bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Acetazolamide Test
Authors: Okudaira Yojiro , Bandoh Kuniaki , Arai Hajime , Sato Kiyoshi
Published: June 2011

Background and Purpose
We evaluated the potential usefulness of the acetazolamide test by investigating whether acetazolamide vasoreactivity reflected the change in resting cerebral blood volume caused by compensatory vasodilation due to a decline in cerebral perfusion pressure.

Methods
We measured resting and acetazolamide-activated cerebral blood flow with a stable xenon-enhanced CT system and resting cerebral blood volume with the subtraction technique using contrast-enhanced CT in 30 patients with various diseases. These parameters were measured in the anterior, middle, and posterior cerebral arterial territories of both hemispheres separately. We evaluated the statistical relationships between resting cerebral blood volume and vasoreactivity in these three territories, and the significance of the correlations was tested by ANOVA/ANCOVA to adjust for the double entries.

Results
Significant negative linear relationships were demonstrated between the resting cerebral blood volume and the change in cerebral blood flow, expressed as a percentage induced by acetazolamide activation, for the anterior (
r
=−.607,
P
=.0004), middle (
r
=−.551,
P
=.0015), and posterior (
r
=−.523,
P
=.0078) cerebral arterial territories and between the resting cerebral blood volume and the increase in cerebral blood flow (absolute values) for the anterior (
r
=−.512,
P
=.0164) and middle (
r
=−.523,
P
=.0001) but not the posterior (
r
=−.571,
P
=.0563) cerebral arterial territories.

Conclusions
The acetazolamide test appears to be useful for the investigation of compensatory vasodilation: the vasoreactivity can be calculated as the increased cerebral blood flow expressed as a percentage or an absolute value, which both reflect cerebral blood volume directly.
Emboli Enter Penetrating Arteries of Monkey Brain in Relation to Their Size
Authors: Macdonald R. Loch , Kowalczuk Andrew , Johns Lydia
Published: June 2011

Background and Purpose
Controversy exists regarding whether lacunar infarction is due to embolism or whether it is always due to lipohyalinosis of small penetrating arteries. We hypothesized that emboli can enter penetrating arteries in relation to the blood flow to these arteries and to the diameter of the emboli.

Methods
We injected agarose spheres of three different mean diameters (31±4, 68±14, and 92±28 μm [n=50 for each]) into one internal carotid artery of 3 monkeys for each sphere size (total, n=9 monkeys). After injection of spheres, monkeys were killed, the brains were removed and fixed in formalin, and serial hematoxylin and eosin sections of three coronal sections of the cerebrum were examined by light microscopy. Sphere diameter (n=25 for each territory and sphere size) and distribution in circumferential and penetrating artery territories were measured with the use of an image analyzer. Corrections were made for shrinkage of spheres during fixation and for the effect of random sampling of 10-μm sections through spheres of different diameter.

Results
Mean numbers of spheres for each size were significantly higher in circumferential than penetrating artery territories (
P
<.05,
t
test). When correction was made for the volume of brain supplied by each territory, there was no significant difference in the number of spheres in circumferential versus penetrating artery territories for the two smaller sphere sizes. For spheres of mean diameter of 92 μm, significantly more spheres entered circumferential rather than penetrating artery territories (
P
<.05,
t
test). The percentage of the total number of spheres that entered penetrating artery territories was 5%, 6%, and 1.4% for beads of 31±4, 68±14, and 92±28 μm mean diameter, respectively.

Conclusions
Small emboli can enter penetrating arteries and could therefore produce lacunar infarction. The majority of emboli, however, enter circumferential arteries. The larger the emboli, the more likely that they will enter circumferential arteries rather than penetrating arteries.
The Sheffield Model of Subarachnoid Hemorrhage in Rats
Authors: Veelken Julian A. , Laing Rodney J. C. , Jakubowski Jan
Published: June 2011

Background and Purpose
There is no comprehensive and reliable model available in small animals that is suitable for the study of subarachnoid hemorrhage (SAH). Most of the existing models either require extensive surgery to achieve SAH or neglect the importance of an injury to the vessel and the impact of suddenly raised intracranial pressure (ICP). The presented model is designed to overcome these shortcomings.

Methods
Forty-three male Wistar rats were anesthetized. Regional cerebral blood flow was measured using the H
2
clearance method bilaterally in the middle cerebral artery territory. ICP and blood pressure were continuously monitored. Blood gases were kept within physiological limits. SAH was produced by passing a nylon thread up through the right internal carotid artery and piercing a hole in the right anterior cerebral artery. The animals were divided into three experimental groups treated with varied operative techniques. After 3 hours the surviving animals were killed, and SAH was confirmed by postmortem examination.

Results
The described method proved to be a reliable way of producing SAH in rats. The onset of SAH was characterized by a sudden increase in ICP. There were some differences in the reduction of regional cerebral blood flow and the survival rate in the experimental groups. This may represent differing degrees of severity of the produced SAH.

Conclusions
We present an inexpensive and reliable model of SAH in the rat that allows the early course of biochemical, physiological, and pathological changes to be studied.
Subjective Experiences of 24 Patients Dramatically Recovering From Stroke
Authors: Grotta James , Bratina Patti
Published: June 2011

Background
There are no reports describing patients’ perception of having a stroke and then dramatically recovering.

Summary of Report
We interviewed 24 patients randomized at our center to intravenous tissue plasminogen activator or placebo in an ongoing multicenter blinded prospective study. These patients demonstrated at least 50% improvement or an absolute improvement of 5 points on the National Institutes of Health Stroke Scale during the first 24 hours after treatment, with 7 patients returning completely to normal. Twelve of 24 of the strokes involved the right middle cerebral artery, 2 of 24 the right posterior cerebral artery, 8 of 24 the left middle cerebral artery, and 2 of 24 the basilar artery territory. CT scans at 24 hours or 1 week showed infarction in 19 of 24. Most patients (19 of 24) could clearly recall the exact circumstances involving the onset of their stroke, but only 12 of 24 were aware of the magnitude of their neurological deficit (7 of 14 right hemisphere and 4 of 8 left hemisphere patients). Only 6 of 24 were aware of their improvement when it occurred (3 of 14 right hemisphere and 2 of 8 left hemisphere patients). Five of 24 remembered positive phenomena such as warmth or tingling during their recovery, and only 2 patients demonstrated euphoria. Most patients seemed peculiarly unaware or blasé about their deficit and improvement.

Conclusions
Most patients with acute stroke are not aware of the severity of their problem, and recovering patients do not remember important events during the next 24 hours. This occurs with either right or left hemisphere lesions and may have a significant impact on early stroke recognition.
Coping With an Embarrassment of Riches
Authors: Saver Jeffrey L.
Published: June 2011

Background
The recent remarkable proliferation of multicenter clinical trials investigating novel treatments for acute ischemic stroke has created a new dilemma for stroke investigators. Promising agents and trials are many, competent clinical centers few. May a single clinical center, without scientific bias, participate in multiple, concurrent clinical trials recruiting overlapping populations of subjects with acute stroke?

Summary of Comment
Many clinical stroke centers already participate in multiple overlapping trials. I delineate a variety of patient-allotment strategies that are presently used, although often not explicitly stated. Methods include assignment by time window, unique criteria, site, belief in agent efficacy, remuneration, and quota urgency. All have drawbacks, chiefly the introduction of bias into the selection of subjects for clinical trials, compromising the generalizability of trial findings to broader clinical populations. Several solutions are proposed that permit single centers to participate in multiple studies while minimizing or eliminating selection bias, including within-center use of a permuted-block enrollment strategy. The issue of trial allocation among multiple available studies has received insufficient attention from clinical trial designers, epidemiologists, and statisticians. Currently an inescapable problem for clinical stroke investigators, it arises in any clinical medical research field with rapid basic-to-clinical scientific advances.

Conclusions
It is recommended that centers participating in multiple, concurrent clinical trials (1) use an articulated, formal method of patient allocation that is blinded or indifferent to clinical variables; (2) avoid assignment solely according to time since onset or unique patient criteria; and (3) avoid any influence of belief in agent efficacy on allocation.
Effects of a Specialized Team on Stroke Care
Authors: Webb Deborah J. , Fayad Pierre B. , Wilbur Christine , Thomas Angela , Brass Lawrence M.
Published: June 2011

Background and Purpose
Strategies have been proposed for stroke care to improve quality or reduce cost. We sought to document the effects of a new program of specialized stroke care.

Methods
In a programmatic review using historical and concurrent control subjects, we evaluated patients discharged with a stroke diagnosis (diagnosis-related group 14) over a 6-year period between January 1987 and December 1992. Patients were from an academic medical center. The intervention was consultation (on university neurology patients) by a specialized multidisciplinary team during the last 2 years of the review period. The main outcome measures were median length of stay and rate of common complications before and after implementation compared with other hospital services (private neurology and medicine).

Results
Stroke team involvement was associated with a shortened median length of stay from 10 to 8 days (
P
<.0001). There was no significant change in the median length of stay for the private neurology or medicine services. After stroke team involvement, there were fewer urinary tract infections (
P
=.056), and those patients who developed infection had a shorter length of stay (
P
=.0007). There was no change in the rate of aspiration pneumonia or in length of stay for patients with aspiration pneumonia. Mortality did not change.

Conclusions
A coordinated, multidisciplinary approach to stroke care may reduce length of stay and morbidity in patients hospitalized because of stroke.
Circulating Selectin- and Immunoglobulin-Type Adhesion Molecules in Acute Ischemic Stroke
Authors: Fassbender Klaus , Mössner Rainald , Motsch Lilian , Kischka Udo , Grau Armin , Hennerici Michael
Published: June 2011

Background and Purpose
Cellular adhesion molecules mediate adhesion between endothelial cells and leukocytes as a precondition for extravasation of leukocytes at sites of tissue injury. The pattern of release of circulating adhesion molecules has been characterized in patients with acute ischemic stroke.

Methods
Serum concentrations of soluble selectin-type adhesion molecules (soluble endothelial leukocyte adhesion molecule–1 [sELAM-1], soluble lymph node homing receptor [sL-selectin]) and immunoglobulin-type adhesion molecules (soluble vascular cell adhesion molecule–1 [sVCAM-1], soluble intercellular adhesion molecule–1 [sICAM-1]) were serially determined (at hours 4, 8, and 10 and at days 1, 3, and 5) in 22 patients with acute ischemic stroke. As control subjects, age- and sex-matched individuals with (n=40) and without (n=22) vascular risk factors were studied.

Results
We observed increased concentrations of sICAM-1 and decreased levels of sL-selectin in patients with risk factors even in the absence of stroke. Patients with acute stroke had, in addition, an initial transient increase of sELAM-1 and a persistent increase of sVCAM-1.

Conclusions
The results suggest a chronic alteration of expression of adhesion molecules sICAM-1 and sL-selectin in subjects with risk factors for atherosclerosis; they also indicate acute changes of levels of sELAM-1 and sVCAM-1 in response to acute ischemic stroke. Determination of soluble adhesion molecules could allow in vivo monitoring of the initial steps of leukocyte-mediated brain damage in acute ischemic stroke.
Autonomic and Thermal Sensory Symptoms and Dysfunction After Stroke
Authors: Naver Hans , Blomstrand Christian , Ekholm Sven , Jensen Christer , Karlsson Thomas , Wallin B. Gunnar
Published: June 2011

Background and Purpose
Symptoms interpreted as unilateral disturbances of autonomic function, such as coldness, dryness, sweating, and trophic changes, are well known but incompletely understood clinical problems after stroke. The present study provides data related to the incidence and mechanisms behind such symptoms.

Methods
Temperature perception thresholds, skin temperatures, evaporation rates, and skin blood flow responses were measured bilaterally in 37 stroke patients aged 58±13 years (mean±SD) and in a control group of 15 patients aged 64±15 years with a single transient ischemic attack.

Results
Of the 37 stroke patients, 43% reported a sensation of coldness in the contralesional side of the body. Basal skin blood flow and temperature were relatively lower in the contralesional side. There was an excess of evaporation in the contralesional side after brain stem lesions and in the ipsilesional side after hemispheric lesions. Vasomotor reflex asymmetries occurred in 34% of the patients and were due to weak vasodilator or vasoconstrictor reflexes in the ipsilesional side. These abnormalities correlated significantly to sensations of unilateral coldness, hypalgesia, and thermohypesthesia in the contralesional side and anatomically to lesions in spino-thalamo-cortical pathways.

Conclusions
Focal central nervous system lesions due to stroke may result in symptoms and measurable evidence of unilateral disturbance of skin sympathetic function. Vasomotor asymmetries are probably due to lesions of vasomotor pathways descending uncrossed. Subjective coldness may be due to disturbed central processing.
Clinical Relevance and Frequency of Transient Stenoses of the Middle and Anterior Cerebral Arteries in Bacterial Meningitis
Authors: Müller Martin , Merkelbach Stefan , Huss Georg Peter , Schimrigk Klaus
Published: June 2011

Background and Purpose
We sought to examine the frequency and clinical relevance of intracranial artery stenoses in patients with bacterial meningitis in whom the occurrence of stroke has angiographically been reported to be associated with stenoses or occlusions of the large basal cerebral arteries.

Methods
Thirty-five unselected patients (24 men, 11 women; mean age, 51±18 years) with bacterial (n=33) or fungal (n=2) meningitis prospectively underwent serial transcranial Doppler sonography recordings of mean blood velocity (MBV) and pulsatility index in the middle (MCA) and anterior (ACA) cerebral arteries, as well as recordings of the ratio of the MBV of the MCA and internal carotid artery (MCA/ICA ratio) on days 1, 3, 5, 8, 14, and 21 after admission. The results were correlated with the Glasgow Coma Scale (days 1 to 14), the occurrence of focal cerebral signs, and the Glasgow Outcome Scale (short-term outcome, day 21). An MCA stenosis was diagnosed by an MBV of 120 cm/s or more or an MCA/ICA ratio of more than 3. An ACA stenosis was diagnosed by an MBV of 100 cm/s or more.

Results
Transient stenoses occurred most frequently between days 3 and 5 and were detected in 18 patients (51%). Seventeen patients remained without a stenosis. Patients with stenoses showed a significantly poorer mean Glasgow Coma Scale score from day 3 (9±4) to day 14 (11±4) than patients without a stenosis (day 3: 13±4,
P
<.01 by
t
test; day 14: 14±1,
P
<.05). The mean Glasgow Outcome Scale score was not significantly different between both groups. The occurrence of mainly transient focal cerebral signs was significantly related to the number of narrowed vessels per patient (
P
<.05, χ
2
test).

Conclusions
Stenoses of the intracranial arteries occur frequently in bacterial meningitis and are associated with a complicated course of the disease.
Anti–Intercellular Adhesion Molecule–1 Antibody Reduces Ischemic Cell Damage After Transient But Not Permanent Middle Cerebral Artery Occlusion in the Wistar Rat
Authors: Zhang Rui Lan , Chopp Michael , Jiang Ning , Tang Wen Xue , Prostak Jonathan , Manning Anthony M. , Anderson Donald C.
Published: June 2011

Background and Purpose
Postischemic cerebral inflammation may contribute to ischemic cell damage. Intercellular adhesion molecule–1 (ICAM-1) is a glycoprotein expressed on endothelial cells that facilitates leukocyte adhesion. We investigated the effect of administration of an anti–ICAM-1 antibody (1A29) on ischemic cell damage after transient (2-hour) or permanent middle cerebral artery (MCA) occlusion in the Wistar rat.

Methods
Groups studied were as follows: (1) transient MCA occlusion: rats were subjected to 2 hours of MCA occlusion, and after 1 hour of reperfusion they were treated with 1A29 (n=11) or an isotype control antibody (n=9); and (2) permanent MCA occlusion: rats were treated with 1A29 (n=9) or an isotype control antibody (n=7) 2 hours after onset of MCA occlusion. All animals were killed 1 week after onset of ischemia. Brain sections were stained with hematoxylin and eosin for histological evaluation.

Results
Significant reductions (
P
<.05) in both volume (44%) of the ischemic lesion and weight loss were found in animals subjected to transient MCA occlusion and treated with 1A29 compared with vehicle-treated animals. In contrast, in animals subjected to permanent MCA occlusion the lesion and the temporal profile of body weight were not altered by 1A29 administration.

Conclusions
Ischemic cell damage is promoted by postischemic inflammatory response after 2 hours of transient MCA occlusion, and ischemic cell damage is reduced by administration of an anti–ICAM-1 antibody during reperfusion.
The Stroke Council of the American Heart Association
Authors: Siekert Robert G.
Published: June 2011

An account of the origin, within the American Heart Association, of a council devoted to vascular disease of the central nervous system, with particular attention to the context in which that occurred, is presented in this article. The forces of a service-charitable organization, political action, medical practice in general, and interested, strong-witted citizens provided the stimuli for the development of the Stroke Council.
Nylon Monofilament for Intraluminal Middle Cerebral Artery Occlusion in Rats
Authors: Kuge Yuji , Minematsu Kazuo , Yamaguchi Takenori , Miyake Yoshihiro
Published: June 2011

Background and Purpose
In rat middle cerebral artery (MCA) occlusion models with an intraluminal nylon monofilament, lesion volume and its reproducibility vary among laboratories. These variations may be caused by differences in the properties of nylon monofilaments. We performed the present study to compare the effects of two different types of 4-0 nylon monofilament on neurological and morphological outcomes in this model.

Methods
We randomly and blindly used two types of 4-0 nylon monofilament (Ethilon, n=15, and Nitcho, n=15) to permanently occlude the ostium of the right MCA intraluminally in rats. Neurological outcome and lesion size were compared 24 hours after MCA occlusion between the two groups. The diameter, tensile strength, and extensibility of each filament were measured.

Results
Neurological outcome was not different between the groups. The mortality within 24 hours was 13% (2/15) in the Ethilon group and 0% in the Nitcho group. Total lesion volume in the former was 295.9±97.2 mm
3
(mean±SD), significantly larger and more reproducible than that in the latter (190.3±144.7 mm
3
,
P
=.026). The Ethilon filament had a significantly larger diameter (Ethilon, 0.193±0.001 mm; Nitcho, 0.180±0.001 mm;
P
<.0001), poorer tensile strength, and better extensibility than the other.

Conclusions
Exact diameter and quality are not always the same among nylon monofilaments, even if they meet the standard for the designation 4-0. The present study indicates that slight differences of filament characteristics significantly affect lesion volume and its reproducibility. This result may explain some conflicting observations in this MCA occlusion model.
Stroke and Alcohol Intake in a Hospital Population
Authors: Beghi E. , Bogliun G. , Cosso P. , Fiorelli G. , Lorini C. , Mandelli M. , Bellini A.
Published: June 2011

Background and Purpose
The aim of the study was to assess whether excessive alcohol intake is an independent risk factor for stroke.

Methods
A case-control study was undertaken in 200 consecutive ischemic and hemorrhagic stroke patients and 372 age- and sex-matched control subjects (170 hospital-based and 202 community-based individuals). Data were collected through direct interview regarding demographics, risk factors for stroke, current daily alcohol consumption, and diagnosis of alcoholism. Blood was also taken to test the common biological markers of alcohol intake (erythrocyte mean cell volume, uric acid, aspartate aminotransferase, and γ-glutamyl transferase).

Results
After controlling for the most significant risk factors (antecedent strokes, hypertension, diabetes, smoking) and using hospital control subjects for reference, we determined the risk of stroke to be 2.2 (95% confidence interval [CI], 1.2 to 4.0) in moderate drinkers (men, ≤60 g/d; women, ≤40 g/d) and 2.9 (95% CI, 1.4 to 6.1) in heavy drinkers (men, >60 g/d; women, >40 g/d). The corresponding risk values obtained when we compared case subjects and external control subjects were 1.4 (95% CI, 0.8 to 2.7) and 3.0 (95% CI, 1.3 to 7.0). Even with some fluctuations across groups, the risk did not change significantly after subgroup analysis in men, patients with first-ever stroke, patients with ischemic stroke, and after exclusion of subjects with risk factors for stroke. Compared with hospital and external control subjects, stroke patients included a higher proportion of heavy drinkers (26.6% versus 20.6% versus 10.8%), alcoholics (14.6% versus 7.7% versus 2.5%), and cases with abnormal erythrocyte mean cell volume (63.0% versus 47.6% versus 34.2%) or γ-glutamyl transferase (35.5% versus 32.4% versus 12.9%). Mean alcohol consumption was 42.2 g/d in the case subjects, 30.8 g/d in the hospital control subjects, and 23.2 g/d in the external control subjects.

Conclusions
The study indicates that alcohol can be considered an independent risk factor for stroke in Italy.
Amelioration of Impaired Cerebral Metabolism After Severe Acidotic Ischemia by Tirilazad Posttreatment in Dogs
Authors: Kim Hotaek , Koehler Raymond C. , Hurn Patricia D. , Hall Edward D. , Traystman Richard J.
Published: June 2011

Background and Purpose
Acidosis may contribute to ischemic injury by mobilizing iron because the iron chelator deferoxamine improves early metabolic recovery from hyperglycemic ischemia. Mobilized iron may then promote oxygen radical-induced lipid peroxidative injury during reperfusion. We tested the hypothesis that administration of the antioxidant tirilazad at the start of reperfusion improves early metabolic recovery after severe acidotic ischemia and ameliorates depletion of the endogenous antioxidant glutathione.

Methods
In anesthetized dogs, arterial glucose concentration was increased to 500 to 600 mg/dL and global incomplete cerebral ischemia was produced for 30 minutes by ventricular fluid infusion to reduce perfusion pressure to 10 to 12 mm Hg. Metabolic recovery and intracellular pH were measured by phosphorus MR spectroscopy. In the first experiment, four groups of eight dogs each received either vehicle or 0.25, 1, or 2.5 mg/kg of tirilazad mesylate at reperfusion. Cerebral blood flow was measured with microspheres. In the second experiment, two groups of eight dogs each received either vehicle or 2.5 mg/kg of tirilazad at reperfusion, and cortical glutathione was measured at 3 hours of reperfusion.

Results
Cerebral blood flow decreased to approximately 6 mL/min per 100 g and intracellular pH decreased to approximately 5.6 during ischemia in all groups. In the vehicle group, ATP recovery was transient and pH remained less than 6.0. Cerebral blood flow, O
2
consumption, and ATP eventually declined to near-zero levels by 3 hours. Recovery was improved by tirilazad posttreatment in a dose-dependent fashion. At the highest dose, cerebral blood flow and O
2
consumption were sustained near preischemic levels, and five of eight dogs had recovery of ATP greater than 50% and of pH greater than 6.7. Recovery of ATP and phosphocreatine became significantly greater than that in the vehicle group by 17 minutes of reperfusion despite similar levels of early hyperemia, indicating that the drug was acting before the onset of hypoperfusion. Cortical glutathione concentration in the vehicle group was 27% less than that in the tirilazad group and 34% less than that in nonischemic controls.

Conclusions
Decreased depletion of the endogenous antioxidant glutathione is consistent with tirilazad acting as an antioxidant in vivo. Improvement in high-energy phosphate recovery 17 minutes after starting tirilazad infusion during reperfusion is consistent with an early onset of a functionally significant oxygen radical injury. Thus, severe acidosis appears to contribute to early ischemic injury through an oxygen radical mechanism sufficient to impede metabolic recovery.
Relationship Between the Volume of Craniotomies for Cerebral Aneurysm Performed at New York State Hospitals and In-Hospital Mortality
Authors: Solomon Robert A. , Mayer Stephan A. , Tarmey John J.
Published: June 2011

Background and Purpose
After a craniotomy for cerebral aneurysm, postoperative mortality can be significant. Previous studies have shown that hospitals performing frequent high-risk procedures (such as coronary artery bypass) have a lower mortality than hospitals where these procedures are performed infrequently.

Methods
The Statewide Planning and Research Cooperative System of the New York State Department of Health reviewed all discharges in New York State from 1987 through 1993 for the diagnoses of subarachnoid hemorrhage and/or cerebral aneurysm and for patients with the procedure code for craniotomy for ruptured or unruptured cerebral aneurysm. In-hospital mortality and length of stay were examined in relation to the volume of craniotomies for aneurysm performed at each individual hospital.

Results
A total of 15 376 discharges for subarachnoid hemorrhage and 5638 craniotomies for aneurysm were tabulated in 208 hospitals. For all patients who underwent craniotomy for ruptured cerebral aneurysm (n=4034), there was a 43% (95% confidence interval, 29% to 57%) reduction in mortality rate in hospitals performing more than 30 craniotomies per year for cerebral aneurysm compared with hospitals performing less surgery (8.8% versus 15.5%,
P
<.0001). For all patients who underwent craniotomy for unruptured cerebral aneurysm (n=1604), there was an identical 43% (95% confidence interval, 14% to 73%) reduction in mortality in hospitals performing more than 30 craniotomies per year for cerebral aneurysm (4.6% versus 8.1%,
P
=.0087).

Conclusions
Hospitals that frequently perform aneurysm operations have lower mortality rates for patients undergoing craniotomy for cerebral aneurysm than hospitals that perform fewer operations.
Stroke in Williams Syndrome
Authors: Wollack Jan B. , Kaifer Marie , LaMonte Marian P. , Rothman Michael
Published: June 2011

Background
Williams syndrome is a genetic disorder characterized by a high incidence of heart disease, arterial stenosis, and hypertension. Despite these features, cerebrovascular accidents have been described only recently and only in association with stenoses of the cerebral vasculature.

Case Description
A 19-year-old girl with Williams syndrome developed an acute-onset hemiparesis. MRI demonstrated an infarct involving the internal capsule and putamen. No stenotic areas were seen on angiography.

Conclusions
Stroke should be considered as a possible consequence of Williams syndrome, even in the absence of stenoses of the cerebral vasculature. Comparison of this case with those previously reported in the literature emphasizes the multiplicity of features in Williams syndrome that can contribute to the risk of stroke.
Comparison of Different Diagnostic Criteria for Vascular Dementia (ADDTC, DSM-IV, ICD-10, NINDS-AIREN)
Authors: Wetterling Tilman , Kanitz Rolf-Dieter , Borgis Karl-Jochen
Published: June 2011

Background and Purpose
Vascular dementia (VD) has been an ill-defined term thus far. Recently detailed criteria for the diagnosis of VD have been proposed (Alzheimer’s Disease Diagnostic and Treatment Centers [ADDTC], 1992;
Diagnostic and Statistical Manual of Mental Disorders,
4th edition [DSM-IV], 1994;
International Classification of Diseases,
10th revision [ICD-10], 1992, 1993; and National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences [NINDS-AIREN], 1993). Until now the clinical feasibility of these diagnostic guidelines has not been evaluated.

Methods
This study aimed to compare these criteria in an unselected sample of 167 elderly patients (mean age, 72.0±9.9 years) admitted with probable dementia.

Results
The number of cases that could be classified as VD differed widely between the various diagnostic guidelines. According to DSM-IV criteria, 45 cases were diagnosed as VD. Twenty-one cases fulfilled the ICD-10 research criteria, but only 12 met the NINDS-AIREN criteria for VD. Twenty-three cases were classified as ischemic VD as defined by the ADDTC criteria. The concordance was very poor since only 5 cases met the criteria for VD of all diagnostic guidelines.

Conclusions
Our results show that the classification according to different diagnostic guidelines yields rather distinct groups of patients. The reasons responsible for these findings are as follows: (1) different criteria for dementia, (2) limitation to ischemic VD in the ADDTC criteria, (3) no further differentiation of VD into subtypes according to CT or MRI findings (DSM-IV), and (4) the multifactorial etiopathology of VD. Major diagnostic difficulties ensue from the very frequent cases with white matter lesions, since their etiology and classification remain widely unknown.
Ischemic Stroke in the Elderly
Authors: Press Richard D. , Liu Xiao-Yuan , Beamer Nancy , Coull Bruce M.
Published: June 2011

Background and Purpose
A common missense mutation in coagulation factor V (Arg 506 Gln) creates phenotypic resistance to the anticoagulant effects of activated protein C and predisposes carriers to venous thrombosis. To assess a correlation between this common hypercoagulable state and ischemic cerebrovascular disease, we have compared the prevalence of this mutation in a group of stroke patients with that in several control patient groups.

Methods
The presence of the factor V Arg 506 Gln mutation was determined by a direct polymerase chain reaction–based assay on peripheral blood leukocytes from 161 elderly patients with acute ischemic stroke, 116 elderly patients with stroke risk factors but without acute stroke, 54 healthy elderly control subjects, and 287 younger control individuals (197 blood donors and 90 neonates).

Results
The prevalence of the heterozygous Arg 506 Gln factor V mutation was not significantly different in the elderly stroke patients (2.5%) compared with either of the age-matched control groups (2% to 4%). The prevalence of this mutation was significantly higher in each of two younger control groups (≈8%) than in the elderly stroke patients (2.5%).

Conclusions
The common factor V Arg 506 Gln mutation predisposing to venous thrombosis is not a significant genetic risk factor for ischemic stroke in the elderly.
Factor V Leiden Mutation in Cerebral Venous Thrombosis
Authors: Zuber Mathieu , Toulon Pierre , Marnet Laurence , Mas Jean-Louis
Published: June 2011

Background and Purpose
Resistance to activated protein C is a common inherited risk factor for venous thrombosis, which is due to a mutation in coagulation factor V (factor V Leiden mutation). It is present in approximately 20% of unselected consecutive patients with deep vein thrombosis. The rate of resistance to activated protein C in patients with cerebral venous thrombosis (CVT) is unknown.

Methods
We investigated the association of factor V mutation with CVT using a case-control study. Nineteen unselected patients with CVT and 57 healthy control subjects were tested for the point mutation.

Results
The mutation was found in a heterozygous form in 4 of the 19 patients with CVT (21%) and in only 1 of the 57 control subjects (2%) (
P
=.02, Fisher's exact test). The prevalence of the coagulation defect found in our patients with CVT was consistent with that observed in previous studies in patients with deep vein thrombosis. In 3 of the 4 patients positive for the mutation, CVT developed in the presence of an acquired prothrombotic state, including oral contraceptive use in 2 patients and puerperium in the third.

Conclusions
Factor V Leiden mutation is a risk factor for CVT and may be the most common inherited coagulation defect associated with this condition.
Leukocyte Activation Detected by Increased Plasma Levels of Inflammatory Mediators in Patients With Ischemic Cerebrovascular Diseases
Authors: Elneihoum A.M. , Falke P. , Axelsson L. , Lundberg E. , Lindgärde F. , Ohlsson K.
Published: June 2011

Background and Purpose
Leukocytes have been implicated in the development of ischemic atherosclerotic vascular diseases. In a prospective study we investigated whether the plasma concentrations of inflammatory mediators, ie, proteases and cytokines, as markers for systemic leukocyte activation, are increased in patients with acute ischemic cerebrovascular diseases.

Methods
Using enzyme-linked immunosorbent assays, we measured the plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil proteinase 4 (NP4), tumor necrosis factor-α (TNF), and soluble TNF receptor protein-1 p55 (sTNFR-1) in 120 patients with acute ischemic cerebrovascular insult (72 with stroke and 48 with transient ischemic attack [TIA]) and in 35 age- and sex-matched healthy subjects.

Results
Compared with the control group, plasma NGAL levels were higher in the stroke group (
P
<.0001) and the TIA group (
P
<.01); plasma NP4 levels were higher in the stroke group (
P
<.0001) and the TIA group (
P
<.01); and plasma sTNFR-1 levels were higher in the stroke group (
P
<.04). There was significant correlation between the plasma levels of fibrinogen and those of both sTNFR-1 (
r
=.32;
P
=.005) and NGAL (
r
=.40;
P
=.0001) and between the erythrocyte sedimentation rate and the plasma levels of both sTNFR-1 (
r
=.35;
P
=.001) and NGAL (
r
=.34;
P
=.002).

Conclusions
Our study demonstrated that markers for systemic leukocyte activation, ie, plasma levels of cytokines and proteases, were higher in patients with acute ischemic cerebrovascular disease than in healthy control subjects. Activated leukocytes and leukocytic mediators may have an important role in acute cerebrovascular ischemia and its consequences.
Apolipoprotein E Polymorphism Is Associated With Segment-Specific Extracranial Carotid Artery Intima-Media Thickening
Authors: Terry James G. , Howard George , Mercuri Michele , Bond M. Gene , Crouse John R.
Published: June 2011

Background and Purpose
Apolipoprotein E (apoE) polymorphism affects plasma cholesterol and may influence risk of atherosclerosis. We investigated the association of apoE with carotid artery wall thickening (an index of atherosclerosis) in individuals with and without coronary artery disease (CAD).

Methods
ApoE phenotypes were resolved in 260 individuals equally represented by angiographically determined CAD case subjects and disease-free control subjects. Carotid artery intima-media thickening (IMT) was evaluated by B-mode ultrasound. Associations of apoE (E2, E3, or E4) with risk factors and IMT were evaluated in general linear models adjusted for age, sex, and CAD status with and without other traditional risk factors.

Results
Total cholesterol (TC) and LDL cholesterol were associated with apoE isoforms. Mean TC and LDL cholesterol were lower in E2 (n=33) carriers than E3 (n=155) and E4 (n=66) carriers (each
P
<.001). IMT also varied by apoE. E2 carriers had less common carotid IMT than E3 and E4 carriers (
P
<.01), while internal carotid IMT was less in E2 and E3 carriers than in E4 carriers (
P
<.02). Bifurcation IMT was not associated with apoE (
P
=.24). ApoE polymorphism remained associated with common (
P
<.01) and internal (
P
<.04) IMT, and the association of apoE with mean IMT of all sites reached significance (
P
<.04) after adjustment for age, sex, CAD status, TC, LDL cholesterol, HDL cholesterol, triglycerides, diabetes, hypertension, and smoking.

Conclusions
ApoE polymorphism is associated with segment-specific carotid IMT. The association of apoE with carotid IMT was statistically independent of apoE-associated variation in LDL cholesterol levels.
Management of Subarachnoid Hemorrhage Patients Who Presented With Respiratory Arrest Resuscitated With Bystander CPR
Authors: Shapiro Scott
Published: June 2011

Background and Purpose
The sudden death rate from aneurysmal subarachnoid hemorrhage (SAH) is 10%. Since 1989, 26 SAH patients who were witnessed to collapse into coma with respiratory arrest and required cardiopulmonary resuscitation (CPR) at the scene survived to reach the hospital and be diagnosed. Although reports on hospital management of grade V SAH suggest improved outcome, no report has previously addressed the issue of respiratory arrest after acute SAH. We analyze our experience with this unique subgroup of aneurysmal SAH patients.

Methods
This is a retrospective analysis of 26 consecutive SAH patients who collapsed at the scene and required CPR for respiratory arrest and survived to reach the hospital and be diagnosed. Statistical analysis was performed using the
t
test and Mann-Whitney rank-sum test.

Results
All patients were grade V on arrival at the emergency department. Twenty-one patients received mouth-to-mouth resuscitation only, and 5 received chest compressions as well. The mean duration of bystander CPR was 12 to 15 minutes. CT scan showed diffuse, thick SAH in all patients, an associated subdural hemorrhage in 2, and an intraparenchymal hemorrhage in 4. After CT scan, an intracranial pressure (ICP) monitor was placed in 24, and 2 were taken to emergency surgery for subdural and intracerebral hemorrhage. ICP was elevated in 24 patients (mean, 54 mm Hg), and a ventriculostomy was placed in all 24. ICP was unresponsive in 12, and all suffered brain death. ICP lessened to <25 mm Hg in 12, and all underwent angiography. All 12 had an aneurysm and underwent emergency surgical clipping. Time to surgery from SAH was ≤11 hours in all 12 patients. All were managed with calcium channel blockers and hyperdynamic therapy in addition to aggressive control of ICP. The outcome at 12 months in the 14 surgical cases was normal in 3 patients (21%), good in 2 (14%), vegetative in 1 (7%), and death in 8 (57%).

Conclusions
Aneurysmal SAH patients that present with respiratory arrest present as grade V patients with elevated ICP. Bystander CPR coupled with early retrieval, diagnosis, and therapy can lead to 20% functional survival in what used to be sudden death from aneurysmal SAH.
Asymmetry of Intracranial Hemodynamics as an Indicator of Mass Effect in Acute Intracerebral Hemorrhage
Authors: Mayer Stephan A. , Thomas Carole E. , Diamond Beverly E.
Published: June 2011

Background and Purpose
Hematoma volume is an important determinant of outcome and predictor of clinical deterioration in patients with intracerebral hemorrhage. In many cases, worsening results from herniation due to compartmentalized pressure gradients. We used transcranial Doppler sonography (TCD) to assess the impact of hematoma volume on symmetry of intracranial hemodynamics in patients with acute intracerebral hemorrhage. The goal was to evaluate TCD as a noninvasive method for monitoring compartmentalized mass effect.

Methods
TCD was performed an average of 1.1 days (range, 0 to 3 days) after onset in 30 patients with supratentorial intracerebral hemorrhage. Hematoma, hematoma+edema, and intraventricular hemorrhage volumes were calculated from admission CT scans using computerized planimetry and were compared with combined TCD values from the middle cerebral and internal carotid arteries.

Results
Ipsilateral pulsatility indexes were consistently elevated and mean velocities consistently depressed when intracerebral hemorrhage volumes exceeded 25 mL. Compared with patients with small hemorrhages, those with large hemorrhages (≥25 mL, n=10) had significantly higher ipsilateral pulsatility indexes (1.72 versus 1.13,
P
<.0001) and higher ratios of ipsilateral-to-contralateral pulsatility (1.29 versus 1.06,
P
=.001). The ratio of ipsilateral-to-contralateral mean velocity was similarly reduced in patients with large versus small hemorrhages (0.87 versus 1.06,
P
=.01), but this effect was less pronounced. In a multiple regression analysis, ipsilateral and contralateral pulsatility indexes correlated primarily with intraventricular hemorrhage volume (
P
<.001), whereas the ratio of ipsilateral-to-contralateral pulsatility correlated with total hemispheric lesion (hematoma+edema) volume (
P
=.003).

Conclusions
Asymmetry of intracranial hemodynamics as assessed by TCD occurs when intracerebral hemorrhage volumes exceed 25 mL. Alterations of pulsatility index reflect intracranial lesion volume more reliably than mean velocity. Although pulsatility is strongly influenced by the presence of intraventricular blood, elevated ratios of ipsilateral-to-contralateral pulsatility correlate primarily with hemispheric lesion volume and may reflect compartmentalized intracranial pressure gradients.
Monitoring of Cerebral Autoregulation in Head-Injured Patients
Authors: Czosnyka Marek , Smielewski Piotr , Kirkpatrick Peter , Menon David K. , Pickard John D.
Published: June 2011

Background and Purpose
Disturbed cerebral autoregulation has been reported to correlate with an unfavorable outcome after head injury. Using transcranial Doppler ultrasonography, we investigated whether hemodynamic responses to spontaneous variations of cerebral perfusion pressure (CPP) provide reliable information on cerebral autoregulatory reserve.

Methods
We studied 82 patients with head injury daily. Waveforms of intracranial pressure (ICP), arterial pressure, and transcranial Doppler flow velocity (FV) were captured during 2-hour periods. Time-averaged mean FV (FVm) and the FV during cardiac systole (FVs) were resolved. The correlation coefficient indices between FVm and CPP (Mx) and between FVs and CPP (Sx) during spontaneous fluctuations of CPP were calculated during 3-minute epochs and averaged for each investigation.

Results
Mx and Sx correlated with CPP (
r
=−.34,
P
=<.002;
r
=−.2,
P
=NS, respectively), with ICP (
r
=.46,
P
<.0001;
r
=.34,
P
<.003, respectively), with admission Glasgow Coma Scale score (
r
=−.34,
P
<.0025;
r
=−.38,
P
<.0008, respectively), and with outcome after head injury (
r
=.41,
P
<.0002;
r
=.48,
P
<.00009, respectively). In patients who died, cerebral autoregulation was severely disturbed during the first 2 days after injury.

Conclusions
Indices derived from spontaneous fluctuations of FV waveform and CPP describe cerebral vascular pressure reactivity. They correlate with outcome after head injury and therefore may be used to guide autoregulation-oriented intensive therapy.
Relationships Between Cerebral Regional Blood Flow Velocities and Volumetric Blood Flows and Their Respective Reactivities to Acetazolamide
Authors: Démolis Pierre , Dinh Yves R. Tran , Giudicelli Jean-François
Published: June 2011

Background and Purpose
The technique of transcranial Doppler ultrasonography (TCD) is widely used for assessment of cerebral blood flow velocity. Whether measurement of changes in TCD velocity can be used for studying volumetric cerebral blood flow variations remains a matter of debate. We therefore investigated the relationship between flow velocity and volumetric cerebral blood flow before and during acetazolamide-induced vasodilation.

Methods
The middle cerebral artery mean blood flow velocity (MV) measured by TCD and the corresponding regional and hemispheric cerebral blood flows assessed with
133
Xe single-photon emission CT were measured in 52 unselected patients. Absolute values of flow and velocity before and after stimulation and their reactivity to acetazolamide were compared. When the correlation was statistically significant, the linearity of the relationship was tested.

Results
Absolute values of hemispheric cerebral blood flow were correlated with MV both before (
r
=.315,
P
=.02) and after acetazolamide (
r
=.436,
P
=.001), whereas regional cerebral blood flow was correlated with MV only after acetazolamide (before,
r
=.262,
P
=.06; after,
r
=.446,
P
=.001). All these relationships fitted a linear model. In contrast, there was no correlation between acetazolamide-induced relative increments of flow and velocity.

Conclusions
Our results support a linear model describing the relationship between absolute values of flow and velocity when arterial section is the slope and anastomotic blood flow is the intercept. In contrast, relative increments in volumetric flow and velocity may be proportional only if anastomotic flow is negligible, ie, in subjects without cerebrovascular disease. We conclude that, for patients with cerebrovascular disease, TCD does not satisfactorily model cerebral vasoreactivity in terms of volumetric cerebral blood flow.
Automatic Embolus Detection Compared With Human Experts
Authors: Van Zuilen Erik V. , Mess Werner H. , Jansen Cees , Van Der Tweel Ingeborg , Van Gijn Jan , Ackerstaff Rob G.A.
Published: June 2011

Background and Purpose
Transcranial Doppler ultrasound (TCD) reliably detects the occurrence of microembolic signals (MES). Unfortunately, TCD monitoring is a time-consuming and mentally strenuous procedure. The purpose of this study was to assess whether automatic embolus detection software devices acting as a “stand-alone system” are able to identify MES in patients with solid cerebral microemboli.

Methods
Ten records of TCD monitoring of the middle cerebral artery in patients with symptomatic high-grade carotid artery stenosis were analyzed for the moments at which MES occurred by four observers and three automatic detection software devices (RB11 on TC2000, Pioneer Version 2.10, and Embotec). The results of the three software systems were assessed on the basic assumption that MES were present if at least three of the four observers agreed.

Results
The average number of 1-second periods in which MES were detected by the four observers per tape ranged from 5 to 39. The overall κ values (and SEs) for chance-corrected interobserver agreement between the four observers ranged from .94 (.02) to .99 (.01). The agreement between the software devices and the observers was lower, with κ values (and SEs) ranging from .18 (.17) to .93 (.07). The RB11 and Embotec systems achieved a κ value higher than 0.4 in all tapes. The Pioneer system failed to reach a κ value of 0.4 in three tapes. The RB11 showed a sensitivity of 70% for detecting MES, the Embotec 62%, and the Pioneer 44%.

Conclusions
In patients with symptomatic high-grade carotid artery stenosis, a high degree of agreement in the detection of moments of MES can be achieved between observers. The three automatic detection software devices reached less agreement. Supervision of TCD monitoring and assessment of MES by an experienced observer is still necessary.