bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Calcium Regulation in Subcortical Vascular Encephalopathy
Authors: Eckert Anne , Oster Manfred , Förstl Hans , Hennerici Michael , Müller Walter E.
Published: June 2011

Background and Purpose
A number of clinical observations and first in vitro findings indicate that chronic cerebral ischemia influences immunologic status, such as the proliferative response of T lymphocytes. The purpose of the present report was to assess (1) whether changes of immune function are likewise detectable in patients with progressive subcortical vascular encephalopathy (SVE) by investigating the [Ca
2+
]
i
homeostasis of lymphocytes and (2) whether differences exist in calcium regulation between lymphocytes from SVE patients and from Alzheimer’s disease (AD) patients. This is of great interest, since specific changes have been reported recently in AD patients.

Methods
[Ca
2+
]
i
was recorded in 26 patients with SVE, 26 age-matched nondemented control subjects, and 26 age-matched patients with AD. Basal [Ca
2+
]
i
and [Ca
2+
]
i
after lymphocyte activation with the mitogen phytohemagglutinin (PHA) were measured with the fura 2 method. In addition, modulation of the Ca
2+
signaling by the peptide β-amyloid and the potassium channel blocker tetraethylammonium was studied.

Results
Basal [Ca
2+
]
i
was not different between patients and control subjects. After stimulation with PHA, however, a significant reduction of the Ca
2+
response could be observed in lymphocytes of SVE patients compared with control subjects and with AD patients, providing evidence that the Ca
2+
homeostasis of lymphocytes is impaired in SVE. The effect of the peptide β-amyloid, the major constituent of senile plaques in AD brain, on Ca
2+
signaling was similar in SVE patients and nondemented control subjects but typically reduced in cells of AD patients. Potassium channels were not involved in the impaired Ca
2+
response of SVE lymphocytes after cell activation.

Conclusions
[Ca
2+
]
i
is not only one of the most important second messengers in signal transduction of many cells but also an early event in the signal cascade of cell proliferation as a reaction to antigen recognition. This mechanism seems to be impaired in SVE. These findings may result in new insights regarding the pathogenesis of this disease and the possible involvement of inflammatory or immunologic disturbances.
T2-Weighted Hyperintense MRI Lesions in the Pons in Patients With Atherosclerosis
Authors: Kwa Vincent I. H. , Stam Jan , Blok Laura M. , Verbeeten Bernard
Published: June 2011

Background and Purpose
Pontine hyperintense lesions (PHL) on T2-weighted MRI have been recognized recently. Histopathological findings resemble periventricular leukoaraiosis, and a vascular etiology has been suggested. We studied the frequency and the associated factors of PHL in patients with symptomatic atherosclerosis.

Methods
Two independent observers assessed brain MRIs in a prospective cohort of patients with symptomatic atherosclerosis. Only patients in whom both observers scored PHL on T2- and proton density–weighted images, but not on T1-weighted images, were considered to have the lesion.

Results
We studied 229 patients: 31% presenting with ischemic stroke, 31% with myocardial infarction, and 38% with peripheral artery disease. Both observers scored PHL in 23% of all patients. Patients with PHL were significantly older and had more lacunar infarcts and periventricular leukoaraiosis than patients without PHL. There were more women, more hypercholesterolemic and diabetic patients, and more cortical infarcts on MRI (
P
=NS). After logistic regression the presence of leukoaraiosis (odds ratio, 2.4; 95% confidence interval, 1.6 to 3.4) and lacunar infarcts (odds ratio, 2.2, 95% confidence interval, 1.5 to 3.1) remained independently associated with PHL. PHL was more common in patients with ischemic strokes (39%) than in patients with myocardial infarctions (11%) or peripheral artery disease (19%) (
P
<.001).

Conclusions
We found that PHL on T2- and proton density–weighted MR images are often found in patients with symptomatic atherosclerosis. The association with periventricular leukoaraiosis and lacunar infarcts suggests that PHL is a variant of leukoaraiosis, with possibly the same pathophysiology. The clinical symptoms and consequences of PHL, however, are not yet clear.
Assessing Quality of Life After Stroke
Authors: Sneeuw K. C. A. , Aaronson N. K. , de Haan R. J. , Limburg M.
Published: June 2011

Background and Purpose
Because many stroke survivors have cognitive and communication disorders, self-reported information on a patient’s quality of life (QL) cannot always be obtained. Proxy ratings may be used to prevent exclusion of this highly relevant subgroup of patients from QL studies. The purpose of this study was to evaluate both the value and possible limitations of such proxy ratings.

Methods
The patient sample was composed of 437 patients who had suffered a stroke 6 months earlier. QL was assessed by means of the Sickness Impact Profile (SIP). For 108 patients who were not communicative because of cognitive or linguistic deficits, proxy ratings on the SIP were provided by the patients’ significant others. For 228 of the 329 communicative patients, both self-reported and proxy SIP ratings were obtained.

Results
When mean SIP scores for patients with both self-reported and proxy-derived data available were compared, the proxy mean scores were generally in close agreement with those of the patients. However, systematic differences were noted for several SIP scales, with proxies rating patients as having more QL impairments than the patients themselves. Intraclass correlations were moderate to high for most SIP subscales (average intraclass correlation coefficient [ICC]=.63), the physical (ICC=.85) and psychosocial dimensions (ICC=.61), and the total SIP score (ICC=.77). The proxy SIP scores were sensitive to differences in patients’ functional health, which supports the validity of these ratings. For all patients combined, more QL impairments were found for patients with supratentorial cortical or subcortical infarctions and hemorrhages than for patients with lacunar infarctions and infratentorial strokes. Although proxy respondents were more frequently needed for patients with the first two types of stroke, we found no evidence of biased results as a consequence of an unbalanced use of proxy respondents across the different types of stroke.

Conclusions
These results suggest that the benefits of using proxy ratings for noncommunicative patients outweigh their limitations. The findings stress the need for inclusion of this important subgroup of patients in QL studies. Their significant others are able to provide useful information on these patients’ QL.
Harmonic Imaging of the Vertebrobasilar System
Authors: Seidel G. , Kaps M.
Published: June 2011

Background and Purpose
Gas bubbles of ultrasound contrast agents resonate at frequencies used for diagnostic ultrasound and produce harmonics or multiples of the transmitted frequency. Processing of the second harmonic frequency results in a reduction of the signal-to-noise ratio and the signal-to-tissue artifacts. This study is the first to evaluate second harmonic imaging in the cerebral circulation.

Methods
We used a duplex system (HP SONOS 2500) in connection with a 1.8/3.6-MHz (second harmonic) and a 2.5-MHz (conventional) sector transducer. Levovist (6.5 mL; 400 mg/mL) was injected intravenously for second harmonic and conventional color duplex imaging in 13 healthy volunteers (age range, 23 to 34 [median, 29] years).

Results
When second harmonic imaging was compared with conventional color duplex imaging, more cerebellar arteries were detected (35 versus 31), the duration of blooming artifact was significantly reduced (7.9 versus 29.9 seconds;
P
=.03), and the duration of diagnostically useful signal enhancement was increased (248.5 versus 117.4 seconds;
P
=.0003), but the maximal investigation depth was reduced (8.4 versus 9.3 cm;
P
=.001). When conventional and second harmonic duplex were compared, there was a significant (
P
<.04) difference in the systolic blood flow velocity in the vertebral and basilar arteries.

Conclusions
Second harmonic color duplex imaging in the vertebrobasilar system increases the time of diagnostic useful signal enhancement and produces a better spatial resolution compared with conventional color duplex imaging.
Three-Dimensional Analysis of Vasospastic Major Cerebral Arteries in Rats With the Corrosion Cast Technique
Authors: Ono Shigeki , Date Isao , Nakajima Masaaki , Onoda Keisuke , Ogihara Kotaro , Shiota Tomomi , Asari Shoji , Ninomiya Yoshifumi , Yabuno Nobuyoshi , Ohmoto Takashi
Published: June 2011

Background and Purpose
Although mice, rats, and other small animals are commonly used for molecular biology research, their use in the evaluation of cerebral vasospasm after subarachnoid hemorrhage is somewhat problematic because of the correspondingly small size of their cerebral vessels. We have already reported that the corrosion cast technique was useful for evaluating newly formed cerebral vessels in neural grafts in these small animals. In the present study we applied the corrosion cast technique to the evaluation of hemolysate-induced cerebral vasospasm in rats and performed three-dimensional analysis for comparison. The casting was done 10 minutes after the hemolysate injection, so that only acute “vasospasm” was assessed.

Methods
After withdrawal of 0.1 mL cerebrospinal fluid, 0.2 mL hemolysate (n=9) or saline (n=10) was injected into the cisterna magna of male Sprague-Dawley rats weighing between 300 and 350 g. Ten minutes later, perfusion of a semipolymerized casting medium was performed at an injection pressure of 100 to 120 mm Hg. The brains were immersed and corroded in 10% NaOH solution. After these procedures, the basilar artery as well as peripheral vessels was analyzed morphologically with scanning electron microscopy. Conventional histological analysis with the use of paraffin-embedded section with hematoxylin-eosin staining was also performed, and the results were compared with those for the corrosion cast methods.

Results
In the saline-injected group, SEM showed that the inner surface of the basilar artery was smooth and the form of the endothelial cell was printed on the surface of the cast. In the hemolysate-injected group, the basilar artery showed an apparent vasospasm over its entire length, and corrugation was observed on the inner surface of the basilar artery in a three-dimensional fashion. Higher magnification revealed that the nuclei of the endothelial cells were distorted. Local narrowing of the basilar artery and vasospasm in the arteries of the anterior circulation and in peripheral arteries were also observed. Measurement of the inner diameter of the basilar artery showed 37.8% contraction in the hemolysate-injected group compared with the saline-injected group by the corrosion cast method. This degree of vasospasm was similar to that observed by the conventional histological method.

Conclusions
In this report we show that detailed three-dimensional observation in the rat can be performed qualitatively and quantitatively with the corrosion cast technique. We conclude that this method derives an accurate measurement of the diameter of rat major cerebral arteries and is more reliable for analyzing vasospasm in rats than angiography and other conventional procedures.
Diffusion-Weighted MRI in Acute Subcortical Infarction
Authors: Singer Michael B. , Chong June , Lu Dongfeng , Schonewille Wouter J. , Tuhrim Stanley , Atlas Scott W.
Published: June 2011

Background and Purpose
—Conventional imaging lacks sensitivity and specificity for the detection of early subcortical cerebral infarction. The purposes of our study were (1) to determine the accuracy of diffusion-weighted (DW) MRI for early subcortical infarction and (2) to determine the efficacy of DW MRI for differentiating acute from nonacute subcortical infarctions when conventional MR demonstrates multiple infarctions.

Methods
—Thirty-nine patients with clinically diagnosed acute subcortical infarction and 17 control subjects were imaged with both conventional and DW MRI from 7 hours to 4 days (mean, 2.0 days) after onset of symptoms. All images were read blinded to specific clinical findings. In all cases, the precise neuroanatomic locations of lesions were noted. These lesions were subsequently correlated by an experienced stroke neurologist to determine whether their locations correlated to the patients’ symptoms.

Results
—The accuracy of DW MRI for acute subcortical infarction was 94.6%. In 4 of 39 cases, the acute infarction was not detected on conventional MRI. In 24 of 39 cases, conventional MRI showed the acute lesion as well as multiple other subcortical lesions. In each of these 24 cases, the DW MRI showed a single lesion to be acute, and in all 24 cases, that lesion corresponded to the patients’ acute symptoms.

Conclusions
—DW MRI has very high accuracy for acute subcortical infarction and can differentiate acute from nonacute lesions. These data have significant implications in guiding patient management and patient selection for clinical trials.
Six-Hour Window of Opportunity for Calpain Inhibition in Focal Cerebral Ischemia in Rats
Authors: Markgraf Carrie G. , Velayo Nelson L. , Johnson Michael P. , McCarty Deborah R. , Medhi Shujaath , Koehl Jack R. , Chmielewski Paula A. , Linnik Matthew D.
Published: June 2011

Background and Purpose
—Stroke patients often experience a significant temporal delay between the onset of ischemia and the time to initiation of therapy. Thus, there is a need for neuroprotectants with a long therapeutic window of opportunity. The efficacy of a potent, central nervous system–penetrating calpain inhibitor (MDL 28,170) was evaluated in a temporary model of focal cerebral ischemia to determine the window of opportunity for intracellular protease inhibition.

Methods
—An ex vivo brain protease inhibition assay established pharmacodynamic dosing parameters for MDL 28,170. Middle cerebral artery (MCA) occlusion was accomplished by advancing a monofilament through the internal carotid artery to the origin of the MCA. Postmortem infarct volumes were determined by quantitative image analysis of triphenyltetrazolium-stained brain sections.

Results
—Maximal inhibition of brain protease activity was observed 30 minutes after injection of MDL 28,170 with an estimated pharmacodynamic half-life of 2 hours. MDL 28,170 caused a dose-dependent reduction in infarct volume when administered 30 minutes after MCA occlusion. A window of opportunity study was conducted to determine the maximal delay between the onset of ischemia and the initiation of efficacious therapy. MDL 28,170 reduced infarct volume when therapy was delayed for 0.5, 3, 4, and 6 hours after the initiation of ischemia. The protective effect of MDL 28,170 was lost after an 8-hour delay.

Conclusions
—These data indicate that the therapeutic window of opportunity for calpain inhibition is at least 6 hours in a reversible focal cerebral ischemia model. This protection is observed despite the lethal hypoxic and excitotoxic challenge, suggesting that calpain activation may be an obligatory, downstream event in the ischemic cell death cascade.
Stroke Units Versus General Medical Wards, I: Twelve- and Eighteen-Month Survival
Authors: Rønning Ole Morten , Guldvog Bjørn
Published: June 2011

Background and Purpose
—The long-term effect on survival of treatment in stroke units is still under debate. The hypothesis that a stroke unit with short length of stay increases 1-year and 18-month survival rates was tested in this study.

Methods
—A quasi-randomized, controlled study was undertaken among 802 patients ≥60 years old admitted to the Central Hospital of Akershus in Norway with a diagnosis of stroke between January 1, 1993, and February 1, 1995. All patients with onset of symptoms <24 hours before admittance were included and enrolled and were followed until death or to the end of the observation 18 months after stroke. Patients were allocated to a stroke unit (n=364) or a general medical ward (n=438).

Results
—Case fatality within the first 10 days was 8.2% among patients in the stroke unit and 15.1% among patients in the general medical ward (
P
=.0019). One-year survival among patients treated in the stroke unit was 70.6% and in the general medical wards 64.6% (
P
=.026); 18-month survival rates were 65.1% and 58.0%, respectively (
P
=.021). Among patients with cerebral hemorrhage, 10-day case fatality was 24.5% and 51.6% (
P
=.004) in favor of the stroke unit.

Conclusions
—Stroke units increase survival rates among stroke patients compared with general medical wards. The effect on survival occurs early after the stroke and sustains during at least 18 months of observation.
Three-Dimensional Ultrasound Study of Carotid Arteries Before and After Endarterectomy
Authors: Yao Jiefen , van Sambeek Marc R. H. M. , Dall’Agata Anita , van Dijk Lukas C. , Kozakova Micheala , Koudstaal Peter J. , Roelandt Jos R. T. C.
Published: June 2011

Background and Purpose
—It has been proved that symptomatic patients with severe carotid stenosis benefit from endarterectomy. Currently used methods for quantitation of the severity of carotid stenosis have limitations, and the impact of endarterectomy on the operated region of carotid artery remains unknown. The purpose of this study was to examine the accuracy of a 3-D ultrasound system for quantitation of stenotic lesions and to evaluate changes in regional vessel volume and cross-sectional area after carotid endarterectomy.

Methods
—We studied 14 patients with both carotid angiography and 3-D ultrasound. Of 13 patients who underwent surgery, 12 were reexamined with 3-D ultrasound after surgery. The length and volume of 20 randomly selected plaques were measured from 3-D data sets. The severity of stenosis was quantified by 3-D ultrasound using both a diameter method and an area method on cross-sectional views at the most stenotic site; the results were then compared with those from carotid angiography. The segmental vessel volume and average cross-sectional area of the operated artery both before and after endarterectomy were measured from 3-D ultrasound data.

Results
—Good correlation was obtained between 3-D ultrasound and carotid angiography in quantitative analysis of carotid stenosis (SEE=12.4%,
r
=0.76, and mean difference=7.0±12.3% with the diameter method; SEE=10.5%,
r
=0.82, and mean difference=1.8±10.5% with the area method by 3-D ultrasound). 3-D ultrasound had excellent reproducibility and small intraobserver and interobserver variability in plaque length and volume measurements. No significant changes in segmental vessel volume and average cross-sectional area of the operated artery were observed after surgery in patients with suture closure. However, a significant increase in segmental vessel volume was obtained in patients with polyfluorethylene patches applied to the surgical opening of the artery.

Conclusions
—3-D ultrasound can be used for both qualitative and quantitative analysis of plaques in the carotid artery and to detect and quantify significant carotid stenosis. Its volumetric potential has important clinical implications in serial follow-up studies for observing the progression or regression of stenotic lesions and for evaluating the outcome of interventional procedures such as endarterectomy or stent placement.
A Randomized, Controlled Pilot Study of a Home-Based Exercise Program for Individuals With Mild and Moderate Stroke
Authors: Duncan Pamela , Richards Lorie , Wallace Dennis , Stoker-Yates Joni , Pohl Patricia , Luchies Carl , Ogle Abna , Studenski Stephanie
Published: June 2011

Background and Purpose
—Many stroke survivors have minimal to moderate neurological deficits but are physically deconditioned and have a high prevalence of cardiovascular problems; all of these are potentially modifiable with exercise. The purposes of this randomized, controlled pilot study were (1) to develop a home-based balance, strength, and endurance program; (2) to evaluate the ability to recruit and retain stroke subjects; and (3) to assess the effects of the interventions used.

Methods
—Twenty minimally and moderately impaired stroke patients who had completed inpatient rehabilitation and who were 30 to 90 days after stroke onset were randomized to a control group or to an experimental group that received a therapist-supervised, 8-week, 3-times-per-week, home-based exercise program. The control group received usual care as prescribed by the patients’ physicians. Baseline and postintervention assessments included the Fugl-Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL), the Lawton Scale of Instrumental ADL, and the Medical Outcomes Study–36 Health Status Measurement. Functional assessments of balance and gait included a 10-m walk, 6-Minute Walk, and the Berg Balance Scale. Upper extremity function was evaluated by the Jebsen Test of Hand Function.

Results
—Of 22 patients who met study criteria, 20 completed the study and 2 refused to participate. The experimental group tended to improve more than the control group in motor function (Fugl-Meyer Upper Extremity: mean change in score, 8.4 versus 2.2; Fugl-Meyer Lower Extremity: 4.7 versus −0.9; gait velocity: median change, 0.25 versus .09 m/s; 6-Minute Walk: 195 versus 114 ft; Berg Balance Score: 7.8 versus 5; and Medical Outcomes Study–36 Health Status Measurement of Physical Function: 15.5 versus 9). There were no trends in differences in change scores by the Jebsen Test of Hand Function, Barthel Index, and Lawton Instrumental ADL Scale.

Conclusions
—This study demonstrated that a randomized, controlled clinical trial of a poststroke exercise program is feasible. Measures of neurological impairments and lower extremity function showed the most benefit. Effects of the intervention on upper extremity dexterity and functional health status were equivocal. The lasting effects of the intervention were not assessed.
Risk Factors for Early Recurrence After Ischemic Stroke
Authors: Moroney Joan T. , Bagiella Emilia , Paik Myunghee C. , Sacco Ralph L. , Desmond David W.
Published: June 2011

Background and Purpose
—Information regarding risk factors for early recurrence is limited. Our aim was to identify the clinical predictors of early recurrence after ischemic stroke.

Methods
—We prospectively examined 297 patients (mean age, 72.0±8.4 years) hospitalized with ischemic stroke to identify recurrent strokes occurring within 90 days of the index stroke. Survival free of recurrence was estimated using Kaplan-Meier analysis stratified by demographic variables; vascular risk factors; stroke syndrome, subtype, vascular territory, and severity; scores on the Barthel Index and Mini-Mental State Examination during hospitalization; blood pressure on admission; and selected laboratory data. We estimated the relative risk (RR) of early recurrence associated with those variables using proportional hazards analysis.

Results
—We identified 22 recurrent events in the first 90 days after the index stroke, resulting in an early stroke recurrence rate of 7.4%, and death occurred immediately after recurrence in 6 of the 22 patients. A major hemispheric stroke syndrome (RR=2.9; 95% confidence interval [CI]=1.2 to 7.1), atherothrombotic stroke mechanism (RR=3.3; CI=1.3 to 8.3), and atrial fibrillation (RR=2.2; CI=0.8 to 6.1) were independent predictors of early recurrence, after adjustment for demographic variables.

Conclusions
—Early recurrence was frequent and resulted in increased mortality. Attention to the clinical features of the index stroke, including the presenting syndrome and the ischemic mechanism, and the recognition of atrial fibrillation may help in the selection of patients for the initiation of targeted interventions to prevent early recurrence and subsequent mortality.
Myosin Light Chain Phosphorylation and Contractile Proteins in a Canine Two-Hemorrhage Model of Subarachnoid Hemorrhage
Authors: Sun Hong , Kanamaru Kenji , Ito Masaaki , Suzuki Hidenori , Kojima Tadashi , Waga Shiro , Kureishi Yasuko , Nakano Takeshi
Published: June 2011

Background and Purpose
—Subarachnoid hemorrhage (SAH) impairs both contraction and relaxation response in cerebral arteries. We tested the hypothesis that cerebral vasospasm might be ATP-independent contraction, such as latch state, and protein synthesis might be substantially downregulated due to ATP consumption after long-lasting contraction.

Methods
—Chronic cerebral vasospasm was induced in the canine 2-hemorrhage model of SAH. The normal and spastic basilar arteries were stabilized in Krebs-Henseleit solution, and contraction was induced by 30 μmol/L prostaglandin F
2α
(PGF
2α
) in vitro and in vivo. Before and at 15 minutes and 1 hour after the treatment with PGF
2α
, the levels of phosphorylated 20-kDa myosin light chain (MLC
20
) were measured. The time course of expression of contraction proteins actin and MLC
20
, and contraction-inhibiting proteins
h
-caldesmon and calponin was determined by immunoblotting techniques.

Results
—A significant vasospasm occurred in the basilar artery during days 4 to 21, most prominently on days 7 and 14. There were no significant differences in the baseline levels of phosphorylated MLC
20
between normal and spastic basilar arteries. The increase in MLC
20
phosphorylation by PGF
2α
was significantly attenuated in the spastic basilar artery in vitro and in vivo (
P
<0.05). The immunoreactivity for actin,
h
-caldesmon, and calponin in the spastic basilar arteries was progressively decreased until day 14 and returned to the normal level on day 21. In contrast, protein levels of MLC
20
did not significantly change during days 0 to 21.

Conclusions
—Chronic cerebral vasospasm closely resembles the latch state, and temporary deficiencies of contractile proteins may result from increased destruction and inhibition of protein synthesis.
Matrix Metalloproteinases and TIMPs Are Associated With Blood-Brain Barrier Opening After Reperfusion in Rat Brain
Authors: Rosenberg G. A. , Estrada E. Y. , Dencoff J. E.
Published: June 2011

Background and Purpose
—Reperfusion disrupts cerebral capillaries, causing cerebral edema and hemorrhage. Middle cerebral artery occlusion (MCAO) induces the matrix-degrading metalloproteinases, but their role in capillary injury after reperfusion is unknown. Matrix metalloproteinases (MMPs) and tissue inhibitors to metalloproteinases (TIMPs) modulate capillary permeability. Therefore, we measured blood-brain barrier (BBB) permeability, brain water and electrolytes, MMPs, and TIMPs at multiple times after reperfusion.

Methods
—Adult rats underwent MCAO for 2 hours by the suture method. Brain uptake of
14
C-sucrose was measured from 3 hours to 14 days after reperfusion. Levels of MMPs and TIMPs were measured by zymography and reverse zymography, respectively, in contiguous tissues. Other rats had water and electrolytes measured at 3, 24, or 48 hours after reperfusion. Treatment with a synthetic MMP inhibitor, BB-1101, on BBB permeability and cerebral edema was studied.

Results
—Brain sucrose uptake increased after 3 and 48 hours of reperfusion, with maximal opening at 48 hours and return to normal by 14 days. There was a correlation between the levels of gelatinase A at 3 hours and the sucrose uptake (
P
<0.05). Gelatinase A (MMP-2) was maximally increased at 5 days, and TIMP-2 was highest at 5 days. Gelatinase B and TIMP-1 were maximally elevated at 48 hours. The inhibitor of gelatinase B, TIMP-1, was also increased at 48 hours. Treatment with BB-1101 reduced BBB opening at 3 hours and brain edema at 24 hours, but neither was affected at 48 hours.

Conclusions
—The initial opening at 3 hours correlated with gelatinase A levels and was blocked by a synthetic MMP inhibitor. The delayed opening, which was associated with elevated levels of gelatinase B, failed to respond to the MMP inhibitor, suggesting different mechanisms of injury for the biphasic BBB injury.
Direct Costs of Transient Ischemic Attacks
Authors: Porsdal Vibeke , Boysen Gudrun
Published: June 2011

Background and Purpose
—Knowledge of costs of health care and social services for patients who have transient ischemic attacks (TIAs) is scarce. This study investigates the resource use and estimates direct costs during the first year after a TIA.

Methods
—All patients admitted to a university hospital in Copenhagen, Denmark, because of TIA during 12 months in 1994–1995 were included in a database. The patients were followed until 1 year after admission, and data on resource use during and after the hospital stay were collected prospectively at interviews.

Results
—The cost of the hospital stay had a mean of DKr 10100 (US $1800), and the cost of health care and social services after discharge had a mean of DKr 8800 (US $1600).

Conclusions
—The total cost of health care and social services during the first year after a TIA had a mean of DKr 18800. The hospital stay and the services after discharge each made up half of the total direct cost.
Systolic Blood Pressure Tracking Over 25 to 30 Years and Cognitive Performance in Older Adults
Authors: Swan Gary E. , Carmelli Dorit , Larue Asenath
Published: June 2011

Objective
—To determine the extent to which individual changes in systolic blood pressure (SBP) over a 30-year interval are associated with differential neuropsychological outcomes in old age.

Methods
—Seven hundred seventeen survivors from the Western Collaborative Group Study, a longitudinal study of cardiovascular risk factors now in its 38th year of follow-up, with blood pressures measured in middle age (mean=45 years) and in old age (mean=75 years) and neuropsychological tests administered at follow-up were included in this analysis. Participants were grouped according to 30-year change in SBP (increased, decreased, or “normal”). Analyses focused on comparisons of neuropsychological performance of “high SBP trackers” (ie, those with persistent SBP≥140 mm Hg throughout adult life) and of SBP “decreasers” with the performance of those whose SBP was either stable or changed in an expected way over time.

Results
—Only 7.5% of participants had elevated SBP in middle age, but 43.8% of participants had elevated SBP in old age. After adjustment for age, education, depression, clinically defined stroke, and use of antihypertensive medications and after exclusion of individuals with impaired cognitive performance at follow-up, high SBP trackers, 5.0% (n=36), performed consistently less well than the “normal” SBP subgroups on a composite measure of verbal learning and memory (
P
=0.04). When compared with the “normal” SBP subgroup, the SBP decreasers, 5.3% (n=38), performed less well on speeded performance (
P
=0.03).

Conclusions
—There is a relatively small group of people who maintain elevated SBP throughout their adult lives. These persons are at increased risk for reduced verbal learning and memory function. There is also a group of individuals who experience a decrease in SBP and who are at risk for decreased psychomotor speed. Delineation of these 2 SBP subgroups may lead to further clarification of the effects of SBP on neurobehavioral function in older adults.
Potent ς
1
-Receptor Ligand 4-Phenyl-1-(4-Phenylbutyl) Piperidine Modulates Basal and
N
-Methyl-
d
-Aspartate–Evoked Nitric Oxide Production In Vivo
Authors: Bhardwaj Anish , Sawada Masahiko , London Edythe D. , Koehler Raymond C. , Traystman Richard J. , Kirsch Jeffrey R.
Published: June 2011

Background and Purpose
—ς-Receptor ligands ameliorate ischemic neuronal injury and modulate neuronal responses to
N
-methyl-
d
-aspartate (NMDA) receptor stimulation. Because NMDA-evoked synthesis of nitric oxide (NO) may play an important role in excitotoxic-mediated injury, we tested the hypothesis that ς-receptor ligands attenuate basal and NMDA-evoked NO production in the striatum in vivo.

Methods
—Microdialysis probes were placed bilaterally into the striatum of halothane-anesthetized adult Wistar rats. Rats were divided into 7 treatment groups and perfused with artificial cerebrospinal fluid (aCSF) containing 3 μmol/L [
14
C]
l
-arginine for 2 to 3 hours followed by NMDA in various combinations with the following drugs:
l
-nitroarginine (L-NNA); the ς
1
-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP); the selective ς
1
-receptor antagonist 1-(cyclopropylmethyl)-4-(2′-oxoethyl) piperidine hydrobromide (DuP 734); and the noncompetitive NMDA receptor blocker MK-801 in aCSF. Right-left differences between [
14
C]
l
-citrulline in the effluent from rats treated with different drug combinations were assumed to reflect differences in NO production.

Results
—After a 3-hour loading period with [
14
C]
l
-arginine, addition of 1 mmol/L NMDA increased [
14
C]
l
-citrulline recovery compared with aCSF alone. This NMDA-evoked increase was inhibited by 1 mmol/L of L-NNA and PPBP. Perfusion of 1 mmol/L of the ς
1
-receptor antagonist DuP 734 with 1 mmol/L PPBP augmented NMDA-evoked [
14
C]
l
-citrulline recovery compared with perfusion with PPBP and NMDA. MK-801 attenuated the basal as well as NMDA-evoked [
14
C]
l
-citrulline recovery. PPBP did not cause any further attenuation in the basal and NMDA-evoked [
14
C]
l
-citrulline recovery in the presence of MK-801.

Conclusions
—These data indicate that a ς
1
-receptor ligand attenuates basal as well as NMDA-evoked NO production. Because the attenuated NO production was reversed by DuP 734, PPBP appears to act as an agonist at the ς
1
-receptor. Attenuated NO production by ς
1
-receptor agonists provides one possible mechanism for focal ischemic neuroprotection.
Butyrylcholinesterase K Variant and Cerebral Amyloid Angiopathy
Authors: Yamada Masahito , Sodeyama Nobuyuki , Itoh Yoshinori , Suematsu Naomi , Otomo Eiichi , Matsushita Masaaki , Mizusawa Hidehiro
Published: June 2011

Background and Purpose
—Cholinesterases are found histochemically in the vessels affected with cerebral amyloid angiopathy (CAA). A gene for the K variant of butyrylcholinesterase (
BCHE-K
) may be associated with late-onset Alzheimer’s disease (AD). In search of genetic risk factors for CAA, we investigated the association of
BCHE-K
with CAA.

Methods
—The association between the severity of CAA and
BCHE-K
was investigated in 155 autopsy cases of the elderly, including 48 patients with AD.

Results
—There was no significant association of
BCHE-K
with the severity of CAA in the total, AD, or non-AD cases. Status of the ε4 allele of apolipoprotein E gene did not influence the results.

Conclusions
—Our results may suggest that
BCHE-K
is not a definitive risk factor for CAA in the elderly, although further study with larger samples is necessary to confirm this.
Angioplasty after Intra-Arterial Thrombolysis for Acute Occlusion of Intracranial Arteries
Authors: Ueda Toshihiro , Sakaki Saburo , Nochide Ichiro , Kumon Yoshiaki , Kohno Kanehisa , Ohta Shinsuke
Published: June 2011

Background and Purpose
—The purpose of this study was to report our experience with percutaneous transluminal angioplasty (PTA) of intracranial arteries in acute stroke patients who were resistant to intra-arterial thrombolysis alone.

Methods
—PTA was performed within 6 hours from symptom onset in 13 acute stroke patients in whom no hypodensity areas were observed on initial CT. PTA was classified into 3 categories: immediate (3 patients), delayed (3 patients), and rescue (7 patients) angioplasty. Treatment results in the PTA group for 9 cases of middle cerebral artery (MCA) occlusion were compared with those in the thrombolysis alone group for 12 cases of thrombotic MCA occlusion.

Results
—Technical success rates for immediate, delayed, and rescue angioplasty were 100%, 100%, and 71%, respectively, and that of angioplasty for the MCA was 100%. Ten patients (77%) showed improvement in the National Institutes of Health (NIH) stroke score after treatment. Improvement in NIH stroke scores in the PTA group for MCA occlusion was greater than that in the thrombolysis alone group (
P
<0.01). Nine patients (69%) had an excellent, good, or fair outcome 3 months after treatment. In 9 patients who had follow-up angiography 1 month after treatment, no restenosis or reocclusion was demonstrated. There were no symptomatic complications during or after treatment.

Conclusions
—This limited study demonstrates the technical feasibility of angioplasty for intracranial arteries in acute ischemic stroke and suggests that angioplasty may be an effective option for improving the success rate of recanalization and preventing reocclusion of the MCA. The present results encourage us to perform further clinical trials in a larger number of patients to assess the efficacy of this procedure.
Functional Magnetic Resonance Imaging of Regional Cerebral Blood Oxygenation Changes During Breath Holding
Authors: Kastrup Andreas , Li Tie-Qiang , Takahashi Atsuchi , Glover Gary H. , Moseley Michael E.
Published: June 2011

Background and Purpose
—Recently, noninvasive MRI methods have been developed that are now capable of detecting and mapping regional hemodynamic responses to various stress tests, which involve the use of vasoactive substances such as acetazolamide or inhalation of carbon dioxide. The aim of this study was to assess regional cerebral blood oxygenation changes during breath holding at 1.5 T.

Methods
—In 6 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 10 minutes during alternating periods of breath holding and normal breathing at 40-second intervals after inspiration, at 30-second intervals after expiration, and at 18 seconds after expiration. To quantify the relative signal changes, 2.5-minute baseline image sampling with normal breathing was carried out.

Results
—Repeated challenges of breath holding of various durations induced an overall rise in blood oxygen level–dependent (BOLD) signal intensities. In general, BOLD signal intensity increases were greatest in gray matter and nonsignificant in white matter. Depending on the breath-holding duration and techniques, BOLD signal intensity increases of all activated pixels varied from 0.8% to 3.5%.

Conclusions
—The present study demonstrates that cerebral blood oxygenation changes during breath holding can be detected by means of fMRI at 1.5 T. The breath-holding test, a short and noninvasive method to study cerebral hemodynamics with fMRI, could become a useful alternative to the acetazolamide or CO
2
test.
Differences in Medical and Surgical Therapy for Stroke Prevention Between Leading Experts in North America and Western Europe
Authors: Masuhr Florian , Busch Markus , Einhäupl Karl M.
Published: June 2011

Background and Purpose
—Large multicenter trials have evaluated the benefit of different medical and surgical therapies to prevent stroke. However, the application of trial results to clinical practice remains uncertain for some areas of stroke prevention and has been discussed passionately among international experts. As part of a worldwide survey, the purpose of this analysis was to provide an informative and comparative view of the current practice of leading experts in North America (NA) and Western Europe (WE), where most of the large prevention trials have been performed.

Methods
—The survey was performed worldwide among 185 neurologists who are currently leading the discussions of stroke prevention practices. It contained questions on the use of antiplatelet agents, oral anticoagulation, and surgery for the prevention of ischemic stroke. The population of this present analysis is the two groups of experts from WE (n=73) and NA (n=48) exclusively.

Results
—Of each group, >90% responded to the survey. Nearly all respondents reported prescribing aspirin in patients at risk of atherothrombotic stroke, but significant differences between NA and WE are shown by the recommended doses (
P
<.0001): aspirin doses of >500 mg daily are given exclusively by American participants (36%), whereas doses <200 mg are recommended only in Europe (51%). Eighty-six percent of American versus 59% of European respondents reported using ticlopidine as their second choice (
P
<.005), and 23% of respondents from WE used warfarin compared with 5% from NA (
P
<.05). The reported use of anticoagulants in patients with atrial fibrillation increased in accordance with the patient’s individual risk of stroke, but respondents from WE were more reluctant to use anticoagulants in patients older than 75 years. Relatively higher target international normalized ratio values were reported by European respondents. Nearly all participants recommend carotid endarterectomy in patients with symptomatic carotid stenosis. The use of carotid endarterectomy in asymptomatic patients was significantly more common among responding experts from NA (48% versus 28%;
P
<.05), particularly in patients with >95% stenosis (89% versus 53%;
P
<.0005).

Conclusions
—This analysis shows significant differences in several areas of stroke prevention practices between leading experts from NA and WE. These differences may be explained partly by divergent results of trials from the two continents, but in some areas of controversy currently available trial data are not sufficient to form an international consensus to guide daily clinical practice.
Effects of Induced Hypertension on Transcranial Doppler Ultrasound Velocities in Patients After Subarachnoid Hemorrhage
Authors: Manno E. M. , Gress D. R. , Schwamm L. H. , Diringer M. N. , Ogilvy C. S.
Published: June 2011

Background and Purpose
—Transcranial doppler ultrasound (TCD) is used after subarachnoid hemorrhage to detect cerebral vasospasm and is often treated with induced hypertension. Cerebral autoregulation, however, may be disturbed in this population, raising the possibility that TCD velocities may be elevated by induced hypertension. To study this possibility, we performed continuous TCD monitoring of the middle cerebral artery during the induction and withdrawal of induced hypertension in patients after subarachnoid hemorrhage.

Methods
—Twenty-eight patients were studied during the induction and withdrawal of hypertension using primarily phenylephrine. Continuous monitoring was performed on the middle cerebral artery with the highest flow velocity. Treatment was based on rising TCD velocities or clinical evidence for cerebral vasospasm. Mean arterial pressure and mean TCD velocities were recorded every minute. A change of >15% from starting TCD values was considered significant. Cerebral autoregulation was calculated as a percentage of intact autoregulation. Patients were subsequently divided into groups of disturbed and intact autoregulation.

Results
—In 10 of 19 patients (53%), TCD velocities changed by >15% and paralleled changes in mean arterial pressure. This directly altered the TCD interpretation of the grade of vasospasm in 7 of 19 patients (36%). Three additional patients had smaller absolute changes in TCD velocities. No clinical difference could be identified between patients with disturbed and intact autoregulation.

Conclusions
—In patients with disturbed autoregulation after subarachnoid hemorrhage, induced hypertension can alter cerebral blood flow velocities. The level of autoregulation needs to be considered when interpreting TCD velocities in patients after subarachnoid hemorrhage.
Ischemic Stroke Is Associated With a Systemic Increase of Blood Mononuclear Cells Expressing Interleukin-8 mRNA
Authors: Kostulas Nikolaos , Kivisäkk Pia , Huang Yumin , Matusevicius Darius , Kostulas Vasilios , Link Hans
Published: June 2011

Background and Purpose
—Ischemic brain injury secondary to an arterial occlusion is characterized by acute local inflammation. Blood polymorphonuclear leukocytes (PMNL), primarily neutrophils, adhere to endothelial cells and rapidly invade the injured brain after the arterial occlusion. This neutrophilic invasion might correlate with the production of certain chemoattractants by blood mononuclear cells (MNC). We evaluated mRNA expression of the CXC chemokine interleukin (IL)-8, and the CC chemokines monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1α, and MIP-1β in blood MNC from patients with ischemic stroke.

Methods
—Peripheral blood was obtained at 8
am
on days 1 to 7 (mean, day 3) after onset of symptoms. In situ hybridization with radiolabeled synthetic oligonucleotide probes for the chemokines was adopted to measure chemokine mRNA expression in MNC. An enzyme-linked immunosorbent assay for IL-8 was used to measure IL-8 levels in plasma.

Results
—Most patients with ischemic stroke had high numbers of IL-8 mRNA expressing blood MNC, regardless of the time interval between onset of clinical symptoms and examination. There was a marked difference between patients with ischemic stroke and healthy subjects (median, 6228 versus 885 positive cells per 10
5
MNC;
P
<.0001). IL-8 levels in plasma correlated positively to IL-8 mRNA expression in examined patients (n=7) with ischemic stroke (
r
=.78,
P
<.05). In contrast, mRNA expression for the CC chemokines showed no significant difference between patients with ischemic stroke and healthy control subjects.

Conclusions
—This study demonstrated a systemic increase of IL-8 mRNA expressing MNC and IL-8 levels in plasma from patients with ischemic stroke, suggesting that IL-8 could be involved in recruiting blood PMNL to the sites of cerebral ischemia.
Randomized Comparison of Guglielmi Detachable Coils and Cellulose Acetate Polymer for Treatment of Aneurysms in Dogs
Authors: Loch Macdonald R. , Mojtahedi Saied , Johns Lydia , Kowalczuk Andrew
Published: June 2011

Background and Purpose
—Endovascular treatments for aneurysms are being used more frequently in patients in the absence of a large body of information on their histopathological effects. This study determined the efficacy and histopathological effects of treatment of experimental aneurysms with Guglielmi detachable coils (GDC) or cellulose acetate polymer (CAP).

Methods
—Fourteen dogs had 13 terminal and 30 sidewall aneurysms created with venous pouches sutured to the cervical carotid arteries. Two weeks later, dogs had angiography followed by randomization to no treatment (n=2) or to aneurysm occlusion with GDC (n=4) or CAP (n=6). Two months later, angiography was repeated, animals were killed, and aneurysms were excised, fixed, photographed, and examined by light and electron microscopy.

Results
—Two dogs were excluded because of common carotid artery occlusion at 2-week angiography. There were 11 terminal and 16 sidewall aneurysms available for treatment. The rate of spontaneous thrombosis of untreated aneurysms was 0% (0/5). Treatment with GDC showed complete terminal and sidewall aneurysm obliteration rates of 33% (1/3) and 80% (4/5), respectively. Greater than 90% occlusion occurred in the remaining cases. There were no parent or branch artery occlusions. Treatment with CAP showed complete terminal and sidewall aneurysm obliteration rates of 20% (1/5) and 0% (0/5), respectively, and incomplete sidewall aneurysm obliteration in 1 of 5 cases. Aneurysms reformed at 2 months in 2 of 5 terminal and 1 of 5 sidewall cases. There were parent or branch artery occlusions with CAP in 2 and 4 cases, respectively. The rate of aneurysm occlusion was significantly lower and the rate of arterial occlusion significantly higher with CAP than with GDC (
P
<.05). Histopathology showed complete endothelialization across the orifice of the aneurysm successfully treated with CAP, whereas aneurysms treated with GDC were significantly more likely to show fresh or organizing thrombus without complete endothelialization (
P
<.05).

Conclusions
—It is concluded that both treatments have limitations. Complete packing of aneurysms with GDC obliterates the aneurysm, but endothelialization does not always occur within 2 months. There are substantial problems with CAP. It is thrombogenic and carries a higher risk of causing arterial thrombosis. Even if an aneurysm is successfully obliterated initially with CAP, the CAP may disappear, leaving the aneurysm completely untreated.