bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcranial Doppler Assessment of Cerebrovascular Reactivity in Symptomatic and Asymptomatic Severe Carotid Stenosis
Authors: Silvestrini Mauro , Troisi Elio , Matteis Maria , Cupini Letizia M. , Caltagirone Carlo
Published: June 2011

Background and Purpose
Some studies have suggested a link between impaired cerebral hemodynamics and stroke in patients with carotid stenosis. The aim of this study was to assess the effects of severe carotid stenosis on cerebrovascular reactivity and the possible changes after endarterectomy.

Methods
Using bilateral transcranial Doppler ultrasound, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries of 10 control subjects and 24 patients (13 symptomatic and 11 asymptomatic) with unilateral severe carotid stenosis before and after endarterectomy. Cerebrovascular reactivity was evaluated with the breath-holding index (BHI).

Results
Before endarterectomy, BHI (mean value±SD) was significantly lower (
P
<.001) in the stenotic side of symptomatic patients (0.40±0.2) than in control subjects (1.12±0.3), the stenotic side of asymptomatic patients (0.80±0.4), and the normal side of both symptomatic (0.93±0.3) and asymptomatic (1.03±0.2) patients. On the other hand, no significant difference in BHI was detected in control subjects, on the normal side of symptomatic and asymptomatic patients, and the stenotic side of asymptomatic patients. After endarterectomy, BHI significantly increased (
P
<.0001) on the stenotic side of symptomatic patients (1.06±0.2) while remaining substantially stable on the normal side of both symptomatic and asymptomatic patients and on the stenotic side of asymptomatic patients.

Conclusions
These findings suggest that the study of cerebrovascular reactivity to hypercapnia may be relevant in evaluating the functional effects of carotid stenosis. Further investigations are needed to confirm the reliability of the breath-holding method in the selection of patients who might benefit most from carotid endarterectomy.
Race and Sex Differences in the Distribution of Cerebral Atherosclerosis
Authors: Wityk R. J. , Lehman D. , Klag M. , Coresh J. , Ahn H. , Litt B.
Published: June 2011

Background and Purpose
The purpose of this study was to assess the influence of race, sex, and other risk factors on the location of atherosclerotic occlusive lesions in cerebral vessels. Previous angiographic studies of patients with stroke or transient ischemic attack (TIA) suggest that extracranial atherosclerosis is more common in whites and intracranial disease is more common in blacks. Noninvasive techniques such as duplex ultrasound, transcranial Doppler (TCD), and magnetic resonance angiography (MRA) allow vascular assessment of a more representative proportion of patients than does conventional angiography alone.

Methods
Consecutive patients evaluated at a community hospital for stroke or TIA over a 2-year period were reviewed. Lesions were defined as a 50% or greater atherosclerotic stenosis by angiography, duplex ultrasound, or TCD, or a moderate stenosis by MRA.

Results
Whites were more likely than blacks to have extracranial carotid artery lesions (33% versus 15%,
P
=.001), but the proportion of patients with intracranial lesions was similar (24% versus 22%). Men were more likely to have intracranial lesions than women (29% versus 14%,
P
=.03). When multivariate logistic regression analysis was used, white race was the only predictor for extracranial carotid artery lesions, and male sex was the only predictor for intracranial lesions. The cause of stroke/TIA was extracranial carotid artery disease in 8% and intracranial disease in 8% of all patients in the study.

Conclusions
The distribution of cerebral atherosclerosis is influenced by race and sex but not by other vascular risk factors. In our patient population, intracranial disease is as common a cause of cerebral ischemia as extracranial carotid disease.
Low Total Serum Cholesterol and Intracerebral Hemorrhagic Stroke: Is the Association Confined to Elderly Men?
Authors: Iribarren Carlos , Jacobs David R. , Sadler Marianne , Claxton Ami J. , Sidney Stephen
Published: June 2011

Background and Purpose
Epidemiological studies indicate a higher incidence of intracerebral (but not subarachnoid) hemorrhagic stroke among persons with low total serum cholesterol levels. This report further examines the prospective relationship of total serum cholesterol with subsequent intracerebral hemorrhage in a large, well-defined population.

Methods
The cohort included 61 756 enrollees in a health plan from the San Francisco–Oakland metropolitan area (46% men, 63% white), aged 40 to 89 years and free of cardiovascular disease at baseline. Sixteen-year incidence of combined nonfatal and fatal intracerebral hemorrhagic stroke (
International Classification of Diseases
[ICD], 8th revision, code 431, or ICD, 9th revision, codes 431 and 432) was investigated in relation to serum cholesterol measured in multiphasic health checkups made in 1977 through 1985. Intracerebral hemorrhagic events were ascertained using hospital discharge records and as underlying cause of death by the California Mortality Linkage Information System.

Results
From 1978 through 1993 (average of 10.7 years), there were 386 events (201 in men, 29% fatal; 185 in women, 42% fatal). By multivariate proportional hazards life-table regression analysis, serum cholesterol level below the sex-specific 10th percentile (<4.62 mmol/L [178 mg/dL] in men), compared with higher cholesterol level, was associated with a significantly increased risk of intracerebral hemorrhage in men aged 65 years or older (relative risk, 2.7; 95% confidence interval, 1.4 to 5.0). An excess risk was also observed among elderly women at the lowest cholesterol range, but a chance finding could not be ruled out. No relationship was seen among men or women aged 40 to 64, and no statistical interaction of low serum cholesterol with hypertension was found in either sex.

Conclusions
In these data, the association between low serum cholesterol level and intracerebral hemorrhage was confined to elderly men.
Precipitants of Brain Infarction
Authors: Macko Richard F. , Ameriso Sebastian F. , Barndt Robert , Clough Wendy , Weiner John M. , Fisher Mark
Published: June 2011

Background and Purpose
Antecedent febrile infection and psychological stress are described as predisposing risk factors for brain infarction. We examined the temporal relationship between preceding infection/inflammation and stroke onset as well as the role of recent psychological stress as a potential precipitant for brain infarction.

Methods
In this case-control study, a standardized evaluation including a signs/symptoms-based questionnaire was used to characterize the prevalence and timing of recent prior (<1 month) infectious and inflammatory syndromes in 37 adults with acute brain infarction, 47 community control subjects, and 34 hospitalized nonstroke neurological patient controls. Recent psychological stress was measured with scales of stressful life events and negative affect.

Results
The prevalence of infection/inflammation was significantly higher in the stroke group only within the preceding 1 week compared with either community control subjects (13/37 versus 6/47,
P
<.02) or hospitalized neurological patient controls (3/34,
P
<.02). Upper respiratory tract infections constituted the most common type of infection. A substantial proportion of stroke patients with preceding (<1 week) infection/inflammation (5/13) had no accompanying fever or chills. There were no significant differences between the stroke and control groups in the levels of stressful life events within the prior 1 month or in negative-affect scale scores within the prior 1 week.

Conclusions
Our data suggest that both febrile and nonfebrile infectious/inflammatory syndromes may be a common predisposing risk factor for brain infarction and that the period of increased risk is confined within a brief temporal window of less than 1 week. Results of this study argue against a role for recent psychological stress as a precipitant for cerebral infarction.
Risk Factors for Cerebral Hemorrhage in the Era of Well-Controlled Hypertension
Authors: Thrift Amanda G. , McNeil John J. , Forbes Andrew , Donnan Geoffrey A.
Published: June 2011

Background and Purpose
Given that hypertension is now relatively well controlled and use of antiplatelet agents has increased, our primary aims were to investigate the risk of intracerebral hemorrhage (ICH) associated with hypertension and use of antiplatelet agents.

Methods
In this city-wide case-control study, 370 consecutive cases of primary ICH, verified by CT or autopsy, were identified from one of 13 Melbourne hospitals. Ten subjects (or their next of kin) could not be located and 29 refused to participate, resulting in 331 eventual cases. Patients were aged between 18 and 80 years and had no prior stroke. Population-based control subjects were individually age- (±5 years), sex-, and geographically matched to subject cases. A questionnaire administered to participants (or next of kin) elicited information about prior exposure to various potential risk factors.

Results
Hypertension approximately doubled the risk of ICH (odds ratio, 2.55; 95% confidence interval, 1.72 to 3.79). The use of aspirinlike drugs, in doses used for secondary prevention of ischemic stroke or cardiac disease, was not associated with an increased risk of ICH (odds ratio, 0.66; 95% confidence interval, 0.20 to 2.21). Factors associated with a reduced risk of ICH were a history of cardiovascular disease, arthritis, or high cholesterol level; being moderately overweight or using hormone replacement therapy; and drinking coffee.

Conclusions
Hypertension was the most important risk factor for ICH but not as high as previously reported, nor was it higher than that reported for ischemic stroke. There was no evidence for any association between the use of aspirinlike drugs and ICH.
Proteinuria Predicts Stroke and Other Atherosclerotic Vascular Disease Events in Nondiabetic and Non–Insulin-Dependent Diabetic Subjects
Authors: Miettinen Heikki , Haffner Steven M. , Lehto Seppo , Rönnemaa Tapani , Pyörälä Kalevi , Laakso Markku
Published: June 2011

Background and Purpose
Increased urinary albumin and protein excretion is associated with cardiovascular disease mortality independent of other cardiovascular risk factors in subjects with non–insulin-dependent diabetes mellitus (NIDDM). We assessed the relationship between the different degrees of proteinuria at baseline and the incidence of stroke, as well as other atherosclerotic vascular disease events, in a prospective study of nondiabetic and NIDDM subjects.

Methods
Our study was based on the 7-year follow-up of cohorts of nondiabetic (n=1375) and NIDDM (n=1056) subjects in Finland. The urinary protein concentration at baseline was stratified into three categories: no proteinuria (<150 mg/L), borderline (150 to 300 mg/L), and clinical proteinuria (>300 mg/L).

Results
The association between the different degrees of proteinuria and the atherosclerotic vascular events was similar in nondiabetic and NIDDM subjects. Cardiovascular disease mortality was higher both in nondiabetic and NIDDM subjects with clinical proteinuria than in those without proteinuria. The incidence of stroke was 1.6% in nondiabetic subjects without proteinuria, 3.2% in subjects with borderline proteinuria, and 8.5% in subjects with clinical proteinuria (
P
<.001 for trend). In NIDDM patients, the corresponding rates were 7.2%, 11.1%, and 23.0%, respectively (
P
<.001 for trend). The association between clinical proteinuria and the incidence of stroke remained significant both in nondiabetic and in NIDDM subjects after adjustment for other cardiovascular risk factors. Clinical proteinuria was also associated with the incidence of coronary heart disease events and that of lower-extremity amputation. NIDDM independently increased the risk of atherosclerotic vascular disease events regardless of the proteinuria status.

Conclusions
Clinical proteinuria significantly predicted stroke and other atherosclerotic vascular disease events independent of other cardiovascular risk factors. This finding is compatible with the view that increased urinary protein excretion rate may be associated with widespread vascular damage.
Identification of Posttraumatic Ischemia and Hyperperfusion by Determination of the Effect of Induced Arterial Hypertension on Carbon Dioxide Reactivity
Authors: Steiger H.J. , Ciessinna E. , Seiler R.W.
Published: June 2011

Background and Purpose
Both ischemia and hyperperfusion are known phenomena that follow traumatic brain injury. Cerebral carbon dioxide reactivity is diminished in both conditions. Differentiation is important because ischemia is thought to be a major factor of secondary neuronal loss and is potentially amenable to therapy by manipulation of cerebral perfusion pressure.

Methods
The response of transcranial Doppler–based carbon dioxide reactivity to pharmacologically induced hypertension was studied sequentially in 29 patients with severe to moderate head injury to identify ischemia and luxury perfusion. After simultaneous baseline registration of the carbon dioxide reactivity of both middle cerebral arteries by two-channel transcranial Doppler, systolic arterial pressure was raised approximately 20 mm Hg by means of phenylephrine (Neosynephrine) infusion, and the carbon dioxide reactivity test was repeated.

Results
A significant improvement of impaired (<2%/mm Hg) carbon dioxide reactivity after arterial pressure was raised by 20 mm Hg (signaling ischemia) was found in 32 of 124 evaluated middle cerebral arteries. Further deterioration of impaired reactivity occurred in only four tested hemispheres. While ischemic conditions were identified during the entire study period, hyperperfusion was encountered only after day 3.

Conclusions
Ischemia after traumatic brain injury is a frequent phenomenon, whereas hyperperfusion is rare. Whether therapeutic optimization of carbon dioxide reactivity can improve the outcome of head-injury patients needs to be evaluated in further studies.
Abnormal Heart Rate Variability as a Manifestation of Autonomic Dysfunction in Hemispheric Brain Infarction
Authors: Korpelainen Juha T. , Sotaniemi Kyösti A. , Huikuri Heikki V. , Myllylä Vilho V.
Published: June 2011

Background and Purpose
Abnormal heart rate variability is related to prognostically unfavorable ventricular arrhythmias and sudden arrhythmic death in coronary artery disease. Short-term electrocardiographic (ECG) recordings have shown similar abnormalities of heart rate variability in patients with acute stroke. However, there is no information regarding the clinical significance of these abnormalities and of heart rate variability in long-term ECG recordings in stroke.

Methods
In this prospective study, we analyzed the time domain and frequency domain measures of heart rate variability from 24-hour ECG recordings in 31 consecutive patients with hemispheric brain infarction in the acute phase and at 1 and 6 months after the infarction and in 31 age- and sex-matched healthy control subjects.

Results
All the measured components of heart rate variability, ie, standard deviation of RR intervals (
P
<.001), total power (
P
<.0001), very-low-frequency power (
P
<.0001), low-frequency power (
P
<.001), and high-frequency power (
P
<.05), were significantly lower than those of the control subjects in both the acute phase and 1 and 6 months later. Impaired heart rate variability correlated with the severity of neurological deficits and disability. In five patients with increased intracranial pressure due to large brain infarction, no relevant spectral components were found.

Conclusions
Hemispheric brain infarction seems to cause significant long-lasting damage to the cardiovascular autonomic regulatory system manifested as abnormalities of heart rate variability. Distorted heart rate variability in the acute phase of stroke may be prognostically unfavorable.
Hemodynamic Study of the Anterior Communicating Artery
Authors: Ujiie H. , Liepsch Dieter W. , Goetz Max , Yamaguchi R. , Yonetani H. , Takakura K.
Published: June 2011

Background and Purpose
The anterior communicating artery (ACoA) is a site of predilection for intracranial saccular aneurysms causing subarachnoid hemorrhage. ACoA aneurysms are frequently associated with an asymmetrical circle of Willis. In such cases, the ACoA is probably exposed to high hemodynamic stress caused by a considerable shunt flow across the ACoA to the distal segment of the contralateral anterior cerebral artery (ACA). In the present study, the flow pattern and flow-induced shear stress in the ACoA complex that may initiate aneurysmal lesions were studied under steady and pulsatile flow conditions.

Methods
Flow visualization was studied with dye injection and birefringent flow visualization in symmetrical and asymmetrical models of various sizes of ACoA. The distribution of wall shear stress was measured using an electrochemical method based on a diffusion-controlled reaction of ferricyanide ion to ferrocyanide ion at a platinum electrode embedded in the wall of the ACoA model.

Results
With equal flow rate (Reynolds number 150 to 600), vortical flow was formed in the mouth of the ACoA, and no cross flow through the ACoA was observed. The wall shear stress on the mid-wall of the ACoA was almost zero. However, as soon as the flow rate became unequal, a cross flow through the ACoA was observed. The stagnation point also appeared at the medial junction of the ACoA and ACA. The wall shear stress increased to a very high level at the wall of the ACoA and around the stagnation point.

Conclusions
Geometric changes from the symmetrical to the asymmetrical ACoA develop higher shear stress on the ACoA than critical values and the stagnation point at the ACoA junction. A combination of these hemodynamic factors is considered to play an important role in initiation of aneurysm.
Evolution of Photochemically Induced Focal Cerebral Ischemia in the Rat
Authors: Lee Vee Meng , Burdett Newman G. , Carpenter T. Adrian , Hall Laurance D. , Pambakian Perouz S. , Patel Sara , Wood Nigel I. , James Michael F.
Published: June 2011

Background and Purpose
Magnetic resonance imaging (MRI) is increasingly used to study the pathophysiological evolution of cerebral ischemia in humans and animals. We have investigated photochemically induced (rose bengal) focal cerebral ischemia, a relatively noninvasive, reproducible model for stroke, and compared the evolution of the ischemic response in vivo and postmortem with MRI and histology, respectively.

Methods
MR images weighted for T
2
, diffusion, and T
2
* and parallel histological sections stained with cresyl fast violet (CFV) and for glial fibrillary acid protein were obtained from 34 adult male Hooded Lister rats at seven time points (3.75 to 196 hours) after bilateral ischemia induction. From CFV histology, lesion volumes and cell counts were calculated; from diffusion-weighted and T
2
-weighted images, apparent diffusion coefficients and lesion volumes were determined.

Results
Both MRI and histology revealed a well-defined lesion at 3.75 hours after irradiation and a consistent pattern of temporal evolution; lesion apparent diffusion coefficients decreased significantly by 3.75 hours, increased significantly by day 2, and correlated strikingly with the decline in lesion CFV-positive cell numbers. After day 2, astrocytes and connective tissue cells invaded the infarct. Throughout the time course, lesion volumes determined in vivo and postmortem (after shrinkage correction) agreed well.

Conclusions
MRI changes quantitatively reflect histopathology, revealing reproducible primary and secondary damage characteristics noninvasively. These changes essentially replicate those reported for other animal stroke models and clinically, emphasizing the value both of MRI and the photochemically induced focal cerebral ischemia model in stroke research.
Moyamoya and Down Syndrome
Authors: Cramer Steven C. , Robertson Richard L. , Dooling Elizabeth C. , Scott R. Michael
Published: June 2011

Background and Purpose
Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by progressive stenosis of the supraclinoid internal carotid artery, with the secondary development of enlarged basal collateral vessels. It may occur as a primary disease or as a syndrome in association with a variety of conditions, and its pathogenesis remains unexplained. There are relatively few reports describing the occurrence of moyamoya in Down syndrome. The aim of this study is to describe the clinical and radiological features of moyamoya syndrome associated with Down syndrome (MM-DS) and to explore theories of moyamoya pathogenesis in these patients.

Methods
Seven children with MM-DS underwent brain imaging, transfemoral angiography, and serial neurological exams. Neurological deficits, poststroke recovery, radiographic infarct characteristics, and angiographic abnormalities were reviewed.

Results
The clinical and radiological features of primary moyamoya disease overlap with those of MM-DS. Hemiplegia and aphasia were the most common presentations. Motor recovery was excellent in five of seven cases. Cerebral infarcts were superficial or deep and can occur in a watershed distribution. Angiography demonstrated involvement of the internal carotid artery and its branches bilaterally in all seven cases and the posterior cerebral arteries in four cases.

Conclusions
The clinical and radiological features of MM-DS overlap with primary moyamoya disease. We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of moyamoya disease. Although the neuronal substrate is abnormal in Down syndrome patients, recovery from hemiplegic stroke in patients with MM-DS is comparable to recovery in patients with primary moyamoya.
Ultrasound Densitometric Analysis of Carotid Plaque Composition
Authors: Beletsky Vadim Y. , Kelley Roger E. , Fowler Marjorie , Phifer Travis
Published: June 2011

Background and Purpose
The components of a carotid artery plaque might affect the risk of ipsilateral stroke. The accuracy of carotid duplex scan in assessing stroke risk reflects the experience of the scan reader. Thus, methods that can enhance ultrasonic evaluation of plaque morphology might allow a more objective means of determining carotid-mediated stroke risk.

Methods
We performed densitometric analysis of B-mode images of carotid plaques in nine patients scheduled for carotid endarterectomy. All patients had preoperative duplex color imaging and cerebral arteriography. The surgical specimen was analyzed histologically to determine the plaque components (soft plaque/organized thrombus, intraplaque hemorrhage/lipid deposition, fibrosis, and calcification). The specimen findings were correlated with the densitometric measurements to determine whether the density analysis would allow a reliable determination of the plaque substratum.

Results
With 1.0 as a reference point for the moving column of blood, the mean acoustic densities (±SD) were as follows: organized thrombus, 1.8±0.5; intraplaque hemorrhage/lipid deposition, 5.15±0.9; fibrosis, 9.51±2.9; and calcification, 15.5±8.6.

Conclusions
We conclude that densitometric evaluation allows differentiation of the various possible components of carotid plaque. The determination of plaque composition, based on density measurement, may provide information about its potential for thromboembolization.
Vitamin D Deficiency and Osteopenia in the Hemiplegic Limbs of Stroke Patients
Authors: Sato Yoshihiro , Maruoka Hiroshi , Oizumi Kotaro , Kikuyama Munetsugu
Published: June 2011

Background and Purpose
Little is known about bone changes in hemiplegic stroke patients. We evaluated the vitamin D status and bone changes on the hemiplegic and intact sides of stroke patients.

Methods
Sera were collected from 87 hemiplegic stroke patients (42 outpatients and 45 inpatients) and from 28 control subjects. The sera were assayed for 25-hydroxyvitamin D (25-OHD). Bone density was measured bilaterally from radiographs of the hands. Diet and sunlight exposure were assessed for all subjects.

Results
Serum 25-OHD concentrations were lower in patients (9.1±4.9 ng/mL for outpatients, 5.9±4.1 ng/mL for inpatients) than in control subjects (21.6±3.1 ng/mL). The difference in serum 25-OHD between the two patient groups also was statistically significant. The patients' microdensitometric scores for osteopenia were higher on the hemiplegic side than on the nonhemiplegic side. The microdensitometric scores and their side-to-side differences in patients correlated negatively with the serum 25-OHD concentration and positively with the degree of paralysis. Dietary intake of vitamin D was below the recommended level in 72% of the patients, and 89% of the patients were considered sunlight-deprived.

Conclusions
Bone mass was reduced significantly on the hemiplegic side in the stroke patients, which might increase the risk of hip fracture. Vitamin D deficiency and disuse are the probable causes of osteopenia in this population. The hypovitaminosis D might be corrected readily by routine use of vitamin D supplements.
α-Thrombin Upregulates Gα
i3
in Human Vascular Endothelial Cells
Authors: Shreeve S. Martin , Shatos Marie A. , Thorin Eric
Published: June 2011

Background and Purpose
During thrombosis, α-thrombin becomes sequestered by fibrin and the subendothelial basement membrane, and it is available to interact with the vasculature over prolonged periods. In this study, we investigated the long-term effect of α-thrombin on Gα
i3
and Gα
s
levels in human vascular endothelial cells (EC). Because obesity is associated with changes in receptor signaling in many animal models, we also explored the influence of this clinical risk factor.

Methods
Primary cultures of human EC were exposed to α-thrombin for 16 hours, and immunologically detectable Gα
i3
and Gα
s
levels were measured.

Results
α-Thrombin (100 nmol/L) increased Gα
i3
levels in EC derived from the cerebral microvasculature and superficial temporal artery (4.2±1.2-fold and 2.8±0.32-fold, respectively) but had no significant effect on EC derived from omental artery (
P
>.6) or from the superficial temporal artery of obese (body mass index ≥28 kg/m
2
) patients (
P
>.4). The expression of Gα
s
was unchanged in all cell types (
P
≥.1). Two other circulating peptides, vasoactive intestinal peptide and endothelin-1, failed to alter the expression of either G protein in EC from the cerebral microvasculature, further demonstrating the specificity of the α-thrombin effect. However, thrombin receptor activating protein-14 mimicked the α-thrombin response and increased Gα
i3
in EC derived from the cerebral microvasculature and superficial temporal artery.

Conclusions
We conclude that α-thrombin increases Gα
i3
expression in some EC through activation of its tethered liganded receptor. Obesity appears to suppress this action of α-thrombin.
Diagnosis of Transient Ischemic Attack by the Nonneurologist
Authors: Ferro J.M. , Falcão I. , Rodrigues G. , Canhão P. , Melo T.P. , Oliveira V. , Pinto A.N. , Crespo M. , Salgado A.V.
Published: June 2011

Background and Purpose
Interobserver reliability of the diagnosis of transient ischemic attack (TIA) is low, and diagnosis of TIA made by nonneurologists is often erroneous. We sought to validate the diagnosis of TIA made by general practitioners (GPs) and by hospital emergency service physicians (emergency MDs).

Methods
A list of 20 neurological symptoms was distributed to 20 GPs and 22 neurologists who graded the compatibility of each symptom with the TIA diagnosis. At least two neurologists validated TIA diagnoses made by GPs for patients under their care or by emergency MDs.

Results
Compared with neurologists, GPs considered “confusion” and “unexplained fall” more often compatible with TIA and “lower facial palsy” and “monocular blindness” less often compatible with TIA. Validation of diagnosis by GP was confirmed in 10 patients (19%); 26 patients had strokes, and 16 (31%) had a noncerebrovascular disorder. Validation of diagnosis by emergency MD was confirmed in 4 patients (13%); 10 patients had strokes, and 17 (55%) had noncerebrovascular disorders. The most frequent conditions misdiagnosed as TIAs were transient disturbances of consciousness, mental status, and balance.

Conclusions
The TIA concept is understood differently by neurologists and nonneurologists. GPs and emergency MDs often label minor strokes and several nonvascular transient neurological disturbances as TIAs. Until this misconception of TIA is changed, the term TIA should probably be avoided in the communication between referring physicians and neurologists. If not referred to a neurologist, one third to one half of patients labeled with a diagnosis of TIA will be inappropriately managed.
Indexes of Flow and Cross-sectional Area of the Middle Cerebral Artery Using Doppler Ultrasound During Hypoxia and Hypercapnia in Humans
Authors: Poulin Marc J. , Robbins Peter A.
Published: June 2011

Background and Purpose
This study examined changes in cross-sectional area of the middle cerebral artery as assessed by changes in Doppler signal power during hypoxia and hypercapnia. In addition, it examined the degree of consistency among three indexes of cerebral blood flow and velocity: the velocity spectral outline (V̄
P
), the intensity-weighted mean velocity (V̄
IWM
), and an index of middle cerebral artery flow (P·V̄
IWM
). P·V̄
IWM
was calculated as the product of V̄
IWM
multiplied by the total power signal. Power is proportional to cross-sectional area of the vessel; this calculation therefore allows for any changes in this variable.

Methods
Four protocols were used, each repeated six times for six healthy adults aged 20.8±1.7 years (mean±SD). The first was a control protocol (A) with end-tidal P
o
2
(
et
P
o
2
) maintained at 100 mm Hg and
et
P
co
2
at 1 to 2 mm Hg above eucapnia throughout. The second was a hypoxic step protocol (B) with
et
P
o
2
lowered from control values to 50 mm Hg for 20 minutes. The third was a hypercapnic step protocol (C) with
et
P
co
2
elevated from control by 7.5 mm Hg for 20 minutes. The fourth was a combined hypoxic and hypercapnic step protocol (D) lasting 20 minutes. A dynamic end-tidal forcing system was used to control
et
P
co
2
and
et
P
o
2
. Doppler data were collected and stored every 10 milliseconds, and mean values were determined later on a beat-by-beat basis. V̄
P
, V̄
IWM
, power, and P·V̄
IWM
were expressed as a percentage of the average value over a 3-minute period before the step.

Results
In protocols A and B, there were no changes in power and there were no differences between V̄
P
, V̄
IWM
, and P·V̄
IWM
. In C, at the relief from hypercapnia, there was a transient nonsignificant increase in power and a transient nonsignificant decrease in both V̄
P
and V̄
IWM
compared with P·V̄
IWM
. In D, during the stimulus period, V̄
P
was significantly higher than V̄
IWM
(paired
t
test,
P
<.05), but both indexes were not different from P·V̄
IWM
. In the period that followed relief from hypoxia and hypercapnia, the Doppler power signal was significantly increased by 3.8%. During this period, V̄
P
and V̄
IWM
were significantly lower than P·V̄
IWM
.

Conclusions
At the levels of either hypoxia or hypercapnia used in this study, there were no changes in cross-sectional area of the middle cerebral artery, and changes in both V̄
P
and V̄
IWM
accurately reflect changes in P·V̄
IWM
. With combined hypoxia and hypercapnia, however, at the relief from the stimuli when there is a very large and rapid decrease in P·V̄
IWM
, power is increased, suggesting an increase in the cross-sectional area. During this period, changes in V̄
P
and V̄
IWM
underestimate the changes in P·V̄
IWM
.
Experimental Intracerebral Hemorrhage in Rats
Authors: Bigio Marc R. Del , Yan Hui-Jin , Buist Richard , Peeling James
Published: June 2011

Background and Purpose
Intracerebral hemorrhage is associated with a considerable proportion of strokes and head injuries. The mechanism of brain cell injury associated with hemorrhage may be different from that due to pure ischemia. Therefore, it is essential that models of intracerebral hemorrhage be developed and well characterized. The purpose of this study was to obtain high-field MR images of rat brain at progressive times after induction of intracerebral hemorrhage and to correlate the images with behavior and histological evolution.

Methods
Intracerebral hemorrhage was induced in rats by injection of bacterial collagenase and heparin into the caudate nucleus. Histopathological changes and corresponding MR images were studied from 30 minutes to 3 weeks after injection. Behavioral changes were also followed for 3 weeks.

Results
Histological correlation showed that MR is capable of resolving the accumulation and degeneration of the hematoma, a centripetal wave of neutrophils infiltrating from the surrounding tissue beginning at 12 hours, and centripetal invasion of macrophages beginning at 48 hours. Widespread white matter edema was clearly evident on MR images for 1 week after the hemorrhage. Medium-sized striatal neurons were lost in the tissue surrounding the hematoma. Behavioral improvement was rapid during resolution of the edema but incomplete at 3 weeks.

Conclusions
MR images correlate very well with histological changes in this experimental model of intracerebral hemorrhage and can therefore be used to follow changes due to drug treatments in vivo. The intense neutrophilic response to this lesion may contribute to neuronal injury at the periphery of the hematoma.
Detection of Hyperacute Primary Intraparenchymal Hemorrhage by Magnetic Resonance Imaging
Authors: Patel Mahesh R. , Edelman Robert R. , Warach Steven
Published: June 2011

Background
MRI has become increasingly used in the acute setting to manage patients with stroke. There has been concern that MRI may not be sensitive in the detection of acute intracranial hemorrhage. We assessed whether strongly susceptibility-weighted MRI would be sensitive to intraparenchymal hemorrhage in the first few hours.

Case Descriptions
In the course of our ongoing studies of MRI of acute ischemic stroke in more than 200 patients, 35 patients had MR studies within 6 hours. Six of these patients who presented with acute focal symptoms with definite time of clinical onset (2.5 to 5 hours) were found to have evidence of intraparenchymal hemorrhage. Standard T
1
- and T
2
-weighted MR scans were performed. In 5 of the patients, echo-planar imaging and gradient-echo sequences were performed to increase the sensitivity of magnetic susceptibility effects of the pulse sequences. Four of the cases were of putaminal hemorrhage and 2 were lobar hemorrhages. The hemorrhage was most evident as foci of T
2
* hypointensity (signal loss) and unambiguous on the more susceptibility-weighted sequences, particularly echo-planar gradient-echo images.

Conclusions
MRI can detect hemorrhage within 2.5 to 5 hours of onset of clinical symptoms as regions of marked signal loss due to susceptibility effects, whereas conventional MR scans of ischemic stroke may appear normal. These results demonstrate that MR susceptibility sequences may be sensitive to hyperacute hemorrhage and suggest that MR may be an adequate screen for primary intraparenchymal hemorrhage.
Bilateral Vertebral Artery Dissection in a Patient With Afibrinogenemia
Authors: García-Moncó Juan C. , Cantón Guillermo Fernández , Beldarrain Marian Gómez
Published: June 2011

Background
Afibrinogenemia, a rare coagulation disorder, has not been associated with vertebral artery dissections.

Case Description
A 28-year-old woman with afibrinogenemia developed spontaneous neck pain followed by a right medullary infarction, and MR angiography showed extensive bilateral vertebral artery dissection. She was treated with fibrinogen replacement and anticoagulants and showed a favorable evolution, with only mild residual right upper arm incoordination.

Conclusions
In this patient spontaneous bilateral vertebral artery dissection complicated afibrinogenemia. Since anticoagulant therapy is usually indicated for arterial dissection, this association created a therapeutic problem. This patient received anticoagulants with fibrinogen replacement, which resulted in a favorable evolution.
Influence of Apolipoprotein E Genotype on Cerebral Amyloid Angiopathy in the Elderly
Authors: Itoh Yoshinori , Yamada Masahito , Suematsu Naomi , Matsushita Masaaki , Otomo Eiichi
Published: June 2011

Background and Purpose
The inheritance of the ε4 allele of the apolipoprotein E gene (APOE) is associated with increased risk of developing dementia of the Alzheimer type (DAT). We have investigated whether the APOE genotype influences the severity of cerebral amyloid angiopathy (CAA) in elderly individuals with or without DAT.

Methods
From a consecutive autopsy series, we studied 88 patients (85.2±8.1 years) without degenerative disorders other than DAT. The percentages of amyloid-laden vessels in the occipital lobes were calculated and compared between APOE genotypes.

Results
For ε3/3 and ε3/4 genotypes, there was a trend toward increased CAA in ε3/4 individuals for non-DAT and conversely in ε3/3 individuals for DAT patients, but these did not achieve significance.

Conclusions
The present study suggests that the ε4 allele is not a strong risk factor for CAA in elderly people.
Agreement on Disease-Specific Criteria for Do-Not-Resuscitate Orders in Acute Stroke
Authors: Alexandrov Andrei V. , Pullicino Patrick M. , Meslin Eric M. , Norris John W.
Published: June 2011

Background and Purpose
The do-not-resuscitate (DNR) order is a mechanism of withholding cardiopulmonary resuscitation (CPR). The lack of DNR guidelines specific for acute stroke may result in many stroke patients receiving unnecessary and futile resuscitation and ventilator-assisted breathing.

Methods
A prospective multicenter evaluation of disease-specific criteria for DNR orders in acute stroke was initiated using a modified Delphi process. The participants were the Canadian and Western New York Stroke Consortium members who are closely involved in caring for acute stroke patients and conducting clinical trials at the academic centers. Previously published provisional criteria were reviewed by the participants. Modifications were made to the criteria until statistically significant agreement (
P
<.05,
z
score, or 67% similar answers) was achieved.

Results
Disease-specific criteria for DNR orders in acute stroke were discussed by 26 physicians in three rounds of the opinion survey. An agreement was reached that a “no resuscitation” decision is appropriate when any two of the following three clinical criteria are present (the degree of agreement is given in parentheses): severe stroke (88%,
P
=.00007), life-threatening brain damage (73%,
P
<.01), and significant comorbidities (92%,
P
=.00003). The poor prognosis implied by these criteria should be discussed whenever possible among physician(s), the patient, and family members before the decision to withhold CPR is made. Eighty-one percent of the participants agreed that these disease-specific criteria are appropriate for clinical use (
P
=.0008).

Conclusions
Disease-specific criteria for DNR orders were developed to supplement general DNR policies for patients with hemispheric brain infarction and intracerebral hemorrhage during the first 2 weeks of stroke. A significant agreement was reached by a panel of physicians that patients with acute stroke should not be resuscitated if these disease-specific criteria are met.
Preoperative and Postoperative Evaluation of Cerebral Perfusion and Vasodilatory Capacity With
99m
Tc-HMPAO SPECT and Acetazolamide in Childhood Moyamoya Disease
Authors: Touho Hajime , Karasawa Jun , Ohnishi Hideyuki
Published: June 2011

Background and Purpose
The results of long-term follow-up studies of cerebral perfusion and vasodilatory capacity following administration of acetazolamide after serial vascular reconstructions in 25 patients with childhood moyamoya disease are reported.

Methods
Cerebral perfusion was measured with
99m
Tc-hexamethylpropyleneamine oxime single-photon emission CT before and after IV administration of 10 mg/kg acetazolamide, which was performed both before and after vascular reconstruction by superficial temporal artery-middle cerebral artery anastomosis and encephalomyosynangiosis (first and second operations) and/or omental transplantation to the brain (third operation).

Results
Follow-up periods ranged between 12 and 24 months (mean±SD, 18.5±3.2 months) after the first operation. Repetitive transient ischemic attacks disappeared completely after serial vascular reconstructions in all patients. Before the first operation, cerebral perfusion in the territory of the middle cerebral artery on the side of initial operation was 83.9±4.7% and was significantly lower than that in the contralateral side (88.3±4.9%, n=25;
P
<.0001, paired
t
test). Vasodilatory capacity on the side of the first operation was −18.4±2.5% and that on the contralateral side −14.4±2.1%. The former value was significantly lower than the latter value (n=25;
P
<.0001, paired
t
test). After the first operation, cerebral perfusion and vasodilatory capacity on the side of initial operation were markedly improved, to 87.8±4.5% and −14.7±2.7%, respectively (n=25;
P
<.0001, both cases, paired
t
test). Before the second operation, cerebral perfusion and vasodilatory capacity on the side of the second operation were 76.6±4.1% and −20.1±1.9%, respectively, and significantly lower than those before the first operation (n=25;
P
<.0001, both cases, paired
t
test). Eight patients subsequently required bifrontal omental transplantation for repetitive paraparetic transient ischemic attacks after the second operation; they had low cerebral perfusion and vasodilatory capacity bilaterally in the territories of the anterior cerebral arteries (72.4±2.7% and −18.6±1.7%, respectively). After omental transplantation, both were significantly increased, to 81.9±3.4% and −11.8±1.9%, respectively (n=25;
P
<.0001, both cases, paired
t
test).

Conclusions
Hemodynamic compromise existed in patients with childhood moyamoya disease and was a major cause of development of ischemic symptoms. Regions in which hemodynamic compromise was present could be determined by measuring regional cerebral perfusion and vasodilatory capacity.
Vasomotor Reactivity and Pattern of Collateral Blood Flow in Severe Occlusive Carotid Artery Disease
Authors: Müller M. , Schimrigk K.
Published: June 2011

Background and Purpose
The compromise of cerebrovascular autoregulation in severe occlusive carotid artery disease depends on the functional capacity of collateral pathways. In previous reports correlating hemodynamic disturbances with collateral pathways, collateral blood supply was often evaluated by invasive cerebral angiography. In this study noninvasive transcranial Doppler ultrasound was used to determine both collateral pathways and vasomotor reactivity.

Methods
With the use of blood flow direction, compression tests, and evident side-to-side asymmetries of blood velocities, the collateral supply through the anterior and posterior communicating arteries, the ophthalmic artery, and leptomeningeal anastomoses was evaluated by transcranial Doppler ultrasound in 48 patients (42 men, 6 women; mean±SD age, 59±9 years) with occlusion (n=36) or stenosis of more than 90% (n=12) of one internal carotid artery. Ipsilateral vasomotor reactivity was determined by the percent increase of middle cerebral artery mean blood velocity with the use of (1) the breath-holding maneuver and (2) acetazolamide (1 g IV) as vasodilatory stimulus. Additional stenoses (50% to <90%) of the contralateral internal carotid artery were present in 20 of the 48 patients.

Results
Vasomotor reactivity was not affected by the presence of a contralateral internal carotid artery stenosis. Both vasodilatory stimuli similarly indicated poor vasomotor reactivity when an ophthalmic or a leptomeningeal pathway accompanied an anterior communicating artery pathway compared with a lone anterior communicating artery pathway (
P
<.05). The acetazolamide challenge indicated significantly better preserved vasomotor reactivity when blood supply was provided through a lone anterior communicating artery pathway (66±30%) than through an anterior and posterior communicating artery pathway (33±20%,
P
<.05), whereas the breath-holding method failed to show such a difference.

Conclusions
The presence of an ophthalmic artery pathway may provide the first evidence of disturbed vasomotor reactivity. The use of cerebral angiography to evaluate collateral pathways must be considered carefully since transcranial Doppler ultrasound is a reliable noninvasive alternative.
Low Pulsatility Signals Through the Orbits
Authors: Gymnopoulos Constantinos , Ramadan Nabih M.
Published: June 2011

Background and Purpose
Low pulsatility signals (LPS) on transcranial Doppler ultrasonography are detected (1) with arteriovenous malformations, (2) distal to hemodynamically significant stenosis, and (3) in venous structures. We describe focal LPS in the territory of the internal carotid artery siphon that do not represent any of the above conditions.

Methods
We performed retrospective and prospective reviews of transcranial Doppler studies on 3225 patients over 5 years. Clinical and radiological data of all patients with focal LPS were extracted. LPS was defined as a focal signal identified through the orbital windows with a low pulsatility index (<0.6).

Results
Sixteen LPS (mean flow velocity [mean±SD], 62±11 cm/s; pulsatility index [mean±SD], 0.41±0.08; depth range, 46 to 72 mm) from 15 patients (mean±SD age, 45±15 years; 4 men, 11 women) were identified. LPS flow direction was away from the probe in 13 cases and toward it in 3. Presenting symptoms included headache, focal neurological deficits, dizziness, and pulsatile tinnitus. All patients had cranial MRI (MRI and MR angiography in 11). Three patients underwent conventional cerebral angiography. Arteriovenous malformations or significant arterial stenoses were not detected on any study.

Conclusions
A focal signal from the internal carotid artery siphon region with low pulsatility index and normal mean flow velocity, identified in the absence of other transcranial Doppler abnormalities, is not related to an arteriovenous malformation or proximal arterial stenosis. LPS, as defined, are not of venous origin since mean flow velocity was in the arterial range. LPS are likely related to prominent venous flow in the cavernous sinus secondary to unusually strong pulsation of the intracavernous internal carotid artery.