bluuebunny/crossref_metadata_2025 huggingface dataset:
Gelatinase Activity and the Occurrence of Cerebral Aneurysms
Authors: Chyatte Douglas , Lewis Isabel
Published: June 2011

Background and Purpose
Cerebral aneurysms are associated with decreased arterial collagen content; however, whether this deficiency results from impaired collagen synthesis or enhanced collagen degradation is unknown. This study tested the hypothesis that enhanced collagen degradation, not impaired collagen synthesis, is associated with the occurrence of cerebral aneurysms.

Methods
Cultured skin fibroblasts and serum samples were studied in patients with angiographic evidence of aneurysm (n=31) and control subjects (n=14). Transcription of the type III collagen gene was assessed with the use of Northern blots prepared from RNA harvested from confluent cultured fibroblasts. Translation of type III collagen was assessed by Western blot analysis of proteins produced by cultured skin fibroblasts. Collagen metabolism was assessed by radioimmunoassay for type I (PICP) and type III (PIIINP) procollagen peptides in conditioned tissue culture media and serum. We assessed collagen degradation in serum and conditioned tissue culture media by evaluating gelatinase activity using quantitative zymography.

Results
Type III collagen synthesis was the same in aneurysm and control patients. Neither the molecular weight nor the relative amount of type III collagen mRNA differed between aneurysm and control patient fibroblasts. Western blot analysis revealed no difference in the relative amount or molecular weight of procollagen III synthesized by aneurysm and control cells. Aneurysm patients had a threefold increase in native serum gelatinase activity compared with control subjects (
P
=.004). This increase occurred along with serum evidence of increased collagen metabolism. Serum levels of PICP (
P
=.03) and PIIINP (
P
=.02) were decreased in aneurysm patients. Elevated serum gelatinase activity and altered collagen metabolism could not be explained by enhanced secretion of gelatinase by cultured fibroblasts or altered net collagen synthesis by fibroblasts. High serum gelatinase activity was more common in men than in women (
P
=.04).

Conclusions
These findings are consistent with the hypothesis that accelerated enzymatic degradation of collagens and other structural proteins compromises the mechanical integrity of the cerebral vessel wall and leads to conditions that favor aneurysm formation.
Duration of Diabetes and Carotid Wall Thickness
Authors: Wagenknecht Lynne E. , D’Agostino Ralph , Savage Peter J. , O’Leary Daniel H. , Saad Mohammed F. , Haffner Steven M.
Published: June 2011

Background and Purpose
Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. However, the role of the primary metabolic abnormality of diabetes (chronic hyperglycemia) in this disease process has not been fully elucidated.

Methods
A cross-sectional analysis was conducted among 489 persons with non–insulin-dependent diabetes mellitus; 299 were established diabetics (diagnosed previously) and 190 were newly diagnosed at the time of the Insulin Resistance Atherosclerosis Study (IRAS) examination. These men and women, of three different ethnic groups, were participants in IRAS. Established diabetes (versus newly diagnosed diabetes) and mean fasting glucose level were used as measures of hyperglycemic burden. Intimal-medial wall thickness (IMT) of the internal (ICA) and common (CCA) carotid arteries were used as indices of atherosclerosis.

Results
The mean duration of disease among established diabetics was 7 years. The mean CCA IMT and ICA IMT were 872 and 946 μm, respectively. Established diabetes and mean fasting glucose level were positively associated with increased CCA IMT (
P
<.05) but not ICA IMT, even after adjustment for numerous cardiovascular disease risk factors. CCA IMT was increased by 70 μm in established diabetics (versus newly diagnosed diabetics) and by 26 μm per 1 SD of fasting glucose. Among established diabetics, however, duration of known diabetes (number of years) was not significantly related to IMT.

Conclusions
Among diabetics in IRAS, established diabetes and fasting glucose level were each independently associated with CCA IMT, suggesting that chronic hyperglycemia or its associated metabolic abnormalities may lead to increased risk of atherosclerosis.
Poststroke Depression Among the Chinese Elderly in a Rural Community
Authors: Fuh Jong-Ling , Liu Hsiu-Chih , Wang Shuu-Jiun , Liu Chia-Yih , Wang Pei-Ning
Published: June 2011

Background and Purpose
A door-to-door survey was conducted in two townships in the Kinmen islets to investigate the prevalence and other characteristics related to depressive disorders of stroke survivors in an elderly Chinese population.

Methods
Our target population comprised the registered residents ≥65 years old (n=2056) of a total population of 26 105 on August 1, 1993. All participants answered a questionnaire, filled in a Geriatric Depression Scale–short form (GDS-S), and received a neurological examination. Depression was defined as a GDS-S score ≥5.

Results
Twenty-eight of 45 stroke survivors (62.2%) and 491 of 1471 nonstroke subjects (33.4%) were classified as depressed. The frequency of stroke survivors’ depressive disorders was significantly higher that of nonstroke subjects (
P
<.001). Multiple regression analysis indicated that GDS-S scores were most related with the activities of daily living (
R
2
=.19,
P
=.004) in the stroke survivors.

Conclusions
Depressed mood was common after stroke, and activities of daily living were an important factor for depression in stroke survivors in the community.
Prognostic Value of Admission Blood Pressure in Patients With Intracerebral Hemorrhage
Authors: Terayama Yasuo , Tanahashi Norio , Fukuuchi Yasuo , Gotoh Fumio
Published: June 2011

Background and Purpose
Patients with acute stroke on admission to the hospital are often found to have high blood pressure. The purpose of the present study was to investigate the prognostic value of admission blood pressure in patients with acute intracerebral hemorrhage, including putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage.

Methods
A total of 1701 patients with intracerebral hemorrhage of the putamen (n=776; mean±SD age, 58±14 years), thalamus (n=538; 63±12 years), subcortex (n=153; 61±16 years), cerebellum (n=110; 64±11 years), and pons (n=124; 59±13 years) were examined. The mean blood pressure on admission in patients with a fatal outcome was compared with that in patients who survived.

Results
The mean age in each patient group (putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage) with fatal outcome was older than that with nonfatal outcome, while ANCOVA indicated no correlation between age and blood pressure on admission or age and volume of hematoma. The mean arterial blood pressure on hospital admission was 126.9±25.8 mm Hg (±SD) in cases of putaminal, 127.4±22.6 mm Hg in thalamic, 116.4±20.6 mm Hg in subcortical, 123.5±23.9 mm Hg in cerebellar, and 133.0±26.0 mm Hg in pontine hemorrhage. The mean blood pressure on admission in patients with a fatal outcome among those with putaminal (136.0±36.3 mm Hg) and thalamic (133.2±22.1 mm Hg) hemorrhage was significantly higher than that in those with a nonfatal outcome (123.8±20.6 mm Hg for putaminal, 101.6±22.5 mm Hg for thalamic) (
P
<.01). No correlation between mean blood pressure and outcome was observed in the patients with subcortical (116.5±22.2 mm Hg for nonfatal, 114.9±22.0 mm Hg for fatal outcome), cerebellar (125.2±22.2 mm Hg, 116.9±28.8 mm Hg), and pontine (129.9±23.8 mm Hg, 136.0±27.7 mm Hg) hemorrhage. The volume of hematoma on admission in patients with fatal outcome with putaminal (58.2±24.4 mL), thalamic (27.0±13.1 mL), subcortical (32.9±14.4 mL), and cerebellar (31.4±28.6 mL) hemorrhage was greater than that in those with nonfatal outcome (20.8±11.4 mL, 7.1±4.8 mL, 18.3±10.6 mL, and 8.1±4.2 mL, respectively;
P
<.01), while no correlation between volume of hematoma and outcome was observed in patients with pontine hemorrhage.

Conclusions
The above data suggest that an increased mean blood pressure and volume of hematoma on admission in putaminal and thalamic hemorrhage were related to increased mortality, while in patients with subcortical, cerebellar, and pontine hemorrhage, the mean blood pressure was not related to the clinical outcome.
Intercenter Agreement in Reading Doppler Embolic Signals
Authors: Markus Hugh S. , Ackerstaff Rob , Babikian Viken , Bladin Chris , Droste Dirk , Grosset Donald , Levi Chris , Russell David , Siebler Mario , Tegeler Charles
Published: June 2011

Background and Purpose
Different frequencies of asymptomatic Doppler embolic signals have been reported in studies. There has been concern that different criteria for identification may account for some of this variation. A previous reproducibility study between two centers found good agreement, but no studies among large numbers of centers have been performed. We performed an international reproducibility study among nine centers, each of which had published recent studies of embolic signal detection in peer-reviewed journals.

Methods
Each center performed blinded analysis of a taped audio Doppler signal composed of transcranial Doppler middle cerebral artery recordings from 6 patients with symptomatic carotid artery stenosis. The exact time of any embolic signal was recorded. Six centers also measured the intensity increase of any embolic signals detected. Interobserver agreement was determined by a method based on the proportion of specific agreement.

Results
Seven centers reported between 39 and 55 signals, but one center reported 142 embolic signals. The probability of agreement between observers was .678, which rose to .791 when the data from the highest reporting center were excluded. Introducing a decibel threshold resulted in a significant increase in the probability of agreement; a decibel threshold of >7 dB resulted in a probability of agreement of .902. Intensity measurements made by different centers were usually highly correlated, but this was not always the case, and 3 of the 15 correlations were not significant. The absolute values of the intensities measured varied between centers by as much as 40%.

Conclusions
Although most centers report similar numbers of embolic signals, some use less specific criteria and report more events. The use of a decibel threshold improves reproducibility. However, intensity thresholds developed by one center cannot be directly transferred without validation to another center; differing methods of measurement are being used, and this results in different intensity values for the same embolic signals, even when the same equipment is used.
Assessment of the Efficacy of Noninvasive Screening for Patients With Asymptomatic Neck Bruits
Authors: Obuchowski Nancy A. , Modic Michael T. , Magdinec Michele , Masaryk Thomas J.
Published: June 2011

Background and Purpose
Several recent clinical trials have shown that endarterectomy is efficacious in patients with asymptomatic carotid artery stenosis. The purpose of this study was to evaluate the effectiveness of various test strategies for screening and diagnosing carotid artery disease.

Methods
We constructed a model of the natural history of carotid artery disease using literature-based estimates of the prevalence and incidence of carotid artery stenosis and associated morbidity and mortality. Markov cohort simulation was used to estimate the mean quality-adjusted life years and monetary costs associated with various management strategies.

Results
Screening is cost-effective in the baseline model. Key parameters affecting the efficacy of screening are prevalence of operable lesions, benefit of surgery, surgical complication rates, quality of life with stroke, rate of stenosis progression, and excess morbidity and mortality.

Conclusions
Asymptomatic patients with carotid bruits may benefit from screening if the prevalence rate is ≥20%, the benefits and risks associated with surgery are similar to those observed in the Asymptomatic Carotid Atherosclerosis Study, and the quality of life with stroke is considerably lower than the quality of life without stroke. Ultrasound followed by three-dimensional time-of-flight MR angiography, if indicated, is a promising test strategy.
Alterations in Glia and Axons in the Brains of Binswanger’s Disease Patients
Authors: Akiguchi Ichiro , Tomimoto Hidekazu , Suenaga Toshihiko , Wakita Hideaki , Budka Herbert
Published: June 2011

Background and Purpose
Although increasing attention is being paid to Binswanger’s disease, a form of vascular dementia characterized by diffuse white matter lesions, only limited information is available on the pathological changes that occur in the glia and axons in the white matter. We therefore investigated the brains of patients with Binswanger’s disease to gain further insight into its pathophysiology.

Methods
Autopsied brains from patients with Binswanger’s disease (group 3; n=17) were compared with those of non-neurological controls (group 1; n=5) and controls with large cortical infarcts but without significant white matter lesions (group 2; n=5). Glial fibrillary acidic protein (GFAP) was used as an immunohistochemical marker for astroglia, leukocyte common antigen (LCA) was used as a marker for microglia, and HLA-DR was used as a marker for activated microglia. Axonal damage was assessed by the accumulation of proteins, which are transported by fast axonal flow, amyloid protein precursor (APP), synaptophysin, and chromogranin A.

Results
Although there was no difference in numerical density of GFAP-immunoreactive astroglia in each group, regressive astroglia were observed in 7 of 17 patients with Binswanger’s disease. LCA-immunoreactive microglia were 1.7 times more numerous in Binswanger’s disease than in group 1 (
P
<.05). HLA-DR–immunoreactive–activated microglia were 3.4 times and 2.1 times more numerous in Binswanger’s disease as compared with group 1 (
P
<.01) and group 2 (
P
<.05), respectively. There was frequent perivascular lymphocyte cuffing, and clusters of macrophages with a decreased number of oligodendroglia were observed in the rarefied white matter. The grading scores for the number of axons immunoreactive for either APP, synaptophysin, or chromogranin A were significantly higher in Binswanger’s disease than in group 1 or 2.

Conclusions
The pathological alterations in Binswanger’s diseased brains include regressive changes in the astroglia and activation of the microglia with a decrease in the oligodendroglia, which were associated with the degradation of both myelin and axonal components. These results indicate that an inflammatory reaction and compromised axonal transport, mediated by chronic ischemia, may play an important role in the pathophysiology of Binswanger’s disease.
Cerebral Blood Flow in Single and Multiple Lacunar Infarctions
Authors: Mochizuki Yoko , Oishi Minoru , Takasu Toshiaki
Published: June 2011

Background and Purpose
Single and multiple lacunar infarctions may have some difference in underlying diseases and cerebral blood flows. To determine the difference, we investigated underlying diseases and cerebral blood flows in single and multiple lacunar infarctions.

Methods
Fifteen cases of lacunar infarction, 10 cases of multiple lacunar infarctions, and 16 control subjects were studied. Regional cerebral blood flow was measured within 14 days after stroke onset with the stable xenon CT method.

Results
The rate of association of diabetes mellitus was higher in the multiple lacunar infarctions group than in the single lacunar infarction group. The blood flow in the cerebral cortex was significantly lower in the multiple lacunar infarctions group than in the single lacunar infarction group. The blood flow change by acetazolamide in the cerebral cortex was significantly lower in the multiple lacunar infarctions group than in the single lacunar infarction group.

Conclusions
There is some difference in underlying diseases and cerebral blood flows between single and multiple lacunar infarctions.
Mitral Valve Strands and the Risk of Ischemic Stroke in Elderly Patients
Authors: Cohen Ariel , Tzourio Christophe , Chauvel Christophe , Bertrand Bernard , Crassard Isabelle , Bernard Yvette , Goullard Luc , Falcon Sylvie , Bousser Marie-Germaine , Amarenco Pierre
Published: June 2011

Background and Purpose
Strands are thin and filamentous attachments on the cardiac valves shown by transesophageal echocardiography. Their nature and their potential for embolization are largely unknown. The objective was to estimate the risk of brain infarction in patients with mitral valve strands.

Methods
Using transesophageal echocardiography, we compared the frequency of strands on native mitral valves in 284 consecutive patients admitted with brain infarction and 276 control patients, all older than 60 years. In a second part, case subjects were followed up over a 2- to 4-year period, and the risk of recurrence of brain infarction was estimated in patients with and without strands.

Results
In the case-control study, mitral valve strands were found in 22.5% of the case patients and in 12.1% of the control subjects. In case subjects, mitral valve strands were more frequent in those with mitral valve dystrophy (52.4% versus 37.4%;
P
=.03). Strands were not associated with mitral valve prolapse, annular calcifications, or left atrial spontaneous echocardiographic contrast. After adjustment for age, sex, and mitral valve dystrophy, the odds ratio for ischemic stroke among patients with mitral strands was 2.2 (95% confidence interval, 1.4 to 3.6;
P
=.005). The frequency of strands was not different in patients with a known cause of brain infarction (24.4%) from that in patients with no other apparent cause (20.9%). During 646 per 100 person-years of follow-up, the incidence of recurrent brain infarction was 6.0 person-years in patients with strands and 4.2 in those without. In the Cox analysis, including potential confounders and poststroke treatment, mitral valve strands did not appear as independent predictors of recurrent brain infarction (relative risk, 1.3; 95% confidence interval, 0.5 to 3.0;
P
=.54).

Conclusions
The present study shows an independent association between mitral valve strands and the risk of brain infarction. However, the lack of an increased relative risk of recurrence raises doubts about the potential causal relation with brain infarction in patients aged 60 years or older.
Dose-Response Relationship Between Prevalence of Cerebrovascular Disease and Ingested Inorganic Arsenic
Authors: Chiou Hung-Yi , Huang Wei-I , Su Che-Long , Chang Shu-Feng , Hsu Yi-Hsiang , Chen Chien-Jen
Published: June 2011

Background and Purpose
Circulatory diseases such as ischemic heart disease and peripheral vascular disease induced by long-term arsenic exposure have been well documented in previous studies, but the dose-response relationship between cerebrovascular disease and ingested inorganic arsenic remains to be elucidated. The prevalence of cerebrovascular disease among residents of the Lanyang Basin on the northeast coast of Taiwan was surveyed to examine its association with exposure to arsenic in well water.

Methods
A total of 8102 men and women from 3901 households were recruited in this study. The status of cerebrovascular disease of study subjects was identified through home-visit personal interviews and ascertained by review of hospital medical records according to the World Health Organization criteria. Information on consumption of well water, sociodemographic characteristics, cigarette smoking, and alcohol consumption habits, as well as personal and family history of diseases, was also obtained. Arsenic concentration in the well water of each household was determined by hydride generation and atomic absorption spectrometry. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals for various risk factors of cerebrovascular disease.

Results
A significant dose-response relationship was observed between arsenic concentration in well water and prevalence of cerebrovascular disease after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, and alcohol consumption. The biological gradient was even more prominent for cerebral infarction, showing multivariate-adjusted odds ratios of 1.0, 3.4, 4.5, and 6.9, respectively, for those who consumed well water with an arsenic content of 0, 0.1 to 50.0, 50.1 to 299.9, and >300 μg/L.

Conclusions
Long-term exposure to inorganic arsenic from well water was associated with an increased prevalence of cerebrovascular disease, especially cerebral infarction.
Overexpression of CuZn-Superoxide Dismutase Reduces Hippocampal Injury After Global Ischemia in Transgenic Mice
Authors: Murakami Kensuke , Kondo Takeo , Epstein Charles J. , Chan Pak H.
Published: June 2011

Background and Purpose
The role of copper, zinc-superoxide dismutase (CuZn-SOD) in hippocampal injury after transient global ischemia was studied using transgenic (Tg) mice and wild-type littermates.

Methods
Global ischemia was induced by bilateral common carotid artery occlusion. The hemisphere with the hypoplastic posterior communicating artery was determined and then the hippocampus in this hemisphere was evaluated qualitatively using a score of 0 to 4 and quantitatively using an image analyzer.

Results
Hippocampal injury was reduced in Tg mice after both 5 and 10 minutes of ischemia. In the 5-minute ischemia group, the mean score of the injury was significantly lower in Tg than nontransgenic (nTg) mice at 3 days. In the 10-minute group, the hippocampal injury was reduced more in Tg than nTg mice at 1 day. Quantitative evaluation by an image analyzer confirmed the qualitative data. Neurons with fragmented DNA were also studied in the hippocampal injury. In the 5-minute group, despite the reduction of the injury in Tg mice, their neurons with fragmented DNA were relatively increased at 1 day. In the 10-minute group, this ratio was almost the same in both nTg and Tg mice.

Conclusions
CuZn-SOD plays a protective role in the pathogenesis of selective hippocampal injury after brief ischemia, whether the insult is relatively mild or intense. Furthermore, CuZn-SOD may reduce both necrotic and DNA fragmented neuronal death after global ischemia.
Long-term Prognosis After a Minor Stroke
Authors: Prencipe Massimiliano , Culasso Franco , Rasura Maurizia , Anzini Alexia , Beccia Mario , Cao Marina , Giubilei Franco , Fieschi Cesare
Published: June 2011

Background and Purpose
—Determinants of long-term outcome are not well defined in minor stroke patients. This study aims to evaluate which factors are independent long-term predictors of death and major stroke recurrence in a cohort of minor ischemic strokes.

Methods
—A cohort of 322 patients with first-ever minor ischemic strokes (mean age, 55 years; 89% were treated with antiplatelet or anticoagulant drugs) with minor (Rankin score=2) or no disability (Rankin score <2) were followed for 10 years, with only 6% lost to follow-up. Death and major stroke recurrence rates were evaluated by Kaplan-Meier analysis. Hazard ratios and 95% confidence intervals (CI) of factors with
P
<.1 at the log-rank test were evaluated by multivariate Cox analysis.

Results
—The 10-year mortality rate was 32%, with a relative risk of 1.7 (95% CI, 1.4 to 2.1) compared with the age- and sex-matched general population. The 10-year recurrence rate of major strokes was 14%. The hazard ratio (95% CI) of death was 1.1 (1.05 to 1.09) for age (1-year increments), 3.4 (2.2 to 5.2) for minor disability, 1.8 (1.1 to 3.1) for myocardial infarction (MI), 2.0 (1.1 to 3.7) for nonvalvular atrial fibrillation, and 1.8 (1.2 to 2.7) for hypercholesterolemia. The hazard ratio (95% CI) of major stroke recurrence was 2.8 (1.3 to 6.2) for recurrent minor strokes, 3.1 (1.9 to 4.6) for nonlacunar stroke, 2.9 (1.3 to 6.8) for MI, and 3.0 (1.4 to 6.4) for hypertension.

Conclusions
—In minor ischemic strokes, age, minor disability, MI, nonvalvular atrial fibrillation, and hypercholesterolemia increase the risk of death; recurrent minor strokes, nonlacunar stroke, MI, and hypertension increase the risk of major stroke.
Gender-Linked Brain Injury in Experimental Stroke
Authors: Alkayed Nabil J. , Harukuni Izumi , Kimes Alane S. , London Edythe D. , Traystman Richard J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
—Premenopausal women are at lower risk than men for stroke, but the comparative vulnerability to tissue injury once a cerebrovascular incident occurs is unknown. We hypothesized that female rats sustain less brain damage than males during experimental focal ischemia and that the gender difference in ischemic outcome can be eliminated by ovariectomy.

Methods
—Age-matched male (M), intact female (F), and ovariectomized female (O; plasma estradiol: 4.1±1.6 pg/mL compared with 7.4±1.5 in F and 4.0±1.1 in M) rats from two different strains, normotensive Wistar and stroke-prone spontaneously hypertensive rats, were subjected to 2 hours of intraluminal middle cerebral artery occlusion, followed by 22 hours of reperfusion. Cerebral blood flow (CBF) was monitored throughout the ischemic period by laser-Doppler flowmetry. Infarction volume in the cerebral cortex (Ctx) and caudoputamen (CP) was determined by 2,3,5-triphenyltetrazolium chloride staining. In a separate cohort of M, F, and O Wistar rats, absolute rates of regional CBF were measured at the end of the ischemic period by quantitative autoradiography using [
14
C]iodoantipyrine.

Results
—F rats of either strain had a smaller infarct size in Ctx and CP and a higher laser-Doppler flow during ischemia compared with respective M and O rats. Mean end-ischemic CBF was higher in F compared with M and O rats in CP, but not in Ctx. Cerebrocortical tissue volume with end-ischemic CBF <10 mL/100 g/min was smaller in F than M rats, but not different from O rats.

Conclusions
—We conclude that endogenous estrogen improves stroke outcome during vascular occlusion by exerting both neuroprotective and flow-preserving effects.
Apoptosis of Medial Smooth Muscle Cells in the Development of Saccular Cerebral Aneurysms in Rats
Authors: Kondo Soichiro , Hashimoto Nobuo , Kikuchi Haruhiko , Hazama Fumitada , Nagata Izumi , Kataoka Hideo
Published: June 2011

Background and Purpose
—Using an animal model, we examined the role of apoptosis in the disappearance of medial smooth muscle cells (SMCs) during the development and growth of cerebral aneurysms.

Methods
—Various degrees of cerebral aneurysms were induced in the right anterior cerebral artery–olfactory artery bifurcations in 65 Sprague-Dawley rats with ligation of the left common carotid artery and renal hypertension. We performed in situ end labeling of fragmented DNA with the lesions in 45 rats and electron microscopic study in the other 20 rats.

Results
—With in situ end labeling of fragmented DNA, 4±3 apoptotic medial SMCs were detected in 35 of the 45 bifurcations. Apoptotic SMCs appeared in the medial layer in the “preaneurysm” group, the site speculated to show an aneurysmal change in the near future (6±3), and in the media in the “early aneurysm” group, which showed characteristics such as a small depression (5±3). In the “progressive aneurysm” group, they appeared more frequently at the aneurysmal neck (3±2) than the dome (1±1). By electron microscopic study, shrunken medial SMCs exhibiting morphological apoptotic changes such as chromatin condensation and fragmentation of the cytoplasm and nucleus were observed in the preaneurysm and early aneurysm groups and at the neck portion in the progressive aneurysm group. In the aneurysmal dome, SMCs showed late characteristics of apoptosis such as more advanced nuclear and cytoplasmic condensation and formation of apoptotic bodies.

Conclusions
—The present findings indicate that there is an association between apoptosis of medial SMCs and the formation of saccular cerebral aneurysms.
Prevalence and Risk of Rupture of Intracranial Aneurysms
Authors: Rinkel Gabriel J. E. , Djibuti Mamuka , Algra Ale , van Gijn J.
Published: June 2011

Background and Purpose
—The estimates on the prevalence and the risk of rupture of intracranial saccular aneurysms vary widely between studies. We conducted a systematic review on prevalence and risk of rupture of intracranial aneurysms and classified the data according to study design, study population, and aneurysm characteristics.

Methods
—We searched for studies published between 1955 and 1996 by means of a MEDLINE search and a cumulative review of the reference lists of all relevant publications. Two authors independently assessed eligibility of all studies and extracted data on study design and on numbers and characteristics of patients and aneurysms.

Results
—For data on prevalence we found 23 studies, totalling 56 304 patients; 6685 (12%) of these patients were from 15 angiography studies. Prevalence was 0.4% (95% confidence interval, 0.4% to 0.5%) in retrospective autopsy studies, 3.6% (3.1 to 4.1) for prospective autopsy studies, 3.7% (3.0 to 4.4) in retrospective angiography studies, and 6.0% (5.3 to 6.8) in prospective angiography studies. For adults without specific risk factors, the prevalence was 2.3% (1.7 to 3.1); it tended to increase with age. The prevalence was higher in patients with autosomal dominant polycystic kidney disease (relative risk [RR], 4.4 [2.7 to 7.2]), a familial predisposition (RR, 4.0 [2.7 to 6.0]), or atherosclerosis (RR, 2.3 [1.7 to 3.1]). Only 8% (5 to 11) of the aneurysms were >10 mm. For the risk of rupture, we found nine studies, totalling 3907 patient-years. The overall risk per year was 1.9% (1.5 to 2.4); for aneurysms =10 mm, the annual risk was 0.7% (0.5 to 1.0). The risk was higher in women (RR, 2.1[1.1 to 3.9]) and for aneurysms that were symptomatic (RR, 8.3 [4.0 to 17]), >10 mm (RR, 5.5 [3.3 to 9.4]), or in the posterior circulation (RR, 4.1 [1.5 to 11]).

Conclusions
—Data on prevalence and risk of rupture vary considerably according to study design, study population, and aneurysm characteristics. If all available evidence with inherent overestimation and underestimation is taken together, for adults without risk factors for subarachnoid hemorrhage, aneurysms are found in approximately 2%. The vast majority of these aneurysms are small (=10 mm) and have an annual risk of rupture of approximately 0.7%.
Clinical Determinants of Poststroke Dementia
Authors: Pohjasvaara Tarja , Erkinjuntti Timo , Ylikoski R. , Hietanen M. , Vataja Risto , Kaste Markku
Published: June 2011

Background and Purpose
—Frequency of poststroke dementia is high, and stroke considerably increases the risk of dementia. The risk factors for dementia related to stroke are still incompletely understood. We sought to examine clinical determinants of poststroke dementia in a large well-defined stroke cohort.

Methods
—The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischemic stroke completed a comprehensive neuropsychological test battery and MRI, including structured medical, neurological, and laboratory evaluations; clinical mental status examination; interview of a knowledgeable informant; detailed history of risk factors; and evaluation of stroke type, localization, and syndrome. The DSM-III definition for dementia was used.

Results
—Frequency of any poststroke dementia was 31.8% (107/337), that of stroke-related dementia (mixed Alzheimer’s disease plus vascular dementia excluded) was 28.4% (87/306), and that of dementia after first-ever stroke was 28.9% (79/273). The patients with poststroke dementia were older and more often had a low level of education, history of prior cerebrovascular disease and stroke, left hemispheric stroke (reflecting laterality), major dominant stroke syndrome (reflecting laterality and size), dysphasia, gait impairment, and urinary incontinence. The demented patients were also more frequently current smokers, had lower arterial blood pressure values, and more frequently had an orthostatic reaction compared with the nondemented stroke patients. The correlates of dementia in logistic regression analysis were dysphasia (odds ratio [OR], 5.6), major dominant stroke syndrome (OR, 5.0), history of prior cerebrovascular disease (OR, 2.0), and low educational level (OR, 1.1). When we excluded those with cerebrovascular disease plus Alzheimer’s disease or those with recurrent stroke, the order of correlates remained the same. When the patients with dysphasia (n=30) were excluded, the correlates were major dominant syndrome (OR, 4.6) and low educational level (OR, 1.1).

Conclusions
—Our data suggest that a single explanation for poststroke dementia is not adequate; rather, multiple factors including stroke features (dysphasia, major dominant stroke syndrome), host characteristics (educational level), and prior cerebrovascular disease each independently contribute to the risk.
Effects of High Atmospheric Pressure and Oxygen on Middle Cerebral Blood Flow Velocity in Humans Measured by Transcranial Doppler
Authors: Omae Tsuyoshi , Ibayashi Setsuro , Kusuda Kenji , Nakamura Hidefumi , Yagi Hiroshi , Fujishima Masatoshi
Published: June 2011

Background and Purpose
—There are several reports that have studied the effects of hyperbaric oxygen (HBO) on cerebral blood flow (CBF). However, most of the reports have been of animal experiments, and human studies are few so far. The aim of this study is to clarify the relationship between HBO and CBF in humans.

Methods
—Middle cerebral arterial blood flow velocity (MCV) was measured using transcranial Doppler (TCD) technique in a multiplace hyperbaric chamber. The Doppler probe was fixed on the temporal region by a head belt, and the transcutaneous gas measurement apparatus (tcP
o
2
and tcP
co
2
) was fixed on the chest wall. MCV and transcutaneous gas were measured continuously in eight healthy volunteers under four various conditions: 1 atmosphere absolute (ATA) air, 1 ATA oxygen (O
2
), 2 ATA air, and 2 ATA O
2
. On the next step, the effect of environmental pressure was studied in another eight healthy volunteers, in whom the tcPo
2
was kept at almost the same level under conditions of both 1 ATA and 4 ATA by inhaling oxygen at 1 ATA.

Results
—MCV of 1 ATA O
2
, 2 ATA air, and 2 ATA O
2
decreased, and tcP
o
2
increased significantly in comparison with that of 1 ATA air. A significant difference in MCV was observed between the O
2
group and the air group under the same pressure circumstance. On the other hand, there were no differences in MCV or tcP
o
2
between 4 ATA air and 1 ATA plus O
2
, and the influence for the MCV of the environmental pressure was not observed.

Conclusions
—We conclude that hyperoxemia caused by HBO reduces the CBF, but the high atmospheric pressure per se does not influence the CBF in humans.
The Geographic Variation in Stroke Incidence in Two Areas of the Southeastern Stroke Belt
Authors: Lackland Daniel T. , Bachman David L. , Carter Timothy D. , Barker Derek L. , Timms Stephen , Kohli Harvinder
Published: June 2011

Background and Purpose
—South Carolina and the southeastern United States have maintained the highest stroke mortality in the country. The Anderson and Pee Dee Stroke Study is an assessment of cerebrovascular disease incidence in 2 geographically defined communities in the stroke belt.

Methods
—Strokes were identified in the Anderson and Pee Dee areas of South Carolina. All hospitalized and out-of-hospital deaths occurring during 1990 among the residents of these 2 areas were included. Strokes were classified by an independent panel of neurologists using a standard protocol that included specific criteria for stroke and subtypes.

Results
—The overall age-adjusted stroke incidence rates (per 100 000 population) were significantly higher in the Pee Dee population (293.1) compared with Anderson (211.2). The geographic differences were more dramatic in the younger age groups of 35 to 64 years. Likewise, incidence rates for blacks were nearly twice the rates for whites. The rates in the Pee Dee were higher than the rates from other studies in the United States and other parts of the world. Although the stroke subtypes did not vary between the 2 regions, race-sex differences were identified.

Conclusions
—High stroke incidence and disease rates persist for all 4 race-sex groups in the Southeast and reflect similar risks as mortality rates. However, geographic variability in stroke rates suggests that the pattern of disease in the region is not so much a “belt” of increased stroke in contiguous areas but rather more a “necklace” of different levels of risk. These results should be useful in the identification of factors associated with this geographic enigma.
Diffusion MR Imaging During Acute Subarachnoid Hemorrhage in Rats
Authors: Busch Elmar , Beaulieu Christian , de Crespigny Alex , Moseley Michael E.
Published: June 2011

Background and Purpose
—We analyzed the temporal and spatial pattern of water diffusion changes during acute subarachnoid hemorrhage (SAH) in rat brain to identify factors contributing to the acute pathophysiology of SAH.

Methods
—Subarachnoid hemorrhage was remotely induced via perforation of the circle of Willis with an endovascular suture during MR imaging. A fast echo-planar imaging technique was used to acquire 60 maps of the apparent diffusion coefficient (ADC) beginning 1 min before and continuing for 11 min after induction of SAH. A high-resolution spin-echo diffusion sequence was used to follow diffusion changes over 6 h after SAH. Sham-operated control (n=3), nonheparinized (n=6), and heparinized (n=5) groups were studied.

Results
—Sham-operated control animals did not show ADC changes over time. In both SAH groups, however, a sharp decline of ADC within 2 min of SAH was consistently observed in the ipsilateral somatosensory cortex. These decreases in diffusion then spread within minutes over the ipsilateral hemisphere. Similar ADC decreases on the contralateral side started with a further time delay of 1 to 3 min. From 30 min onward, the extent of the diffusion abnormality decreased progressively in the nonheparinized animals. No recovery was observed in heparinized rats.

Conclusions
—MR diffusion imaging allows new insight into the pathophysiology of acute SAH: The spatial and temporal pattern of diffusion changes suggests the initial occurrence of acute vasospasm and subsequently “spreading depolarization” of brain tissue. Persistent hemorrhage in heparinized animals was reflected by early decline of ADC values throughout the entire brain.
β-Amyloid Precursor Protein and β-Amyloid Peptide Immunoreactivity in the Rat Brain After Middle Cerebral Artery Occlusion
Authors: Popa-Wagner A. , Schröder E. , Walker L.C. , Kessler C.
Published: June 2011

Background and Purpose
—Previous studies have shown that the β-amyloid precursor protein (βAPP) is upregulated after cerebral ischemia and that the β-amyloid (Aβ) fragment may be toxic to brain cells. Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. To test the hypothesis that the upregulation and/or persistence of amyloidogenic proteins is exacerbated in aged rats after cerebral ischemic stroke, we studied the expression of βAPP and its proteolytic product Aβ in the brains of young and old rats 7 days after temporary cerebral ischemia.

Methods
—Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. After 1 week, brains were removed and immunostaining was performed for βAPP, Aβ, and ED1 for macrophages and glial fibrillary acidic protein (GFAP).

Results
—Histological staining revealed that the degree of necrotic cavitation in the infarct core was relatively less in aged rats than in young rats, suggesting a slower pace of degenerative change and/or tissue removal in older animals. βAPP immunoreactivity was robustly increased, primarily in macrophage-like, ED1-positive cells in the infarct core and in the penumbra of both young and aged animals. Aβ immunoreactivity was evident in GFAP-positive astrocytic somata and processes, and also in clusters of small spherical structures in the penumbra. These Aβ-immunoreactive minispheres were more numerous in aged rats than in young rats.

Conclusions
—The presence of βAPP and Aβ immunoreactivity in the infarct core and penumbra indicates that cerebral ischemia promotes conditions that are favorable to the focal accumulation of βAPP and its proteolytic fragments, especially in the aged brain.
Stroke and Use of Low-Dose Oral Contraceptives in Young Women
Authors: Schwartz Stephen M. , Petitti Diana B. , Siscovick David S. , Longstreth W. T. , Sidney Stephen , Raghunathan Trivellore E. , Quesenberry Charles P. , Kelaghan Joseph
Published: June 2011

Background and Purpose
—The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population–based case-control studies.

Methods
—We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age.

Results
—For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were ≥35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1.19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke.

Conclusions
—Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.
Stroke Was Predicted by Dimensions of Quality of Life in Treated Hypertensive Men
Authors: Agewall Stefan , Wikstrand John , Fagerberg Björn
Published: June 2011

Background and Purpose
—Psychosocial factors have been suggested as risk factors for atherosclerotic disease. The purpose of the present study was to examine whether quality of life predicted strokes and acute coronary events in a prospective study.

Methods
—The study included 412 treated hypertensive men, aged 50 to 72 years, with ≥1 of the following: serum cholesterol ≥6.5 mmol/L, smoking, or diabetes mellitus. The Minor Symptoms Evaluation Profile (MSEP) was used to estimate quality of life at entry. Incidences of stroke and acute coronary events were recorded during follow-up. The median follow-up time was 6.6 years.

Results
—Sixty-four patients had an acute coronary event, and 37 had a stroke during the follow-up period. The Cox regression analyses revealed that the 3 dimensions of MSEP at entry were significant predictors of stroke. The relationship between low contentment at entry and the incidence of stroke during follow-up remained significant (relative risk=1.04; 95% CI, 1.01 to 1.06;
P
=0.003) even after adjustment for other potential cardiovascular risk factors. Vitality also remained an independent predictor for stroke after adjustment for these potential cardiovascular risk factors (relative risk=1.04; 95% CI, 1.02 to 1.06;
P
<0.0001). There was no relationship between MSEP score at entry and myocardial infarction during follow-up.

Conclusions
—An independent and significant association between reduced well-being at entry and future stroke was observed in hypertensive men at high cardiovascular risk. The causal relationship is not known, however.
Electroencephalographic Correlates of Vasovagal Syncope Induced by Head-Up Tilt Testing
Authors: Ammirati Fabrizio , Colivicchi Furio , Di Battista Giancarlo , Garelli Fausto Fiume , Santini Massimo
Published: June 2011

Background and Purpose—
We sought to determine whether the introduction of EEG monitoring during head-up tilt testing could significantly improve the understanding of the cerebral events occurring during tilt-induced vasovagal syncope and the potential danger to the patient of this diagnostic procedure.

Methods—
EEG monitoring was performed during head-up tilt testing in a group of 63 consecutive patients (27 males and 36 females; mean age, 41.5 years) with a history of recurrent syncope of unknown origin despite extensive clinical and laboratory assessment.

Results—
Syncope occurred in 27 of 63 patients (42.8%) during head-up tilt testing and was found to be cardioinhibitory in 11 of 27 (40.7%) and vasodepressor in 16 of 27 (59.3%). All patients with a negative response to head-up tilt testing showed no significant EEG modifications. In patients with vasodepressor syncope, a generalized high-amplitude, 4- to 5-Hz (theta range) slowing of EEG activity appeared at the onset of syncope, followed by an increase of brain-wave amplitude with the reduction of frequency at 1.5 to 3 Hz (delta range). The return to the supine position was associated with brain-wave amplitude reduction and frequency increase to 4 to 5 Hz, followed by restoration of a normal EEG pattern and arousal (mean total duration of syncope, 23.2 seconds.). In patients with cardioinhibitory syncope, a generalized high-amplitude EEG slowing in the theta range was noted at the onset of syncope, followed by a brain-wave amplitude increase and slowing in the delta range. A sudden reduction of brain-wave amplitude then ensued, leading to the disappearance of electrocerebral activity (“flat” EEG). The return to the supine position did not allow either the immediate resolution of EEG abnormalities or consciousness recovery, both of which occurred after a further time interval (mean total duration of syncope, 41.4 seconds.).

Conclusions—
EEG monitoring during head-up tilt testing allowed recording and systematic description of electrocerebral abnormalities developing in the course of tilt-induced vasovagal syncope.