bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Stroke With Mitral Valve Prolapse in Population-Based Cohort Study
Authors: Orencia Anthony J. , Petty George W. , Khandheria Bijoy K. , Annegers John F. , Ballard David J. , Sicks JoRean D. , O’Fallon W. Michael , Whisnant Jack P.
Published: June 2011

Background and Purpose
The purpose of this study was to clarify whether mitral valve prolapse increases the subsequent risk of stroke.

Methods
A historical cohort study was conducted on 1079 residents of Olmsted County, Minnesota, who had an initial echocardiographic diagnosis of mitral valve prolapse between 1975 and 1989 without prior stroke or transient ischemic attack and who were followed up for first stroke occurrence.

Results
There was an overall twofold increase in the incidence of stroke among individuals with mitral valve prolapse relative to the reference population (standardized morbidity ratio, 2.1; 95% confidence interval, 1.3 to 3.2). Sex, duration of follow-up from the diagnosis of mitral valve prolapse, or calendar year of initial diagnosis did not modify the association. Within the cohort of patients who were at least 35 years old at diagnosis of mitral valve prolapse, a time-dependent proportional-hazards multivariate model and a person-years analysis revealed that age, ischemic heart disease, congestive heart failure, and diabetes mellitus were important determinants for stroke when person-years of observation after mitral valve replacement were excluded. Among seven persons with mitral valve replacement, three strokes occurred in 24 person-years of follow-up. For those with an auscultatory diagnosis of mitral valve prolapse only as the indication for echocardiography (44%), the risk of stroke relative to the population was 1.0 (95% confidence interval, 0.2 to 2.9); for those with another cardiac diagnosis, the standardized morbidity ratio was 2.5 (95% confidence interval, 1.5 to 4.0).

Conclusions
Individuals with uncomplicated mitral valve prolapse did not have an increased risk of stroke, although a small increase in the risk may not have been detected.
Cerebral Autoregulation Dynamics in Premature Newborns
Authors: Panerai Ronney B. , Kelsall A. Wilfred R. , Rennie Janet M. , Evans David H.
Published: June 2011

Background and Purpose
Autoregulation of cerebral blood flow is easily disrupted, and loss of this normal physiological reflex may worsen the neurological outcome for patients undergoing intensive care. We studied the response of cerebral blood flow velocity to changes in mean arterial blood pressure.

Methods
Cerebral blood flow velocity was measured with Doppler ultrasonography in one middle cerebral artery for 5-minute periods in 33 babies of gestational age <33 weeks admitted to a neonatal intensive care unit. Two methods of evaluating autoregulation were developed. The first used linear regression analysis of blood flow velocity on blood pressure. Records were classified as showing loss of autoregulation if the regression slope was greater than a critical value. A minimum change in mean arterial blood pressure of 5 mm Hg and a critical slope of 1.5 %/mm Hg were found to be adequate criteria for the classification of records by the regression method. The second method used coherent averaging, a technique similar to that used in recording evoked potentials. Spontaneous transient increases in blood pressure were automatically detected, and the instant corresponding to its maximum rate of rise was used to synchronize averages of the blood pressure and blood velocity transients. The resulting coherent averages were classified into two groups based on the morphology of the cerebral blood flow velocity average.

Results
Whereas the regression method allowed the classification of only 51 of 106 records, the coherent average method classified 101 of 106 (95.3%) of the records available. For 51 records that were classified by both methods, there was agreement in 42 cases (82.3%). The coherent average of all records classified as having an active autoregulation showed cerebral blood flow velocity returning to baseline much earlier than blood pressure, suggesting that autoregulation was taking place within 1 to 2 seconds. This pattern was absent in records in which autoregulation was classified as absent.

Conclusions
Computerized coherent averaging of the cerebral blood flow velocity response to spontaneous blood pressure transients offers a promising new method for noninvasive bedside assessment of autoregulation in patients undergoing intensive care. The time course for autoregulation, when present, is in agreement with that reported in adults.
Crossed Cerebellar Diaschisis and Brain Recovery After Stroke
Authors: Infeld Bernard , Davis Stephen M. , Lichtenstein Meir , Mitchell Peter J. , Hopper John L.
Published: June 2011

Background and Purpose
Although crossed cerebellar diaschisis is well recognized after stroke, there is controversy concerning its clinical correlations and serial changes, and little is known about its prognostic value.

Methods
We studied crossed cerebellar diaschisis and cerebral hypoperfusion in 47 patients with acute middle cerebral cortical infarction using
99m
Tc-hexamethylpropyleneamine oxime and single-photon emission computed tomography within 72 hours of stroke onset. Thirty-one of these patients had outcome studies at 3 months; 15 of the 31 underwent an additional scan after acetazolamide injection. Tissue loss was determined with computed tomography, performed at outcome in 28 patients. Clinical stroke severity was assessed with the Canadian Neurological Scale and Barthel Index. Cerebellar blood flow asymmetry was studied in 22 healthy, age-matched control subjects.

Results
Cerebellar blood flow asymmetry was significant in patients (mean±SE, 9.76±0.78%;
P<
.001) but not in control subjects (−0.22±0.56%). Crossed cerebellar diaschisis was strongly associated with infarct hypoperfusion volume at both acute (regression coefficient±SE
b
, b=6.76±0.65;
P
<.001) and outcome stages (b=6.13±0.63;
P
<.001). Cross-sectionally over the first 72 hours, infarct hypoperfusion volume decreased by 2% for each hour from onset (
P
<.05), while crossed cerebellar diaschisis remained unchanged. Canadian Neurological Scale score at the acute stage was negatively associated with acute crossed cerebellar diaschisis (b=−0.10±0.05;
P
<.05) after allowing for infarct hypoperfusion volume. Crossed cerebellar diaschisis did not change between acute-stage, outcome, and postacetazolamide scans. Acute-stage crossed cerebellar diaschisis predicted outcome Barthel Index score (b=−0.28±0.14;
P
=.05) and tissue loss (b=3.81±0.96;
P
<.001) but was no longer an independent prognostic factor after allowing for acute-stage infarct hypoperfusion volume.

Conclusions
This study shows that crossed cerebellar diaschisis is a functional phenomenon that correlates with both stroke severity and infarct hypoperfusion volume and persists despite neurological recovery. Although acute-stage crossed cerebellar diaschisis has no prognostic value independent of acute-stage hypoperfusion volume, it might indicate the proportion of nutritional to nonnutritional perfusion at the infarct site and hence be useful in the evaluation of reperfusion therapies in the acute stage.
Role of Social Class in Excess Black Stroke Mortality
Authors: Howard George , Russell Gregory B. , Anderson Roger , Evans Gregory W. , Morgan Timothy , Howard Virginia J. , Burke Gregory L.
Published: June 2011

Background and Purpose
It has been suggested that a substantial proportion of the excess stroke mortality among black Americans may be attributable to relatively lower socioeconomic status (SES) in this group. In this report we provide the first quantitative estimates of the proportion of excess black stroke mortality attributable to SES for a large population-based cohort.

Methods
We used data from the National Longitudinal Mortality Study for persons 45 years and older (73 400 white men, 87 528 white women, 6522 black men, and 8816 black women). Sex-specific proportional hazards model were used to estimate excess black stroke mortality with and without adjustment for education and income (measures of SES). The contribution of SES to the excess black stroke risk was estimated from the difference in regression coefficients for race in these models.

Results
In men, low SES was associated with increased stroke mortality (
P
≤.0001) and accounted for 14% to 46% of the excess black stroke risk (
P
<.05). However, we could find no association between SES and stroke mortality in women, and SES did not account for a significant proportion of the excess stroke mortality in black women.

Conclusions
Although SES proved to account for a statistically significant proportion of excess male black stroke mortality, overall SES explained less than one quarter of the observed excess between ages 45 and 65. In women, SES did not significantly reduce the estimated excess black stroke mortality. Although SES may be playing a role in excess black stroke mortality, a substantial proportion of the excess appears attributable to other sources, including cerebrovascular risk factors that are unrelated to SES, unmeasured lifestyle influences, social resources, and genetic factors.
Ischemic Stroke Events and Carotid Atherosclerosis
Authors: Handa Nobuo , Matsumoto Masayasu , Maeda Hiroaki , Hougaku Hidetaka , Kamada Takenobu
Published: June 2011

Background and Purpose
To clarify the clinical significance of carotid atherosclerosis for ischemic stroke events, a follow-up study was performed in Japanese patients.

Methods
Two hundred fourteen patients were registered from nine hospitals in the Osaka community. All patients were checked for a prior history of stroke, and the risk factors for stroke and atherosclerosis were evaluated. Carotid atherosclerosis was assessed by 7.5-MHz duplex ultrasonography. We studied the relationship between the ischemic stroke event rate and the severity and appearance of the carotid atherosclerosis. We also studied the relationship between stroke events and various risk factors.

Results
The average duration of follow-up was 16 months. Ten patients suffered new ischemic stroke episodes during this follow-up period. At the initial ultrasonographic study, 16 patients had high-grade stenosis and 21 had ulcerated plaque. Proportional hazard regression analysis showed that grade of stenosis and plaque ulceration were positively related to the event rate. Patients with ulcerated plaque had a sevenfold higher hazard ratio for stroke in comparison to those without (
P
<.01). The ipsilateral stroke recurrence rate was 11 times higher in patients with ulcerated high-grade stenotic carotid lesions.

Conclusions
The present findings demonstrate that the severity of carotid atherosclerosis as evaluated by ultrasonography is a useful indicator of the risk of ischemic stroke in symptomatic patients.
Is Blood Pressure Really a Triggerfor the Circadian Rhythm of Subarachnoid Hemorrhage?
Authors: Kleinpeter Günther , Schatzer Roland , Böck Fritz
Published: June 2011

Background and Purpose
Circadian blood pressure changes are not infrequently cited as a trigger for the onset of subarachnoid hemorrhage (SAH). Our purpose was to determine the reliability of this chronorisk and study the variability and consequences of it as it occurs in hypertensive and normotensive individuals.

Methods
Of 273 consecutive patients with proven SAH of aneurysmal origin seen between January 1990 and December 1993, we studied 120 (44%) for whom the exact time of hemorrhage could be reliably determined. Beyond the recognition of a circadian rhythm for this collective, the patients were then sorted by blood pressure, yielding one group each of 80 normotensive (group N, 66.7%) and hypertensive (group H, 33.3%) individuals. The differential chronorisk of these two groups was studied.

Results
A circadian rhythm with a definitive characteristic acrophase was observed for the entire group, occurring between 9
am
and 10
am
(χ
2
test,
P
<.0005) with a possible secondary peak in the afternoon hours. The separation into two blood pressure groups somewhat surprisingly revealed a different curve for each group (χ
2
test,
P
=.01). Statistical analysis of each group’s separate chronorisk revealed that this acrophase only holds true for hypertensive individuals, whereas normotensive patients not only lack a morning peak, but an apparent elevation in the afternoon is statistically irrelevant, leading to the impression that SAH in normotensive persons seems to be subject to no circadian rhythm at all.

Conclusions
The incidence of SAH conforms to circadian blood pressure variation in hypertensive patients, similar to the diurnal rhythms observed with strokes and myocardial infarctions. This leads to the hypothesis that blood pressure elevation is a trigger for the onset of bleeding in this group. In clear contrast, normotensive individuals with cerebrovascular aneurysms seem to have a random 24-hour distribution of SAH onset times, thus leaving the nature of a possible trigger mechanism unresolved.
Selection of Patients for Transesophageal Echocardiography After Stroke and Systemic Embolic Events
Authors: Leung Dominic Y. , Black Ian W. , Cranney Gregory B. , Walsh Warren F. , Grimm Richard A. , Stewart William J. , Thomas James D.
Published: June 2011

Background and Purpose
This study examined whether patients suffering from stroke and other systemic embolic events may be selected for transesophageal echocardiography on the basis of clinical and transthoracic echocardiographic findings.

Methods
We performed transthoracic and transesophageal echocardiography on 824 patients after stroke and other suspected embolic events. Patients were classified into group A if they were in sinus rhythm and had a normal transthoracic echocardiogram. Group B consisted of all other patients. Transesophageal echocardiographic findings of left atrial spontaneous contrast, left atrial thrombus, complex aortic atheroma, and interatrial septal anomalies were correlated with clinical and transthoracic echocardiographic results.

Results
Transesophageal echocardiography detected at least one potential source of embolism in 399 patients (49%): spontaneous contrast in 214 patients (26%), left atrial thrombus in 54 (7%), complex atheroma in 111 (13%), and interatrial septal anomalies in 126 (15%). In group A (n=236), only 3 (1%) had spontaneous contrast, 11 (4.6%) had complex atheroma, and none had left atrial thrombus. In group B (n=588), 211 patients (36%,
P
<.001) had spontaneous contrast, 54 (9.2%,
P
<.001) had atrial thrombus, and 100 (17%,
P
<.001) had complex atheroma. Interatrial septal anomalies were detected in similar proportions of patients (18% in group A versus 14% in group B). Left atrial spontaneous echo contrast, thrombus, and complex atheroma were significantly more prevalent in older patients, but interatrial septal anomalies were more prevalent in younger patients irrespective of transthoracic echocardiographic findings. Multivariate analysis identified both an abnormal transthoracic echocardiogram and patient age to be independent predictors of transesophageal echocardiographic findings of left atrial spontaneous echo contrast, left atrial thrombus, or complex atheroma.

Conclusions
Transesophageal echocardiography has a low yield for left atrial spontaneous contrast, left atrial thrombus, or complex aortic atheroma in patients with normal transthoracic echocardiogram and sinus rhythm and in younger patients. Interatrial septal anomalies are more prevalent in younger patients. Transthoracic echocardiogram should be performed in patients after stroke or systemic embolic events as a noninvasive screening tool. We recommend transesophageal echocardiogram for patients with abnormal transthoracic echocardiogram and in younger patients when the finding of a patent foramen ovale may contribute to patient management.
Selective Depression of Endothelium-Dependent Dilations During Cerebral Ischemia
Authors: Rosenblum William I. , Wormley Brandon
Published: June 2011

Background and Purpose
Pial arterioles have diverse mechanisms for endothelium-dependent dilations. In mice, different mechanisms or endothelium-derived mediators exist for each of the following dilators: acetylcholine, bradykinin, and calcium ionophore A-23187. This study tests the response to each of these dilators during profound ischemia. The response to sodium nitroprusside, an endothelium-independent dilator, was also tested.

Methods
In each mouse, ischemia was produced by bilateral carotid artery ligation that reduced cortical blood flow by approximately 90% as determined by laser-Doppler flowmetry. In separate studies of 10 mice each, dilations of pial arterioles to two doses of each dilator were compared before and after 10 minutes of occlusion, with the occlusion continuing during the second set of measurements. The dilator was applied in the suffusate bathing the pial surface exposed at a craniotomy site. Diameters were monitored by in vivo television microscopy and image splitting.

Results
The dose-dependent dilations to acetylcholine, bradykinin, and calcium ionophore A-23187 were each profoundly depressed during ischemia. The response to sodium nitroprusside was not depressed. In all cases, the ischemia was accompanied by arteriolar narrowing of approximately 25% and by obvious slowing of blood flow observed by intravital microscopy. Superoxide dismutase plus catalase failed to prevent the depressed response to acetylcholine.

Conclusions
Endothelium-dependent dilations, mediated by diverse endothelium-derived relaxing factors, are depressed during ischemia of 10 to 15 minutes’ duration. This cannot be a nonselective effect on vessel responsivity caused by constriction, reduced flow, or reduced intraluminal pressure during ischemia because under the same conditions dilation to endothelium-independent sodium nitroprusside is preserved. The selective endothelial dysfunction may play a role in exacerbating ischemia by precluding the ability of some dilators, released during ischemia, to dilate the resistance vessels.
Reduction of Infarct Size by Intra-Arterial Nimodipine Administered at Reperfusion in a Rat Model of Partially Reversible Brain Focal Ischemia
Authors: Roda José M. , Carceller Fernando , Díez-Tejedor Exuperio , Avendaño Carlos
Published: June 2011

Background and Purpose
When blood flow to a brain region that has undergone an ischemic attack is reestablished, additional injury is to be expected from the reperfusion. The purpose of the study was to determine the effect of the intra-arterial injection of nimodipine at reperfusion on infarct volume in rats subjected to partially reversible focal neocortical ischemia.

Methods
Two groups of Long-Evans rats with transient bilateral common carotid artery occlusion and permanent middle cerebral artery occlusion were subjected to retrograde cannulation of the external carotid artery close to the carotid bifurcation to allow the administration of isotonic saline (group 1) or nimodipine solution (group 2) just before and during reperfusion. The estimate for the actual amount of infarcted cortex was calculated by the volume ratio between the spared cortex in the infarcted hemisphere and the total cortex of the contralateral hemisphere by means of a stereological method based on the Cavalieri principle.

Results
The percentage of cortex that was infarcted in control rats was 63.8±3.1%, whereas nimodipine-treated rats exhibited a significantly smaller (
P
<.005) percentage of infarct volume (31.3±12.7%).

Conclusions
Our data show that the intra-arterial injection of nimodipine just before and during reperfusion reduced neocortical infarct volume in rats subjected to partially reversible focal cerebral ischemia.
Three Distinct Phases of Fodrin Proteolysis Induced in Postischemic Hippocampus
Authors: Yokota Masayuki , Saido Takaomi C. , Tani Eiichi , Kawashima Seiichi , Suzuki Koichi
Published: June 2011

Background and Purpose
Fodrin, a neuronal cytoskeleton protein, is proteolyzed by calpain after ischemic insult. We examined proteolysis of fodrin induced by global forebrain ischemia in gerbil hippocampus in spatial terms by using the antibody specific to the calpain-proteolyzed form of fodrin.

Methods
In gerbils, a 10-minute forebrain ischemia was produced by occlusion of both carotid arteries. After recirculation, the hippocampus was processed for immunohistochemical and immunoblot study with the antibody against the calpain-proteolyzed form of fodrin. Additionally, short-term ischemia was studied to find the threshold of fodrin proteolysis.

Results
Three phases of fodrin proteolysis distinct in chronology and distribution arose: (1) an early predegeneration phase in the molecular layer and stratum oriens of the CA1 and CA3 sectors within the first 15 minutes, which lasted up to 4 hours; (2) a late predegeneration phase in the whole CA1 sector, except for the pyramidal cells, between 12 hours and 2 days; and (3) a postdegeneration phase in the cytoplasm of the CA1 neurons, which arose in 3 to 7 days. A 4-minute (not a 3-minute) forebrain ischemia induced the late predegeneration phase of fodrin proteolysis and delayed neuronal death in CA1. Immunoblotting showed that the primary product of calpain action was further proteolyzed by an unidentified protease.

Conclusions
Calpain induced proteolysis of fodrin in ischemic hippocampus, and the late predegeneration phase of the proteolysis was closely associated with the delayed neuronal death in the CA1 sector. Calpain and another protease may play a role in the development of neuronal death after transient forebrain ischemia.
Chronological Changes of Arterial Diameter, cGMP, and Protein Kinase C in the Development of Vasospasm
Authors: Nishizawa Shigeru , Yamamoto Seiji , Yokoyama Tetsuo , Ryu Hiroshi , Uemura Kenichi
Published: June 2011

Background and Purpose
We hypothesized that nitric oxide exerts a negative feedback control on protein kinase C (PKC) activation, and the disturbance of the feedback control after subarachnoid hemorrhage results in vasospasm due to PKC activation. This study was undertaken to verify this hypothesis.

Methods
Different dogs were prepared for three separate experiments: measurement of the angiographic diameter of the basilar artery and determination of cGMP and PKC activity in vascular smooth muscle cells. In each experiment, two models were used: the single-hemorrhage model for mild vasospasm and the two-hemorrhage model for severe vasospasm. In both models, chronological changes of these three parameters were examined from day 1 until day 7.

Results
In the single-hemorrhage model, mild vasospasm and a slight decrease of the cGMP level were noted on day 4, then both returned to the baseline levels on day 7. PKC activity was slightly enhanced throughout the study period. In the two-hemorrhage model, severe vasospasm and a significant decrease of the cGMP level were observed on day 5 and persisted until day 7. PKC activity was remarkably enhanced from day 5 until day 7. The differences between the two models with regard to the three parameters were statistically significant.

Conclusions
The decrease of cGMP level and the enhancement of PKC activity were obviously associated with the development of severe vasospasm. We conclude that subarachnoid hemorrhage disturbed the feedback control exerted by nitric oxide on PKC activation, leading to PKC-dependent vasospasm.
Transcranial Doppler Ultrasonography and Transesophageal Echocardiography in the Investigation of Pulmonary Arteriovenous Malformation in a Patient With Hereditary Hemorrhagic Telangiectasia Presenting With Stroke
Authors: Yeung M. , Khan K.A. , Antecol D.H. , Walker D.R. , Shuaib A.
Published: June 2011

Background
Hereditary hemorrhagic telangiectasia (HHT) is associated with a high incidence of pulmonary arteriovenous malformations (PAVMs), which can be the underlying cause for cerebral ischemia or brain abscess. The diagnosis of these malformations may be difficult, as clinical or radiological findings may be absent. Transcranial Doppler ultrasound (TCD) with saline contrast and transesophageal echocardiography (TEE) with saline contrast are useful in identifying patients with right-to-left shunts and may help identify PAVMs.

Case Description
A 68-year-old woman with HHT presented with two strokes over a 1-year period. After the first stroke, a transthoracic echocardiogram with saline contrast demonstrated significant right-to-left shunt that was interpreted as a patent foramen ovale. After the second stroke, a TCD contrast study confirmed this right-to-left shunt; however, a TEE contrast study discovered an extracardiac shunt. Pulmonary angiography revealed a left lower lobe PAVM and three telangiectasias involving the right lung. The PAVM was subsequently embolized. Postembolization radiographic imaging showed complete occlusion of the feeding vessel to the PAVM. However, repeated contrast TCD and TEE demonstrated persistent right-to-left shunting.

Conclusions
In our patient, stroke may have resulted from peripheral venous emboli passing through the PAVM or from endogenous thromboemboli originating within the PAVM. TCD and TEE contrast studies were helpful in judging the efficacy of catheter embolization therapy of PAVM. TCD and TEE with saline contrast may be clinically useful follow-up examinations for recurrence or development of new PAVMs.
Prognosis for Survival After an Initial Stroke
Authors: Lai Sue Min , Alter Milton , Friday Gary , Sobel Eugene
Published: June 2011

Background and Purpose
We studied prognosis for survival after an initial stroke in 662 patients who survived at least 30 days after onset while taking into account age, sex, the number of neurological deficits from the initial stroke, stroke type, and five selected medical conditions: hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus, and history of transient ischemic attacks.

Methods
All patients were enrolled between July 1, 1987, and August 1, 1989, and were followed regularly at about 6-month intervals until death or the end of the study (mean of 24 months).

Results
At 6 months, 90.8% of the 30-day stroke survivors were still alive. At 1, 2, 3, and 4 years, the cumulative survival rates were 86.9%, 78.7%, 73.2%, and 72.0%, respectively. Older age and the number of neurological deficits at onset of initial stroke increased risk of death. Compared with patients of the same age, sex, number of neurological deficits, and comorbidities, increased risk of death is present among those with myocardial infarction, cardiac arrhythmia, and diabetes mellitus. Hazard ratios were 1.7 (
P
=.006), 1.5 (
P
=.023), and 1.4 (
P
=.059), respectively. Hypertension and transient ischemic attacks were not significantly associated with increased mortality.

Conclusions
This study clarifies prognosis for survival after an initial stroke by taking into account other confounding variables that could also contribute to risk of death.
Functional Outcome for Patients With Hemiparesis, Hemihypesthesia, and Hemianopsia
Authors: Dromerick Alexander W. , Reding Michael J.
Published: June 2011

Background and Purpose
Patients with hemiparesis, hemisensory loss, and hemianopsia (“HHH” deficits) due to stroke may have large cortical lesions caused by middle cerebral trunk vessel occlusion or smaller subcortical lesions due to lenticulostriate involvement. We studied the usefulness of lesion location in predicting functional recovery within this syndrome.

Methods
We reviewed our records and found 41 patients who had a single ischemic hemispheric stroke, HHH deficits, and an available CT scan performed more than 24 hours after the onset of symptoms. CT scans were read independently and blindly by the authors. Lesions were initially categorized by arterial distribution on the basis of CT templates published by Kinkel. The numerous combinations of arterial branch vessel occlusions observed did not allow for statistical analyses because of the small number of subjects within each subgroup. Lesions were therefore classified as cortical (C), subcortical (S), or mixed (M).

Results
There were no significant differences among the three anatomic groups for age, sex, interval after stroke, Mini-Mental Status Examination score, or admission Barthel Index score. Functional outcome measures did not differ significantly for the three groups: mean±SD discharge Barthel score (C, 64±31; S, 47±20; M, 57±21), length of stay ([days] C, 64±25; S, 77±24; M, 73±28), and frequency of nursing home placement (C, 4/8; S, 3/6; M, 2/16).

Conclusions
For patients with HHH deficits, the anatomic location of the lesion (C versus S versus M) does not affect functional outcome.
Occurrence of Transcranial Doppler High-Intensity Transient Signals in Patients With Potential Cardiac Sources of Embolism
Authors: Sliwka Ulrich , Job Frank-Peter , Wissuwa Dorothee , Diehl Rolf R. , Flachskampf Frank-Arnold , Hanrath Peter , Noth Johannes
Published: June 2011

Background and Purpose
Cerebral emboli can be recognized by typical “high-intensity transient signals” (HITS) in the transcranial Doppler (TCD) spectral curves. Patients with potential cardiac sources of embolism are at higher risk for stroke.

Methods
We examined the frequency of HITS in the left middle cerebral artery (MCA) with TCD over periods of 30 minutes in 100 patients having potential cardiac sources of embolism, as indicated by transthoracic or transesophageal echocardiography.

Results
Thirty-six (36%) of the patients presented with HITS. Sex, age, sufficient anticoagulation level, antiplatelet therapy, neurological symptoms, and a history of thrombosis had no influence on the prevalence and number of HITS. The patients with a single echocardiographic diagnosis were separated into eight echocardiographically defined groups: patients with (1) atrial fibrillation, (2) coronary artery disease plus ejection fraction of more than 30% including at least three wall segments of hypokinesia/akinesia, (3) coronary artery disease with less than 30% ejection fraction, (4) dilated cardiomyopathy, (5) infectious endocarditis, (6) aortic stenosis, (7) mitral stenosis, and (8) patent foramen ovale. A significant difference in HITS occurrence could not be found in any of the defined groups. Only patients with infectious endocarditis showed a tendency for a higher HITS prevalence.

Conclusions
HITS are common phenomena in patients with potential cardiac sources of embolism. The clinical relevance of these HITS remains unclear.
Global Incomplete Cerebral Ischemia Produces Predominantly Cortical Neuronal Injury
Authors: Sieber Frederick E. , Palmon Sally C. , Traystman Richard J. , Martin Lee J.
Published: June 2011

Background and Purpose
We determined the neuropathologic damage in a canine model of global incomplete ischemia commonly used in a variety of physiological experiments.

Methods
We induced 20 minutes of incomplete ischemia in dogs (n=9) by increasing intracranial pressure via intraventricular infusion of artificial cerebrospinal fluid to maintain a cerebral perfusion pressure of 10 mm Hg while keeping body temperature at 38°C during and immediately after ischemia. After a 7-day recovery period, animals were perfusion-fixed for neuropathology. In hematoxylin and eosin preparations, ischemic neuronal injury was assessed, neurons were counted, and percentage of cell damage was determined.

Results
No focal neurological deficits or overt seizures were observed during the 7-day recovery period. In superior temporal gyrus, 49±11% and 70±10% damage (mean±SEM) was observed in layer III pyramidal cells in the crown and sulcus, respectively. All neocortical regions examined showed neuronal damage in layers III and/or V. In hippocampus, 59±11% damage of pyramidal neurons occurred in CA1, with dorsal (septal) hippocampus showing more injury than ventral (temporal) portions. The caudate nucleus (head) exhibited 27±7% neuronal injury. In cerebellar cortex (anterior lobule), 70±7% damage of Purkinje cells occurred, but different folia of cerebellum showed varying degrees of injury. Brain stem and thalamus were minimally affected despite reduced blood flow. Inflammatory changes (leukocytic infiltration and neuronal incrustations) were observed, but only when neuronal degeneration was severe. Pancellular necrosis and infarction did not occur.

Conclusions
This animal model of ischemia causes reproducible neuronal injury primarily in cortical regions without pancellular necrosis and infarction. Damage to subcortical areas is less severe than to cortical areas, despite comparable reductions in regional cerebral blood flow. Therefore, in the presence of regionally uniform but incomplete cerebral ischemia, neocortical and hippocampal pyramidal neurons and cerebellar cortical Purkinje cells are more likely than subcortical neurons to degenerate; alternatively, pyramidal and Purkinje neurons degenerate before neostriatal neurons in this model. This neuronal degeneration may represent an intrinsic cellular mechanism without major contribution of cytotoxic pathways associated with inflammation.
Failure of Isradipine to Reduce Infarct Size in Mouse, Gerbil, and Rat Models of Cerebral Ischemia
Authors: Bailey Sarah J. , Wood Nigel I. , Samson Nicole A. , Rothaul Alan L. , Roberts Jennifer C. , King Penny D. , Hamilton Tom C. , Harrison David C. , Hunter A. Jackie
Published: June 2011

Background and Purpose
The dihydropyridine L-type calcium channel blocker isradipine has been reported to exhibit neuroprotective properties in some, but not all, studies performed in the rat middle cerebral artery occlusion (MCAO) model. In the present study, we examined isradipine in several other models of focal and global ischemia: rat rose bengal, mouse MCAO, and gerbil bilateral carotid artery occlusion (BCAO). For comparison, a novel calcium channel blocker, SB201823A, that we have previously shown to be neuroprotective in rat and gerbil models was also examined in the mouse.

Methods
In the gerbil BCAO model, isradipine was administered at 2.5 mg/kg IP as a single dose 60 minutes after ischemia (n=10). Corresponding controls received vehicle (n=10), and sham-operated animals received no treatment (n=6). Locomotor activity and histological assessments were made at 4 days after ischemia. In the rat photothrombotic occlusion model, isradipine was administered at 2.5 mg/kg IP as a single dose 60 minutes after ischemia (n=10), and corresponding controls (n=10) received vehicle. Histological assessment was made at 7 days after ischemia. In the mouse MCAO model, isradipine was also administered at 2.5 mg/kg IP as a single dose 60 minutes after ischemia. Histological assessments were made at 1 (n=13), 2 (n=9), and 4 (n=9) days after ischemia. Vehicle numbers were n=10, n=6, and n=8, respectively. Isradipine and SB201823A were also examined using a combined preischemia and postischemia regimen. Isradipine was administered at 2.5 mg/kg IP before occlusion, 1.25 mg/kg IP 1 hour after occlusion, 1.25 mg/kg IP 2 hours after occlusion, and 2.5 mg/kg twice a day for 3 days after occlusion (n=16). Corresponding controls received vehicle at the same time points (n=14). SB201823A was administered 30 minutes before occlusion, 30 minutes after occlusion, and twice daily for 3 days (n=12). Corresponding controls received vehicle (n=9). Histological assessment was performed at 4 days after ischemia.

Results
When given after ischemia, isradipine failed to affect lesion volume in both the rat and mouse models. In the gerbil, locomotor hyperactivity and hippocampal cell loss were unaffected. Given before and after ischemia in the mouse, isradipine was also ineffective, whereas SB201823A produced a significant reduction in lesion volume.

Conclusions
The L-type calcium channel blocker isradipine was devoid of neuroprotective activity in focal and global models of cerebral ischemia in three species of normotensive animals. These results were compared with data for the novel calcium channel blocker SB201823A, which exhibited a significant effect after pre- and postocclusion administration in the mouse model of permanent focal ischemia.
Delayed Onset of Fatal Basilar Thrombotic Embolus After Whiplash Injury
Authors: Viktrup L. , Knudsen G.M. , Hansen S.H.
Published: June 2011

Background
Whiplash injuries are generally seen after rear-end rather than frontal car collisions. Previous reports have documented death up to 8 days after serious whiplash injury. We report a case of lethal basilar thrombotic embolus that occurred 2 months after the patient’s injury in a collision.

Case Description
After whiplash trauma in a car accident, a 50-year-old taxi driver suffered from headache and episodic visual disturbances. Two months after the accident he suddenly lost consciousness and was admitted to the hospital. A CT scan performed at that time was indicative of basilar thrombosis. The patient died 3 days later. The autopsy revealed a thrombosis in the right vertebral artery and a thrombotic embolus in the basilar artery. Microscopically, a lesion of the right vertebral artery was found at the level of the atlantoaxial joint.

Conclusions
We conclude that the whiplash injury caused a lesion of the right vertebral artery, leading to repeated transient ischemic attacks and finally to a fatal basilar thrombotic embolus. We suggest that in patients with disturbances of the vertebrobasilar circulation, attention should be paid to occurrence of neck trauma in the preceding 3 months. Further, anticoagulant therapy should particularly be considered in patients who after suffering neck injuries develop signs of transient ischemic attacks with origin from the posterior cerebral circulation.
Safety of Hypertensive Hypervolemic Therapy With Phenylephrine in the Treatment of Delayed Ischemic Deficits After Subarachnoid Hemorrhage
Authors: Miller Janice A. , Dacey Ralph G. , Diringer Michael N.
Published: June 2011

Background and Purpose
Hypertensive hypervolemic therapy has been shown to reverse delayed ischemic deficits after aneurysmal subarachnoid hemorrhage. Concern has been raised about systemic complications of therapy, including pulmonary edema and myocardial ischemia, especially when high doses of vasopressors are used. Patients in whom delayed ischemic deficits were treated with hypervolemia and phenylephrine were prospectively evaluated for signs of systemic toxicity.

Methods
Twenty-four consecutive patients treated with hypertensive hypervolemic therapy after aneurysmal subarachnoid hemorrhage were studied. Sixty-seven percent had underlying cardiac disease, vascular disease, or hypertension. No patient was excluded because of age or preexisting cardiac disease. Patients were closely monitored for signs of congestive heart failure (physical examination, chest x-ray films, arterial blood gases, cardiac index, pulmonary artery wedge pressure, and oxygen requirement). Indicators of cardiac ischemia and other extracerebral toxicity that were monitored included cardiac enzymes, electrocardiograms, serum creatinine, electrolyte and lactic acid levels, gastrointestinal motility, and urine output.

Results
Volume expansion and phenylephrine infusion produced an increase in several hemodynamic parameters including pulmonary artery wedge pressure, which rose 28% (13±3.6 to 16±1.9 mm Hg), mean arterial blood pressure, which rose 25% (99±12.5 to 123±11.4 mm Hg), and systemic vascular resistance, which rose 46% (1234±294 to 1739±315 dyne · s
−1
· cm
−5
); however, there was no change in cardiac index (3.9±0.9 to 4.0±0.6 L · min
−1
· m
−2
). There were no clinically significant episodes of pulmonary edema requiring a change in vasopressor therapy and no myocardial infarctions. Phenylephrine was stopped in only one patient (incidence, 4%; 95% confidence interval, 0% to 12%), who developed an exacerbation of his preexisting bradycardia. There was no evidence of noncardiac organ system toxicity. Eighty-eight percent of the patients exhibited neurological improvement.

Conclusions
Hypertensive hypervolemic therapy with the use of high-dose phenylephrine can be administered with acceptable systemic toxicity, even in patients with previous cardiac disease, provided that close monitoring is performed. To minimize risk, aggressive treatment should probably be reserved for patients with signs of delayed ischemia rather than administered prophylactically.
Measurement of Infarct Size Using MRI Predicts Prognosis in Middle Cerebral Artery Infarction
Authors: Saunders Dawn E. , Clifton Andrew G. , Brown Martin M.
Published: June 2011

Background and Purpose
An accurate measure of the severity of ischemic insult and the resulting prognosis is needed to assess the effectiveness of new treatments for acute stroke. We studied the reproducibility and accuracy of measurements of infarct volume with MRI and correlated the measurements with outcome.

Methods
Infarct volume was measured on T
2
-weighted images with the A
nalyze
image analysis software. This technique was found to be highly accurate and reproducible.

Results
Measurements of infarct volume were found to be highly accurate and reproducible. Twenty-one patients (mean age, 66.5 years; range, 28 to 90 years) with cortical middle cerebral artery territory infarcts in whom adequate data could be obtained were studied within 72 hours from onset (mean delay to MRI, 27.5 hours; range, 5 to 72 hours). The Scandinavian Stroke Scale was used to calculate a prognostic score, and clinical outcome was assessed at 3 months. Infarct volume was found to significantly predict outcome. Mean infarct volume in the independent patients was 35.7±29.7 cm
3
compared with 88.3±71.3 cm
3
in dependent patients and 166.5±65.9 cm
3
in dead patients (F=10.52,
P
<.001). Patients with an initial infarct volume less than 80 cm
3
were found to have a better outcome than those with larger infarct volumes. Secondary hemorrhage visible on MRI also predicted a poor outcome. In contrast, the Scandinavian Stroke Scale did not significantly predict outcome.

Conclusions
The results demonstrate that measurement of the size of middle cerebral artery infarction with MRI is a useful tool in assessing prognosis and will have a valuable role in assessing new therapeutic agents.
Nonocclusive Common Carotid Artery Thrombosis in the Rat Results in Reversible Sensorimotor and Cognitive Behavioral Deficits
Authors: Alexis Nancy E. , Dietrich W. Dalton , Green Edward J. , Prado Ricardo , Watson Brant D.
Published: June 2011

Background and Purpose
Microemboli released during transient ischemic attack, stroke, and cardiac surgery are thought to cause a variety of functional deficits in humans. The purpose of this study was to characterize the type and extent of neurobehavioral deficits present after photochemically induced common carotid artery thrombosis (CCAT), a thromboembolic model of stroke in the rat that results in a platelet emboli shower.

Methods
Thirty-two male Wistar rats were assigned to four groups. Groups 1 (n=8) and 3 (n=8) were long-term (6-week survival) and short-term (2-week survival) experimental groups subjected to right CCAT with the use of the photochemical technique. Groups 2 (n=8) and 4 (n=8) served as sham-operated controls for each experimental group. A battery of behavioral tests was applied daily beginning 24 hours after thrombosis; this consisted of elicited forelimb placing, postural reflex, beam balance, beam walking, and open field activity. Cognitive testing with a water maze task was performed on post-CCAT days 30 to 33 for groups 1 and 2 and on post-CCAT day 2 for groups 3 and 4. Ten-micrometer coronal brain sections were stained with hematoxylin and eosin, and infarct location and frequency were determined.

Results
Significant sensorimotor deficits were observed, which recovered within 2 weeks after CCAT. The data that follow are derived by combining the two experimental groups and comparing these with the two sham groups. The following tests showed significant effects after CCAT: contralateral elicited forelimb placing, ipsilateral elicited forelimb placing, beam balance, and beam walking score. Cognitive dysfunction was seen acutely (group 3 animals) at 2 days after CCAT; Morris water maze length and latency to target were significantly greater in the experimental group. No deficits were seen in postural reflex, open field activity, or delayed cognitive testing. Histopathological assessment revealed small infarcts in 11 of 16 thrombosed rats. However, a strong relationship between neurobehavioral deficits and infarct location was not consistently demonstrated.

Conclusions
CCAT produces consistent sensorimotor and cognitive behavioral deficits that recover within 2 weeks of injury. Behavioral outcome was not necessarily associated with overt histopathological damage, suggesting that reversible injury mechanisms, both vascular and neuronal, may be partly responsible for the temporary loss of function. These data strengthen the role of CCAT as a clinically relevant model of thromboembolic stroke.
Transient Ischemic Attacks and Minor Stroke During Sleep
Authors: Pressman M.R. , Schetman W.R. , Figueroa W.G. , Van Uitert B. , Caplan H.J. , Peterson D.D.
Published: June 2011

Background
It is reported that 13% to 44% of all cerebrovascular accidents (CVAs) occur during sleep. In addition to other well-known risk factors, snoring, sleep apnea, obesity, and daytime sleepiness have been shown to significantly increase the risk of stroke. We describe two cases that support the statistical relationship between snoring, sleep apnea, and CVA during sleep.

Case Descriptions
In the first case, motor aphasia was noted in a 64-year-old, 5-ft, 1-in, 218-lb woman when she awakened from sleep at approximately 4
am
. This completely resolved within 3 hours. During her subsequent hospitalization she was found to have severe obstructive sleep apnea that responded well to treatment with nasal continuous positive airway pressure. There has been no recurrence of symptoms in this patient. The second patient was a 59-year-old, 5-ft, 6-in, 260-lb woman who presented to the Sleep Disorders Center with signs and symptoms of severe sleep apnea. In addition, she had awakened from sleep approximately 6 months earlier with numbness and weakness on her right side. Although these symptoms had greatly improved, she continued to complain about residual weakness that was worse on awakening from sleep. Sleep studies confirmed severe obstructive sleep apnea that responded very well to treatment with nasal continuous positive airway pressure.

Conclusions
Snoring and obstructive sleep apnea not only increase the statistical risk of CVA but could be the proximal trigger that precipitates these events during sleep. These two cases provide clinical support for this relationship. Successful diagnosis and treatment of obstructive sleep apnea in the patient with transient ischemic attacks and minor stroke may be an important tool for preventing recurrence.