bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Resolution EEG in Poststroke Hemiparesis Can Identify Ipsilateral Generators During Motor Tasks
Authors: Green Joseph B. , Bialy Yolanda , Sora Elena , Ricamato Anthony
Published: June 2011

Background and Purpose
—Multimodal neuroimaging with positron emission tomography (PET) scanning or functional MRI can detect and display functional reorganization of the brain’s motor control in poststroke hemiplegia. We undertook a study to determine whether the new modality of 128-electrode high-resolution EEG, coregistered with MRI, could detect changes in cortical motor control in patients after hemiplegic stroke.

Methods
—We recorded movement-related cortical potentials with left and right finger movements in 10 patients with varying degrees of recovery after hemiplegic stroke. All patients were male, and time since stroke varied from 6 to 144 months. All patients were right-handed. There was also a comparison group of 20 normal control subjects.

Results
—Five of 8 patients with left hemiparesis had evidence of ipsilateral motor control of finger movements. There were only 2 cases of right hemiparesis; in addition, 1 patient had a posteriorly displaced motor potential originating behind a large left frontal infarct (rim).

Conclusions
—Reorganization of motor control takes place after stroke and may involve the ipsilateral or contralateral cortex, depending on the site and size of the brain lesion and theoretically, the somatotopic organization of the residual pyramidal tracts. Our results are in good agreement with PET and functional MRI studies in the current literature. High-resolution EEG coregistered with MRI is a noninvasive imaging technique capable of displaying cortical motor reorganization.
Delayed Increase in Infarct Volume After Cerebral Ischemia
Authors: Pantano Patrizia , Caramia Francesca , Bozzao Luigi , Dieler Christiane , von Kummer Rüdiger
Published: June 2011

Background and Purpose
—Growing experimental evidence indicates that the development of cerebral ischemic damage is slower than previously believed. The aims of this work were (1) to study the evolution of CT hypoattenuation between 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether thrombolytic treatment given within 6 hours of stroke affects delayed infarction evolution; and (3) to investigate possible correlations between lesion volume changes over time and clinical outcome.

Methods
—Of 620 patients included in the European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients whose control CT scans at day 1 (CT
1
) and day 7 (CT
7
) were available. They had been randomly divided into 2 groups: 206 patients had been treated with rtPA and 244 with placebo. CT
1
and CT
7
were classified according to the location of the infarct. The volume of CT hypoattenuation was measured using the formula A×B×C/2 for irregular volumes. The 95% confidence interval of inter- and intrarater variability was used to determine whether significant changes in lesion volume had occurred between CT
1
and CT
7
. Clinical severity was evaluated by means of the Scandinavian Stroke Scale (SSS) at entry (SSS
0
) and at day 30 (SSS
30
).

Results
—Mean lesion volumes were significantly (
P
<0.0001) higher at day 7 than at day 1 in all the subgroups of patients and particularly in patients with a subcortical lesion. Of the 450 patients studied, 287 (64%) did not show any significant change in lesion volume between CT
1
and CT
7
, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decrease. No significant correlation was observed between treatment and lesion evolution between CT
1
and CT
7
. Both clinical scores (SSS
0
and SSS
30
) and degree of neurological recovery were significantly (
P
<0.05) lower in the subgroup of patients with a significant lesion volume increase than in the other 2 groups.

Conclusions
—In approximately two thirds of patients, infarct size is established 24 to 36 hours after stroke onset, whereas in the remaining one third, changes in lesion volume may occur later than the first 24 to 36 hours. Many factors may be responsible for delayed infarct enlargement and for a lower degree of clinical recovery, both of which may occur despite early recombinant tissue plasminogen activator treatment.
Predictors of Brain Morphology for the Men of the NHLBI Twin Study
Authors: DeCarli C. , Miller B. L. , Swan G. E. , Reed T. , Wolf P. A. , Garner J. , Jack L. , Carmelli D.
Published: June 2011

Background and Purpose
—Cross-sectional studies show that cerebrovascular risk factors are associated with increased brain atrophy, accumulation of abnormal cerebral white matter signals, and clinically silent stroke. We extend these findings by examining the relationship between midlife cerebrovascular risk factors and later-life differences in brain atrophy, amount of abnormal white matter, and stroke on MRI.

Methods
—Subjects were the 414 surviving members of the prospective National Heart, Lung, and Blood Institute Twin Study, who have been examined on 4 separate occasions, spanning the 25 years between 1969–1973 and 1995–1997. Quantitative measures of brain volume, volume of abnormal white matter signal (WMHI), and volume of stroke, when present, were obtained from those participating in the fourth examination.

Results
—The mean±SD age of the subjects was 47.2±3.0 years at initial examination and 72.5±2.9 years at final examination. Average blood pressure (BP) levels were normal, although 32% of the subjects had received or were currently taking antihypertensive medications. As a group, 31% had symptomatic cardiovascular disease, 11% had symptomatic cerebrovascular disease, and 8% had symptomatic peripheral vascular disease. Both systolic and diastolic BP levels at initial examination were inversely related to brain volume and positively related to WMHI volume. Multiple regression analysis identified BP-related measures and vascular risk factors as significant predictors of brain and WMHI volumes. In addition, the magnitude of orthostatic BP change was significantly associated with WMHI volume. Subjects with extensive amounts of WMHI had significantly higher systolic BP at the final examination and a higher prevalence of symptomatic cardiovascular and cerebrovascular disease, without significant differences in the prevalence of hypertension treatment.

Conclusions
—Midlife BP measures are significantly associated with later-life brain and WMHI volumes and the prevalence of symptomatic vascular disease. Since WMHI share cerebrovascular risk factors and extensive WMHI are associated with symptomatic vascular disease, extensive WMHI may be a subclinical expression of cerebrovascular disease. Careful treatment of midlife BP elevations may diminish these later-life brain changes.
Outcome of Carotid Artery Occlusion Is Predicted by Cerebrovascular Reactivity
Authors: Vernieri Fabrizio , Pasqualetti Patrizio , Passarelli Francesco , Rossini Paolo M. , Silvestrini Mauro
Published: June 2011

Background and Purpose
—The purpose of this study was to investigate the possibility of obtaining prognostic indications in patients with internal carotid occlusion on the basis of intracranial hemodynamic status, presence of previous symptoms of cerebrovascular failure, and baseline characteristics.

Methods
—Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. Cerebrovascular reactivity to apnea was calculated by means of the breath-holding index (BHI) in the middle cerebral arteries. Sixty-five patients with internal carotid artery occlusion were followed-up prospectively (median, 24 months), 23 patients were asymptomatic and 42 symptomatic (20 with transient ischemic attack and 22 with stroke).

Results
—During the follow-up period, 11 symptomatic patients and 1 asymptomatic patient had another ischemic event ipsilateral to carotid occlusion. Among factors considered, only lower BHI values in the middle cerebral arteries ipsilateral to carotid occlusion and older age were significantly associated with the risk of developing symptoms (
P
=0.002 and
P
=0.003, respectively; Cox regression multivariate analysis). Based on our data, a cut point of the BHI value for distinguishing between pathological and normal cerebrovascular reactivity was determined to be 0.69. All patients except one, who developed TIA or stroke during the follow-up period, had BHI values ipsilateral to carotid occlusion of <0.69.

Conclusions
—These data suggest that impaired cerebrovascular reactivity is predictive for cerebral ischemic events in patients with carotid occlusion.
Myocardial Injury and Left Ventricular Performance After Subarachnoid Hemorrhage
Authors: Mayer Stephan A. , Lin Julie , Homma Shunichi , Solomon Robert A. , Lennihan Laura , Sherman David , Fink Matthew E. , Beckford Avis , Klebanoff Louise M.
Published: June 2011

Background and Purpose
—Electrocardiographic abnormalities and elevations of the creatine kinase myocardial isoenzyme (CK-MB) occur frequently after subarachnoid hemorrhage. In some patients, a reversible and presumably neurogenic form of left ventricular dysfunction is demonstrated by echocardiography. It is not known whether cardiac injury of this type adversely affects cardiovascular hemodynamic performance.

Methods
—We retrospectively studied 72 patients admitted to our neuro-ICU for aneurysmal subarachnoid hemorrhage over a 2.5-year period. We selected patients who met the following criteria: (1) CK-MB levels measured within 3 days of onset, (2) pulmonary artery catheter placed, (3) echocardiogram performed, and (4) no history of preexisting cardiac disease. Hemodynamic profiles were recorded on the day after surgery (n=67) or on the day of echocardiography (n=5) if surgery was not performed (mean, 3.3±1.7 days after onset). The severity of cardiac injury was classified as none (peak CK-MB <1%, n=36), mild (peak CK-MB 1% to 2%, n=21), moderate (peak CK-MB >2%, n=6), or severe (abnormal left ventricular wall motion, n=9).

Results
—Abnormal left ventricular wall motion occurred exclusively in patients with peak CK-MB levels >2% (
P
<0.0001), poor neurological grade (
P
=0.002), and female sex (
P
=0.02). Left ventricular stroke volume index and stroke work index were elevated above the normal range in patients with peak CK-MB levels <1% and fell progressively as the severity of cardiac injury increased, with mean values for patients with abnormal wall motion below normal (both
P
<0.0001 by ANOVA). Cardiac index followed a similar trend, but the effect was less pronounced (
P
<0.0001). Using forward stepwise multiple logistic regression, we found that thick subarachnoid clot on the admission CT scan (odds ratio, 1.9; 95% confidence interval [95% CI], 1.0 to 3.4;
P
=0.04) and depressed cardiac index (odds ratio, 2.1; 95% CI, 1.0 to 4.1;
P
=0.04) were independent predictors of symptomatic vasospasm.

Conclusions
—Myocardial enzyme release and echocardiographic wall motion abnormalities are associated with impaired left ventricular performance after subarachnoid hemorrhage. In severely affected patients, reduction of cardiac output from normally elevated levels may increase the risk of cerebral ischemia related to vasospasm.
Aortic Plaque in Atrial Fibrillation
Authors: Blackshear Joseph L. , Pearce Lesly A. , Hart Robert G. , Zabalgoitia Miguel , Labovitz Arthur , Asinger Richard W. , Halperin Jonathan L.
Published: June 2011

Background and Purpose
—Thoracic aortic plaque identified by transesophageal echocardiography heightens the risk of stroke associated with atrial fibrillation (AF). We sought to identify the prevalence, predictors, and implications of aortic plaque in patients with nonvalvular AF.

Methods
—Thoracic aortic plaque was prospectively sought in 770 persons with AF with the use of transesophageal echocardiography and classified as simple or complex on the basis of thickness ≥4 mm, ulceration, or mobility. Clinical and echocardiographic features of thromboembolism were correlated by multivariate analysis.

Results
—Aortic plaque was detected in 57% of the cohort, and complex plaque was detected in 25%. Both were found more frequently in the descending than in the proximal aorta. Potentially etiologic patient characteristics independently associated with complex plaque included advanced age, history of hypertension, diabetes, and past or present tobacco use. Comorbidities associated with aortic plaque were prior thromboembolism, increased pulse pressure, ischemic heart disease, stenosis or sclerosis of the aortic valve, mitral annular calcification (>10%), elevated serum creatinine concentration, spontaneous echo contrast in the left atrium or appendage, and left atrial appendage thrombus. The prevalence of complex plaque in patients aged <70 years with <10% mitral annular calcification, without ischemic heart disease, or without pulse pressure ≥65 mm Hg was 4% (95% CI, 1% to 6%).

Conclusions
—Aortic plaque is prevalent in patients with AF and is associated with atherosclerosis risk factors and with left atrial stasis or thrombosis, which are themselves independent stroke risk factors. Since the predominant location of complex plaque was in the descending aorta, the role of aortic plaque as a source of embolism in AF is uncertain.
Thromboembolic Events Predispose the Brain to Widespread Cerebral Infarction After Delayed Transient Global Ischemia in Rats
Authors: Dietrich W. Dalton , Danton Gary , Hopkins Aviva C. , Prado Ricardo
Published: June 2011

Background and Purpose
—Transient distal platelet accumulation after common carotid artery thrombosis (CCAT) leads to hemodynamic, metabolic, and molecular events that may influence the response of the postthrombotic brain to secondary insults. We investigated how a thromboembolic insult would affect histopathological outcome when combined with an ischemic insult induced 24 hours later.

Methods
—Three groups of rats underwent either (1) CCAT+10 minutes of normothermic 2-vessel occlusion (n=6), (2) CCAT+sham ischemia procedures (n=6), or (3) sham CCAT procedures+10 minutes of 2-vessel occlusion (n=6). At 7 days, rats were perfused for quantitative histopathological and immunocytochemical analysis.

Results
—Rats undergoing combined insults (group 1) had significantly larger areas of ischemic injury (
P
<0.05) within the cerebral cortex, striatum, and thalamus compared with the other, single-injury groups. Increased ischemic damage included selective neuronal necrosis, infarction, and focal hemorrhage. By means of glial fibrillary acidic protein immunocytochemistry and lectin histochemistry, reactive astrocytes and microglia were found to be associated with widespread tissue necrosis. In contrast, infrequent infarction or CA1 hippocampal neuronal necrosis was observed in groups 2 and 3, respectively.

Conclusions
—A prior thromboembolic event is a risk factor for widespread cerebral infarction and hemorrhage when combined with a delayed ischemic insult. The understanding of what factors enhance the susceptibility of the postthrombotic brain to secondary insults may aid in the development of neuroprotective strategies to be applied after transient ischemic attacks to prevent the initiation of stroke.
Associations of Risk Factors With Segment-Specific Intimal-Medial Thickness of the Extracranial Carotid Artery
Authors: Espeland Mark A. , Tang Rong , Terry James G. , Davis Donna H. , Mercuri Michele , Crouse John R.
Published: June 2011

Background and Purpose
—It is generally assumed that risk factors affect extracranial carotid intimal-medial thickness similarly among all arterial segments. This assumption underlies use of single segments or walls of segments as outcome variables for risk factor studies and clinical trials. However, if the impact of risk factors was unequal for various segments or circumferentially asymmetrical within segments, then inferences drawn from a single segment or wall might not be generalizable; furthermore, since individual segments and walls have unique histological characteristics and are differentially exposed to turbulent flow, risk factor relationships with a particular segment or wall may provide inferences regarding pathogenesis of atherosclerosis.

Methods
—We evaluated associations of risk factors with intimal-medial thickness at the near and far walls of the common carotid artery, bifurcation, and internal carotid artery in 280 individuals older than 45 years equally divided between coronary artery disease cases and controls and between men and women.

Results
—The patterns of differences in mean intimal-medial thickness among segments vary, depending on age, history of hypertension, body mass index in women, and coronary (case-control) status. The asymmetry of disease depended on blood glucose concentrations, prior history of diabetes, smoking, and coronary status. Sex, postmenopausal status, LDL cholesterol, systolic blood pressure, and history of myocardial infarction all had statistically significant relationships with intimal-medial thickness that were fairly homogeneous among arterial sites.

Conclusions
—Focus on an individual segments or walls of the extracranial carotid arteries may lead to overestimation or underestimation of associations of risk factors with extracranial carotid intimal-medial thickness.
Changes in Arterial Structure and Function Under Trandolapril-Verapamil Combination in Hypertension
Authors: Topouchian J. , Asmar R. , Sayegh F. , Rudnicki A. , Benetos A. , Bacri A. M. , Safar M. E.
Published: June 2011

Background and Purpose
—Converting enzyme inhibition and calcium blockade alter large arteries in hypertension. However, the heterogeneity of the response according to the site of cardiovascular measurements has never been investigated.

Methods
—In a double-blind study, we compared for 180 days 3 hypertensive patient groups treated with verapamil, trandolapril, or their combination. Using echo-Doppler technique and applanation tonometry, we independently measured mean pressure, local pulse pressure, arterial diameter, and distensibility at 3 arterial sites (brachial and common carotid arteries and abdominal aorta), as well as cardiac and carotid wall structure.

Results
—Mean and pulse pressure decreased significantly to a greater extent with the drug combination. Regarding arterial and cardiac hemodynamics, significant and similar changes were noted in the 3 groups: decreases in abdominal aorta and carotid but not brachial diameter; increases in carotid artery, abdominal aorta, and brachial distensibility even after adjustment to mean blood pressure reduction; and more substantial regression of cardiac mass than carotid wall thickness.

Conclusions
—This study shows that both compounds and more significantly combination therapy decreased mean and pulse pressures measured independently and that the changes in diameter, thickness, and stiffness were influenced primarily by the site of cardiovascular measurements, resulting in a predominant increase in distensibility of muscular arteries, little change in carotid wall thickness, but a significant regression of cardiac hypertrophy.
Controlled Safety Study of a Hemoglobin-Based Oxygen Carrier, DCLHb, in Acute Ischemic Stroke
Authors: Saxena Ritu , Wijnhoud Annemarie D. , Carton Herwig , Hacke Werner , Kaste Markku , Przybelski Robert J. , Stern Kathleen N. , Koudstaal Peter J.
Published: June 2011

Background and Purpose
—Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke.

Methods
—DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours.

Results
—DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months.

Conclusions
—Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin.
Early Neurobehavioral Outcome After Stroke Is Related to Release of Neurobiochemical Markers of Brain Damage
Authors: Wunderlich Michael T. , Ebert Anne D. , Kratz Torsten , Goertler Michael , Jost Stefan , Herrmann Manfred
Published: June 2011

Background and Purpose
—–The study aimed to investigate the predictive value of neurobiochemical markers of brain damage (protein S-100B and neuron-specific enolase [NSE]) with respect to early neurobehavioral outcome after stroke.

Methods
—–We investigated 58 patients with completed stroke who were admitted to the stroke unit of the Department of Neurology at Magdeburg University. Serial venous blood samples were taken after admission and during the first 4 days, and protein S-100B and NSE were analyzed by the use of immunoluminometric assays. In all patients, lesion topography and vascular supply were analyzed and volume of infarcted brain areas was calculated. The neurological status was evaluated by a standardized neurological examination and the National Institutes of Health Stroke Scale (NIHSS) on admission, at days 1 and 4 on the stroke unit, at day 10, and at discharge from the hospital. Comprehensive neuropsychological examinations were performed in all patients with first-ever stroke event and supratentorial brain infarctions. Functional outcome was measured with the Barthel score at discharge from the hospital.

Results
—–NSE and protein S-100B concentrations were significantly correlated with both volume of infarcted brain areas and NIHSS scores. Patients with an adverse neurological outcome had a significantly higher and significantly longer release of both markers. Neuropsychological impairment was associated with higher protein S-100B release, but this did not reach statistical significance.

Conclusions
—–Serum concentrations and kinetics of protein S-100B and NSE have a high predictive value for early neurobehavioral outcome after acute stroke. Protein S-100B concentrations at days 2 to 4 after acute stroke may provide valuable information for both neurological status and functional impairment at discharge from the acute care hospital.
Prevalence of Intracranial Saccular Aneurysms in a Japanese Community Based on a Consecutive Autopsy Series During a 30-Year Observation Period
Authors: Iwamoto Hiromitsu , Kiyohara Yutaka , Fujishima Masatoshi , Kato Isao , Nakayama Keizo , Sueishi Katsuo , Tsuneyoshi Masazumi
Published: June 2011

Background and Purpose
—Subarachnoid hemorrhage is a life-threatening disease that occurs mostly because of the rupture of intracranial saccular aneurysms. However, little is known about the prevalence of ruptured and unruptured aneurysms in the general population. The aim of the present study was to examine the prevalence of intracranial aneurysms on the basis of a consecutive autopsy series over a 30-year observation period in a general Japanese population in Hisayama.

Methods
—We evaluated 1230 consecutive autopsy cases with craniotomy among the total deaths of Hisayama residents during 1962 through 1991 (overall autopsy rate, 80.1%).

Results
—A total of 73 intracranial saccular aneurysms were found in 57 cases (4.6%). The prevalence of aneurysms for women was 2.4 times higher than that for men (7.1% versus 2.9%). Among men, the prevalence of aneurysms remained unchanged across the range of age groups. In contrast, there were 2 peaks in the prevalence of aneurysms for women falling in the 40- to 49-year (14.3%) and 60- to 69-year age groups (14.5%). The most common site of the aneurysms was the middle cerebral artery (31.5%), followed by the anterior communicating artery (30.1%), anterior cerebral artery (15.1%), vertebrobasilar artery (12.3%), and internal carotid artery (11.0%). Among these 73 aneurysms, 29 (39.7%) were ruptured. Ruptured aneurysms were common in subjects <80 years of age, whereas unruptured aneurysms were prevalent in those ≥80 years of age. The frequency of ruptured aneurysms was highest in the vertebrobasilar system (66.7%) and lowest in the middle cerebral artery (13.0%).

Conclusions
—Our data suggest that intracranial aneurysms are more frequent in women in the general Japanese population. Aneurysms are more prevalent in the middle cerebral artery, but the risk of rupture is highest in the vertebrobasilar system.
Use of the Barthel Index and Modified Rankin Scale in Acute Stroke Trials
Authors: Sulter Geert , Steen Christel , Jacques De Keyser
Published: June 2011

Background and Purpose
—The Barthel Index (BI) and the Modified Rankin Scale (MRS) are commonly used scales that measure disability or dependence in activities of daily living in stroke victims. The objective of this study was to investigate how these scales were used and interpreted in acute stroke trials.

Methods
—We identified from MEDLINE the major efficacy trials with neuroprotective drugs, thrombolytic drugs, and anticoagulants in acute ischemic stroke published between January 1995 and December 1998. We selected those trials that used the BI and/or MRS as outcome parameters.

Results
—Fifteen trials fulfilling the inclusion criteria were identified. The BI was used in 13 and the MRS in 8. In 4 trials mean and median scores of the BI were used, and in 1 trial median scores of the MRS were compared. Primary end points included the BI in 7, the MRS in 6, and both the BI and MRS in 3. With regard to the BI, a variety of sum scores between 50 and 95 were used as cutoff scores to define favorable outcome. Favorable outcome on the MRS was defined as either ≤1 or ≤2.

Conclusions
—Among the efficacy trials in acute stroke, we found remarkable differences in the choice of primary end points and in the definition of favorable outcome on both the BI and MRS. This lack of consensus strongly hinders the design, interpretation, and comparison of acute stroke trials. In general, it may be easier to define poor outcome instead of favorable outcome. Poor outcome could be defined if any of the following end points are reached: death, institutionalization due to stroke, MRS >3, or BI <60.
Homocyst(e)ine and Risk of Cerebral Infarction in a Biracial Population
Authors: Kittner Steven J. , Giles Wayne H. , Macko Richard F. , Hebel J. Richard , Wozniak Marcella A. , Wityk Robert J. , Stolley Paul D. , Stern Barney J. , Sloan Michael A. , Sherwin Roger , Price Thomas R. , McCarter Robert J. , Johnson Constance J. , Earley Christopher J. , Buchholz David W. , Malinow M. Rene
Published: June 2011

Background and Purpose
—Genetic enzyme variation and vitamin intake are important determinants of blood homocyst(e)ine levels. The prevalence of common genetic polymorphisms influencing homocyst(e)ine levels varies by race, and vitamin intake varies by socioeconomic status. Therefore, we examined the effect of vitamin intake, race, and socioeconomic status on the association of homocyst(e)ine with stroke risk.

Methods
—All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. One hundred sixty-seven cases of first ischemic stroke among women aged 15 to 44 years were compared with 328 controls identified by random-digit dialing from the same region. Risk factor data were collected by standardized interview and nonfasting phlebotomy. Plasma homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection.

Results
—Blacks and whites did not differ in median homocyst(e)ine levels, nor did race modify the association between homocyst(e)ine and stroke. After adjustment for cigarettes per day, poverty status, and regular vitamin use, a plasma homocyst(e)ine level of ≥7.3 μmol/L was associated with an odds ratio for stroke of 1.6 (95% CI, 1.1 to 2.5).

Conclusions
—The association between elevated homocyst(e)ine and stroke was independent not only of traditional vascular risk factors but also of vitamin use and poverty status. The degree of homocyst(e)ine elevation associated with an increased stroke risk in young women is lower than that previously reported for middle-aged men and the elderly and was highly prevalent, being present in one third of the control group.
Diffusion- and Perfusion-Weighted MRI
Authors: Neumann-Haefelin Tobias , Wittsack Hans-Jörg , Wenserski Frank , Siebler Mario , Seitz Rüdiger J. , Mödder Ulrich , Freund Hans-Joachim
Published: June 2011

Background and Purpose
—Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are relatively new MR techniques increasingly used in acute stroke. During the first hours of stroke evolution, the regions with abnormal perfusion are typically larger than the DWI lesions, and this mismatch region has been suggested to be “tissue at risk.” The aim of this study was to evaluate the PWI/DWI mismatch region in acute stroke patients and find parameters indicative of both infarct progression and functional impairment.

Methods
—Twenty patients with nonlacunar ischemic stroke were imaged with DWI, PWI, and conventional MRI within 24 hours of symptom onset and after 1 week; in addition, the European Stroke Scale (ESS) score was recorded. With PWI, the volumes of regions with “time-to-peak” (TTP) delays of ≥2, 4, 6, 8, and 10 seconds were measured; these volumes were compared with the acute DWI lesion volumes, final infarct size, and ESS score.

Results
—In 80% of patients the acute DWI lesion was surrounded by regions with abnormal TTP delays (PWI>DWI lesion). A TTP delay of ≥6 s in the mismatch region was found to be associated with lesion enlargement between the initial and follow-up MRI scans. Lesions increased in 9 of 12 patients (75%) in whom the area with TTP delay ≥6 s was larger than the DWI lesion, but they increased in only 1 of 8 (12.5%) of the remaining patients, in whom the area with a TTP delay ≥6 s was smaller than the DWI lesion. The volume of the regions with TTP delays of ≥4 s correlated better with ESS (
r
=−0.88,
P
<0.001) than other PWI (or DWI) volumes, which indicated that a TTP delay of ≈4 s might be the threshold for functional impairment of brain tissue.

Conclusions
—Only patients with severe perfusion deficits in the PWI/DWI mismatch (TTP delays of ≥6 s) are at high risk of lesion enlargement. Functionally, more moderate perfusion deficits (TTP delays ≥4 and <6 s) appear to also contribute to the acute clinical deficit.
Time Course of Serum Neuron-Specific Enolase
Authors: Schoerkhuber Waltraud , Kittler Harald , Sterz Fritz , Behringer Wilhelm , Holzer Michael , Frossard Martin , Spitzauer Susanne , Laggner Anton N.
Published: June 2011

Background and Purpose
—The prediction of neurological outcome in comatose cardiac arrest survivors has enormous ethical and socioeconomic implications. The purpose of the present study was to investigate the prognostic relevance of the time course of serum neuron-specific enolase (NSE) as a biochemical marker of hypoxic brain damage.

Methods
—Serial analysis of serum NSE levels was performed in 56 patients resuscitated from witnessed, nontraumatic, normothermic, in- or out-of-hospital cardiac arrest. The neurological outcome was evaluated with the use of the cerebral performance category (CPC) within 6 months after restoration of spontaneous circulation (ROSC). The Mann-Whitney
U
test was used to compare patients with good (CPC 1 to 2) and bad (CPC 3 to 4) neurological outcome. The diagnostic performance at different time points after ROSC was described in terms of areas under receiver operating characteristic curves according to standard methods.

Results
—Patients with a bad neurological outcome (CPC 3 to 4) had significantly higher NSE levels than those with a good neurological outcome at 12 (
P
=0.004), 24 (
P
=0.04), 48 (
P
<0.001), and 72 hours (
P
<0.001) after ROSC. The maximum NSE level measured within 72 hours after ROSC was also significantly higher in patients with a bad neurological outcome (
P
<0.001). The NSE value at 72 hours after ROSC was the best predictor of neurological outcome (area under the curve=0.92±0.04). In addition, we also found a significant difference in the time course of NSE concentrations during the first 3 days after ROSC.

Conclusions
—Serum NSE levels are valuable adjunctive parameters for assessing neurological outcome after cardiac arrest.
Cerebral Amyloid Angiopathy–Related Hemorrhage
Authors: McCarron Mark O. , Nicoll James A. R. , Ironside James W. , Love Seth , Alberts Mark J. , Bone Ian
Published: June 2011

Background and Purpose
—Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) ε4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas ε2 is associated with CAA-related hemorrhage (CAAH). The clinical risk factors for other forms of intracranial hemorrhage are a less-frequent feature of CAAH. In this study we examined potential clinical risk factors in patients with CAAH and assessed these with respect to APOE genotype.

Methods
—Thirty-six patients were identified with a pathological diagnosis of CAAH. Clinical notes were reviewed to document age of hemorrhage onset, history of dementia, antiplatelet/anticoagulant medication, hypertension, minor head trauma, or transient neurological events. In a review of reported cases of CAAH, the frequency of these clinical features was also recorded. APOE genotypes were determined with use of polymerase chain reaction techniques.

Results
—There were 24 women and 12 men; the mean age was 70.3 years. One third (n=12) had been taking antiplatelet medication, and a similar number were demented. Nine patients were hypertensive, and 4 had a history of recent minor head trauma. The relative frequency of each of these clinical features was similar to that in previous reports. Forty-four percent (16 of 36) possessed an ε2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in ε2 carriers than in non–ε2 carriers (81% versus 35%,
P
=0.008), antiplatelet/anticoagulant medication in particular (
P
=0.038).

Conclusions
—Our findings suggest that antiplatelet or anticoagulant medication, hypertension, or minor head trauma are most likely to precipitate cerebral hemorrhage in patients with CAA who are also ε2 carriers. This may result from isoform-specific effects of apoE on the structure of amyloid-laden blood vessel walls.
Increased Cerebral CO
2
Reactivity After Heparin-Mediated Extracorporal LDL Precipitation (HELP) in Patients With Coronary Heart Disease and Hyperlipidemia
Authors: Pfefferkorn Thomas K. , Knüppel Hans-Peter , Jaeger Beate R. , Thiery Joachim , Hamann Gerhard F.
Published: June 2011

Background and Purpose
—There is experimental and clinical evidence that hypercholesterolemia leads to an impairment of endothelial function in coronary and cerebral arteries. Using transcranial Doppler sonography, we examined CO
2
reactivity as a marker of cerebral vasoreactivity in patients with coronary heart disease and hyperlipidemia before and after drastic lowering of LDL cholesterol, lipoprotein(a) [Lp(a)], and fibrinogen levels by heparin-mediated extracorporal LDL precipitation (HELP).

Methods
—CO
2
reactivity was determined in 13 patients with coronary artery disease and hyperlipidemia undergoing regular HELP therapy. Middle cerebral artery mean blood flow velocity (MFV) was detected by transcranial Doppler. CO
2
reactivity was calculated as the percent change of MFV during hypercapnia, induced by ventilation of carbogene (5% CO
2
, 95% O
2
), to normocapnia. Patients with extracranial or intracranial stenoses were excluded. Other parameters such as blood viscosity, heart rate, and blood pressure were measured to control hemorheologic and systemic influences on CO
2
reactivity.

Results
—A single HELP treatment reduced total cholesterol, LDL cholesterol, Lp(a), triglycerides, and fibrinogen levels by >50% (
P
<0.001). Blood viscosity significantly decreased from 1.24±0.04 to 1.07±0.02 mPa (
P
<0.001). Blood pressure, heart rate, and MFV did not change significantly. CO
2
reactivity increased from 22% ± 21% to 36% ± 18% (
P
<0.05).

Conclusions
—Fast and drastic removal of LDL cholesterol, Lp(a), and fibrinogen from plasma results in an improvement of cerebrovascular reactivity in patients with coronary heart disease and hyperlipidemia. The clinical use of HELP in patients with impaired cerebrovascular reactivity might be promising.
Early Surgical Treatment for Supratentorial Intracerebral Hemorrhage
Authors: Zuccarello Mario , Brott Thomas , Derex Laurent , Kothari Rashmi , Sauerbeck Laura , Tew John , Van Loveren Harry , Yeh Hwa-Shain , Tomsick Thomas , Pancioli Arthur , Khoury Jane , Broderick Joseph
Published: June 2011

Background and Purpose
—The safety and the effectiveness of the surgical treatment of spontaneous intracerebral hemorrhage (ICH) remain controversial. To investigate the feasibility of urgent surgical evacuation of ICH, we conducted a small, randomized feasibility study of early surgical treatment versus current nonoperative management in patients with spontaneous supratentorial ICH.

Methods
—Patients with spontaneous supratentorial ICH who presented to 1 university and 2 community hospitals were randomized to surgical treatment or best medical treatment. Principal eligibility criteria were ICH volume >10 cm
3
on baseline CT scan with a focal neurological deficit, Glasgow Coma Scale score >4 at the time of enrollment, randomization and therapy within 24 hours of symptom onset, surgery within 3 hours of randomization, and no evidence for ruptured aneurysm or arteriovenous malformation. The primary end point was the 3-month Glasgow Outcome Scale (GOS). A good outcome was defined as a 3-month GOS score >3.

Results
—Twenty patients were randomized over 24 months, 9 to surgical intervention and 11 to medical treatment. The median time from onset of symptoms to presentation at the treating hospitals was 3 hours and 17 minutes, the time from randomization to surgery was 1 hour and 20 minutes, and the time from onset of symptoms to surgery was 8 hours and 35 minutes. The likelihood of a good outcome (primary outcome measure: GOS score >3) for the surgical treatment group (56%) did not differ significantly from the medical treatment group (36%). There was no significant difference in mortality at 3 months. Analysis of the secondary 3-month outcome measures showed a nonsignificant trend toward a better outcome in the surgical treatment group versus the medical treatment group for the median GOS, Barthel Index, and Rankin Scale and a significant difference in the National Institutes of Health Stroke Scale score (4 versus 14;
P
=0.04).

Conclusions
—Very early surgical treatment for acute ICH is difficult to achieve but feasible at academic medical centers and community hospitals. The trend toward less 3-month morbidity with surgical intervention in patients with spontaneous supratentorial ICH warrants further investigation of very early clot removal in larger randomized clinical trials.
Evidence for Selective Effects of Chronic Hypertension on Cerebral Artery Vasodilatation to Protease-Activated Receptor-2 Activation
Authors: Sobey Christopher G. , Moffatt James D. , Cocks Thomas M.
Published: June 2011

Background and Purpose
—Protease-activated receptor-2 (PAR-2) can be activated after proteolysis of the amino terminal of the receptor by trypsin or by synthetic peptides with a sequence corresponding to the endogenous tethered ligand exposed by trypsin (eg, SLIGRL-NH
2
). PAR-2 mediates nitric oxide (NO)–dependent dilatation in cerebral arteries, but it is unknown whether PAR-2 function is altered in cardiovascular diseases. Since hypertension selectively impairs NO-mediated cerebral vasodilatation in response to acetylcholine and bradykinin, we sought to determine whether PAR-2–mediated vasodilatation is similarly adversely affected by this disease state.

Methods
—We studied basilar artery responses in Wistar-Kyoto rats (WKY) (normotensive) and spontaneously hypertensive rats (SHR) in vivo (cranial window preparation) and in vitro (isolated arterial rings). The vasodilator effects of acetylcholine, sodium nitroprusside, and activators of PAR-2 and protease-activated receptor-1 (PAR-1) were compared in WKY versus SHR. Immunohistochemical localization of PAR-2 was also assessed in the basilar artery.

Results
—Increases in basilar artery diameter in response to acetylcholine were 65% to 85% smaller in SHR versus WKY, whereas responses to sodium nitroprusside were not different. In contrast to acetylcholine, vasodilatation in vivo to SLIGRL-NH
2
was largely preserved in SHR, and SLIGRL-NH
2
was ≈3-fold more potent in causing vasorelaxation in SHR versus WKY in vitro. In both strains, responses to SLIGRL-NH
2
were abolished by
N
G
-nitro-
l
-arginine, an inhibitor of NO synthesis. Activators of PAR-1 had little or no effect on the rat basilar artery. PAR-2–like immunoreactivity was observed in both the endothelial and smooth muscle cells of the basilar artery in both strains of rat.

Conclusions
—These data indicate that NO-mediated vasodilatation to PAR-2 activation is selectively preserved or augmented in SHR and may suggest protective roles for PAR-2 in the cerebral circulation during chronic hypertension.
Effects of Lipopolysaccharide Priming on Acute Ischemic Brain Injury
Authors: Ahmed Shah-Hinan , He Yong Y. , Nassief Abdullah , Xu Jian , Xu Xiao Ming , Hsu Chung Y.
Published: June 2011

Background and Purpose
—Infection has been implicated as a stroke risk factor. Activation and infiltration of polymorphonuclear neutrophils (PMNs) after cerebral ischemia may contribute to ischemic brain injury. This study was conducted to investigate how enhanced postischemic PMN infiltration by lipopolysaccharide (LPS) altered the acute ischemic outcomes.

Methods
—LPS (0.05 mg/kg SC) or vehicle was given to Long-Evans male rats 24 hours before ischemia. Focal cerebral ischemia was induced by temporary ligation of the right middle cerebral artery and both common carotid arteries for 45 minutes. Animals were killed 6 and 24 hours after reperfusion to determine the extent of PMN infiltration (myeloperoxidase assay), brain edema (wet-dry weight method), and vascular injury (fluorescein isothiocyanate–conjugated dextran extravasation). The infarct volumes were measured on the basis of TTC stain 24 hours after ischemia.

Results
—LPS had little effect on body temperature or peripheral white count but substantially enhanced PMN infiltration into the ischemic right middle cerebral artery cortex on the basis of myeloperoxidase activity (6 hours: control, 0 U/g; LPS, 0.186±0.025 U/g; 24 hours: control, 0.185±0.025 U/g; LPS, 0.290±0.040 U/g;
P
<0.001) and morphological studies. The extent of vascular injury defined by the extravasation of fluorescein isothiocyanate–conjugated dextran into the ischemic tissue (6 hours: control, 3.11±0.41 μL/mg protein; LPS, 0.48±0.16 μL/mg protein; 24 hours: control, 1.77±0.23 μL/mg protein; LPS, 0.90±0.19 μL/mg protein;
P
<0.001) and brain edema determined by the brain water content (6 hours: control, 84.77±1.63%; LPS, 82.09±1.25%; 24 hours: control, 89.40±0.43%; LPS, 87.88±0.58%;
P
<0.01) were paradoxically reduced by LPS priming. LPS-primed rats also had smaller infarct volumes (control, 135±5 mm
3
; LPS, 108±12 mm
3
;
P
<0.05).

Conclusions
—Enhanced postischemic PMN infiltration is anticipated to facilitate ischemic brain injury. Contrary to this expectation, results from the present study suggest that an increase in postischemic PMN infiltration after LPS priming was not detrimental. These findings challenge the notion that postischemic PMN infiltration is uniformly deleterious.
Role of Phosphatidylinositol 3-Kinase in Acetylcholine-Induced Dilatation of Rat Basilar Artery
Authors: Kitayama Jiro , Kitazono Takanari , Ibayashi Setsuro , Wakisaka Masanori , Watanabe Yoshimasa , Kamouchi Masahiro , Nagao Tetsuhiko , Fujishima Masatoshi
Published: June 2011

Background and Purpose
—We tested the hypothesis that activation of phosphatidylinositol (PI) 3-kinase is involved in dilator responses of the basilar artery to acetylcholine in vivo.

Methods
—Responses of the basilar artery were measured by the cranial window technique in anesthetized rats. To examine the role of PI 3-kinase in acetylcholine-induced calcium signaling, we measured intracellular free calcium concentration ([Ca
2+
]
i
) of cultured rat basilar arterial endothelial cells using a fluorescent calcium indicator, indo 1.

Results
—Topical application of acetylcholine (10
−
6
, 10
−
5.5
, and 10
−
5
mol/L) increased the diameter of the basilar artery by 8±1%, 14±2%, and 24±3%, respectively. An inhibitor of PI 3-kinase, wortmannin (10
−
8
mol/L), did not change the baseline diameter of the artery. In the presence of wortmannin, acetylcholine (10
−
6
, 10
−
5.5
, and 10
−
5
mol/L) dilated the artery only by 3±2%, 6±2%, and 12±2%, respectively. Thus, wortmannin attenuated acetylcholine-induced dilatation of the basilar artery (
P
<0.05 versus control). Wortmannin had no effect on dilatation of the artery in response to a nitric oxide donor, sodium nitroprusside. LY294002, another inhibitor of PI 3-kinase, also inhibited dilator response of the basilar artery to acetylcholine. Acetylcholine produced an increase in [Ca
2+
]
i
of the endothelial cells. Genistein, an inhibitor of tyrosine kinase, markedly attenuated acetylcholine-induced calcium influx to the cells; however, wortmannin had no effect on acetylcholine-induced calcium changes.

Conclusions
—These results suggest that acetylcholine-induced dilatation of the basilar artery is mediated, at least in part, by activation of PI 3-kinase in vivo. Acetylcholine-induced [Ca
2+
]
i
changes of the endothelial cells may not be mediated by activation of the kinase. PI 3-kinase as well as [Ca
2+
]
i
may play an important role in the acetylcholine-induced nitric oxide production of the basilar arterial endothelial cells.