bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Basic Fibroblast Growth Factor on Experimental Focal Ischemia Studied by Diffusion-Weighted and Perfusion Imaging
Authors: Tatlisumak Turgut , Takano Kentaro , Carano Richard A.D. , Fisher Marc
Published: June 2011

Background and Purpose
Basic fibroblast growth factor (bFGF) has documented neuroprotective properties. This study was performed to evaluate the effects of bFGF on infarct size when administered 30 minutes after induction of focal cerebral ischemia in rats. Diffusion-weighted and perfusion MRI were used during the drug infusion.

Methods
We blindly randomized 20 Sprague-Dawley rats to receive either drug (n=10) or vehicle (n=10). The animals underwent middle cerebral artery (MCA) occlusion using the suture model. Diffusion-weighted MRI was initiated 30 minutes after induction of ischemia and repeated frequently for 3.5 hours. Drug (45 μg/kg per hour) or vehicle (saline) infusion began 30 minutes after MCA occlusion and continued for 3 hours. Perfusion images were made at 25, 90, and 150 minutes after MCA occlusion. The animals were killed after 24 hours of permanent MCA occlusion, and brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC).

Results
The TTC-derived, corrected infarct volume postmortem in the bFGF-treated group was significantly smaller than that in controls (126.6±51.9 versus 180.2±54.9 mm
3
, mean±SD,
P
=.038). Diffusion imaging showed essentially equal lesion volumes 3 hours after MCA occlusion (195.4±61 mm
3
in the drug-treated group and 194.4±65 mm
3
in controls). At 4 hours, ischemic lesion size was 182.1±56.9 mm
3
in treated animals and 222.9±88.7 mm
3
in the controls (
P
=.24, NS). Perfusion imaging did not show a change of cerebral perfusion within ischemic brain regions in the bFGF group during the infusion. No behavioral or physiological side effects were observed.

Conclusions
bFGF is a safe and effective treatment for focal cerebral ischemia in rats. We observed a modest delayed difference of ischemic lesion size in vivo with diffusion MRI. The diffusion-weighted MRI findings suggest a potential delayed therapeutic effect of bFGF, and the perfusion imaging findings imply that the effect is not due to increased blood flow to the ischemic region.
Factors Delaying Hospital Admission After Acute Stroke
Authors: Fogelholm Rainer , Murros Kari , Rissanen Aimo , Ilmavirta Matti
Published: June 2011

Background and Purpose
Clinical trials of new drugs that reverse neurological deficits when used in the first hours of stroke onset suggest that early hospital admission is important. We analyzed a database of patients with acute stroke to determine the factors that delay hospital admission.

Methods
We analyzed all patients with their first stroke during 1993 in the province of Central Finland (population, 256 000). Patients referred to the Central Hospital, the only tertiary referral hospital in the area, were included in the study.

Results
Of the patients with first stroke, 363 (79%) were admitted to the Central Hospital. The stroke subtype was confirmed in 356 (98%) patients with CT scan, and the patient population included 272 (75%) with brain infarction, 51 (14%) with intracerebral hemorrhage, and 40 (11%) with subarachnoid hemorrhage. The most important factor associated with a delay in reaching the hospital was the referral pattern. The median delay was 2 hours for patients brought directly to the Central Hospital, 8 hours if a physician at the local health center was consulted, and 47 hours if the patient was first admitted to the health center for observation. Other factors associated with a delay were ischemic stroke and stroke onset in the evening or night or during the weekend.

Conclusions
The majority of patients who are candidates for acute stroke trials arrive at the hospital after prolonged delays for multiple reasons. Public and medical personnel education could result in significant reduction in these delays.
Complications After Acute Stroke
Authors: Davenport R.J. , Dennis M.S. , Wellwood I. , Warlow C.P.
Published: June 2011

Background and Purpose
We sought to observe the type, timing, and frequency of complications occurring in hospitalized patients after an acute stroke.

Methods
In a single hospital, we prospectively identified a consecutive cohort of patients who were either admitted after an acute stroke or who suffered a stroke while already an inpatient (n=613). We retrieved the case notes for 607 (99%) of these strokes, and a single observer, using predefined diagnostic criteria, reviewed the notes and recorded the type, timing, and frequency of complications that occurred during the inpatient period. We also measured the reliability of complication identification from case note review by comparing two observers on a sample of records.

Results
Complications were recorded after 360 strokes (59%); the most common individual complications were falls (complicating 22% of all strokes), skin breaks (18%), and urinary tract (16%) or chest (12%) infections. Miscellaneous “other” complications complicated 32% of strokes. Seizures and chest infections occurred early, whereas depression and painful shoulder were later problems. Complications were more common in older patients, who were more disabled before their stroke and had suffered more severe strokes. We demonstrated moderate to good agreement between the two observers for most complications.

Conclusions
Complications after acute stroke are common, confirming that stroke rehabilitation requires active and knowledgeable medical input. Knowing the nature and timing of complications, together with the identification of high-risk patients, may be useful to those planning stroke services. The differences in our results and those previously reported, most notably for skin breaks, are probably due to the different methods used, in particular patient selection and diagnostic criteria for complications. Although complications may be useful as a measure of outcome in comparative studies (eg, therapeutic trials and audit), the methodological difficulties in accurately and reliably measuring them must be addressed.
Gastrointestinal Hemorrhage After Acute Stroke
Authors: Davenport R.J. , Dennis M.S. , Warlow C.P.
Published: June 2011

Background and Purpose
Although patients with critical illness or acute head injury are known to be at risk of gastrointestinal hemorrhage, there is little information concerning acute stroke. We sought to record the frequency, possible causes, and course of gastrointestinal hemorrhage in a cohort of hospitalized stroke patients.

Methods
During a 36-month period we prospectively identified 613 strokes (excluding subarachnoid hemorrhage). We then retrieved the case notes, and a single observer reviewed all available records (n=607), noting any episodes of gastrointestinal hemorrhage together with details concerning the course, possible precipitating factors, management, and outcome.

Results
Eighteen patients (3%) experienced a gastrointestinal hemorrhage, half of which were severe. These patients were older and had suffered more severe strokes than those without any gastrointestinal bleeding. The source was identified in 5 patients; 2 had gastric ulceration, 2 duodenal ulceration, and the remaining one had esophageal/duodenal ulceration. In 17 patients there was a potential risk factor for hemorrhage, although the odds ratios comparing the use of antithrombotic drugs in the hemorrhage and nonhemorrhage groups did not achieve statistical significance. Death during the acute admission period was more common in the 18 hemorrhage patients (odds ratio, 4.6; 95% confidence interval, 1.7 to 13.2; two-tailed
P
=.002, Fisher’s exact test); of the 10 who died, gastrointestinal hemorrhage appeared to have been a contributing factor in 3.

Conclusions
Our study provides a reasonably accurate estimate of the frequency of gastrointestinal hemorrhage after acute stroke. The higher frequency found in our study than the previously published data is probably due to study methodology. Older patients with more severe strokes may be at increased risk of this complication, and it may adversely affect outcome.
Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Cerebrovascular Disease
Authors: Catto Andrew , Carter Angela M. , Barrett Jennifer H. , Stickland Max , Bamford John , Davies J. Andrew , Grant Peter J.
Published: June 2011

Background and Purpose
There is evidence that an allelic variation in the angiotensin-converting enzyme (ACE) gene may confer an increased risk of vascular disease. The roles of the ACE insertion/deletion polymorphism and circulating ACE levels are unknown in cerebrovascular disease.

Methods
We studied an insertion/deletion polymorphism within intron 16 of the ACE gene by polymerase chain reaction and plasma ACE activity in 467 cases of stroke, the pathological type of which was established by cranial CT, and 231 control subjects. ACE genotype and activity were related to stroke type and mortality at 4 weeks and 3 months.

Results
No difference in genotype frequency was observed between all subjects with stroke and control subjects or between control subjects and subjects with cerebral infarction or cerebral hemorrhage. Plasma ACE activity was significantly lower in stroke patients at presentation (64.1 IU/L) than in control subjects (79.6 IU/L;
P
<.0001). Twenty-one patients (4.5%) with cerebral infarction died within 4 weeks and 56 patients (12%) within 3 months. These patients had significantly lower plasma ACE activity than patients who survived. There was some evidence that risk of death within 4 weeks increased with the number of
D
alleles (
P
=.02). Among survivors, plasma ACE activity showed a mean increase of 6.9 IU/L (95% confidence interval, 3.0 to 10.8) between levels at presentation and at 3 months (73.6 IU/L), the latter being similar to ACE activity in control subjects.

Conclusions
Low ACE activity at stroke presentation and possession of the
D
allele may be associated with increased risk of early death from acute cerebral infarction.
Magnetic Resonance Imaging Correlates of Transient Cerebral Ischemic Attacks
Authors: Fazekas Franz , Fazekas Gudrun , Schmidt Reinhold , Kapeller Peter , Offenbacher Hans
Published: June 2011

Background and Purpose
MRI of patients with a transient ischemic attack (TIA) may provide more detailed morphological insights than CT. We therefore studied the frequency and type of TIA-related infarcts shown by MRI, examined the utility of intravenous contrast material, and searched for potential predictors of infarct occurrence.

Methods
We performed 1.5-T MRI of the brain on 62 patients (age range, 28 to 93 years; mean, 61 years) with a hemispheric TIA. Contrast material (Gd-DTPA) was given to 45 individuals. We recorded type, number, size, and location of ischemic brain lesions and related the presence of acute infarction to features of clinical presentation and probable causes for the TIA.

Results
MRI showed focal ischemic lesions in 50 patients (81%), but an acute TIA-associated infarct was seen in only 19 subjects (31%). In patients with an acute lesion, the infarcts were smaller than 1.5 cm in 13 (68%), purely cortical in 11 (58%), and multiple in 7 (37%) individuals. Contrast enhancement contributed to the delineation of an acute lesion in only 2 of 45 patients (4%). Acute infarction was unpredictable by clinical TIA features, but the frequency of identifiable vascular or cardiac causes was significantly higher in those patients with TIA-related morphological damage (odds ratio, 5.2 [95% confidence interval, 1.6 to 17.3]).

Conclusions
More than two thirds of TIA patients showed no associated brain lesion even when MRI and contrast material were used, but the overall frequency of ischemic damage was high. TIA-related infarcts on MRI were mostly small and limited to the cortex and tended to consist of multiple lesions. A positive MRI underscores the need for comprehensive diagnostic workup since evidence of infarction appears to be associated with a higher frequency of significant vascular or cardiac disorders.
Cigarette Smoking Is Correlated With the Periventricular Hyperintensity Grade on Brain Magnetic Resonance Imaging
Authors: Fukuda Hitoshi , Kitani Mitsuhiro
Published: June 2011

Background and Purpose
A few studies have observed a significant inverse correlation between cigarette smoking or lipid abnormalities and periventricular hyperintensities (PVHs) on T
2
-weighted magnetic resonance imaging (MRI) scans of the brain, which is surprising because smoking and hyperlipidemia are considered risk factors for cerebrovascular disease. We investigated the relation between smoking and lipid abnormalities and PVHs on T
2
-weighted MRIs.

Methods
MRI scans were performed in 253 patients over the age of 40 years, and PVHs were assessed retrospectively by use of a five-point scale. Patients who were receiving medical treatment for hyperlipidemia were excluded. Serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides were determined in the fasting state by an automated enzymatic procedure. The low-density lipoprotein (LDL) cholesterol level was calculated by use of Friedewald’s equation. Age, sex, hypertensive status, antihypertensive treatment, presence or absence of diabetes mellitus, and history of stroke were included in the analysis.

Results
Multiple linear regression analysis showed that age, hypertension, smoking, and antihypertensive treatment were significantly and independently correlated with the PVH score. The standard partial regression coefficients were .39 (
P
<.0001) for age, .33 (
P
<.0001) for hypertension, .16 (
P
=.0062) for smoking, and −.18 (
P
=.0124) for antihypertensive treatment. Hypercholesterolemia (total cholesterol level >220 mg/dL), HDL hypocholesterolemia (HDL cholesterol level <40 mg/dL), LDL hypercholesterolemia (LDL cholesterol level >130 mg/dL), hypertriglyceridemia (triglyceride level >150 mg/dL), sex, diabetes mellitus, and a history of stroke were not correlated with the PVH score.

Conclusions
Cigarette smoking was a weak but significant positive predictor of the PVH score and was independent of age, hypertension, and antihypertensive treatment. Lipid abnormalities were not related to the PVH score.
Evaluation of Intracranial and Extracranial Carotid Steno-Occlusive Diseases in Taiwan Chinese Patients With MR Angiography
Authors: Liu Hon-Man , Tu Yong-Kwang , Yip Ping-Keung , Su Cheng-Tau
Published: June 2011

Background and Purpose
We attempted to evaluate the location of vascular lesions in cases of cerebrovascular steno-occlusive diseases in Chinese persons living in Taiwan.

Methods
With three-dimensional time-of-flight magnetic resonance angiography (MRA) as a screening tool, 108 symptomatic patients with cerebrovascular steno-occlusive diseases were examined. Cardioembolic disease and cerebral hemorrhage cases were excluded. The degrees of stenosis of bilateral cervical carotid arteries and their major intracranial tributaries were recorded. They were categorized as nonsignificant stenosis (0% to 49%), significant stenosis (50% to 99%), and total occlusion.

Results
Our data revealed that 32.4% of the cases were normal in either cervical carotid arteries or their intracranial tributaries. In 24.1% of the cases, significant extracranial-carotid stenosis or occlusion was the only finding on MRA. In 25.9% of the cases, only significant intracranial-tributary stenosis was found. In 17.6% of them, significant lesions were found in both extracranial and intracranial carotid artery tributaries.

Conclusions
A racial difference between Chinese and white patients in location of lesion in cerebrovascular steno-occlusive diseases was confirmed. About one third of symptomatic Chinese patients living in Taiwan showed small-vessel disease. Approximately 24% of patients had only extracranial carotid disease, and about 26% had only intracranial carotid tributary disease. We need a larger series of patients to confirm these findings. However, MRA might be a good screening tool for steno-occlusive cerebrovascular diseases, especially in persons of a race with more intracranial carotid disease, such as the Chinese.
Long-term Prognosis of First-Ever Lacunar Strokes
Authors: Salgado António Vasco , Ferro José M. , Gouveia-Oliveira António
Published: June 2011

Background and Purpose
Information concerning the long-term prognosis of lacunar strokes is still limited and has shown different results. The aim of this study was to investigate the long-term prognosis of first-ever lacunar strokes and the possible role of clinical prognostic factors and different pathogenic mechanisms.

Methods
Between March 1990 and November 1993, a cohort of consecutive patients presenting with first-ever lacunar infarcts was prospectively evaluated after stroke onset at day 0 to 3 and/or day 7, every 3 months up to 1 year, and every 6 months thereafter. All patients were studied according to a protocol that included demographic and clinical data, neurological examination, Toronto Stroke Scale, Barthel Index, Rankin Scale, CT scan, routine laboratory workup, electrocardiogram, carotid duplex scanning, and echocardiogram. More recently, patients have also been evaluated with transcranial Doppler ultrasonography. Recurrent strokes, myocardial infarction, and death were registered through direct observation, chart review, or interviews with the attending physician or family members.

Results
One hundred forty-five patients—94 (65%) with pure hemiparesis, 33 (23%) with sensorimotor stroke, 11 (8%) with ataxic hemiparesis, 5 (3%) with pure sensory stroke, and 2 (1%) with dysarthria-clumsy hand syndrome—were followed for a median period of 39 months. During follow-up there were 17 deaths (3 vascular), 30 first recurrent strokes (1 fatal), and 4 myocardial infarctions. Five-year survival rate free of recurrent stroke was 63% (95% confidence interval [CI], 52% to 73%), while 5-year survival rate was 86% (95% CI, 78% to 91%). Cox proportional hazards analysis showed that age (
P
=.02) was the only significant predictor of survival free of recurrent stroke. Age (
P
<.001) and the degree of neurological dysfunction and functional disability at 7 days after the index stroke measured by the Toronto Stroke Scale (
P
=.05) and a Barthel Index score <40 (
P
=.04) were the only significant predictors of death. The 5-year probability rate of stroke-free recurrence was 72% (95% CI, 60% to 81%). Sixty-three percent of the first recurrent strokes were lacunar infarcts. When clinical, laboratory, and CT data as well as possible etiopathogenic mechanisms of lacunar strokes were considered, Cox proportional hazards analysis could not identify any predictor of stroke recurrence.

Conclusions
Our study confirms that lacunar infarcts are associated with low stroke recurrence and mortality rates. In our series, the majority of first recurrent strokes were also lacunar infarcts. Age, degree of neurological dysfunction, and functional disability at day 7 after the index stroke were significant predictors of death.
Incidence of Transient Ischemic Attacks and Minor Ischemic Strokes in Segovia, Spain
Authors: Sempere Angel P. , Duarte Jacinto , Cabezas C. , Clavería Luis E.
Published: June 2011

Background and Purpose
The aim of this study was to determine the incidence of transient ischemic attacks (TIAs) and minor ischemic strokes (MISs) in Segovia, Spain.

Methods
A 2-year prospective community-based register of TIAs and MISs was established in Segovia from February 16, 1992, to February 15, 1994. Every patient underwent a complete clinical evaluation and cranial CT scan. Sex- and age-specific incidence rates with 95% confidence intervals (CIs) were calculated for all ages.

Results
The total series included 235 patients; 103 suffered TIAs and 132 suffered MISs. Mean age was 70.8 years (range, 29 to 96 years); 92 were women and 143 were men. The crude annual incidence was 0.80/1000 (95% CI, 0.70 to 0.90): 0.35/1000 (95% CI, 0.28 to 0.42) for TIAs and 0.45/1000 (95% CI, 0.37 to 0.53) for MISs. The incidence of TIAs and MISs increased with age. Approximately 78% of TIAs and MISs were in the carotid distribution, 19% were vertebrobasilar, and 3% were considered of uncertain vascular distribution. Cranial CT scan was performed in all patients. CT showed cerebral infarcts in 30.1% (31/103; 95% CI, 21% to 39%) of TIAs and 70% (92/132; 95% CI, 62% to 78%) of MISs (
P
<.00001).

Conclusions
Our study is the first community-based register that provides sex- and age-specific rates for MISs and in which a CT scan was obtained in all patients. The incidence of TIAs in Segovia is comparable to that in other previous similar studies.
Transesophageal Echocardiography in Patients With Focal Cerebral Ischemia of Unknown Cause
Authors: Rauh Günter , Fischereder Michael , Spengel Florentin A.
Published: June 2011

Background and Purpose
Identification of cardioembolic stroke is often limited by the difficulties involved in the detection of thrombi or the risk factors for thrombus formation. Patients in sinus rhythm with nondiagnostic transthoracic echocardiogram (TTE) and without carotid artery stenosis represent a subset in whom diagnostic recommendations are lacking. The aim of this study was to determine the value of transesophageal echocardiography (TEE) for diagnosis and therapy in this population.

Methods
Thirty patients with the characteristics described above were studied prospectively with the use of blood analysis, TTE, TEE, and Holter monitoring (in patients with atrial thrombus).

Results
TTE was abnormal in 16 of 30 patients, but no embolic source was identified. TEE disclosed left atrial appendage thrombus in 3 of 30 patients, atrial septal aneurysm in 2 of 30 patients, patent foramen ovale in 7 of 30 patients, and aortic plaques in 19 of 30 patients. The TEE resulted in a change of therapy in 3 of the 30 patients studied.

Conclusions
This study demonstrates that TEE is a helpful diagnostic tool in delineating the risk of cardioembolic stroke and demonstrates significant pathology even in a subset of patients deemed to be at low risk. This additional new information led to a substantial change in therapy in 3 of 30 patients.
Ten-Year Trends in Stroke Incidence and Mortality in the FINMONICA Stroke Study
Authors: Tuomilehto Jaakko , Rastenyte Daiva , Sivenius Juhani , Sarti Cinzia , Immonen-Räihä Pirjo , Kaarsalo Esko , Kuulasmaa Kari , Narva Erkki V. , Salomaa Veikko , Salmi Kalervo , Torppa Jorma
Published: June 2011

Background and Purpose
The trends in stroke incidence reported so far have not been entirely consistent, although declining trends in mortality from stroke have been reported from a number of studies around the world. This study aims to evaluate the 10-year trends (from 1983 through 1992) in incidence, attack rate, and mortality of stroke in the Finnish population.

Methods
A population-based stroke register was set up in the early 1980s to collect data on all suspected events of acute stroke that occurred in the population aged 25 to 74 years permanently residing in three geographic areas of Finland: the provinces of Kuopio and North Karelia in eastern Finland and the Turku-Loimaa area in southwestern Finland. Trends in age-standardized attack rates, incidence, and mortality were calculated for the period studied.

Results
During the 10-year study period, 11 392 acute stroke events occurred in the monitored populations. A statistically significant decline was observed in the pooled FINMONICA data, both in the incidence of stroke (−1.7% with 95% confidence interval [CI], −3.0% to −0.5% per year in men; −2.2% with 95% CI, −3.6% to −0.7% per year in women) and in mortality from stroke (−5.2% with 95% CI, −8.2% to −2.2% per year; −4.7% with 95% CI, −8.2% to −1.2% per year). The attack rate of stroke also declined significantly in both sexes. When the areas were considered separately, the declining trends were observed within each area. The decline in incidence of stroke was, however, statistically significant only among men and women in Kuopio and among women in Turku/Loimaa. Mortality declined significantly in all three areas among men but among women only in Kuopio. The incidence to mortality rate ratio increased during the study period, indicating a steeper fall in mortality than in incidence.

Conclusions
A substantial decline in both stroke incidence and mortality was observed in the adult and elderly population in the FINMONICA study areas. Part but not all of the decline in stroke mortality, observed also in the official mortality statistics, can be attributed to the decline in stroke incidence during this 10-year period.
Role of the Nondominant Hemisphere and Undamaged Area During Word Repetition in Poststroke Aphasics
Authors: Ohyama Masashi , Senda Michio , Kitamura Shin , Ishii Kenji , Mishina Masahiro , Terashi Akiro
Published: June 2011

Background and Purpose
Although the resting regional cerebral blood flow (rCBF) in aphasic patients has been thoroughly investigated with positron emission tomography (PET) and single-photon emission CT, and PET studies in normal subjects have elucidated the functional localization of language processing, little is known about the activation pattern of language processing in aphasic patients.

Methods
We measured the changes in rCBF during a repetition task (hearing a single word and repeating it aloud) and the resting state using the H
2
15
O PET activation technique in 6 normal subjects (mean±SD age, 58.3±8.1 years) and 16 aphasic patients: 10 fluent aphasics (age, 60.3±12.5 years) and 6 nonfluent aphasics (age, 50.5±8.3 years).

Results
In normal subjects, the posteroinferofrontal area (PIF) including Broca’s area, the posterosuperotemporal area (PST) including Wernicke’s area, the rolandic areas, and a few other areas were activated with left side dominance by the repetition task. In the resting state, the rCBF in the left PIF and the left posterotemporal area was reduced in both fluent and nonfluent aphasics. In aphasic patients, the magnitude of activation in the right PIF and PST by the repetition task was greater than in normal subjects. The increase in rCBF during the repetition task in the left PIF correlated with the Western Aphasia Battery score of spontaneous speech in the nonfluent aphasics with a left inferofrontal lesion.

Conclusions
This study shows the importance in aphasic patients of the mirror regions of the left PIF and PST in the nondominant (right) hemisphere for performing the word repetition task. The results also show the importance for nonfluent aphasic patients of the recruitment of the undamaged PIF for spontaneous speech.
Effect of Mild Hypothermia on Cerebral Energy Metabolism During the Evolution of Hypoxic-Ischemic Brain Damage in the Immature Rat
Authors: Yager Jerome Y. , Asselin Johanne
Published: June 2011

Background and Purpose
Intraischemic hypothermia (34°C and 31°C) has a profound neuroprotective effect on the brain of the immature rat. Hypothermia immediately after hypoxia-ischemia is not beneficial. To determine the mechanisms by which mild to moderate hypothermia affects cerebral energy metabolism of the brain of the newborn rat pup, we examined alterations in cerebral glycolytic intermediates and high-energy phosphate compounds during intraischemic and postischemic hypothermia and correlated these findings with known neuropathologic injury.

Methods
Seven-day-old rat pups underwent unilateral common carotid artery ligation and exposure to hypoxia in 8% oxygen at either 37°C, 34°C, or 31°C for 3.0 hours. Separate groups were exposed to hypoxia-ischemia at 37°C for 3 hours but recovered at either 37°C, 34°C, or 31°C. At 60, 120, and 180 minutes of intraischemic hypothermia and at 10, 30, 60, and 240 minutes of postischemic hypothermia, individual rat pups were quick-frozen in liquid nitrogen for later determination of cerebral concentrations of glucose, lactate, ATP, and phosphocreatine.

Results
Cerebral glucose was significantly higher and lactate significantly lower in the 31°C animals during hypoxia-ischemia than either the 34°C or 37°C groups. Brain ATP concentrations were completely preserved during hypoxia-ischemia at 31°C, whereas 34°C of hypothermia had no effect on preserving high-energy phosphate compounds compared with those animals in the 37°C group. Postischemic hypothermia of either 34°C or 31°C had no effect on the rate or extent of recovery of glycolytic intermediates or high-energy phosphate compounds compared with the normothermic 37°C rat pups.

Conclusions
Moderate hypothermia of 31°C completely inhibits the depletion of ATP during hypoxia-ischemia, a mechanism that likely accounts for its neuroprotective effect. No preservation of ATP was seen, however, during intraischemic mild hypothermia of 34°C despite the relatively profound neuroprotective effect of this degree of temperature reduction. Thus, the mechanisms by which mild hypothermia is neuroprotective are temperature dependent and may act at more than one point along the cascade of events eventually leading to hypoxic-ischemic brain damage in the immature rat.
23
Na Nuclear Magnetic Resonance Spectral Changes During and After Forebrain Ischemia in Hypoglycemic, Normoglycemic, and Hyperglycemic Rats
Authors: Tyson Randy L. , Sutherland Garnette R. , Peeling James
Published: June 2011

Background and Purpose
The severity of brain injury in animal models of forebrain ischemia increases with blood glucose level. During ischemia, energy failure is slower and maintenance of ion gradients is prolonged as the level of glycemia increases. It is not clear how the level of glycemia influences recovery of ion homeostasis on reperfusion. It has been shown that changes in the intensity of the multiple-quantum
23
Na nuclear magnetic resonance (NMR) signals reflect changes in intracellular Na
+
levels. We have used
23
Na NMR spectroscopy to evaluate the influence of the level of glycemia on changes in Na
+
concentration during and after forebrain ischemia in rats.

Methods
Single-quantum (SQ) and double-quantum (DQ)
23
Na NMR spectra were measured before and during 10-minute forebrain ischemia and during reperfusion in hypoglycemic, normoglycemic, and hyperglycemic rats.

Results
The DQ
23
Na NMR signal increased to 210% of preischemia intensity in all rats, but a delay in this increase was observed in normoglycemic and hyperglycemic animals. The rate of the DQ
23
Na NMR signal increase was fastest in hypoglycemic (apparent first-order rate constant 0.673±0.046 min
−1
,
P
<.002 compared with normoglycemic animals) and slowest in hyperglycemic (0.285±0.024 min
−1
,
P
<.03) rats. During reperfusion, the signal intensity recovered rapidly in hypoglycemic (0.385±0.050 min
−1
) and normoglycemic (0.464±0.047 min
−1
) rats, whereas in hyperglycemic animals recovery was slow (0.108±0.044 min
−1
,
P
<.0001 compared with normoglycemic animals). The SQ
23
Na NMR signal intensity increased to 117% of preischemia level in hypoglycemic (
P
<.05 compared with normoglycemic animals) and to 107% in normoglycemic and hyperglycemic animals during reperfusion.

Conclusions
The slower increase in the
23
Na DQ NMR signal intensity during forebrain ischemia in rats with higher blood glucose levels suggests that Na
+
homeostasis is maintained longer in these animals. On reperfusion, the slower recovery of the DQ
23
Na NMR signal intensity in hyperglycemic animals likely indicates a slower recovery of Na
+
homeostasis, perhaps contributing to the increased neuronal injury after cerebral ischemia in hyperglycemic animals.
Glutamate-Induced Disruption of the Blood-Brain Barrier in Rats
Authors: Mayhan William G. , Didion Sean P.
Published: June 2011

Background and Purpose
The first goal of this study was to determine the effect of glutamate on permeability and reactivity of the cerebral microcirculation. The second goal of this study was to determine a possible role for nitric oxide in the effects of glutamate on the cerebral microcirculation.

Methods
We examined the pial microcirculation in rats with intravital microscopy. Permeability of the blood-brain barrier was quantified by the clearance of fluorescent-labeled dextran (molecular weight, 10 000 D; FITC-dextran-10K) before and during application of glutamate (0.1 and 1.0 mmol/L). In addition, we examined the permeability of the blood-brain barrier during application of a nitric oxide donor,
S
-nitroso-acetyl-penicillamine (SNAP; 10 μmol/L). Diameter of pial arterioles was measured before and during application of glutamate or SNAP. To determine a potential role for nitric oxide in glutamate-induced effects on the cerebral microcirculation, we examined the effects of
N
G
-monomethyl-
l
-arginine (10 μmol/L).

Results
In control rats, clearance of FITC-dextran-10K from pial vessels was minimal, and the diameter of pial arterioles remained constant during the experimental period. Topical application of glutamate (0.1 and 1.0 mmol/L) and SNAP (10 μmol/L) produced an increase in clearance of FITC-dextran-10K and in diameter of pial arterioles. In addition,
N
G
-monomethyl-
l
-arginine (10 μmol) attenuated glutamate-induced increases in permeability of the blood-brain barrier and glutamate-induced dilatation of cerebral arterioles.

Conclusions
The findings of the present study suggest that glutamate, a major neurotransmitter in the brain, increases permeability of the blood-brain barrier to low-molecular-weight molecules and dilates cerebral arterioles via a nitric oxide–dependent mechanism.
Restricted Nonacral Sensory Syndrome
Authors: Kim Jong S.
Published: June 2011

Background
Restricted sensory symptoms due to stroke most often occur at distal parts of the body, manifesting as cheiro-oral or cheiro-oral-pedal syndrome. Sensory symptoms restricted to proximal body parts have rarely been recognized.

Case Descriptions
I describe four patients presenting with restricted sensory disturbances at the proximal parts of the body. The sensory symptoms were restricted to discrete areas of the contralateral proximal arm, shoulder, trunk, and upper thigh. The face and the distal parts of the extremities were largely spared. On MRI, three patients had a small thalamic infarction and one had a putaminal infarction.

Conclusions
Strategically located minor strokes can produce restricted sensory syndromes at discrete areas of nonacral parts of the body. These observations highlight the diverse patterns of restricted sensory syndromes after unilateral stroke and support the theory of somatotopic-anatomic proximity of certain parts of the body in the human sensory pathway.
Role of Oxidants in Ischemic Brain Damage
Authors: Chan Pak H.
Published: June 2011

Background and Purpose
Oxygen free radicals or oxidants have been proposed to be involved in acute central nervous system injury that is produced by cerebral ischemia and reperfusion. Because of the transient nature of oxygen radicals and the technical difficulties inherent in accurately measuring their levels in the brain, experimental strategies have been focused on the use of pharmacological agents and antioxidants to seek a correlation between the exogenously supplied specific radical scavengers (ie, superoxide dismutase and catalase) and the subsequent protection of cerebral tissues from ischemic injury. However, this strategy entails problems (hemodynamic, pharmacokinetic, toxicity, blood-brain barrier permeability, etc) that may cloud the data interpretation. This mini-review will focus on the oxidant mechanisms in cerebral ischemic brain injury by using transgenic and knockout mice as an alternative approach.

Methods
Transgenic and knockout mutants that either overexpress or are deficient in antioxidant enzyme/protein levels have been successfully produced. The availability of these genetically modified animals has made it possible to investigate the role of certain oxidants in ischemic brain cell damage in molecular fashion.

Results
It has been shown that an increased level of CuZn–superoxide dismutase and antiapoptotic protein
Bcl-2
in the brains of transgenic mice protects neurons from ischemic/reperfusion injury, whereas a deficiency in CuZn–superoxide dismutase or mitochondrial Mn–superoxide dismutase exacerbates ischemic brain damage. Target disruption of neuronal nitric oxide synthase in mice also provides neuronal protection against permanent and transient focal cerebral ischemia.

Conclusions
I conclude that molecular genetic approaches in modifying antioxidant levels in the brain offer a unique tool for understanding the role of oxidants in ischemic brain damage.
Evaluation of Impaired Cerebral Autoregulation by the Valsalva Maneuver
Authors: Tiecks Frank P. , Douville Colleen , Byrd Sheila , Lam Arthur M. , Newell David W.
Published: June 2011

Background and Purpose
Transcranial Doppler sonography has recently been used to describe cerebral hemodynamics during the Valsalva maneuver in normal human subjects. Since some changes in flow velocity during the Valsalva maneuver seem to reflect the brain's autoregulatory response to a decrease in cerebral perfusion pressure during the strain, we hypothesized that this method could identify vascular territories with impaired autoregulatory capacity.

Methods
Eight patients with unilateral (n=7) or bilateral (n=1) severe obstruction of the internal carotid artery and impaired vascular responses to the CO
2
reactivity test and to dynamic autoregulation testing were studied. We compared changes in flow velocities and blood pressures during defined phases of the Valsalva maneuver in the patients with the results in a group of 17 normal volunteers. We defined two indices to evaluate autoregulatory capacity based on the response to the Valsalva maneuver.

Results
During the Valsalva maneuver, changes in flow velocity in the middle cerebral arteries ipsilateral to the lesions showed characteristic abnormalities compared with the normal pattern. Autoregulatory indices of these vessels as defined by the Valsalva maneuver were significantly different from those with normal vascular reactivity to CO
2
(
P
<.0001). There were good correlations between an index based on the changes in flow velocity and blood pressure in phase II and the results of the CO
2
test (
r
=.78;
P
<.0001) or those of dynamic autoregulatory testing (
r
=.6;
P
<.0001).

Conclusions
Vascular territories with severely impaired vasomotor reactivity due to carotid obstruction can be identified by transcranial Doppler sonography by their pattern of flow velocity changes if their autoregulatory capacity is challenged during the Valsalva maneuver.
Mitral Valve Strands in Patients With Focal Cerebral Ischemia
Authors: Tice Frank D. , Slivka Andrew P. , Walz Elizabeth T. , Orsinelli David A. , Pearson Anthony C.
Published: June 2011

Background and Purpose
Filamentous strands attached to the mitral valve are a recently described finding in occasional patients undergoing transesophageal echocardiography (TEE), but the frequency and clinical significance of these strands remain poorly defined. The purpose of the present study was to review the prevalence of mitral valve strands in patients undergoing TEE examination and to explore the relation of these strands to cardioembolic cerebral ischemia.

Methods
All patients with native mitral valves referred for clinically indicated TEE over a 2-year period at our institution were evaluated for the presence of mitral valve strands (defined as highly mobile filamentous masses <1 mm thick attached to the atrial surface of mitral leaflets).

Results
Of 968 study patients, mitral valve strands were identified in 22 individuals (2.3%). Mitral valve strands were significantly more common in patients referred for TEE as a result of a recent ischemic cerebrovascular event compared with patients referred for other study indications (6.3% versus 0.3%, respectively;
P
<.00001). Among patients ≤50 years of age with likely cardioembolic stroke or transient ischemic attack, 16% were found to have mitral valve strands on TEE examination. In 9% of these young patients, no other TEE finding associated with cardioembolic risk was present.

Conclusions
Filamentous strands attached to the mitral valve appear to represent another risk factor for embolic cerebral ischemia, particularly in patients ≤50 years of age.
Hospitalization and Case-Fatality Rates for Stroke in Canada From 1982 Through 1991
Authors: Mayo Nancy E. , Neville Doreen , Kirkland Susan , Ostbye Truls , Mustard Cameron A. , Reeder Bruce , Joffres Michel , Brauer Gerhard , Levy Adrian R.
Published: June 2011

Background and Purpose
The purpose of this study was to estimate rates of hospitalization and in-hospital case-fatality for cerebral infarction and intracerebral hemorrhage in Canada and to describe variation in rates by age, sex, and calendar period.

Methods
Data were obtained from hospitalization databases for each of Canada's 10 provinces for the 10 fiscal years of 1982 through 1991. All hospitalizations of persons 15 years of age or older with a primary diagnosis at discharge coded 431, 434, or 436 according to the
International Classification of Disease, 9th Revision
, were included. Rates per 100 000 population were calculated for intracerebral hemorrhage and cerebral infarction, for men and women, and for five age groups. Annual age- and sex-specific, 30-day, in-hospital case-fatality rates were also calculated.

Results
A total of 335 283 discharges for stroke were enumerated over the 10-year period (309 631 cerebral infarctions and 25 652 intracerebral hemorrhages). A significant decline of approximately 1% per year was observed for the rate of cerebral infarctions. For hemorrhages, the reverse was seen. For men there was a 44% increase over the 10-year period, and for women there was a 34% increase. In-hospital case-fatality rates for cerebral infarctions increased with age but did not differ by sex when age was considered. For the five age groups of 15 to 54, 55 to 64, 65 to 74, 75 to 84, and ≥85 years, rates were 6%, 8%, 12%, 18%, and 27%, respectively. For intracerebral hemorrhage, the in-hospital case-fatality rates declined significantly over time from approximately 36% to 29%, 55% to 37%, 49% to 41%, 66% to 45%, and 72% to 59% for the five age groups, respectively.

Conclusions
The possibility that these changes are artifactual could not be ruled out, but because there is no obvious risk in assuming that they are not, it would be prudent to investigate their causes further.
Lipoprotein(a) in Patients With Acute Cerebral Ischemia
Authors: van Kooten Fop , van Krimpen Johannes , Dippel Diederik W.J. , Hoogerbrugge Nicoline , Koudstaal Peter J.
Published: June 2011

Background and Purpose
In several cross-sectional studies, a high serum lipoprotein(a) [Lp(a)] level was found to be an independent risk factor for cerebral infarction. In a recent prospective study, however, no association was found between Lp(a) levels at baseline and future risk of stroke. Whether Lp(a) is a prognostic factor in a high-risk population of patients with acute ischemic stroke remains unclear.

Methods
We assessed Lp(a) level on admission to study its relationship with cardiovascular risk profile, stroke severity, and prognosis in 151 consecutive patients with acute cerebral ischemia. The mean follow-up period was 2.5±1.2 years. Lp(a) was measured by means of a solid-phase two-site immunoradiometric assay.

Results
Increased Lp(a) levels were found in 53 (35%) of the patients with cerebral ischemia. Median (5th and 95th percentile) values of Lp(a) were 191 (12 and 1539) mg/L and 197 (10 and 1255) mg/L for patients with transient ischemic attack and patients with ischemic stroke, respectively. No relationship was found between Lp(a) levels and stroke severity (
P
=.68) or the occurrence of vascular events during follow-up (
P
log rank=0.81).

Conclusions
We conclude that Lp(a) is increased in about one third of patients with acute cerebral ischemia, but it does not appear to be associated with the cardiovascular risk profile, stroke characteristics, or the prognosis of such patients.
Risk Factors for Incident Dementia After Stroke
Authors: Moroney J.T. , Bagiella E. , Desmond D.W. , Paik M.C. , Stern Y. , Tatemichi T.K.
Published: June 2011

Background and Purpose
Stroke significantly increases the risk of dementia in the elderly, yet the risk factors for incident dementia after ischemic stroke are not well understood. We attempted to determine whether hypoxic-ischemic (HI) disorders, which may result from comorbid medical conditions (eg, seizures, cardiac arrhythmias, pneumonia), would be an independent risk factor for the development of new dementia after stroke.

Methods
We prospectively followed 185 initially nondemented patients with ischemic stroke (age, 70.3±7.7 years) for a maximum of 52.8 months. We diagnosed the presence of dementia at annual examinations based on neuropsychological testing and modified DSM-III-R criteria. HI disorders were identified by record review or examination during hospitalization. We used Kaplan-Meier analysis to determine the cumulative proportion of patients with and without HI disorders who survived free of dementia and used Cox models to estimate the relative risk of dementia associated with HI disorders.

Results
The cumulative proportion (±SE) surviving without dementia was 51.7±10.9% in the HI group versus 78.2±4.3% in the non-HI group after 52.8 months of observation. The relative risk of incident dementia associated with HI events was 4.3 (95% confidence interval=1.9 to 9.6) after we adjusted for demographic factors, recurrent stroke, and baseline cognitive function.

Conclusions
We conclude that HI disorders may be a significant independent risk factor for incident dementia after stroke, even after adjustment for other recognized predictors of cognitive decline. Recognition of HI cerebral damage as a possible pathogenic mechanism for dementia after stroke may allow targeted therapeutic interventions to prevent subsequent cognitive deterioration.
Angular Biofeedback Device for Sitting Balance of Stroke Patients
Authors: Dursun Erbil , Hamamci Nigar , Dönmez Semra , Tüzünalp Önder , Çakci Aytül
Published: June 2011

Background and Purpose
Impaired sitting balance is an important and time-consuming complication for stroke patients. We examined the effect of the use of an angular biofeedback device in addition to physical therapy in training stroke patients with impaired sitting balance compared with outcome in patients receiving conventional physical therapy only.

Methods
The biofeedback group consisted of 24 patients who received angular biofeedback training in addition to conventional physical therapy. The number of biofeedback signals and the lengths of time a patient could sit balanced throughout a period of 5 minutes before the training program, after 10 days of treatment, and at discharge were recorded and compared with those of the control group of 13 patients who received conventional physical therapy only.

Results
It was found that 75% of the biofeedback group gained sitting balance after 10 days of treatment in comparison with 15.4% of the control group (
P
<.001). At discharge, 91.6% of the biofeedback group and 84.6% of the control group gained sitting balance (
P
=.510), and 45.8% of the biofeedback group and 46.2% of the control group managed independent ambulation (
P
=.985). The mean rehabilitation periods among the ambulatory patients of the biofeedback and control groups were 9.45±0.71 and 13.83±1.70 weeks, respectively (
P
=.049). The mean training time in which the biofeedback group gained sitting balance was significantly shorter than that of the control group (
P
<.001).

Conclusions
Angular biofeedback intervention, by providing earlier postural trunk control, is a useful adjunct to conventional physical therapy in the rehabilitation of stroke patients with impaired sitting balance.