bluuebunny/crossref_metadata_2025 huggingface dataset:
Dementia as a Predictor of Adverse Outcomes Following Stroke
Authors: Desmond David W. , Moroney Joan T. , Bagiella Emilia , Sano Mary , Stern Yaakov
Published: June 2011

Background and Purpose
—Although it is understood that dementia is a risk factor for adverse outcomes, little is known about the predictive validity of the numerous methods that have been proposed for its diagnosis. Thus, we performed the present study to assess the utility of a variety of diagnostic methods in the prediction of adverse outcomes following stroke.

Methods
—We administered neuropsychological, neurological, and functional examinations to 244 patients (age, 71.7±8.5 years) 3 months after ischemic stroke. We diagnosed dementia using each of the following methods: (1) neuropsychological testing, requiring deficits in increasing numbers of cognitive domains, both with and without memory impairment, as well as functional impairment; (2) Mini-Mental State Examination (MMSE) score of <24; and (3) neurologists’ clinical judgment. We then used survival analyses to investigate the ability of diagnoses based on those methods to predict death and recurrent stroke during long-term follow-up.

Results
—Log-rank tests and Cox proportional hazards analyses, with recurrent stroke entered as a time dependent covariate, determined that all of the paradigms were significant predictors of mortality, but the performance of paradigms based on neuropsychological testing was superior to the use of the MMSE and clinical judgment, particularly when memory impairment was required. Log-rank tests determined that paradigms based on neuropsychological testing were the only significant predictors of recurrent stroke and performed best when memory impairment was required.

Conclusions
—Our results suggest that dementia diagnosis based on neuropsychological assessment and an operationalized paradigm requiring deficits in memory and other cognitive domains is superior to other conventional methods in its ability to identify patients at elevated risk of adverse outcomes following stroke.
Paraoxonase PON1 Polymorphism Leu-Met54 Is Associated With Carotid Atherosclerosis
Authors: Schmidt Helena , Schmidt Reinhold , Niederkorn Kurt , Gradert Anita , Schumacher Martin , Watzinger Norbert , Hartung Hans-Peter , Kostner Gert M.
Published: June 2011

Background and Purpose
—Genetic polymorphism at the paraoxonase locus is associated with serum concentration and activity of paraoxonase and with increased risk for coronary heart disease. Two frequent polymorphisms present at the paraoxonase gene are the methionine (M allele) leucine (L allele) interchange at position 54 and the arginine (B allele) glutamine (A allele) interchange at position 191. This is the first study to determine the effect of these polymorphisms on carotid atherosclerosis.

Methods
—The paraoxonase genotypes at positions 54 and 191 of 316 randomly selected individuals aged 44 to 75 years were determined by polymerase chain reaction–based restriction enzyme digestion. Carotid atherosclerosis was assessed by color-coded Duplex scanning and was graded on a 5-point scale ranging from 0 (normal) to 5 (complete luminal obstruction).

Results
—The LL, LM, and MM genotypes at position 54 were noted in 137 (43.4%), 132 (41.8%), and 47 (14.9%) subjects; the AA, AB, and BB genotypes at position 191 occurred in 172 (54.4%), 124 (39.2%), and 20 (6.3%) individuals. The LL genotype was significantly associated with the presence and severity of carotid disease (
P
=0.022), whereas the 191 polymorphism had no effect. Logistic regression analysis with age and sex forced into the model demonstrated plasma fibrinogen (odds ratio [OR], 1.005 per mg/dL), LDL cholesterol (OR, 1.01 per mg/dL), cardiac disease (OR, 1.75), and the paraoxonase LL genotype to be significant predictors of carotid atherosclerosis. The ORs for the associations with age and sex were 1.09 (
P
=0.0003) and 1.66 (
P
=0.052) per year.

Conclusions
—These data suggest that the paraoxonase LL genotype may represent a genetic risk factor for carotid atherosclerosis.
The CAMCOG: A Useful Screening Instrument for Dementia in Stroke Patients
Authors: de Koning Inge , van Kooten Fop , Dippel Diederik W.J. , van Harskamp Frans , Grobbee Diederick E. , Kluft Cornelis , Koudstaal Peter J.
Published: June 2011

Background and Purpose
—Most mental screening tests focus on the detection of cognitive deficits compatible with Alzheimer’s disease. Stroke patients who develop a dementia syndrome, however, constitute a more heterogeneous group with both cortical and subcortical disturbances. We assessed the diagnostic accuracy of the CAMCOG (the cognitive and self-contained part of the Cambridge Examination for Mental Disorders of the Elderly) and the Mini-Mental State Examination (MMSE) for dementia in patients with a recent stroke.

Methods
—In patients aged 55 and older who were admitted in the Rotterdam Stroke Databank, cognitive functioning was assessed between 3 and 9 months after the most recent stroke. The “gold standard” diagnosis of dementia was compatible with the criteria of the
Diagnostic and Statistical Manual of Mental Disorders, Third Edition,
Revised
. The CAMCOG and MMSE scores were obtained independent of the diagnostic procedure.

Results
—Of 300 consecutive patients, 71 (23.7%) were demented. Sixteen severely demented patients could not be tested and were excluded. The CAMCOG and MMSE scores were significantly related to dementia (both
P
<0.0001) in a logistic regression model. Receiver operating characteristic analysis showed that the CAMCOG was a more accurate screening instrument (area under the curve for CAMCOG, 0.95; for MMSE, 0.90). Two other clinical variables independently improved the diagnostic accuracy of the MMSE and CAMCOG: patients with a left hemispheric lesion had a lower (odds ratio, 0.3; 95% confidence interval, 0.1 to 0.7), and patients with hemorrhagic stroke had a greater chance of being demented (odds ratio, 3; 95% confidence interval, 1 to 10). The effect of left hemispheric lesion as an independent diagnostic factor could not be explained by selection or its association with aphasia alone.

Conclusions
—The CAMCOG is a feasible instrument for use in patients with a recent transient ischemic attack or stroke. It is a more accurate screening tool for dementia than the MMSE, especially when type and site of stroke are taken into account.
Microembolic Signals and Risk of Early Recurrence in Patients With Stroke or Transient Ischemic Attack
Authors: Valton Luc , Larrue Vincent , le Traon Anne Pavy , Massabuau Pierre , Géraud Gilles
Published: June 2011

Background and Purpose
—Asymptomatic microembolic signals (MES) can be demonstrated in patients with cerebral ischemia using transcranial Doppler (TCD) ultrasonographic monitoring of the middle cerebral artery. However, the clinical relevance of MES remains uncertain. The purpose of this study was to estimate the independent contribution of microembolism to the risk of early ischemic recurrence (EIR) in patients with stroke or transient ischemic attack (TIA) of presumed arterial origin.

Methods
—We studied the incidence of EIR in 73 consecutive patients with carotid stroke or TIA in whom TCD scanning of the symptomatic middle cerebral artery was performed within 7 days from the onset of symptoms. Patients with a potential cardiac source of embolism were excluded from the study.

Results
—Eight patients had EIR during a mean±SD follow-up of 10±8 days. The incidence of EIR was 4.3 per 100 patient-days in patients with MES and only 0.5 per 100 patient-days in patients without MES. The presence of MES was a significant predictor of EIR after adjustment for the presence of carotid stenosis or aortic arch atheroma, antiplatelet therapy during follow-up, and other potential confounding variables (relative risk, 8.7; 95% confidence interval, 2 to 38.2;
P
=0.0015).

Conclusions
—Microembolism is a significant independent predictor of EIR in patients with stroke or TIA of presumed arterial origin.
YM872, a Highly Water-Soluble AMPA Receptor Antagonist, Preserves the Hemodynamic Penumbra and Reduces Brain Injury After Permanent Focal Ischemia in Rats
Authors: Shimizu-Sasamata Masao , Kano Tsuneo , Rogowska Jadwiga , Wolf Gerald L. , Moskowitz Michael A. , Lo Eng H.
Published: June 2011

Background and Purpose
—We recently described an image analysis technique based on the temporal correlation mapping (TCM) of injected contrast agents that can be used to distinguish the hemodynamic core and hemodynamic penumbra after focal ischemia. In this study we used this technique for the first time to investigate the effects of the water-soluble AMPA receptor antagonist YM872 in permanent focal ischemia.

Methods
—Fischer 344 rats were subjected to permanent occlusion of the middle cerebral artery. Approximately 30 minutes after ischemia, functional CT images were collected with the use of a dynamic scanning protocol with bolus injections of nonionic contrast agent iohexol (1 mL/kg). TCM analysis defined the distributions of hemodynamic core and hemodynamic penumbra. Cerebral perfusion indices were calculated on the basis of the area under the first-pass transit curves. One hour after ischemia, animals were randomly treated with YM872 (n=8, 20 mg/kg per hour over 4 hours) or normal saline (n=10). Twenty-four hours later, neurological deficits were evaluated, and conventional CT and triphenyltetrazolium chloride staining were used to define volumes of ischemic damage.

Results
—At 24 hours after ischemia, hypodense lesions were visible on conventional CT scans that were highly correlated with triphenyltetrazolium chloride lesion volumes. YM872 improved neurological deficits and reduced volumes of ischemic damage in cortex (90±14 versus 170±16 mm

3

in controls) but not striatum (57±14 versus 79±6 mm

3

in controls). Comparison of early TCM images with conventional CT scans of ischemic injury showed that the hemodynamic core was always damaged in all rats. In controls, 54% of the tissue within the hemodynamic penumbra evolved into ischemic damage compared with 24% in YM872-treated rats. Furthermore, the perfusion index corresponding to the ischemic damage threshold was significantly reduced by YM872 (28±2% versus 37±2% in controls).

Conclusions
—These results indicate that YM872 is a neuroprotective compound that ameliorates the deterioration of the hemodynamic penumbra after focal ischemia.
Cationic Polymer and Lipids Enhance Adenovirus-Mediated Gene Transfer to Rabbit Carotid Artery
Authors: Toyoda Kazunori , Ooboshi Hiroaki , Chu Yi , Fasbender Al , Davidson Beverly L. , Welsh Michael J. , Heistad Donald D.
Published: June 2011

Background and Purpose
—Improvement of efficiency of gene transfer to endothelium could be useful for several applications. We tested the hypothesis that cationic nonviral molecules augment adenovirus-mediated gene transfer to blood vessels, perhaps by alteration of the surface charge of adenovirus and facilitation of binding to endothelium.

Methods
—Carotid arteries from rabbits were incubated in vitro for 0.5 to 2 hours with an adenoviral vector alone or noncovalent complexes of adenovirus with poly-
l
-lysine (a cationic polymer) or lipofectin (a cationic lipid). Binding of adenovirus to the vessels was evaluated immediately after incubation with virus, and assay of transgene (β-galactosidase) activity and histochemistry were performed 24 hours after gene transfer. To determine whether cationic molecules can be used to augment alteration of vascular function by adenovirus-mediated gene transfer, we also examined effects on gene transfer of endothelial nitric oxide synthase.

Results
—Assay of β-galactosidase activity indicated that both cationic molecules increased transgene expression in vessels by ≈5- to 6-fold. In contrast, when endothelium was removed from the vessels after gene transfer, poly-
l
-lysine and lipofectin did not significantly increase transgene activity. Histochemistry for β-galactosidase also suggested that the adenovirus-cationic molecule complexes augmented transgene expression mainly in the endothelium. In addition, we found that complexing adenovirus with cationic molecules increased binding of adenovirus to the vessels. After gene transfer with recombinant adenovirus containing endothelial nitric oxide synthase, calcium ionophore (A23187) produced greater relaxation of vessels treated with adenovirus complexed with poly-
l
-lysine or lipofectin than those treated with adenovirus alone.

Conclusions
—Cationic molecules improve the efficiency of adenovirus-mediated gene transfer to blood vessels.
Neurometabolite Markers of Cerebral Injury in the Antiphospholipid Antibody Syndrome of Systemic Lupus Erythematosus
Authors: Sabet Arman , Sibbitt Wilmer L. , Stidley Christine A. , Danska Jeff , Brooks William M.
Published: June 2011

Background and Purpose
—To determine the neurometabolic patterns of brain injury in systemic lupus erythematosus with antiphospholipid antibody syndrome (SLE-aPLS).

Methods
—Forty-nine SLE patients (12 SLE-aPLS) and 23 control subjects were studied using magnetic resonance imaging and spectroscopy.
N
-Acetylaspartate/creatine (NAA/Cre) and choline/Cre (Cho/Cre) were measured in normal-appearing tissue. IgG and IgM antiphospholipid antibodies (aPL) were measured by enzyme-linked immunosorbent assay.

Results
—Stroke, epilepsy, and elevated IgG-aPL were more common in SLE-aPLS patients than in SLE patients (
P
<0.001). NAA/Cre was lower (
P
<0.05) and Cho/Cre higher (
P
<0.001) in SLE-aPLS patients than in SLE patients without aPLS. Regression models showed NAA/Cre was most related to injury seen by imaging (
P
<0.01), disease duration (
P
<0.05), and prior neuropsychiatric SLE (NPSLE) (
P
=0.07). Reduced NAA/Cre was more closely related to IgG-aPL (
P
<0.01) than the presence of stroke or aPLS. When adjusted for all factors, Cho/Cre was most associated with the presence of aPLS (
P
=0.05).

Conclusions
—SLE and SLE-aPLS are actually a clinical continuum describing brain injury in SLE, with SLE-aPLS being characterized by increased aPL, NPSLE, stroke, epilepsy, and disturbed neurochemistry. An elevated IgG-aPL level is a potent risk factor for brain injury as measured by NAA/Cre in SLE that is independent of stroke and aPLS. However, thrombotic phenomena and the presence of aPL (aPLS) are most closely associated with increased Cho/Cre in SLE. These results suggest that aPLs exacerbate SLE, resulting in increased thrombotic and nonthrombotic brain injuries. Spectroscopy detects brain injury in SLE and may permit better understanding of the neurological consequences of SLE and SLE-aPLS.
Socioeconomic Inequalities in Stroke Mortality Among Middle-Aged Men
Authors: Kunst Anton E. , del Rios Marina , Groenhof Feikje , Mackenbach Johan P.
Published: June 2011

Background and Purpose
—Several studies observed that people from lower socioeconomic groups have higher chances of dying of stroke. There are reasons to expect that these differences are relatively small in southern European countries or in Nordic welfare states. This report therefore presents an international overview of socioeconomic differences in stroke mortality.

Methods
—Unpublished data on mortality by occupational class were obtained from national longitudinal studies or cross-sectional studies. The data refer to deaths among men aged 30 to 64 years in the 1980s. A common occupational class scheme was applied to most countries. The mortality difference between manual classes and nonmanual classes was measured in relative terms (by rate ratios) and in absolute terms (by rate differences).

Results
—In all countries, manual classes had higher stroke mortality rates than nonmanual classes. This difference was relatively large in England and Wales, Ireland, and Finland and relatively small in Sweden, Norway, Denmark, Italy, and Spain. Differences were intermediate in the United States, France, and Switzerland. In Portugal, mortality differences were intermediate in relative terms but large in absolute terms. In most countries, inequalities were much larger for stroke mortality than for ischemic heart disease mortality.

Conclusions
—Socioeconomic differences in stroke mortality are a problem common to all countries studied. There are probably large variations, however, in the contribution that different risk factors, such as tobacco and alcohol consumption, make to the stroke mortality excess of lower socioeconomic groups. Medical services can contribute to reducing socioeconomic differences in stroke mortality.
Relationship Between Provider Volume and Mortality for Carotid Endarterectomies in New York State
Authors: Hannan Edward L. , Popp A. John , Tranmer Bruce , Fuestel Paul , Waldman John , Shah Dhiraj
Published: June 2011

Background and Purpose
—The objective of this study was to assess the relationship between each of 2 provider volume measures for carotid endarterectomies (CEs) (annual hospital volume and annual surgeon volume) and in-hospital mortality. New York’s Statewide Planning and Research (SPARCS) administrative database was used to identify all 28 207 patients for whom carotid endarterectomy was the principal procedure performed in New York State hospitals between January 1, 1990, and December 31, 1995.

Methods
—A statistical model was developed to predict in-hospital mortality using age, admission status, and several conditions found to be associated with higher-than-average mortality. This model was then used to calculate risk-adjusted mortality rates for various intersections of hospital and surgeon volume ranges.

Results
—Risk-adjusted in-hospital mortality ranged from 1.96% (95%confidence interval, 1.47 to 2.57) for patients having surgeons with annual CE volumes of <5 in hospitals with annual CE volumes of ≤100 to 0.94% (95% confidence interval, 0.73 to 1.19) for patients having surgeons with annual volumes of ≥5 in hospitals with annual CE volumes of >100. These 2 rates were statistically different.

Conclusions
—We conclude that the in-hospital mortality rates for carotid endarterectomies performed by surgeons with extremely low annual volumes (<5) and for hospitals with low volumes (≤100) are significantly higher than the in-hospital rates of higher-volume surgeons and hospitals, even after taking preprocedural patient severity of illness into account.
Acute Stroke Teams
Authors: Alberts Mark J. , Chaturvedi Seemant , Graham Glenn , Hughes Richard L. , Jamieson Dara G. , Krakowski Frank , Raps Eric , Scott Phillip
Published: June 2011

Background and Purpose
—The sensitivity of the brain to brief periods of profound ischemia or prolonged periods of modest ischemia mandates an aggressive approach to acute stroke care. Past studies have shown that many stroke patients do not receive acute care in an urgent and timely fashion. The formation of acute stroke teams (AST) is one approach that can be used to accelerate the delivery of acute stroke care.

Methods
—We conducted a survey of major stroke program directors and neurovascular experts throughout the United States. The survey focused on issues related to the presence of AST, their staffing, operational features, and utilization at the surveyed programs and hospitals.

Results
—Surveys were returned from 45 of 60 centers. Ninety-one percent of the respondents indicated that they currently had an AST, with 66% formed between 1995 and 1997. Staffing of ASTs consisted of attending physicians (95%), nurses or study coordinators (73%), fellows (49%), and residents (46%). In almost all cases (98%), the AST was led by a neurologist or neurosurgeon, and 98% of the ASTs operated on a 24-hours-per-day, 7-days-per-week basis. The most common call frequency was 2 to 3 times per week (41%), followed by >5 calls per week (29%). In 59% of the cases, the teams cost ≤$5000 per year to operate. The vast majority (78%) of ASTs responded within 10 minutes of receiving a call.

Conclusions
—The formation of ASTs is quite common at the surveyed programs. Although staffing patterns vary, most teams are led by neurologists or neurosurgeons. The utilization of ASTs varies by facility, but they appear to be useful, with only a modest incremental financial cost. The use of ASTs may assist in providing more rapid medical care to stroke patients and increase the use of some acute therapies. Extension of the AST concept to nonacademic hospitals appears feasible.
State Self-Esteem Following Stroke
Authors: Chang Anne M. , Mackenzie Ann E.
Published: June 2011

Background and Purpose
—Physical rehabilitation after stroke is often highlighted in the absence of consideration of psychosocial factors. This study sought to determine the relationship between state self-esteem and functional independence in patients recovering from stroke.

Methods
—In a longitudinal study, data were collected from 152 stroke patients within 48 hours of admission to a rehabilitation hospital and at 2 weeks and 3 months after admission. The Modified Barthel Index was used to assess functional ability. Patients’ current feelings of self-worth were assessed with use of the State Self-Esteem Scale. Additional variables included perceived social support, trait self-esteem, age, previous stroke, side of stroke, comorbidity, marital status, and gender.

Results
—State self-esteem was significantly correlated to functional independence. The results of linear stepwise regression analysis indicated that functional ability and state self-esteem at 2 weeks, as well as the presence of heart disease, were significant predictors (55%) of functional ability at 3 months. For those with a functional ability score of ≥81 on admission to the rehabilitation unit, state self-esteem and functional ability at 2 weeks as well as previous stroke explained 53% of the variance in functional ability at 3 months. When functional ability was ≤80, baseline and 2-week functional ability, state self-esteem at 2 weeks, and age predicted 53% of the variance in functional ability at 3 months.

Conclusions
—Functional ability at 2 weeks was a stronger predictor than baseline functional ability in this study. The level of state self-esteem was also a consistent factor in the prediction of functional outcome of patients after stroke.
Changes Over Time in Optimal Duplex Threshold for the Identification of Patients Eligible for Carotid Endarterectomy
Authors: Elgersma Otto E. H. , van Leersum Marc , Buijs Pieter C. , van Leeuwen Maarten S. , van de Schouw Yvonne T. , Eikelboom Bert C. , van der Graaf Yolanda
Published: June 2011

Background and Purpose
—Two surgical trials established that carotid endarterectomy is beneficial to symptomatic patients who have a severe internal carotid artery (ICA) stenosis on angiograms. Duplex ultrasonography–derived hemodynamic parameters show a good correlation with angiography and are often used for detecting severe ICA stenoses. However, duplex performance is ultrasound machine and operator dependent. Over time both may change, possibly affecting duplex performance. We compared duplex performance of 2 time periods in 1 specific vascular laboratory using angiography as the gold standard.

Methods
—Consecutive patients who underwent both angiography and duplex examinations of the ICA were evaluated (first period, 60 patients; second period, 61 patients). Peak systolic velocity and several other hemodynamic parameters and ratios were analyzed by receiver operating characteristic curves in their ability to detect severe ICA stenoses. The optimal parameter and threshold were determined for each period. Subsequently, duplex test characteristics were compared after the optimal thresholds of both the first and the second periods were applied in the second period.

Results
—In both periods peak systolic velocity of the ICA was the best test parameter; areas under the receiver operating characteristic curve were similar (0.957 and 0.954, respectively). However, the optimal threshold was different. The optimal threshold in the second period was 270 cm/s. When the optimal threshold of 210 cm/s of the first period was applied in the second period, test characteristics changed significantly. Sensitivity increased from 98% to 100%, and specificity decreased from 85% to 71% (
P
=0.004).

Conclusions
—The optimal threshold for detecting severe ICA stenoses with duplex ultrasonography in our laboratory changed over time. Individual laboratories should assess duplex accuracy regularly and adjust adopted criteria if necessary to keep diagnostic performance optimal.
Neuroprotection of the Brain During Cardiopulmonary Bypass
Authors: Arrowsmith J.E. , Harrison M.J.G. , Newman S.P. , Stygall J. , Timberlake N. , Pugsley W.B.
Published: June 2011

Background and Purpose
—Neuropsychological impairment may follow coronary artery bypass surgery as a result of peroperative cerebral microembolism. The hypothesis that remacemide, an NMDA receptor antagonist, would provide protection against such ischemic damage has been tested in a randomized trial.

Methods
—One hundred seventy-one patients undergoing coronary artery bypass surgery by a single cardiothoracic surgical team were randomized to receive remacemide (up to 150 mg every 6 hours) or placebo from 4 days before to 5 days after their bypass procedure. Peroperative monitoring included an estimate of the number of microembolic events detected by transcranial Doppler ultrasonography of the middle cerebral artery. A battery of 9 neuropsychological tests was administered before and 8 weeks after surgery.

Results
—The proportion of patients showing a decline in performance of 1 SD or more in 2 or more tests was reduced in the treated group (9% versus 12%), but this was not statistically significant. On the other hand, overall postoperative change (reflecting learning ability in addition to reduced deficits) was more favorable in the remacemide group, which demonstrated significantly greater improvement in a global
z
score (
P
=0.028) and changes in 3 individual tests (
P
<0.05). The 2 patient groups were well matched, including for the burden of microembolic events.

Conclusions
—This is the first study to show statistically significant drug-based neuroprotection during cardiac surgery. In addition to offering improvement in cerebral outcome for such at-risk patients, it supports the hypothesis that drugs acting on the excitotoxic mechanism of ischemic cerebral damage can be effective in humans.
Serum S-100 and Neuron-Specific Enolase for Prediction of Regaining Consciousness After Global Cerebral Ischemia
Authors: Martens Patrick , Raabe Andreas , Johnsson Per
Published: June 2011

Background and Purpose
—The aim of our study was to assess the use of S-100 protein (S-100) and neuron-specific enolase (NSE) in serum and cerebrospinal fluid (CSF) for the prediction of patients’ regaining consciousness after acute global cerebral ischemia.

Methods
—Sixty-four unconscious patients were followed until the return of consciousness or until death/vegetative state. Serum and CSF samples for measurement of S-100 and NSE using an immunoradiometric assay technique were obtained 24 hours (serum) and 48 hours (CSF) after the acute event and correlated with patient outcome.

Results
—Values for serum S-100 protein, serum NSE, CSF S-100, and CSF NSE were significantly different in the 2 outcome groups. A serum S-100 value of >0.7 μg/L was found to be a predictor of not regaining consciousness, with a high positive predictive value (95%) and high specificity (96%).

Conclusions
—S-100 protein used as serum marker 24 hours after acute global cerebral ischemia gives reliable and independent information on the outcome of the patient that is comparable or superior to that obtained with CSF markers. Therefore, S-100 may be a serum marker of brain cell damage useful for clinical assessment of these patients.
Asymptomatic Internal Carotid Artery Stenosis Defined by Ultrasound and the Risk of Subsequent Stroke in the Elderly
Authors: Longstreth W. T. , Shemanski Lynn , Lefkowitz David , O’Leary Daniel H. , Polak Joseph F. , Wolfson Sidney K.
Published: June 2011

Background and Purpose
—We sought in this study to relate carotid ultrasound findings in asymptomatic older adults to the 5-year risk of various cerebrovascular outcomes used in the Asymptomatic Carotid Atherosclerosis Study (ACAS).

Methods
—The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years and older. Analyses of internal carotid artery stenosis defined by multiple different cutoffs of peak systolic velocity, rather than one particular cutoff, were performed in the 5441 participants who underwent carotid ultrasound and lacked a history of transient ischemic attack or stroke. The 5-year risks of 7 cerebrovascular disease outcomes used in ACAS were estimated for each cutoff.

Results
—Associations with the 5-year risk of outcomes were substantially elevated only at cutoffs with high peak systolic velocities. In this population, the number of people with such high velocities was small. For example, with a cutoff of approximately 2.5 m/s, suggesting a stenosis of >70%, the 5-year risk of an ipsilateral fatal or nonfatal stroke was 5%, and only 0.5% of the group had velocities at least this high.

Conclusions
—In a group of older adults likely to participate in a screening program, as evidenced by willingness to participate in CHS, high peak systolic velocities consistent with high-grade carotid stenosis were uncommon and risk of subsequent cerebrovascular disease outcomes was relatively low. These findings do not suggest that similar populations of older adults would benefit from a program using ultrasound to screen for asymptomatic carotid stenosis.
Endothelial Cell Culture From Human Cerebral Cavernous Malformations
Authors: Baev Nikolay I. , Awad Issam A.
Published: June 2011

Background and Purpose
—The cerebral cavernous malformation (CCM) is a common and frequently unrecognized cause of stroke and epilepsy. It consists of blood-filled caverns lined by endothelial cells (EC) and devoid of mature vessel wall structure. Cultured EC obtained from CCM may express phenotypic and genotypic alterations contributing to CCM pathogenesis. We report the first successful isolation and growth in vitro of primary EC lines from human CCM lesions.

Methods
—We developed a procedure for the isolation and growth of EC from human CCM, confirmed their EC origin by a panel of molecular markers, and determined by immunocytochemistry the basic expression patterns of 6 transmembrane receptor protein kinases comparing brain, skin, and CCM primary EC lines grown identically.

Results
—Several CCM EC lines were established from 2 patients after we treated the excised specimens with 0.3% trypsin/1% EDTA, selective cloning, and growth in MCDB107 containing 0.3 g/L heparin, 0.15 g/L endothelial cell growth supplement, and 15% FBS. The CCM EC showed contact inhibition and a rounded cobblestone appearance. The cells expressed CD31, CD105, von Willebrand factor, and binding sites for
Ulex europaeus
agglutinin, type 1 and acetylated LDL. They showed low levels of Flt-1, Flk-1, transforming growth factor (TGF)-β RI, and TGF-β RII expression but stained strongly with antibodies against Tie-1 and Tie-2.

Conclusions
—Cultured CCM EC retained their endothelial phenotype. Brain, skin, and CCM EC lines did not significantly differ in their staining patterns with antibodies against Flt-1, Flk-1, TGF-β RI, TGF-β RII, Tie-1, and Tie-2. These cell lines will assist in defining molecular phenotype and genotype alterations in association with CCM.
Intake of Beer, Wine, and Spirits and Risk of Stroke
Authors: Truelsen Thomas , Grønbæk Morten , Schnohr Peter , Boysen Gudrun
Published: June 2011

Background and Purpose
—Alcohol consumption has been associated with a protective effect on risk of ischemic stroke. There may, however, be differences in the effect of beer, wine, and spirits due to properties other than ethanol, a topic that has gained only little attention in stroke research.

Methods
—Our analysis was a prospective cohort study of 13 329 eligible men and women, aged 45 to 84 years, participating in the Copenhagen City Heart Study. Information on alcohol habits and a number of socioeconomic and health-related factors was obtained at baseline. During 16 years of follow-up, 833 first-ever strokes occurred. Data were analyzed by means of multiple Poisson regression.

Results
—We found indications of a U-shaped relation between intake of alcohol and risk of stroke. In analyses adjusted for age, sex, and smoking, intake of wine on a monthly, weekly, or daily basis was associated with a lower risk of stroke compared with no wine intake (monthly: relative risk [RR], 0.83; 95% CI, 0.69 to 0.98; weekly: RR, 0.59; 95% CI, 0.45 to 0.77; daily: RR, 0.70; 95% CI, 0.46 to 1.00). This effect of wine intake remained after complete adjustment for confounding variables (monthly: RR, 0.84; 95% CI, 0.70 to 1.02; weekly: RR, 0.66; 95% CI, 0.50 to 0.88; daily: RR, 0.68; 95% CI, 0.45 to 1.02). There was no association between intake of beer or spirits on risk of stroke.

Conclusions
—The differences in the effects of beer, wine, and spirits on the risk of stroke suggest that compounds in the wine in addition to ethanol are responsible for the protective effect on risk of stroke.
99m
Technetium-Ethyl-Cysteinate-Dimer Single-Photon Emission CT Can Predict Fatal Ischemic Brain Edema
Authors: Berrouschot Jörg , Barthel Henryk , von Kummer Rüdiger , Knapp Wolfram H. , Hesse Swen , Schneider Dietmar
Published: June 2011

Background and Purpose
—We sought to study the prognostic value of early
99m
technetium–ethyl-cysteinate-dimer single-photon emission CT (
99m
Tc-ECD SPECT) for fatal ischemic brain edema in patients with middle cerebral artery (MCA) stroke compared with the prognostic value of CT and of clinical findings.

Methods
—We prospectively studied 108 patients clinically, with
99m
Tc-ECD SPECT, and with CT within 6 hours of symptom onset (Scandinavian Stroke Scale <40 points) appropriate to MCA ischemia. The follow-up consisted of Scandinavian Stroke Scale and CT on days 1 and 7, Barthel Index, and Modified Rankin Scale after 3 months. An activity deficit of the complete MCA territory on the SPECT scans and a parenchymal hypoattenuation of the complete MCA territory on CT scans were considered as predictors for a fatal MCA infarction due to mass effect and midbrain herniation.

Results
—In 11 of 108 patients (10%), the MCA infarction was the cause of death. The sensitivity of SPECT for fatal outcome was 82% in both visual and semiquantitative analyses, while specificity was 98% and 99%, respectively. The sensitivity and specificity of baseline CT were 36% and 100%, respectively; the sensitivity and specificity of clinical findings (Scandinavian Stroke Scale, depressed level of consciousness, gaze deviation) varied from 36% to 73% and from 45% to 88%, respectively. In a multivariate logistic regression model, only SPECT findings were found to be independent predictors of malignant MCA infarction/death.

Conclusions
—We were able to identify patients with fatal MCA infarction with high accuracy by using
99m
Tc-ECD SPECT within 6 hours of stroke onset. This technique offers great potential to select stroke patients for specific therapies, eg, decompressive hemicraniectomy, soon after onset of symptoms.
Differentiation Between Intracerebral Hemorrhage and Ischemic Stroke by Transcranial Color-Coded Duplex-Sonography
Authors: Mäurer M. , Shambal S. , Berg D. , Woydt M. , Hofmann E. , Georgiadis D. , Lindner A. , Becker G.
Published: June 2011

Background and Purpose
—The differential diagnosis of intracerebral hemorrhage versus ischemic stroke has critical implications for stroke management. Transcranial color-coded duplex sonography (TCCS) has been shown to identify intracerebral hemorrhages and intracerebral vessel occlusions. We conducted this study to evaluate the sensitivity and specificity of TCCS in this differential diagnosis and in the detection of stroke complications.

Methods
—One hundred fifty-one patients (58 women, 93 men; mean age, 65.6 years [range, 32 to 89 years] ) with acute hemiparesis were enrolled in this prospective study. On admission all patients had a complete neurological examination. A cranial CT scan and a sonographic examination of the brain parenchyma and all extracranial and intracranial cerebral arteries were conducted. The sonographer was blinded for the radiological findings.

Results
—According to CT criteria, 60 patients had an intracerebral hemorrhage and 67 patients had an ischemic stroke, and in 24 patients CT findings were inconclusive, showing neither bleeding nor an ischemic stroke. On sonographic examination, 18 patients (12%) had no sufficient acoustic bone window. Of the remaining 133 patients, 126 (95%) were diagnosed correctly by sonography in agreement with CT. Sonography missed 3 atypical bleedings (2 with upper parietal location). In 4 patients without bleeding, an intracerebral hemorrhage was suspected by TCCS because of increased white matter echo density due to microangiopathy. Stroke complications depicted by CT (disturbance of cerebrospinal fluid circulation, hemorrhagic transformation, midline shift, ventricular bleeding) (n=54) were correctly shown by TCCS in 45 patients (83%). No complication was missed that would have required further treatment.

Conclusions
—In comparison to the “gold standard” of CT, TCCS identified stroke complications and differentiated between intracerebral hemorrhage and ischemic stroke with reasonable sensitivity. Thus, if CT is not readily available, TCCS may complement clinical examination in patients with acute stroke. In addition, it may also be useful in detecting stroke complications in the follow-up of stroke patients.
Functional Changes in Human Pial Arteries (300 to 900 μm ID) Within 48 Hours of Aneurysmal Subarachnoid Hemorrhage
Authors: Bevan John A. , Bevan Rosemary D. , Walters Carrie L. , Wellman Terry
Published: June 2011

Background and Purpose
—Animal studies of cerebral arteries 2 to 3 days after experimental subarachnoid hemorrhage (SAH) provide evidence of arterial change such as hyperresponsiveness to contractile agonists. There is evidence that small arteries, as well as those large enough to be seen on angiography, may be involved. To directly test these possibilities, the contractile and dilator responses of pial artery segments taken from patients up to 48 hours after SAH were compared with those from patients having elective surgery for an aneurysm (Clip) and with those from normal brain vessels overlying tumors (controls).

Methods
—Segments were mounted on a resistance artery myograph for measurements of wall force changes.

Results
—There were no differences in maximum contractility (E
max
) of the 3 groups of segments. The responses of the SAH segments to K
+
(30 mmol/L) were 60.7±4.6% of E
max
(n [number of vessels]=18), which was significantly greater than those of controls (29.9±5% E
max
) (n=20). Clip responses were the same as control. Contractions of SAH segments to norepinephrine (1 μmol/L) were 54.3±7.9% E
max
(n=12), and these were significantly greater than those of controls (15.1±6.2% E
max
) (n=25). All SAH segments showed spontaneous contractile activity of varying patterns. Spontaneous activity did not occur in the Clip group and occurred in only 50% of control segments. Dilation to acetylcholine was numerically less in SAH and Clip segments than in controls, but differences were not statistically significant. The change in agonist responsiveness could result from exposure to agents that damage the blood vessel wall, resulting in partial depolarization of endothelial and smooth muscle cells.

Conclusions
—Small human pial arteries are hyperresponsive to contractile agents and show spontaneous contractile activity within 48 hours of SAH. Such effects could result in narrowed resistance arteries and reduction in cerebral blood flow. These effects emphasize the wisdom of early therapeutic intervention.
Role of Blood Clot Formation on Early Edema Development After Experimental Intracerebral Hemorrhage
Authors: Xi Guohua , Wagner Kenneth R. , Keep Richard F. , Hua Ya , de Courten-Myers Gabrielle M. , Broderick Joseph P. , Brott Thomas G. , Hoff Julian T.
Published: June 2011

Background and Purpose
—Blood “toxicity” is hypothesized to induce edema and brain tissue injury following intracerebral hemorrhage (ICH). Lobar ICH in pigs produces rapidly developing, marked perihematomal edema (>10% increase in water content) associated with clot-derived plasma protein accumulation. Coagulation cascade activation and, specifically, thrombin itself contribute to edema development during the first 24 hours after gray matter ICH in rats. In the present study, we sought to determine whether blood clot formation is necessary for edema development by comparing intracerebral infusions of heparinized and unheparinized blood in pig (white matter) and in rat (gray matter). We also examined heparin’s effect on thrombin-induced gray matter edema.

Methods
—In pigs, we infused autologous blood (with or without heparin) into the cerebral white matter to produce lobar hematomas and froze the brains in situ at 1, 4, or 24 hours after ICH. We determined hematomal and perihematomal edema volumes on coronal sections by computer-assisted morphometry. In rats, we infused either blood or thrombin (with or without heparin) into the basal ganglia and measured water, sodium, and potassium contents at 24 hours after ICH.

Results
—In pigs, unheparinized blood induced rapid (at 1 hour) and prolonged (24 hours) perihematomal edema (average volume, 1.29±0.20 mL; n=6). No perihematomal edema was present following heparinized blood infusions (n=6). In rats, unheparinized blood produced significantly greater edema than heparinized blood infusions. As with whole blood, thrombin-induced gray matter edema at 24 hours was significantly reduced by coinjection of heparin.

Conclusions
—After ICH, blood clot formation is required for rapid and prolonged edema development in perihematomal white and gray matter. Thrombin also contributes to prolonged edema in gray matter.
Diffusion-Weighted Magnetic Resonance Imaging Confirms Marked Neuroprotective Efficacy of Albumin Therapy in Focal Cerebral Ischemia
Authors: Belayev Ludmila , Zhao Weizhao , Pattany Pradip M. , Weaver R. Greg , Huh Pil W. , Lin Baowan , Busto Raul , Ginsberg Myron D.
Published: June 2011

Background and Purpose
—We have recently shown high-dose human serum albumin therapy to confer marked histological protection in experimental middle cerebral artery occlusion (MCAo). We have now used diffusion-weighted magnetic resonance imaging (DWI) in conjunction with morphological methods to expand our understanding of this therapeutic approach.

Methods
—Physiologically controlled Sprague-Dawley rats received 2-hour MCAo by the modified intraluminal suture method. Treated rats received 25% human serum albumin solution (1% by body weight) immediately after the MCA was reopened. Vehicle-treated rats received saline. Computer-based image averaging was used to analyze DWI data obtained 24 hours after MCAo and light-microscopic histopathology obtained at 3 days. In a matched series, plasma osmolality and colloid oncotic pressure, as well as brain water content, were determined.

Results
—Albumin therapy, which lowered the hematocrit on average by 37% and raised plasma colloid oncotic pressure by 56%, improved the neurological score throughout the 3-day survival period. Within the ischemic focus, the apparent diffusion coefficient (ADC) computed from DWI data declined by 40% in vehicle-treated rats but was preserved at near-normal levels (8% decline) in albumin-treated rats (
P
<0.001). Albumin also led to higher ADC values within unlesioned brain regions. Histology revealed large consistent cortical and subcortical infarcts in vehicle-treated rats, while albumin therapy reduced infarct volume at these sites, on average, by 84% and 33%, respectively. Total infarct volume was reduced by 66% and brain swelling was virtually eliminated by albumin treatment. Microscopically, while infarcted regions of vehicle-treated rats had the typical changes of pannecrosis, infarcted zones of albumin-treated brains showed persistence of vascular endothelium and prominent microglial activation, suggesting that albumin therapy may help to preserve the neuropil within zones of residual infarction.

Conclusions
—These findings confirm the striking neuroprotective efficacy of albumin therapy in focal cerebral ischemia and reveal that this effect is associated with DWI normalization and a mitigation of pannecrotic changes within zones of residual injury.
Amelioration of Hippocampal Neuronal Damage After Global Ischemia by Neuronal Overexpression of BCL-2 in Transgenic Mice
Authors: Kitagawa Kazuo , Matsumoto Masayasu , Tsujimoto Yoshihide , Ohtsuki Toshiho , Kuwabara Keisuke , Matsushita Kohji , Yang Gongming , Tanabe Hiroki , Martinou Jean-Claude , Hori Masatsugu , Yanagihara Takehiko
Published: June 2011

Background and Purpose
—Reports suggesting the involvement of apoptosis in ischemic neuronal damage have been accumulating, and protection against apoptotic death by BCL-2 has been shown in many types of cells. Overexpression of BCL-2 has been shown to reduce infarct size after focal ischemia. The purpose of the present study was to assess whether BCL-2 exerted its effect on selective neuronal vulnerability after transient global ischemia.

Methods
—Transgenic mice overexpressing BCL-2 in neurons and their littermates were subjected to transient forebrain ischemia for 12 minutes, and the hippocampus was examined 7 days later with conventional histology, immunohistochemistry, and in situ terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end-labeling of fragmented DNA.

Results
—Although both types of mice showed a similar degree of ischemic insult, transgenic mice showed a lesser degree of neuronal death together with DNA fragmentation in the hippocampus than their littermates.

Conclusions
—Overexpression of BCL-2 in neurons mitigates selective neuronal vulnerability in the hippocampus of transgenic mice after transient global ischemia.
Mydriatic Pupil as the Presenting Sign of Common Carotid Artery Dissection
Authors: Koennecke H.-C. , Seyfert S.
Published: June 2011

Background
—Ipsilateral mydriasis is known to accompany signs of cerebral ischemia in unilaterally compromised carotid blood flow. Mydriasis as the presenting sign of common carotid artery (CCA) dissection has not been reported thus far.

Case Description
—We report the case of a patient who presented with a mydriatic pupil after intraoperative injury of the ipsilateral CCA. Mydriasis preceded complete third-nerve palsy and symptoms of cerebral ischemia for 12 hours. Cerebral angiography revealed occlusion of the CCA with slow collateral flow to the internal carotid artery and fetal origin of the posterior cerebral artery, suggesting a hemodynamic mechanism causing ischemia of the oculomotor nerve. Signs of cerebral ischemia and third-nerve palsy resolved completely after reconstructive surgery of the occluded vessel.

Conclusions
—A mydriatic pupil may be the unusual first sign of compromised carotid blood flow and impending cerebral ischemia.