bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of Stroke in the Netherlands From a Societal Perspective
Authors: Evers S. M. A. A. , Engel G. L. , Ament A. J. H. A.
Published: June 2011

Background and Purpose
Cerebrovascular disorders are associated with a high level of morbidity and mortality and call for considerable resources. The objective of this study was to determine from a societal perspective the medical consumption (direct costs) and productivity losses (indirect costs) caused by cerebrovascular disorders in the Netherlands.

Methods
This study can be characterized as a cost-of-illness study based on prevalence data. All data gathered refer to 1993. Cerebrovascular disorders are defined according to the
International Classification of Diseases, 9th Revision
(ICD-9) classification. Data from medical registrations and national statistics have been analyzed. For both direct and indirect costs, volume and cost components are presented. To test the likelihood of the assumptions, a sensitivity analysis was performed.

Results
The cost of cerebrovascular disorders in the Netherlands in 1993 amounted to 2.5 billion Dutch guilders, of which 1.9 billion were spent on medical consumption. It was found that direct costs are generated mainly by the long-term care of inpatients (nursing homes and hospitals). The productivity losses were relatively low in comparison with other diseases, probably due to the fact that most patients with cerebrovascular disorders are elderly.

Conclusions
More than 3% of the Dutch annual healthcare budget is spent on patients suffering from cerebrovascular disorders. Costs in the future may be influenced by, among other things, demographic changes, new therapies, and cost-reduction programs introduced by the government.
Prognostic Value and Determinants of First-Day Mean Arterial Pressure in Spontaneous Supratentorial Intracerebral Hemorrhage
Authors: Fogelholm Rainer , Avikainen Sari , Murros Kari
Published: June 2011

Background and Purpose
The onset of spontaneous intracerebral hemorrhage (ICH) is often accompanied by transient blood pressure (BP) elevation. The prognostic value and the determinants of this BP reaction have not entirely been solved, and the present study was focused on these questions.

Methods
From 1985 to 1991 in Central Finland (population, 246 000), a total of 425 patients had first-ever ICH verified by CT or necropsy. The hematoma was supratentorial in 337 patients. Of the 306 patients with supratentorial ICH who had CT, 282 had the BP measured at least once within 24 hours of onset, and they formed the study population. The case notes and CT films were reviewed, and mean arterial pressure (MAP) was calculated from the highest BP reading.

Results
The fatality rate was high; 43% of the patients were dead within 28 days of onset. Six independent predictors of the 28-day survival were identified by multiple logistic regression; these predictors were consciousness on admission, first-day MAP, subarachnoid spread of the bleed, lateral shift of hemispheral midline structures, admission blood glucose, and vomiting. The MAPs varied between 66.7 and 203.3 mm Hg, and the cutoff points of the MAP quartiles were 118, 132, and 145 mm Hg. Patients in the first three MAP quartiles had relatively fair outcome, with 71%, 65%, and 60%, respectively, alive 28 days after onset. This was in sharp contrast to the fourth quartile, with only 33% surviving the first 28 days (log-rank,
P
<.0001 to
P
=.0010). Patients unconscious/comatose on admission had significantly higher MAPs than did those who were alert or somnolent/disoriented (ANOVA,
P
=.0079). However, at all levels of consciousness, the 28-day fatality rate increased from the first to the fourth MAP quartile: 69% in the alert, 186% in the somnolent/disoriented, and 45% in the unconscious/comatose patients. Stepwise multiple regression analysis gave four independent predictors of the first-day MAP: hypertension, age (in an inverse fashion), admission blood glucose, and hematoma volume.

Conclusions
The most important predictor of the 28-day survival was the level of consciousness on admission, followed by first-day MAP. Hypertension was the most important predictor of the first-day MAP, followed by age, which had an inverse effect on the MAP level. At all levels of consciousness, high first-day MAP (especially if >145 mm Hg) worsened the 28-day survival rate.
Blood Pressure Changes in Acute Cerebral Infarction and Hemorrhage
Authors: Morfis Litsa , Schwartz Raymond S. , Poulos Roslyn , Howes Laurence G.
Published: June 2011

Background and Purpose
We sought to investigate the changes in blood pressure (BP) that occur after hospitalization of patients with different types of acute stroke.

Methods
Twenty-four–hour ambulatory BP monitoring was performed on days 1 and 7 after admission to the hospital in 72 patients with acute stroke (44 thromboembolic strokes, 18 lacunar infarcts, and 10 intracerebral hemorrhages) and in 22 control patients. Stroke was categorized clinically into the above stroke subtypes with radiological confirmation. The controls were patients admitted with a range of acute medical problems other than stroke who were not severely ill or in significant pain. Left ventricular hypertrophy was assessed with echocardiography. Multiple linear regression was used to determine the effect of stroke category on BP after adjustment for the effects of potential confounders.

Results
Patients with thromboembolic and lacunar strokes had significantly higher systolic BP (SBP) on day 1 than control subjects (mean, 8.6% and 13.2%, respectively). Diastolic BP (DBP) was also significantly higher for patients with thromboembolic and lacunar strokes on day 1 (mean, 11.7% and 14.6%, respectively). Patients with intracerebral hemorrhage had SBP 9.7% and DBP 6.3% higher than control subjects on day 1, but the results did not achieve statistical significance. By day 7 there was no significant difference in SBP or DBP between the stroke subgroups and control subjects.

Conclusions
BP is elevated after stroke but resolves spontaneously after 7 days. This transient elevation in BP does not appear to result solely from the stress of hospitalization.
Spontaneous Intracranial Hemorrhage: Which Patients Need Diagnostic Cerebral Angiography?
Authors: Zhu X. L. , Chan M. S. Y. , Poon W. S.
Published: June 2011

Background and Purpose
In spontaneous intracerebral hemorrhage (ICH), the site, age of the patients, and preexisting hypertension are important factors in determining the possibility of finding an underlying vascular abnormality by cerebral angiography. To what extent these three factors affect the indication for angiography remains controversial. A prospective study was carried out to correlate the angiographic findings with these three factors.

Methods
Two hundred six consecutive spontaneous ICH cases with an age range from 5 to 79 years (median, 45) were investigated with CT and cerebral angiography over a 3-year period (April 1993 through March 1996). Exclusion criteria were (1) poor surgical risk or severely neurologically disabled patients, (2) refusal of angiography, (3) patients in whom severe coagulopathy accounted for the hemorrhage, (4) bleeding into tumor, or (5) subarachnoid hemorrhage–predominant cases.

Results
Angiographic yield (the frequency of positive angiography in a defined patient group) was significantly higher in patients (1) at or below the median age of 45 than those above (53/105, 50%, versus 18/101, 18%;
P
<.001) and (2) without preexisting hypertension than those with (64/145, 44%, versus 5/58, 9%;
P
<.001). The correlation of age and preexisting hypertension to angiographic yield was independent (logistic regression coefficients −0.056 and −1.59 and SE 0.12 and 0.515, respectively, both
P
<.001). In patients of the younger age group without preexisting hypertension, angiographic yield was 48% in putaminal, thalamic, or posterior fossa ICH and 65% in lobar ICH. In the older hypertensive patients, the yields were 0% and 10%, respectively. However, in patients with isolated intraventricular hemorrhage, most were normotensive and the yield was high in both age groups (67% versus 63%).

Conclusion
Diagnostic cerebral angiography should be considered for all spontaneous ICH patients except those over 45 years old with preexisting hypertension in thalamic, putaminal, or posterior fossa hemorrhage.
Interactive Effects of Age and Hypertension on Volumes of Brain Structures
Authors: Strassburger Terri L. , Lee Hing-Chung , Daly Eileen M. , Szczepanik Joanna , Krasuski Jack S. , Mentis Marc J. , Salerno Judith A. , DeCarli Charles , Schapiro Mark B. , Alexander Gene E.
Published: June 2011

Background and Purpose
Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n=27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests.

Methods
Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject.

Results
The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group×age-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups.

Conclusions
Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.
A Near-Infrared Spectroscopic Study of Cerebral Ischemia and Ischemic Tolerance in Gerbils
Authors: Li Ji-Yao , Ueda Hirokazu , Seiyama Akitoshi , Nakano Misa , Matsumoto Masayasu , Yanagihara Takehiko
Published: June 2011

Background and Purpose
To explore the physiological mechanism of ischemic tolerance, we studied intracerebral oxygenation states noninvasively using near-infrared spectroscopy after bilateral common carotid artery occlusion (BCO) in gerbils with and without ischemic pretreatment.

Methods
Under ether anesthesia, gerbils with sham operation (S group, n=8) and those with pretreatment consisting of BCO for 2 minutes, twice at 3 days and 2 days earlier (T group, n=8), were again subjected to BCO for 5 minutes. Changes in oxyhemoglobin (HbO
2
), deoxyhemoglobin (Hb), and total hemoglobin (HbT) as well as reduction in cytochrome oxidase (cyt.
aa
3
) were calculated from the absorbance changes of the light transmitted through the brain. Seven days after the ischemic study, immunohistochemical examination was performed with an antiserum against microtubule-associated proteins.

Results
In both groups, the increase of Hb and decrease of HbO
2
and HbT proceeded rapidly after BCO, and the maximal deoxygenation of hemoglobin occurred within 2.5 minutes. Reduction of cyt.
aa
3
also ensued rapidly and reached the maximal reduction within 3 minutes in both groups. In the T group, however, both deoxygenation of hemoglobin and reduction of cyt.
aa
3
progressed more slowly than in the S group. The time (seconds) necessary for a maximal change for cyt.
aa
3
was significantly longer in the T group (203.8±34.0 [mean±SD];
P
<.01) than in the S group (68.0±14.7). The time necessary for a half-maximal change was also significantly longer in the T group than in the S group for both Hb (22.0±7.5 and 13.5±4.0, respectively;
P
<.05) and cyt.
aa
3
(23.9±5.7 and 11.6±4.3;
P
<.01). After recirculation for 7 days, all gerbils in the S group were found to have neuronal death in the hippocampus, while those in the T group did not.

Conclusions
The present study indicated that mild ischemic stress can induce improvement in oxygen metabolism during subsequent ischemia, which might be causally related to the phenomenon known as “ischemic tolerance,” in which a protective effect toward ischemic/postischemic injury is induced by earlier mild ischemic pretreatment.
Effects of Intensity of Rehabilitation After Stroke
Authors: Kwakkel Gert , Wagenaar Robert C. , Koelman Tim W. , Lankhorst Gustaaf J. , Koetsier Johan C.
Published: June 2011

Background and Purpose
A research synthesis was performed to (1) critically review controlled studies evaluating effects of different intensities of stroke rehabilitation in terms of disabilities and impairments and (2) quantify patterns by calculating summary effect sizes. The influences of organizational setting of rehabilitation management, blind recording, and amount of rehabilitation on the summary effect sizes were calculated.

Methods
A Medline literature search was performed for a critical review of the literature. The internal and external validity of the studies was evaluated. In addition, a meta-analysis was performed by applying the fixed (Hedges’s g) effects model.

Results
The effects of different intensities of rehabilitation were studied in nine controlled studies involving 1051 patients. Analysis of the methodological quality revealed scores varying from 14% to 47% of the maximum feasible score. Meta-analysis demonstrated a statistically significant summary effect size for activities of daily living (0.28±0.12). Lower summary effect sizes (0.19±0.17) were found for studies in which experimental and control groups were treated in the same setting compared with studies in which the two groups of patients were treated in different settings (0.40±0.19). Variables defined on a neuromuscular level (0.37±0.24) showed larger summary effect sizes than variables defined on a functional level (0.10±0.21). Weighting individual effect sizes for the difference in amount of rehabilitation between experimental and control groups resulted in larger summary effect sizes for activities of daily living and functional outcome parameters for studies that were not confounded by organizational setting.

Conclusions
A small but statistically significant intensity-effect relationship in the rehabilitation of stroke patients was found. Insufficient contrast in the amount of rehabilitation between experimental and control conditions, organizational setting of rehabilitation management, lack of blinding procedures, and heterogeneity of patient characteristics were major confounding factors.
Stroke Prevalence in Taiwan
Authors: Huang Zei-Shung , Chiang Tung-Liang , Lee Ti-Kai
Published: June 2011

Background and Purpose
Stroke has been the second leading cause of death for all ages in Taiwan since 1983. However, despite the severity of the threat, stroke prevalence in Taiwan has not yet been addressed in a nationwide survey. In this study, the stroke prevalence in Taiwan was investigated using data from the 1994 National Health Interview Survey.

Methods
This nationwide survey sought to obtain a nationally representative sample of households in Taiwan by using three-stage stratified random sampling with a probability proportional to size. In the first stage, 58 townships were selected, from the 359 townships in Taiwan, according to their administrative structure and level of socioeconomic development. In the second stage, 149 basic administrative regions (tsun or li) were selected from the selected 58 townships. Finally, 3814 households were selected from the 149 selected tsuns or lis. Field interviews were carried out between October 1994 and December 1994. Follow-up interviews with families of stroke patients were made 2 years later.

Results
Of the selected households 3119, or 81.8%, responded. A total of 11 925 persons were interviewed, and 71 of them were stroke patients, with a crude point prevalence rate of 5.95 per 1000. The stroke prevalence increased steadily with age, from 0.51 per 1000 in persons aged 35 to 44 years to 113.6 per 1000 in persons aged 85 years or over. There was a weak association with higher stroke prevalence for persons living in eastern Taiwan or those of lower educational level. The overall male/female prevalence ratio was 1.17. The results of follow-up interviews showed a cumulative mortality rate of 25.4% within the 2-year period and an ischemic/hemorrhagic stroke ratio of 1.33 in 35 patients whose stroke type could be validated.

Conclusions
Age was the most important factor correlating to stroke prevalence. On the basis of this result, planning policies and programs for stroke prevention in Taiwan should give a higher priority to (1) aggressive primary prevention for aged people who are apparently at higher risk of stroke and (2) early reduction of stroke risk factors in younger aged people whose immediate risk of stroke is lower but would increase significantly with age.
Seizures in Acute Stroke: Predictors and Prognostic Significance
Authors: Reith Jakob , Jørgensen Henrik Stig , Nakayama Hirofumi , Raaschou Hans Otto , Olsen Tom Skyhøj
Published: June 2011

Background
Despite the common occurrence of seizures during the early phase of stroke (ES), the effect of ES on prognosis is not known. We determined the relationships between ES and stroke outcome and identified predictors of ES.

Methods
In this community-based study, we prospectively and consecutively studied 1197 patients with acute stroke. We determined the number and type of seizures, initial stroke severity, infarct size, mortality, and outcome in survivors. Stroke severity was measured on admission, weekly, and at discharge using the Scandinavian Stroke Scale (SSS). Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors, including age, gender, stroke severity on admission, atrial fibrillation, ischemic heart disease, diabetes, blood glucose level on admission, claudication, and hypertension.

Results
Fifty patients (4.2%) had seizures within 14 days of the stroke. In the multivariate analyses, only initial stroke severity was related to ES; stroke type and lesion localization were not related. For each 10-point increase in stroke severity (SSS score), the relative risk of ES increased by a factor of 1.65 (95% confidence interval, 1.4 to 1.9) (
P
<.0001). ES did not influence the risk of death during hospital stay (
P
=.56). In survivors, ES was related to a better outcome, equivalent to an increased SSS score of 5.7 points (SE [b]=1.8;
P
=.002).

Conclusions
The decisive factor of ES was initial stroke severity. ES per se was not related to mortality. Surprisingly, in survivors, ES predicted a better outcome. We explain this finding by a relatively larger ischemic penumbra in patients who have an ES after a stroke.
MRA Flow Quantification in Patients With a Symptomatic Internal Carotid Artery Occlusion
Authors: van Everdingen K. J. , Klijn C. J. M. , Kappelle L. J. , Mali W. P. T. M. , van der Grond J.
Published: June 2011

Background and Purpose
Flow measurements in the collateral arteries of patients with internal carotid artery (ICA) occlusions may be important to estimate the risk of future stroke. Quantitative flow measurements in cerebropetal vessels can be reliably assessed by means of magnetic resonance angiography (MRA).

Methods
Fifty-four patients with transient or minor ischemic neurological deficits and an angiographically proven ICA occlusion and 16 control subjects underwent two-dimensional phase-contrast MRA quantitative flow measurements through the common carotid arteries, basilar artery, ICAs, and middle cerebral arteries (MCA).

Results
Patients with a unilateral ICA occlusion and a 0% to 69% stenosis of the contralateral ICA had increased flow in the contralateral ICA (
P
<.005) and in the basilar artery (
P
<.005) compared with control subjects. Even patients with a 70% to 99% stenosis contralateral to the ICA occlusion had increased flow in the ICA (
P
<.05) as well as increased flow in the basilar artery (
P
<.001). Total cerebropetal flow was not significantly different between these patients and control subjects. Patients with bilateral ICA occlusions had an increased flow in the basilar artery (
P
<.001), while the total cerebropetal flow was less than in control subjects (
P
<.001). In all patients, flow was decreased in the ipsilateral MCA (
P
<.001) and in the contralateral MCA (
P
<.05).

Conclusions
The contralateral ICA is the main supplying artery in patients with an ICA occlusion. Total cerebropetal flow decreases only when both ICAs are occluded. In patients with symptomatic ICA occlusions, an open contralateral ICA is probably important to retain the cerebral blood flow within normal limits.
Geographic Variation in Stroke Mortality in Blacks and Whites in the United States
Authors: Pickle Linda W. , Mungiole Michael , Gillum Richard F.
Published: June 2011

Background and Purpose
We sought to determine whether the “Stroke Belt” has continued to shift and to assess variation in geographic patterns by age, sex, and race.

Methods
Mortality data for Health Service Areas for 1988 to 1992 were used for analyses of geographic mortality patterns for stroke by race, sex, and age (50, 70, and 90 years).

Results
In 1988 to 1992, considerable geographic variation in stroke mortality was demonstrated for each sex/race group. In black and white women and men, previously described high mortality in the southeastern United States persisted. Mortality rates were generally higher in the South than in the North and in the East than in the West. Compared with data from 1962 to 1988, there was a continuation of the previously described westward shift of high-rate areas to the Mississippi River valley, a trend more marked at age 50 years than at 70 or 90 years. Although rates in the Pacific region were low overall, a surprising area of high rates was seen in southern California among women at all three ages examined.

Conclusions
In whites, rapid declines in stroke mortality in the Southeast have left West South Central states with relatively high mortality rates; this trend may continue as younger cohorts age. However, rates in the Southeast also remain high, especially for blacks.
IgG Anticardiolipin Antibody Titer >40 GPL and the Risk of Subsequent Thrombo-occlusive Events and Death
Authors: Levine Steven R. , Salowich-Palm Leeza , Sawaya Kara L. , Perry Mary , Spencer H. J. , Winkler H. Jason , Alam Zarina , Carey John L.
Published: June 2011

Background
Anticardiolipin antibodies (aCL) have been associated with an increased risk of stroke and thrombo-occlusive events. Little is known about the influence of aCL on recurrent thrombo-occlusive events.

Methods
Consecutively identified patients (n=132) with focal cerebral ischemia [stroke=112, transient ischemic attack (TIA)=20] harboring aCL of at least 10 GPL units at the time of their index event were prospectively followed to estimate the effect of aCL titer on time to and risk of subsequent thrombo-occlusive events (stroke, TIA, deep venous thrombosis, pulmonary embolism, myocardial infarction) and death. On the basis of prior literature, we divided patients into those with aCL ≤40 GPL (n=111; mean age, 63±14 years; mean follow-up, 1.95 years) and those with aCL >40 GPL (n=21; mean age, 54±20 years; mean follow-up, 1.50 years).

Results
There was no difference between groups for prevalence of hypertension, diabetes mellitus, cigarette smoking, atrial fibrillation, prior TIA, or sex. The GPL >40 group was younger (54±20 versus 63±14 years;
P
=.055), had more prior strokes [9/21 (48%) versus 27/111 (20%);
P
=.030], more frequent subsequent thrombo-occlusive events and death [15/21 (71%) versus 51/111 (48%);
P
=.030], and a shorter median time (years) to event (0.15 versus 0.61, log rank
P
=.005). The risk ratio for recurrent event and death with GPL >40 obtained from Cox proportional hazards models, adjusted for prior strokes, prior TIAs, hypertension, diabetes mellitus, atrial fibrillation, and cigarette smoking was 1.9 (95% confidence interval, 1.0 to 3.5;
P
=.051).

Conclusions
Our data suggest that subsequent thrombo-occlusive events and death after focal cerebral ischemia associated with IgG aCL may occur sooner and more frequently with GPL >40.
Cerebrovascular and Cardiovascular Responses to Graded Tilt in Patients With Autonomic Failure
Authors: Bondar Roberta L. , Dunphy Paul T. , Moradshahi Peyman , Kassam Mahmood S. , Blaber Andrew P. , Stein Flo , Freeman R.
Published: June 2011

Background and Purpose
Patients with autonomic nervous system failure often experience symptoms of orthostatic intolerance while standing. It is not known whether these episodes are caused primarily by a reduced ability to regulate arterial blood pressure or whether changes in cerebral autoregulation may also be implicated.

Methods
Eleven patients and eight healthy age- and sex-matched control subjects were studied during a graded-tilt protocol. Changes in their steady state middle cerebral artery mean flow velocities (MFV), measured by transcranial Doppler, brain-level mean arterial blood pressures (MABP
brain
), and the relationship between the two were assessed.

Results
Significant differences between patients and control subjects (
P
<.05) were found in both their MFV and MABP
brain
responses to tilt. Patients’ MFV dropped from 60±10.2 cm/s in the supine position to 44±14.0 cm/s at 60° head-up tilt, whereas MABP
brain
fell from 109±11.7 to 42±16.9 mm Hg. By comparison, controls’ MFV dropped from 54±7.8 cm/s supine to 51±8.8 cm/s at 60°, whereas MABP
brain
went from 90±11.2 to 67±8.2 mm Hg. Linear regression showed no significant difference in the MFV-MABP
brain
relationship between patients and control subjects, with slopes of 0.228±0.09 cm · s
–1
· mm Hg
–1
for patients and 0.136±0.16 cm · s
–1
· mm Hg
–1
for control subjects.

Conclusions
The present study found significant differences between patients and control subjects in their MFV and MABP
brain
responses to tilt but no difference in the autoregulatory MFV-MABP
brain
relationship. These results suggest that patients’ decreased orthostatic tolerance may primarily be the result of impaired blood pressure regulation rather than a deficiency in cerebral autoregulation.
A Common Polymorphism in the Methylenetetrahydrofolate Reductase Gene, Homocysteine, and Ischemic Cerebrovascular Disease
Authors: Markus Hugh S. , Ali Nadira , Swaminathan R. , Sankaralingam A. , Molloy Jane , Powell John
Published: June 2011

Background and Purpose
A common polymorphism (
T
/
t
) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) enzyme has been associated with elevated serum homocysteine, itself a risk factor for stroke. Some studies have reported an association with ischemic heart disease, but no published studies have examined its relationship with stroke.

Methods
We determined the
TT
genotype frequency and
T
allele frequency in 345 patients with ischemic cerebrovascular disease (CVD) and 161 control subjects. In a subgroup we also determined serum homocysteine and folate concentrations.

Results
In the patient group there was a significant relationship between
TT
genotype and homocysteine concentration after we controlled for other risk factors. Controlling for serum folate weakened this relationship, and folate itself was independently related to serum homocysteine. There was no difference between patients and control subjects in either
TT
genotype frequency (10.7% versus 13.7%;
P
=.34) or
T
allele frequency (0.68 versus 0.67;
P
=.67). There was no association when analysis was limited to individuals deficient in folate (serum folate <25th centile) or to younger individuals (<65 years). There was no association between
TT
genotype and any stroke subtype or with degree of carotid stenosis.

Conclusions
In patients with CVD we confirmed a relationship between the MTHFR genotype and serum homocysteine concentration and an interaction with serum folate concentration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could still be a risk factor in populations with a low folic acid intake.
Intravenous Thrombolysis With Recombinant Staphylokinase Versus Tissue-Type Plasminogen Activator in a Rabbit Embolic Stroke Model
Authors: Vanderschueren S. , Van Vlaenderen I. , Collen D.
Published: June 2011

Background and Purpose
Timely intravenous administration of recombinant tissue-type plasminogen activator (alteplase, rTPA) to patients with evolving ischemic stroke improves neurological outcome. The present study was designed to compare the effects of rTPA and recombinant staphylokinase (Sak), a highly fibrin-specific thrombolytic agent, in an experimental model of rabbit embolic stroke.

Methods
Groups of 5 to 12 rabbits were given intravenous saline or heparin and aspirin with, in addition, either Sak (1 or 2 mg/kg infused over 30 minutes or 2 mg/kg injected over 1 minute) or rTPA (3 or 6 mg/kg infused over 30 minutes or 6 mg/kg injected over 1 minute). Infusions were started 15 minutes after selective injection of standardized
125
I-fibrin labeled rabbit plasma clots into the internal carotid artery.

Results
Mean clot lysis over 60 minutes increased from 3.8% after saline to between 27% and 44% after Sak regimens (
P
=.0001 versus control) and to between 15% and 34% after rTPA regimens (
P
=.0001). Median volume of the ischemic lesion at 5 hours decreased from 190 mm
3
after saline to between 11 and 17 mm
3
after Sak (
P
=.02) and to between 0.5 to 54 mm
3
after rTPA (
P
=.04). Mean neurological impairment at 5 hours (on a scale of 0 to 3) decreased from 2.3 after saline to between 1.3 to 1.6 after Sak (
P
=.003) and to between 1.1 to 1.9 after rTPA (
P
=.02). At the highest doses used, fibrinogen depletion was marginal with Sak but total with rTPA. Marked prolongation of ear puncture and cuticle bleeding times was only observed after bolus administration of rTPA.

Conclusions
In the present rabbit model of embolic stroke, Sak was significantly more fibrin-specific than rTPA and at least as effective in lysing arterial emboli and limiting ischemia and neurological impairment.
Strain-Related Differences in Susceptibility to Transient Forebrain Ischemia in SV-129 and C57Black/6 Mice
Authors: Fujii Masazumi , Hara Hideaki , Meng Wei , Vonsattel Jean Paul , Huang Zhihong , Moskowitz Michael A.
Published: June 2011

Background and Purpose
We explored susceptibility to injury after global ischemia in SV-129 and C57Black/6 mice, two commonly used background strains in genetically engineered mice.

Methods
Mice (n=84) were subjected to 15, 30, or 75 minutes of bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 72 hours. BCCA occlusion was performed under halothane or chloral hydrate anesthesia; in one experiment, mean arterial blood pressure and regional cerebral blood flow (laser Doppler flowmetry) were matched by controlled exsanguination. Baseline absolute blood flow measurements were obtained in both strains using a tracer,
N
-isopropyl-[methyl 1,3-
14
C]-
p
-iodoamphetamine, indicator fractionation technique (n=5 per group). Vascular anatomy of the circle of Willis was visualized by intravascular perfusion of carbon black ink (n=10 per group). Cerebrovascular reactivity was assessed by measuring the diameter of pial vessels (intravital microscopy) to acetylcholine (ACh) superfusion (0.1 to 10 mmol/L) in a closed cranial window preparation (n=29).

Results
Resting blood flow values did not differ between groups in striatum, cerebellum, and brain-stem regions. SV-129 mice were less susceptible than C57Black/6 mice to ischemic injury (0.0±0.0 versus 1.3±0.3 damage in hippocampal CA1 region after 30 minutes of ischemia in SV-129 and C57Black/6, respectively;
P
<.01). Cellular damage (grade 1 to 3 injury) comparable to 30-minute BCCA occlusion was achieved only after 75 minutes of ischemia in SV-129 mice (1.1±0.3). Ischemic damage was also significantly less in SV-129 mice after blood pressure and flow were matched during ischemia in halothane-anesthetized SV-129 mice (0.5±0.3 versus 1.4±0.2,
P
<.05), or after chloral hydrate anesthesia (0.4±0.2 versus 1.5±0.4,
P
<.05). Hypoplastic posterior communicating arteries were found in all 10 C57Black/6 mice and may explain the greater susceptibility of these mice to injury after BCCA occlusion. More robust vasodilation to ACh in C57Black/6 mice could also indicate genetic differences in responses to vasoactive substances.

Conclusions
C57Black/6 mice exhibit enhanced susceptibility to global cerebral ischemic injury, an incompletely formed circle of Willis, and augmented pial vessel dilation to ACh compared with SV-129 mice. Our findings suggest that strain differences may confound results when genetically engineered mice generated from more than a single background strain are used.
Ebselen in Acute Ischemic Stroke
Authors: Yamaguchi Takenori , Sano Keiji , Takakura Kintomo , Saito Isamu , Shinohara Yukito , Asano Takao , Yasuhara Hajime
Published: June 2011

Background and Purpose
—The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase–like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial.

Methods
—Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures.

Results
—Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149 given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (
P
=.023, Wilcoxon rank sum test) but not at 3 months (
P
=.056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores.

Conclusions
—Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent.
Automated Intraoperative Detection of Doppler Microembolic Signals Using the Bigate Approach
Authors: Georgiadis D. , Wenzel A. , Zerkowski H. R. , Zierz S. , Lindner A.
Published: June 2011

Background and Purpose
—We undertook this study to evaluate the performance of an automated detection software in the detection of Doppler microembolic signals (MES) during cardiac surgery.

Methods
—Intraoperative monitoring was performed over two spatially separated vessel segments of each middle cerebral artery in 18 patients undergoing coronary artery bypass surgery (n=16) or cardiac valve replacement (n=2). All monitoring sessions were saved on digital audiotape and subsequently played back to the same ultrasound machine, set up to automatically detect MES by evaluating the temporary delay in their appearance between the two segments, in the presence of an experienced examiner. Software sensitivity and specificity in MES detection were then evaluated, with the results of the human observer considered the gold standard.

Results
—A total of 44 933 high-intensity signals (artifacts and MES) were evaluated. Overall sensitivity and specificity of the software, with the human observer considered the gold standard, were 64% and 78.5%, respectively, ranging from 54% to 96% and from 74% to 90% in individual patients. When the overall results of the software were compared with those of the human observer, κ was 0.72.

Conclusions
—The tested software displayed a satisfactory specificity. Provided that the sensitivity is further improved, it could provide a valuable tool in intraoperative monitoring.
Prediction of Impending Hemorrhagic Transformation in Ischemic Stroke Using Magnetic Resonance Imaging in Rats
Authors: Knight R. A. , Barker P. B. , Fagan S. C. , Li Y. , Jacobs M. A. , Welch K. M. A.
Published: June 2011

Background and Purpose
—Hemorrhagic transformation (HT) of ischemic brain tissue may occur in stroke patients either spontaneously or after thrombolysis. A method to assess the risk of HT in ischemic tissue after stroke would improve the safety of thrombolytic therapy. As a means of predicting HT, we investigated the role of contrast-enhanced MRI at acute time points in a rat middle cerebral artery occlusion model with reperfusion.

Methods
—Intraluminal suture occlusion of the middle cerebral artery was used to produce transient ischemia in male Wistar rats (n=11). Reperfusion was performed by withdrawal of the occluding filament after 2 (n=4), 3 (n=6), or 4 (n=1) hours. MRI studies were performed before and after reperfusion with the use of conventional T1-weighted imaging, with and without gadolinium (Gd-DTPA) contrast agent, and T2-weighted imaging. Follow-up MRI and histological studies were obtained at 24 hours.

Results
—Petechial hemorrhage occurred by 24 hours in 9 of 11 animals. All animals showed brain swelling and cellular death throughout the ischemic region at 24 hours. A hyperintense region in the preoptic area became visible after Gd-DTPA injection within minutes after reperfusion in animals with subsequent HT. All animals showing acute Gd-DTPA enhancement subsequently developed petechial hemorrhage (or died) by 24 hours. In these animals, statistically significant differences in signal intensity (
P
=.0005) between the ipsilateral enhancing region and a homologous contralateral region were detected on post–Gd-DTPA T1-weighted imaging. There was also a statistically significant correlation (
P
=.01) between the rate of Gd-DTPA uptake and the size of the enhancing area. Two animals did not enhance with Gd-DTPA and did not exhibit hemorrhage on histological examination or MRI at 24 hours. No abnormalities were seen on precontrast T1-weighted images before and shortly after reperfusion or postcontrast T1-weighted images before reperfusion.

Conclusions
—The primary finding of this study was the detection of early Gd-DTPA parenchymal enhancement in 82% of the animals after reperfusion. Enhancement was seen before any detectable hemorrhage, suggesting that early endothelial ischemic damage occurs before gross brain infarction and hemorrhage. Thus, we suggest that acute Gd-DTPA enhancement may provide an early prediction of petechial hemorrhage.
Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke
Authors: Chiu David , Krieger Derk , Villar-Cordova Carlos , Kasner Scott E. , Morgenstern Lewis B. , Bratina Patti L. , Yatsu Frank M. , Grotta James C.
Published: June 2011

Background and Purpose
—The feasibility, safety, and efficacy of intravenous tissue plasminogen activator (t-PA) for patients with acute ischemic stroke in clinical practice need to be assessed.

Methods
—We initiated a prospective open-label study at a university hospital and two community hospitals in Houston, Tex, immediately after the publication of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA study. A total of 30 patients, age 32 to 90 years, were treated with 0.9 mg/kg of intravenous t-PA (maximum dose, 90 mg) within 3 hours of acute ischemic stroke between December 1995 and December 1996.

Results
—Six percent (6%) of all patients hospitalized with ischemic stroke received intravenous t-PA at the university hospital and 1.1% at the community hospitals. The rates of total, symptomatic, and fatal intracerebral hemorrhage were 10%, 7%, and 3%. Thirty-seven percent (37%) of patients recovered to fully independent function. The average time from stroke onset to emergency department arrival was 57 minutes; emergency department arrival to computed tomography scan 41 minutes; and computed tomography scan to administration of treatment 59 minutes.

Conclusions
—When treatment guidelines are carefully followed in an urban hospital setting, intravenous t-PA for acute ischemic stroke is feasible and shows safety and efficacy comparable to the results of the NINDS study.
Effects of Ischemia on Cerebral Arteriolar Dilation to Arterial Hypoxia in Piglets
Authors: Bari Ferenc , Louis Thomas M. , Busija David W.
Published: June 2011

Background and Purpose
—Arterial hypoxia mediates cerebral arteriolar dilation primarily via mechanisms involving activation of ATP-sensitive K
+
channels (K
ATP
), which we have shown to be sensitive to ischemic stress. In this study, we determined whether ischemia/reperfusion alters cerebral arteriolar responses to arterial hypoxia in anesthetized piglets. Since adenosine plays an important role in cerebrovascular responses to hypoxia, we also determined whether adenosine-induced arteriolar dilation is affected by ischemic stress. We tested the hypothesis that reductions in cerebral arteriolar dilator responses after ischemia would be proportional to the contribution of K
ATP
to hypoxia and adenosine.

Methods
—Pial arteriolar diameters were measured using a cranial window and intravital microscopy. We examined arteriolar responses to arterial hypoxia (inhalation of 8.5% and 7.5% O
2
), to topical adenosine (10
–5
and 10
–4
mol/L) and to arterial hypercapnia (inhalation of 5% and 10% CO
2
in air) before and after 10 minutes of global ischemia. Ischemia was achieved by increasing intracranial pressure. Arterial hypercapnia was used as a positive control for the effectiveness of the ischemic insult. In addition, we evaluated cerebral arteriolar responses to 10
–5
and 10
–4
mol/L adenosine applied topically with or without glibenclamide, a selective inhibitor of K
ATP
(10
–5
and 10
–6
mol/L). Finally, we administered theophylline (20 mg/kg, IV) to assess the contribution of adenosine to cerebral arteriolar dilation to arterial hypoxia.

Results
—Before ischemia, cerebral arterioles dilated by 19±3% to moderate and 29±4% to severe hypoxia (n=7;
P
<.05); 13±2% to 10
–5
and 20±1% to 10
–4
mol/L adenosine (n=9;
P
<.05); and by 17±2% to moderate and 28±3% to severe hypercapnia (n=6;
P
<.05). After ischemia, cerebral arteriolar responses to hypoxia and adenosine were unchanged. In contrast, cerebral arteriolar dilation to hypercapnia was impaired by ischemia (1±1% and 2±1% at 1 hour; n=6). Glibenclamide reduced cerebral arteriolar dilation to adenosine by approximately one half (n=7). In addition, blockade of adenosine receptors by theophylline (20 mg/kg, IV) almost totally suppressed cerebral arteriolar dilation to arterial hypoxia (n=6).

Conclusions
—Cerebrovascular responsiveness is selectively affected by anoxic stress. In addition, cerebral arteriolar dilation to hypoxia and adenosine is maintained after ischemia despite the expected impairment in K
ATP
function.
Vertebral Body Infarction as a Confirmatory Sign of Spinal Cord Ischemic Stroke
Authors: Faig Jochen , Busse Otto , Salbeck Rainer
Published: June 2011

Background
—Acute spontaneous spinal cord syndromes often remain etiologically ambiguous despite extensive diagnostic efforts. In the previous literature five cases are described with acute spinal cord syndromes interpreted as spinal cord ischemic strokes because of association with vertebral body infarctions on MRI.

Case Descriptions
—Three cases are presented, and the literature is reviewed. In addition to an extensive diagnostic battery including an initial MRI without pathological signs, follow-up MRI at different time intervals from the onset of symptoms showed T2 hyperintense signals in vertebral bodies. Patient 1, who had plaques in the abdominal aorta, had suffered a thoracolumbar spinal infarction; this and a concomitant infarction of the left portion of T-12 could be demonstrated on follow-up MRI on day 12. Patient 2, who had incomplete transverse spinal artery syndrome below T-3, had an abnormal signal at the T-2 level of the spinal cord on follow-up MRI on day 5; this was one segment above infarction of the dorsal area of T-3, corresponding to the ascending course of the medullary artery. The spinal cord of patient 3, who had a posterior spinal artery syndrome below T-11, was unremarkable on follow-up MRI on day 14, but a T2 hyperintense signal was noted in the dorsal area of T-10.

Conclusions
—Vertebral body infarction represents the only confirmatory sign for the otherwise exclusionary diagnostic procedure for spinal cord ischemic stroke and must be searched for on follow-up MRI as a key to correct diagnosis.
Carotid Recurrent Stenosis and Risk of Ipsilateral Stroke
Authors: Frericks H. , Kievit J. , van Baalen J. M. , van Bockel J. H.
Published: June 2011

Background
—The main goal of follow-up after carotid endarterectomy is to prevent new strokes caused by recurrent stenosis. To determine the most cost-effective follow-up schedule, it is necessary to know the incidence of recurrent stenosis and the risk of stroke it carries.

Methods
—A systematic review of the literature was performed using standard meta-analytical techniques.

Results
—Incidence of recurrent stenosis: The data were very heterogeneous. The risk of recurrent stenosis was 10% in the first year, 3% in the second, and 2% in the third. Long-term risk of recurrent stenosis is about 1% per year. Risk of stroke: The reported relative risks of stroke in patients with recurrent stenosis compared with patients without recurrent stenosis showed extreme heterogeneity and ranged from 10 to 0.10. The random effects summary estimator of relative risk was 1.88.

Conclusions
—The data were very heterogeneous, and much better data are needed to arrive at truly reliable estimates of these important parameters of follow-up. It is clear, though, that the risk of recurrent stenosis is highest in the first few years after carotid endarterectomy and very low in later years. By use of general decision-analytic arguments, it can be argued that, given the test characteristics of carotid ultrasound, a small number of tests can be done in the first few years and that testing for restenosis should not be done after 4 years.