, these rates correlated with the care used to prevent, dagnose and treat pneumonia.

Examination of the care process for these stroke patients also suggested: (a)that the brain scan and electroencephalogram can be used less frequently in some hospitals in cases of acute stroke, (b) that a more careful neurological examination and other diagnostic work is needed for young or comatose patients with vague syndrome, (c) that oral papaverine is used with unnecessary frequency, and (d) that the indications for anticoagulation of stroke patients should be reviewed.
Exercise and Risk of Stroke in Male Physicians
Authors: Lee I-Min , Hennekens Charles H. , Berger Klaus , Buring Julie E. , Manson JoAnn E.
Published: June 2011

Background and Purpose
—From a physiological perspective, physical activity might be expected to decrease the risk of developing stroke. However, epidemiological studies of physical activity and stroke risk have yielded divergent findings. We therefore sought to examine the association between exercise and stroke risk.

Methods
—This was a prospective cohort study of 21 823 men, followed up for an average of 11.1 years. Participants were from the Physicians’ Health Study, a randomized trial of low-dose aspirin and beta carotene. Men, aged 40 to 84 years at baseline, were free of self-reported myocardial infarction, stroke, transient ischemic attack, and cancer. At baseline, they reported on the frequency of exercise vigorous enough to work up a sweat. Stroke occurrence was reported by participants and confirmed after medical record review (n=533). We used Cox proportional hazards regression to analyze the data.

Results
—With adjustment for age, treatment assignment, smoking, alcohol intake, history of angina, and parental history of myocardial infarction, the relative risks of total stroke associated with vigorous exercise <1 time, 1 time, 2 to 4 times, and ≥5 times per week at baseline were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.61 to 1.03), 0.80 (95% CI, 0.65 to 0.99), and 0.79 (95% CI, 0.61 to 1.03), respectively;
P
for trend=0.04. In subgroup analyses, the inverse association appeared stronger with hemorrhagic than ischemic stroke. When we additionally adjusted for body mass index, history of hypertension, high cholesterol, and diabetes mellitus, corresponding relative risks for total stroke were 1.00 (referent), 0.81 (95% CI, 0.61 to 1.07), 0.88 (95% CI, 0.70 to 1.10), and 0.86 (95% CI, 0.65 to 1.13), respectively;
P
for trend=0.25.

Conclusions
—Exercise vigorous enough to work up a sweat is associated with decreased stroke risk in men. In the present study, the inverse association with physical activity appeared to be mediated through beneficial effects on body weight, blood pressure, serum cholesterol, and glucose tolerance. Apart from its favorable influences on these variables, physical activity had no significant residual association with stroke incidence.
Influence of Acetazolamide and CO
2
on Extracranial Flow Volume and Intracranial Blood Flow Velocity
Authors: Eicke B. M. , Buss E. , Bähr R. R. , Hajak G. , Paulus W.
Published: June 2011

Background and Purpose
—The vasomotor response can be tested by means of transcranial Doppler sonography. If a constant vessel diameter is assumed, the flow velocity changes will reflect blood flow volume changes. This hypothesis is difficult to verify. Simultaneous assessment of intracranial flow velocity and extracranial flow volume changes may solve this problem.

Methods
—We tested vasomotor response in 32 volunteers (age, 42±18 years) with 5% CO
2
. Acetazolamide (1 g) was tested in 15 volunteers (age, 28±8 years). To evaluate drug-dependent flow changes in the external carotid artery territory, acetazolamide was administered in 7 patients with unilateral occlusion of the internal carotid artery without evidence of collateralization through the ophthalmic artery (age, 67±12 years). Simultaneous recording included measurements of flow volume in the common carotid arteries (M-mode color duplex system) and flow velocity in the middle cerebral arteries.

Results
—With CO
2
and acetazolamide, intracranial flow velocity increased by 31% and 39%, respectively, with a simultaneous increase of common carotid artery flow volume of 47% and 50%, respectively. No change in extracranial flow volume was observed in patients with an occluded internal carotid artery.

Conclusions
—These data show not only the expected increase of flow velocity in the middle cerebral artery but also suggest an increase in cross-sectional vessel diameter of 6% and 4% with CO
2
and acetazolamide, respectively. It remains unresolved whether this observation is due to a direct effect of the drug on the vessel walls or is simply pressure dependent.
Analysis of CO
2
Vasomotor Reactivity and Vessel Diameter Changes by Simultaneous Venous and Arterial Doppler Recordings
Authors: Valdueza José Manuel , Draganski Bogdan , Hoffmann Olaf , Dirnagl Ulrich , Einhäupl Karl Max
Published: June 2011

Background and Purpose
—The use of flow velocity changes in the middle cerebral artery (MCA) measured by Doppler techniques as an index of corresponding cerebral blood flow (CBF) changes is based on the assumption that the insonated arterial diameter remains stable. The postulate of unchanging vessel calibers during CBF changes, however, is still under debate. We performed simultaneous measurements of arterial and venous blood flow velocities by transcranial Doppler ultrasound during various stages of hypercapnia to analyze diameter changes in the insonated vessels by comparing differences in the vasomotor reactivity.

Methods
—Simultaneous Doppler recordings of 1 MCA and of a contralateral venous vessel thought to represent the sphenoparietal sinus (SPS) were carried out with a pair of 2-MHz range-gated transducers in 16 young healthy subjects during variations of end-tidal Pa
co
2
.

Results
—During hypercapnia the mean blood flow velocity of the MCA rose from 62.5±10.2 to a maximum of 99±12.2 cm/s (vasomotor reactivity of 60.1±17.3%). The corresponding values in the SPS were significantly higher (
P
<0.001), revealing a rise from 17.8±5.7 to 34.9±14.3 cm/s (vasomotor reactivity of 91.4±25.9%). Exponential and linear regression analyses revealed an identical high correlation (
r
2
=0.97 and 0.98 for the MCA and SPS, respectively). Slopes were 0.034±0.01 on the arterial and 0.048±0.01 on the venous side. The CO
2
reactivity (percentage per mm Hg, Et
co
2
) was found to be 4.5±1%/mm Hg in the MCA and 6.8±1.5%/mm Hg in the SPS. This difference indicates a vasodilation of the MCA in comparison to the venous vessel.

Conclusions
—We have demonstrated a different reaction pattern between intracranial venous and arterial vessels related to end-tidal CO
2
. Relating the flow velocities to the square of the vessel diameter and assuming a global rise of CBF and not extensible sinus walls, our results indicate that the MCA undergoes a vasodilation of 9.5±7% in maximal hypercapnia.
Thiopental Attenuates Hypoxic Changes of Electrophysiology, Biochemistry, and Morphology in Rat Hippocampal Slice CA1 Pyramidal Cells
Authors: Wang Ting , Raley-Susman Kathleen M. , Wang Jun , Chambers Geoffrey , Cottrell James E. , Kass Ira S.
Published: June 2011

Background and Purpose
—Thiopental has been shown to protect against cerebral ischemic damage; however, it has undesirable side effects. We have examined how thiopental alters histological, physiological, and biochemical changes during and after hypoxia. These experiments should enable the discovery of agents that share some of the beneficial effects of thiopental.

Methods
—We made intracellular recordings and measured ATP, sodium, potassium, and calcium concentrations from CA1 pyramidal cells in rat hippocampal slices subjected to 10 minutes of hypoxia with and without 600 μmol/L thiopental.

Results
—Thiopental delayed the time until complete depolarization (21±3 versus 11±2 minutes for treated versus untreated slices, respectively) and attenuated the level of depolarization at 10 minutes of hypoxia (−33±6 versus −12±5 mV). There was improved recovery of the resting potential after 10 minutes of hypoxia in slices treated with thiopental (89% versus 31% recovery). Thiopental attenuated the changes in sodium (140% versus 193% of prehypoxic concentration), potassium (62% versus 46%), and calcium (111% versus 197%) during 10 minutes of hypoxia. There was only a small effect on ATP (18% versus 8%). The percentage of cells showing clear histological damage was decreased by thiopental (45% versus 71%), and thiopental improved protein synthesis after hypoxia (75% versus 20%).

Conclusions
—Thiopental attenuates neuronal depolarization, an increase in cellular sodium and calcium concentrations, and a decrease in cellular potassium and ATP concentrations during hypoxia. These effects may explain the reduced histological, protein synthetic, and electrophysiological damage to CA1 pyramidal cells after hypoxia with thiopental.
Spontaneous Hyperthermia and its Mechanism in the Intraluminal Suture Middle Cerebral Artery Occlusion Model of Rats
Authors: Li Fuhai , Omae Tsuyoshi , Fisher Marc
Published: June 2011

Background and Purpose
—The intraluminal suture middle cerebral artery occlusion (MCAO) model is increasingly used in experimental stroke studies. The purposes of this study were to determine whether (1) spontaneous hyperthermia occurs after different periods of MCAO in this model, (2) hypothalamic injury contributes to hyperthermia, and (3) hyperthermia increases infarct volume after permanent MCAO.

Methods
—Rats were subjected to 60, 90, and 120 minutes of transient MCAO (n=8 per group), permanent MCAO (n=8 per group, 5 groups), and permanent hypothalamic occlusion, in which an occluder was inserted 15 to 15.5 mm to block only the hypothalamic branch from the internal carotid artery (n=4) with the use of the intraluminal suture MCAO method. In one group undergoing permanent MCAO, the body temperature was maintained at 37°C throughout the experiment. In another group (n=4) undergoing 90 minutes of temporary MCAO, diffusion- and perfusion-weighted imaging were performed to document the in vivo ischemic changes in the hypothalamus. Body temperature was measured hourly for 12 hours. At 24 hours (12 hours in 2 permanent MCAO groups), triphenyltetrazolium chloride staining was used to verify ischemic hypothalamic injury and to calculate corrected infarct volumes.

Results
—Spontaneous hyperthermia (>39°C) occurred in the 120-minute group, all permanent MCAO groups, and the hypothalamic occlusion group but not in the 60-minute or the 90-minute groups. Hypothalamic infarction was found in 1 rat each in the 60-minute and 90-minute groups, 6 of the 8 rats in the 120-minute group, 37 of the 40 rats in the permanent occlusion groups, and all 4 rats in the hypothalamic occlusion group. After 90 minutes of transient MCAO, the decreased cerebral blood flow and apparent diffusion coefficient values in the hypothalamic region during occlusion recovered fully 2 hours after reperfusion. The corrected infarct volumes were identical in all permanent occlusion groups.

Conclusions
—The intraluminal suture MCAO lasting for ≥2 hours induces spontaneous hyperthermia that is associated with hypothalamic injury, and delayed spontaneous hyperthermia does not increase infarct volume after permanent intraluminal suture MCAO.
Functional Polymorphism in the Matrix Metalloproteinase-9 Promoter as a Potential Risk Factor for Intracranial Aneurysm
Authors: Peters David G. , Kassam Amin , St. Jean Pamela L. , Yonas Howard , Ferrell Robert E.
Published: June 2011

Background and Purpose
—There is convincing evidence that susceptibility to intracranial aneurysms (ICAs) has a genetic component. However, few studies have sought to identify functional variation in specific candidate genes that may predispose individuals to develop an ICA.

Methods
—ICA cases and controls were genotyped for a simple length polymorphism in the promoter of matrix metalloproteinase-9 (MMP-9) to test for association between variation in the promoter and the occurrence of ICA. Alternative alleles were cloned into an in vitro reporter vector, transfected into human HT1080 fibroblasts, and assayed for promoter activity by β-gal and luciferase assays. Electrophoretic gel shift assays were used to assess nuclear factor binding.

Results
—A length polymorphism in the promoter of MMP-9 was nonrandomly associated with the occurrence of ICA in a case-control study. This polymorphism was shown, by direct sequencing of 36 individuals, to be the only sequence variation within a 736–base pair region proximal to the transcriptional start site of the gene. Variation in the length of this repetitive element was shown to modulate promoter activity in an in vitro reporter assay, with the highest promoter activity being observed in constructs bearing the longest [(CA)23] element. Electrophoretic mobility shift assays were used to show that the (CA) element is bound by a sequence-specific DNA-binding protein.

Conclusions
—Genetic variation in the promoter of the MMP-9 gene results in variation in its expression at the level of transcription. This may result in subtle differences in MMP-9 activity within the circle of Willis, leading to increased susceptibility to ICA formation.