bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcortical Silent Brain Infarction as a Risk Factor for Clinical Stroke
Authors: Kobayashi Shotai , Okada Kazunori , Koide Hiromi , Bokura Hirokazu , Yamaguchi Shuhei
Published: June 2011

Background and Purpose
No prospective studies have examined the rate of symptomatic ischemic or hemorrhagic stroke in patients with subcortical silent brain infarction (SSBI) who were otherwise neurologically normal at entry into the study. This report investigates SSBI, detected by MRI, as a clinical stroke risk factor.

Methods
MRI scans were performed in 933 neurologically normal adults (30 to 81 years; mean age, 57.5±9.2 years) without history of cerebrovascular diseases who received our health screening of the brain 1 to 7 years before investigation. We obtained information of their clinical stroke onset through sending out a questionnaire for subjects. We detected SSBI (focal T2 hyperintensities larger than 3 mm with correlative T1 hypointensity), FWT2HL (focal white matter T2 hyperintensity lesions similar to SSBI but without correlative T2-hypointensity), and PVH (periventricular hyperintensity) by MRI. Age, sex, family history of stroke, history of hypertension, diabetes mellitus, lipids, hematocrit, blood pressure, fasting blood sugar, smoking, alcohol habits, ischemic changes on electrocardiogram, and sclerotic changes of retinal arteries were included in the analysis.

Results
Incidence of SSBI was 10.6% in all subjects. No cortical infarct was detected in this series. Multiple logistic regression analysis showed that hypertension (odds ratio [OR], 4.07; 95% CI, 2.57 to 6.45), diabetes (OR, 2.41; 95% CI, 1.20 to 4.85), alcohol habits ≥58 g/day (OR, 2.58; 95% CI, 1.50 to 4.45), retinal artery sclerosis (OR, 2.14; 95% CI, 1.32 to 2.38), and age (OR, 1.77; 95% CI, 1.32 to 2.38) were significant and independent risk factors for SSBI. For FWT2HL, hypertension (OR, 4.49; 95% CI, 2.54 to 7.96) and age (OR, 2.08; 95% CI, 1.45 to 3.00) were also independent risk factors. Risk factors for PVH were age (OR, 3.46; 95% CI, 2.23 to 5.36), hypertension (OR, 3.06; 95% CI, 1.62 to 5.78), and retinal artery sclerosis (OR, 2.25; 95% CI, 1.02 to 4.96). We found 14 brain infarctions, 4 brain hemorrhages, and 1 subarachnoid hemorrhage during observation. Annual incidence of clinical stroke was higher in the subjects with SSBI than in those without focal lesions (10.1% versus 0.77%). ORs for clinical stroke onset were 10.48 for SSBI (95% CI, 3.63 to 30.21) and 4.81 for FWT2HL (95% CI, 1.13 to 20.58). The PVH did not relate to clinical stroke onset.

Conclusions
The strong association of SSBI, FWT2HL, and PVH with hypertension suggests a common underlying mechanism (presumably small-vessel vasculopathy). The SSBI showed the most significant association for clinical subcortical stroke. The FWT2HL was also a risk factor for the stroke but was less significant than SSBI. The subjects with SSBI should be considered at high risk for clinical subcortical brain infarction or brain hemorrhage.
S-100 Protein: Serum Marker of Focal Brain Damage After Ischemic Territorial MCA Infarction
Authors: Büttner Thomas , Weyers Stephan , Postert Thomas , Sprengelmeyer Reiner , Kuhn Wilfried
Published: June 2011

Background and Purpose
Elevations of protein S-100 (S-100) in cerebrospinal fluid and serum have been reported after cerebral infarctions. The aim of our study was to evaluate the time course of serum S-100 concentrations after territorial middle cerebral artery (MCA) infarctions in correlation with clinical data and prognosis.

Methods
S-100 serum levels were serially determined in 26 patients with an acute infarction in the territory of the MCA at day 0 (within 12 hours after onset of symptoms), day 1 (24 hours after stroke onset), and days 2, 3, 4, 5, 7 or 8, and 10 after stroke and in 26 age- and sex-matched control subjects. S-100 assays were performed using a two-site radioimmunoassay technique. The clinical status was documented using the Scandinavian Stroke Scale. The functional deficit 4 weeks after stroke onset was scored by use of the modified Rankin scale. A cranial computed tomography (CCT) was performed initially and at day 4 or 5.

Results
Elevated concentrations of S-100 (>0.2 μg/L) were observed in 21 of 26 patients with MCA infarction but in none of the control subjects. S-100 levels peaked at days 2 and 3 after stroke. The S-100 concentrations in serum were significantly higher in patients with severe neurological deficits at admission, with extensive infarctions and a space-occupying effect of ischemic edema as compared with the rest of the population. S-100 values were not significantly correlated with the functional prognosis.

Conclusions
Presence of S-100 in serum after ischemic stroke may be due to combined leakage out of necrotic glial cells and passage through an impaired brain-blood barrier, indicating severe ischemic cell injury. Therefore, S-100 in serum can be used as a peripheral marker of ischemic focal brain damage and may be helpful for therapeutic decisions in acute ischemic stroke.
Early Detection of Irreversibly Damaged Ischemic Tissue by Flumazenil Positron Emission Tomography in Cats
Authors: Heiss Wolf-Dieter , Graf Rudolf , Fujita Toshiaki , Ohta Kouichi , Bauer Bernd , Löttgen Jan , Wienhard Klaus
Published: June 2011

Background and Purpose
Ligands for cerebral benzodiazepine receptors were used in the past to indicate the intactness of cortical neurons in subacute to chronic states after stroke and thus to differentiate among brain regions with complete or incomplete infarction and with functional deactivation. For planning acute interventional therapy, however, a marker of irreversible damage in early ischemia is needed. We studied the applicability of [
11
C]flumazenil (FMZ) for differentiation between tissue with and without potential of recovery in the first hours after focal experimental ischemia.

Methods
In 11 cats, cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction, and FMZ binding were studied repeatedly by positron emission tomography before, during, and up to 12 hours after transient middle cerebral artery occlusion (MCAO) (30 minutes in 2, 60 minutes in 7, and 120 minutes in 2 cats, respectively). Development of the defects in energy metabolism were compared with the defects in FMZ binding (2 to 3 hours and 8 to 9 hours after MCAO), with the pattern of disturbed glucose metabolism (determined 12 hours after MCAO), and with the size of the infarcts (determined ≈15 hours after MCAO).

Results
Irrespective of the level of reperfusion, defects in FMZ binding (2 to 3 hours after MCAO) were closely related to areas with severely depressed oxygen consumption and predicted the size of the final infarcts, whereas preserved FMZ binding indicated intact cortex. Depression of glucose metabolism was in all animals larger than the defects in FMZ binding and the infarcts, indicating functional deactivation of brain areas beyond the permanent morphological damage. In addition, FMZ distribution within 2 minutes after injection was significantly correlated to flow and yielded reliable perfusion images.

Conclusions
The reduction of FMZ binding early after focal ischemia reflects irreversible neuronal damage that otherwise only can be detected by multitracer studies. Our experimental data and first clinical applications suggest that FMZ has potential as an indicator of developing infarction. Since FMZ distribution additionally images perfusion, this tracer might be useful for the selection of patients who would benefit from acute therapeutic intervention.
Surgery for Primary Intracerebral Hemorrhage: Is It Safe and Effective?
Authors: Hankey Graeme J. , Hon Christine
Published: June 2011

Background and Purpose
The surgical treatment of primary intracerebral hemorrhage (PICH) varies thoughout the world, mainly because of the lack of evidence of its safety and effectiveness. This study compares the outcome of patients with PICH who are treated surgically with those who are not.

Methods
We conducted a systematic overview (meta-analysis) of all studies of the outcome of surgery for PICH by means of a Medline search of relevant randomized trials and case series published since 1966. Cited references and presentations were also reviewed.

Results
The 15 case series of surgery for PICH involving a total of 1524 patients (654 treated surgically) are potentially confounded and the results inconclusive. The pooled results of the three randomized controlled trials of open craniotomy and one trial of endoscopic evacuation for supratentorial PICH in a total of 349 patients (173 treated surgically) indicate a nonsignificant increase in odds of death and dependency at 6 months for patients treated surgically (odds ratio, 1.23; 95% confidence interval, 0.77 to 1.98). The odds of death or dependency at 6 months were 2.1 (1.1 to 4.1) for patients undergoing craniotomy and 0.45 (0.2 to 1.0) for endoscopic evacuation.

Conclusions
There is insufficient evidence of the risks and benefits of surgery for PICH. Further randomized trials are needed to identify whether there is a favorable treatment effect of surgery, the types of PICH and patients who are likely to benefit and not benefit, and the safety and effectiveness of the different surgical interventions.
Postural Dysregulation in Systolic Blood Pressure Is Associated With Worsened Scoring on Neurobehavioral Function Tests and Leukoaraiosis in the Older Elderly Living in a Community
Authors: Matsubayashi Kozo , Okumiya Kiyohito , Wada Tomoko , Osaki Yasushi , Fujisawa Michiko , Doi Yoshinori , Ozawa Toshio
Published: June 2011

Background and Purpose
Postural hypotension, which occurs frequently in community-living, apparently healthy elderly adults, is usually asymptomatic. However, the relation between postural changes in blood pressure and quantitative higher cerebral function or silent brain lesions remains unclear. We examined the association of exaggerated postural changes in systolic blood pressure with cognitive and quantitative neurobehavioral functions and with brain lesions on MRI in the community-dwelling older elderly.

Methods
The study population consisted of 334 community-dwelling elderly adults, aged 75 years or older (mean age, 80 years). Postural changes in systolic blood pressure (SBP) were assessed using an autosphygmomanometer (BP-203 I). By the difference between the mean of two measurements of SBP at standing and at supine position (dSBP=SBP at upright−SBP at supine position), we divided the subjects into three groups: (1) 20 subjects with postural hypotension (d-SBP ≦−20 mm Hg), (2) 29 subjects with postural hypertension (dSBP ≧20 mm Hg), and (3) 285 subjects with postural normotension (20<dSBP<20 mm Hg). We defined the former two groups as the postural dysregulation group. Scores in four neurobehavioral function tests (Mini-Mental State Exam, Hasegawa Dementia Scale Revised, computer-assisted visuospatial cognitive performance score, and the Up and Go Test) and activities of daily living were compared among the three groups. Brain lesions on MRI, including number of lacunes and periventricular hyperintense lesions, were compared among 15 age- and sex-matched control subjects with postural hypotension, 15 with postural hypertension, and 30 with postural normotension.

Results
Twenty subjects (6.0%) exhibited postural hypotension and 29 (8.7%) postural hypertension. Scores in neurobehavioral functions and activities of daily living were significantly lower in the postural dysregulation group (both postural hypotension and hypertension groups) than in the postural normotension group. The postural dysregulation group exhibited significantly more advanced periventricular hyperintensities than the normotension group.

Conclusions
Asymptomatic community-dwelling elderly individuals with postural hypotension as well as those with postural hypertension had poorer scores on neurobehavioral function tests and more advanced leukoaraiosis demonstrated on MRI than those without exaggerated postural changes in SBP.
Mechanisms of Bradykinin-Induced Cerebral Vasodilatation in Rats
Authors: Sobey Christopher G. , Heistad Donald D. , Faraci Frank M.
Published: June 2011

Background and Purpose
Relatively little is know regarding mechanisms by which reactive oxygen species produce dilatation of cerebral arterioles. The goal of this study was to test the hypothesis that vasodilator responses of cerebral arterioles to bradykinin, which produces endogenous generation of reactive oxygen species, involve activation of calcium-dependent potassium channels.

Methods
We used a cranial window in anesthetized rats to examine effects of catalase (which degrades hydrogen peroxide) on responses to bradykinin. In addition, we examined effects of tetraethylammonium (TEA) and iberiotoxin, inhibitors of calcium-dependent potassium channels, on responses of cerebral arterioles to hydrogen peroxide, bradykinin, and papaverine.

Results
In cerebral arterioles (baseline diameter=40±1 μm) (mean±SE), hydrogen peroxide (10 and 100 μmol/L) produced concentration-dependent dilatation. TEA (1 mmol/L), an inhibitor of calcium-dependent potassium channels, produced marked inhibition of vasodilatation in response to hydrogen peroxide. For example, 100 μmol/L hydrogen peroxide dilated arterioles by 13±2% in the absence and 4±1% (
P
<.05 versus control) in the presence of TEA. Bradykinin (10 nmol/L to 1 μmol/L) also produced concentration-dependent dilatation of cerebral arterioles that was inhibited completely by catalase (100 U/mL). TEA or iberiotoxin markedly inhibited vasodilatation in response to bradykinin. For example, 100 nmol/L bradykinin dilated arterioles by 21±3% in the absence and 2±2% (
P
<.05 vs control) in the presence of iberiotoxin (50 nmol/L).

Conclusions
These findings suggest that dilatation of cerebral arterioles in the rat in response to hydrogen peroxide, or hydrogen peroxide produced endogenously in response to bradykinin, is mediated by activation of calcium-dependent potassium channels. Thus, activation of potassium channels may be a major mechanism of dilatation in response to reactive oxygen species in the cerebral microcirculation.
A Clinical Comparison of Definite Moyamoya Disease Between South Korea and Japan
Authors: Ikezaki Kiyonobu , Han Dae Hee , Kawano Teruaki , Kinukawa Naoko , Fukui Masashi
Published: June 2011

Background and Purpose
The goal of the present study was to clarify whether South Korean patients with moyamoya disease have clinical features similar to those of Japanese patients.

Methods
From 26 South Korean neurosurgical institutes, 296 definite cases were collected and analyzed statistically. These cases were then compared with 731 Japanese definite cases registered to the Research Committee on Moyamoya Disease of the Ministry of Health and Welfare, Japan.

Results
The Korean age distribution patterns showed two peaks that were similar to those seen in Japanese patients. The incidence of adult moyamoya disease in South Korea, however, was 20% higher than that in Japanese patients. The family occurrence rate was 1.8% in Koreans. The incidence of cerebral infarction and bleeding in Koreans was statistically higher, whereas transient ischemic attack and seizure were less than those in Japanese subjects. The incidence of infarction in children and that of hemorrhage in both children and adults were also statistically higher in Koreans. The incidence of hemorrhage was higher in females than in males. Both the age at onset and sex affected the disease type. Although most Japanese patients underwent direct bypass surgery and/or combined indirect bypass procedures, single encephaloduroarteriosynangiosis was performed on 87.6% of all surgical cases in Koreans. Despite the higher incidence of hemorrhagic type in South Korea, the outcomes of the patients were similar to those of the Japanese patients.

Conclusions
This study suggests that the clinical background of moyamoya disease in South Korea is essentially similar to that in Japan.
Clinically Silent Microemboli in Patients With Artificial Prosthetic Aortic Valves Are Predominantly Gaseous and Not Solid
Authors: Kaps Manfred , Hansen Jochen , Weiher Michael , Tiffert Karsten , Kayser Iris , Droste Dirk W.
Published: June 2011

Background and Purpose
Microembolic signals (MES) are frequently observed by transcranial Doppler ultrasound after prosthetic heart valve implantation. Whether these MES are due to solid or gaseous particles is uncertain. We hypothesized that MES are gaseous and that if they are due to cavitation effects, their occurrence should respond to changes of dissolved oxygen concentration in the blood.

Methods
Transcranial monitoring of MES was performed in five patients with prosthetic aortic valves, who inspired 100% oxygen through a facial mask. In one patient 100% oxygen was administered under hyperbaric (2.5 kPa) conditions in a hyperbaric chamber.

Results
Inspiration of 100% oxygen reduced the total number of MES from 96/30 min to 2/30 min. Increasing the concentration of dissolved oxygen in the hyperbaric chamber led to an increase from 0.3 MES per minute (1.0 kPa) to 0.9 MES per minute (2.5 kPa).

Conclusions
The dependence of occurrence of MES in patients with prosthetic cardiac valves on the oxygen partial pressure in blood provides strong evidence that these microemboli are gaseous.
Medical Therapy for Intracerebral Hematoma With the γ-Aminobutyric Acid-A Agonist Muscimol
Authors: Lyden Patrick D. , Jackson-Friedman Catherine , Lonzo-Doktor Lisa
Published: June 2011

Background and Purpose
No therapy has been rigorously proven effective for intracerebral hematoma, although surgery is frequently used for some types of lobar hemorrhages. Since intracerebral mass causes significant ischemia in surrounding brain, we reasoned that anti-ischemia therapy might improve outcome after experimental hematoma.

Methods
We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats. Four hours later we administered intravenously 2 mg/kg muscimol, a potent agonist of the γ-aminobutyric acid-A receptor (n=20); 1 mg/kg MK-801, an antagonist of the
N
-methyl-
d
-aspartate receptor (n=17); or saline (n=28). Forty-eight hours after collagenase injection we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase by the quantal bioassay procedure. Brains were then prepared for histomorphometry and brain volumes estimated.

Results
We found that the ED
50
for collagenase (amount of enzyme that renders 50% of the subjects abnormal) was 0.77±0.09 U in saline-treated subjects. Treatment with muscimol significantly increased the ED
50
to 1.2±0.21 U, for a potency ratio of 1.55±0.34 (
t
=1.7,
P
<.05). MK-801 did not affect outcome. Volume of hematoma was significantly correlated with amount of injected collagenase (n=33,
r
=.64,
P
<.001). Volumes of basal ganglia and white matter were significantly reduced by hemorrhage, and muscimol partially ameliorated this.

Conclusions
We conclude that muscimol significantly improves neurological outcome after intracerebral hematoma.
Cerebral Aneurysms Arising at Nonbranching Sites
Authors: Kondo Soichiro , Hashimoto Nobuo , Kikuchi Haruhiko , Hazama Fumitada , Nagata Izumi , Kataoka Hideo
Published: June 2011

Background and Purpose
The origin and pathogenesis of cerebral aneurysms arising at nonbranching sites are not clear. Using our animal model to induce cerebral aneurysms in rats, we examined induced aneurysms that developed at nonbranching sites.

Methods
In 35 Sprague-Dawley rats, the left common carotid artery was ligated and renal hypertension was produced to induce cerebral aneurysms. Twelve months later, the circle of Willis was carefully examined under a dissecting microscope.

Results
Other than cerebral aneurysms at branching sites of the circle of Willis, aneurysmal bulges developing at nonbranching sites were found in the proximal portion of the posterior cerebral artery (P1) on the side of carotid ligation, which supposedly acted as a major collateral pathway after the ligation, in 19 of 35 treated rats. A total of 30 lesions were found in these 19 rats, and they were classified into fusiform aneurysms (22 lesions) involving the entire vessel wall for a short distance and saccular aneurysms (8 lesions) involving only a part of the wall and expanding laterally from the vessel wall. These P1s became larger in caliber and more tortuous after ligation. Aneurysms developed more frequently in proportion to these changes in these vessels. Moreover, most aneurysms in these vessels developed at or near the curvatures. All of the lateral aneurysms were found on the lateral wall of the curvatures of the vessels.

Conclusions
The present findings indicate that cerebral aneurysms at nonbranching sites and saccular aneurysms at branching sites can occur under the same etiologic conditions. The site of origin is strongly related to hemodynamic stress.
High Glucose Concentrations Dilate Cerebral Arteries and Diminish Myogenic Tone Through an Endothelial Mechanism
Authors: Cipolla Marilyn J. , Porter John M. , Osol George
Published: June 2011

Background and Purpose
Diabetes is associated with cerebrovascular disease and impaired autoregulation of cerebral blood flow. The purpose of this study was to determine the effect of acute glucose exposure on basal tone and myogenic reactivity of isolated rat cerebral arteries.

Methods
Posterior cerebral arteries (PCAs, n=38) were dissected from male Wistar rats and mounted on glass cannulas in a system that allowed control of transmural pressure (TMP) and measurement of lumen diameter. Arteries were exposed to various concentrations of glucose, and the amount of basal tone and reactivity to TMP was measured. The effect of elevated glucose on cerebral endothelial modulation of basal tone was determined by mechanical denudation and the use of inhibitors of both nitric oxide and prostaglandin synthesis.

Results
Arteries exposed to 44 versus 5.5 mmol/L glucose developed significantly less intrinsic tone (percent tone, 2±1% versus 28±2%;
P
<.01) and responded passively to increases in TMP. Preexisting tone present in 5.5 mmol/L glucose was eliminated on exposure to 44 mmol/L glucose, which decreased tone from 30±5% to 5±4% (
P
<.01). Glucose-induced dilations were concentration dependent such that half-maximal responses were obtained at 25±2 mmol/L. Endothelial removal abolished this effect, and the amount of tone was similar in 5.5 versus 44 mmol/L glucose (percent tone, 46±6% versus 49±5%;
P
>.05), as did inhibition of nitric oxide production with 0.3 mmol/L nitro-
l
-arginine (percent tone, 52±4% versus 46±3%;
P
>.05); however, blockade of the cyclooxygenase pathway with indomethacin (10
−5
mmol/L) only partially inhibited the dilation to glucose (percent tone, 32±3% in 5.5 mmol/L versus 12.4±3% in 44 mmol/L;
P
<.01).

Conclusions
Acute glucose exposure dilates arteries with intrinsic tone and impairs cerebrovascular reactivity to TMP via an endothelium-mediated mechanism that involves nitric oxide and prostaglandins.
Prevalence and Determinants of Carotid Atherosclerosis in Healthy Postmenopausal Women
Authors: Lassila Holly C. , Tyrrell Kim Sutton , Matthews Karen A. , Wolfson Sidney K. , Kuller Lewis H.
Published: June 2011

Background and Purpose
Subclinical atherosclerosis in the carotid arteries can be assessed noninvasively with B-mode ultrasound. Few studies have included enough younger postmenopausal women to examine risk factors specific to this group that were related to subclinical carotid atherosclerosis.

Methods
A subgroup of 200 participants of the Healthy Women Study underwent B-mode ultrasound of the carotid arteries. Intima-media thickness (IMT) and focal plaque were assessed in each carotid artery. Data regarding risk factors, including blood pressure parameters, lipid values, body mass index, smoking history, and hormone status, were collected at three separate time points ( before menopause, 1 year after menopause, and 5 or 8 years after menopause).

Results
The mean IMT was 0.76±0.11 mm, and 50% of the population had at least one focal plaque. Smoking had the strongest association with the presence of plaque. Women who smoked at the time of the ultrasound evaluation had five times the odds of having at least one focal plaque compared with women who had never smoked (95% confidence interval, 2.0 to 13.0;
P
≤.01). After we controlled for age and years after menopause, premenopausal values of pulse pressure (
P
≤.05), LDL cholesterol (
P
≤.05), and a history of smoking (
P
≤.01) were independently predictive of plaque. Premenopausal values of triglycerides, pulse pressure, and ever smoking were independently related to average IMT after we controlled for age and years after menopause.

Conclusions
This study has provided valuable information about the prevalence of carotid atherosclerosis and the risk factors related to carotid atherosclerosis in a group of healthy postmenopausal women.
Stroke, Disability, and Dementia
Authors: Prencipe Massimiliano , Ferretti Cinzia , Casini Anna R. , Santini Manuela , Giubilei Franco , Culasso Franco
Published: June 2011

Background and Purpose
Stroke, disability, and dementia often coexist in elderly people. We assessed the prevalence and mutual association of these disorders in an elderly rural population.

Methods
We carried out a door-to-door survey on all subjects aged 65 years or over (n=1032) living in a rural community. To evaluate the associations between stroke and disability and between stroke and dementia, we compared stroke patients with all stroke-free subjects by means of two multiple logistic regression analyses. Subsequently, we performed a case-control analysis by comparing each stroke patient with two age- and sex-matched population control subjects.

Results
We identified 80 stroke patients. After the exclusion of five incident cases, the prevalence of stroke was 7.3% (95% confidence interval [CI], 5.7 to 8.9). Sixty-five percent of stroke survivors and 23% of stroke-free subjects were disabled (age- and sex-adjusted odds ratio [OR], 6.3; 95% CI, 3.7 to 10.9). Thirty percent of stroke survivors and 5.7% of stroke-free subjects were demented. The OR for dementia (stroke patients versus all stroke-free subjects) was 5.8 (95% CI, 3.1 to 10.8) and became 3.4 (95% CI, 1.5 to 8.0) in the case-control analysis.

Conclusions
In our population, the prevalence of stroke was higher than in previous studies. Stroke survivors were more disabled and more at risk for dementia than stroke-free subjects.
Bigated Transcranial Doppler for the Detection of Clinically Silent Circulating Emboli in Normal Persons and Patients With Prosthetic Cardiac Valves
Authors: Droste D. W. , Hagedorn G. , Nötzold A. , Siemens H.-J. , Sievers H. H. , Kaps M.
Published: June 2011

Background and Purpose
Detection of clinically silent circulating microemboli by transcranial Doppler sonography is now being widely investigated in the hope of identifying patients at increased risk for stroke. Automatic detection by bigated Doppler, which uses sampling from two different depths in the artery under study and considers the motion of the embolus, may help to define “periods of interest” that can be evaluated off-line.

Methods
In 12 normal volunteers and 10 patients with prosthetic aortic valves, we performed 1-hour recordings from one middle cerebral artery. In the normal subjects, we produced additional artifacts to use them as false-positives. Detection of microemboli was done off-line from digital audiotapes by an experienced blinded investigator (used as the gold standard) and was compared with on-line detection using specially designed software.

Results
With the setting used, 91.5% of all recorded artifacts could correctly be identified as such with the software. Embolic signals were detected by the software with a specificity of 59.9% and a sensitivity of 74.3%.

Conclusions
Bigated Doppler adds a new dimension to the definition and detection of microembolic signals. It constitutes an important step forward toward automatic screening of stroke-prone patients. Assessing on-line periods of interest during the recording and going over the recorded data again off-line helps to save time for the discrimination of embolic signals from both the normal Doppler spectrum background and artifacts.
Prognosis of Stroke Patients Requiring Mechanical Ventilation in a Neurological Critical Care Unit
Authors: Steiner Thorsten , Mendoza Gabriel , Michael De Georgia  , Schellinger Peter , Holle Rolf , Hacke Werner
Published: June 2011

Background and Purpose
Intubation and mechanical ventilation are sometimes necessary during treatment of acute stroke. Indications include neurological deterioration, pulmonary complications, and elective intubation for procedures and surgery. Prognosis in severe stroke patients requiring mechanical ventilation has often been reported to be poor. This study was performed to prospectively assess the prognosis of stroke patients who require ventilation in a neurological intensive care unit and to determine factors that may influence outcome.

Methods
Analysis was made of 124 consecutive stroke patients who required mechanical ventilation over a 2-year period. We determined the survival rate at 1 year after admission. Initial clinical data, history of previous diseases, and indication for intubation were analyzed for prognostic significance by univariate and multiple logistic regression analysis.

Results
The 1-year survival rate was 33.1% (n=41). Sixty-five patients (52%) died in the neurological intensive care unit. Among 17 variables analyzed, seven were found to significantly influence 2-month fatality in the univariate analysis: age greater than 65 years, atrial fibrillation, bilateral absence of pupillary light reflex, bilateral absence of corneal reflex, bilateral Babinski’s sign, infratentorial stroke, and Glasgow Coma Scale (GCS) score less than 10. Independent predictors of death at 2 months were age greater than 65 years (
P
=.03), GCS score less than 10 (
P
=.01), and intubation performed because of coma or acute respiratory failure (
P
=.04).

Conclusions
Overall prognosis of ventilated patients with severe stroke is better than previously reported. Older patients comatose on admission who need to be intubated because of neurological or respiratory deterioration have the poorest prognosis. We conclude that intubation and mechanical ventilation of severe stroke patients should be performed in a timely manner, before irreversible damage occurs.
Comparison of Stroke Features and Disability in Daily Life in Patients With Ischemic Stroke Aged 55 to 70 and 71 to 85 Years
Authors: Pohjasvaara Tarja , Erkinjuntti Timo , Vataja Risto , Kaste Markku
Published: June 2011

Background and Purpose
This study compared stroke features and poststroke disability in two age groups of patients with ischemic stroke: younger (55 to 70 years) and older (71 to 85 years). Stroke has an impact on daily living in many areas, but whether risk factors, stroke features, and poststroke disability differ between young and old patients with stroke is not so well established.

Methods
A cohort of 486 ischemic stroke patients aged 55 to 85 years admitted consecutively to the Helsinki University Central Hospital (Finland) between December 1, 1993, and March 31, 1995, were examined 3 months after the index stroke. Structured medical, neurological, and radiological (MRI or CT) examinations, mental status, and emotional examination and interview of a close informant were done. Prestroke and poststroke activities of daily living were assessed with five scales: the Index of ADL, Instrumental Activities of Daily Living Scale, Functional Activities Questionnaire, Blessed Functional Activities Scale, and Barthel Index.

Results
History of cardiac failure (
P
<.001), atrial fibrillation (
P
<.001), and cardioembolic stroke (
P
=.011) was more frequent in the older age group, whereas stroke due to large-artery atherosclerosis (
P
=.048) was more common in the younger age group. The older patients more often had major dominant stroke syndrome (
P
=.018).

Comparison of activities of daily living before and after stroke showed that the older age group deteriorated significantly more than the younger age group after adjustment for sex, education, and living conditions (Barthel Index,
P
=.005; other scales,
P
<.0001).

Conclusions
The stroke patients in young and old age groups had different risk profiles and stroke features. The older stroke patients were more dependent and disabled beforehand, and after stroke they were relatively even more dependent than the patients in the younger age group. Because older patients already constitute the majority of stroke victims, the importance of early active diagnosis, treatment, rehabilitation, and guidance is stressed.
Transient Neurological Attacks in the General Population
Authors: Bots Michiel L. , van der Wilk Eline C. , Koudstaal Peter J. , Hofman Albert , Grobbee Diederick E.
Published: June 2011

Background and Purpose
Patients with typical transient ischemic attacks (TIAs) have a higher risk of stroke but a lower risk of cardiac events than patients with nonspecific transient neurological symptoms. We assessed the prevalences of typical TIAs and nonspecific transient neurological attacks (TNAs) and their determinants in the general population because such data are virtually absent.

Methods
The Rotterdam Study is a population-based cohort study of 7983 subjects, aged 55 years and over, conducted in a district of Rotterdam, the Netherlands. At baseline examination, a history of episodes of disturbances in sensibility, strength, speech, and vision that lasted less than 24 hours and occurred within the preceding 3 years was determined by a trained physician. When such a history was present, information on time of onset, duration, and disappearance of symptoms and a detailed description of the symptoms (in ordinary language) were obtained. Subjects were classified by a neurologist as typical TIA or nonspecific TNA.

Results
Prevalence of TNAs was 1.9% in subjects aged 55 to 64 years, 3.5% in subjects aged 65 to 74 years, 4.3% in subjects aged 75 to 84 years, and 5.1% in subjects aged 85 years or over. Prevalence figures for typical TIA were 0.9%, 1.7%, 2.3%, and 2.2% and for nonspecific TNA 1.0%, 1.8%, 2.0%, and 2.9%, respectively. Clinical parameters such as number of attacks, onset, duration, and disappearance of symptoms were similar for typical TIA and nonspecific TNA. Increased age, male sex, diabetes mellitus, low HDL cholesterol, Q-wave myocardial infarction on electrocardiogram, and carotid atherosclerosis were related to typical TIA, whereas increased age, hypertension, low HDL cholesterol, smoking, and angina pectoris were associated with nonspecific TNA.

Conclusions
About half of the subjects with a TNA had symptoms that were not entirely typical for a TIA. Differences in associations with risk factors between typical TIA and nonspecific TNA point toward different underlying mechanisms of symptoms and may lead to different ancillary investigations and possibly treatment.
Paramedian Pontine Infarction
Authors: Kataoka Satoshi , Hori Ariyuki , Shirakawa Tomoyasu , Hirose Genjiro
Published: June 2011

Background and Purpose
There have been few reports of pontine syndromes secondary to paramedian pontine infarctions. To clarify the clinicotopographical correlation and prognosis of paramedian pontine infarct syndromes, we analyzed the clinical signs and their association with MRI findings.

Methods
We studied 49 patients with acute paramedian pontine infarcts and classified them into three subtypes on the basis of lesion location on MRI. Patient clinical status was assessed by Rankin Disability Scale (RDS) scores on admission and at 60 days after onset of stroke.

Results
Twenty-seven patients had basal infarcts. Clinical findings included dysarthria (n=27), hemiparesis with upper extremity predominance (n=15), brachial monoparesis (n=4), and pathological laughing (n=3). Fifteen patients had basal-tegmental infarcts. Clinical findings presented with hemiparesis and horizontal gaze abnormalities, including abducens nerve palsy (n=1), internuclear ophthalmoplegia (INO) (n=5), horizontal gaze palsy (n=1), one-and-a-half syndrome (n=1), and superficial or proprioceptive sensory dysfunction (n=8). Seven patients had tegmental infarcts. Clinical findings included INO (n=1), horizontal gaze palsy (n=2), one-and-a-half syndrome (n=3), and sensory changes (n=2). On both admission and 60 days later, the RDS scores of the patients with upper pontine lesions were significantly better than those with lower pontine lesions (
P
<.01). The RDS scores of the patients with basal-tegmental infarct in the upper pons were significantly better than those with infarct in the lower pons (
P
<.02).

Conclusions
Paramedian pontine infarcts, which are usually due to thrombosis of perforating arteries, presented with a faciobrachial dominant hemiparesis with dysarthria, somatosensory disturbance, and horizontal gaze abnormalities. The favorable outcome may be related to the level of the pontine lesion, which influences the effect on the corticospinal tract.
Rapid Disruption of an Astrocyte Interaction With the Extracellular Matrix Mediated by Integrin α
6
β
4
During Focal Cerebral Ischemia/Reperfusion
Authors: Wagner Simone , Tagaya Masafumi , Koziol James A. , Quaranta Vito , del Zoppo Gregory J.
Published: June 2011

Background and Purpose
Integrins participate in cerebral microvascular integrity and signaling during focal ischemia/reperfusion. The integrin subunits α
1
, α
6
, and β
1
are distributed identically on normal cerebral microvessels. Studies in epithelium indicate that integrin α
6
β
4
, which interacts with laminin-5 in the basal lamina/extracellular matrix, is unique. This study describes the exact location of α
6
, β
4
, and α
6
β
4
and that their responses in focal cerebral ischemia are relevant to astrocyte-matrix interactions.

Methods
The effect of middle cerebral artery occlusion and subsequent reperfusion on the microvascular expression of α
6
β
4
and laminin-5 in regions of cellular injury (dUTP incorporation) was examined in 15 nonhuman primates. Well-characterized antibodies against human α
6
, β
4
, α
6
β
4
, laminin-5 and laminin-1, endothelial CD31, and vascular markers were measured with computerized video imaging and laser confocal microscopy.

Results
Integrin α
6
β
4
was localized on astrocytes where it connects with the extracellular matrix at the astrocyte-vessel interface. It represented 59.3±16.4% of α
6
antigen in cerebral microvessels <100 μm in diameter. By 2 hours of ischemia, the significant reduction in α
6
expression (2
P
<.001) was accompanied by decreases in β
4
/laminin-5 (0.76±0.03 to 0.20±0.09; 2
P
=.001) and α
6
β
4
/laminin-5 (0.73±0.18 to 0.25±0.11; 2
P
=.001) in the region of dUTP incorporation. Parallel changes in laminin-5 and laminin-1 were less pronounced and coincided by 24 hours.

Conclusions
This is the first description of a potential role of integrin α
6
β
4
in the brain, where it mediates astrocyte-matrix interactions. The dramatic disappearance of α
6
β
4
relative to its ligands reflects early loss of integrity between the astrocyte and the vessel wall in selected microvessels in response to ischemia.
Global Ischemia Activates Nuclear Factor-κB in Forebrain Neurons of Rats
Authors: Clemens James A. , Stephenson Diane T. , Smalstig E. Barry , Dixon Eric P. , Little Sheila P.
Published: June 2011

Background and Purpose
After global ischemia, brain levels of hydrogen peroxide, oxygen radicals, and the cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are increased. Oxygen radicals, TNF-α, and IL-1β are known to activate nuclear factor-κB (NF-κB) in vitro. The present study was performed to determine whether NF-κB was activated in vivo by global ischemia in hippocampal CA1 neurons.

Methods
Adult male rats were subjected to 30 minutes of four-vessel occlusion and killed 72 hours later. Levels of NF-κB p50 and p65 subunits in hippocampus were determined by immunocytochemistry, Western blot, and gel-shift analysis. Specific labeling of DNA strand breaks was demonstrated by means of an Apoptag apoptosis detection kit.

Results
Labeling of DNA strand breaks was present at 72 hours. Chromatin compaction and segregation, a characteristic of apoptosis, was observed in sections stained with hematoxylin and eosin. NF-κB p50 and p65 immunoreactivity localized only to nuclei of CA1 neurons at 72 hours after reperfusion. Induction of the activated p50 and p65 subunits was confirmed by Western blot and electromobility shift analysis. The results demonstrate that NF-κB is activated selectively in hippocampal CA1 neurons at 72 hours after four-vessel occlusion, which is at the approximate time of CA1 neuronal cell death.

Conclusions
Transient forebrain ischemia resulted in a marked activation of nuclear NF-κB in the highly vulnerable CA1 sector. Intense nuclear localization of NF-κB was associated only with dying neurons; regions of the hippocampus that were not vulnerable to four-vessel occlusion did not exhibit nuclear NF-κB localization. The elevation of NF-κB in degenerating CA1 neurons may be associated mechanistically with apoptotic or necrotic cell death.
Knowledge of Risk Among Patients at Increased Risk for Stroke
Authors: Samsa Gregory P. , Cohen Stuart J. , Goldstein Larry B. , Bonito Arthur J. , Duncan Pamela W. , Enarson Cam , DeFriese Gordon H. , Horner Ronnie D. , Matchar David B.
Published: June 2011

Background and Purpose
Patients who recognize their increased risk for stroke are more likely to engage in (and comply with) stroke prevention practices than those who do not. We describe perceived risk of stroke among a nationally diverse sample of patients at increased risk for stroke and determine whether patients’ knowledge of their stroke risk varied according to patients’ demographic and clinical characteristics.

Methods
Respondents were recruited from the Academic Medical Center Consortium (n=621, five academic medical centers, inpatients of varying age); the Cardiovascular Health Study (n=321, population-based sample of persons aged 65+ years); and United HealthCare (n=319, five health plans, inpatients and outpatients typically younger than 65 years). The primary outcome was awareness of being at risk for stroke.

Results
Only 41% of respondents were aware of their increased risk for stroke (including less than one half of patients with previous minor stroke). Approximately 74% of patients who recalled being told of their increased stroke risk by a physician acknowledged this risk in comparison with 28% of patients who did not recall being informed by a physician. Younger patients, depressed patients, those in poor current health, and those with a history of TIA were most likely to be aware of their stroke risk.

Conclusions
Over one half of patients at increased risk of stroke are unaware of their risk. Healthcare providers play a crucial role in communicating information about risk, and successful communication encourages adoption of stroke prevention practices. Educational messages should be targeted toward patients least likely to be aware of their risk.
Hemorrhagic Transformation in Acute Ischemic Stroke
Authors: Larrue Vincent , von Kummer Rüdiger , del Zoppo Gregory , Bluhmki Erich
Published: June 2011

Background and Purpose
Recent studies suggest that thrombolytic therapy may be of benefit to patients with acute ischemic stroke. However, the treatment also carries a significant risk of hemorrhagic transformation (HT). The purpose of this study was to select potential contributors to HT.

Methods
We provide an explanatory analysis of the European Cooperative Acute Stroke Study (ECASS) data. ECASS was a multicenter, placebo-controlled, randomized trial of recombinant tissue plasminogen activator in ischemic stroke, within 6 hours of symptom onset, which enrolled 620 patients. HTs were classified into either hemorrhagic infarction or parenchymal hemorrhage according to their CT scan appearance. We used logistic regression analysis to select potential contributing factors to each type of HT.

Results
The severity of initial clinical deficit (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.6 to 4.0) and the presence of early ischemic changes on CT scan (OR, 3.5; 95% CI, 2.3 to 5.3) were associated with increased risk of hemorrhagic infarction. Increasing age (in decades; OR, 1.3; 95% CI, 1.0 to 1.7) and treatment with recombinant tissue plasminogen activator (OR, 3.6; 95% CI, 2.1 to 6.1) were related to the risk of parenchymal hemorrhage.

Conclusions
Since all potential contributing factors are readily discernible upon hospital admission, they should be used to improve selection of patients into future studies.
Intra-arterial Nitrovasodilators Do Not Increase Cerebral Blood Flow in Angiographically Normal Territories of Arteriovenous Malformation Patients
Authors: Joshi Shailendra , Young William L. , Pile-Spellman John , Fogarty-Mack Patricia , Sciacca Robert R. , Hacein-Bey Lotfi , Duong Hoang , Vulliemoz Yvonne , Ostapkovich Noeleen , Jackson Tara
Published: June 2011

Background and Purpose
The mechanism of adaptation to chronic cerebral hypotension in normal brain adjacent to cerebral arteriovenous malformations (AVMs) is unknown. To clarify these mechanisms, we performed cerebral blood flow (CBF) studies in structurally and functionally normal vascular territories during 53 distal cerebral angiographic procedures in 37 patients with AVMs.

Methods
CBF was measured using the superselective intra-arterial
133
Xe method before and after a 3-minute infusion of either verapamil (1 mg·min
−1
, n=23), acetylcholine (1.33 μg·kg
−1
·min
−1
, n=7), nitroprusside (0.5 μg·kg
−1
·min
−1
, n=16) or nitroglycerin (0.5 μg·kg
−1
·min
−1
, n=7).

Results
Mean±SD systemic (76±13 mm Hg) and distal cerebral arterial (55±16 mm Hg; range, 20 to 97 mm Hg) pressures were not different among groups. Verapamil increased CBF (45±12 to 65±21 mL·100 g
−1
·min
−1
,
P
<.001). There was no effect of acetylcholine (no change [46±9 to 46±9 mL·100 g
−1
·min
−1
], NS) or nitroglycerin (36±14 to 36±13 mL·100 g
−1
·min
−1
, NS). Nitroprusside decreased CBF (40±12 to 31±11 mL·100 g
−1
·min
−1
,
P
<.001). The percent change in CBF after drug administration was proportional to cerebral arterial pressure for verapamil only (
r
=.57,
P
=.0051).

Conclusions
When infused intra-arterially in clinically relevant doses in both hypotensive and normotensive normal vascular territories remote from an AVM nidus, calcium channel blockade caused vasodilation, but there was an absence of response to nitric oxide–mediated vasodilators. These data suggest that (1) the nitric oxide pathway probably is not involved in the adaptation to chronic cerebral hypotension in AVM patients and (2) if our findings in vessels remote from or contralateral to the AVM are applicable to vessels of patients with other forms of cerebrovascular disease, clinically relevant doses of intra-arterial nitrovasodilators may not be useful in the manipulation of cerebrovascular resistance.