bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Vein Thrombosis in Stroke
Authors: Harvey Richard L. , Roth Elliot J. , Yarnold Paul R. , Durham Joseph R. , Green David
Published: June 2011

Background and Purpose
Venous thromboembolism is a leading cause of morbidity and mortality during the acute recovery period after stroke. This study investigated the utility of plasma
d
-dimer level as a diagnostic test for deep vein thrombosis (DVT) in patients hospitalized for stroke rehabilitation.

Method
Plasma samples were drawn from 105 nonambulatory rehabilitation patients with recent ischemic or hemorrhagic stroke and assayed for
d
-dimer with an enzyme-linked immunosorbent method. Samples were drawn within 24 hours of venous duplex ultrasound (VDU) screening for DVT. Optimal discriminant analysis was used to determine whether plasma
d
-dimer level, age, sex, days after stroke onset, stroke etiology, National Institutes of Health Stroke Scale score, and ambulatory status could correctly classify patients' DVT status.

Results
Fourteen of 105 patients had DVT identified by VDU scan. Of all attributes, only
d
-dimer level had significant ability to discriminate between patients with or without DVT (
P
<.0001). The optimal cut point for predicting DVT was
d
-dimer=1591 ng/mL, resulting in 79% sensitivity, 78% specificity, 35% positive predictive value, and 96% negative predictive value. Reducing the
d
-dimer cut point to 1092 ng/mL improved both sensitivity and negative predictive value to 100% but reduced specificity to 66% and positive predictive value to 31%.

Conclusions
A
d
-dimer level ≤1092 ng/mL can exclude the presence of DVT in stroke rehabilitation patients. When a
d
-dimer level >1092 ng/mL occurs, further diagnostic testing is necessary to confirm DVT. Plasma
d
-dimer level is a simple and inexpensive screening test for DVT during stroke rehabilitation.
Angiotensin-Converting Enzyme Gene Polymorphism in Hypertensive Individuals With Parental History of Stroke
Authors: Maeda Yoshikazu , Ikeda Uichi , Ebata Hitoshi , Hojo Yukihiro , Seino Yoshitane , Hayashi Yuji , Kuroki Shigehiro , Shimada Kazuyuki
Published: June 2011

Background and Purpose
It has been suggested that the insertion (
I
)/deletion (
D
) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease, but its relation to stroke has not yet been proven. We investigated an association of ACE gene polymorphism with parental history of stroke (PHS) in patients with hypertension.

Methods
We studied 70 hypertensive patients (ambulatory blood pressure >140/90 mm Hg; age, 59±11 years) with (n=27) or without (n=43) PHS, defined as either one or both parents having had a stroke before 60 years of age. The ACE genotype was analyzed by polymerase chain reaction.

Results
Casual blood pressure and mean ambulatory blood pressure levels were not significantly different between patients with and without PHS. The incidence of left ventricular hypertrophy also did not differ significantly between the two groups. However, the frequency of the
D
allele was significantly higher in patients with PHS (0.72) than in patients without PHS (0.52) (χ
2
=5.472,
P
=.019). The frequency of the
DD
genotype of the ACE gene was also significantly higher in patients with than in those without PHS (
DD
, 63.0%;
ID
, 18.5%;
II
, 18.5% versus
DD
, 32.6%;
ID
, 39.5%;
II
, 27.9%; χ
2
=6.395,
P
=.041).

Conclusions
The
DD
genotype of the ACE gene is associated with PHS in patients with hypertension, which is independent of blood pressure levels or presence of cardiac hypertrophy.
Simple Visual Analysis of Brain Perfusion on HMPAO SPECT Predicts Early Outcome in Acute Stroke
Authors: Alexandrov Andrei V. , Black Sandra E. , Ehrlich Lisa E. , Bladin Christopher F. , Smurawska Liliana T. , Pirisi Angelo , Caldwell Curtis B.
Published: June 2011

Background and Purpose
Single-photon emission computed tomography (SPECT) is used in patients with acute stroke but as yet is of controversial value. We investigated an association of brain perfusion changes in stroke patients with stroke severity, volume of brain damage, and recovery.

Methods
Consecutive patients with hemispheric stroke were studied prospectively with serial neurological examinations using the Canadian Neurological Scale (CNS), CT, and
99m
Tc–hexamethylpropyleneamine oxime (HMPAO) SPECT. Visual SPECT patterns of brain perfusion (normal, high, mixed, low, and absent) were correlated with the severity of stroke, lesion volume, and short-term outcome.

Results
SPECT studies were performed in a total of 458 consecutive acute stroke patients within 2 weeks after the onset (mean time, 5 days; range, 1 to 12 days). SPECT perfusion patterns correlated with stroke severity (CNS score) during the first 2 weeks (
P
<.001). Focal absence of brain perfusion on SPECT was associated with the largest volume of brain damage: 104±84 mL (
P
<.0001). SPECT perfusion patterns predicted the short-term outcome: 97% of patients with normal and increased HMPAO uptake made good recovery, 52% of those with decreased perfusion had moderate stroke, and 62% of patients with absent patterns fared badly. In a multiple logistic regression model, admission CNS scores had the strongest predictive value (
P
=.0001). SPECT had its own prognostic value independent of clinical judgment (
P
=.03). SPECT statistically improved predictive power of the CNS score (+1% receiver operating characteristic curve area, [χ
2
]
2
=20,
P
<.001) because of distinction between focal decrease or absence of brain perfusion in patients studied within the first 72 hours of stroke.

Conclusions
Visual brain perfusion patterns correlate with the extent, severity, and short-term outcome of hemispheric stroke. HMPAO SPECT may improve the prognostic value of clinical examination if performed during the first 72 hours of stroke.
Combined Neuroprotection and Reperfusion Therapy for Stroke
Authors: Aronowski J. , Strong R. , Grotta J.C.
Published: June 2011

Background and Purpose
In search of a better treatment for acute ischemic stroke, we evaluated the use of lubeluzole and hemodilution with diaspirin cross-linked hemoglobin (DCLHb) therapy to test whether treatment with two complementary acting compounds provides more potent protection than either treatment alone.

Methods
We used unilateral reversible middle cerebral artery (MCA) and common carotid artery (CCA) occlusion of various durations in Long-Evans rats to produce ischemic cortical lesions. We calculated the average maximal lesion volume (Vol
max
) and the time required to produce half maximal lesion size (T
50
) in control animals (n=31) and evaluated the effects on cerebral perfusion and infarct size of treatment with lubeluzole (n=23), hemodilution (to 30% hematocrit) with albumin (n=17) or DCLHb (n=23), and combined lubeluzole+DCLHb therapy initiated 15 minutes after MCA/CCA occlusion.

Results
The Vol
max
produced by MCA/CCA occlusion in control animals was 138.5±7.7 mm
3
, and T
50
was 98.5±10.2 minutes. Lubeluzole alone reduced Vol
max
by 53% with no significant effect on T
50
. In contrast to lubeluzole, DCLHb hemodilution prolonged T
50
by 68% with no significant effect on Vol
max
. Prolongation of T
50
by DCLHb was not due to hemodilution itself, since a similar degree of hemodilution with albumin had no effect. Finally, combined lubeluzole+DCLHb rescued 72% of the tissue and augmented the effect of lubeluzole alone by 40% (Vol
max
, 66.3±13.0 versus 39.4±12.2 mm
3
) while prolonging T
50
by 31%.

Conclusions
Combination therapy for acute stroke using compounds with complementary action can result in more complete attenuation of neuronal damage and demonstrates the possible clinical utility of combined neuroprotective and reperfusion therapies.
Gene Therapy for Cerebral Vascular Disease
Authors: Heistad Donald D. , Faraci Frank M.
Published: June 2011

Background
Gene transfer to peripheral arteries has been accomplished with catheter-based approaches. Recently, gene transfer to the carotid artery and intracranial vessels has been achieved both in vitro and in vivo. Although gene therapy for cerebral vascular disease may not be accomplished for years, currently available methods probably will allow novel approaches to the study of vascular biology.

Purpose
This mini-review summarizes current methodology and describes some potential goals of gene therapy. Transfection of vessels might be used to prevent vasospasm after subarachnoid hemorrhage, stimulate growth of collateral blood vessels, stabilize atherosclerotic plaques, and prevent restenosis after angioplasty. Gene transfer approaches also may be useful in treating ischemia by inhibition or overexpression of cytokines and by effects on neurons. Some formidable barriers to gene therapy are the current lack of safe and effective vectors for gene transfer, the difficulty in delivering vectors to intracranial vessels, and the transience of transfection.

Conclusions
At present, gene transfer is a promising tool for the study of vascular biology. Obstacles to gene therapy for cerebral vascular disease seem sufficiently large that new approaches, rather than refinement of current approaches, may be needed. Progress toward gene therapy probably will be made in steps rather than leaps.
A Computational Model of Acute Focal Cortical Lesions
Authors: Goodall Sharon , Reggia James A. , Chen Yinong , Ruppin Eytan , Whitney Carol
Published: June 2011

Background and Purpose
Determining how cerebral cortex adapts to sudden focal damage is important for gaining a better understanding of stroke. In this study we used a computational model to examine the hypothesis that cortical map reorganization after a simulated infarct is critically dependent on perilesion excitability and to identify factors that influence the extent of poststroke reorganization.

Methods
A previously reported artificial neural network model of primary sensorimotor cortex, controlling a simulated arm, was subjected to acute focal damage. The perilesion excitability and cortical map reorganization were measured over time and compared.

Results
Simulated lesions to cortical regions with increased perilesion excitability were associated with a remapping of the lesioned area into the immediate perilesion cortex, where responsiveness increased with time. In contrast, when lesions caused a perilesion zone of decreased activity to appear, this zone enlarged and intensified with time, with loss of the perilesion map. Increasing the assumed extent of intracortical connections produced a wider perilesion zone of inactivity. These effects were independent of lesion size.

Conclusions
These simulation results suggest that functional cortical reorganization after an ischemic stroke is a two-phase process in which perilesion excitability plays a critical role.
Transcranial Doppler Ultrasound Battery Reliably Identifies Severe Internal Carotid Artery Stenosis
Authors: Wilterdink J.L. , Feldmann E. , Furie K.L. , Bragoni M. , Benavides J.G.
Published: June 2011

Background and Purpose
There is a clinical imperative for noninvasive tests for carotid disease that have high sensitivity. Previous studies have shown that transcranial Doppler ultrasound (TCD) can identify intracranial collateral flow patterns and other hemodynamic consequences of carotid occlusion. We hypothesized that a battery of such TCD findings would have a greater sensitivity than any one TCD finding alone and would have clinical utility in identifying carotid disease.

Methods
We determined the prevalence of seven TCD findings in patients with various degrees of carotid stenosis as measured by a blinded observer on 138 cerebral angiograms. We further determined the sensitivity and specificity of any one finding or any single abnormality in the TCD battery (the combination of all seven findings) for identifying severe (≥70%) carotid stenosis by angiography.

Results
The following four individual TCD findings were associated (
P
<.001) with ≥70% carotid stenosis on cerebral angiography: ophthalmic and anterior cerebral artery flow reversal and low middle cerebral artery flow acceleration and pulsatility. The presence of any single abnormality in the TCD battery had a similar association (
P
<.001) with ≥70% carotid stenosis. The individual TCD findings had sensitivities of 3% to 83% and specificities of 60% to 100% for identifying ≥70% carotid stenosis. The TCD battery had a sensitivity of 95% and specificity of 42% for identifying ≥70% carotid stenosis.

Conclusions
A battery of TCD findings that can be routinely measured reliably identified patients with ≥70% angiographic internal carotid artery stenosis with high sensitivity.
Endothelin Production Links Superoxide Generation to Altered Opioid-Induced Pial Artery Vasodilation After Brain Injury in Pigs
Authors: Kasemsri Thivakorn , Armstead William M.
Published: June 2011

Background and Purpose
Traumatic brain injury conveys significant morbidity and mortality to infants and children. In the newborn pig, opioids contribute to pial artery vasconstriction after fluid percussion injury (FPI). FPI attenuates vasodilation and cGMP production by methionine enkephalin (Met) and leucine enkephalin (Leu) and reverses dynorphin (Dyn) from a dilator to a constrictor. Superoxide anion (O
2
−
) production contributes to altered cerebral hemodynamics after FPI, and O
2
−
scavengers partially restore decreased dilator responses after FPI. Endothelin-1 (ET-1), a purported mediator of cerebral vasospasm, has been suggested to alter nitric oxide function and cGMP concentration. The present study was designed to determine the contribution of ET-1 to altered opioid-induced dilation after FPI and the role of O
2
−
in such altered responses.

Methods
Injury of moderate severity (1.9 to 2.3 atm) was produced by the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase (SOD)–inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O
2
−
generation.

Results
FPI increased cerebrospinal fluid ET-1 from 20±2 to 93±6 pg/mL (≈10
−10
mol/L). Topical ET-1 (10
−10
mol/L) increased SOD-inhibitable NBT reduction from 1±1 to 16±3 pmol/mm
2
, similar to previously reported NBT reduction after FPI (14±2 pmol/mm
2
). BQ123 (10
−6
mol/L), an ET-1 antagonist, blunted the NBT reduction observed after FPI (4±1 pmol/mm
2
). Met produced pial vasodilation that was attenuated by FPI and partially restored by BQ123 pretreatment (7±1%, 11±1%, and 17±1% versus 3±1%, 6±1%, and 9±2% versus 5±1%, 9±1%, and 14±2% for 10
−10
, 10
−8
, and 10
−6
mol/L Met during control conditions, after FPI, and after FPI pretreated with BQ123, respectively). Met-induced dilation was associated with increased cerebrospinal fluid cGMP, and these biochemical changes were likewise blunted by FPI and partially restored by BQ123 (357±12, 455±15, 500±19, and 632±11 versus 264±4, 267±4, 295±12, and 305±15 versus 309±19, 432±11, 529±10, and 593±4 pg/mL for resting conditions, 10
−10
, 10
−8
, and 10
−6
mol/L Met during control conditions, after FPI, and after FPI pretreated with BQ123, respectively). Similar partial restoration of vascular and biochemical parameters was observed for Leu and Dyn.

Conclusions
These data show that ET-1, in concentrations similar to that present in cerebrospinal fluid after FPI, increases O
2
−
production. These data also indicate the opioid-induced vasodilation and cGMP production are partially restored after FPI by ET-1 receptor blockade. These data suggest that ET-1 contributes to altered cerebral hemodynamics after FPI, at least in part, through elevated O
2
−
production.
When Is Thrombolysis Justified in Patients With Acute Ischemic Stroke?
Authors: Furlan Anthony J. , Kanoti George
Published: June 2011

Background
Thrombolytic therapy for acute ischemic stroke raises several unsettled bioethical issues related to risk versus benefit. Excluding the National Institutes of Neurological Disorders and Stroke (NINDS) rt-PA trial, the risk of intracerebral hemorrhage averages 10.3%, and there is a 44% increase in the odds of death among fibrinolysis-treated patients. Some investigators have suggested that as yet unidentified subgroups may benefit despite an increased early risk of hemorrhage and death, while others have warned that the widespread use of thrombolysis cannot currently be recommended despite recent Food and Drug Administration approval. The NINDS rt-PA trial showed a net benefit, but the relative risk to benefit ratio in individual patients is uncertain because of incomplete subgroup analysis. We explore these and related issues by applying the bioethical principle of justification to the selection of stroke patients for thrombolysis.

Summary of Comment
Justification of a therapy rests on the criteria of safety, efficacy (net benefit under ideal conditions), effectiveness (net benefit under routine conditions), efficiency (cost-effectiveness or cost benefit), and outcome (proportionality and informed consent). The ethical principal of proportionality states that positive outcomes must be proportional to negative outcomes; only the NINDS trial sets equipoise between risk and benefit. The relative risk to benefit ratio and cost-effectiveness of thrombolysis will likely vary among treating physicians and patient subgroups. Although some potential selection factors such as early CT changes, National Institutes of Health Stroke Scale score >22, and age >77 years have been identified, it is not yet possible to predict response to treatment in individual patients. The effectiveness of thrombolysis outside of a clinical trial has not yet been demonstrated, and it is not clear that thrombolysis is cost-effective for all potential patient subgroups.

Conclusions
No stroke thrombolysis regimen has met all five justification criteria. Proportional outcome standards that take into account patient preferences must be established. The risk to benefit ratio of thrombolysis in patient subgroups requires clarification and should incorporate cost-efficiency analyses. These issues should be kept in mind when considering thrombolysis therapy in patients with acute ischemic stroke and when designing clinical trials.
Geographic Distribution of Stroke Mortality Among Immigrants to the United States
Authors: Lanska Douglas J.
Published: June 2011

Background and Purpose
This study examines the geographic distribution of stroke mortality among immigrants and natives of the United States.

Methods
National Center for Health Statistics and Bureau of the Census data were used to determine the geographic distribution of age-adjusted, race-, and race/sex-specific stroke mortality rates among immigrants and natives of the United States for 1979 to 1981.

Results
For whites and blacks and for each of the respective race/sex groups, immigrants had markedly and highly statistically significantly lower age-adjusted stroke mortality rates than either the entire US-born resident population or the US-born interregional migrant population. The spatial pattern of immigrant rates did not parallel the patterns for US-born populations. Immigrant rates were highest in the West and lowest in the Midwest for whites and highest in the Midwest and lowest in the Northeast for blacks, whereas for both US-born whites and blacks, resident and native rates were highest in the South and lowest in the Midwest. With few exceptions, region-specific immigrant rates for whites and blacks were significantly lower than rates for either US-born regional residents, US-born migrants to the regions, or US-born natives of the regions. In contrast, white immigrants to the West had significantly higher rates than US-born groups in that region.

Conclusions
Selection factors strongly influence stroke mortality rates among immigrants to the United States. The aberrantly high rates among white immigrants to the West may in part reflect a bias due to large census undercounts of this population.
Trends in Stroke Incidence
Authors: Truelsen T. , Prescott E. , Grønbæk M. , Schnohr P. , Boysen G.
Published: June 2011

Background and Purpose
Stroke incidence has increased in some countries and decreased in others. After 20 years of intensive antihypertensive treatment the latter could be expected, and we have evaluated the sex-specific temporal trends in stroke incidence using 17 years of follow-up in the Copenhagen City Heart Study.

Subjects and Methods
Our cohort comprised 19 698 subjects living in Copenhagen, Denmark. They were invited for health examinations in the following time periods: 1976 through 1978, 1981 through 1983, and 1992 through 1994. Trends are presented for all persons who attended at least one of the two first examinations as well as the total cohort including nonresponders. Subjects between 45 and 84 years of age were followed from March 1, 1976 until March 1, 1993. Changes in age-specific stroke incidence were calculated by means of Poisson regression analysis.

Results
For subjects aged 45 to 64 years, no significant trends were observed, with an annual incidence rate ratio of 1.00 (95% confidence interval [CI], 0.97 to 1.03) and 1.04 (95% CI, 0.99 to 1.08) for men and women, respectively. In subjects aged 65 to 84 years a significant decrease in stroke incidence was found in men, whose annual rate ratio was 0.97 (95% CI, 0.95 to 0.99), but not in women, whose annual rate ratio was 0.98 (95% CI, 0.95 to 1.00). Throughout four observed periods the stroke incidence among men remained significantly higher than that for women.

Conclusions
During the period from 1976 to 1993 there has been a decline in incidence of stroke in men and women aged 65 to 84 years that was significant only in men, whereas no changes were found for persons aged 45 to 64 years.
Risk Factors for Stroke Due to Cerebral Infarction in Young Adults
Authors: You Roger X. , McNeil John J. , O’Malley Heather M. , Davis Stephen M. , Thrift Amanda G. , Donnan Geoffrey A.
Published: June 2011

Background and Purpose
Stroke in the young is particularly tragic because of the potential for a lifetime of disablement. More than 10% of patients with stroke due to cerebral infarction are aged 55 years or younger. While a number of studies have addressed the issue of stroke mechanism in the young, quantitation of risk factors has rarely been undertaken. Given the importance of risk factor assessment in primary prevention, we aimed to assess this using case-control methodology in a hospital-based series and community-based control subjects.

Methods
A total of 201 consecutive patients with first-onset stroke due to cerebral infarction aged 15 to 55 years (mean, 45.5 years) were accrued from four teaching hospitals during 1985 to 1992 and compared with their age- and sex-matched neighborhood controls. Information concerning potential risk factor exposure status was collected by structured questionnaire at interview. Stroke risks were estimated by calculating the odds ratios with multivariate logistic regression.

Results
Significantly increased risk of stroke was found among those with diabetes (odds ratio, 11.6 [95% confidence intervals, 1.2 to 115.2]), hypertension (6.8 [3.3 to 13.9]), heart disease (2.7 [1.1 to 6.4]), current cigarette smoking (2.5 [1.3, 5.0]), and long-term heavy alcohol consumption (≥60 g/d) (15.3 [1.0 to 232.0]). However, heavy alcohol ingestion (≥60 g) within 24 hours preceding stroke onset was not a risk factor (0.9 [0.3 to 3.4]).

Conclusions
Diabetes, hypertension, heart disease, current smoking, and long-term heavy alcohol consumption are major risk factors for stroke in young adults. Given that the majority of these factors are either correctable or modifiable, prevention strategies may have the potential to reduce the impact of stroke in this age group.
S-100 Protein and Neuron-Specific Enolase Concentrations in Blood as Indicators of Infarction Volume and Prognosis in Acute Ischemic Stroke
Authors: Missler Ulrich , Wiesmann Martin , Friedrich Christine , Kaps Manfred
Published: June 2011

Background and Purpose
Better techniques are needed to monitor infarction volume and predict neurological outcome after ischemic brain infarction. We evaluated the usefulness of serial measurements of S-100 protein versus neuron-specific enolase (NSE) in blood samples from patients with acute stroke.

Methods
Using nonisotopic sandwich immunoassays, we measured plasma concentrations of S-100 protein and NSE on admission and on days 3, 4, 7, and 14 after infarction in 44 patients (age range, 22 to 86 years; mean age, 65.1 years; 12 female, 32 male). Infarct volume was measured by volumetric CT on day 4 after ictus, and clinical outcome was assessed at discharge from hospital with the Activities of Daily Living Scale and 6 months after infarction with the Glasgow Outcome Scale.

Results
Peak blood levels of S-100 protein were found on day 2.5±1.3, and peak levels of NSE were found on day 1.9±0.8 after infarction. Peak plasma levels of S-100 protein correlated well with infarct volume (
r
=.75,
P
<.001) and with clinical outcome assessed with the Glasgow Outcome Scale (
r
=.51,
P
<.001). Serum levels of NSE correlated with infarct volume (
r
=.37,
P
<.05) but not with clinical outcome (
r
=.18,
P
>.05).

Conclusions
The results of our study indicate that measuring blood concentrations of S-100 protein periodically in the first 10 days after cerebral infarction helps to predict infarct volume and the long-term neurological outcome more accurately than periodic measurements of blood concentrations of NSE.
Transcranial Doppler Ultrasound Criteria for Hemodynamically Significant Internal Carotid Artery Stenosis Based on Residual Lumen Diameter Calculated From En Bloc Endarterectomy Specimens
Authors: Can Ufuk , Furie Karen L. , Suwanwela Nijasri , Southern James F. , Macdonald Nancy R. , Ogilvy Christopher S. , Buonanno Ferdinando S. , Koroshetz Walter J. , Kistler J. Philip
Published: June 2011

Background and Purpose
Transcranial Doppler (TCD) is often used in conjunction with carotid duplex ultrasonography (CDUS) to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis. We examined the sensitivity and specificity of TCD criteria for detection of a hemodynamically significant stenosis (residual lumen diameter <1.5 mm) at the origin of the ICA.

Methods
We selected patients who underwent carotid endarterectomy (CEA) and had preoperative TCD data available. Eighty-one patients underwent transorbital evaluation, 49 of whom also had transtemporal TCD performed. The endarterectomy specimens were removed en bloc and sectioned, and the minimal residual lumen diameter calculated by computer analysis.

Results
For the transorbital approach, the strongest indicators of a residual lumen diameter <1.5 mm were reversed flow in the ipsilateral ophthalmic artery and a >50% peak systolic velocity difference between the carotid siphons (distal ICAs) in patients with unilateral ICA origin stenosis. They were 100% specific and 31% and 26% sensitive, respectively. For the transtemporal approach in patients with a unilateral stenosis, a >35% difference in ipsilateral middle cerebral artery (MCA) peak systolic velocity relative to the contralateral MCA or a >50% difference in contralateral anterior cerebral artery (ACA) peak systolic velocity relative to the ipsilateral ACA were 100% specific for identifying a residual lumen diameter of <1.5 mm. Sensitivities were 32% and 43%, respectively. Irrespective of contralateral stenosis, a >35% difference in ipsilateral MCA peak systolic velocity relative to the ipsilateral posterior cerebral artery had a 100% specificity and a 23% sensitivity for detecting a <1.5 mm minimal residual lumen diameter.

Conclusions
Although the TCD sensitivity for detecting a hemodynamically significant stenosis is relatively low, it can be highly specific (up to 100%). We conclude that TCD enhances the specificity of highly sensitive CDUS criteria for detecting a hemodynamically significant ICA stenosis.
Superior Neuroprotective Efficacy of a Novel Antioxidant (U-101033E) With Improved Blood-Brain Barrier Permeability in Focal Cerebral Ischemia
Authors: Schmid-Elsaesser Robert , Zausinger Stefan , Hungerhuber Edwin , Plesnila Nikolaus , Baethmann Alexander , Reulen Hanns-Juergen
Published: June 2011

Background and Purpose
The vascular endothelium and parenchyma of the brain have the potential to generate free radicals under pathological conditions, but it is unclear which of these two sites prevails in the production of free radicals and should be the primary target of therapeutic intervention. To clarify this issue, we compared the neuroprotective properties of a 21-aminosteroid (U-74389G) that acts on the microvasculature and a pyrrolopyrimidine (U-101033E), a novel antioxidant compound that has significantly improved potential to enter the brain parenchyma.

Methods
In Sprague-Dawley rats the middle cerebral artery was occluded for 90 minutes by an intraluminal filament. Local cortical blood flow was recorded by bilateral laser Doppler flowmetry throughout ischemia and 1 hour of reperfusion. Three groups of rats were studied: controls that received vehicle only and animals that received either U-74389G or U-101033E. Neurological examinations were performed daily, and infarct size was assessed histologically 7 days after ischemia.

Results
U-101033E reduced infarct volume significantly by 51%, whereas U-74389G led to a nonsignificant decrease in infarct volume. U-101033E improved neurological function immediately after ischemia, whereas U-74389G led to improvement only at the end of the observation period. Laser Doppler measurements showed no significant difference in local cortical blood flow among the treatment groups.

Conclusions
We conclude that for treatment of transient focal ischemia, an antioxidant that crosses the blood-brain barrier might be superior to agents that predominantly act on the endothelium of the cerebral microvasculature.
Correlation Between Motor Impairment and Infarct Volume After Permanent and Transient Middle Cerebral Artery Occlusion in the Rat
Authors: Rogers Derek C. , Campbell Colin A. , Stretton Jennifer L. , Mackay Kenneth B.
Published: June 2011

Background and Purpose
There have been a number of recent reports describing the relationship between ischemic damage and various behavioral and functional measures, although there have been few studies that have demonstrated a direct correlation between functional impairment and lesion volume. The purpose of the present study was to assess functional outcome by measurement of motor impairment and to determine whether this correlated to a range of infarct volumes induced by varying the duration of focal ischemic insult in the rat.

Methods
Male Sprague-Dawley rats were subjected to 0, 30, 60, or 120 minutes or permanent middle cerebral artery (MCA) occlusion by the intraluminal filament technique. Motor impairment was assessed by the accelerating rota-rod and grid-walking tests, and the brains were perfusion-fixed for histological determination of infarct volume and brain swelling 24 hours after MCA occlusion.

Results
Marked impairment in performance of both motor tests was recorded in the 60-minute, 120-minute, and the permanent MCA occlusion groups when compared with sham-operated rats. There were significant correlations between regional infarct volume, brain swelling, and all behavioral measurements (all
r
2
>.5,
P
<.001).

Conclusions
The rota-rod and grid-walking tests of motor performance provide quantitative, objective, and reproducible measures of functional impairment of rats following an ischemic insult. These impairments correlate directly with infarct volume and provide information integral to future studies evaluating the effects of potential neuroprotective agents.
Intracranial Aneurysm Rupture Presenting as Delayed Stroke Secondary to Cerebral Vasospasm
Authors: Nussbaum E. Spencer , Sebring L. A. , Wen Dennis Y. K.
Published: June 2011

Background
Days after aneurysmal subarachnoid hemorrhage (SAH), cerebral vasospasm can result in the delayed appearance of ischemic neurological deficit identical to that produced by other causes of stroke. Despite the well-described, “classic” presentation of SAH, up to 25% of patients are initially misdiagnosed, and the initial hemorrhage from a ruptured aneurysm will not always bring the patient to medical attention.

Case Descriptions
We report our experience with two patients who presented with signs and symptoms of ischemic stroke resulting from cerebral vasospasm that followed unrecognized rupture of a brain aneurysm. In one case, it was the recent complaint of significant headache and a prior history of SAH that led to the correct diagnosis. In the other case, a major rebleed occurred before the accurate diagnosis was recognized.

Conclusions
It is critical to make the correct diagnosis of stroke due to vasospasm so that appropriate treatment can be instituted, thrombolytic and anticoagulant therapy can be avoided, and the unsecured aneurysm can be obliterated to prevent potentially catastrophic rebleeding.
Effect of Extracranial Carotid Artery Stenosis and Other Risk Factors for Stroke on Periventricular Hyperintensity
Authors: Adachi Tomohide , Takagi Makoto , Hoshino Haruhiko , Inafuku Tetsuya
Published: June 2011

Background and Purpose
The pathogenesis of periventricular hyperintensity (PVH) is still uncertain. We investigated the relationship between PVH and risk factors for cerebrovascular diseases, especially extracranial carotid artery stenosis (ECAS).

Methods
We studied PVH and ECAS in 323 subjects between 1991 and 1994. Using 1.5-T MRI scan images, we measured PVH quantitatively at eight points and evaluated cerebral infarction. Duplex carotid sonography was performed on the carotid arteries bilaterally and used to divide the severity of ECAS into five grades. Risk factors for cerebrovascular diseases and atherosclerotic complications were assessed from the clinical history.

Results
Age was significantly correlated with the size of frontal and whole PVH (
P
<.01). Frontal PVH was significantly more severe in subjects with hypertension (
P
<.05). Frontal, occipital, and whole PVH were significantly more severe in subjects with a history of cerebrovascular accident (
P
<.01). Other risk factors and atherosclerotic complications were not correlated with PVH. There were no significant differences in the severity of PVH among the five groups of ECAS. The severity of PVH in each region was not related to ECAS. There was no significant difference in the age of patients in relation to the five grades of ECAS. However, PVH was significantly more severe in subjects with lacunar infarction or infarction of the deep border zone (
P
<.05). There was no relationship between PVH and cortical infarction or infarction of the cortical border zone.

Conclusions
PVH correlated with age, hypertension, and past history of cerebrovascular disease but not with ECAS. PVH was significantly more severe in lacunar infarction and infarction of the deep border zone. These results suggest that small-vessel disease may underlie the pathogenesis and development of PVH.
Soluble Adhesion Molecules Reflect Endothelial Cell Activation in Ischemic Stroke and in Carotid Atherosclerosis
Authors: Frijns C.J.M. , Kappelle L.J. , Gijn J. van , Nieuwenhuis H.K. , Sixma J.J. , Fijnheer R.
Published: June 2011

Background and Purpose
Activation of endothelial cells and platelets plays an important role in the development of atherosclerosis and thrombotic disorders. Soluble adhesion molecules originating from these cells can be demonstrated in plasma. We hypothesized that elevated plasma concentrations of soluble P-selectin (sP-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) can reflect activation of endothelial cells and/or platelets in acute ischemic stroke and in previously symptomatic internal carotid artery stenosis.

Methods
Plasma was sampled from patients within 2 days of acute ischemic stroke (n=28), from patients with a previous (>1 week) transient or persistent ischemic neurological deficit associated with stenosis of the internal carotid artery (n=34), and from control patients without a history of vascular disease (n=34). Concentrations of sP-selectin, sICAM-1, sVCAM-1, and sE-selectin were measured by means of an enzyme-linked immunosorbent assay.

Results
Compared with control subjects, sP-selectin and sE-selectin were significantly elevated in the acute stage of ischemic stroke (
P
<.0001 and
P
=.001, respectively) as well as in previously symptomatic carotid stenosis (
P
<.0001 and
P
=.0007). sICAM-1 and sVCAM-1 were not increased.

Conclusions
The elevated levels of sE-selectin indicate that endothelial cell activation occurs both in the acute stage of ischemic stroke and in previously symptomatic carotid atherosclerosis. Increased sP-selectin concentrations reflect endothelial cell activation as well but may also be caused by platelet activation.
Association of Presenilin-1 Polymorphism With Cerebral Amyloid Angiopathy in the Elderly
Authors: Yamada Masahito , Sodeyama Nobuyuki , Itoh Yoshinori , Suematsu Naomi , Otomo Eiichi , Matsushita Masaaki , Mizusawa Hidehiro
Published: June 2011

Background and Purpose
An intronic polymorphism of presenilin-1 (PS-1), a gene responsible for early-onset familial Alzheimer’s disease, has been reported to be associated with late-onset sporadic Alzheimer’s disease. In a search for a genetic risk factor of sporadic cerebral amyloid angiopathy (CAA), we investigated the association of the polymorphism of PS-1 with CAA.

Methods
The association between the severity of CAA and genotypes of a polymorphism in intron 8 of PS-1 was investigated in 137 autopsy cases of the elderly.

Results
A significant decrease of PS-1 2/2 genotype frequency was associated with severe or moderate CAA.

Conclusions
Our results suggest that PS-1 intronic polymorphism may be associated with the severity of CAA in the elderly.
Lamotrigine Protects Hippocampal CA1 Neurons From Ischemic Damage After Cardiac Arrest
Authors: Crumrine R. Christian , Bergstrand Kristine , Cooper Amy T. , Faison Walter L. , Cooper Barrett R.
Published: June 2011

Background and Purpose
Lamotrigine (LTG) is an anticonvulsant drug whose mechanism of action may involve the inhibition of glutamate release by blocking voltage-dependent sodium channels. Glutamate neurotoxicity may contribute to cerebral ischemic damage after recovery from cardiac arrest. Thus, LTG may prevent the brain damage associated with global cerebral ischemia by reducing the release of glutamate from presynaptic vesicles during the ischemic insult or the early recovery period.

Methods
LTG was studied in cardiac arrest–induced global cerebral ischemia with reperfusion in rats. In the first set of experiments, LTG (100 mg/kg, PO) was administered before induction of ischemia; and in the second experiment, LTG (10 mg/kg, IV) was given 15 minutes after ischemia and a second dose (10 mg/kg,IV) was given 5 hours later.

Results
In both experiments LTG reduced the damage to the hippocampal CA1 cell population by greater than 50%. Neuroprotection was not associated with changes in brain temperature or plasma glucose concentration. Plasma concentrations of LTG ranged between 8 and 13 μg/mL. Patients taking LTG as a monotherapy for epilepsy typically have plasma levels of LTG in the 10 to 15 μg/mL range.

Conclusions
These data suggest that LTG may be effective in preventing brain damage after recovery from cardiac arrest. Patients on LTG monotherapy for epilepsy have plasma concentrations very similar to those found to be neuroprotective in this study. Although difficult to extrapolate, our data suggest that LTG at neuroprotective doses may be well tolerated by humans.
Neither
l
-Arginine nor L-NAME Affects Neurological Outcome After Global Ischemia in Cats
Authors: Kirsch Jeffrey R. , Bhardwaj Anish , Martin Lee J. , Hanley Daniel F. , Traystman Richard J.
Published: June 2011

Background and Purpose
We attempted to determine whether
N
ω
-nitro-
l
-arginine methyl ester (L-NAME) would improve neurological outcome and whether
l
-arginine (L-ARG) would worsen neurological outcome after transient global ischemia.

Methods
Halothane-anesthetized cats (n=6 for each group) were treated with intravenous saline, L-NAME (5 mg/kg or 10 mg/kg), or
l
-arginine (300 mg/kg) 30 minutes before 10 minutes of ischemia (temporary ligation of the left subclavian and brachiocephalic arteries with hemorrhagic hypotension to 50 mm Hg). At 30 minutes of reperfusion, cats in the L-ARG group were administered an additional 300 mg/kg dose of intravenous
l
-arginine.

Results
Time (mean±SE) to isoelectric electroencephalography was similar among groups (saline, 26±11 seconds; L-NAME–5, 15±4 seconds; L-NAME–10, 36±27 seconds; and L-ARG, 22±7 seconds). At 72 hours, reperfusion pathological injury was severe and neurological deficit score (mean, range) was similar among groups (saline, 38 [11 to 70]; L-NAME–5, 52 [40 to 73]; L-NAME–10, 47 [23 to 70]; and L-ARG, 40 [0 to 79]).

Conclusions
Nitric oxide is not important in the mechanism of brain injury after global ischemia in cats.
Cardiopulmonary and Arterial Baroreflex-Mediated Control of Forearm Vasomotor Tone Is Impaired After Acute Stroke
Authors: Robinson Thompson , Potter John
Published: June 2011

Background and Purpose
Elevated blood pressure (BP) levels are well recognized after acute stroke and are associated with increased BP variability. The underlying mechanisms producing such changes are unclear but may include abnormalities of baroreceptor-mediated control of heart rate and vasomotor tone. Lower body negative pressure (LBNP) can be used to assess the integrity of “low-pressure” cardiopulmonary and “high-pressure” arterial baroreceptor–derived responses by inducing nonhypotensive and hypotensive stimuli.

Methods
Cardiovascular responses, including BP, heart rate, forearm blood flow, and forearm vascular resistance, to nonhypotensive and hypotensive LBNP were assessed in 13 consecutive stroke patients. Patients were studied within 72 hours of stroke (acute) and again at 10 to 14 days (subacute) and were compared with 13 control subjects individually matched for age, sex, and BP.

Results
At an LBNP of −10 mm Hg, BP was unchanged in all groups, but a significant increase in forearm vascular resistance occurred only in the control group (11 U [interquartile range, 7 to 15];
P
<.05) compared with stroke patients in the acute (9 U [3 to 14];
P
=NS) or subacute phases (7 U [2 to 12];
P
=NS). After LBNP at −40 mm Hg, the reductions in systolic BP levels were similar in all groups (control: −9 mm Hg [−16 to −3]; acute stroke: −9 mm Hg [−22 to 3]; subacute stroke: −7 mm Hg [−35 to 20]), as was the associated increase in heart rate (control: 8 bpm ([4 to 11]; acute stroke: 6 bpm ([1 to 12]; subacute stroke: 9 bpm [2 to 19]). However, forearm vascular resistance increased significantly only in control subjects (20 U [9 to 30];
P
<.01).

Conclusions
The present study has identified abnormal vasomotor responses to LBNP after acute stroke, with an increase in FVR only being observed in control subjects in response to nonhypotensive and similar hypotensive levels of LBNP. In acute stroke patients, the stimulus of hypotensive LBNP appears to be compensated by an increase in cardiac output since there appears to be no increase in peripheral vascular resistance, unlike the changes seen in control subjects. However, the exact mechanisms for these changes are still unclear and are the subject of further study.
Quality of Life of Stroke in Younger Individuals
Authors: Shin Anne Y. , Porter Phillip J. , Wallace M. Christopher , Naglie Gary
Published: June 2011

Background and Purpose
Patients with arteriovenous malformations are younger individuals who are at risk of a stroke or have experienced one. Our objective was to determine these patients’ perceptions of quality of life with a stroke by eliciting utility values.

Methods
Utility values were obtained with the standard gamble technique. Utilities are a holistic, quality of life measure between 0 and 1. We evaluated the patients’ current health state and written descriptions of major and minor stroke.

Results
Thirty-one consecutive outpatients participated. The mean age was 37 years (range, 18 to 57 years). Approximately 65% had suffered a stroke, of which 55% were major. Approximately 61% had a persistent deficit. The mean utilities were 0.45 for major stroke (95% confidence interval [CI], 0.33 to 0.56; range, 0.00 to 1.00), 0.81 for minor stroke (95% CI, 0.75 to 0.88; range, 0.30 to 1.00), and 0.81 for current health (95% CI, 0.73 to 0.89; range, 0.01 to 1.00). Subgroup analyses by demographic and clinical characteristics showed no significant differences. However, in both those patients who had never had a stroke and those who had survived a major stroke, values for the major stroke scenario were clustered at the two extremes. Among those with a current deficit, 79% preferred their own health state to that of the stroke scenario that was similar in severity.

Conclusions
Younger people who have had a stroke or are at risk demonstrate wide variations in their perception of quality of life. Furthermore, patients tend to be more risk averse with their own lives than with theoretical scenarios. We suggest tailoring medical decision making to individual preferences.
Spontaneous Oscillations in Cerebral Blood Flow Velocities in Middle Cerebral Arteries in Control Subjects and Patients With Epilepsy
Authors: Diehl Beate , Diehl Rolf R. , Stodieck Stefan R. G. , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
Cardiac arrhythmias mediated by the sympathetic nervous system have been implicated in sudden, unexplained deaths in patients with epilepsy. Cerebral blood flow velocities (CBFV) as measured by transcranial Doppler are characterized by slow spontaneous oscillations in part attributed to changes in sympathetic activity (M waves, 3 to 9 cycles per minute) and to discharges of monoaminergic neurons in the brain stem (B waves, 0.5 to 2 cycles per minute). This study was designed to compare spontaneous fluctuations of CBFV in patients with epilepsy with those in normal control subjects .

Methods
Simultaneous registrations of scalp electroencephalograms, with electrodes placed according to the 10–20 System, and transcranial Doppler recordings of both middle cerebral arteries were performed in 27 patients (9 with primary generalized epilepsy, 18 with focal epilepsy). Data analysis of CBFV was based on the envelope curves of the Doppler spectrum. A fast Fourier transformation over the 20-minute CBFV curve was performed, and the amplitudes of B and M waves were calculated and compared with those in 20 normal, age-matched control subjects.

Results
While the amplitudes of the B waves in both groups were similar, patients with epilepsy showed significantly increased M waves. Patients with focal epilepsy did not present asymmetries between the normal hemisphere and the side of the epileptic focus with respect to both M and B waves.

Conclusions
Enhanced M waves in epileptic patients may reflect increased sympathetic activity even in the absence of seizures. This study provides further evidence for an autonomic dysfunction as a possible mechanism for sudden unexplained death in patients with epilepsy.