bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperglycemia and the Vascular Effects of Cerebral Ischemia
Authors: Kawai Nobuyuki , Keep Richard F. , Betz A. Lorris
Published: June 2011

Background and Purpose
A well-demarcated infarct was observed after 4 hours of rat middle cerebral artery (MCA) occlusion with xylazine/ketamine but not pentobarbital or isoflurane anesthesia. This study examined whether this reflected vascular changes and, because xylazine induces hyperglycemia, whether glucose could cause similar vascular effects in cerebral ischemia.

Methods
To examine the effects of anesthetics, rats were anesthetized for thread occlusion of the MCA with either xylazine/ketamine, pentobarbital, or isoflurane. To evaluate the effects of glycemia, acute hyperglycemia was induced by glucose injection. In both experiments, cerebral plasma volume (CPV) was determined using
3
H-inulin after 4 hours of permanent occlusion, and cerebral blood flow was measured using [
14
C]iodoantipyrine following 2 hours of reperfusion after 2 or 4 hours of occlusion. The presence of cerebral hemorrhage after reperfusion was checked macroscopically and infarct volume with 2,3,5-triphenyltetrazolium staining.

Results
The ischemic CPV was about 50% of the contralateral values with xylazine/ketamine but not with the other anesthetics. On reperfusion, ischemic cerebral blood flow with xylazine/ketamine anesthesia was approximately half that with pentobarbital. Use of xylazine/ketamine also resulted in more frequent hemorrhagic infarcts and a larger infarct volume. Induced hyperglycemia resulted in a CPV decrease in the ischemic compared with nonischemic tissue (4.0±0.5 versus 7.4±0.2 μL/g;
P
<.001). Hyperglycemia also caused poor reperfusion and increased the occurrence of hemorrhagic infarction (hyperglycemia, 15 of 20; normoglycemia, 1 of 11;
P
<.01).

Conclusions
Hyperglycemia induces marked cerebrovascular changes, both during ischemia and during reperfusion, that may exacerbate tissue damage. Change in CPV during ischemia may be a useful clinical indicator in predicting poor hemodynamic recovery and occurrence of hemorrhagic infarction after reperfusion therapy.
Subtle Neuronal Death in Striatum After Short Forebrain Ischemia in Rats Detected by In Situ End-Labeling for DNA Damage
Authors: Schmidt-Kastner Rainald , Fliss Henry , Hakim Antoine M.
Published: June 2011

Background and Purpose
Neuronal cell death after global brain ischemia occurs predominantly by necrosis, whereas only a minor fraction of cell death may occur through apoptosis. Brief or moderate insults are thought to facilitate apoptosis, which is associated with DNA fragmentation. After 10 minutes of four-vessel occlusion in rats, conventional neuropathological analysis shows neuronal cell death in hippocampal CA1 but not in the striatum. Thus, we compared hippocampus and striatum for occurrence of cells with DNA fragmentation.

Methods
A brief insult of 10 minutes of forebrain ischemia was induced in rats using four-vessel occlusion, and groups of brains were studied at 1, 3, 6, and 12 hours and at 1, 3, and 7 days after ischemia. In situ end-labeling (ISEL) was used to detect neurons undergoing DNA fragmentation. The hippocampal CA1 area was compared with the striatum. Conventional staining and immunohistochemical markers served to exclude ischemic neuronal cell death in the striatum.

Results
Hippocampal CA1 neurons were ISEL-positive by 3 days after ischemia. In contrast, positive cells became evident in the striatum between 3 hours to 3 days after ischemia. The ISEL-positive cells were scattered throughout the striatum with a preference for the dorsomedial areas and accounted for about 0.2% of the neurons per striatal area at 1 day. Conventional staining and immunohistochemical markers failed to reveal areas of overt cell damage in the striatum.

Conclusions
The scattered cell damage in the striatum after brief forebrain ischemia suggests the occurrence of an apoptotic process. The striatum therefore may be prone to subtle cell death due to metabolic insults.
Extracellular Potassium in a Neocortical Core Area After Transient Focal Ischemia
Authors: Gido Gunilla , Kristian Tibor , Siesjo Bo K.
Published: June 2011

Background and Purpose
Occlusion of the middle cerebral artery (MCAO) results in bioenergetic failure in the densely ischemic core areas. During reperfusion, transient recovery of the bioenergetic state is followed by secondary deterioration. In this study, we recorded the extracellular potassium concentrations in the cortical core during 2 hours of MCAO, as well as during recovery. One group of animals with recirculation periods of 6 to 8 hours was given the free radical spin trap α-phenyl-
N
-tert-butyl nitrone (PBN).

Methods
The experiments were performed on adult male Wistar rats (305 to 335 g). The right MCA was occluded by an intraluminal filament technique. For [K
+
]
e
measurements a craniotomy was made over the right cortex, and an ion-sensitive microelectrode was lowered into the ischemic focus. Recording of [K
+
]
e
was continued for 2 hours. After 48 hours of reperfusion, infarction size was estimated with 2,3,5-triphenyltetrazolium chloride.

Results
During MCA occlusion, [K
+
]
e
rose to ≈60 mmol/L. However, several animals showed transient (and partial) periods of repolarization accompanied by a decrease in [K
+
]
e
. Immediately on reperfusion, the [K
+
]
e
started to recover and reached baseline levels (2.5 mmol/L) within 3 to 5 minutes. During the first 6 hours of recovery, [K
+
]
e
was stable at about 2.5 mmol/L, but after this period a moderate increase in the [K
+
]
e
was observed. This was not observed in animals injected with PBN 1 hour after reperfusion.

Conclusions
The data suggest that delayed cell membrane dysfunction, as reflected in a rise in [K
+
]
e
, occurs after about 6 hours of reperfusion and that treatment with PBN in a single dose ameliorates or delays such deterioration of plasma membrane function.
Ambulatory Blood Pressure Monitoring in Acute Stroke
Authors: Lip Gregory Y.H. , Zarifis John , Farooqi I. Sadaf , Page Alison , Sagar Gian , Beevers D. Gareth
Published: June 2011

Background and Purpose
Ambulatory blood pressure monitoring (ABPM) devices are increasingly used in the assessment of hypertension, but their value in patients after a stroke is unknown, despite the fact that hypertension is an important cause of stroke and many patients have relatively high blood pressure (BP) levels at presentation. We therefore investigated the clinical use of a 24-hour oscillometric ABPM device in patients after acute stroke. We also investigated ABPM in different types of stroke (thrombosis, hemorrhage, and transient ischemic attack) and ethnic and sex differences.

Methods
BP was measured manually with a standard mercury sphygmomanometer, and ABPM measurements were made with an oscillometric device. The first reading obtained with the ABPM device was compared with simultaneous manual BP measurements. Mean daytime and nighttime pressures were also analyzed to determine the frequency of nocturnal BP falls (“dipping”).

Results
We studied 86 patients (48 men; mean±SD age, 64.2±9.2 years) admitted with acute-onset stroke (ictus within 12 hours) in a district general hospital. Thirty-one patients (36.0%) had a previous history of hypertension. The median percentage of successful BP readings by ABPM was 92% (interquartile range, 72 to 98). There was no significant difference in manual BP levels compared with the first simultaneous systolic or diastolic ABPM measurements. Systolic BPs recorded by ABPM were significantly higher in black patients with acute stroke and in patients with intracerebral hemorrhage, who also showed a trend toward higher nocturnal BPs. There was no difference in BPs between men and women and those who were alive or dead 6 months later (
P
=NS). There was also no difference between mean day and night systolic BP (mean difference, 1.9 mm Hg;
P
=.08), although mean daytime diastolic BP was higher than mean nighttime diastolic BP (mean difference, 2.4 mm Hg;
P
=.01). Patients with stroke therefore demonstrated a loss of diurnal BP rhythm and may be considered “nondippers”; there was also a trend toward “reverse dipping” in patients with intracranial hemorrhage.

Conclusions
This study demonstrates higher systolic BPs as recorded by ABPM (but not manually) in patients with intracerebral hemorrhage than in those with cerebral infarcts; higher levels were also found in blacks. ABPM recordings are useful in the assessment of BP in patients with stroke, who may be considered nondippers.
Localization of Lesion in Denial of Hemiplegia After Acute Stroke
Authors: Ellis Simon , Small Marian
Published: June 2011

Background and Purpose
Previous studies of lesion localization in denial of hemiplegia have often been confounded by factors such as the cerebral etiology, which aspects of the disorder are denied, and whether delusions are present. Our investigation focuses on denial of hemiplegia, without concomitant delusions, after cerebrovascular accident (CVA).

Methods
The CT scans of 30 patients with denial of hemiplegia after acute stroke were compared with those from 10 CVA patients with hemiplegia and visuospatial neglect but no denial. Lesion sites were detailed using the templates of Damasio and Damasio and, for the deep structures, those of Talairach and Tournoux.

Results
Analysis of the CT scans demonstrated that 26 of 30 denial patients had unilateral right-sided lesions and that this group showed a significantly higher incidence of lesions in deep white matter and the basal ganglia.

Conclusions
The results are discussed in relation to recent ideas regarding the role of the basal ganglia and subcortical circuits in movement and executive function.
Is the EuroQol a Valid Measure of Health-Related Quality of Life After Stroke?
Authors: Dorman Paul J. , Waddell Fiona , Slattery Jim , Dennis Martin , Sandercock Peter
Published: June 2011

Background and Purpose
The EuroQol measures aspects of quality of life that are highly relevant to stroke patients. It is short and simple and many stroke patients can complete the form without help. However, its validity has not been adequately assessed after stroke. We therefore assessed its concurrent and discriminant validity in a group of prospectively studied stroke survivors.

Methods
We assessed the validity of the EuroQol in a series of 152 patients with stroke who were all visited by a study nurse. The nurse gave the patients the EuroQol, the Frenchay Activities Index, a visual analogue pain scale, and the Hospital Anxiety and Depression Scale in the form of questionnaires to be self-completed where possible. The nurse interviewed the patient directly to assess disability using the Office of Population Censuses and Surveys Disability scale and Barthel Index.

Results
The nurse assessed 152 patients; of these 92 were able to complete the EuroQol without help, the remaining 60 could only be assessed by interview. The EuroQol had reasonable concurrent validity; median scores on the relevant standard instruments varied significantly (and in the appropriate direction) for groups defined by their response to the relevant EuroQol domain. The EuroQol had reasonable discriminant validity since the responses enabled separation between patients with differing stroke syndromes and stroke severities. Accuracy for predicting outcome after stroke was good for both self-completed and interview-completed questionnaires.

Conclusions
The EuroQol appears to have acceptable concurrent and discriminant validity for the measurement of health-related quality of life after stroke. It may be administered by either a questionnaire for self-completion in patients with mild to moderate stroke or by interview in patients with significant motor deficits.
Use of the Health Utilities Index With Stroke Patients and Their Caregivers
Authors: Mathias Susan D. , Bates Molly M. , Pasta David J. , Cisternas Miriam G. , Feeny David , Patrick Donald L.
Published: June 2011

Background and Purpose
Few studies currently assess the health-related quality of life of individuals following a stroke. One of the major challenges of assessing quality of life is the high likelihood that after a stroke a patient will not be able to complete such an assessment. One practical solution is to have a family caregiver complete the assessment on behalf of these individuals. This current pilot study examined the interrater reliability of having family caregivers complete the Health Utilities Index (HUI) on behalf of stroke patients.

Methods
A total of 74 patients who experienced an ischemic stroke and 37 family caregivers completed the interviewer-administered HUI (data were available for 33 pairs). The HUI is designed to produce a single summary measure of health-related quality of life, the global multiattribute utility score, as well as descriptive information on each of its attributes. Interrater reliability was measured by evaluating the percent agreement, Cohen’s κ statistics, intraclass correlation coefficients (ICCs), Pearson’s
R
correlations, and paired
t
tests between the patient and caregiver responses.

Results
In most instances interrater reliability was acceptable, with values suggesting moderate to high agreement. The mean global multiattribute utility scores for the HUI 2 were identical for patients and caregivers (0.64±0.29), with an ICC of .72. A preponderance of patients reported decrements in several attributes of the HUI.

Conclusions
These data indicate a substantial decrement in functioning in stroke patients and suggest that family caregivers can complete the HUI reliably when patients are unable to do so.
Reproducibility of Ultrasonographically Determined Intima-Media Thickness Is Dependent on Arterial Wall Thickness
Authors: Stensland-Bugge Eva , Bønaa Kaare H. , Joakimsen Oddmund
Published: June 2011

Background and Purpose
We compared the reproducibility of B-mode ultrasonographic measurements of intima-media thickness (IMT) in various segments of the right carotid artery and examined whether measurement error was associated with IMT or cardiovascular risk factor levels.

Methods
In 1994/1995 a total of 6676 participants in the Tromsø Study underwent ultrasound examination of common carotid artery IMT. Reproducibility of measurements was assessed by inviting 111 participants to a second ultrasound scan within 3 weeks of the first scan. On each occasion the subjects were examined by three sonographers.

Results
The mean between-observer absolute differences in IMT in the far wall of the bifurcation and the near and far walls of the common carotid artery were 0.15, 0.10, and 0.08 mm, respectively. The corresponding within-observer differences were 0.15, 0.10, and 0.06 mm, respectively. Approximately 70% to 80% of total measurement variability was due to differences among sonographers; the rest was attributable to within-reader variability. Measurement error increased significantly with increasing IMT: the increase was more than twofold over the range of measurements. Cardiovascular risk factor levels were not associated with measurement variability when we controlled for IMT.

Conclusions
We conclude that B-mode ultrasound provides reproducible estimates of the IMT in both the near and far walls of the carotid artery. Although measurement error is generally small, it increases proportionally with the level of IMT.
Power Doppler Imaging of Carotid Artery Stenosis
Authors: Steinke W. , Ries S. , Artemis N. , Schwartz A. , Hennerici M.
Published: June 2011

Background and Purpose
Power Doppler imaging (PDI) is a new sonographic technique that has recently been introduced for vascular application. Since the technical principles of PDI may provide increased sensitivity to visualize the continuity of blood flow in arterial stenoses, we investigated the diagnostic significance of PDI and the intermethod relationship for the measurement and classification of internal carotid artery (ICA) stenosis in comparison with both color Doppler flow imaging (CDFI) and angiography.

Methods
One hundred patients with a total of 128 ICA stenoses (50% to 69%, n=37; 70% to 79%, n=27; 80% to 99%, n=64) and 12 ICA occlusions were consecutively investigated by means of PDI, CDFI, and intra-arterial angiography (n=48). Reduction of the intrastenotic lumen was measured on longitudinal and transverse views of PDI and CDFI for the calculation of the degree of diameter and area stenosis, respectively. Angiographic stenosis was determined with the use of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), European Carotid Surgery Trial (ECST), and common carotid (CC) methods.

Results
PDI provided significantly more excellent or good (92% versus 79%;
P
<.01) displays of the intrastenotic lumen than CDFI, particularly in complicated high-grade stenosis. While linear regression analysis demonstrated a high overall correlation between PDI and CDFI for diameter (
r
=.88;
P
<.001) and area stenosis (
r
=.79;
P
<.001), categorization of ICA stenosis revealed best agreement for 80% to 99% area stenoses. Since angiography frequently either underclassified (NASCET method) or overclassified (ECST, CC methods) the degree of ICA stenosis in comparison to both PDI and CDFI, the sonographic-angiographic correlation was only moderate (regression coefficients ranged from .62 to .70;
P
<.001).

Conclusions
PDI further improves the assessment of ICA stenosis by providing better visualization of the stenotic vascular lumen than CDFI. Sonographic imaging of the stenotic plaque on both PDI and CDFI provided a direct measurement of the local degree of stenosis, while the angiographic grade of stenosis essentially depended on the method used for evaluation.
A New Method for Quantitative Regional Cerebral Blood Volume Measurements Using Computed Tomography
Authors: Muizelaar J. Paul , Fatouros Panos P. , Schröder Marc L.
Published: June 2011

Background and Purpose
Knowledge of cerebral blood volume (CBV) is invaluable in identifying the primary cause of brain swelling in patients with stroke or severe head injury, and it might also help in clinical decision making in patients thought to have hemodynamic transient ischemic attacks (TIAs). This investigation is concerned with the development and clinical application of a new method for quantitative regional CBV measurements.

Methods
The technique is based on consecutive measurements of cerebral blood flow (CBF) by xenon/CT and tissue mean transit time (MTT) by dynamic CT after a rapid iodinated contrast bolus injection. CBV maps are produced by multiplication of the CBF and MTT maps in accordance with the Central Volume Principle: CBV=CBF×MTT. The method is rapid and easily implemented on CT scanners with the xenon/CBF capability. It yields CBV values expressed in milliliters of blood per 100 grams of tissue.

Results
The method was validated under controlled physiological conditions causing changes that were determined both with our technique and from pressure-volume index (PVI) measurements. The two independent estimates of CBV changes were in agreement within 15%. CBV measurements using this method were carried out in normal volunteers to establish baseline values and to compare with values using the ratio-of-areas method for calculating both CBF and CBV from the dynamic study alone. Average CBV was 5.3 mL/100 g. The method was also applied in 71 patients with severe head injuries and in 1 patient with hemodynamic TIAs.

Conclusions
The primary conclusions from this study were (1) the proposed method for measuring CBV accurately determines changes in CBV; (2) the MTT×CBF determinations are in agreement with the ratio-of-areas method for CBV measurements in normal volunteers and are consistent with other methods reported in the literature; (3) MTTs are significantly prolonged early after severe head injury, which when combined with the finding of decreased CBF and increased arteriovenous difference of oxygen indicates increased cerebrovascular resistance due to narrowing of the microcirculation consistent with the presence of early ischemia; and (4) CBV in the patient with TIAs was increased in the hemisphere with the occluded internal carotid artery, indicating compensatory vasodilation and probable hemodynamic cause.
Biophysical Mechanisms of Stroke
Authors: Hademenos George J. , Massoud Tarik F.
Published: June 2011

Background
Stroke is the third leading cause of death and the leading cause of long-term disability in the United States. Although a host of genetic, biochemical, physiological, anatomic, and histological factors have been implicated, to varying degrees, in the pathogenesis of stroke, biophysical factors are believed to play a significant role in the development, diagnosis, and therapy of stroke. The purpose of this review article is to identify, describe, and illustrate these causes and biophysical and hemodynamic mechanisms predisposing a person to stroke, which often form the basis for novel methods of diagnosis and therapy.

Summary of Review
This mini-review begins by describing the physical principles that govern the flow of blood through normal and stenosed carotid artery bifurcations. In addition to the tortuosity, curvature, and tensile forces of the carotid artery bifurcation, the effects of biophysical phenomena from flowing blood such as viscous forces, pressure forces, velocity, kinetic energy, momentum, impulse, shear stress, and vibrational displacements exerted by the flowing blood on the vessel wall are conducive to abnormal flow behavior and patterns, degrading the vessel wall and creating the potential for stroke.

Conclusions
Recent advances in the treatment of stroke are based on increasing knowledge of its underlying biophysical mechanisms, as well as on better-publicized advances in imaging instrumentation and procedures for the management and treatment of patients.
Symptomatic Carotid Artery Occlusion
Authors: Klijn Catharina J. M. , Kappelle L. Jaap , Tulleken Cornelis A. F. , van Gijn Jan
Published: June 2011

Background
Over the last several years evidence has accumulated that in addition to embolism, a compromised cerebral blood flow may play an important role in causing transient ischemic attacks and ischemic stroke in patients with occlusion of the internal carotid artery. This evidence is found in both clinical features and ancillary investigations, particularly measurements of cerebral blood flow.

Summary of Review
On the basis of 20 follow-up studies in patients with transient ischemic attacks or minor ischemic stroke associated with an occluded carotid artery, the annual risk of stroke was 5.5% (95% confidence interval [CI], 5.0% to 6.0%), and that of ipsilateral stroke (distinguished in 11 of the 20 studies) was 2.1% (95% CI, 1.6% to 2.8%). Patients with a compromised cerebral blood flow as measured by positron emission tomography, single-photon emission CT, transcranial Doppler, or stable xenon CT (six studies) have an even higher annual risk of stroke (all strokes: 12.5%; 95% CI, 8.9% to 17.6%; ipsilateral stroke: 9.5%; 95% CI, 6.4% to 14.0%).

Conclusions
Because a compromised cerebral blood flow may be an important causal factor in patients with symptomatic carotid artery occlusion, medical and surgical options for treatment are reviewed in this light.
Pharmacological Elevation of Blood Pressure in Acute Stroke
Authors: Rordorf Guy , Cramer Steven C. , Efird James T. , Schwamm Lee H. , Buonanno Ferdinando , Koroshetz Walter J.
Published: June 2011

Background and Purpose
Lowering of blood pressure can adversely affect ischemic symptoms in acute stroke. The aim of our study was to determine whether induced hypertension in stroke is safe and to examine its effects on neurological deficits in patients presenting with acute cerebral ischemia.

Methods
We retrospectively reviewed all patients admitted to our neurological intensive care unit with the diagnosis of ischemic stroke over a 2.5-year period. Thirty-three patients were not given a pressor agent (Ph− group), while 30 were treated with phenylephrine (Ph+ group) in an attempt to improve cerebral perfusion.

Results
Baseline characteristics showed few differences between the Ph+ and Ph− groups. Intracerebral hemorrhage, brain edema, cardiac morbidity, and mortality were not increased in the Ph+ group. In 10 of 30 Ph+ patients, a systolic blood pressure threshold was identified below which ischemic deficits worsened and above which deficits improved. The mean threshold was 156 mm Hg (range, 120 to 190 mm Hg). The mean number of stenotic/occluded cerebral arteries was greater in those Ph+ patients with an identified clinical blood pressure threshold (mean, 2.1 per patient) than in Ph+ patients without a threshold (mean, 1.2 per patient;
P
<.05).

Conclusions
The results suggest that careful use of phenylephrine-induced hypertension is not associated with an increase in morbidity or mortality in acute stroke. Although based on a retrospective analysis of clinical practice, this report suggests that a subset of patients, particularly those with multiple stenosis of cerebral arteries, may improve neurologically upon elevation of the blood pressure.
Computerized Measurement of Motor Performance After Stroke
Authors: Cramer Steven C. , Nelles Gereon , Schaechter Judith D. , Kaplan Jill D. , Finklestein Seth P.
Published: June 2011

Background and Purpose
Stroke scales usually convert motor status to a score along an ordinal scale and do not provide a permanent recording of motor performance. Computerized methods sensitive to small changes in neurological status may be of value for studying and measuring stroke recovery.

Methods
We developed a computerized dynamometer and tested 23 stroke subjects and 12 elderly control subjects on three motor tasks: sustained squeezing, repetitive squeezing, and index finger tapping. For each subject, scores on the Fugl-Meyer and National Institutes of Health stroke scales were also obtained.

Results
Sustained squeezing by the paretic hand of stroke subjects was weaker (9.2 kg) than the unaffected hand (20.2 kg;
P
<.0005), as well as control dominant (23.1 kg;
P
<.0005) and nondominant (19.9 kg;
P
<.005) hands. Paretic index finger tapping was slower (2.5 Hz) than the unaffected hand (4.2 Hz;
P
<.01), as well as control dominant (4.7 Hz;
P
<.0005) and nondominant (4.9 Hz;
P
<.0005) hands. Many features of dynamometer data correlated significantly with stroke subjects’ Fugl-Meyer scores, including sustained squeeze maximum force (ρ=.91) and integral of force over 5 seconds (ρ=.91); repetitive squeeze mean force (ρ=.92) and mean frequency (ρ=.73); and index finger tap mean frequency (ρ=.83). Correlation of these motor parameters with National Institutes of Health stroke scale score was weaker in all cases, a consequence of the scoring of nonmotor deficits on this scale. Dynamometer measurements showed excellent interrater (
r
=.99) and intrarater (
r
=.97) reliability.

Conclusions
The degree of motor deficit quantitated with the dynamometer is strongly associated with the extent of neurological abnormality measured with the use of two standardized stroke scales. The computerized dynamometer rapidly measures motor function along a continuous, linear scale and produces a permanent recording of hand motor performance accessible for subsequent analyses.
Epidemiology of Stroke in Innherred, Norway, 1994 to 1996
Authors: Ellekjær Hanne , Holmen Jostein , Indredavik Bent , Terent Andreas
Published: June 2011

Background and Purpose
In Norway, as well as other industrialized countries, mortality from stroke has declined over the past decades. Data on stroke morbidity are lacking. This study was conducted to determine the incidence, case fatality, and risk factors of stroke in a defined Norwegian population.

Methods
During the period 1994 to 1996, a population-based stroke registry collected uniform information about all cases of first-ever and recurrent stroke occurring in people aged ≥15 years in the region of Innherred in the central part of Norway (target population 70 000), where the prevalence of cardiovascular risk factors was screened in 1984 to 1986 and 1995 to 1997.

Results
During the 2 years of registration (September 1, 1994, to August 31, 1996), 432 first-ever (72.8%) and 161 recurrent (27.2%) strokes were registered. The crude annual incidence rate was 3.12/1000 (2.85/1000 for males and 3.38/1000 for females). Adjusted to the European population, the annual incidence rate of first-ever stroke was 2.21/1000. The annual incidence rate of cerebral infarction was 2.32/1000, intracerebral hemorrhage 0.32/1000, subarachnoid hemorrhage 0.19/1000, and unspecified stroke 0.38/1000. The 30-day case-fatality rate was 10.9% for cerebral infarction, 37.8% for intracerebral hemorrhage, and 50.0% for unspecified stroke. Fourteen percent of the patients were found outside the hospital, and only 50% of the suspected stroke cases in the hospital (at admission or reviewed discharge diagnosis of ICD-9 codes 430 to 438) fitted the final inclusion criteria.

Conclusions
This first population-based stroke register in Norway revealed incidence rates of stroke similar to other Scandinavian countries, and comparison between other European countries did not indicate regional variations within Western Europe.
Ischemic Stroke Injury Is Reduced in Mice Lacking a Functional NADPH Oxidase
Authors: Walder Claire E. , Green Simon P. , Darbonne Walter C. , Mathias Joanne , Rae Julie , Dinauer Mary C. , Curnutte John T. , Thomas G. Roger
Published: June 2011

Background and Purpose
Free radicals account for a significant proportion of the brain damage that occurs during ischemic stroke. Using mutant mice (X-CGD) with a dysfunctional phagocytic NADPH oxidase, we investigated the role of this superoxide-generating enzyme as a mediator of the reperfusion injury in a mouse model of middle cerebral artery occlusion.

Methods
Transient (2 hour) middle cerebral artery occlusion was performed in X-CGD or wild-type litter mates (8- to 10-week-old). After 22 hours of reperfusion, brains were harvested and infarct volume delineated using 2,3,5-triphenyltetrazolium chloride. To elucidate the origin of the damaging NADPH oxidase, transient ischemia was also performed in X-CGD or wild-type mice transplanted with wild-type C57 Bl/6J or X-CGD bone marrow, respectively.

Results
The infarct volume induced by transient ischemia was significantly less in X-CGD mice (29.1±5.6 mm
3
; n=13) than wild-type littermates (54.0±10.6 mm
3
; n=10;
P
<.05). The elimination of a functional NADPH oxidase from either the circulation or the central nervous system, by performing the appropriate bone marrow transplant experiments, did not reduce the infarct size induced by transient ischemia. This suggests that in order to confer protection against transient ischemia and reperfusion, a putative neuronal and circulating NADPH oxidase need to be inactivated.

Conclusions
Brain injury was reduced in mice lacking a functional NADPH oxidase in both the central nervous system and peripheral leukocytes, suggesting a pivotal role for the NADPH oxidase in the pathogenesis of ischemia-reperfusion injury in the brain.
Vascular Effects of Statins in Stroke
Authors: Delanty Norman , Vaughan Carl J.
Published: June 2011

Background
Recent clinical trials and meta-analyses of β-hydroxy-β-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated a reduction in ischemic stroke in patients with a history of coronary artery disease both with and without elevations of serum cholesterol. This review summarizes clinical trials of these compounds and their recent impact on stroke and explores the underlying vascular mechanisms of their actions.

Summary of Review
Use of statins in patients with vascular disease has been shown to lower the incidence of stroke by approximately 30%. Statins exhibit a number of antiatherosclerotic and antithrombotic properties that likely underlie the recently observed reductions in cerebrovascular disease. Statins reduce inflammatory, proliferative, and thrombogenic processes in plaque, making it less likely to rupture. Additionally, they reverse the endothelial dysfunction and platelet activation accompanying hypercholesterolemia and may reduce the tendency to thrombosis.

Conclusions
Hypercholesterolemia has reemerged as a risk factor for ischemic stroke. Statins protect against thromboembolic stroke through multiple beneficial effects within the vascular milieu. Further data are awaited to support the growing importance of cholesterol as a risk factor for ischemic stroke and the benefits of statin therapy in patients with cerebrovascular disease.
Lubeluzole Treatment of Acute Ischemic Stroke
Authors: Grotta James
Published: June 2011

Background and Purpose
Lubeluzole is a novel benzothiazole compound that has shown neuroprotective activity in preclinical models of ischemic stroke. The present multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of lubeluzole in the treatment of ischemic stroke.

Methods
Seven hundred twenty-one patients with clinical symptoms of acute ischemic stroke were randomized to receive either lubeluzole (7.5 mg over 1 hour, followed by a continuous daily infusion of 10 mg for up to 5 days) or placebo. Treatment was initiated within 6 hours of symptom onset. Mortality at 12 weeks was the primary efficacy end point. Secondary efficacy end points included neurological recovery (based on the National Institutes of Health Stroke Scale [NIHSS]), functional status (based on the Barthel Index), and level of disability (based on the Rankin Scale). Safety assessments included standard and continuous electrocardiographic monitoring, physical examination, measurements of vital signs, clinical laboratory evaluation, and adverse events reports.

Results
The overall mortality rate at 12 weeks for lubeluzole-treated patients was 20.7% compared to 25.2% for placebo-treated patients (NS). Controlling for relevant covariates, the degree of neurological recovery (NIHSS) at week 12 significantly favored lubeluzole over placebo (
P
=.033). Lubeluzole treatment similarly resulted in significantly greater improvements in functional status (Barthel Index) (
P
=.038) and overall disability (Rankin Scale) (
P
=.034) after 12 weeks. A global test statistic confirmed that lubeluzole-treated patients had a more favorable clinical outcome at 12 weeks (
P
=.041). The safety profile of lubeluzole resembled that of placebo.

Conclusions
Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.
Treatment of Acute Ischemic Stroke With Piracetam
Authors: De Deyn Peter Paul , De Reuck Jacques , Deberdt Walter , Vlietinck Robert , Orgogozo Jean-Marc
Published: June 2011

Background and Purpose
Piracetam, a nootropic agent with neuroprotective properties, has been reported in pilot studies to increase compromised regional cerebral blood flow in patients with acute stroke and, given soon after onset, to improve clinical outcome. We performed a multicenter, randomized, double-blind trial to test whether piracetam conferred benefit when given within 12 hours of the onset of acute ischemic stroke to a large group of patients.

Methods
Patients received placebo or 12 g piracetam as an initial intravenous bolus, 12 g daily for 4 weeks and 4.8 g daily for 8 weeks. The primary end point was neurologic outcome after 4 weeks as assessed by the Orgogozo scale. Functional status at 12 weeks as measured by the Barthel Index was the major secondary outcome. CT scan was performed within 24 hours of the onset of stroke but not necessarily before treatment. Analyses based on the intention to treat were performed in all randomized patients (n=927) and in an “early treatment” population specified in the protocol as treatment within 6 hours of the onset of stroke but subsequently redefined as less than 7 hours after onset (n=452).

Results
In the total population, outcome was similar with both treatments (the mean Orgogozo scale after 4 weeks: piracetam 57.7, placebo 57.6; the mean Barthel Index after 12 weeks: piracetam 55.8, placebo 53.1). Mortality at 12 weeks was 23.9% (111/464) in the piracetam group and 19.2% (89/463) in the placebo group (relative risk 1.24, 95% confidence interval, 0.97 to 1.59;
P
=.15). Deaths were fewer in the piracetam group in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke. Post hoc analyses in the early treatment subgroup showed differences favoring piracetam relative to placebo in mean Orgogozo scale scores after 4 weeks (piracetam 60.4, placebo 54.9;
P
=.07) and Barthel Index scores at 12 weeks (piracetam 58.6, placebo 49.4;
P
=.02). Additional analyses within this subgroup, confined to 360 patients with moderate and severe stroke (initial Orgogozo scale score <55), showed significant improvement on piracetam in both outcomes (
P
<.02).

Conclusions
Piracetam did not influence outcome when given within 12 hours of the onset of acute ischemic stroke. Post hoc analyses suggest that piracetam may confer benefit when given within 7 hours of onset, particularly in patients with stroke of moderate and severe degree. A randomized, placebo-controlled, multicenter study, the Piracetam Acute Stroke Study II (PASS II) will soon begin.
Outcome in 43 Patients With Distal Anterior Cerebral Artery Aneurysms
Authors: Proust François , Toussaint Patrick , Hannequin Didier , Rabenenoïna Charles , Le Gars Daniel , Fréger Pierre
Published: June 2011

Background and Purpose
The aim of this retrospective multicenter study was to evaluate the outcome of distal anterior cerebral artery (DACA) aneurysms and to determine the incidence, causes, and consequences of unfavorable outcomes.

Methods
43 patients with 50 DACA aneurysms (27 females and 16 males, mean age 49 years) were studied retrospectively. Forty-four DACA aneurysms were treated surgically (83% with an interhemispheric approach), and 2 were embolized. At postoperative day 10, all patients underwent routine angiography. The outcome at 6 to 12 months was scored according to the Glasgow Outcome Scale (GOS).

Results
35 DACA aneurysms were ruptured. Among the 26 “good”-grade patients (Hunt and Hess grades I through III), 18 (69.2%) were in GOS 1, 2 in GOS 2 (7.7%), 2 in GOS 3 (7.7%), and 4 in GOS 5 (15.4%); among the 9 “poor”-grade patients (Hunt and Hess grades IV and V), 1 (11.1%) was in GOS 1, 2 in GOS 2 (22.2%), 2 in GOS 3 (22.2%), and 4 in GOS 5 (44.5%). The initial intracerebral hemorrhage (ICH) (40%) induced neurological aftereffects in 8 patients. An operative rupture occurred in 40%, with a temporary occlusion in 28.6% that was responsible for mediocre results in 3 patients (8.7%). A postoperative thrombosis was observed in 4 patients (11.4%) and an aneurysmal remnant in 1 (2.8%). Ten DACA unruptured aneurysms were clipped without operative rupture or thrombosis.

Conclusions
The authors suggest that the proportion of ruptured DACA aneurysms evolving to a GOS 1 or 2 was similar to that of aneurysms found in other locations, after early surgery. Endovascular treatment should be considered in the management of uncommon ruptured fusiform DACA aneurysms.
Contrast-Enhanced Transcranial Color-Coded Duplex Sonography in Ischemic Cerebrovascular Disease
Authors: Baumgartner Ralf W. , Arnold Marcel , Gönner Friedrich , Staikow Iwan , Herrmann Cornelia , Rivoir Anita , Müri René M.
Published: June 2011

Background and Purpose
Echo contrast agents have been shown to provide conclusive examinations in most patients with insufficient ultrasound penetration through the temporal bone. We investigated the diagnostic value of contrast-enhanced (CE) transcranial color-coded duplex sonography (TCCD) in patients with ischemic cerebrovascular disease and insufficient temporal windows and evaluated TCCD criteria that predict whether CE-TCCD studies may become conclusive.

Methods
Thirty-three patients presenting with ischemic strokes (n=21) and transient ischemic attacks (n=12) were investigated. Extracranial color duplex imaging showed normal findings in 24 patients, eight ≥70% stenoses and one occlusion of the carotid arteries in 8 patients, and severe occlusive disease of both vertebral arteries in 1 patient. Seven carotid stenoses and vertebral artery obstructions were confirmed by angiography. The galactose/palmitic acid–based echo contrast agent was injected intravenously as bolus of 200, 300, or 400 mg/mL in a dosage of 10, 5, and 5 mL, respectively.

Results
Thirty-two of the 33 patients were completely examined because 1 patient who felt pain at the injection site declined further investigations. Twenty-one (66%) of 32 CE studies were conclusive and showed cross-flow through three anterior and two posterior communicating arteries, but no stenoses and occlusions. Precontrast identification of any cerebral artery provided an overall accuracy of 97% in predicting a conclusive CE investigation. Precontrast TCCD identified no arterial Doppler signals in patients with inconclusive CE studies.

Conclusions
CE-TCCD provided conclusive examinations in two thirds of patients with ischemic cerebrovascular disease and ultrasound-refractory temporal windows. Precontrast detection of any cerebral artery reliably predicted a conclusive CE investigation.
A Functional MRI Study of Subjects Recovered From Hemiparetic Stroke
Authors: Cramer Steven C. , Nelles Gereon , Benson Randall R. , Kaplan Jill D. , Parker Robert A. , Kwong Ken K. , Kennedy David N. , Finklestein Seth P. , Rosen Bruce R.
Published: June 2011

Background and Purpose
Stroke recovery mechanisms remain incompletely understood, particularly for subjects with cortical stroke, in whom limited data are available. We used functional magnetic resonance imaging to compare brain activations in normal controls and subjects who recovered from hemiparetic stroke.

Methods
Functional magnetic resonance imaging was performed in ten stroke subjects with good recovery, five with deep, and five with cortical infarcts. Brain activation was achieved by index finger-tapping. Statistical parametric activation maps were obtained using a
t
test and a threshold of
P
<.001. In five bilateral motor regions, the volume of activated brain for each stroke subject was compared with the distribution of activation volumes among nine controls.

Results
Control subjects activated several motor regions. During recovered hand finger-tapping, stroke subjects activated the same regions as controls, often in a larger brain volume. In the unaffected hemisphere, sensorimotor cortex activation was increased in six of nine stroke subjects compared with controls. Cerebellar hemisphere contralateral and premotor cortex ipsilateral to this region, as well as supplementary motor areas, also had increased activation. In the stroke hemisphere, activation exceeding controls was uncommon, except that three of five cortical strokes showed peri-infarct activation foci. During unaffected hand finger-tapping, increased activation by stroke subjects compared with controls was uncommon; however, decreased activation was seen in unaffected sensorimotor cortex, suggesting that this region’s responsiveness increased to the ipsilateral hand and decreased to contralateral hand movements. Use of a different threshold for defining activation (
P
<.01) did not change the overall findings (κ=.75).

Conclusions
Recovered finger-tapping by stroke subjects activated the same motor regions as controls but to a larger extent, particularly in the unaffected hemisphere. Increased reliance on these motor areas may represent an important component of motor recovery. Functional magnetic resonance imaging studies of subjects who recovered from stroke provide evidence for several processes that may be related to restoration of neurologic function.
Incidence of Stroke and Myocardial Infarction in Women of Reproductive Age
Authors: Petitti Diana B. , Sidney Stephen , Quesenberry Charles P. , Bernstein Allan
Published: June 2011

Background and Purpose
Information on the incidence of vascular disease in women of reproductive age has been limited. These diseases are rare in this age group, and a large population base is required for reliable estimation of incidence.

Methods
For a case-control study of vascular disease and low-dose oral contraceptive use, we used emergency department logs and hospital admission and discharge records to ascertain fatal and nonfatal cases of first-ever stroke and myocardial infarction (MI) in women 15 to 44 years of age who were members of a large California HMO. Incidence rates of stroke and MI were calculated on the basis of these data.

Results
The incidence of MI not associated with pregnancy was 5.0 per 100 000 women-years. The incidence of stroke not associated with pregnancy was 10.7 per 100 000 women-years. MI was very rare until age 35 years. At every age, about half of hemorrhagic strokes were due to subarachnoid hemorrhage.

Conclusions
The incidence rates of stroke and MI are low in women of reproductive age in the United States.
Stroke in a Defined Elderly Population, 1967-1985
Authors: Barker William H. , Mullooly John P.
Published: June 2011

Background and Purpose
Decline in stroke mortality in recent decades has been well documented in the United States and other countries. This study, based on a well-defined population with comprehensive medical records available for research purposes, seeks to explain decline in stroke mortality among older persons between 1967 and 1985. The study specifically explores the competing explanatory mechanisms of decreased incidence of stroke versus decreased case-fatality rate.

Methods
We conducted a retrospective analysis of three successive period cohorts (1967 through 1971, 1974 through 1978, and 1981 through 1985) of persons ≥65 years of age enrolled in a large group model HMO in a metropolitan community. All new hospitalized and a sample of nonhospitalized strokes were ascertained, and samples of first-ever strokes were studied. Incidence, case-fatality rates, survival times, and comorbidities were compared across cohorts.

Results
There was no significant change in stroke incidence over time; however, 1-month case fatality declined dramatically from 33% in 1967 through 1971 to 18% in 1981 through 1985 (
P
<.01); median survival increased from 213 to 1092 days. Indices of reduced severity included declines in coma from 27% to 12% (
P
<.01) and in wheelchair- or bed-bound status from 40% to 30% (
P
=.067). Cases with and without CT scan in 1981 to 1985, when this procedure became widely available in the health plan, were similar in severity, thereby reducing the possibility of ascertainment bias.

Conclusions
In this well-defined older population, stroke has become a less lethal and disabling though no less common disease. This finding fails to support the “compression of morbidity” hypothesis while supporting a model of delayed progression for stroke in this age group.