bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Subarachnoid Hemorrhage
Authors: Teunissen Laurien L. , Rinkel Gabriel J.E. , Algra Ale , van Gijn J.
Published: June 2011

Background and Purpose
Knowledge of modifiable risk factors for subarachnoid hemorrhage (SAH) is important in terms of prevention. We therefore conducted a systematic review of studies on risk factors for SAH, with emphasis on sufficiently precise criteria for the diagnosis of SAH.

Methods
To identify studies we performed a Medline search from 1966 to 1994 and searched the reference lists of all relevant publications. Studies were included only if they fulfilled predefined methodological criteria. Case-control studies were included if the diagnosis of SAH was proved by CT, angiography, or autopsy in at least 70% of patients. Longitudinal studies were included if the criteria for SAH were based on a review of the medical records.

Results
Nine longitudinal studies and 11 case-control studies were included. Significant risk factors were as follows: (1) smoking (relative risk [RR] for longitudinal studies, 1.9; 95% confidence interval [CI], 1.5 to 2.3; odds ratio [OR] for case-control studies, 3.5; 95% CI, 2.9 to 4.3); (2) hypertension (RR, 2.8; 95% CI, 2.1 to 3.6; OR, 2.9; 95% CI, 2.4 to 3.7) and (3) drinking 150 g or more of alcohol per week (RR, 4.7; 95% CI, 2.1 to 10.5; OR, 1.5; 95% CI, 1.1 to 1.9). Use of oral contraceptives, hormone replacement therapy, hypercholesterolemia, and physical activity were not significantly related to the risk of SAH.

Conclusions
We conclude that smoking, hypertension, and alcohol abuse are important risk factors for SAH. Reduction of exposure to these risk factors might result in a decreased incidence of SAH.
Improvement in Cerebral Hemodynamics After Carotid Angioplasty
Authors: Markus Hugh S. , Clifton Andrew , Buckenham Tim , Taylor Robert , Brown Martin M.
Published: June 2011

Background and Purpose
Carotid percutaneous transluminal angioplasty (PTA) may offer an alternative treatment to carotid endarterectomy. However, in contrast to carotid endarterectomy, which has been shown to normalize impaired cerebral hemodynamics, the effects of carotid PTA are unknown. Therefore, we prospectively studied the effect of carotid PTA on both perioperative and postoperative cerebral hemodynamics.

Methods
Eleven patients undergoing carotid PTA for symptomatic carotid artery stenosis were prospectively studied. Transcranial Doppler recordings from the ipsilateral middle cerebral artery (MCA) were performed during the procedure. In addition, MCA blood flow velocity and CO
2
reactivity were determined before PTA and at 2 days, 1 month, and 6 months after the procedure. The results were compared with those in 11 similar patients undergoing carotid endarterectomy in whom measurements were performed before and 1 month after the operation.

Results
During carotid PTA, in 2 of 11 patients during passage of the balloon catheter through the stenosis, MCA blood flow velocity fell transiently. In 6 of 11 patients there was a reduction in flow velocity (>50%) during balloon deflation, but this lasted only a few seconds. After the procedure there was a significant improvement in ipsilateral hypercapnic reactivity: preoperative value, 59.8±42.2% (mean±SD); 2 days, 77.9±31.4%; 1 month, 88.7±45.0%; 6 months, 89.8±33.9%; and (ANOVA
P
=.003) preoperative value versus 1 month,
P
<.02; versus 6 months,
P
<.02. In all cases in which reactivity was significantly impaired preoperatively, it returned to the normal range. Pulsatility index also increased significantly: preoperative value, 0.827±0.251 (mean±SD); 2 days, 0.992±0.262 (
P
=.002). Contralateral MCA hypercapnic reactivity also improved after carotid PTA. There was a similar improvement in ipsilateral hypercapnic reactivity after carotid endarterectomy.

Conclusions
Carotid PTA results in a normalization of impaired hemodynamics, as assessed by CO
2
reactivity. The degree of improvement is similar to that seen after carotid endarterectomy.
Computed Tomographic Brain Scans and Antiplatelet Therapy After Stroke
Authors: van der Meulen J.H.P. , Limburg M. , van Straten A. , Habbema J.D.F.
Published: June 2011

Background and Purpose
We sought to develop a measure (“quality weight”) that indicates the severity of a deviation from optimal care with respect to secondary prevention with antiplatelet treatment after stroke. We also sought to estimate the effects that efforts to improve the quality of secondary prevention may have on health outcome and healthcare costs in the Netherlands.

Methods
First, we developed quality weights with decision analysis techniques. These quality weights express the excess risk of vascular events in the first 2 years after stroke compared with the optimal strategy (CT brain scan in all patients and aspirin in case of cerebral infarction). Second, these weights were applied in a follow-up study of 738 stroke patients older than 45 years. The number of stroke patients admitted to a hospital in 1991 in the Netherlands was used to estimate nationwide effects. We used data from 23 neurological departments and from the Information Center for Health Care in the Netherlands.

Results
The 2-year excess risk of fatal and nonfatal vascular events caused by omitting a CT brain scan and giving aspirin to all patients is rather small (on average, 0.6%). The 2-year excess risk caused by not giving aspirin to a patient with cerebral infarction is much higher (4.1%). The follow-up study indicated that only 6% of the admitted patients had not been evaluated with a CT brain scan and that 14% of the patients with cerebral infarction proven by CT scan did not get antiplatelet treatment at discharge. Efforts to improve the quality of secondary prevention after stroke may prevent 74 vascular events annually in the Netherlands at an expense of 6200 Dutch guilders per prevented event (1 Dutch guilder=0.53 US dollar, 1991).

Conclusions
Efforts to improve the quality of secondary prevention with antiplatelet treatment might reduce the number of new vascular events within the first 2 years after stroke by approximately 3%. The total costs related to the extra diagnostic and therapeutic activities are approximately 0.2% of the total annual hospital costs for acute stroke patients in the Netherlands (250 million Dutch guilders).
Discriminative Sensory Dysfunction After Unilateral Stroke
Authors: Kim Jong S. , Choi-Kwon Smi
Published: June 2011

Background and Purpose
Although sensory deficits caused by stroke have been reported occasionally, dysfunction of discriminative sensation has seldom been studied in patients with unilateral stroke. The frequency and modality of bilaterally impaired discriminative sensation also remain to be clarified.

Methods
With the use of specifically designed methods, we tested discriminative sensations including texture discrimination, two-point discrimination, stereognosis, point localization, and position sense in 67 patients with acute unilateral stroke. The locations of the lesions were identified with the use of CT and/or MRI. Thirty-two age- and sex-matched healthy subjects were used as a control.

Results
Impaired discriminative sensation was common in patients with unilateral stroke (detected in 57 of the 67 patients) regardless of lesion location except for patients with lateral medullary infarction. Discriminative sensation remained intact in only 3 of 25 patients who were initially diagnosed as having pure motor stroke on the basis of conventional sensory tests. Point localization and stereognosis were bilaterally impaired in 17 of 39 patients and 7 of 38 patients, respectively, regardless of the laterality of the lesion. Dysfunction of other sensory modalities was observed exclusively on the side contralateral to the lesion.

Conclusions
Discriminative sensory disturbances, which often occur bilaterally in some modalities, are common in patients with unilateral stroke even in those with intact sensory function on routine examination. The subtle disturbances of this sensation may explain, at least in part, the clumsiness of the patients that is not readily explained by conventional neurological tests.
Characterization of the Cardiac Effects of Acute Subarachnoid Hemorrhage in Dogs
Authors: Elrifai Amr M. , Bailes Julian E. , Shih Shou-Ren , Dianzumba Sinda , Brillman Jon
Published: June 2011

Background and Purpose
We know that significant cardiac involvement can occur in patients with acute intracranial hemorrhage, particularly in those with subarachnoid hemorrhage. These patients may present with electrocardiographic abnormalities that were previously thought to be benign. However, many die of cardiovascular sequelae, which suggests more serious cardiac problems. To characterize the cardiac, rhythmic, and myocardial disturbances that occur 2 to 4 hours after subarachnoid hemorrhage, we conducted an experimental study using autologous blood (7.9±0.3 mL) injected into the right frontal lobe and subarachnoid space in canines.

Methods
Nine adult mongrel dogs were anesthetized with isoflurane and their rectal temperatures maintained at 37°C. Electrocardiogram, heart rate, mean arterial pressure, mean pulmonary artery pressure, and intracranial pressure were continuously measured. Transesophageal echocardiography was performed to assess myocardial wall motion changes and aortic and pulmonary flow velocities before, immediately after, and 2 and 4 hours after intracranial hemorrhage. Blood samples were collected and analyzed for catecholamines and cardiac enzymes, and cardiac output was measured. Animals were killed at 2 to 4 hours after subarachnoid hemorrhage, and a piece of the myocardium was freeze-clamped for analysis of tissue catecholamines. Light and electron microscopy were used for histopathologic assessment.

Results
Subarachnoid hemorrhage produced significant increases in intracranial pressure, cardiac output, and aortic and pulmonary flow velocities. Also, significant changes in creatine kinase and catecholamines were observed. Electrocardiographic recordings showed changes of tachycardia, ST-segment depression, inverted T wave, and premature ventricular contractions in four animals at 1 to 5 minutes after injection, and echocardiographic changes were evident in all animals at 20 to 240 minutes. Microscopic examination of the heart showed evidence of myocardial changes in one animal with the use of light microscopy and in nine with the use of electron microscopy.

Conclusions
This study demonstrates the high incidence of cardiac involvement, specifically wall motion abnormalities, that occur after subarachnoid hemorrhage and suggests the importance of continuous cardiac monitoring, particularly echocardiographic measurements, in those patients.
Effect of Dietary Calcium and Milk Consumption on Risk of Thromboembolic Stroke in Older Middle-aged Men
Authors: Abbott Robert D. , Curb J. David , Rodriguez Beatriz L. , Sharp Dan S. , Burchfiel Cecil M. , Yano Katsuhiko
Published: June 2011

Background and Purpose
Evidence suggests that dietary calcium is protective against hypertension. This report examines whether the effect has an influence on thromboembolic stroke.

Methods
Since 1965, the Honolulu Heart Program has followed a cohort of men in a study of cardiovascular disease. This report examines the effect of baseline dietary calcium and milk intake on stroke risk in 22 years of follow-up in 3150 older middle-aged men (55 to 68 years).

Results
Men who were nondrinkers of milk experienced stroke at twice the rate (
P
<.05) of men who consumed 16 oz/d or more (7.9 versus 3.7 per 100, respectively). While the rate of stroke decreased with increasing milk intake (
P
<.05), the decline in stroke risk with increased consumption was modest for those who consumed under 16 oz/d. Intake of dietary calcium was also associated with a reduced risk of stroke (
P
<.01), although its association was confounded with milk consumption. Calcium intake from nondairy sources was not related to stroke, suggesting that other constituents or covariates related to milk consumption may be important.

Conclusions
We conclude that an association between milk consumption and a reduced risk of stroke in older middle-aged men cannot be explained by intake of dietary calcium. Since milk is often part of a diverse pattern of dietary intake, it is difficult to determine whether milk consumption has a direct role in reducing the risk of stroke. Data suggest that consumption of milk in older middle age is not harmful, and when combined with a balanced diet, weight control, and physical activity, reductions in the risk of stroke may occur.
Evaluating Neuroprotective Agents for Clinical Anti-Ischemic Benefit Using Neurological and Neuropsychological Changes After Cardiac Surgery Under Cardiopulmonary Bypass
Authors: Grieco Giacinto , d’Hollosy Marilyn , Culliford Alfred T. , Jonas Saran
Published: June 2011

Background and Purpose
Many neuroprotective agents (NPAs) are effective in acute experimental cerebral ischemia in animals. None have proven effective in human stroke trials. Even short treatment delays cause substantial efficacy loss. Cardiac surgery under cardiopulmonary bypass (CS-CPB) causes cerebral ischemia with cognitive impairment at a predeterminable time point and should permit efficient screening of NPAs for stroke benefit. We sought to develop sensitive methods to assess dysfunction from CS-CPB in a double-blind trial of the NPA GM
1
ganglioside.

Methods
Eighteen GM
1
and 11 Control patients received GM
1
300 mg or placebo, two doses intravenously, before nonemergency CS-CPB. Independent examiners administered structured neurological examinations and neuropsychological test batteries at Baseline and 1 day (Acute Postop; neurological only), 1 week (Early F/U), and ≥6 months (Long-term F/U) postoperatively; using defined procedures they employed ordinal Clinical Change Scores (CCSs) to quantify neurological cerebral, neurological noncerebral, and neuropsychological performance changes. Several methods to analyze CCSs and neuropsychological test score changes were evaluated.

Results
The most sensitive indicators were the mean Acute Postop Neurologist’s CCS-Cerebral (
P
<10
−5
) and the mean Early F/U Neuropsychologist’s CCS (
P
<.01), with statistically nonsignificant differences favoring GM
1
. No significant mean changes in Neurologist’s CCS-Noncerebral or any Long-term F/U CCSs occurred. CCS distributions and neuropsychological test score mean changes showed similar temporal patterns, with less sensitivity to change. When, as usual in prior CS-CPB studies, impairment was defined by neuropsychological test score declines (increases ignored), results were spurious.

Conclusions
The strokelike cerebral dysfunction (maximal acutely, with eventual recovery) that occurs after CS-CPB is useful to screen NPAs for clinical efficacy. CCSs based on detailed neurological examination and neuropsychological testing are sensitive measures; refinement of this approach should enhance the efficiency of the CS-CPB model. Further testing of GM
1
is warranted.
Optimal Timing of Hemodilution for Brain Protection in a Canine Model of Focal Cerebral Ischemia
Authors: Yanaka Kiyoyuki , Camarata Paul J. , Spellman Stephen R. , McDonald Drew E. , Heros Roberto C.
Published: June 2011

Background and Purpose
Hemodilution is known to ameliorate the effects of focal ischemia when used shortly after cerebral arterial occlusion; however, it remains to be proved whether hemodilution will be effective when used at more clinically relevant times, ie, with some delay between the onset of ischemia and initiation of therapy.

Methods
Thirty-two dogs were selected for inclusion in this study. Cerebral infarction was induced by permanent occlusion of the middle cerebral and the azygos anterior cerebral arteries. The animals were allocated to 1 of 4 groups of eight animals each: arterial occlusion without hemodilution (group 1); hemodilution immediately after occlusion (group 2); hemodilution 3 hours after occlusion (group 3); and hemodilution 6 hours after occlusion (group 4). Isovolemic hemodilution to a hematocrit of 30% was performed. The animals were killed 6 days after induction of ischemia, and the infarct size was determined.

Results
Groups 2 and 3 showed significant reduction of infarct size (
P
<.0001) when compared with group 1. The neurological grade of group 3 on postoperative days 4, 5, and 6 was significantly better than those of groups 1 and 4 (
P
<.01). Group 4 showed a significant increase in the incidence of hemorrhagic infarction when compared with groups 1 and 2 (
P
<.01).

Conclusions
The current study indicates that hemodilution administered as much as 3 hours after ischemia is effective in reducing infarct size and improving neurological status. When administered 6 hours after ischemia, hemodilution is not helpful and may be harmful.
Effects of Hypothermia on the Rate of Excitatory Amino Acid Release After Ischemic Depolarization
Authors: Nakashima Ken , Todd Michael M.
Published: June 2011

Background and Purpose
Hypothermia slows the increase in extracellular excitatory amino acid (EAA) concentrations during temporary cerebral ischemia. However, it is unclear whether hypothermia slows the rate of EAA release or just delays the time until the first sharp increase (which occurs coincident with terminal depolarization).

Methods
Pericranial temperatures were adjusted to 38°C, 34°C, 31°C, or 25°C in halothane-anesthetized rats. The cortical DC voltage was recorded from a glass microelectrode while the cortical concentrations of glutamate, aspartate, glycine, and γ-aminobutyric acid (GABA) were measured by microdialysis. A cardiac arrest was induced with intravenous KCl, and the times until electroencephalograph isoelectricity and terminal depolarization were recorded. Dialysate concentrations of the four compounds were measured at 10, 20, and 30 minutes after depolarization.

Results
The times to isoelectricity and depolarization varied inversely with temperature; depolarization time increased from 70±9 seconds at 38°C (mean±SD) to 294±34 seconds at 25°C. The dialysate concentrations of all four compounds increased during ischemia, and the rate of increase was inhibited by cooling. After 30 minutes of ischemia, glutamate concentration in 38°C animals was 58.4±31.8 μmol/L; this decreased to 15.9±8.4 μmol/L at 25°C. The magnitude of the effects of temperature on amino acid release differed with the compound measured. For glutamate, the calculated Q10 was 3.63. Corresponding values for aspartate and glycine were 3.68 and 1.95, respectively. By contrast, Q10 for GABA release was 6.31, indicating greater sensitivity to cooling.

Conclusions
These results suggest that effects of hypothermia on EAA concentrations during cerebral ischemia may be the result of both a delay until initial EAA release as well as a direct effect of temperature on the rate of amino acid release. The observed temperature effects are more consistent with carrier-mediated processes controlling EAA release.
Effect of Short-term Regression of Atherosclerosis on Reactivity of Carotid and Retinal Arteries
Authors: Sobey Christopher G. , Faraci Frank M. , Piegors Donald J. , Heistad Donald D.
Published: June 2011

Background and Purpose
This study tested the hypothesis that functional abnormalities of carotid and ocular arteries may improve after short-term regression of atherosclerosis, before regression of structural abnormalities.

Methods
We examined effects of short-term dietary treatment of atherosclerosis on carotid and ocular vascular responses to serotonin and to platelet activation by collagen in vivo. Three groups of monkeys were studied: normal cynomolgus monkeys, monkeys fed an atherogenic diet for 34 months, and atherosclerotic monkeys that were fed a regression diet for 8.6±1.1 months (mean±SE). We measured changes in carotid blood flow (using a Doppler probe), retinal blood flow (using microspheres), and diameter of the internal carotid artery (using quantitative angiography). Endothelium-dependent relaxation to acetylcholine was studied in rings of internal carotid artery in vitro.

Results
Carotid blood flow increased in response to both serotonin and collagen in normal monkeys, decreased in response to both agents in atherosclerotic monkeys, and was restored toward normal after regression. Serotonin had little effect on retinal blood flow in normal monkeys and produced a marked decrease in retinal blood flow in atherosclerotic monkeys; the vasoconstrictor response to serotonin was reduced after regression. Activation of platelets by collagen increased blood flow in normal monkeys, decreased blood flow in atherosclerotic monkeys, and had little effect after regression. Alterations in responses of the internal carotid artery were consistent with changes in carotid and ocular blood flow. Endothelium-dependent relaxation in vitro was impaired by atherosclerosis and was restored toward normal by regression. There was no reduction in intimal area of the atherosclerotic lesion in common carotid and ophthalmic arteries from regression monkeys, despite a marked reduction in cholesteryl ester.

Conclusions
Within a few months of regression of atherosclerosis, endothelial function and hyperresponsiveness of carotid and ocular arteries to serotonin and platelet activation return toward normal. Functional improvement is associated with resorption of lipid from atherosclerotic lesions, but with little reduction in size of intimal lesions.
Molecular Characterization of an Arachidonic Acid Epoxygenase in Rat Brain Astrocytes
Authors: Alkayed Nabil J. , Narayanan Jayashree , Gebremedhin Debebe , Medhora Meetha , Roman Richard J. , Harder David R.
Published: June 2011

Background and Purpose
Brain parenchymal tissue metabolizes arachidonic acid (AA) via the cytochrome P450 (P450) epoxygenase to epoxyeicosatrienoic acids (EETs). EETs dilate cerebral arterioles and enhance K
+
current in vascular smooth muscle cells from large cerebral arteries. Because of the close association between astrocytes and the cerebral microcirculation, we hypothesized that brain epoxygenase activity originates from astrocytes. This study was designed to identify and localize an AA epoxygenase in rat brain astrocytes. We also tested the effect of EETs on whole-cell K
+
current in rat cerebral microvascular smooth muscle cells.

Methods
A functional assay was used to demonstrate endogenous epoxygenase activity of intact astrocytes in culture. Oligonucleotide primers derived from the sequence of a known hepatic epoxygenase, P450 2C11, were used in reverse transcription/polymerase chain reaction of RNA isolated from cultured rat astrocytes. The appropriate size reverse transcription/polymerase chain reaction product was cloned into a plasmid vector and sequenced. A polyclonal peptide antibody was raised against P450 2C11 and used in Western blotting and immunocytochemical staining of cultured astrocytes. A voltage-clamp technique was used to test the effect of EETs on whole-cell K
+
current recorded from rat cerebral microvascular muscle cells.

Results
Based on elution time of known standards and inhibition by miconazole, an inhibitor of P450 AA epoxygenase, cultured astrocytes produce 11,12- and 14,15-EETs when incubated with AA. The sequence of a cDNA derived from RNA isolated from cultured rat astrocytes was 100% identical to P450 2C11. Immunoreactivity to glial fibrillary acidic protein, a marker for astrocytes, colocalized with
2C11
immunoreactivity in double immunochemical staining of cultured astrocytes. EETs enhanced outward K
+
current in muscle cells from rat brain microvessels.

Conclusions
Our results demonstrate that a P450 2C11 mRNA is expressed in astrocytes and may be responsible for astrocyte epoxygenase activity. Given the vasodilatory effect of EETs, our findings suggest a role for astrocytes in the control of cerebral microcirculation mediated by P450 2C11-catalyzed conversion of AA to EETs. The mechanism of EET-induced dilation of rat cerebral microvessels may involve activation of K
+
channels.
Recovery of Apparent Diffusion Coefficient After Ischemia-Induced Spreading Depression Relates to Cerebral Perfusion Gradient
Authors: Röther Joachim , de Crespigny Alexander J. , D’Arceuil Helen , Iwai Kumiko , Moseley Michael E.
Published: June 2011

Background and Purpose
Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression. DWI and dynamic contrast-enhanced MRI were applied to study the characteristics of spreading depression and the correlation between ADC recovery time and tissue perfusion in focal ischemia.

Methods
Serial DWI was performed during remote middle cerebral artery occlusion in rats (n=5) with an echo-planar imaging technique. ADC maps were calculated and ADC values displayed as a function of time in user-defined regions of interest with a time resolution of 12 to 16 seconds. Dynamic contrast-enhanced MRI was performed for qualitative correlation of ADC changes with tissue perfusion.

Results
Recovery time of transient ADC decreases correlated with the degree of the perfusion deficit (
r
=.81,
P
<.001). Slowly recovering ADC declines were found close to the ischemic core and correlated with severe perfusion deficit, while short-lasting ADC declines were typically found in moderately malperfused or normal tissue. Transient ADC decreases originated in the subcortical and cortical ischemic border zones and propagated along the cortex with a velocity of 2.9±0.9 mm/min.

Conclusions
The variation in the recovery time of transient ADC decreases in the ischemic periphery reflects the gradient of the tissue perfusion. Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra.
Effect of Malnutrition After Acute Stroke on Clinical Outcome
Authors: Dávalos Antoni , Ricart Wifred , Gonzalez-Huix Ferran , Soler Silvia , Marrugat Jaume , Molins Albert , Suñer Rosa , Genís David
Published: June 2011

Background and Purpose
Malnutrition has received little attention in acute stroke, although it represents a risk of decreased immunity and nosocomial infections. Our objectives were to determine the prevalence of malnutrition after 1 week of hospitalization in acute stroke and to establish its relation to the stress response and neurological outcome.

Methods
The study included 104 patients with an acute stroke of less than 24 hours’ duration. Nutritional parameters (triceps skinfold thickness, midarm muscle circumference, serum albumin, and calorimetry) were evaluated at admission and after 1 week. Stress response (free urinary cortisol) was measured daily during the first week. Neurological deficit was evaluated by the Canadian Stroke Scale. Clinical outcome was estimated by the Barthel Index 1 month after the acute stroke. Patients received an oral standard diet or polymeric enteral nutrition when they had swallowing difficulties.

Results
Protein-energy malnutrition was observed in 16.3% of patients at inclusion and in 26.4% after the first week, with a significant decrease in fat (
P
=.002) and visceral protein compartments (
P
=.049). Malnourished patients showed higher stress reaction and increased frequency of infections and bedsores in comparison with the appropriately nourished group. Multiple logistic regression analysis showed that malnutrition after 1 week (odds ratio, 3.5; 95% confidence interval, 1.2 to 10.2) and elevated free urinary cortisol (odds ratio, 3.3; confidence interval, 1.05 to 10.2) increased the risk of poor outcome (death or Barthel Index ≤50 on the 30th day of follow-up) independently of age and nutritional status at admission.

Conclusions
Our findings suggest that protein-energy malnutrition after acute stroke is a risk factor for poor outcome. Early appropriate enteral caloric feeding did not prevent malnutrition during the first week of hospitalization.
Implementation of an Acute Stroke Program Decreases Hospitalization Costs and Length of Stay
Authors: Wentworth Deidre A. , Atkinson Richard P.
Published: June 2011

Background and Purpose
A large community hospital implemented an acute stroke program to respond to stroke patients in a consistent, systematic, and efficient manner. The primary objectives were to monitor the care delivered, improve the quality of care, and move the patients through their initial hospital stay in a timely manner.

Methods
Acute stroke standing orders were developed, with a critical path developed on the basis of these orders and an expected length of stay. A multidisciplinary team began the rehabilitation process early in the hospital stay, monitored patient progress and length of stay, and provided appropriate discharge placement. Retrospective chart reviews were performed over a 4-year period, and the data were collated on a yearly basis.

Results
Over a 4-year period, 414 Medicare patients demonstrated a steady decline of initial hospital length of stay from 7.0 to 4.6 days. During this same period of time, there was a decline in total hospital charges from $14 076 to $10 740 per patient. This represented a total dollar savings in charges of $1 621 296 (≈$453 000 per year). The mortality rate for 1994 was 4.6%, with 46.5% of survivors discharged to home, 16.9% to acute rehabilitation, and 32.6% to nursing homes.

Conclusions
The implementation of a multidisciplinary acute stroke program decreased length of stay and hospitalization costs of Medicare patients.
Risk of Intracranial Arteriovenous Malformation Rupture Due to Venous Drainage Impairment
Authors: Hademenos George J. , Massoud Tarik F.
Published: June 2011

Background and Purpose
Increased resistance in the venous drainage of intracranial arteriovenous malformations (AVMs) may contribute to their increased risk of hemorrhage. Venous drainage impairment may result from naturally occurring stenoses/occlusions, or if draining veins (DVs) undergo occlusion before feeding arteries during surgical removal, or after surgery in the presence of “occlusive hyperemia.” We employed a detailed biomathematical AVM model using electrical network analysis to investigate theoretically the hemodynamic consequences and the risk of AVM rupture due to venous drainage impairment.

Methods
The AVM model consisted of a noncompartmentalized nidus with 28 vessels (24 plexiform components and 4 fistulous components), 4 arterial feeders, and 2 DVs. An expression for the risk of AVM nidus rupture was derived on the basis of functional distribution of the critical radii of component vessels. Risk was calculated from biomathematical simulations of volumetric flow rate with both DVs patent and for four stages of venous drainage obstruction: (1) 25%, (2) 50%, (3) 75%, and (4) 100%. Each stage of occlusion was applied to each DV while the other DV was patent and then to the patent DV while the other DV was totally occluded.

Results
For flow through the AVM when both DVs were unobstructed, the baseline risk of AVM nidus rupture ranged from 4.4% to 91.2%. Theoretical rupture occurred in nidus components proximal to the DVs when the risk exceeded 100%, as was observed with the obstruction of DV1 and a patent DV2. The ranges for risk of rupture across the nidus for the four stages were (1) 4.7% to 90.5%, (2) 5.9% to 86.9%, (3) 0% to 98.4%, and (4) 0% to 106.3%, respectively. Rupture was observed for an 86% occlusion of DV1 (ie, the DV fed by the intranidal fistula) and DV2 patent, primarily because of the dramatic shift in the hemodynamic burden toward the weaker plexiform nidus vessels.

Conclusions
On theoretical grounds, venous drainage impairment was predictive of AVM nidus rupture and was strongly dependent on AVM morphology (presence of intranidal fistulas and their spatial relation to DVs) and hemodynamics. Specifically, stenosis/occlusion of a high-flow DV induces a rapid redistribution of blood into the weak plexiform vessels of the opposing region of the nidus, causing a hemodynamic overload and an increased risk of rupture. These findings should be carefully considered among all factors affecting the natural history of intracranial AVMs and the mechanisms implicated in their spontaneous rupture. They may also provide a theoretical rationale for some of the hemorrhagic complications that occur during and after surgical treatment.
Assessment of Normal Flow Velocity in Basal Cerebral Veins
Authors: Valdueza José Manuel , Schmierer Klaus , Mehraein Susan , Einhaüpl Karl Max
Published: June 2011

Background and Purpose
Transcranial Doppler ultrasound has not yet been applied systematically to the analysis of the venous system and cerebrovenous disorders. Assessment of the intracranial venous system, however, would contribute to the understanding of cerebral hemodynamics and thus allow new possibilities for clinical application of the Doppler technique. Therefore, we demonstrated the validity of the transcranial Doppler technique in analyzing the basal cerebral veins.

Methods
Venous transcranial Doppler ultrasound was performed with a range-gated 2-MHz transducer in 60 healthy volunteers and patients without central nervous disorders ranging in age from 10 to 71 years (mean±SD, 41.9±15 years).

Results
A venous signal away from the probe and adjacent to the posterior cerebral artery, considered to correspond to the basal vein of Rosenthal, was found in all subjects on at least one side. Mean blood flow velocity ranged from 4 to 17 cm/s (mean±SD, 10.1±2.3 cm/s). Analysis for age dependency revealed a trend of decreasing values with increasing age, exclusively caused by a significant reduction of velocity in men aged 40 years or older. No significant intraindividual side-to-side differences were found. A venous signal away from the probe and paralleling the middle cerebral artery, interpreted as corresponding to the deep middle cerebral vein, was found in 21.7% of the subjects with similar velocities.

Conclusions
We have shown that transcranial Doppler methods can also be used for evaluation of the basal cerebral veins in both sexes, in differing age groups, and without major difficulty. The cerebral basal veins could be identified on the basis of their anatomic relation to specific arteries.
Clinical Correlates of White Matter Findings on Cranial Magnetic Resonance Imaging of 3301 Elderly People
Authors: Longstreth W.T. , Manolio Teri A. , Arnold Alice , Burke Gregory L. , Bryan Nick , Jungreis Charles A. , Enright Paul L. , O'Leary Daniel , Fried Linda
Published: June 2011

Background and Purpose
Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people.

Methods
Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information.

Results
Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all
P
<.01) and independently associated with increased grade were greater age, clinically silent stroke on MRI, higher systolic blood pressure, lower forced expiratory volume in 1 second (FEV
1
), and income less than $50 000 per year. If excluded, FEV
1
was replaced in the model by female sex, history of smoking, and history of physician-diagnosed hypertension at the baseline examination. Many clinical features were correlated with the white matter grade, especially those indicating impaired cognitive and lower extremity function.

Conclusions
White matter findings were significantly associated with age, silent stroke, hypertension, FEV
1
, and income. The white matter findings may not be considered benign because they are associated with impaired cognitive and lower extremity function.
Ultrasonographic Assessment of Carotid Wall Characteristics and Cognitive Functions in a Community Sample of 59- to 71-Year-Olds
Authors: Auperin A. , Berr C. , Bonithon-Kopp C. , Touboul P.-J. , Ruelland I. , Ducimetiere P. , Alperovitch A.
Published: June 2011

Background and Purpose
This study was aimed at analyzing cross-sectional relationships between cognitive performance and ultrasonographic assessment of carotid wall characteristics.

Methods
A cohort of 1279 subjects (men, 41%) aged 59 to 71 years was recruited from the electoral rolls of the city of Nantes (western France). Cognitive performances were evaluated with the Mini-Mental State Examination (MMSE) and seven neuropsychological tests assessing attention, psychomotor rapidity, verbal abilities, memory, and visuospatial perception. For each test, subjects were classified into three performance levels with a quartile distribution: 25% highest, 25% lowest, and 50% middle. The intima-media thickness of common carotid arteries and the presence of plaques in the carotid arteries were assessed with B-mode ultrasound examination.

Results
Only 28% of men and 17% of women had carotid plaques inducing moderate stenosis of the lumen (<40%). After adjustment for possible confounders, odds ratios for poor cognitive performance associated with plaques were above 1 for all cognitive tests in men. This association was statistically significant for the MMSE and another test assessing attention skills. There was a slight association between increase of the common carotid intima-media thickness and poor cognitive scores in men with plaques. In women, no association was found between cognitive functions and presence of plaques or intima-media thickness.

Conclusions
This study indicated a moderate association between atherosclerosis of the carotid arteries and poor cognitive functioning in men aged 59 to 71 years. In view of these moderate cross-sectional results, further studies are required to better assess the relationship between carotid atherosclerosis and cognitive impairment.
Posterior Circulation Infarcts Simulating Anterior Circulation Stroke
Authors: Argentino Corrado , De Michele Manuela , Fiorelli Marco , Toni Danilo , Sacchetti Maria Luisa , Cavalletti Cristina , Sette Giuliano , Falcou Anne , Bastianello Stefano , Bozzao Luigi
Published: June 2011

Background and Purpose
Ischemic stroke patients whose initial clinical presentation suggests an involvement of the anterior circulation (AC) are sometimes found to have a posterior circulation (PC) infarct, a fact that may generate erroneous decisions in clinical management. We investigated the prevalence of this misdiagnosis in the first few hours after stroke onset.

Methods
We performed a cohort study of 158 patients hospitalized within 5 hours of onset of a presumed AC ischemic stroke, as diagnosed on clinical grounds.

Results
Final CT or pathology diagnosis was AC infarct in 128 patients (81%), a repeatedly negative CT in 14 (9%), PC infarct (5 pons, 1 midbrain and cerebellum, 6 supratentorial territory of the posterior cerebral artery) in 12 (8%), and other or undiagnosed lesions in 4 (3%). AC and PC stroke patients did not differ in terms of age, vascular risk factors, and initial severity, but the latter were more frequently men (83% versus 53%;
P
=.04), were hospitalized later (mean±SD, 168±86 versus 109±55 minutes;
P
=.001), and presented a pure motor hemiparesis or a sensorimotor stroke (50% versus 33%) more often than their counterparts. At baseline CT, PC stroke patients never exhibited an early parenchymal hypodensity in the carotid territory or a hyperdense middle cerebral artery, which were instead found in 59% (
P
=.0003) and 31% (
P
=.02) of AC stroke patients, respectively. Early neurological deterioration, 1 month case-fatality rate, and disablement in survivors were comparable in the two groups.

Conclusions
Shortly after onset the clinical discrimination between AC and nontypical PC infarcts is not reliable, which explains the frequent occurrence of this misdiagnosis. Emergency CT scan helps in the differential diagnosis only when it demonstrates an early focal hypodensity within the carotid territory.
Surgical Therapy for Adult Moyamoya Disease
Authors: Houkin Kiyohiro , Kamiyama Hiroyasu , Abe Hiroshi , Takahashi Akihiro , Kuroda Satoshi
Published: June 2011

Background and Purpose
It is well recognized that revascularization surgery using direct and/or indirect bypass provides effective surgical management for pediatric moyamoya disease. However, surgical treatment of the adult hemorrhagic type remains controversial. In this study, the effect of surgery for adult moyamoya disease was investigated.

Methods
We analyzed 35 patients with adult moyamoya disease (patient age, over 20 years), 24 patients with initial onset of intracerebral hemorrhage, and 11 patients with initial onset of cerebral ischemia who underwent both direct bypass surgery of the superficial temporal artery to the middle cerebral artery anastomosis and indirect revascularization of encephalo-duro-arterio-myo-synangiosis.

Results
Of 24 patients with hemorrhagic-type disease, 3 showed rebleeding; of 11 patients with the ischemic type, 2 showed intracerebral hemorrhage after surgery. Overall, 5 of 35 patients (14.3%) had hemorrhage after revascularization surgery (mean follow-up period, 6.4 years). Postoperative angiography revealed that direct anastomosis is effective whereas indirect revascularization is not always effective for adult moyamoya disease. Moyamoya vessels, which are supposed to be responsible for hemorrhage, decreased in 25% of patients.

Conclusions
Revascularization surgery cannot always prevent rebleeding. However, a decrease in moyamoya vessels was induced by surgery, which may reduce the risk of hemorrhage more effectively than conservative treatment. In cases of adult moyamoya disease, direct bypass is particularly important, since the indirect revascularization is not as useful in adult cases as in pediatric cases.
Inducible Nitric Oxide Synthase Gene Expression in Vascular Cells After Transient Focal Cerebral Ischemia
Authors: Iadecola Costantino , Zhang Fangyi , Casey Robyn , Clark H. Brent , Ross M. Elizabeth
Published: June 2011

Background and Purpose
We investigated whether inducible nitric oxide synthase (iNOS) is expressed after transient cerebral ischemia and, if so, we sought to define the temporal profile and cellular localization of the expression and the role of iNOS in the mechanism of ischemic brain injury.

Methods
The middle cerebral artery in rats was occluded for 2 hours by an intraluminal filament. The occurrence of transient ischemia and reperfusion was confirmed by laser-Doppler flowmetry (n=5). iNOS message in the ischemic neocortex was determined by reverse-transcription polymerase chain reaction. iNOS enzymatic activity was assessed by citrulline assay. The cellular localization of iNOS expression was determined by immunohistochemistry.

Results
iNOS mRNA was maximally expressed in postischemic brain at 12 hours and was not present at 4 days (n=3 per time point). iNOS mRNA was not observed in the contralateral cerebral cortex. iNOS enzymatic activity developed in the postischemic brain between 12 and 24 hours (
P
<.05) and subsided at 4 days (n=4 to 8 per time point). iNOS immunoreactivity in the ischemic region was restricted to the wall of capillaries and of larger blood vessels at 12 to 24 hours. In regions of early necrosis, inflammatory cells were iNOS positive. Treatment with the iNOS inhibitor aminoguanidine (n=5; 100 mg/kg IP, BID for 4 days), starting 6 hours after ischemia, reduced infarct size in neocortex by 36±7% in comparison with vehicle-treated controls (n=5) (
P
<.05).

Conclusions
Transient focal ischemia leads to iNOS expression in postischemic brain. However, the spatial and temporal patterns of expression differ from those occurring in permanent ischemia: iNOS is induced earlier and predominantly in vascular cells rather than in neutrophils. Thus, the temporal profile and localization of postischemic iNOS expression depend on the nature of the ischemic insult. The finding that aminoguanidine reduces infarct size adds further support to the hypothesis that postischemic iNOS expression contributes to ischemic brain damage.
Impaired Autoregulation in an Experimental Model of Chronic Cerebral Hypoperfusion in Rats
Authors: Irikura Katsumi , Morii Seiji , Miyasaka Yoshio , Yamada Masaru , Tokiwa Kaichi , Yada Kenzoh
Published: June 2011

Background and Purpose
To verify the hypothesis that impaired autoregulation may contribute to cerebral swelling or hemorrhage after a sudden recovery of perfusion pressure, we studied the chronic effects of cerebral hypoperfusion on the autoregulatory responses of the pial arterioles in situ.

Methods
Eight to 12 weeks after a carotid-jugular fistula was created in rats, experiments were performed under α-chloralose and urethane anesthesia. Regional cerebral blood flow (rCBF) was determined by the hydrogen clearance method, and carotid pressure was measured. Using a closed cranial window, we determined the autoregulatory responses of the arterioles (30 to 50 μm) to both hypertension induced by norepinephrine and sudden fistula closure at various mean arterial pressures (MAPs).

Results
rCBF on the fistula side was reduced by 27%. Carotid pressure was significantly lower than normal but was immediately increased by fistula closure. The pial arterioles showed marked elongation and enlargement. During induced hypertension, the arterioles in the fistula group started to dilate at an MAP lower than that of the control group (130 versus 180 mm Hg, respectively). The arterioles constricted when the fistula was occluded at normal MAP. However, when the fistula was occluded at an MAP higher than 130 mm Hg, the vessels dilated.

Conclusions
It was demonstrated that (1) chronic hypoperfusion induced impairment of the upper limit of autoregulation and (2) sudden fistula closure under hypertensive conditions caused vasodilation of the arterioles. These findings suggest that rapid restoration of perfusion pressure is possibly followed by a pressure breakthrough phenomenon in a chronically hypoperfused cerebrovasculature.
GABAergic and Asymmetrical Synapses on Somata of GABAergic Neurons in CA1 and CA3 Regions of Rat Hippocampus
Authors: Yao Zhi B. , Li Xiaoda , Xu Zao C.
Published: June 2011

Background and Purpose
CA1 pyramidal neurons in hippocampus die while CA3 neurons survive after transient ischemia. The imbalance of excitation and inhibition may contribute to this selective vulnerability. The purpose of this study was to examine the morphological basis of the above hypothesis.

Methods
Male Wistar rats were perfused with 4% paraformaldehyde and 0.2% glutaraldehyde in 0.15 mol/L phosphate buffer. Coronal sections (50 μm) cut on a microtome were processed for γ-aminobutyric acid (GABA) immunocytochemistry. Sections for electron microscopy were postfixed in 0.5% osmium tetroxide and embedded in high-viscosity epoxy resin. Ultrathin sections were cut and observed with an electron microscope.

Results
GABA-positive neurons in the stratum pyramidale received more GABAergic synapses than asymmetrical synapses. The percentage of somatic membrane of GABA-positive neurons covered by asymmetrical synapses in the CA1 region (3.17±1.13%) was higher than that in the CA3 region (2.15±0.18%,
P
<.05). The ratio of asymmetrical to GABAergic synapses per 10 μm somatic membrane in the CA1 region (0.71±0.22) was higher than that in the CA3 region (0.53±0.14,
P
<.05). The ratio of the percentage of somatic membrane covered by asymmetrical/GABAergic synapses in the CA1 region (0.33±0.14) was also significantly higher than that in the CA3 region (0.20±0.07,
P
<.05).

Conclusions
The GABAergic neurons in the CA1 region receive stronger excitatory inputs than those in the CA3 region, which provides a morphological basis for differences in excitability that may contribute to selective vulnerability after transient ischemia.