bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Stroke With Dementia, Cognitive Impairment, and Functional Disability in the Very Old
Authors: Zhu Li , Fratiglioni Laura , Guo Zhenchao , Agüero-Torres Hedda , Winblad Bengt , Viitanen Matti
Published: June 2011

Background and Purpose
—Stroke is a major cause of disability in the elderly and is also related to the development of dementia, which is another important source of disability in old age. The aim of the present study was to examine the potential impact of stroke on cognitive and functional status in a community-based cohort of individuals aged 75 years and older.

Methods
—The data were derived from a cross-sectional survey on aging and dementia that included all inhabitants of the Kungsholmen district in central Stockholm who were aged ≥75 years. Cases of stroke were identified through the computerized inpatient register system that has been widely used to study stroke in Sweden. Dementia was defined according to the
Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised.
Dementia onset was considered the appearance, according to an informant, of the first symptom. Cognitive impairment without dementia was defined as the presence of a Mini-Mental State Examination score of <24 and the absence of dementia. Functional disability was assessed according to Katz Index of independence in activities of daily living.

Results
—The prevalence of stroke was 10.0% in men and 8.0% in women. One third of stroke survivors were diagnosed as demented, which was 3 times higher than those without stroke: adjusted odds ratio (OR) was 3.6 (95% confidence interval, 2.5 to 5.8). Stroke was also significantly related to cognitive impairment without dementia (adjusted OR, 2.4 [95% confidence interval, 1.3 to 4.6]). The population-attributable risks of dementia and cognitive impairment in relation to stroke were 18.4% and 8.5%, respectively. Among the 49 stroke patients with dementia, 15 cases (30.6%) had missing information on dementia onset, 22 (44.9%) had been reported by the informant to have dementia-related symptoms after or close to the occurrence of stroke, and 12 (24.5%) had symptoms before stroke occurrence. The prevalence rates of disability in activities of daily living were much higher among stroke patients than among stroke-free subjects, even after adjustment for age, sex, heart disease, hip fracture, and dementia: the corresponding adjusted ORs for bathing, dressing, toileting, transfer, and continence were 3.5 (2.4 to 5.3), 2.2 (1.4 to 3.3), 3.0 (2.0 to 4.5), 3.3 (1.9 to 5.7), and 2.1 (1.3 to 3.3), respectively. After dementia and hip fracture, stroke was the third largest contributor to disability in bathing, dressing, and transfer. Stroke was the second contributor to disability in toileting.

Conclusions
—Stroke is strongly associated with dementia, although it may relate to dementia in different ways: it can be the main cause or a precipitating factor of dementia, or they may share common etiological bases. Together with dementia and hip fracture, stroke is a major contributor to disability in most aspects of activities of daily living in very old people.
Three-Year Survival and Recurrence After Stroke in Malmö, Sweden
Authors: Elneihoum A. M. , Göransson M. , Falke P. , Janzon L.
Published: June 2011

Background and Purpose
—Data from the Malmö Stroke Registry were analyzed to determine whether any change in survival or nonfatal stroke recurrence rates had occurred during the 4-year period from 1989 through 1992 and whether prognosis was related to area of residence.

Methods
—The series comprised 2290 patients, 1051 men and 1239 women, followed up for 3 years after their first stroke during the period 1989 through 1992.

Results
—Of the series as a whole, 959(43.4%) died and 137(6%) suffered a second nonfatal stroke. Multivariate analysis showed age, type of stroke, severity of stroke, and the presence of diabetes mellitus or cardiac disease each to be an independent predictor of mortality, and the presence of diabetes, atrial fibrillation, and history of transient ischemic attacks each to be associated with increased risk of recurrence. Treatment for hypertension was associated with a protective effect. As compared to those with first stroke in 1989, those with first stroke in 1992 were characterized by a lower recurrence rate, which was reduced by 70% in the male subgroup (
P
=0.003) and by 80% in the female subgroup (
P
=0.006), the corresponding reduction in all-cause mortality being 30% (
P
=0.007) and 10% (
P
=0.5, NS). Recurrence-free survival rates differed markedly between the 17 residential areas studied.

Conclusions
—The present study showed that survival rates after stroke have improved and recurrence rates have declined in this urban population. Further studies are needed to ascertain to what extent intraurban variation in the proportion of recurrence-free 3-year survivors is to be explained by differences in the severity of initial stroke and other prognostic markers, or in initial treatment and secondary preventive measures.
Citicoline Treatment for Experimental Intracerebral Hemorrhage in Mice
Authors: Clark Wayne , Gunion-Rinker Lisa , Lessov Nikola , Hazel Kristin
Published: June 2011

Background and Purpose
—Citicoline sodium (cytidine-5′-diphosphocholine) has been shown previously to reduce ischemic injury in focal central nervous system models. Intracerebral hemorrhage (ICH) appears to be associated with an area of edema and ischemic injury surrounding the hematoma that may be reduced by neuroprotective therapy. The present study was designed to test whether treatment with citicoline reduces ischemic injury and improves functional neurological outcome in an experimental model of ICH.

Methods
—In 68 Swiss albino mice (26 to 36 g), ICH was induced by collagenase injection into the caudate nucleus. Animals were randomized to receive either: citicoline 500 mg/kg or saline IP prior to collagenase and at 24 and 48 hours. Animals were rated on a 28-point neurological scale and sacrificed at 54 hours. The brains were sectioned, and the volume of hematoma, total lesion, and surrounding ischemic injury was determined.

Results
—In terms of functional outcome, animals treated with citicoline had improved neurological outcome scores compared with placebo-treated animals: 10.4±2.0 versus 12.1±2.4 (
P
<0.01). Regarding ischemic injury, although there was no difference in the underlying hematoma volumes, animals treated with citicoline had a smaller surrounding volume of ischemic injury than placebo-treated animals: citicoline, 13.8±5.8 mm
3
(10.8±4.3% of hemisphere); placebo, 17.0±7.1 mm
3
(13.3±5.1%) (
P
<0.05).

Conclusions
—In this animal model of ICH, treatment with citicoline significantly improved functional outcome and reduced the volume of ischemic injury surrounding the hematoma. This study supports a potential role for citicoline in clinical ICH treatment.
A Critical Reevaluation of the Intraluminal Thread Model of Focal Cerebral Ischemia
Authors: Schmid-Elsaesser Robert , Zausinger Stefan , Hungerhuber Edwin , Baethmann Alexander , Reulen Hanns-Juergen
Published: June 2011

Background and Purpose
—The intraluminal thread model for middle cerebral artery occlusion (MCAO) has gained increasing acceptance. Numerous modifications have been reported in the literature, indicating that the technique has not been standardized. The present study was performed to evaluate and optimize the reliability of this model.

Methods
—One hundred Sprague-Dawley rats were subjected to MCAO by 2 different intraluminal filaments. Cortical blood flow was continuously monitored over both hemispheres by laser-Doppler flowmetry (LDF). In part I (3-0 filament), we evaluated the incidence of adequate MCAO, subarachnoid hemorrhage (SAH), intraluminal thrombus formation, and the effects of heparinization. In part II (silicone-coated 4-0 filament), we also determined the influence of insufficient MCAO on morphological and functional outcome and the incidence of postischemic hyperthermia.

Results
—In part I, SAH occurred in 30% and premature reperfusion in 24%. All animals with a decrease in contralateral flow had suffered SAH. Thrombus formation was not observed in any group. In part II, SAH occurred in 8% and premature reperfusion in 26%. There was no difference in outcome between rats with primary MCAO and rats with filament correction. Animals with uncorrected premature reperfusion had significantly smaller infarct volumes and fewer neurological deficits.

Conclusions
—SAH and insufficient MCAO may be more common in the intraluminal thread model than previously reported. Inadvertent premature reperfusion contributes to the interanimal variability associated with this model. The incidence of valid experiments increases with the use of a silicone-coated 4-0 filament. Continuous bilateral LDF is indispensable to monitor adequate MCAO and is highly sensitive to recognize SAH.
Increased Fibrinogen Levels and Acquired Hypofibrinolysis in Young Adults With Ischemic Stroke
Authors: Kristensen Bo , Malm Jan , Nilsson Torbjörn K. , Hultdin Johan , Carlberg Bo , Olsson Tommy
Published: June 2011

Background and Purpose
—Elevated fibrinogen levels and abnormalities in the fibrinolytic system are related to the occurrence of cardiovascular events. However, the role of these factors in the evolution of cerebrovascular disease has received less attention, in particular in young stroke patients. The aim of this study was to evaluate possible abnormalities in plasma fibrinogen levels and the state of the fibrinolytic system in young adults with a first-ever ischemic stroke.

Methods
—This study is based on 102 consecutive patients aged 18 to 44 years admitted between January 1991 and May 1996 as a result of a first ischemic stroke. Forty-one healthy controls were recruited. Evaluations of anthropometric/metabolic variables, plasma fibrinogen levels, and the fibrinolytic system were undertaken ≥3 months (mean, 5.4±2.0 months) after admission.

Results
—Patients had lower tissue plasminogen activator activity and increased plasminogen activator inhibitor type 1 activity at baseline, as well as increased tissue plasminogen activator mass concentration both at baseline and after a venous occlusion test. Overall, there were no significant differences between the main etiologic subgroups regarding plasma fibrinogen levels and fibrinolytic variables. Baseline fibrinolytic variables were strongly correlated with body mass index, serum triglycerides, and cholesterol levels. After adjustments in multivariate models, fibrinogen levels and tissue plasminogen activator mass concentration both at baseline and after venous occlusion test remained significantly increased in patients. Logistic multiple regression analyses indicated that plasma fibrinogen was a strong predictor of ischemic stroke (odds ratio, 11.25; 95% CI, 3.27 to 38.69).

Conclusions
—Increased fibrinogen levels and tissue plasminogen activator mass concentration are independently associated with ischemic stroke in young adults. Metabolic perturbations are closely interrelated with aberrations in tissue plasminogen activator and plasminogen activator inhibitor type 1 activity in these patients, findings consistent with an acquired hypofibrinolysis.
Time Course of Lesion Development in Patients With Acute Stroke
Authors: Schwamm Lee H. , Koroshetz Walter J. , Sorensen A. Gregory , Wang Bing , Copen William A. , Budzik Ronald , Rordorf Guy , Buonanno Ferdinando S. , Schaefer Pamela W. , Gonzalez R. Gilberto
Published: June 2011

Background and Purpose
—We sought to characterize the evolution of acute ischemic stroke by MRI and its relationship to patients’ neurological outcome.

Methods
—Fourteen patients with acute ischemic stroke underwent MRI within 13 hours of symptom onset (mean, 7.4±3 hours) and underwent repeated imaging and concurrent neurological examination at 8, 24, 36, and 48 hours and 7 days and >42 days after first imaging.

Results
—Diffusion-weighted imaging (DWI) lesion volumes increased between the first and second scans in 10 of 14 patients; scans with maximum DWI lesion volume occurred at a mean of 70.4 hours. Initial DWI lesion volume correlated with the largest T2 lesion volume (
r
=0.97;
P
<0.001). Final lesion volume was smaller than maximum lesion volume in 12 of 14 patients. There was positive correlation between the follow-up National Institutes of Health Stroke Scale score and the initial DWI lesion volume (
r
=0.67;
P
=0.01) and maximum T2 lesion volume (
r
=0.77;
P
<0.01) and negative correlation with initial mean apparent diffusion coefficient ratio (ADCr) (
r
=−0.64;
P
<0.05). The ADCr was 0.73 at initial imaging and fell between the initial and second scans in 10 of 14 patients. Mean ADCr did not rise above normal until 42 days after stroke onset (
P
<0.001).

Conclusions
—Serial MRI demonstrates the dynamic nature of progressive ischemic injury in acute stroke patients developing over hours to days, and it suggests that both primary and secondary pathophysiological processes can be valuable targets for neuroprotective interventions.
Unilateral Saccadic Pursuit in Patients With Sensory Stroke
Authors: Johkura Ken , Matsumoto Shunsuke , Komiyama Atsushi , Hasegawa Osamu , Kuroiwa Yoshiyuki
Published: June 2011

Background and Purpose
—Pure hemisensory syndrome can be caused by small strokes occurring in a number of regions, including the thalamus and pons. Differentiation of the pontine sensory syndrome from the thalamic sensory syndrome has generally been made on the basis of distribution of sensory loss and involvement of specific sensory modalities but not without uncertainties and difficulties. Because the pontine tegmentum plays a pivotal role in generating horizontal eye movement, we attempted to discriminate these 2 syndromes by analyzing horizontal eye movements in stroke patients with pure hemisensory syndrome.

Methods
—Horizontal saccade, pursuit, vestibulo-ocular reflex (VOR), and VOR cancellation (VORC) were evaluated using electro-oculography in 6 patients with hemisensory syndromes, 3 due to pontine stroke and 3 due to thalamic stroke, and all were verified by MRI or CT. In addition, somatosensory evoked potentials (SEPs) were recorded.

Results
—Smooth pursuit and VORC directed toward the side of the lesion were impaired unilaterally in patients with pontine sensory stroke, whereas those 2 movements were intact bilaterally in patients with thalamic sensory stroke. Saccade and VOR were preserved in all patients. SEPs were normal in all patients with pontine and thalamic sensory strokes. No difference was found in the pattern of sensory disturbance between the 2 types of stroke patients.

Conclusions
—Ipsilateral impairment of the smooth pursuit system may be a sign of a pontine lesion in patients with hemisensory stroke.
Relation of Plasma Homocyst(e)ine to Cerebral Infarction and Cerebral Atherosclerosis
Authors: Yoo Jun-Hyun , Chung Chin-Sang , Kang Soo-Sang
Published: June 2011

Background and Purpose
—A number of investigations support the theory that the elevated plasma homocyst(e)ine is associated with occlusive vascular disease. The aim of this study is to examine whether moderate hyperhomocyst(e)inemia is an independent risk factor for cerebral infarction. In addition, we examined the association between plasma homocyst(e)ine and the severity of cerebral atherosclerosis.

Methods
—We conducted a hospital-based case-control study with 140 male controls and 78 male patients with nonfatal cerebral infarction, aged between 39 and 82 years. Plasma homocyst(e)ine levels were analyzed in 218 subjects. Fifty-five patients were evaluated for cerebral vascular stenosis by MR angiography.

Results
—The mean plasma level of homocyst(e)ine was higher in cases than in controls (11.8±5.6 versus 9.6±4.1 μmol/L;
P
=0.002). The proportion of subjects with moderate hyperhomocyst(e)inemia was significantly higher in cases than in controls (16.7% versus 5.0%;
P
=0.004). Based on the logistic regression model, the odds ratio of the highest 5% of homocyst(e)ine levels in control group was 4.17 (95% confidence interval, 3.71 to 4.71)(
P
=0.0001). After additional adjustment for total cholesterol, hypertension, smoking, diabetes, and age, the odds ratio was 1.70 (95% confidence interval, 1.48 to 1.95) (
P
=0.0001). The plasma homocyst(e)ine levels of patients having vessels with 3 or 2 stenosed sites were significantly higher than those of patients having vessels with 1 stenosed site or normal vessels (14.6±1.4, 11.0±1.4 versus 7.8±1.5, 8.9±1.4 μmol/L respectively;
P
<0.02). Multiple logistic regression analysis revealed that moderate hyperhomocyst(e)ienemia was significantly associated with the number of stenosed vessels (
P
=0.001).

Conclusions
—These findings suggest that moderate hyperhomocyst(e)inemia is an independent risk factor for cerebral infarction and may predict the severity of cerebral atherosclerosis in patients with cerebral infarction.
The Process of Rehabilitation and Discharge Planning in Stroke
Authors: Patel Mehool , Potter Jonathan , Perez Inigo , Kalra Lalit
Published: June 2011

Background and Purpose
—Stroke units improve outcome for stroke patients. Comparative controlled studies between stroke units are required to determine which components of stroke unit rehabilitation influence outcome and which may be investigated further in randomized controlled trials. This study compares 2 stroke units with regard to the effect differences in practice have on functional recovery (Barthel Index score) and discharge planning (length of stay).

Methods
—Stroke unit patients with moderate disability (Barthel score of 4 to 10 at week 1) admitted over 18 months were studied. Barthel measurements were obtained weekly from week 1 to discharge. Details of stroke unit function were recorded. The core features of stroke units were in place in both units. Rehabilitation was impairment focused (theoretically driven) on one unit and disability oriented (pragmatic) on the other.

Results
—Numbers of patients were comparable (85 versus 99). Median Barthel score at week 1 (6 versus 6), time to maximal Barthel score (14 versus 14 weeks), discharge Barthel score (14 versus 14), and institutionalization (32% versus 28%) were similar in both units. Median lengths of stay differed (68 versus 49 days;
P
<0.001).

Conclusions
—Comparisons with regard to the rehabilitation process can be made between stroke units. Differences in rehabilitation process between 2 units showed no effect on the rate of functional recovery. Length of stay was significantly different between units, an effect that cannot be attributed to functional recovery and therefore reflects differences in discharge planning, including postdischarge support.
Value of Repeat Angiography in Patients With Spontaneous Subcortical Hemorrhage
Authors: Hino Akihiko , Fujimoto Masahito , Yamaki Tarumi , Iwamoto Yoshihiro , Katsumori Tetsuya
Published: June 2011

Background and Purpose
—Neuroradiological investigations do not disclose a source of bleeding in some patients with spontaneous subcortical hemorrhage. These patients may harbor undetected vascular malformations and may be at risk of rebleeding in the future. We investigated patients with subcortical hemorrhage with use of repeat angiography and MRI to determine the incidence of occult vascular malformations and the risk of bleeding during follow-up.

Methods
—We reviewed a consecutive series of 137 patients with subcortical hemorrhage during a 10-year period (June 1987 through June 1997). If the patient was <65 years old and the first angiogram and/or MRI did not show a source of bleeding, repeat angiography was recommended. All angiographic and MRI studies were reviewed. The relationship between the identified bleeding source and clinical variables such as patient age, sex, and history of hypertension and the size and location of the hematoma were examined.

Results
—One hundred seven patients (78%) underwent angiography on admission
,
10 (7%) had immediate surgery for hematoma without angiography, and 20 (15%) had neither angiography nor surgery. Overall, an etiology for the hemorrhage was found in 55 cases (40%). Vascular malformations were common in young patients without preexisting hypertension. A second angiogram was obtained in 22 patients, and 4 arteriovenous malformations were demonstrated. Rebleeding at the site of the initial hemorrhage was not observed after a mean follow-up of 68 months.

Conclusions
—Angiography performed acutely after hemorrhage may not demonstrate vascular malformations. Consideration should be given to repeat angiography in patients who do not have a specific cause for hemorrhage.
Apoptosis in a Neonatal Rat Model of Cerebral Hypoxia-Ischemia
Authors: Pulera Mark R. , Adams Lisa M. , Liu Hantao , Santos Donaldson G. , Nishimura Robert N. , Yang Fusheng , Cole Greg M. , Wasterlain Claude G.
Published: June 2011

Background and Purpose
—The mechanisms of excitotoxic cell death in cerebral ischemia are poorly understood. In addition to necrosis, apoptotic cell death may occur. The purpose of this study was to determine whether an established model of cerebral hypoxia-ischemia in the neonatal rat demonstrates any features of apoptosis.

Methods
—Seven-day-old neonatal rats underwent bilateral, permanent carotid ligation followed by 1 hour of hypoxia, and their brains were examined 1, 3, and 4 days after hypoxia-ischemia. The severity of ischemic damage was assessed in the dentate gyrus and frontotemporal cortex by light microscopy. Immunocytochemistry was performed to detect the cleavage of actin by caspases, a family of enzymes activated in apoptosis. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling (TUNEL) reactivity was examined in the cortical infarction bed and dentate gyrus. Neonatal rat brain DNA was run on agarose gel electrophoresis to detect DNA fragmentation. Ethidium bromide–staining and electron microscopy were used to determine whether apoptotic bodies, 1 of the hallmarks of apoptosis, were present.

Results
—The frontotemporal cortex displayed evidence of infarction, and in most rats the dentate gyrus showed selective, delayed neuronal death. Immunocytochemistry demonstrated caspase-related cleavage of actin. TUNEL and DNA electrophoresis provided evidence of DNA fragmentation. Ethidium bromide–staining and electron microscopy confirmed the presence of chromatin condensation and apoptotic bodies.

Conclusions
—Features of apoptosis are present in the described model of cerebral hypoxia-ischemia. Apoptosis may represent a mode of ischemic cell death that could be the target of novel treatments that could potentially expand the therapeutic window for stroke.
Mannitol at Clinical Concentrations Activates Multiple Signaling Pathways and Induces Apoptosis in Endothelial Cells
Authors: Malek Adel M. , Goss Greg G. , Jiang Lianwei , Izumo Seigo , Alper Seth L.
Published: June 2011

Background and Purpose
—Hyperosmotic mannitol therapy is widely used in the clinical setting for acute and subacute reduction in brain edema, to decrease muscle damage in compartment syndrome, and to improve renal perfusion. Though beneficial rheological effects commonly are attributed to mannitol, its direct effects on endothelial cells are poorly understood.

Methods
—We studied the effect of hypertonic and hypotonic stress on bovine aortic endothelial (BAE) cells, using mannitol, urea, and sodium chloride and medium dilution in vitro.

Results
—Exposure to incremental osmolar concentrations of 300 mOsm of each osmotic agent increased apoptosis in BAE cells (mannitol≅NaCl>urea). Induced programmed cell death was detected by DAPI staining of intact cell nuclei, and by TUNEL and DNA fragmentation ladder assays. Mannitol-induced apoptosis exhibited dose dependence (42% of cells at 300 mOsm [
P
<0.0001] compared with 1.2% of control cells) and was also observed in bovine smooth muscle cells. Mannitol-induced apoptosis was attenuated ≈50% in the presence of cycloheximide or actinomycin D. Hypertonic mannitol and NaCl, but not urea, increased tyrosine phosphorylation of the focal adhesion contact-associated proteins paxillin and FAK. Hypotonic medium, which did not lead to apoptosis, increased protein tyrosine phosphorylation of FAK but not of paxillin. Addition of mannitol or NaCl also produced sustained increases in c-Jun NH2-terminal kinase (JNK) activity. In addition, hypertonic mannitol increased intracellular free [Ca
2+
] in a dose-dependent manner. Chelation of intracellular Ca
2+
with quin2-AM (10 μmol/L) inhibited mannitol-induced apoptosis ≈50%, as to a lesser extent did inhibition of tyrosine kinase activity with herbimycin (1 μmol/L).

Conclusions
—We have shown that hypertonic mannitol exposure induces endothelial cell apoptosis, accompanied by activation of tyrosine and stress kinases, phosphorylation of FAK and paxillin, and elevation of intracellular free [Ca
2+
]. The apoptosis is attenuated by inhibition of transcription or translation, by inhibition of tyrosine kinases, or by intracellular Ca
2+
buffering. These data suggest that clinical use of the osmotic diuretic mannitol may exert direct deleterious effects on vascular endothelium.
Epidemiology of Carotid Endarterectomy Among Medicare Beneficiaries
Authors: Hsia David C. , Moscoe Linda M. , Krushat W. Mark
Published: June 2011

Background and Purpose
—This article describes changes in the rate and outcome of carotid endarterectomies among Medicare beneficiaries.

Methods
—We analyzed
International Classification of Diseases, 9th Revision, Clinical Modification
(ICD-9-CM) codes as shown on Medicare bills to calculate carotid endarterectomy frequency, rate, and perioperative mortality by patient demography and hospital characteristics.

Results
—After initially peaking at 61 273 procedures (20.6 per 10 000 beneficiaries) in 1985, the frequency of carotid endarterectomy among Medicare beneficiaries declined to 46 571 (14.3 per 10 000) in 1989 and then rose to 108 275 (28.6 per 10 000) in 1996. Patients were predominantly aged 65 to 74 years, male, and white; surgery occurred mainly in large, urban, nonprofit, and teaching hospitals. Perioperative mortality declined from 3.0% in 1985 to 1.6% in 1996.

Conclusions
—The frequency and rate of carotid endarterectomy showed prompt response to reports from clinical trials. Perioperative mortality both improved and converged over time but did not attain the rates reported by the trials. Patients aged 85+ years suffered twice the average perioperative mortality.
Relationship Between ApoE, MRI Findings, and Cognitive Function in the Cardiovascular Health Study
Authors: Kuller Lewis H. , Shemanski Lynn , Manolio Teri , Haan Mary , Fried Linda , Bryan Nick , Burke Gregory L. , Tracy Russell , Bhadelia Rafeeque
Published: June 2011

Background and Purpose
—We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores.

Methods
—The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years.

Results
—The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]).

Conclusions
—These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.
Chlamydia pneumoniae
Antibody Titers Are Significantly Associated With Acute Stroke and Transient Cerebral Ischemia
Authors: Cook Peter J. , Honeybourne David , Lip Gregory Y. H. , Beevers D. Gareth , Wise Richard , Davies Paul
Published: June 2011

Background and Purpose
—Several studies have implied an association between
Chlamydia pneumoniae
and atherosclerosis. Our research was designed to investigate the association of this organism with strokes and transient cerebral ischemia.

Methods
—Antibodies to
C pneumoniae
were measured in 176 patients with stroke or transient cerebral ischemia and 1518 control subjects with noncardiovascular, nonpulmonary disorders. Acute infection or reinfection was defined by IgG ≥512 or IgM ≥8 or fourfold rise in IgG, and previous infection was defined by IgG 64 to 256 or lgA ≥8. Logistic regression was used to examine the influences of ethnic origin, age, sex, smoking habit, diabetes mellitus, steroid medication, and social deprivation on antibody levels. Some patients underwent CT and carotid ultrasound examinations and cholesterol, triglyceride, fibrinogen, and von Willebrand factor estimations.

Results
—We found that 13.6% of stroke/transient ischemic attack (TIA) patients and 5.7% of control subjects had antibody titers suggesting acute
C pneumoniae
(re)infection, while 32.4% of stroke/TIA patients and 12.7% of control subjects had titers suggesting previous infection (
P
<.05). Stroke/TIA patients differed from control subjects in their levels of acute and previous infection, with adjusted odds ratios of 4.2 (95% CI, 2.5 to 7.1) and 4.4 (95% CI, 3.0 to 6.5), respectively. These did not differ notably between strokes resulting from major nonhemorrhagic infarcts, small-vessel infarcts, or hemorrhage. Cholesterol, triglyceride, fibrinogen, and von Willebrand factor concentrations showed no apparent association with titers.

Conclusions
—These data support the association of cerebral vascular disease with previous
C pneumoniae
infection and the association of stroke and transient cerebral ischemia with recrudescence of infection.
Tumor Necrosis Factor-α–Induced Dilatation of Cerebral Arterioles
Authors: Brian Johnny E. , Faraci Frank M.
Published: June 2011

Background and Purpose
—In brain, several cell types produce tumor necrosis factor-α (TNFα) after injury or exposure to endotoxin. TNFα alone or in combination with endotoxin or other cytokines can cause expression of inducible nitric oxide (NO) synthase. We have previously demonstrated that endotoxin caused NO-dependent dilatation of cerebral arterioles in vivo. In the present study we examined the hypothesis that TNFα causes NO-mediated dilatation of cerebral arterioles in vivo.

Methods
—Cranial windows were implanted in anesthetized rats and used to measure the diameter of cerebral arterioles. Windows were flushed every 30 minutes for 4 hours with artificial cerebrospinal fluid (aCSF) (n=6); aCSF with TNFα (100 ng/mL; n=10); aCSF with TNFα and aminoguanidine (0.3 mmol/L; n=5), an inhibitor of inducible NO synthase; or aCSF with TNFα and dexamethasone (1 μmol/L; n=6), which attenuates expression of inducible NO synthase. In some animals, brain from beneath the cranial window was examined by immunocytochemistry for inducible NO synthase expression.

Results
—Application of TNFα caused marked, progressive dilatation of cerebral arterioles, with a maximum increase in diameter of 46±9% (mean±SEM) at 4 hours. Coapplication of either aminoguanidine or dexamethasone with TNFα prevented dilatation of cerebral arterioles compared with TNFα alone (4±2% and 1±1% dilatation at 4 hours, respectively;
P
<.05). Dexamethasone did not inhibit dilatation of cerebral arterioles in response to adenosine diphosphate. However, 2 hours of aminoguanidine treatment produced moderate inhibition of adenosine diphosphate–induced dilatation of cerebral arterioles. After treatment with TNFα, immunocytochemistry for inducible NO synthase demonstrated expression in perivascular and arachnoid cells but not brain cells. There was no detectable expression of inducible NO synthase after treatment with aCSF.

Conclusions
—The present study indicates that TNFα causes cerebral vasodilatation and expression of inducible NO synthase in perivascular and arachnoid cells. Inhibition of TNFα-induced dilatation by aminoguanidine and dexamethasone suggests that the vasodilatation was due predominantly to expression of inducible NO synthase. These findings support the concept that cerebral vasodilatation that occurs during pathophysiological conditions associated with increased TNFα production in brain is mediated by expression of inducible NO synthase.
Risk of Stroke in Young Women and Two Prothrombotic Mutations: Factor V Leiden and Prothrombin Gene Variant (G20210A)
Authors: Longstreth W. T. , Rosendaal F. R. , Siscovick D. S. , Vos H. L. , Schwartz S. M. , Psaty B. M. , Raghunathan T. E. , Koepsell T. D. , Reitsma P. H.
Published: June 2011

Background and Purpose
—Factor V Leiden and a prothrombin gene variant, G20210A, are mutations associated with a thrombotic risk. The aim of our study was to assess whether these mutations increase the risk of stroke in women under 45 years of age.

Methods
—We conducted a case-control study in western Washington state. Case patients were women aged 18 to 44 years with a first stroke (n=106). Control subjects were women without stroke recruited from the same region by use of random-digit telephone dialing (n=391). All were interviewed and provided blood specimens, which were genotyped for these mutations.

Results
—Factor V Leiden was found in 0.9% of case patients, a single patient with a subarachnoid hemorrhage, and in 4.1% of control subjects. The odds ratio (OR) for any stroke was 0.2 (95% confidence interval [CI], 0.03 to 1.7). The prothrombin variant was found in 1.9% of case patients, 1 with a venous stroke and 1 with an ischemic stroke, and in 1.6% of control subjects. The OR for any stroke was 1.48 (95% CI, 0.14 to 9.17). ORs for stroke types were also not statistically significant.

Conclusions
—In this study, neither factor V Leiden nor the prothrombin variant (G20210A) was an important risk factor for stroke in young women. In this setting, screening for these mutations cannot be recommended. Unanswered by this study is whether screening would be useful in select patients, such as those with a strong family history of thrombophilia or those with venous strokes.
Stroke Unit Versus General Medical Wards, II: Neurological Deficits and Activities of Daily Living
Authors: Rønning Ole Morten , Guldvog Bjørn
Published: June 2011

Background and Purpose
—The efficacy of stroke units has been extensively examined. It is unknown, however, whether the superiority of the stroke unit will remain after the increased focus on stroke treatment in general medicine. This study of patients admitted to the hospital early and with a short length of stay determines the effect and identifies certain important components of a stroke unit.

Methods
—Five hundred fifty patients aged 60 years or older with acute stroke were allocated by a quasi-randomized design to a stroke unit or a general medical ward based on date of birth in the month. Patients admitted within 24 hours of onset were enrolled. Outcomes after 7 months were death, proportion needing long-term care, and change in neurological and functional state assessed by the Scandinavian Stroke Scale and Barthel Index.

Results
—Seven months after admission there was a trend in favor of the stroke unit in all outcome measures, but no significant differences in clinical outcomes were found except for change in the Scandinavian Stroke Scale score. Recurrent stroke during hospitalization occurred more often in the general medical ward (
P
=.03). The stroke unit was significantly more aggressive in mobilization out of bed (
P
<.01) and use of parenteral fluid (
P
<.0001), aspirin (
P
<.0001), antipyretics (
P
<.0001), and antibiotics (
P
<.0001).

Conclusions
—Our study confirms the benefit of the stroke unit, but the effects on the most reliable clinical outcomes were modest and insignificant. Treatment in this stroke unit hastened recovery. More aggressive rehabilitation and use of parenteral fluid, aspirin, antipyretics, and antibiotics appeared in the stroke unit.
Muscle Sympathetic Nerve Activity During Cold Pressor Test in Patients With Cerebrovascular Accidents
Authors: Mizushima Takashi , Tajima Fumihiro , Nakamura Takeshi , Yamamoto Mitsuru , Lee Kyu-Ha , Ogata Hajime
Published: June 2011

Background and Purpose
—Autonomic dysfunction is frequently present in patients with cerebrovascular accidents (CVA). However, the pathophysiological mechanisms of these disorders are not clear. The purpose of the study was to assess the effects of CVA on the autonomic nervous system.

Methods
—In eight male patients with a history of CVA with damage of the cortical or subcortical structures, we measured the cold pressor response during recording of muscle sympathetic nerve activity (MSNA) from the peroneal nerve on the hemiplegic side. We also studied 10 age-matched male control subjects. Tests were performed before, during, and after immersion of the nonhemiplegic hand in ice water for a period of 3 minutes in each phase. We also recorded changes in heart rate (HR), arterial blood pressure, skin temperature of the middle finger, and perception of pain using the Borg’s score.

Results
—During the control period, the mean burst count of MSNA in CVA (57.2±3.9 beats/100 HR) was higher than in control subjects (36.3±3.2 beats/100 HR) (
P
<.05). Total MSNA (the mean burst amplitude per minute times burst rate) increased significantly in CVA and control during the immersion period by 79.9±18.4% and 133.1±25.6%, respectively. The percent change in total MSNA in CVA was attenuated during immersion compared with control subjects. The HR and skin temperature responses as well as the Borg’s score were similar in both groups during control, hand immersion, and recovery periods.

Conclusions
—The present results suggest that increased MSNA in CVA may be due to damage of cortical or subcortical structures or stroke-related changes in other areas or nonspecific changes that cause continuous increase in basal MSNA.
Neuroanatomic Localization of Magnetic Resonance Imaging Signal Hyperintensities in Geriatric Depression
Authors: Greenwald Blaine S. , Kramer-Ginsberg Elisse , Krishnan K. Ranga Rama , Ashtari Manzar , Auerbach Charles , Patel Mahendra
Published: June 2011

Background and Purpose
—Increased frequency and severity of signal hyperintensities have been regularly reported in elderly depressed patients compared with normal subjects, however, greater neuroanatomic localization of lesions has been limited.

Methods
—T2-weighted MRI scans in elderly depressed patients (n=35) and normal comparison subjects (n=31) were assessed for signal hyperintensities in lateralized discrete brain regions.

Results
—Logistic regression revealed that left frontal deep white matter (
P
<.005) and left putaminal (
P
<.04) hyperintensities significantly predicted depressive group assignment.

Conclusions
—Findings suggest that greater neuroanatomic localization of hyperintensities than heretofore appreciated may relate to late-life depression.
The Sunnybrook Stroke Study
Authors: Herrmann N. , Black S.E. , Lawrence J. , Szekely C. , Szalai J.P.
Published: June 2011

Background and Purpose
—To assess the prevalence of depressive symptoms, their clinical correlates, and the effects of depressive symptoms on stroke recovery, a relatively unselected, well-diagnosed cohort of consecutive stroke survivors was followed prospectively.

Methods
—Consecutive admissions to a regional stroke center who met World Health Organization and National Institute of Neurological Disorders and Stroke criteria for stroke were eligible. Subarachnoid hemorrhage and brain stem strokes were excluded. Patients underwent CT, single-photon emission CT, and standardized neurological and cognitive examinations at entry. At 3 months and 1 year after stroke, depressive symptoms were assessed with the Montgomery Asberg Depression Rating Scale (MADRS) and the Zung Self-Rating Depression Scale (SDS). Functional outcome was measured with the Functional Independence Measure, and handicap was assessed by the Oxford Handicap Scale.

Results
—We assessed 436 patients at entry (mean±SD age, 74.9±11.6 years). There were 150 patients available for assessment at 3 months and 136 at 1 year. Marked depressive symptoms were noted in 22% (SDS) to 27% (MADRS) at 3 months and 21% (SDS) to 22% (MADRS) at 1 year. Patents with marked depressive symptoms had more neurological impairment (
P
<.008), were more likely to be female (
P
<.05), and were more likely to have previous histories of depression (
P
<.03). There was no relationship between depressive symptoms and age, lesion volume, or side of lesion. Depressive symptoms were correlated with functional outcome (
r
=−.31,
P
<.0001) and handicap (
r
=.41,
P
<.0001) at 3 months and 1 year (
r
=−.28,
P
<.001;
r
=.35,
P
<.0001).

Conclusions
—Depressive symptoms and functional outcome are correlated. In view of the prevalence of depressive symptoms in this population, diagnosis and treatment of depression are important in optimizing recovery.
Calcium in Ischemic Cell Death
Authors: Kristián Tibor , Siesjö Bo K.
Published: June 2011

Background
—This review article deals with the role of calcium in ischemic cell death. A calcium-related mechanism was proposed more than two decades ago to explain cell necrosis incurred in cardiac ischemia and muscular dystrophy. In fact, an excitotoxic hypothesis was advanced to explain the acetylcholine-related death of muscle end plates. A similar hypothesis was proposed to explain selective neuronal damage in the brain in ischemia, hypoglycemic coma, and status epilepticus.

Summary of Review
—The original concepts encompass the hypothesis that cell damage in ischemia-reperfusion is due to enhanced activity of phospholipases and proteases, leading to release of free fatty acids and their breakdown products and to degradation of cytoskeletal proteins. It is equally clear that a coupling exists between influx of calcium into cells and their production of reactive oxygen species, such as ·O
2
−
, H
2
O
2
, and ·OH. Recent results have underscored the role of calcium in ischemic cell death. A coupling has been demonstrated among glutamate release, calcium influx, and enhanced production of reactive metabolites such as ·O
2
−
, ·OH, and nitric oxide. It has become equally clear that the combination of ·O
2
−
and nitric oxide can yield peroxynitrate, a metabolite with potentially devastating effects. The mitochondria have again come into the focus of interest. This is because certain conditions, notably mitochondrial calcium accumulation and oxidative stress, can trigger the assembly (opening) of a high-conductance pore in the inner mitochondrial membrane. The mitochondrial permeability transition (MPT) pore leads to a collapse of the electrochemical potential for H
+
, thereby arresting ATP production and triggering production of reactive oxygen species. The occurrence of an MPT in vivo is suggested by the dramatic anti-ischemic effect of cyclosporin A, a virtually specific blocker of the MPT in vitro in transient forebrain ischemia. However, cyclosporin A has limited effect on the cell damage incurred as a result of 2 hours of focal cerebral ischemia, suggesting that factors other than MPT play a role. It is discussed whether this could reflect the operation of phospholipase A
2
activity and degradation of the lipid skeleton of the inner mitochondrial membrane.

Conclusions
—Calcium is one of the triggers involved in ischemic cell death, whatever the mechanism.
Clusters of Microembolic Signals: A New Form of Cerebral Microembolism Presentation in a Patient With Middle Cerebral Artery Stenosis
Authors: Segura Tomas , Serena Joaquin , Molíns Albert , Dávalos Antoni
Published: June 2011

Background
—Middle cerebral artery (MCA) stenosis is a rare occlusive disease in western populations, with a high risk of stroke recurrence. An artery-to-artery embolic mechanism has been argued. We report the detection of a new pattern of microembolic signals (MES) in the MCA poststenotic segment in a patient with multiple recurrent transient ischemic attacks.

Case Description
—A 75-year-old man was admitted to our hospital with a transient leg monoparesis on the left side. Right MCA stenosis was detected by transcranial Doppler ultrasonography (TCD). In spite of aspirin treatment, the patient had a recurrent right hemispheric transient ischemic attack, and anticoagulant therapy was started. A new, similar event happened after correct anticoagulation. The bigated TCD monitoring study of both MCAs disclosed clusters of MES at the poststenotic MCA segment. Each cluster contained between 12 and 45 embolic signals. The patient became asymptomatic and clusters of MES disappeared, coinciding with the combination of ticlopidine and oral anticoagulants.

Conclusions
—We describe a new presentation of MES, ie, grouped in clusters of signals, that may be associated with a high risk of stroke recurrence.
Subclinical Atherosclerosis in Relation to Hysterectomy Status in Black Women
Authors: Zeigler-Johnson Charnita M. , Holmes Janice L. , Lassila Holly C. , Sutton-Tyrrell Kim , Kuller Lewis H.
Published: June 2011

Background and Purpose
—This study was designed to investigate whether black women who underwent hysterectomy only (n=59) or hysterectomy plus bilateral oophorectomy (n=25) were at increased risk of subclinical carotid atherosclerosis compared with black women who underwent natural menopause (n=54). The effects of both surgery and menopausal status were evaluated.

Methods
—Women aged 34 to 58 years were recruited from the Pittsburgh, Pa, area. Postmenopausal status was defined as a serum follicle-stimulating hormone level of >30 mIU/mL. Carotid duplex scans were performed to assess the degree of focal plaque.

Results
—Among premenopausal women, focal plaque was present in 20% of nonhysterectomized versus 49% of hysterectomized-only women (
P
=.004). Among postmenopausal women, plaque was present in 69% of nonhysterectomized women, 86% of women with hysterectomy only, and 48% of women with oophorectomy and hysterectomy (
P
=.056). Among postmenopausal women, hormone replacement therapy was used by 23% of women who had undergone natural menopause, 0% of women with hysterectomy only, and 36% of women with oophorectomy and hysterectomy. The prevalence of plaque was 33% among hormone replacement therapy users versus 73% among nonusers (
P
=.014). In multivariate analysis, independent associations with the presence of at least 1 plaque were postmenopausal status and hysterectomy only.

Conclusions
—These data suggest that black women who undergo hysterectomy without oophorectomy may be at higher risk of subclinical carotid atherosclerosis than black women who undergo natural menopause or hysterectomy plus oophorectomy.