bluuebunny/crossref_metadata_2025 huggingface dataset:
US National Survey of Physician Practices for the Secondary and Tertiary Prevention of Ischemic Stroke
Authors: Goldstein Larry B. , Bonito Arthur J. , Matchar David B. , Duncan Pamela W. , Samsa Gregory P.
Published: June 2011

Background and Purpose
Aspirin or other platelet antiaggregants and anticoagulants are commonly used in many types of patients at elevated stroke risk. However, relatively little is known concerning how practicing physicians use these medications in their patients with extracranial carotid artery stenosis. The identification of variations in practice may help to both direct specific educational efforts and guide further research.

Methods
Between August 1993 and February 1994, we surveyed the stroke prevention practices of a stratified random sample of 2000 US physicians. The survey included clinical scenarios that probed the use of aspirin or other platelet antiaggregants and anticoagulants in symptomatic and asymptomatic patients with carotid artery stenoses of 50% to 70% or more than 70%, with and without known surgical contraindications.

Results
Sixty-seven percent of those eligible completed the survey (n=1006). More than 85% of physicians responded that they always or often prescribe aspirin or other platelet antiaggregants regardless of degree of carotid artery stenosis, symptom status, or presence of surgical contraindications. However, the reported frequency of use of these medications varied independently according to physician specialty (
P
=.044). In contrast, in addition to physician specialty, the reported frequency of anticoagulant use varied independently with degree of carotid artery stenosis, symptom status, and presence of surgical contraindications (
P
<.0001 for each variable). Fifteen percent of physicians responded that they always or often use anticoagulants for asymptomatic patients with 50% to 70% carotid artery stenosis versus 43% who reported doing so for symptomatic patients with a similar degree of stenosis (
P
<.001); 28% often or always prescribe anticoagulants for asymptomatic patients with more than 70% carotid artery stenosis versus 49% who do so if symptoms are present (
P
<.001). The odds of noninternist primary care physicians responding that they always or often use anticoagulants were more than five times higher (odds ratio, 5.32; 95% confidence interval [CI], 3.79 to 7.45) than surgical specialists. Compared with surgical specialists, the odds ratios for the use of anticoagulants were 3.65 for internists (95% CI, 2.63 to 5.06) and 1.88 (95% CI, 1.40 to 2.53) for neurologists.

Conclusions
These data show the following: (1) Aspirin or other platelet antiaggregants are used by most physicians regardless of degree of carotid artery stenosis, symptom status, or presence of surgical contraindications; (2) anticoagulants are prescribed selectively, with each of these variables influencing their use; and (3) the use of both classes of agents varies with physician specialty training.
Short-term Predictors of Incident Stroke in Older Adults
Authors: Manolio Teri A. , Kronmal Richard A. , Burke Gregory L. , O'Leary Daniel H. , Price Thomas R.
Published: June 2011

Background and Purpose
Risk factors for incident stroke have been examined in middle-aged persons, but less is known about stroke precursors in the elderly, who suffer the highest rates of stroke. Short-term risk factors for incident stroke were examined in a longitudinal, population-based study including extensive measures of subclinical disease.

Methods
Prospective study of 5201 women and men aged 65 years and older was undertaken in the multicenter Cardiovascular Health Study.

Results
During an average 3.31-year follow-up, 188 incident strokes occurred. Stroke incidence increased significantly with age and was similar in women and men. Factors associated with increased stroke risk in multivariate analysis included age, aspirin use, diabetes, impaired glucose tolerance, higher systolic blood pressure, increased time needed to walk 15 ft, frequent falls, elevated creatinine level, abnormal left ventricular (LV) wall motion and increased LV mass on echocardiography, ultrasound-defined carotid stenosis, and atrial fibrillation. Increased LV mass and carotid stenosis were associated with twofold and threefold increases in incidences of stroke, respectively (
P
<.001). Aspirin users had a 52% higher risk of stroke (relative risk, 1.52; 95% confidence interval, 1.1 to 2.0;
P
<.007) after adjustment for other factors. This association was present only among aspirin users without prior coronary disease, atrial fibrillation, claudication, or transient ischemic attack, who had an 84% higher risk (relative risk, 1.84; 95% confidence interval, 1.2 to 2.8).

Conclusions
Short-term risk of stroke has a complex relationship with aspirin use and is strongly related to subclinical disease in this sample of older adults. These relationships should be considered in assessing stroke risk in the elderly, in whom recognized and subclinical cardiovascular disease is highly prevalent.
Thalamic Vascular Lesions
Authors: del Mar Sáez de Ocariz María , Nader Juan A. , Santos José A. , Bautista Miguel
Published: June 2011

Background and Purpose
The data of patients with an MRI-confirmed diagnosis of thalamic stroke were analyzed to identify risk factors and to describe the clinical syndromes according to the thalamic arterial territory involved.

Methods
We examined the records of all patients with a diagnosis of thalamic stroke confirmed by MRI who attended the National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez” from 1987 through 1995. A database containing demographic features, risk factors, clinical course, type and mechanism of stroke, and vascular territory was analyzed.

Results
Twenty-eight patients (19 men and 9 women; mean age, 48.2 years) had MRI-confirmed thalamic stroke. Infarct was present in 22 patients and hemorrhage in 6. Eleven (39.3%) patients were younger than 45 years. In these young patients, cigarette smoking was the main risk factor associated with the development of stroke. In young patients, isolated and multiple thalamic lesions were present in almost equal proportions. The remaining 17 patients were older adults (45 to 84 years of age). In such patients, most lesions were multiple and were associated with atherosclerosis-predisposing factors. The main distinguishing clinical feature for hemorrhages and paramedian infarcts in comparison with infarcts in the other thalamic territories was the presence of an altered level of consciousness. No patient died as a direct result of the stroke.

Conclusions
Thalamic stroke commonly occurs in young adults, and its mechanism is often undetermined. Increased awareness of this type of stroke in young adults should lead to better delineation of its clinical features, course, and management.
Microemboli During Carotid Angiography
Authors: Gerraty Richard P. , Bowser David N. , Infeld Bernard , Mitchell Peter J. , Davis Stephen M.
Published: June 2011

Background and Purpose
Carotid angiography is associated with a 1% risk of major stroke. Recently, transcranial Doppler ultrasonography (TCD) has shown cerebral microemboli during carotid angiography. To determine their significance, we correlated the number of microemboli during angiography with clinical characteristics, angiography findings, and preangiography and postangiography cerebral magnetic resonance imaging (MRI).

Methods
One middle cerebral artery was monitored with TCD in 24 patients during angiography for carotid territory ischemia. The number of microemboli was correlated with angiographic and clinical characteristics. T2-weighted cerebral MRI was performed before and ≤48 hours after angiography, and the number of new ischemic lesions was determined in a blinded review.

Results
Microemboli were seen in all patients, with an average of 51 per procedure (range, 12 to 154). The majority of microemboli had signal characteristics typical of air. Sixteen of the 24 patients had both preangiography and postangiography MRI. One of 24 patients had an angiographic stroke, with a single new thalamic lesion on MRI. No other patient had a new lesion. The microembolus count correlated with the angiographic contrast volume (
P
<.001) but not with any other radiological or clinical characteristic.

Conclusions
This study confirmed the presence of numerous cerebral microemboli during carotid angiography. The microembolic signal characteristics and the correlation with contrast volume indicate that introduced air is the cause. These microemboli are usually clinically silent and do not lead to new changes on cerebral MRI.
Performance of the ‘Unaffected’ Upper Extremity of Elderly Stroke Patients
Authors: Desrosiers Johanne , Bourbonnais Daniel , Bravo Gina , Roy Pierre-Michel , Guay Manon
Published: June 2011

Background and Purpose
The main objective of this study was to compare the sensorimotor performance of the unaffected upper extremity (UE) of elderly stroke patients with that of healthy elderly people.

Methods
The group of stroke patients was composed of 43 hemiplegic/paretic subjects who had had a cerebrovascular accident at least 6 months earlier. They were ≥60 years old, were right-handed before the stroke, had visual perception within normal limits, and showed no major cognitive impairments. A group of 43 healthy subjects matched for dominance, age, and sex was used for comparison. The main parameters of the performance of the unaffected UE of the stroke subjects and of the same side of the healthy subjects were measured with valid, reliable instruments. Some variables potentially related to the unaffected UE were also measured: affected UE motor function, functional independence, length of time since the stroke, self-perceived health status, activity level, and hand anthropometry.

Results
Statistical analyses showed significant deficits in the unaffected UE of hemiplegic/paretic subjects compared with normal subjects with regard to the following parameters: gross manual dexterity, fine manual dexterity, motor coordination, global performance, and kinesthesia (
P
<.01 to
P
<.0001). No significant clinical or statistical difference was found for grip strength (
P
<.81), static and moving two-point discrimination (
P
=.21 and
P
=.12), or touch/pressure threshold (
P
<.91).

Conclusions
Many factors (frequency of use of the unaffected hand, sensorimotor interaction tasks, severity of the deficits in corticifugal projections, and deficits in postural stabilization) could interact to provide the clinical picture obtained in the present study. (Stroke. 1996;27:1564-1570.)
Morphological and Hemodynamic Assessments of Carotid Stenosis Using Quantitative Digital Subtraction Angiography
Authors: Bladin Christopher F. , Colchester Alan C.F. , Hawkes David J. , Seifalian Alexander M. , Iqbal Najma , Hardingham Charles R.
Published: June 2011

Background and Purpose
Digital angiography is the best established tool for assessing atheromatous disease of extracranial blood vessels. Advances in computer technology have now made it possible and practicable to extract quantitative information (length, width, cross-sectional area, and flow velocity) from good-quality clinical angiograms, allowing calculation of volume flow and pressure gradient. The technique of quantitative angiography (QA) is used for assessing coronary artery disease, but to date there has been no clinical application in patients with cerebrovascular disease.

Summary of Report
We have developed a computer program for off-line analysis of routine digital subtraction angiographic images. From biplanar images, the program reconstructs the angiogram in three dimensions and performs quantitative analysis of each vessel. From this data, the pressure drop from the aortic arch to the circle of Willis is then calculated. We assessed the clinical applicability of QA in five patients investigated for transient ischemic attack. The carotid artery ipsilateral to the symptomatic hemisphere was occluded in one patient and had minor plaque in another. In the remaining three patients, ipsilateral internal carotid artery stenosis was measured by QA as producing area reductions of 55%, 72%, and 88% (equivalent to diameter reductions of 33%, 48%, and 65%, respectively). In these patients, the quantitative stenosis pressure gradients were calculated as 1.2, 3.0, and 3.5 mm Hg, respectively. Further calculation showed that each stenosis contributed to 18%, 24%, and 60%, respectively, of the total carotid pressure gradient from the aortic arch to the circle of Willis. These carotid arteries carried 47%, 42%, and 26%, respectively, of the total cerebral flow. The results of quantitative analysis were validated by comparing, within each patient, the differences in pressure gradients between right and left carotid systems or between right and left vertebral arteries (overall mean difference in pressure gradient, 0.6±0.5 mm Hg;
P
=NS). Finally, comparison was made of pressure gradients across the circle of Willis between the carotid and vertebrobasilar circulations (mean difference in pressure gradient, 4.1±5.3 mm Hg;
P
=NS).

Conclusions
Quantitative angiography allows determination of the hemodynamic parameters of a vessel or stenosis. It has significant potential, both as a research tool and in routine clinical practice, for the investigation of cerebrovascular disease.
Interleukin-1 Receptor and Receptor Antagonist Gene Expression After Focal Stroke in Rats
Authors: Wang Xinkang , Barone Frank C. , Aiyar Nambi V. , Feuerstein Giora Z.
Published: June 2011

Background and Purpose
The expression of interleukin-1β (IL-1β) is upregulated after focal brain ischemia, and previous work has demonstrated its involvement in ischemic injury. The IL-1 receptor antagonist (IL-1ra), a natural competitive antagonist of IL-1 receptors (IL-1Rs), has been demonstrated to play a role in attenuating brain ischemic injury. To hypothesize the involvement of the IL-1 system in ischemic injury, we examined other IL-1 components, including IL-1ra, IL-1RI, and IL-1RII for their mRNA expression after focal stroke.

Methods
Quantitative reverse transcription and polymerase chain reaction (RT-PCR) technique was used to examine the mRNA expression profile of IL-1ra and two IL-1R isoforms in a temporal fashion (n=4 for each time point) after permanent occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rats. IL-1ra and IL-1R mRNA expression was confirmed by Northern blot analysis using poly(A) RNA isolated after 2 and 12 hours of MCAO.

Results
Very low levels of IL-1ra mRNA were detected in sham-operated or nonischemic cortex. IL-1ra mRNA in ischemic cortex was greatly increased at 12 hours (16.5-fold increase over sham samples,
P
<.001) and remained elevated for up to 5 days (17.2-fold increase,
P
<.01) after MCAO. IL-1RI mRNA was relatively highly expressed in normal cortex and was further elevated late after ischemic injury (3.3-fold increase at day 5,
P
<.001). In contrast, the low basal expression of IL-1RII mRNA was remarkably elevated at 6 hours (5.3-fold increase,
P
<.05), reaching peak levels 12 hours (10.3-fold increase,
P
<.001) after MCAO.

Conclusions
Differential expression of IL-1β, IL-1ra, IL-1RI, and IL-1RII mRNAs after focal stroke may suggest a distinct role(s) for each component of the IL-1 system in ischemic injury. The data also stress the importance of evaluating all the components of a given cytokine system (eg, agonist, receptors, and natural antagonist) after focal stroke.
Age-Related Changes in Response of Brain Stem Vessels to Opening of ATP-Sensitive Potassium Channels
Authors: Toyoda Kazunori , Fujii Kenichiro , Takata Yutaka , Ibayashi Setsuro , Kitazono Takanari , Nagao Tetsuhiko , Fujikawa Megumi , Fujishima Masatoshi
Published: June 2011

Background and Purpose
This study was designed to determine regional differences and age-related changes in the contribution of ATP-sensitive potassium (K
ATP
) channels to vasodilator responses in the brain stem circulation in vivo.

Methods
Changes in diameter of the basilar artery (baseline diameter, 270±5 μm [mean±SEM]), its large branch (112±5 μm), and its small branch (49±2 μm) in response to K
ATP
channel openers levcromakalim and Y-26763 were measured through a cranial window in anesthetized adult (4 to 6 months) and aged (24 to 26 months) Sprague-Dawley rats.

Results
Topical application of levcromakalim and Y-26763 produced concentration-dependent vasodilation that was similar among the three vessel groups in adult rats. In aged rats, dilator responses of the branches, but not of the basilar artery, to the K
ATP
channel openers were smaller than those in adult rats (
P
<.05). Glibenclamide, a selective K
ATP
channel blocker, almost abolished this vasodilation in both groups of rats. Vasodilator responses to sodium nitroprusside were preserved in aged rats.

Conclusions
In adult rats, there is no regional heterogeneity in vasodilator response to K
ATP
channel openers in the brain stem circulation in vivo. In aged rats, although K
ATP
channels are also functional in the brain stem circulation, dilator response of the microvessels but not of the large arteries to direct activation of K
ATP
channels is impaired.
Mechanisms of Adrenomedullin-Induced Dilatation of Cerebral Arterioles
Authors: Lang Markus G. , Paterno Roberto , Faraci Frank M. , Heistad Donald D.
Published: June 2011

Background and Purpose
Adrenomedullin is a recently discovered vasoactive peptide that is structurally related to calcitonin gene–related peptide (CGRP). Adrenomedullin is produced by vascular endothelium and smooth muscle and is present in the brain. The goals of this study were to determine (1) whether adrenomedullin produces dilatation of cerebral arterioles and whether this effect is mediated by activation of CGRP receptors and (2) whether vasodilatation to adrenomedullin was mediated by K
+
channels.

Methods
Diameter of cerebral arterioles (mean±SE baseline, 46±1 μm) was measured using a closed cranial window in anesthetized rats.

Results
Application of rat adrenomedullin (10
−7
and 10
−6
mol/L) increased vessel diameter by 16±3% and 45±8% (n=5), respectively. Vasodilator responses to repeated application of adrenomedullin were reproducible. Pretreatment of cerebral arterioles with the specific CGRP
1
receptor antagonist CGRP-(8-37) (5×10
−7
mol/L) selectively inhibited the vasodilator responses to adrenomedullin without inhibiting responses to ADP (10
−5
to 10
−3
mol/L). Responses to adrenomedullin (10
−7
and 10
−6
mol/L) were 14±1% and 40±3% before and 2±2% and 6±1% after CGRP-(8-37), respectively (
P
<.01). Glibenclamide (10
−6
mol/L), an inhibitor of ATP-sensitive K
+
channels, reduced the responses to adrenomedullin without attenuating responses to ADP. Responses to adrenomedullin were 19±4% and 35±6% before and 6±3% and 19±5% after glibenclamide, respectively (
P
<.05). Iberiotoxin (10
−7
mol/L), an inhibitor of calcium-dependent K
+
channels, also significantly attenuated responses to adrenomedullin and did not inhibit vasodilatation to papaverine. Responses to adrenomedullin were 16±2% and 55±8% before and 12±4% and 26±3% after iberiotoxin, respectively (
P
<.01 for 10
−6
mol/L adrenomedullin).

Conclusions
Adrenomedullin produces substantial dilatation of cerebral arterioles in vivo, and the response is mediated in large part by activation of CGRP
1
receptors. Cerebral vasodilatation to adrenomedullin appears to be dependent on activation of K
+
channels.
Tetrahydrobiopterin, a Cofactor for Nitric Oxide Synthase, Produces Endothelium-Dependent Dilation of Mouse Pial Arterioles
Authors: Rosenblum William I.
Published: June 2011

Background and Purpose
Tetrahydrobiopterin (THBP) is an essential cofactor for nitric oxide synthase (NOS), which is responsible for the synthesis of the endothelium-derived relaxing factor (EDRF) responsible for mediating the vasorelaxation produced by acetylcholine (ACh). Previous publications suggest that EDRF
ACh
is continuously synthesized and released from the endothelium of mouse pial arterioles. If so, then one may predict that addition of THBP will increase the local production of EDRF
ACh
and produce an endothelium-dependent relaxation that can be blocked by application of a known inhibitor of NOS. This study tests the prediction.

Methods
The pial vessels were observed at a continuously suffused craniotomy site by means of intravital television microscopy. The effects of topically applied THBP on diameter were monitored before and after endothelial damage and before and after local treatment with the NOS inhibitor
N
-guanidino-
l
-monomethyl arginine (LNMMA). The endothelial damage was produced by a helium-neon laser in the presence of Evans blue dye.

Results
A dose-dependent relaxation was produced by 10
−3
and 10
−2
mol/L THBP. The response was virtually eliminated by endothelial injury. LNMMA 10
−6
mol/L also greatly inhibited dilation.

Conclusions
The data are consistent with all reports that THBP is a cofactor for constitutive endothelial NOS. The data are consonant with previous results suggesting that EDRF
ACh
is continually synthesized and released. It appears that THBP increases this synthesis and consequently the local level of released EDRF
ACh
. The continuous spontaneous synthesis/release of EDRF
ACh
modulates basal tone and, according to other studies, helps maintain a platelet-free endothelial surface.
Racial Differences in the Utilization of Inpatient Rehabilitation Services Among Elderly Stroke Patients
Authors: Horner Ronnie D. , Hoenig Helen , Sloane Richard , Rubenstein Lisa V. , Kahn Katherine L.
Published: June 2011

Background and Purpose
We undertook this study to ascertain whether elderly black and white patients who are hospitalized for stroke utilize inpatient physical and occupational therapy (PT/OT) services differently, adjusting for characteristics associated with use of these services.

Methods
We retrospectively reviewed medical records regarding the care received by a nationally representative sample of 2497 black and white Medicare patients, aged 65 years or older, who were hospitalized at any of 297 acute-care hospitals located in 30 communities within five states.

Results
Compared with whites, black stroke patients were younger and more likely to have Medicaid coverage, have an ischemic stroke, and have a motor deficit noted at the time of admission. There was no difference in either sex or level of consciousness on admission. Overall, a larger proportion of black stroke patients used inpatient PT/OT at some point during the hospitalization (66.3% versus 55.8%;
P
<.01). However, after adjustment for characteristics associated with use of PT/OT, there was no racial difference in either the likelihood of inpatient PT/OT use (adjusted relative risk, 1.06; 95% confidence limits, 0.89 to 1.27;
P
=.42) or time to initial contact (median: blacks, 6.6 days; whites, 7.4 days;
P
=.42). Adjusted analyses also indicated a similarity between the racial groups in the number of inpatient PT/OT days overall or as a proportion of the hospital stay.

Conclusions
Elderly black and white stroke patients who have Medicare coverage have similar patterns of use of inpatient PT/OT services.
Parallel Antioxidant and Antiexcitotoxic Therapy Improves Outcome After Incomplete Global Cerebral Ischemia in Dogs
Authors: Davis Steve , Helfaer Mark A. , Traystman Richard J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
We have previously shown that incomplete global cerebral ischemia complicated by dense acidosis produces a profound secondary deterioration of energy metabolism and cerebral blood flow. Antioxidant treatment only partially averts this deterioration, suggesting that parallel or sequential mechanisms are involved in cerebral ischemic injury. We tested the hypothesis that a novel competitive
N
-methyl-
d
-aspartate (NMDA) receptor antagonist GPI 3000 (GPI) ameliorates metabolic injury and that the effectiveness of the iron-chelator and antioxidant deferoxamine (DFO) is augmented by combined therapy with GPI after incomplete global cerebral ischemia.

Methods
Anesthetized dogs were treated with 30 minutes of global incomplete cerebral ischemia. Preischemic plasma glucose was raised to approximately 500 mg/dL to exaggerate lactic acidosis. Brain ATP, phosphocreatine, and pH
i
were measured by
31
P MR spectroscopy for 180 minutes of reperfusion. Neurophysiological outcomes were assessed by evoked potential monitoring. Five groups were treated with either saline; 75 mg/kg DFO preischemia plus 75 mg/kg at reperfusion onset, followed by 27.5 mg/kg per hour for the remainder of reperfusion (DFO group); 25 mg/kg GPI pretreatment, followed by 5 mg/kg per hour (GPI-pre group); 25 mg/kg GPI at reperfusion, followed by 5 mg/kg per hour (GPI-post group); or DFO and GPI-pre at the same doses (Combined group).

Results
Ischemic cerebral blood flow (microspheres: 5 to 8 mL/min per 100 g) was similar among the groups. End-ischemic pH
i
was also similar: 5.9 in saline, 6.1 in DFO, 6.2 in GPI-pre, 6.2 in
C
ombined, and 6.1 in GPI-post groups. Progressive hypoperfusion was observed in all groups except
C
ombined during reperfusion. Metabolic recovery was improved relative to saline in all drug-treated groups. Phosphocreatine recovery was improved in
C
ombined compared with DFO and GPI-pre groups. Somatosensory evoked potential recovery was not observed in the saline group and incomplete in all treatment groups. At 60 and 90 minutes of reperfusion, DFO, GPI-pre, and
C
ombined groups demonstrated improved recovery relative to the saline group.

Conclusions
Pretreatment and posttreatment with GPI ameliorated postischemic metabolic failure, suggesting that NMDA-mediated mechanisms are more important in global cerebral ischemia complicated by dense acidosis than early studies indicated.
C
ombined treatment with GPI and DFO improved cerebral blood flow during reperfusion and one indicator of energy recovery. These data support the hypothesis that parallel therapy aimed at antioxidant and antiexcitotoxic mechanisms of ischemic brain injury augment recovery compared with the individual agents.
Large Cerebral Infarction During Praziquantel Therapy in Neurocysticercosis
Authors: Bang Oh Young , Heo Ji Hoe , Choi Sun Ah , Kim Dong Ik
Published: June 2011

Background
Large cerebral infarction is a rare complication of neurocysticercosis. Endarteritis by inflammation of the leptomeninges is known to be its cause.

Case Description
A 59-year-old man with known neurocysticercosis developed a large cerebral infarction during praziquantel therapy. A follow-up MRI obtained immediately after his cerebral infarction demonstrated notable decrease in the size of the cysts and more prominent enhancement around the peripheral margins of the cysts and the major vessels in comparison with the initial MRI. Cerebral angiography disclosed occlusions and narrowing of both internal carotid arteries at the supraclinoid portions, where multiple cysts were found on the MRI.

Conclusions
Findings in our patient strongly suggest that a secondary inflammation reaction caused by the destruction of the cysts might have enhanced the process of endarteritis. The possible deleterious effects of praziquantel therapy should be considered in the treatment of patients with subarachnoid cysticerci.
Effect of Age, Birth Cohort, and Period of Death on Cerebrovascular Mortality in Spain, 1952 Through 1991
Authors: Medrano M.J. , Lopez-Abente G. , Barrado M.J. , Pollan M. , Almazan J.
Published: June 2011

Background and Purpose
The continued decrease in cerebrovascular disease in Spain remains unexplained. Age-period-cohort analysis enables description of birth cohort and period-of-death components. This study sought to describe these effects on the decline of stroke mortality in Spain.

Methods
Deaths due to cerebrovascular diseases in the period from 1952 through 1991 and the corresponding population figures were grouped into 11 age groups and 8 5-year periods, from which age-specific mortality rates for 18 birth cohorts were then computed. These were plotted for graphical presentation purposes and fitted to Poisson regression models to assess age, period, and cohort effects.

Results
An exponential age effect was present for both sexes regardless of cohort or period. A definite downward period effect was observable from 1962 to 1991, except for a sharp fall and peak in the periods 1967 to 1971 and 1972 to 1976, respectively, which was possibly ascribable to changes in diagnostic and coding practices. Age- and period-adjusted stroke mortality increased for earlier cohorts and decreased for generations born between 1892 and 1940. For post-1940 generations, there was an increasing risk of stroke mortality.

Conclusions
The results suggest that a decrease in incidence coupled with an increase in survival may account for the observed decline in stroke mortality, but further studies on the Spanish population are needed to assess these findings. Although not yet definitive, there are signs of an increase in incidence among the more recent generations. If the decreasing period effect fails to offset this increase, future years may see a deceleration in the current decline in stroke mortality.
A 15.5-Year Follow-up Study of Stroke in a Japanese Provincial City
Authors: Nakayama Takeo , Date Chigusa , Yokoyama Tetsuji , Yoshiike Nobuo , Yamaguchi Momoko , Tanaka Heizo
Published: June 2011

Background and Purpose
Change toward Western lifestyles, particularly during the high economic growth period (approximately 1960 to 1975), dynamically altered stroke frequency and the distribution of risk factors in the Japanese. We reexamined their association after this environmental change by a cohort study.

Methods
The cohort (2302 subjects) comprised residents aged 40 years or older of the Akadani-Ijimino district in Shibata City, Niigata Prefecture, Japan, who were followed up from 1977 for 15.5 years.

Results
Crude incidence rates per 1000 person-years for all strokes were 5.22 for men and 4.36 for women (3.02 and 2.18 for cerebral infarction, 0.65 and 1.06 for intracerebral hemorrhage, and 0.41 and 0.34 for subarachnoid hemorrhage, respectively). Multivariate analyses performed with the Cox proportional hazard model revealed these risk factors to be independently significant: for cerebral infarction in men, age, blood pressure, atrial fibrillation, albuminuria, funduscopic abnormality, and current smoking; for cerebral infarction in women, age, atrial fibrillation, and history of ischemic heart disease; for intracerebral hemorrhage in men, age and funduscopic abnormality; for intracerebral hemorrhage in women, age, blood pressure, and light physical activity; for all strokes in men, age, blood pressure, atrial fibrillation, albuminuria, funduscopic abnormality, current smoking, and heavy physical activity; and for all strokes in women, age, atrial fibrillation, and light physical activity.

Conclusions
Most traditional risk factors, including blood pressure and its related organ diseases, were confirmed, but serum total cholesterol had almost no effect. Physical activity had both negative and positive effects on stroke risk. In these findings, however, some differences related to sex were also observed.
Focal Expression of Intercellular Adhesion Molecule-1 in the Human Carotid Bifurcation
Authors: Endres Matthias , Laufs Ulrich , Merz Hartmut , Kaps Manfred
Published: June 2011

Background and Purpose
In the carotid bifurcation, atherosclerotic plaques usually develop in the outer wall of the internal carotid artery. The aim of this study was to analyze the expression of the cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the carotid bifurcation. These molecules play a role in inflammatory cell recruitment and atherosclerosis.

Methods
We examined the expression of ICAM-1, VCAM-1, and E-selectin in 22 human carotid bifurcation specimens by means of immunohistochemistry. Double immunostaining was performed with antibodies against CD-3, CD-31, CD-68, and α-smooth muscle actin combined with each of the cell adhesion molecule antibodies. In situ hybridization for ICAM-1 was performed in selected specimens.

Results
A profound focal expression of ICAM-1 in the outer wall of the internal carotid artery could be demonstrated (86% of all specimens). This focal expression could be shown in histologically normal appearing bifurcations of young adults. ICAM-1 was expressed by subsets of macrophages and smooth muscle cells and by endothelial cells. VCAM-1 and E-selectin showed no focal expression and were not found in normal carotids. In advanced plaques all three adhesion molecules—ICAM-1, VCAM-1, and E-selectin—were expressed.

Conclusions
We were able to demonstrate a focal expression of ICAM-1 in the outer lateral wall of the internal carotid artery, which is a high-risk region for the development of atherosclerotic lesions.
High-Density Lipoprotein Cholesterol and Risk of Ischemic Stroke Mortality
Authors: Tanne David , Yaari Shlomit , Goldbourt Uri
Published: June 2011

Background and Purpose
While there is overwhelming evidence relating low levels of HDL cholesterol (HDL-C) with coronary heart disease, the association with cerebrovascular disease is not clear. The aim of the present report was to assess the association between HDL-C levels and ischemic stroke mortality obtained from a long-term follow-up in the Israeli Ischemic Heart Disease Study.

Methods
The subjects of this report are 8586 men, tenured civil servants and municipal employees, aged 42 years or older at the time of HDL-C measurements in 1965. They were followed up for mortality for 21 years. Death due to cerebrovascular disease included the
International Classification of Disease, 9th Revision
, codes 430 to 438, of which presumed ischemic stroke included codes 433 to 438.

Results
During the 21-year follow-up, 295 men died from cerebrovascular events, of which 241 deaths were due to presumed ischemic stroke. Individuals subsequently experiencing a fatal ischemic stroke had a marginally lower age-adjusted mean HDL-C (1.05 mmol/L) and a significantly lower (
P
<.001) age-adjusted mean percentage of serum cholesterol contained in the HDL fraction (%HDL) (19.3%) than counterparts surviving the follow-up period (1.06 mmol/L and 20.6%, respectively). Decreasing age-adjusted rates of ischemic stroke mortality were observed with increasing %HDL: 14.6, 14.0, and 11.8 per 10 000 person-years in the low, middle, and upper tertiles of %HDL, respectively. In multivariate analysis, a low concentration of HDL-C appeared to be significantly predictive of ischemic stroke mortality. The relative risk associated with a 5% decrease of %HDL was 1.18 (95% confidence interval, 1.03 to 1.34). Men at the lower tertile of HDL-C levels experienced a 1.32-fold increase of covariate-adjusted ischemic stroke mortality risk compared with counterparts at the upper tertile.

Conclusions
In this prospective study of middle-aged and elderly men from a healthy, working population, we have demonstrated an independent negative association between HDL-C and ischemic stroke mortality during a long-term (21-year) follow-up.
Differences in Pain Medication Use in Stroke Patients With Aphasia and Without Aphasia
Authors: Kehayia Eva , Korner-Bitensky Nicol , Singer Fanny , Becker Rubin , Lamarche Micheline , Georges Pamela , Retik Sidney
Published: June 2011

Background and Purpose
While individuals with stroke are known to experience pain for a variety of reasons including premorbid conditions and stroke-specific sequelae, there are some groups of individuals with stroke, who because of aphasia, are unable to express their pain. This study investigated whether there exists an association between severity of aphasia and overall pain medication use as indicated (1) by the proportion of individuals medicated according to aphasia severity and (2) by the dosage of pain medication used according to aphasia severity.

Methods
The study involved a retrospective chart review of 207 charts of patients with stroke admitted to the Jewish Rehabilitation Hospital (JRH), Laval, Canada. Patients were classified into three groups according to level of expressive aphasia: those without aphasia, those with mild-to-moderate aphasia, and those severe aphasia. Information on medications used primarily for pain management was elicited for the first 21 days and the last 5 days of hospitalization. Any substitution, increase, elimination, or addition of pain medication during hospitalization was also monitored.

Results and Conclusions
While the findings indicate that pain medication prescriptions were similar for all patients, a significantly smaller number of individuals with aphasia received
pro re nata
(prn) “as required” pain medication when compared with those without aphasia, for the first 21 days and for the last 5 days of hospitalization at the JRH. Similarly, when daily dose was monitored for the same time periods, individuals with aphasia were found to have received less medication for pain than those without aphasia.
Patients’ Awareness of Stroke Signs, Symptoms, and Risk Factors
Authors: Kothari Rashmi , Sauerbeck Laura , Jauch Edward , Broderick Joseph , Brott Thomas , Khoury Jane , Liu Tiepu
Published: June 2011

Background and Purpose
We sought to determine knowledge at the time of symptom onset regarding the signs, symptoms, and risk factors of stroke in patients presenting to the emergency department with potential stroke.

Methods
Patients admitted from the emergency department with possible stroke were identified prospectively. A standardized, structured interview with open-ended questions was performed within 48 hours of symptom onset to assess patients’ knowledge base concerning stroke signs, symptoms, and risk factors.

Results
Of the 174 eligible patients, 163 patients were able to respond to the interview questions. Of these 163 patients, 39% (63) did not know a single sign or symptom of stroke. Unilateral weakness (26%) and numbness (22%) were the most frequently noted symptoms. Patients aged ≥65 years were less likely to know a sign or symptom of stroke than those aged <65 years (percentage not knowing a single sign or symptom, 47% versus 28%,
P
=.016). Similarly, 43% of patients did not know a single risk factor for stroke. The elderly were less likely to know a risk factor than their younger counterparts.

Conclusions
Almost 40% of patients admitted with a possible stroke did not know the signs, symptoms, or risk factor of a stroke. Further public education is needed to increase awareness of the warning signs and risk factors of stroke.
Are Proxy Assessments of Health Status After Stroke With the EuroQol Questionnaire Feasible, Accurate, and Unbiased?
Authors: Dorman Paul J. , Waddell Fiona , Slattery Jim , Dennis Martin , Sandercock Peter
Published: June 2011

Background and Purpose
It is often difficult to determine the health-related quality of life (HRQoL) of stroke patients because physical and cognitive problems limit their ability to complete complex questionnaires. A proxy, such as a family member or caregiver, may be able to give an estimate of the patients’ health status. We therefore examined the agreement between the HRQoL as assessed by a series of patients and that assessed by their proxies.

Methods
We studied the validity of the EuroQol in a series of 152 patients from our prospective registry of patients with first (or recurrent) stroke. We asked patients to ensure that a friend or relative (a proxy) who knew them well was available at the time of the interview. We asked each proxy to complete a EuroQol questionnaire independently on behalf of the patient.

Results
Proxies completed forms for 130 patients (86%). Agreement between responses from the patients and those from their proxies was better for patients who were able to self-complete the EuroQol than for patients who required the EuroQol to be administered by interview. For both groups, agreement was best for the self-care domain and worst for the domain that assessed psychological outcome. For the more severely affected patients, agreement was only fair for the pain and social functioning domains and no better than chance alone for the psychological functioning domain (κ=0.05, 95% confidence interval, 0 to 0.43). Patients tended to rate their own health status as better than their proxies did (
P
<.05).

Conclusions
We found moderate agreement between responses from patients and those from their proxies for the more directly observable domains of the EuroQol. Proxy agreement was less good for the more subjective domains. In health surveys, allowing responses by a proxy increases response rate. However, the disadvantages inherent in the use of proxy responses must be considered carefully. In general, some domains of HRQoL information obtained from a proxy may be sufficiently valid and unbiased to be useable in most types of trials and surveys.
Cerebral Angiography Practices at US Teaching Hospitals
Authors: Chaturvedi Seemant , Policherla Prasad N. , Femino Lorraine
Published: June 2011

Background and Purpose
Although several clinical trials of carotid endarterectomy (CE) have been carried out in the last decade, the methods for angiographic measurement of carotid stenosis have not been standardized. How one measures carotid stenosis may affect the applicability of clinical trial results. We sought to obtain information on cerebral angiography practices at teaching hospitals in the United States.

Methods
We surveyed hospitals with an accredited radiology residency program.

Results
Of the 200 radiology program directors who were sent the survey, 97 responded. The angiographic complication rate was known in 68 of 97 medical centers and averaged 0.6%. The most common method being used for measurement of carotid stenosis is the NASCET method (70%). Forty-two of 97 program directors reported a decrease in the volume of angiography being performed. Of these 42, one third reported that CE was commonly being performed on the basis of noninvasive tests alone.

Conclusions
The angiographic complication rate at American teaching hospitals is within the “acceptable” range. The NASCET method of stenosis measurement is the most popular among academic radiologists. The volume of cerebral angiography appears to be decreasing. How these data compare with community hospitals without an accredited radiology residency program warrants further study.
Familial History of Stroke and Stroke Risk
Authors: Liao Duanping , Myers Richard , Hunt Steven , Shahar Eyal , Paton Catherine , Burke Gregory , Province Michael , Heiss Gerardo
Published: June 2011

Background and Purpose
Although familial history of stroke is generally perceived to be an important marker of stroke risk, very few epidemiological studies have been published to address this hypothesis. We sought to examine whether familial history of stroke is associated with the prevalence of stroke in the Family Heart Study, a National Heart, Lung, and Blood Institute–supported multicenter study of the familial, genetic, and nongenetic determinants of cardiovascular disease in populations.

Methods
The personal and familial histories of stroke were assessed in 3168 individuals (probands) who were at least 45 years old and 29 325 of their first-degree relatives with the use of a standardized questionnaire.

Results
The age-, ethnicity-, and sex-adjusted stroke prevalences were 4.8%, 4.9%, and 3.9% in probands with a positive familial, paternal, and maternal history of stroke, respectively, in comparison with 2.0% in probands without any positive familial history (
P
<.01). The age-, ethnicity-, and sex-adjusted odds ratios (95% confidence interval) of stroke were 2.00 (1.13, 3.54) for a positive paternal and 1.41 (0.80, 2.50) for a positive maternal history of stroke. Additional statistical adjustment for the proband’s history of elevated cholesterol level, cigarette smoking status, history of coronary heart disease, hypertension, and diabetes did not alter the associations. A similar pattern was seen for African Americans and European Americans.

Conclusions
The increased risk of stroke among persons with a positive familial history of stroke compared with those without a familial history of stroke is consistent with the expression of genetic susceptibility, a shared environment, or both in the etiology of stroke.
Carotid Atherosclerosis in Men With Low Levels of HDL Cholesterol
Authors: Wilt Timothy J. , Rubins Hanna B. , Robins Sander J. , Riley Ward A. , Collins Dorothea , Elam Marshall , Rutan Gale , Anderson James W.
Published: June 2011

Background and Purpose
A low HDL cholesterol (HDL-C) frequently occurs in conjunction with a desirable LDL cholesterol (LDL-C) and is a risk factor for coronary heart disease (CHD). Additionally, the presence of carotid atherosclerosis is a strong and independent predictor of morbidity and mortality in patients with CHD. This article describes the prevalence and correlates of sonographically detected carotid atherosclerosis in men with low levels of HDL-C and CHD but without elevated levels of LDL-C or total cholesterol.

Methods
High-resolution B-mode ultrasonography was used to quantify intima-media wall thickness (IMT) in the common and internal carotid arteries and at the carotid artery bifurcation in 202 randomly selected male veterans with CHD and low levels of HDL-C who are participating in the VA HDL Intervention Trial. Ultrasonographic measurement of carotid artery wall stiffness was determined in a subset of 94 of these individuals.

Results
The mean maximum and single greatest carotid artery IMT measurements were 1.41 and 2.58 mm, respectively. The prevalence of ultrasound-detected carotid atherosclerosis as defined by a mean maximum IMT ≥1.3 mm was 58.9% and by single maximum IMT ≥1.5 mm was 87.1%. IMT was associated with increased age, lower extremity arterial disease, systolic blood pressure, and ultrasonographically measured carotid artery stiffness.

Conclusions
Men with low levels of HDL-C and CHD but without elevated LDL-C or total cholesterol have a very high prevalence of ultrasound-detected carotid artery atherosclerosis.
Endothelin in Cerebrospinal Fluid and Plasma of Patients in the Early Stage of Ischemic Stroke
Authors: Lampl Yair , Fleminger Gideon , Gilad Ronit , Galron Ronit , Sarova-Pinhas Ida , Sokolovsky Mordechai
Published: June 2011

Background and Purpose
Endothelin 1 (ET-1), a highly potent endogenous vasoactive peptide, exerts a sustained vasoconstrictive effect on cerebral vessels. Elevation of ET-1 in plasma has been reported 1 to 3 days after ischemic stroke. Since we assumed that a much faster and more intense response may be observed in the cerebrospinal fluid (CSF) and since an increase in concentration of ET-1 in the CSF may cause constriction of cerebral vessels and eventually influence the neurological outcome, we measured ET-1 values in the CSF within 18 hours of stroke onset and compared the values with those in the plasma.

Methods
Twenty-six consecutive patients with acute stroke were clinically evaluated according to the modified Matthew Scale and underwent two repeat CT scans. Within 5 to 18 hours of stroke onset, lumbar puncture and blood samples were concomitantly obtained and tested; ET-1 levels in CSF and plasma of these patients were analyzed by radioimmunoassay and compared with the levels of a control group of patients with no neurological disease.

Results
The mean CSF concentration of ET-1 in the CSF of stroke patients was 16.06±4.9 pg/mL, compared with 5.51±1.47 pg/mL in the control group (
P
<.001). It was significantly higher in cortical infarcts (mean, 17.7±4.1 pg/mL) than in subcortical lesions (mean, 10.77±4.1 pg/mL) (
P
<.001) and significantly correlated with the volume of the lesion (
P
=.003). The correlation between ET-1 levels in the CSF and the Matthew Scale score was less significant (
P
=.05). Plasma ET-1 level was not elevated in any group.

Conclusions
ET-1 is found to be significantly elevated in the CSF of stroke patients during the 18 hours after stroke. No elevation was demonstrated in plasma at this time period. ET-1 may be used as an additional indicator of ischemic vascular events in the early diagnosis of stroke. The dissimilarity between the CSF and plasma ET-1 concentrations may lead also to an hypothesis that there is a vasoconstrictive effect on the cerebral vessels or a neuronal effect caused by ET-1 in the mechanism of the progression of brain ischemia.