bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Study of Aspirin Use and Risk of Stroke in Women
Authors: Iso Hiroyasu , Hennekens Charles H. , Stampfer Meir J. , Rexrode Kathryn M. , Colditz Graham A. , Speizer Frank E. , Willett Walter C. , Manson JoAnn E.
Published: June 2011

Background and Purpose
—In secondary prevention, aspirin reduces risk of ischemic stroke. In primary prevention of stroke, however, the role of aspirin is uncertain, especially in women.

Methods
—In 1980, 79 319 women in the Nurses’ Health Study cohort, 34 to 59 years of age and free of diagnosed cardiovascular disease, cancer, and rheumatoid arthritis, completed questionnaires that included information on aspirin use. Data on aspirin use were updated in 1982, 1984, and 1988. By 1994, after 994 231 person-years of follow-up, 503 incident strokes (295 ischemic strokes, 100 subarachnoid hemorrhages, 52 intraparenchymal hemorrhages, and 56 strokes of undetermined type) were documented.

Results
—There was no clear relationship between aspirin use and risk of total stroke; risk was slightly reduced among women who took 1 to 6 aspirin per week and slightly increased among women who took 7 or more aspirin per week. Women who took 1 to 6 aspirin per week had a lower risk of large-artery occlusive infarction compared with women who reported no aspirin use; after simultaneous adjustment for other cardiovascular risk factors and selected nutrients, the multivariate relative risk was 0.50 (95% CI 0.29 to 0.85,
P
=0.01). Women who took 15 or more aspirin per week had an excess risk of subarachnoid hemorrhage; the multivariate relative risk was 2.02 (95% CI 1.04 to 3.91,
P
for trend=0.02). The reduction in large-artery occlusive infarction with aspirin was of greater magnitude for older, hypertensive, or smoking women than for younger, nonhypertensive, or nonsmoking women; the elevation in subarachnoid hemorrhage with aspirin was also more apparent for older or hypertensive women than for younger or nonhypertensive women. Aspirin use was not associated with risk of other subtypes of stroke.

Conclusions
—These prospective data indicate that women who take 1 to 6 aspirin per week have a reduced risk of large-artery occlusive infarction, but those who use 15 or more aspirin per week have an increased risk of subarachnoid hemorrhage. This observational study suggests benefits of aspirin for ischemic stroke with low frequency of use and hazards for hemorrhagic stroke with high frequency of use, particularly among older or hypertensive women. Thus, the effect on total stroke will depend on the dose of aspirin and the distribution of stroke subtypes and risk factors in the population.
Validation of a Standardized Assessment of Postural Control in Stroke Patients
Authors: Benaim Charles , Pérennou Dominique Alain , Villy Jacqueline , Rousseaux Marc , Pelissier Jacques Yvon
Published: June 2011

Background and Purpose
—Few clinical tools available for assessment of postural abilities are specifically designed for stroke patients. Most have major floor or ceiling effects, and their metrological properties are not always completely known.

Methods
—The Postural Assessment Scale for Stroke patients (PASS), adapted from the BL Motor Assessment, was elaborated in concordance with 3 main ideas: (1) the ability to maintain a given posture and to ensure equilibrium in changing position both must be assessed; (2) the scale should be applicable for all patients, even those with very poor postural performance; and (3) it should contain items with increasing difficulty. This new scale has been validated in 70 patients tested on the 30th and 90th days after stroke onset.

Results
—Normative data obtained in 30 age-matched healthy subjects are presented. The PASS meets the following requirements: (1) good construct validity: high correlation with concomitant Functional Independence Measure (FIM) scores (
r
=0.73,
P
=10
−6
), with lower-limb motricity scores (
r
=0.78,
P
<10
−6
), and with an instrumental measure of postural stabilization (
r
=0.48,
P
<10
−2
); (2) excellent predictive validity: high correlation between PASS scores on the 30th day and FIM scores on the 90th day (
r
=0.75,
P
<10
−6
); (3) high internal consistency (Cronbach α-coefficient=0.95); and (4) high interrater and test-retest reliabilities (average κ=0.88 and 0.72).

Conclusions
—Our results confirm that the PASS is one of the most valid and reliable clinical assessments of postural control in stroke patients during the first 3 months after stroke.
Poststroke Depression Correlates With Cognitive Impairment and Neurological Deficits
Authors: Kauhanen M.-L. , Korpelainen J. T. , Hiltunen P. , Brusin E. , Mononen H. , Määttä R. , Nieminen P. , Sotaniemi K. A. , Myllylä V. V.
Published: June 2011

Background and Purpose
—The prevalence of poststroke depression is known to be high, but the knowledge of its neuropsychological correlates is limited. This 12-month prospective study was designed to evaluate the natural history of poststroke depression and to study its neuropsychological, clinical, and functional associates.

Methods
—We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65.8 years) with acute first-ever ischemic stroke. The patients underwent a neurological, psychiatric, and neuropsychological examination at 3 and 12 months after the stroke. The psychiatric diagnosis of depression was based on DSM-III-R-criteria.

Results
—Depression was diagnosed in 53% of the patients at 3 months and in 42% of the patients at 12 months after the stroke. The prevalence of major depression was 9% at 3 months and 16% at 12 months. There was an association between poststroke depression and cognitive impairment; the domains most likely to be defective in stroke-related depression were memory (
P
=0.022), nonverbal problem solving (
P
=0.039), and attention and psychomotor speed (
P
=0.020). The presence of dysphasia increased the risk of major depression. The depressive patients were more dependent in ADL and had more severe impairment and handicap than the nondepressive patients.

Conclusions
—More than half of the patients suffer from depression after stroke, and the frequency of major depression seems to increase during the first year. In addition to dysphasia, poststroke depression is correlated with other cognitive deficits. We emphasize the importance of psychiatric evaluation of stroke patients.
Mutations in the
COL5A1
Coding Sequence Are Not Common in Patients With Spontaneous Cervical Artery Dissections
Authors: Grond-Ginsbach Caspar , Weber Ralf , Haas Juergen , Orberk Erdem , Kunz Stefanie , Busse Otto , Hausser Ingrid , Brandt Tobias , Wildemann Brigitte
Published: June 2011

Background and Purpose
—The dermal connective tissue of most patients with spontaneous cervical artery dissections (sCAD) contains abnormal collagen fibers. This suggests a predisposing connective tissue defect. The ultrastructural abnormalities in the skin of patients with sCAD have similarity with the morphological alterations in patients with Ehlers-Danlos syndrome type II, a dominant hereditary disorder that has been correlated in some patients to mutations within the genes encoding type V collagen. The aim of this study was to assess the alpha 1 chain of type V collagen (
COL5A1
) as a candidate gene for sCAD.

Methods
—We searched for mutations in the
COL5A1
gene in cDNA from cultured fibroblasts of 19 patients with sCAD using single-strand conformational polymorphism analysis and nucleotide sequence analysis of polymerase chain reaction–amplified fragments of the whole
COL5A1
coding sequence.

Results
—We detected 1 missense mutation leading to a predicted amino acid (192D/N) substitution within the N-terminal propeptide in 2 siblings. All other patients showed regular
COL5A1
sequences with some silent polymorphisms.

Conclusions
—Mutations in the
COL5A1
gene do not appear to be a major factor in the etiology of sCAD.
Inflammatory Responses in the Cerebral Cortex After Ischemia in the P7 Neonatal Rat
Authors: Benjelloun N. , Renolleau S. , Represa A. , Ben-Ari Y. , Charriaut-Marlangue C.
Published: June 2011

Background and Purpose
—The contribution of inflammatory response to the pathogenesis of ischemic lesions in the neonate is still uncertain. This study described the chronological sequence of inflammatory changes that follow cerebral ischemia with reperfusion in the neonatal P7 rat.

Methods
—P7 rats underwent left middle cerebral artery electrocoagulation associated with 1-hour left common carotid artery occlusion. The spatiotemporal pattern of cellular responses was characterized immunocytochemically with the use of antibodies against rat endogenous immunoglobulins to visualize the area of the breakdown of the blood-brain barrier. Infiltration of neutrophils and T lymphocytes was demonstrated by antibodies against myeloperoxidase and a pan-T cell marker, respectively. Antibodies ED1 and OX-42 were applied to identify microglial cells and macrophages. The response of astrocytes was shown with antibodies against glial fibrillary acidic protein. Cell survival was assessed by Bcl-2 expression. Cell death was demonstrated by DNA fragmentation with the use of the terminal deoxynucleotidyl transferase–mediated dUTP biotin nick end labeling (TUNEL) assay and Bax immunodetection.

Results
—Endogenous immunoglobulin extravasation through the blood-brain barrier occurred at 2 hours of recirculation and persisted until 1 month after ischemia. Neutrophil infiltration began at 24 hours and peaked at 72 to 96 hours (30±3.4 neutrophils per 0.3 mm
2
;
P
<0.0001), then disappeared at 14 days after ischemia. T cells were observed between 24 and 96 hours of reperfusion. Resident microglia-macrophages exhibited morphological remnants and expressed the cell death inhibitor Bcl-2 at 24 hours of recirculation. They became numerous within the next 48 hours and peaked at 7 days after ischemia. Phenotypic changes of resident astrocytes were apparent at 24 hours, and they proliferated between 48 hours and 7 days after ischemia. Progressively inflammatory cells showed DNA fragmentation and the cell death activator Bax expression. Cell elimination continued until there was a complete disappearance of the frontoparietal cortex.

Conclusions
—These data demonstrate that perinatal ischemia with reperfusion triggers acute inflammatory responses with granulocytic cell infiltration, which may be involved in accelerating the destructive processes.
Effects of
S
-Nitrosoglutathione on Acute Vasoconstriction and Glutamate Release After Subarachnoid Hemorrhage
Authors: Sehba Fatima A. , Ding Wan Hong , Chereshnev Igor , Bederson Joshua B.
Published: June 2011

Background and Purpose
—Subarachnoid hemorrhage (SAH) causes acute vasoconstriction that contributes to ischemic brain injury shortly after the initial bleed. It has been theorized that decreased availability of nitric oxide (NO) may contribute to acute vasoconstriction. Therefore we examined the effect of the NO donor
N
-nitroso glutathione (GSNO) on acute vasoconstriction and early ischemic glutamate release after experimental SAH.

Methods
—SAH was induced by the endovascular suture method in anesthetized rats. GSNO (1 μmol/L/kg, n=31) or saline (n=21) was injected 5 minutes after SAH. Sham-operated rats received GSNO (1 μmol/L/kg, n=5) 5 minutes after sham surgery. Arterial and intracranial pressures, cerebral blood flow (CBF), and extracellular glutamate release were measured serially for 60 minutes after SAH. SAH size was determined, and vascular measurements were made histologically.

Results
—GSNO had no effect on resting blood pressure, intracranial pressure, cerebral perfusion pressure, or CBF in sham-operated animals. However, administration of GSNO after SAH was associated with significantly increased CBF (161.6±26.6% versus saline 37.1±5.5%, 60 minutes after SAH,
P
<0.05), increased blood vessel diameter (internal carotid artery [ICA] 285.0±16.5 μm versus saline 149.2±14.1 μm,
P
<0.01), decreased vessel wall thickness (ICA12.9±0.7 μm versus saline 25.1±1.6 μm,
P
<0.01), and decreased extracellular glutamate levels (3315.6±1048.3% versus saline469.7±134.3%,
P
<0.05). Blood pressure decreased transiently, whereas intracranial pressure, cerebral perfusion pressure, and SAH size were not affected.

Conclusions
—These results suggest that GSNO can reverse acute vasoconstriction and prevent ischemic brain injury after SAH. This further implies that acute vasoconstriction contributes significantly to ischemic brain injury after SAH and is mediated in part by decreased availability of NO.
Endovascular Treatment of Ruptured Posterior Circulation Cerebral Aneurysms
Authors: Lempert Todd E. , Malek Adel M. , Halbach Van V. , Phatouros Constantine C. , Meyers Philip M. , Dowd Christopher F. , Higashida Randall T.
Published: June 2011

Background and Purpose
—We sought to describe the clinical outcome and angiographic results obtained in the endovascular therapy of ruptured posterior circulation cerebral aneurysms using Guglielmi detachable coils (GDC) over a 7-year period.

Methods
—A retrospective analysis was performed of 112 patients evaluated at the University of California at San Francisco Medical Center between June 1991 and August 1998. The Hunt-Hess grade at presentation of treated patients was I in 26 patients (24%), II in 24 (22%), III in 27 (25%), IV in 24 (22%), and V in 8 (7%). Clinical follow-up for the total population was achieved in 104 of 109 patients (96%), with a mean duration of 13.1 months. Angiographic follow-up for the subset excluding parent vessel occlusion cases was obtained in 93% of cases, with a mean duration of 7.2 months.

Results
—Technical success, defined as the ability to catheterize and embolize the aneurysm with GDC, was achieved in 109 of 112 of cases (97%). The mean angiographic occlusion rate, or projected area of the aneurysm occluded by the coils, for all 110 successfully treated aneurysms was 94.6%. At latest clinical follow-up, 81 of 109 patients (74%) achieved good recovery with Glasgow Outcome Scale (GOS) score of I, 10 of 109 (9%) were moderately (GOS II) and 5 of 109 (5%) were severely (GOS III) disabled, 1 of 109 (1%) remained in a vegetative state (GOS IV), and 12 of 109 (11%) were dead. Of the subset of 77 patients with Hunt-Hess grades I to III, 68 (88%) achieved a good clinical outcome (GOS I). A statistically significant correlation was demonstrated between Hunt-Hess grade at presentation and final GOS outcome score (χ
2
=41.4,
P
<0.0005). Procedure-related permanent morbidity was 2.8% (3/109 patients). Repeated hemorrhage was observed in a single patient (0.9%) with a partially treated aneurysm.

Conclusions
—The observed favorable outcome and low morbidity in this group of high-risk patients point to GDC embolization as an effective method for the endovascular management of patients with ruptured posterior circulation aneurysms.
Rate of Stroke Recurrence in Patients With Primary Intracerebral Hemorrhage
Authors: Hill Michael D. , Silver Frank L. , Austin Peter C. , Tu Jack V.
Published: June 2011

Background and Purpose
—Primary intracerebral hemorrhage (PICH) is a devastating illness with high early mortality. Hypertension is a major risk factor both for ischemic cerebrovascular disease and for intracranial hemorrhage. Survivors of PICH are at risk for both recurrent hemorrhage and ischemic cerebrovascular disease. We sought to determine the rate of recurrence of ICH or cerebral ischemia in a cohort of PICH patients at the Toronto Hospital, Toronto, Canada.

Methods
—A retrospective search of computerized hospital records from 1986 to 1996 for patients with a discharge diagnosis of intracerebral hemorrhage (
International Classification of Diseases, Ninth Revision–Clinical Modification
[ICD-9-CM] code 431) was conducted to identify the index cases. Charts were abstracted for demographic and clinical characteristics. CT scans, MR scans, or radiologist reports were reviewed. To determine recurrence, the database was linked to the Ontario Provincial Government Vital Statistics Registry and to the Canadian Institute for Health Information database of hospital discharge abstracts. Logistic regression analysis was used to identify predictive factors for mortality after PICH. A Cox proportional hazards model was fitted to identify predictive factors for recurrent ICH or stroke.

Results
—A total of 746 charts were identified by computer search. After abstraction, 423 index patients with PICH were identified. Of these, 27.4% died in the first 30 days of their admission. Predictors of death were age, intraventricular rupture of hemorrhage, and trilobar hemorrhage. The recurrence rate for PICH was 2.4% (95% CI 1.4% to 3.9%) per year, whereas the recurrence rate for ischemic cerebrovascular disease was 3.0% (95% CI 1.8% to 4.7%) per year. The only significant predictor of readmission for ICH was lobar location of the index hemorrhage, with a hazard ratio of 3.8 (95% CI 1.2 to 12.0).

Conclusions
—PICH has a high 30-day mortality rate. Survival from the initial insult portends a moderate risk of recurrence of 2.4% per year for PICH and 3.0% per year for ischemic cerebrovascular disease. Patients with PICH are at risk for both ischemic stroke or TIA and recurrent hemorrhage; thus, PICH may be a marker for ischemic stroke. Patients with lobar hemorrhage have a 3.8-fold increased risk of recurrent ICH.
Physical Activity and Stroke Mortality in Women
Authors: Ellekjær Hanne , Holmen Jostein , Ellekjær Erik , Vatten Lars
Published: June 2011

Background and Purpose
—Few studies have reported a protective effect of physical activity on stroke in women, particularly among elderly women. This study was conducted to examine the association between different levels of leisure-time physical activity and stroke mortality in a large prospective study of middle-aged and elderly women.

Methods
—We conducted a 10-year mortality follow-up of women aged ≥50 years, free from stroke at baseline (n=14 101), who participated in the Nord-Trøndelag Health Survey in Norway during 1984–1986. Main outcome measures were relative risk of stroke mortality according to increasing levels of physical activity, with the least active group used as reference.

Results
—In groups aged 50 to 69, 70 to 79, and 80 to 101 years, the relative risk of dying decreased with increasing physical activity, after adjustment for potentially confounding factors. In groups aged 50 to 69 and 70 to 79 years, the most active women had an adjusted relative risk of 0.42 (95% CI, 0.24 to 0.75) and 0.56 (95% CI, 0.36 to 0.88), respectively. In the group aged 80 to 101 years, there was a consistent negative association with physical activity; the adjusted relative risk for the most active was 0.57 (95% CI, 0.30 to 1.09).

Conclusions
—Physical activity was associated with reduced risk of death from stroke in middle-aged and elderly women. This association persisted after we excluded individuals with prevalent cardiovascular and cerebrovascular disease at baseline and women who died during the first 2 years of follow-up. These observations strengthen the evidence that physical activity should be part of a primary prevention strategy against stroke in women.
Color Duplex Measurement of Cerebral Blood Flow Volume in Healthy Adults
Authors: Scheel Peter , Ruge Christian , Petruch Uwe R. , Schöning Martin
Published: June 2011

Background and Purpose
—Global cerebral blood flow (CBF) is an important yet largely unknown quantity in the treatment of neurological intensive care patients. Color duplex sonography of the extracranial cerebral arteries can be used to measure global CBF volume directly at the bedside. To establish reference data on global CBF volume and to test the influence of sex and age on this parameter, a prospective study was performed in a group of 78 healthy adults aged 20 to 85 years (39 women, 39 men; mean age, 52±19 years in either sex).

Methods
—The common, external, and internal carotid arteries and the vertebral arteries were examined with the use of a 7.0-MHz transducer of a computed sonography system. Angle-corrected time-averaged flow velocity and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the circular vessel. CBF volume was determined as the sum of flow volumes in the internal carotid and vertebral arteries of both sides.

Results
—From 20 to 85 years of age, CBF volume decreased significantly (
P
≤0.0001), on average by ≈3 mL/min per year. There were no sex-linked differences in CBF volume. The mean relative contributions of the internal carotid artery and the vertebral arteries to global CBF volume remained constant with age (76% versus 24%). The reference data on CBF volume established for the groups aged 20 to 39 years, 40 to 59 years, and 60 to 85 years were 727±102, 656±121, and 603±106 mL/min, respectively.

Conclusions
—The data presented here provide additional information on the natural development of global cerebral perfusion in “benign aging.” CBF volume reference data for different age groups were also established. These data provide a basis for the clinical application of CBF volume measurements at the bedside, especially in the monitoring of CBF volume in neurological intensive care patients.
Factors Influencing the Frequency of Fluorescence Transients as Markers of Peri-Infarct Depolarizations in Focal Cerebral Ischemia
Authors: Strong A. J. , Smith S. E. , Whittington D. J. , Meldrum B. S. , Parsons A. A. , Krupinski J. , Hunter A. J. , Patel S.
Published: June 2011

Background and Purpose
—Peri-infarct depolarizations (PIDs) that occur in ischemic boundary zones of the cerebral cortex of experimental animals have been shown to promote rather than simply to indicate the evolution of the lesion and are especially prominent in the rat. To study the influence of one factor, species, on PID incidence, we compared the frequency of PIDs in a primate species, the squirrel monkey, with that in the cat after middle cerebral artery occlusion. Plasma glucose was reviewed as a possible cause of interexperiment variability in the cat experiments.

Methods
—In open-skull experiments under chloralose anesthesia, changes in cortical fluorescence believed to indicate NADH/NAD
+
redox state, as markers of PIDs, were recorded by serial imaging of the cortical surface in vivo for 4 hours after middle cerebral artery occlusion.

Results
—Fluorescence transients occurred in squirrel monkeys at a frequency (mean±SD) of 0.7±0.8 hours
−1
(n=5), which was not significantly less than in that observed in cats (1.3±1.6 hours
−1
, n=8). Data from the cat experiments indicated a relationship between number of transients (dependent) and plasma glucose, with a striking increase in PID frequency in association with values of mean postocclusion plasma glucose <4.1 mmol/L (Mann-Whitney
U
=15.0,
P
=0.034); this observation agrees well with other published findings.

Conclusions
—Transient changes in fluorescence strongly suggestive of peri-infarct depolarizations, either transient or terminal, occur and propagate in the ischemic cerebral cortex of a nonhuman primate. The results also suggest that the relationship of frequency of peri-infarct depolarizations with plasma glucose requires further examination, to confirm the finding and to determine a safe lower limit for a target range for control of plasma glucose if insulin is used in the management of patients with cerebral ischemia.
Incidence of Dementia in Relation to Stroke and the Apolipoprotein E ε4 Allele in the Very Old
Authors: Zhu Li , Fratiglioni Laura , Guo Zhenchao , Basun Hans , Corder Elizabeth Hedlund , Winblad Bengt , Viitanen Matti
Published: June 2011

Background and Purpose
—Both stroke and the apolipoprotein E (APOE) ε4 allele increase the risk of dementia. However, the interaction between stroke and APOE on dementia is still unclear. We addressed this topic by using a longitudinal design.

Methods
—We followed up a community cohort of 1301 subjects aged ≥75 years, who did not have dementia at baseline. Among them, 92 subjects had a history of stroke (from 3 months to 16 years before baseline interview). After the 3-year follow-up, 224 dementia cases had been diagnosed. During the period of follow-up, 91 subjects had a first occurrence of stroke (incident stroke). The APOE genotype was known for 985 subjects. Cox proportional hazards regression models were constructed to estimate the risk for dementia in terms of relative risks (RRs) for stroke and the APOE ε4 allele, with adjustment for age, sex, education, systolic blood pressure, antihypertensive medication use, and heart disease.

Results
—In the entire study population, RRs for dementia related to history of stroke and incident stroke were 1.7 (95% CI, 1.1 to 2.6) and 2.4 (95% CI, 1.6 to 3.5), respectively, after adjustment for all potential confounders. Subjects with stroke that occurred within 3 years before baseline had RR of 2.4 (95% CI, 1.4 to 4.2), whereas those with stroke occurring >3 years before baseline had RR of dementia of 1.1 (95% CI, 0.6 to 2.3). Among those with APOE information, individuals with only history of stroke (that occurred within 3 years before baseline) had RR of 3.1 (95% CI, 1.4 to 6.6), individuals with only the APOE ε4 allele had RR of 1.7 (95% CI, 1.1 to 2.5), and individuals with both factors had RR of 5.3 (95% CI, 2.1 to 13.4). The corresponding figures when incident stroke was examined instead of history of stroke were 2.3 (95% CI, 1.3 to 4.1), 1.7 (95% CI, 1.1 to 2.4), and 4.6 (95% CI, 2.0 to 10.6), respectively. The RR of interaction term for history of stroke and APOE ε4 was 1.1 (95% CI, 0.3 to 3.8;
P
=0.8). The corresponding figure was 1.2 (95% CI, 0.4 to 4.4;
P
=0.7) for incident stroke and APOE ε4. Furthermore, the RRs of dementia without any stroke and dementia with stroke in relation to APOE ε4 were 1.6 (95% CI, 1.1 to 2.3) and 1.2 (95% CI, 0.6 to 2.4), respectively. In addition, the APOE ε4 allele was not significantly related to the occurrence of stroke (RR=0.8; 95% CI, 0.5 to 1.5).

Conclusions
—A relatively fresh stroke is a risk factor for dementia. APOE ε4 increases the risk of dementia without stroke but not dementia with stroke. Our data do not support a multiplicative effect of stroke and the APOE ε4 allele on the risk of dementia. However, both factors seem to have an additive effect on the risk of dementia. The APOE ε4 allele does not increase the risk of stroke in this Swedish elderly population.
North Carolina Stroke Prevention and Treatment Facilities Survey
Authors: Goldstein Larry B. , Hey Lloyd A. , Laney Ronnie
Published: June 2011

Background/Purpose
—The aim of this study was to determine the statewide availability of facilities and programs for stroke prevention and treatment to identify underserved regions and target educational efforts.

Methods
—A single-page survey was mailed to the directors of each inpatient medical facility in North Carolina. Data collected included the availability of selected diagnostic tests, programs, and services. Facilities were categorized as providing basic (emergency department, brain CT, treatment with rtPA, transthoracic echocardiography, carotid ultrasonography, cerebral angiography, carotid endarterectomy) or advanced (basic services plus brain MRI, MR angiography, transesophageal echocardiography, transcranial Doppler ultrasonography, interventional radiology) services. The availability of other programs and services, including having a neurologist on staff, organized anticoagulation clinics, inpatient rehabilitative services, diffusion-weighted MRI, community awareness and rapid stroke identification programs, stroke teams, stroke acute care units or an equivalent, and the use of stroke-care maps, were also determined.

Results
—Complete responses were obtained from all of the state’s 125 inpatient medical facilities. Overall, 97% of the state’s population resided in counties with a hospital providing at least some stroke prevention or treatment procedures or services. Full basic services were provided by 23 facilities located in 19 of the state’s 100 counties and were available to 52% of the state’s population based on county of residence; advanced services were provided by 8 facilities located in 7 counties and were available to 26% of the state’s population based on county of residence. Stroke-care maps were used in 83% of basic or advanced centers versus 23% of other hospitals (
P
<0.001), stroke teams were organized in 48% versus 12% (
P
=0.001), stroke units or equivalents were available in 61% versus 9% (
P
<0.001), rapid patient identification programs were in place in 57% versus 9% (
P
<0.001), and community awareness programs were in place in 57% versus 21% (
P
=0.005).

Conclusions
—Only 52% of the state’s population reside in counties with hospitals providing full basic services; by expanding these services to only 6 additional facilities and thereby encompassing the state’s 50 most populous counties, this proportion would be increased to 84%. Services that may improve outcomes and reduce costs (eg, stroke teams, stroke units, care maps) are not widely used, even in centers with full basic capabilities. Targeting educational efforts to these centers could improve the overall level of stroke care for the majority of the state’s population. The study serves as a model that can be applied to other states and regions.
Elective Stenting of Symptomatic Basilar Artery Stenosis
Authors: Gomez Camilo R. , Misra Vijay K. , Liu Ming W. , Wadlington Van R. , Terry John B. , Tulyapronchote Roekchai , Campbell Morgan S.
Published: June 2011

Background and Purpose
—Percutaneous angioplasty of the intracranial arteries still carries the risk of dissection, with acute closure and embolization. Stenting has been shown to improve the safety and durability of angioplasty in every circulatory bed in which it has been applied. However, stenting of the intracranial arteries has been limited by the availability of stents that can be reliably deployed intracranially.

Methods
—Twelve patients underwent elective stenting of the basilar artery after episodes of vertebrobasilar ischemia. In all patients, either medical therapy had failed or the patient had a contraindication for long-term anticoagulation. Information from independent neurological examinations, quantitative angiography, and clinical follow-up was collected. Differences between pretreatment and posttreatment degree of stenoses were subjected to 1-way ANOVA for repeated measures.

Results
—There were 10 men and 2 women, all white, aged 40 to 82 years (mean age, 62.6 years). Stent placement was successful in all patients, leading to statistically significant changes in the degree of stenosis, from 71.4% (range, 53% to 90%) to 10.3% (range, 0% to 36%) (
P
<0.0001). There were no deaths, stent thromboses, perforations, ruptures, or myocardial infarctions. Clinical follow-up was available for 0.5 to 16 months (mean, 5.9 months). One patient had nonspecific symptoms, and another had a transient ischemic attack. All other patients remained asymptomatic.

Conclusions
—Elective stenting of the basilar artery is feasible, with minimal risk to the patient. Its impact on long-term stroke prevention and its durability are unknown and will require further study.
Intake of Flavonoids, Carotenoids, Vitamins C and E, and Risk of Stroke in Male Smokers
Authors: Hirvonen Tero , Virtamo Jarmo , Korhonen Pasi , Albanes Demetrius , Pietinen Pirjo
Published: June 2011

Background and Purpose
—Antioxidants may protect against atherosclerosis and thus prevent cerebrovascular disease. We studied the association between dietary antioxidants and subtypes of stroke.

Methods
—The study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases were identified through national registers.

Results
—During a 6.1-year follow-up, 736 cerebral infarctions, 83 subarachnoid hemorrhages, and 95 intracerebral hemorrhages occurred. Neither dietary flavonols and flavones nor vitamin E were associated with risk for stroke. The dietary intake of β-carotene was inversely associated with the risk for cerebral infarction (relative risk [RR] of highest versus lowest quartile 0.74, 95% CI 0.60 to 0.91), lutein plus zeaxanthin with risk for subarachnoid hemorrhage (RR 0.47, 95% CI 0.24 to 0.93), and lycopene with risks of cerebral infarction (RR 0.74, 95% CI 0.59 to 0.92) and intracerebral hemorrhage (RR 0.45, 95% CI 0.24 to 0.86). Vitamin C intake was inversely associated with the risk for intracerebral hemorrhage (RR 0.39, 95% CI 0.21 to 0.74). After simultaneous modeling of the antioxidants, a significant association remained only between β-carotene intake and risk for cerebral infarction (RR 0.77, 95% CI 0.61 to 0.99).

Conclusions
—Dietary intake of β-carotene was inversely associated with the risk for cerebral infarction. No association was detected between other dietary antioxidants and risk for stroke.
Carotid Artery Intima-Media Thickness Measured by Ultrasonography in Normal Clinical Practice Correlates Well With Atherosclerosis Risk Factors
Authors: Baldassarre Damiano , Amato Mauro , Bondioli Alighiero , Sirtori Cesare R. , Tremoli Elena
Published: June 2011

Background and Purpose
—The intima-media thickness (IMT) of extracranial carotid arteries determined by B-mode ultrasound is a measurable index of the presence of atherosclerosis. The ultrasonographic scan protocol and the scan reading techniques used until now to measure IMT are, however, time consuming and require the participation of specialized research centers. In this study we present a cross-sectional study of 963 patients attending the Enrica Grossi Paoletti Center in Milan, Italy, with the aim of assessing whether ultrasonographic measurements of carotid artery in routine clinical practice can yield the same results as those obtained with quantitative methods used until now in clinical trials.

Methods
—Maximum and mean maximum IMT of carotid arteries were assessed by B-mode ultrasound with the use of the electronic caliper of the machine in real time.

Results
—The intraobserver and interobserver variability of IMT of carotid arteries performed with the electronic caliper in real time was similar to that of quantitative processing of frozen images (coefficients of variation of intraobserver and interobserver mean maximum IMT measurements were 4.2% and 7.3%, respectively). Carotid artery IMT thus measured correlated with most of the known atherosclerosis risk factors and discriminated between patients with and without previous history of cardiovascular events. IMT was linearly related to the total number of vascular risk factors both in the whole group and after stratification of patients into 3 age classes.

Conclusions
—–These observations establish a strong correlation between B-mode imaging of carotid atherosclerosis evaluated in normal clinical practice and data provided by clinical trials and validate this simple reading technique as a means of identifying IMT as another possible risk factor in patients at high risk of vascular disease.
Atorvastatin Upregulates Type III Nitric Oxide Synthase in Thrombocytes, Decreases Platelet Activation, and Protects From Cerebral Ischemia in Normocholesterolemic Mice
Authors: Laufs Ulrich , Gertz Karen , Huang Paul , Nickenig Georg , Böhm Michael , Dirnagl Ulrich , Endres Matthias
Published: June 2011

Background and Purpose
—Thrombosis superimposed on atherosclerosis causes approximately two thirds of all brain infarctions. We previously demonstrated that statins protect from cerebral ischemia by upregulation of endothelial type III nitric oxide synthase (eNOS), but the downstream mechanisms have not been determined. Therefore, we investigated whether antithrombotic effects contribute to stroke protection by statins.

Methods
—129/SV wild-type and eNOS knockout mice were treated with atorvastatin for 14 days (0.5, 1, and 10 mg/kg). eNOS mRNA from aortas and platelets was measured by reverse-transcriptase polymerase chain reaction. Platelet factor 4 (PF 4) and β-thromboglobulin (β-TG) in the plasma were quantified by ELISA. Transient cerebral ischemia was induced by filamentous occlusion of the middle cerebral artery followed by reperfusion.

Results
—Stroke volume after 1-hour middle cerebral artery occlusion/23-hour reperfusion was significantly reduced by 38% in atorvastatin-treated animals (10 mg/kg) compared with controls. Serum cholesterol levels were not affected by the treatment. eNOS mRNA was significantly upregulated in a dose-dependent manner in aortas and in thrombocytes of statin-treated mice compared with controls. Moreover, indices of platelet activation in vivo, ie, plasma levels of PF 4 and β-TG, were dose-dependently downregulated in the treatment group. Surprisingly, atorvastatin-treatment did not influence PF 4 and β-TG levels in eNOS knockout mice.

Conclusions
—The synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin upregulates eNOS in thrombocytes, decreases platelet activation in vivo, and protects from cerebral ischemia in normocholesterolemic mice. Antithrombotic and stroke-protective effects of statins are mediated in part by eNOS upregulation. Our results suggest that statins may provide a novel prophylactic treatment strategy independent of serum cholesterol levels.
Cell Death After Exposure to Subarachnoid Hemolysate Correlates Inversely With Expression of CuZn–Superoxide Dismutase
Authors: Matz Paul G. , Copin Jean-Christophe , Chan Pak H.
Published: June 2011

Background and Purpose
—Subarachnoid hemolysate (SAH) has been associated with oxidative brain injury, cell death, and apoptosis. We hypothesized that over-expression of CuZn–superoxide dismutase (CuZn-SOD) would protect against injury after SAH, whereas reduction of its expression would exacerbate injury.

Methods
—Saline (n=16) or hemolysate (n=50) was injected into transgenic mice overexpressing CuZn-SOD (SOD1-Tg), CuZn-SOD heterozygous knockout mutants (SOD1+/−), and wild-type littermates (Wt). Mice were killed at 24 hours. Stress gene induction was evaluated by immunocytochemistry and Western blotting for hemeoxygenase-1 and heat shock protein 70. Apoptosis was evaluated by 3′-OH nick end-labeling and DNA gel electrophoresis. Cell death was quantified through histological assessment after cresyl violet staining.

Results
—Histological assessment demonstrated neocortical cell death in regions adjacent to the blood injection. Overall cell death was reduced 43% in SOD1-Tg mutants (n=6) compared with Wt littermates (n=6;
P
<0.02). In contrast, cell death was increased >40% in SOD1+/− mutants (n=6;
P
<0.05). Both hemeoxygenase-1 and heat shock protein 70 were induced after SAH. Apoptosis was also present after SAH, as evidenced by 3′-OH end-labeling and DNA laddering. However, the degree of stress gene induction and apoptosis did not vary between Wt, SOD1-Tg, and SOD1+/− mice.

Conclusions
—The extent of CuZn-SOD expression in the cytosol correlates with cell death after exposure to SAH in a manner separate from apoptosis. Overexpression of CuZn-SOD may potentially be an avenue for therapeutic intervention.
Is Early Ischemic Lesion Volume on Diffusion-Weighted Imaging an Independent Predictor of Stroke Outcome?
Authors: Thijs Vincent N. , Lansberg Maarten G. , Beaulieu Christian , Marks Michael P. , Moseley Michael E. , Albers Gregory W.
Published: June 2011

Background and Purpose
—The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome.

Methods
—We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score ≥85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis.

Results
—Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score ≥85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI.

Conclusions
—DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.
Depression and Other Determinants of Values Placed on Current Health State by Stroke Patients
Authors: Bosworth Hayden B. , Horner Ronnie D. , Edwards Lloyd J. , Matchar David B.
Published: June 2011

Background and Purpose
—This prospective study examined the determinants of the utility (value) placed on health status among a sample of patients with acute ischemic and intracerebral hemorrhagic stroke.

Methods
—Data were from the VA Acute Stroke (VASt) study, a nationwide prospective cohort of 1073 acute stroke patients admitted at any of 9 Department of Veterans Affairs Medical Center sites between April 1, 1995, and March 31, 1997. The primary outcome was the patient’s health status utility as measured by the time-tradeoff method. Data were obtained by telephone interviews at 1, 6, and 12 months and by medical record review. General linear mixed modeling was used to assess the effects of social, psychological, and physical factors on patients’ valuations of their current health state. The analysis was confined to the 327 patients who were able to provide self-reports at ≥2 time points.

Results
—Patients’ valuations of their health state status over the initial 12 months after stroke were very stable over time, with only a slight improvement at 6 months, followed by a slight decline at 12 months. In adjusted analyses, living alone, being institutionalized, decreased physical function, and depression were independently associated with lower levels of patient health status utility over time.

Conclusions
—Stroke patient health status utilities are relatively stable during the initial year after stroke. In addition to physical function, psychological health and social environment are important determinants of patient health status utility. These factors need to be considered when conducting stroke decision analyses if more accurate conclusions are to be drawn regarding preferred patterns of care.
Incidence and Risk Factors for Subtypes of Cerebral Infarction in a General Population
Authors: Tanizaki Yumihiro , Kiyohara Yutaka , Kato Isao , Iwamoto Hiromitsu , Nakayama Keizo , Shinohara Noriyasu , Arima Hisatomi , Tanaka Keiichi , Ibayashi Setsuro , Fujishima Masatoshi
Published: June 2011

Background and Purpose
—We estimated the incidence of first-ever cerebral infarction in regard to its subtypes and analyzed their risk factors separately in a community-based prospective cohort study in Japan.

Methods
—Stroke-free subjects (n=1621) aged ≥40 years were followed up for 32 years from 1961. During this period, 298 cerebral infarctions occurred and were divided into 167 lacunar, 62 atherothrombotic, 56 cardioembolic, and 13 undetermined subtypes of infarction on the basis of clinical information including brain imaging and autopsy findings.

Results
—The age-adjusted incidence of lacunar infarction (3.8 per 1000 person-years for men and 2.0 for women) was higher than that of atherothrombotic infarction (1.2, 0.7) and cardioembolic infarction (1.3, 0.5) in both sexes. Time-dependent Cox’s proportional hazard analysis revealed systolic blood pressure as well as age to be independent risk factors for all subtypes of cerebral infarction except for cardioembolic infarction in men. Additionally, ST depression on ECG, glucose intolerance, and smoking in men and left ventricular hypertrophy on ECG and body mass index in women remained significant risk factors for lacunar infarction. ST depression was also significantly related to events of atherothrombotic infarction in women. The risk of atrial fibrillation for cardioembolic infarction was outstandingly high in both sexes, and left ventricular hypertrophy and lower total cholesterol were additional risk factors for cardioembolic infarction in women.

Conclusions
—In this Japanese population, lacunar infarction was the most common subtype of cerebral infarction and had a greater variety of risk factors, including not only hypertension but also ECG abnormalities, diabetes, obesity, and smoking, than did atherothrombotic infarction or cardioembolic infarction.
Gender Differences in the Risk of Ischemic Stroke Associated With Aortic Atheromas
Authors: Di Tullio Marco R. , Sacco Ralph L. , Savoia Maria Teresa , Sciacca Robert R. , Homma Shunichi
Published: June 2011

Background and Purpose
—Atherosclerotic plaque of the proximal portion of the aorta is associated with an increased risk of ischemic stroke in the elderly. Different cutoffs of plaque thickness have been used in the literature for risk stratification and have been applied to both men and women. However, the assumption that the relationship between plaque thickness and stroke risk is the same in the 2 genders has not been proven. The aim of this study was to evaluate whether the prevalence of different degrees of aortic plaque thickness differed in men and women with ischemic stroke.

Methods
—We performed transesophageal echocardiography in 152 patients aged >59 years with acute ischemic stroke (76 men and 76 women) and in 152 control subjects of similar age (70 men and 82 women). Odds ratios (ORs) for ischemic stroke with 95% CIs for different plaque thickness definitions were calculated for the overall group and separately for men and women by logistic regression analysis after adjusting for age, arterial hypertension, and hypercholesterolemia.

Results
—Aortic plaques ≥4 mm were significantly more frequent in men than in women (31.5% versus 20.3%, respectively;
P
=0.025) and were associated with ischemic stroke in both men (adjusted OR 6.0, CI 2.1 to 16.8) and women (adjusted OR 3.2, CI 1.2 to 8.8). However, plaques 3 to 3.9 mm in thickness had a significant association with stroke in women (adjusted OR 4.8, CI 1.7 to 15.0) but not in men (adjusted OR 0.8, CI 0.2 to 3.0). Plaques <3 mm were not associated with a significantly increased stroke risk for either sex.

Conclusions
—Smaller aortic plaques are significantly associated with ischemic stroke in women but not in men. If the increased prevalence of smaller plaques in women is confirmed to be associated with increased risk for embolic stroke, different cutoff points may have to be adopted in men and women for risk stratification and for decisions regarding medical intervention.