bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid-Subclavian Bypass for Brachiocephalic Occlusive Disease
Authors: Law Michael M. , Colburn Michael D. , Moore Wesley S. , Quiñones-Baldrich William J. , Machleder Herbert I. , Gelabert Hugh A.
Published: June 2011

Background and Purpose
Atherosclerotic disease of the proximal brachiocephalic circulation may produce disabling symptoms referable to cerebral or upper extremity hypoperfusion and embolization. Bypass of occlusive lesions can provide durable relief of symptoms with minimal complications. The ideal conduit for carotid-to-subclavian and subclavian-to-carotid bypass remains controversial, and it is not clear whether the outflow vessel influences patency and survival.

Methods
We performed a retrospective analysis of 60 consecutive carotid-to-subclavian and subclavian-to-carotid bypass procedures. Occlusive lesions were documented preoperatively by arteriography. Patency was determined during follow-up by ultrasound or duplex examination. Actuarial patency, symptom-free survival, and overall survival rates were calculated by the life-table method and analyzed by log-rank test.

Results
Arterial transposition demonstrated the highest long-term patency rate (100.0±0.0%). Polytetrafluoroethylene grafts demonstrated the highest bypass graft patency rate (95.2±4.6%), followed by Dacron grafts (83.9±10.5%) and saphenous vein grafts (64.8±16.5%). Symptom-free survival paralleled patency rates, but these differences did not achieve statistical significance. While there were no differences in patency or symptom-free survival by outflow vessel, the overall survival of patients with common carotid lesions was significantly lower than that of patients with subclavian lesions (62.7±12.8% versus 100.0±0.0%;
P
<.05).

Conclusions
The outflow vessel does not affect long-term patency in carotid and subclavian bypass procedures; however, patients with common carotid disease demonstrate significantly poorer long-term survival. Transposition results in superior long-term patency, with a trend toward lower results for synthetic grafts and relatively poor results for autogenous vein grafts.
Computed Tomographic Angiography for the Evaluation of Carotid Artery Stenosis
Authors: Leclerc X. , Godefroy O. , Pruvo J. P. , Leys D.
Published: June 2011

Background and Purpose
No previous study has compared the reliability of carotid artery measurement provided by axial images, shaded surface display (SSD), and maximum intensity projection (MIP).

Methods
Helical CT and conventional angiography were performed prospectively in 20 patients with atherosclerotic stenosis of the internal carotid artery. Stenosis measurement was performed in a blinded fashion on angiography and CT by two independent examiners. Calcifications were segmented when they were located far enough from the vascular lumen. SSD and MIP were systematically performed for each carotid bifurcation. We measured stenosis using conventional angiography as standard and the different CT reconstructions (axial images, SSD, and MIP) by comparing the stenosis diameter at its narrowest point to the normal internal carotid artery. The degree of stenosis was classified into six groups: no stenosis, mild stenosis (<30%), moderate stenosis (30% to 70%), severe stenosis (>70%), near occlusion, and occlusion (100%). No measurement was made in cases of normal artery, near occlusion, and occlusion.

Results
Correlations between angiography and the three types of reconstruction were very good. Axial sections correctly classified the carotid arteries in 95% of cases. In 10 carotid arteries, stenosis was not assessable by SSD and MIP because of calcifications. In the remaining carotid arteries, MIP correctly classified the degree of stenosis in 96% of cases, whereas SSD misclassified 21% of cases.

Conclusions
Our study showed that axial images provide a reliable evaluation of carotid artery stenosis. Calcifications are limiting factors in SSD or MIP. When atherosclerotic plaques are not calcified, MIP reconstructions provide a more reliable measurement of the vascular lumen than SSD.
Differences Between Treated and Untreated Hypertensive Subjects in the Extent of Periventricular Hyperintensities Observed on Brain MRI
Authors: Fukuda Hitoshi , Kitani Mitsuhiro
Published: June 2011

Background and Purpose
Several reports have stated that the periventricular abnormalities found on T
2
-weighted MRI or CT are associated with age and hypertension. However, there have been no reports on the effect of hypertension treatment on white matter abnormalities. We studied the association between cardiovascular risk factors and periventricular hyperintensities (PVHs) on T
2
-weighted MRI and the differences between treated and untreated hypertensive subjects in the extent of PVHs.

Methods
The extent of PVH observed on 238 MRI scans was assessed retrospectively in 238 patients older than 40 years with the use of a five-point (0 to 4) classification scale. Hypertensive subjects were divided into two groups: patients receiving no or irregular treatment and patients receiving regular treatment for hypertension.

Results
Age, hypertension, treatment of hypertension, and multiple cerebral vascular lesions on MRI correlated significantly and independently with the extent of PVH. Sex and diabetes mellitus did not correlate with PVH. The Mann-Whitney
U
test showed significantly more extensive PVH in subjects with no or irregular treatment of hypertension compared with normotensives (2.5±0.7 versus 1.9±0.6,
P
<.0001) and compared with subjects receiving regular treatment of hypertension (2.5±0.7 versus 2.1±0.5,
P
=.0019). The latter patients had more extensive PVH than normotensives, but the difference was not significant. Mean systolic and diastolic blood pressure differed significantly among the three groups.

Conclusions
Hypertension and age were major predictors of the extent of PVH. Regular treatment for hypertension appeared to prevent the progression of PVH.
Infraputaminal ‘Lacunes’
Authors: Pullicino Patrick M. , Miller Lucia L. , Alexandrov Andrei V. , Ostrow Peter T.
Published: June 2011

Background and Purpose
Single, oval lesions greater than 5 mm in diameter lying inferior to the lateral putamen (infraputaminal lacunes [IPLs]) seen on CT or MR images are commonly reported as lacunar infarcts. To determine the clinical relevance and underlying pathology of IPLs, we evaluated the imaging appearances, clinical features, vascular risk factors, and histopathology in patients with IPLs.

Methods
Consecutive MR scans were reviewed for the presence of IPLs. Serial patients seen in routine clinical practice with IPLs were also included. Vascular risk factors were obtained from a prescan questionnaire. Histology and microangiography were performed on postmortem material. A MEDLINE search for putaminal infarcts was performed to look for imaging lesions typical of IPLs.

Results
Three of 100 serial MR scans had IPLs (3%). Nine other patients with in vivo (7) or postmortem (2) MR scans had IPLs. No neurological symptoms could be related to the IPLs. There were no differences in age, hypertension, diabetes, or presence of cortical enlarged perivascular spaces (EPVSs) between patients with and without IPLs. Unlike infarcts, IPLs were isointense with the cerebrospinal fluid on proton density MR sequences. Histological correlation of three MR scans showed IPLs to be a single large EPVS, situated lateral to the anterior commissure. IPLs were located at a point where multiple lenticulostriates turn sharply dorsally. An IPL was the probable cause of the apparent infarct in six publications from peer-reviewed literature that linked different clinical signs to putaminal infarct.

Conclusions
IPLs are EPVSs that can be differentiated from infarcts on proton density MR images.
Middle Cerebral Artery Blood Flow Velocity and Stable Xenon-Enhanced Computed Tomographic Blood Flow During Balloon Test Occlusion of the Internal Carotid Artery
Authors: Kofke W. Andrew , Brauer Patric , Policare Raymond , Penthany Susan , Barker David , Horton Joseph
Published: June 2011

Background and Purpose
Transcranial Doppler ultrasonography has been reported to reflect changes in cerebral blood flow (CBF) with the use of radioactive tracer techniques, which are weighted to measure primarily cortical structures. We tested the hypothesis that changes in transcranial Doppler ultrasonography would reflect changes in CBF in the middle cerebral artery vascular territory with the use of stable xenon-enhanced CT to assess CBF during carotid occlusion.

Methods
Thirty-one conscious patients underwent balloon test occlusion of the internal carotid artery and transcranial Doppler ultrasonography and xenon-enhanced CT assessment of blood flow velocity and CBF, respectively, of the middle cerebral artery and its distribution during balloon test occlusion.

Results
A significant correlation was seen between the change in CBF and the change in blood flow velocity for both brain levels at which CBF was determined (
P
<.0001). The average change in blood flow velocity was −13.4%, and the change in CBF was −15.1% and −17.7% at the two anatomic levels examined.

Conclusions
The data indicate that changes in blood flow velocity generally reflect changes in CBF throughout the middle cerebral artery vascular territory with abrupt occlusion of the internal carotid artery in unanesthetized humans.
Outcomes of Elderly Stroke Patients
Authors: Hui Elsie , Lum C.M. , Woo Jean , Or K.H. , Kay Richard L.C.
Published: June 2011

Background and Purpose
Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients, and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals. We carried out a prospective, randomized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management.

Methods
One hundred twenty elderly patients with acute stroke were randomized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team. Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential. Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital. Family or community support was arranged when necessary for both treatment groups. On recruitment, patient demographics, medical history, clinical features related to stroke, and functional ability as measured by the Barthel Index were noted. Subjects were reviewed at 3 and 6 months to assess functional level, hospital and outpatient services received, general well-being, mood, and level of satisfaction. Costs of treatment of the two groups were also compared.

Results
Functional improvement (Barthel Index score) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months (
P
=.03). There were also fewer outpatient visits among the day hospital patients at 6 months (
P
=.03). No significant difference was found in costs between the two treatment groups.

Conclusions
Compared with conventional medical management, care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost.
Adenosine Modulates
N
-Methyl-
d
-Aspartate–Stimulated Hippocampal Nitric Oxide Production In Vivo
Authors: Bhardwaj Anish , Northington Frances J. , Koehler Raymond C. , Stiefel Theodore , Hanley Daniel F. , Traystman Richard J.
Published: June 2011

Background and Purpose
Adenosine acts presynaptically to inhibit release of excitatory amino acids (EAAs) and is thus considered to be neuroprotective. Because EAA-stimulated synthesis of nitric oxide (NO) may play an important role in long-term potentiation and excitotoxic-mediated injury, we tested the hypotheses that adenosine agonists attenuate basal and EAA-induced NO production in the hippocampus in vivo and that adenosine A
1
receptors mediate this response.

Methods
Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague-Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 hours with artificial cerebrospinal fluid containing 3 μmol/L [
14
C]
l
-arginine. Recovery of [
14
C]
l
-citrulline in the effluent was used as a marker of NO production. In 10 groups of rats, time-dependent increases in [
14
C]
l
-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of
N
-methyl-
d
-aspartate (NMDA), adenosine agonists, adenosine antagonists, and the NO synthase inhibitor
N
ω
-nitro-
l
-arginine methyl ester (L-NAME).

Results
Recovery of [
14
C]
l
-citrulline during perfusion with artificial cerebrospinal fluid progressively increased to 141±27 fmol/min (±SEM) over 5 hours. Contralateral perfusion with 1 mmol/L NMDA augmented [
14
C]
l
-citrulline recovery to 317±62 fmol/min. Perfusion of 1 mmol/L L-NAME with NMDA inhibited [
14
C]
l
-citrulline recovery compared with NMDA alone. Perfusion with 0.1 mmol/L 2-chloroadenosine attenuated basal as well as NMDA-enhanced [
14
C]
l
-citrulline recovery. This action of 2-chloroadenosine was reversed by infusion of 0.1 mmol/L 8-cyclopentyl-1,3-dipropylxanthine, a specific A
1
receptor antagonist. Infusion of 0.1 mmol/L (2
S
)-
N
6
-[2-endo-norboryl]adenosine, a specific A
1
receptor agonist, also attenuated the 0.1 mmol/L and 1 mmol/L NMDA-enhanced [
14
C]
l
-citrulline recovery.

Conclusions
Using an indirect method of assessing NO production in vivo, these data are consistent with in vitro results showing that NMDA receptor stimulation enhances NO production. Furthermore, we conclude that stimulation of A
1
receptors can attenuate the basal as well as NMDA-induced production of NO. Because NMDA receptor stimulation amplifies glutamate release, our data are consistent with presynaptic A
1
receptor–mediated inhibition of EAA release and consequent downregulation of NO production.
Brain Temperature Modulations During Global Ischemia Fail to Influence Extracellular Lactate Levels in Rats
Authors: Lin Baowan , Busto Raul , Globus Mordecai Y.-T. , Martinez Elena , Ginsberg Myron D.
Published: June 2011

Background and Purpose
While brain tissue lactate increases during cerebral ischemia and is known to be important in the pathogenesis of ischemic brain injury, patterns of extracellular lactate accumulation have been less well characterized, and the influence of brain temperature has not been previously investigated. Mild brain temperature modulations are known to affect the outcome of ischemia dramatically. This study examined changes of extracellular lactate during and after global cerebral ischemia, in which intraischemic brain temperature was held at either 30°C, 37°C, or 39°C.

Methods
Halothane-anesthetized fasted male Wistar rats underwent 20 minutes of global cerebral ischemia produced by bilateral carotid artery occlusions plus systemic hypotension (40 to 50 mm Hg). Rectal temperature was maintained at 37°C throughout, and intraischemic brain temperature was held at either 30°C (n=6), 37°C (n=5), or 39°C (n=5). Before and after the ischemic insult, brain temperature was maintained at 37°C in all groups. A microdialysis cannula was implanted in the right dorsolateral striatum and perfused with Ringer’s solution. Dialysate samples were collected at 10-minute intervals before, during, and after ischemia and were analyzed for lactate by enzymatic-fluorometric techniques.

Results
In all groups, extracellular lactate rose during ischemia and peaked at 10 to 30 minutes of recirculation. Maximal extracellular lactate elevations were sevenfold, eightfold, and eightfold above control in the 30°C, 37°C, 39°C groups, respectively. Significant elevations with respect to control were observed in all groups at 10 to 30 minutes of recirculation. In the 30°C group, these elevations above control were also significant at the 10- and 20-minute ischemic time points (
P
=.001). At 30 minutes of recirculation, however, lactate levels were lower in the 30°C rats than in the other groups.

Conclusions
These data provide evidence that extracellular lactate accumulation is not a crucial determinant of ischemic brain injury. Our results suggest that the increased lactate release during ischemia and the accelerated clearance of lactate during recirculation might contribute in part to the neuroprotection of intraischemic hypothermia.
PPBP [4-Phenyl-1-(4-phenylbutyl) Piperidine], a Potent ς-Receptor Ligand, Decreases Brain Injury After Transient Focal Ischemia in Cats
Authors: Takahashi Hiroshi , Kirsch Jeffrey R. , Hashimoto Kenji , London Edythe D. , Koehler Raymond C. , Traystman Richard J.
Published: June 2011

Background and Purpose
We tested the hypothesis that administration of 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), a potent ς-receptor ligand, during transient focal ischemia would affect early postischemic brain injury.

Methods
Halothane-anesthetized cats underwent left middle cerebral artery occlusion for 90 minutes followed by 4 hours of reperfusion. Control cats received saline (n=10). Experimental cats (2 groups, n=10 per group) were treated with PPBP at a rate of 0.1 μmol/kg per hour (PPBP-0.1) or administered 1 μmol/kg per hour (PPBP-1) intravenously from 75 minutes after initiation of ischemia and continuing during the 4 hours of reperfusion.

Results
As measured by the microsphere method, blood flow to the ipsilateral caudate nucleus was decreased similarly in all groups during ischemia. Blood flow to the ipsilateral inferior temporal cortex was decreased during ischemia in all groups but was higher in cats subsequently treated with PPBP at the highest dose, even before drug administration. There was no difference in blood flow to the ipsilateral caudate nucleus or inferior temporal cortex (area of greatest cortical injury) during reperfusion. Triphenyltetrazolium-determined injury volume of the ipsilateral cerebral hemisphere (control, 29±5%; PPBP-0.1, 17±3%; PPBP-1, 6±1% of ipsilateral hemisphere; mean±SEM) and caudate nucleus (control, 49±5%; PPBP-0.1, 39±6%; PPBP-1, 25±5% of ipsilateral caudate nucleus) was less in cats treated with 1 μmol/kg per hour of PPBP compared with cats treated with saline. Cats treated with 0.1 μmol/kg per hour had a 45% smaller hemispheric injury volume than the control group without differences in intraischemic blood flow. Recovery of somatosensory evoked potential amplitude was greater in cats treated with PPBP-1 compared with control (control, 18±11%; PPBP-0.1, 30±14%; PPBP-1, 54±14% of baseline).

Conclusions
These data indicate that ς-receptors may play an important role in the mechanism of acute injury in both the cortex and the caudate nucleus after 90 minutes of transient focal ischemia in the cat. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, ς-receptors may contribute to the progression of injury in ischemic border regions.
SB 201823-A Antagonizes Calcium Currents in Central Neurons and Reduces the Effects of Focal Ischemia in Rats and Mice
Authors: Barone F. C. , Lysko P. G. , Price W. J. , Feuerstein G. , Al-Baracanji K. A. , Benham C. D. , Harrison D. C. , Harries M. H. , Bailey S. J. , Hunter A. J.
Published: June 2011

Background and Purpose
Excessive calcium entry into depolarized neurons contributes significantly to cerebral tissue damage after ischemia. We evaluated the ability of a novel neuronal calcium channel blocker, SB 201823-A, to block central neuronal calcium influx in vitro and to reduce ischemic injury in two rodent models of focal stroke.

Methods
Patch-clamp electrophysiology and intracellular Ca
2+
imaging in rat hippocampal and cerebellar neurons were used to determine effects on neuronal calcium channel activity. Middle cerebral artery occlusion was performed in Fisher 344 rats and CD-1 mice to determine the effects on rodent focal ischemic injury and neurological deficits. Cardiovascular monitoring in conscious rats was conducted to determine cardiovascular liabilities of the compound.

Results
In cultured rat hippocampal cells, calcium current measured at plateau was reduced by 36±8% and 89±4% after 5 and 20 μmol/L SB 201823-A, respectively. In cerebellar granule cells in culture, pretreatment with 2.5 μmol/L SB 201823-A totally prevented initial calcium influx and reduced later calcium influx by 50±2.5% after
N
-methyl-
d
-aspartate/glycine stimulation (
P
<.01). KCl depolarization–induced calcium influx also was reduced by more than 95%. In rats, a single treatment with 10 mg/kg IV SB 201823-A beginning 30 minutes after focal ischemia decreased (
P
<.05) hemispheric infarct by 30.4% and infarct volume by 29.3% and reduced (
P
<.05) forelimb deficits by 47.8% and hindlimb deficits by 36.3%. In mice, treatments with 10 mg/kg IP SB 201823-A beginning 30 minutes after focal ischemia significantly reduced infarct volume by 41.5% (
P
<.01). No blood pressure effects were observed with the therapeutic dose of the compound.

Conclusions
These results indicate that the new neuronal calcium channel blocker SB 201823-A can block stimulated calcium influx into central neurons and can provide neuroprotection in two models of focal cerebral ischemia without affecting blood pressure. Data from several different studies now indicate that the neuronal calcium channel antagonists are a promising therapy for the postischemic treatment of stroke.
Factors That Predict the Bleeding Risk of Cerebral Arteriovenous Malformations
Authors: Pollock Bruce E. , Flickinger John C. , Lunsford L. Dade , Bissonette David J. , Kondziolka Douglas
Published: June 2011

Background and Purpose
Arteriovenous malformations (AVMs) have an overall 2% to 4% annual risk of hemorrhage. The purpose of this study was to determine whether specific clinical and radiographic factors predispose AVMs to bleed and to predict the bleeding risk for individual AVM patients.

Methods
We reviewed the clinical histories and cerebral angiograms of 315 AVM patients who underwent stereotactic radiosurgery at our center. One half of the patient data (analysis cohort) was used to determine risk factors for bleeding and to construct AVM hemorrhage risk groups. These risk groups were then tested with the second half of the patient data (test cohort).

Results
The mean AVM volume was 4.0±3.4 mL (approximate maximum diameter of 2 cm). One hundred ninety-six initial hemorrhages occurred in 10 348 patient-years for an annual initial bleed rate of 1.89%; 44 of these 196 patients had a repeat bleed in 591 patient-years for an annual rebleed rate of 7.45%. The overall crude annual hemorrhage rate was 2.40%. Multivariate analysis revealed three factors associated with hemorrhage: history of a prior bleed (relative risk [RR], 9.09; 95% confidence interval [CI], 5.44 to 15.19;
P
<.001), a single draining vein (RR, 1.66; 95% CI, 1.13 to 2.38;
P
<.01), and a diffuse AVM morphology (RR, 1.64; 95% CI, 1.12 to 2.46;
P
<.01). Four AVM hemorrhage risk groups were constructed on the basis of the significant factors. The annual rate of bleeding was 0.99% for low-risk AVMs, 2.22% for intermediate-low–risk AVMs, 3.72% for intermediate-high–risk AVMs, and 8.94% for high-risk AVMs.

Conclusions
Analysis of a large group of AVM patients who underwent stereotactic radiosurgery demonstrated that small AVMs have an annual hemorrhage risk similar to that of the general AVM population. AVM patients have a wide variability of bleeding risk that can be predicted from their clinical presentation and the angiographic characteristics of the AVM. The management of AVM patients should be based not only on the morbidity of the proposed treatment but also those factors that predispose individual patients to either a low or high hemorrhage risk.
Vascular Risk Factors and Arteriosclerotic Disease in Idiopathic Normal-Pressure Hydrocephalus of the Elderly
Authors: Krauss Joachim K. , Regel Jens P. , Vach Werner , Droste Dirk W. , Borremans Jan J. , Mergner Thomas
Published: June 2011

Background and Purpose
There is some evidence from previous studies that idiopathic normal-pressure hydrocephalus (NPH) of the elderly might be linked to vascular leukoencephalopathy. The purpose of this study was to examine the prevalence and impact of vascular risk factors and vascular diseases in idiopathic NPH compared with a control cohort.

Methods
The prevalence of arterial hypertension; diabetes mellitus; hypercholesterolemia; hyperlipidemia; smoking; obesity; and cardiac, cerebrovascular, and other arteriosclerotic diseases was assessed in 65 patients with idiopathic NPH. The findings were compared with those of 70 patients with comparable age distribution. To describe the differences of the prevalences of vascular risk factors, odds ratios were obtained by univariate and multivariate analyses.

Results
The univariate analysis revealed significant associations between idiopathic NPH and arterial hypertension (prevalence, 54 of 65 [83%]; control group, 25 of 70 [36%];
P
<.001) and diabetes mellitus (prevalence, 31 of 63 [49%]; control group, 20 of 70 [29%];
P
<.015) but not with other vascular risk factors. After multivariate regression analysis, only hypertension remained significantly associated with NPH (
P
<.0001). There was also a significant association between NPH and cardiac (
P
<.001), cerebral arteriosclerotic (
P
=.007), and other arteriosclerotic diseases (
P
=.001). A positive association was found between the severity of clinical symptoms of NPH and the presence of hypertension, especially for gait disturbance. The presence of hypertension was not related to the duration of NPH.

Conclusions
Our data show a highly significant association between idiopathic NPH and arterial hypertension. Arterial hypertension might be involved in the pathophysiological mechanisms promoting idiopathic NPH.
Role of Insulin Resistance Associated With Compensatory Hyperinsulinemia in Ischemic Stroke
Authors: Shinozaki Kazuya , Naritomi Hiroaki , Shimizu Takao , Suzuki Masaaki , Ikebuchi Motoyoshi , Sawada Tohru , Harano Yutaka
Published: June 2011

Background and Purpose
Although insulin resistance and hyperinsulinemia play a crucial role in the pathogenesis of atherosclerosis, little is known about their roles in ischemic stroke. The purpose of this study was to clarify whether insulin resistance and hyperinsulinemia are causative factors in the pathogenesis of ischemic stroke.

Methods
Thirty-four consecutive patients with ischemic stroke, who were normotensive, nondiabetic, and not obese, were classified into three groups—atherothrombotic infarction (n=16), lacunar infarction (n=10), and cardioembolic infarction (n=8)—based on clinical findings, brain imaging, and cerebral angiography. Both oral glucose tolerance tests and lipid analyses were performed. Insulin sensitivity was determined by the steady state plasma glucose method with the use of octreotide acetate. Data were compared with those of healthy control subjects (n=15).

Results
Steady state plasma glucose levels were significantly higher in the atherothrombotic infarction group compared with control subjects and the other two stroke groups, indicating the presence of insulin resistance in patients with atherothrombotic infarction. In the atherothrombotic infarction group, the 2-hour insulin area (area under the plasma insulin concentration curve) during a 75-g oral glucose tolerance test was significantly increased and dyslipidemic changes (increased triglyceride and apolipoprotein B, decreased high-density lipoprotein) were observed, whereas these changes were not found in the lacunar infarction and cardioembolic stroke groups.

Conclusions
Insulin resistance in association with compensatory hyperinsulinemia and dyslipidemia may be an important pathogenetic factor underlying the development of atherothrombotic infarction.
Cerebral Venous Thrombosis and Activated Protein C Resistance
Authors: Dulli Douglas A. , Luzzio Christopher C. , Williams Eliot C. , Schutta Henry S.
Published: June 2011

Background
Activated protein C resistance (APC-R) due to factor V Leiden has recently been established as an important risk factor for cerebral venous thrombosis (CVT). The clinical significance of abnormal or borderline functional APC-R in the absence of factor V Leiden is uncertain. Our observations suggest that APC-R due to mechanisms other than factor V Leiden may also contribute to the development of CVT.

Case Descriptions
We describe three women who had superior sagittal and lateral sinus thrombosis while taking oral contraceptives and had a number of additional risk factors for CVT. Each had APC-R for different reasons.

Conclusions
Inherited thrombophilia, including APC-R, should be looked for in all patients with CVT. Functional APC-R is a highly prevalent coagulopathy, but the reasons for this abnormality are diverse; abnormal and borderline functional APC-R results should be supplemented by DNA analysis for the presence of factor V Leiden.
Early Development of Intimal Thickening in Superficial Temporal Arteries in Patients With Moyamoya Disease
Authors: Aoyagi Masaru , Fukai Naomi , Yamamoto Mari , Nakagawa Kazuhiko , Matsushima Yoshiharu , Yamamoto Kiyotaka
Published: June 2011

Background and Purpose
Moyamoya disease is a progressive cerebrovascular occlusive disease that occurs in children. The etiology is unknown. We examined the superficial temporal arteries from patients with moyamoya disease, particularly children, to determine whether the extracranial arteries as well as the intracranial arteries are involved in this disease.

Methods
Small branches of the superficial temporal arteries were obtained from 22 patients with moyamoya disease during indirect arterial bypass surgery. Histological examinations were performed, and the findings were compared with those of arteries from 12 control patients.

Results
Intimal thickening was observed in 9 of 17 patients with moyamoya disease younger than 20 years but in none of 7 control patients under the age of 20 years (
P
<.02, Fisher's exact test). Intimal thickening appeared from age 20 years in control patients. The arteries of moyamoya patients showed fibrocellular intimal thickening with a paucity of lipid. The arteries from moyamoya patients contained strongly stained multilayered elastic fibers in the thickened intima, while those from control patients showed only weakly stained elastic fibers in the intima.

Conclusions
Our findings suggest that moyamoya disease is a systemic vascular disease. The results indicate systemic etiologic factors that may promote the early development of intimal thickening in moyamoya disease.
Stroke Severity in Atrial Fibrillation
Authors: Lin Huey-Juan , Wolf Philip A. , Kelly-Hayes Margaret , Beiser Alexa S. , Kase Carlos S. , Benjamin Emelia J. , D'Agostino Ralph B.
Published: June 2011

Background and Purpose
Stroke occurring with atrial fibrillation (AF) is more likely to be fatal or more severe than non-AF stroke based on clinical series, but data from prospective epidemiological studies are sparse and inconsistent.

Methods
Over 40-year follow-up of the original 5070 Framingham cohort, 501 initial ischemic strokes, including 103 with AF, were analyzed. Stroke severity was rated as none, mild, moderate, severe, or fatal. Since 1981, functional status indicated by the Barthel index has been evaluated acutely and at 3, 6, and 12 months. Severity and functional status of AF strokes were compared with non-AF strokes using χ
2
test and Student's
t
test. Thirty-day mortality was assessed by logistic regression analyses.

Results
AF was associated with increased stroke severity (
P
=.048). Thirty-day mortality was greater in AF strokes than in non-AF strokes (25% versus 14%). The multivariate-adjusted odds ratio for 30-day mortality for AF subjects was 1.84 (95% confidence interval, 1.04 to 3.27). Since 1981, follow-up was available for 150 initial ischemic strokes, including 30 with AF. Compared with the non-AF group, the AF group had poorer survival and more recurrences during 1 year of follow-up. The AF subjects had lower mean Barthel index scores acutely (29.6 versus 58.6,
P
<.001) and at 3 months (
P
=.005), 6 months (
P
=.003), and 12 months (
P
=.130) after stroke among survivors.

Conclusions
Ischemic stroke associated with AF was nearly twice as likely to be fatal as non-AF stroke. Recurrence was more frequent, and functional deficits were more likely to be severe among survivors. Since stroke is usually the initial manifestation of embolism in AF, prevention is critical to reducing disability and mortality.
Seasonal Variation in the Occurrence of Stroke in a Finnish Adult Population
Authors: Jakovljević Dimitrije , Salomaa Veikko , Sivenius Juhani , Tamminen Markku , Sarti Cinzia , Salmi Kalervo , Kaarsalo Esko , Narva Vihtori , Immonen-Räihä Pirjo , Torppa Jorma , Tuomilehto Jaakko
Published: June 2011

Background and Purpose
Seasonal influence on the incidence of and mortality from cerebrovascular disease has been reported during the last three decades, but generally with some discrepancy in results, particularly regarding stroke subtypes. The aim of this study was to examine seasonal variation in the incidence, mortality, and case-fatality rate of stroke in data from the FINMONICA population-based stroke register.

Methods
During 1982 to 1992, 15 449 stroke events were registered in the monitored populations aged 25 to 99 years in three geographic areas of Finland: the provinces of Kuopio and North Karelia in eastern Finland and the Turku/Loimaa area in southwestern Finland. We analyzed the seasonal and monthly incidence, mortality, and case-fatality rate of stroke and subtypes of stroke by pooling the data for the three areas and stratifying by sex and age.

Results
The rate of occurrence of ischemic stroke events was 12% (95% confidence interval [CI], 5% to 20%) greater in men and 11% (95% CI, 4% to 19%) greater in women in winter than in summer. For intracerebral hemorrhage, we observed a 28% (95% CI, 3% to 58%) greater rate of occurrence in men and a 33% (95% CI, 6% to 66%) greater rate of occurrence in women in winter than in summer. The occurrence of subarachnoid hemorrhage did not vary significantly by season. The greater incidence of ischemic strokes in winter was particularly prominent among men aged 25 to 64 years and less prominent in elderly men and in women. The 28-day case-fatality rate of ischemic stroke showed significant seasonal variation only in women (
P
=.001), with the lowest rate in summer.

Conclusions
There is a significantly greater incidence of ischemic strokes and intracerebral hemorrhages during winter in Finland. Further research that also takes meteorologic and sociodemographic factors into account is warranted, since it may help to determine new ways to prevent strokes.
Enlargement of Spontaneous Intracerebral Hemorrhage
Authors: Kazui Seiji , Naritomi Hiroaki , Yamamoto Haruko , Sawada Tohru , Yamaguchi Takenori
Published: June 2011

Background and Purpose
Standard radiographic criteria for hematoma enlargement have not been established. We undertook this investigation to assess the incidence and time course of hematoma growth using objective cutoff values.

Methods
We reviewed the clinical records of 204 patients with spontaneous intracerebral hemorrhage treated nonsurgically who underwent initial computed tomography (CT) within 48 hours and repeat CT within 120 hours of the onset of symptoms. The consensus of five observers reading the CT films was considered the “gold standard” for hematoma enlargement. The discriminant values of the difference (V2−V1) or the ratio (V2/V1) of the hematoma volume on the initial (V1) and second (V2) CT scans were determined by use of receiver operating characteristic curves. We chose the cutpoint that had the highest sensitivity and specificity for identifying hematoma expansion.

Results
The cutpoint for hematoma enlargement was determined as V2−V1=12.5 cm
3
or V2/V1=1.4 (sensitivity=94.4%, specificity=95.8%). Forty-one patients (20%) had changes that exceeded these criteria. Frequency of hematoma expansion was greatest among those who underwent the initial CT scan early (27 [36%] of 74 patients at ≤3 hours) and progressively declined as the time to initial scan was prolonged (7 [16%] of 45 patients at 3 to 6 hours; 5 [15%] of 33 patients at 6 to 12 hours; 2 [6%] of 34 patients at 12 to 24 hours; and 0 [0%] of 18 patients at 24 to 48 hours).

Conclusions
The enlargement of hematoma was defined radiographically as the increase of its volume by ≥12.5 cm
3
or by ≥1.4 times. Although expansion of intracerebral hemorrhage on CT scan was common in the hyperacute stage, 17% of hematoma expansion occurred even after 6 hours of onset. Enlargement after 24 hours of onset seems extremely rare. Early CT scanning appears to increase the rate of detection of enlarging hematomas.
Using the Downton Index to Predict Those Prone to Falls in Stroke Rehabilitation
Authors: Nyberg Lars , Gustafson Yngve
Published: June 2011

Background and Purpose
Falls are a major complication in inpatient stroke rehabilitation. An important issue in preventive strategies is the early identification of those at risk. This study aimed at assessing the fall-prediction accuracy of an easily administered fall risk index in stroke rehabilitation.

Methods
A consecutive series of 135 patients admitted to a geriatric stroke rehabilitation unit was studied. A score on the Downton fall risk index was obtained from the admission assessment data and used as a predictive indicator of the risk of falls. The patients' falls were prospectively recorded during their rehabilitation stay. The correlation between falls and the predicted risk was assessed by means of survival analysis and a multiple regression analysis, adjusting for the time of observation.

Results
The risk of falls as a function of the time observed was significantly greater among those predicted to be at high risk (index score ≥3) than among the others (
P
=.009, log-rank test; odds ratio, 2.9). Furthermore, the number of falls during rehabilitation stay was moderately correlated (
R
=.57) with the fall risk index sum when adjusted as for the time of observation. The sensitivity of the fall prediction as to outcome was 91%, whereas the specificity was limited to 27%.

Conclusions
A moderately high correlation was found between the predicted and the observed risk of falls in stroke rehabilitation when the Downton fall risk index was used. However, a low specificity rate limits the accuracy of the prediction.
Effect of Proximal Arterial Perfusion Pressure on Function, Spinal Cord Blood Flow, and Histopathologic Changes After Increasing Intervals of Aortic Occlusion in the Rat
Authors: Taira Yutaka , Marsala Martin
Published: June 2011

Background and Purpose
Cross-clamping of the thoracic aorta results in spinal cord ischemia and prominent systemic hypertension. Using a rat model of transient spinal cord ischemia, we examined the effects of manipulation of proximal aortic blood pressure on spinal cord blood flow (SCBF), neurological dysfunction, and changes in spinal histopathology after increasing intervals of aortic occlusion.

Methods
Aortic occlusion was induced by the inflation of a 2F Fogarty catheter placed into the thoracic aorta in rats anesthetized with halothane (1.5%). A tail artery was cannulated to monitor distal arterial pressure (DAP). To measure SCBF, a laser probe was implanted into the epidural space of the L-2 vertebra. To manipulate proximal arterial pressure (PAP), the left carotid artery was cannulated with a 20-gauge polytetrafluoroethylene catheter to permit blood withdrawal and infusion from a peripheral reservoir during aortic occlusion. In a survey study, spinal cord ischemia was induced in single animals at intervals of 6, 10, 15, 30, or 40 minutes with PAP controlled at 40, 60, 80, and 110 to 120 mm Hg. In a second series, ischemia was induced in groups of animals for 0, 6, 8, 10, and 12 minutes with PAP controlled at 40 mm Hg. After ischemia the animals survived for 2 to 3 days. During this recovery period, neurological functions were evaluated, followed by quantitative histopathology of the spinal cord.

Results
Under normal conditions, cross-clamping yields an acute proximal hypertension (125 to 135 mm Hg), a fall of DAP to 15 to 22 mm Hg, and a decrease in SCBF to 7% to 11% of baseline values. With the use of the external reservoir, proximal hypertension could be abolished and the PAP maintained at target pressures. In these studies a typical syndrome of tactile allodynia, spastic paraplegia, and necrotic changes affecting the central part of the gray matter after 24 to 48 hours of reperfusion was observed at the following combinations of ischemic intervals and PAP values: >10 minutes/40 mm Hg; >12 minutes/60 mm Hg; >16 minutes/80 mm Hg; and >30 minutes/uncontrolled. Lowering PAP resulted in a corresponding decrease in residual SCBF. Systematic studies at a PAP of 40 mm Hg at occlusion intervals of 6, 8, 10, and 12 minutes revealed that 100% of rats were paraplegic after 10- and 12-minute ischemia, and these rats showed corresponding signs of spinal histopathology.

Conclusions
The present study shows that systemic intraischemic hypotension (40 mm Hg) significantly potentiates neurological dysfunction after transient aortic occlusion. The mechanism of the observed effect may include elimination of collateral flow during aortic occlusion and/or consequent potentiation of hypoperfusion during reperfusion. These data indicate that PAP during occlusion should be monitored and/or controlled because it is a critical variable in the determination of outcome in this model of spinal cord ischemia.
VEGF and flt
Authors: Kovács Zsombor , Ikezaki Kiyonobu , Samoto Ken , Inamura Takanori , Fukui Masashi
Published: June 2011

Background and Purpose
Vascular endothelial growth/vascular permeability factor (VEGF) is a candidate for an angiogenic and hyperpermeability inducing factor in an infarct because it is a secretable mitogen specific for endothelial cells and is upregulated by hypoxia. Our study attempts to clarify the chronological expression of VEGF and its receptor (flt) system in experimental cerebral infarction.

Methods
With the use of a reproducible middle cerebral artery occlusion model in rats, VEGF expression was identified by Western blotting with anti-VEGF antibody. The chronological expression of the VEGF/flt system was analyzed semiquantitatively by immunohistochemical means in infarcts with different time courses from 3 hours to 3 weeks.

Results
VEGF and flt were expressed exclusively in the ischemic brain. The bands obtained on the immunoblot at 38 and 45 kD are related to those of VEGF
121
and VEGF
165
isoforms. Macrophages, neurons, and glial cells chronologically expressed VEGF immunoreactivity in a different fashion. Both VEGF (bound) and flt were detected in endothelial cells along with the development of angiogenesis.

Conclusions
In the ischemic brain the macrophages, neurons, and glial cells appear to contain VEGF. The VEGF receptor flt was induced in endothelial cells along with the progression of angiogenesis in infarct. The VEGF/flt system is thus considered to be involved in the healing process of brain infarct.
Role of Extracellular Ca
2+
in Subarachnoid Hemorrhage−Induced Spasm of the Rabbit Basilar Artery
Authors: Zuccarello Mario , Boccaletti Riccardo , Tosun Metiner , Rapoport Robert M.
Published: June 2011

Background and Purpose
The role of extracellular Ca
2+
in the maintenance of chronic vasospasm after subarachnoid hemorrhage (SAH) is largely unknown. Indeed, studies thus far have been limited to demonstrations that L-type Ca
2+
−channel antagonists were unable to reverse the spasm. This study tested whether SAH-induced vasospasm is maintained, at least in part, through the influx of extracellular Ca
2+
and whether the influx of extracellular Ca
2+
occurs through L-type Ca
2+
channels and possibly, in addition, through store operated channels (SOCs). Furthermore, as there is considerable evidence in the literature to suggest that the spasm is mediated through endothelin-1 (ET-1) release, we tested whether the Ca
2+
dependency of the spasm was consistent with the mediation of the spasm by ET-1.

Methods
Chronic spasm of the basilar artery was induced in a double SAH rabbit model. Relaxation of SAH-, ET-1−, serotonin-, and KCl-constricted basilar artery in response to Ca
2+
-free solution, verapamil, and Ni
2+
was measured in situ with the use of a cranial window.

Results
SAH induced 23% constriction of the basilar artery. Ca
2+
-free solution and 1 μmol/L verapamil reversed the constriction of SAH vessels by 60% and 17%, respectively. In contrast, control vessels challenged with 40 to 50 mmol/L KCl, which induced 34% constriction, relaxed in response to Ca
2+
-free solution and verapamil by 98% and 89%, respectively. In SAH vessels, verapamil followed by 0.1 mmol/L Ni
2+
, which is known to block SOCs, induced a combined relaxation of 67%. Control vessels challenged with 3 nmol/L ET-1, which induced a magnitude of constriction similar to that of SAH (29%), relaxed in response to Ca
2+
-free solution, verapamil, and verapamil plus Ni
2+
by 69%, 20%, and 50%, respectively (
P
>.05 versus respective values in SAH vessels). In contrast, control vessels challenged with 2 to 8 μmol/L serotonin, which induced a magnitude of constriction similar to those of SAH and ET-1 (22%), completely relaxed in response to Ca
2+
-free solution and verapamil.

Conclusions
These results demonstrate that the maintenance of chronic spasm in the two-hemorrhage rabbit model after SAH is due to smooth muscle cell contractile mechanisms partly dependent on the influx of extracellular Ca
2+
. The influx of extracellular Ca
2+
results from the opening of L-type Ca
2+
channels and an additional channel or channels. We speculate that the L-type Ca
2+
channel−independent influx of extracellular Ca
2+
results from the opening of SOCs. The Ca
2+
-dependent characteristics of the spasm likely reflect the mediation of the spasm by ET-1.
Cost-Effectiveness of Screening for Asymptomatic Carotid Atherosclerotic Disease
Authors: Derdeyn Colin P. , Powers William J.
Published: June 2011

Background and Purpose
The value of screening for asymptomatic carotid stenosis has become an important issue with the recently reported beneficial effect of endarterectomy. The purpose of this study is to evaluate the cost-effectiveness of using Doppler ultrasound as a screening tool to select subjects for arteriography and subsequent surgery.

Methods
A computer model was developed to simulate the cost-effectiveness of screening a cohort of 1000 men during a 20-year period. The primary outcome measure was incremental present-value dollar expenditures for screening and treatment per incremental present-value quality-adjusted life-year (QALY) saved. Estimates of disease prevalence and arteriographic and surgical complication rates were obtained from the literature. Probabilities of stroke and death with surgical and medical treatment were obtained from published clinical trials. Doppler ultrasound sensitivity and specificity were obtained through review of local experience. Estimates of costs were obtained from local Medicare reimbursement data.

Results
A one-time screening program of a population with a high prevalence (20%) of ≥60% stenosis cost $35 130 per incremental QALY gained. Decreased surgical benefit or increased annual discount rate was detrimental, resulting in lost QALYs. Annual screening cost $457 773 per incremental QALY gained. In a low-prevalence (4%) population, one-time screening cost $52 588 per QALY gained, while annual screening was detrimental.

Conclusions
The cost-effectiveness of a one-time screening program for an asymptomatic population with a high prevalence of carotid stenosis may be cost-effective. Annual screening is detrimental. The most sensitive variables in this simulation model were long-term stroke risk reduction after surgery and annual discount rate for accumulated costs and QALYs.