bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemic and hemorrhagic stroke in patients on oral anticoagulants after reconstruction for chronic lower limb ischemia.
Authors: Dawson I , van Bockel J H , Ferrari M D , van der Meer F J , Brand R , Terpstra J L
Published: June 2011

Information on the long-term fate of patients with chronic lower limb ischemia is limited. We investigated the long-term risk of the first ischemic and hemorrhagic cerebral stroke in patients on long-term anticoagulant therapy after reconstruction for chronic limb ischemia.

In a retrospective study, 376 consecutive patients were seen at regular intervals according to a standard protocol. Only 3 (0.7%) were lost during follow-up (mean duration, 5.9 years). Anticoagulation was with coumarin derivatives followed by prothrombin times periodically. Primary end points were ischemic and hemorrhagic cerebral stroke events, which were confirmed by CT scan, autopsy, or operation in 85% of the cases. Major vascular events were analyzed as a composite secondary end point. The influence of several clinical variables on these outcome events was evaluated in univariate and multivariate analyses.

Thirty-nine patients (10%) had 41 stroke events (23 ischemic, 18 hemorrhagic); 22 of these patients (56%) died from stroke. The cumulative ischemic stroke risk was 5% at 5 years and 12% at 15 years. Prior myocardial infarction was the only independent predictor (relative risk [RR], 3.1; P < .05). The cumulative hemorrhagic stroke risk was 3% at 5 years and 17% at 15 years. Systolic hypertension (RR, 4.8; P < .01) and insulin-dependent diabetes mellitus (RR, 5.4; P < .01) were significant and independent predictors. The risk for a major vascular event was 29% at 5 years and increased to 56% at 15 years. Independent predictors were advanced age (RR, 1.4; P < .005), insulin-dependent diabetes (RR, 2.2; P < .005), and prior myocardial infarction (RR, 1.8; P < .01).

Patients with chronic lower limb ischemia, notably those with prior myocardial infarction, are at high risk for ischemic stroke. Those with systolic hypertension or insulin-dependent diabetes mellitus are at high risk for hemorrhagic stroke.
Clinical features of recurrent embolization in acute cardioembolic stroke.
Authors: Yasaka M , Yamaguchi T , Oita J , Sawada T , Shichiri M , Omae T
Published: June 2011

Recurrent embolization is a serious problem in acute cardioembolic stroke. However, the clinical features and predisposing factors of recurrent embolization have not been fully elucidated.

Subjects were 227 consecutive patients (128 men and 99 women, aged 68.6 +/- 13.2 years) with acute cardioembolic stroke who did not receive anticoagulant therapy during the first 14 days after stroke onset. We assigned the subjects to two groups according to the occurrence or nonoccurrence of recurrent attacks within 14 days of the stroke onset. We assessed their clinical features, coagulation study results, and underlying heart disease.

Recurrent brain or systemic embolization during the first 14 days after onset was noted in 46 patients (20.3%, group A) but not in the other 181 (group B). Recurrent embolization was more frequently noted at an early phase than at a late phase during the initial 14 days. Mortality was higher in group A (19.6%) than in group B (8.8%). The mean plasma level of antithrombin III (77.8 +/- 19.5%) at admission in group A patients was significantly lower than that in group B patients (87.9 +/- 15.5%). After admission, hematocrit decreased in group B patients but slightly increased in group A patients, in whom diuretics were more commonly used. Rheumatic heart disease and prosthetic valves, in addition to the presence of intracardiac thrombi, were seen more commonly in group A patients, whereas atrial fibrillation without organic heart disease and myocardial infarction were more frequent in group B patients.

Low plasma levels of antithrombin III, dehydration, the use of diuretics, and the presence of rheumatic heart disease, prosthetic valves, and intracardiac thrombi seem to be predisposing factors for recurrent embolization. Immediate anticoagulation may be considered in acute cardioembolic stroke patients if such predisposing factors are demonstrated.
Evaluation times for patients with in-hospital strokes.
Authors: Alberts M J , Brass L M , Perry A , Webb D , Dawson D V
Published: June 2011

Each year at least 35,000 people suffer a stroke while hospitalized, but little is known about the clinical characteristics of such patients or how rapidly they are identified and evaluated. With a recent emphasis on the very early treatment of stroke, in-hospital stroke patients may be candidates for some early interventions.

This was a retrospective study using the stroke registries at two academic medical centers. Data were collected about the clinical characteristics of patients with an in-hospital stroke and who recognized the stroke. Detailed time data were analyzed to determine the time of stroke recognition, medical evaluation, and neurological evaluation. These specific time epochs were analyzed to determine which were responsible for any delays in stroke identification and assessment. Data were analyzed using nonparametric methods, including the Wilcoxon rank sum and Kruskal-Wallis procedure.

Sixty-three patients were identified with in-hospital strokes and adequate time data. In-hospital stroke patients were recognized most frequently by nurses (63%) and by the patient (16%). Patients on a cardiology service and general surgery service accounted for 48% of all in-hospital strokes. The mean and median times from stroke recognition to a neurology evaluation were 14.5 and 2.5 hours, respectively. Total delays differed significantly with service and locale (P = .004). Patients on the Duke neurology service were evaluated significantly sooner (median delay, 0.5 hour) than patients on the Duke medical (median delay, 5.8 hours) or Duke surgical (median delay, 20.5 hours; P < .01 by Wilcoxon rank sum) services. Patients on the Yale surgical service were evaluated significantly sooner than patients on the Duke medical (P = .0006) or surgical (P = .0001) services. The time between physician notification and calling for a neurology evaluation accounted for > 60% of the total time delay for patients not on a neurology service.

A substantial number of in-hospital stroke patients experience a long delay between symptom recognition and a neurological evaluation. While medical personnel are usually notified very soon after an in-hospital stroke is recognized, such patients often do not receive a rapid neurological evaluation. Additional education of hospital staff may reduce these time delays.
Early carotid atherosclerosis in healthy middle-aged women. A follow-up study.
Authors: Bonithon-Kopp C , Jouven X , Taquet A , Touboul P J , Guize L , Scarabin P Y
Published: June 2011

Few longitudinal data about early atherosclerotic lesions of the carotid arteries are available in general populations. The main purpose of this study was to investigate risk factors for development and regression of intimal-medial thickening and atheromatous plaques.

Initial and 2-year examinations of the carotid arteries with high-resolution B-mode ultrasonography were performed in 308 apparently healthy women aged 45 to 55 years. The development of new atheromatous plaques and new intimal-medial thickening and the disappearance of preexisting plaques and intimal-medial thickening defined the four outcomes of interest.

The development of plaques occurred more frequently in women with intimal-medial thickening than in women with normal carotid arteries at baseline (14.4% versus 7.2%, P < .053). A regression was seen in 21.7% of the women with preexisting plaques. Development of intimal-medial thickening occurred in 47.5% of the women with normal carotid arteries whereas 20.2% of the women with preexisting intimal-medial thickening showed a regression of their lesions. Multiple logistic regression showed that smoking (regression coefficient +/- SE: 1.281 +/- 0.450; P < .005), baseline levels of systolic blood pressure (regression coefficient +/- SE: 0.031 +/- 0.015; P < .04) and apolipoprotein B (regression coefficient +/- SE: 0.016 +/- 0.007; P < .03) were independently associated with the development of plaques, whereas the presence of an intimal-medial thickening did not reach the significance level (regression coefficient +/- SE: 0.639 +/- 0.436; P < .15). Independent predictors of the development of intimal-medial thickening were age (regression coefficient +/- SE: 0.124 +/- 0.048; P < .04) and, with a borderline significance level, (log)triglycerides (regression coefficient +/- SE: 0.854 +/- 0.451; P < .06). Low levels of low-density lipoprotein cholesterol (regression coefficient +/- SE: 0.027 +/- 0.009; P < .004) were associated with its regression.

This longitudinal study emphasizes the interest of B-mode ultrasonography in the monitoring of early carotid lesions. It gives further support to the hypothesis that intimal-medial thickening may be an early indicator of the atherosclerotic process.
A transpulmonary contrast medium enhances the transcranial Doppler signal in humans.
Authors: Ries F , Honisch C , Lambertz M , Schlief R
Published: June 2011

Transtemporal insonation in transcranial Doppler sonography is often impaired by an insufficient signal-to-noise ratio, especially in elderly patients. A transpulmonary stable air microbubble suspension was injected intravenously in humans as an intracranial ultrasonic contrast agent.

In a clinical phase II study, 20 patients (15 women, 5 men; mean age, 65.5 +/- 11.5 years) presenting with clinical indications for transcranial Doppler investigation were examined. A total of 97 intravenous injections with different concentrations (200, 300, and 400 mg/mL of suspension) of air microbubbles bound to galactose microparticles as a carrier were performed. The signal enhancement of color-coded pulse curves of basal cerebral arteries was evaluated off-line in comparison to an integrated color-coded decibel scale, considering quality, quantity, and time course of enhancement requiring a 3-dB level above the native signal. The overall diagnostic information was assessed according to a reliability score.

The first acoustic signal increase was registered after an average of 21 seconds. Time intervals for a dose-dependent peak intensity and maximal duration were 41.3 +/- 17.1 seconds and 118.0 +/- 69.8 seconds (200 mg/mL); 55.5 +/- 27.7 seconds and 237.0 +/- 112.3 seconds (300 mg/mL); and 66.1 +/- 31.8 seconds and 293.0 +/- 122.0 seconds (400 mg/mL), respectively. Duration of signal enhancement increased significantly (P < .05) with higher concentrations. The extent of signal enhancement during the whole pulse curve reached an average of 9.1 +/- 5.0 dB for 200 mg/mL, 12.0 +/- 5.4 dB for 300 mg/mL (significant on P < .05 level), and 13.1 +/- 5.6 dB for 400 mg/mL concentration (P = NS). Respective maximal intensity spots reached 17.5 +/- 6.0, 20.7 +/- 5.5, and 22.7 +/- 5.9 dB for increasing concentrations, respectively. Overall visual assessment of enhanced pulse curves for diagnostic reliability showed a sufficient result in 38.1% of all injections with 200 mg/mL, in 88.6% with 300 mg/mL, and in 84.2% with 400 mg/mL concentration. Minimal side effects occurring in 12.4% of all injections were all reversible.

Transpulmonary stable air microbubbles bound to a galactose carrier represent a useful and safe contrast agent in case of an insufficient native signal in transcranial Doppler investigation.
Quantification of ultrasound emboli signals in patients with cardiac and carotid disease.
Authors: Grosset D G , Georgiadis D , Kelman A W , Lees K R
Published: June 2011

The use of Doppler ultrasound to detect arterial emboli has major implications for the classification and treatment of stroke. Experimental studies indicate that embolic materials produce different ultrasound signals, depending on their acoustic properties. To examine the possibility of characterizing emboli of different sources in the clinical setting, we compared the emboli signals of patients with cardiac embolic sources with those of patients with signals of carotid embolic sources.

Transcranial Doppler monitoring (30 minutes per patient) of the middle cerebral arteries was performed in 80 patients with prosthetic cardiac valves and 20 patients with internal carotid artery stenosis. The signal power of emboli was calculated in relation to the background Doppler signal.

In patients who were embolizing from prosthetic heart valves, the frequency of embolus signals was greater than in patients with carotid stenosis who were embolizing (mean +/- SEM: 58.2 +/- 11 versus 8.2 +/- 3 signals per hour; P < .0001, two-sample t test), and total signal power and duration also were higher (power, 2231 +/- 63 versus 455 +/- 109 power units; duration, 55.9 +/- 0.8 versus 29.9 +/- 1.4 milliseconds; both P < .001). The majority of emboli signals were seen during cardiac systole, especially in patients with carotid stenosis (89% in the first half of the cardiac cycle versus 72% in prosthetic valve patients). In 19 patients with prosthetic valves, embolus signals were also recorded from the anterior cerebral artery; the signal count was not significantly different from the middle cerebral artery (43.2 +/- 12.5 versus 64.3 +/- 16 per hour), but anterior cerebral artery signals were of higher power (3306 +/- 148 versus 2441 +/- 109 power units, P < .001).

There is promise of being able to distinguish emboli on the basis of power measurements. Emboli of different sources (eg, carotid and cardiac) appear to have different ultrasonic characteristics, which are likely to be based on composition and size.
Functional image of dynamic computed tomography in diagnostic and prognostic evaluation of ischemic stroke within the first 6 hours.
Authors: Toriyama T , Tanizaki Y , Hongo K , Osawa M , Kobayashi S
Published: June 2011

It is important to make a diagnosis before a low-density area appears on computed tomography for appropriate management of acute ischemic stroke. We report the diagnostic and prognostic usefulness of functional image of dynamic computed tomography for acute ischemic stroke.

Forty-seven patients with ischemic strokes within 6 hours of ictus underwent dynamic computed tomography in which functional images were obtained. These findings were compared with angiographic findings, follow-up computed tomography, and clinical outcome.

The functional images were categorized into three groups: (1) cortical type: abnormalities on time to peak image and/or corrected mean transit time image involving mainly cortical structures (29 cases); (2) noncortical type: abnormalities on either or both images limited to noncortical structures (7 cases); and (3) normal type: no abnormalities on both images (11 cases). Cortical type as a diagnostic test for arterial trunk occlusion had a good sensitivity (100%), specificity (95%), and accuracy (98%). Infarction volume on follow-up computed tomography correlated with extension of prolonged time-to-peak area (r = .80, P < .01) and that of prolonged corrected mean transit time area (r = .81, P < .01). Cortical type was associated with significantly unfavorable outcome (P < .01).

Functional image of dynamic computed tomography findings predicted arterial trunk occlusion, infarction volume, and clinical outcome. Therefore, this technique would be useful not only for indicating definitive angiography and subsequent therapy but for evaluating the effectiveness of surgical or medical recanalization.
Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive intracranial major arteries in moyamoya disease.
Authors: Masuda J , Ogata J , Yutani C
Published: June 2011

Stenosis or occlusion due to fibrocellular intimal thickening in the intracranial major arteries is thought to be the primary lesion in moyamoya disease, but its etiology and pathogenesis are unknown. The present study was designed to analyze cellular components of the lesions and their pathological process.

Stenotic or occlusive intracranial arterial lesions were collected from six autopsied patients who died of moyamoya disease. The cellular components were analyzed by immunohistochemical staining using cell-type-specific monoclonal antibodies. The sections were also immunostained for proliferating cell nuclear antigen (PCNA) to detect proliferating cells and for two different types of intermediate filaments, desmin and vimentin, to evaluate phenotypes of the intimal smooth muscle cells.

The thickened intima was composed predominantly of smooth muscle cells with an admixture of some macrophages and T cells. Macrophages and T cells were scattered in the superficial layer of the intimal thickening, and these were occasionally associated with organization of fibrin thrombi. Proliferating smooth muscle cells, indicated by PCNA-positive nuclei and muscle actin-positive cytoplasm, were found in the thickened intima in four patients. Immunohistochemical staining for intermediate filaments revealed intimal smooth muscle cells showing positive staining for vimentin and negative staining for desmin, compatible with the phenotype of synthetic smooth muscle cells.

The present study provides evidence that smooth muscle cells are proliferating in the occlusive lesions in intracranial major arteries in moyamoya disease. The colocalization of inflammatory cells and PCNA-positive cells suggests that inflammatory stimuli may induce proliferative response of smooth muscle and contribute to the formation of the intracranial occlusive lesions in moyamoya disease.
Blood pressure after stroke. A one-year follow-up study.
Authors: Carlsson A , Britton M
Published: June 2011

Blood pressure changes in the year after acute stroke have been poorly documented.

We therefore studied blood pressure for 1 year after discharge from the hospital in 226 consecutive patients (mean age, 73 years) surviving an acute stroke.

Marked increases (p < 0.001) in mean systolic and mean diastolic blood pressures were seen in two thirds (69%) of the patients 1 month after discharge, and blood pressure remained stable at this level during the remainder of the follow-up year. Similar blood pressure changes were seen irrespective of sex, final stroke diagnosis, or whether the patient had a history of hypertension before the stroke. Patients with a history of hypertension had significantly higher blood pressures (p < 0.001) throughout the follow-up year than previously normotensive patients. One month after discharge blood pressure was found to have decreased in 31% of the patients; these were older and had a higher mortality during the follow-up year than patients with blood pressure increases. About 20% of all patients suffered from orthostatism (defined as a decrease in systolic blood pressure of > or = 20 mm Hg when rising from the supine position to standing).

We conclude that antihypertensive treatment should not be reduced before discharge from the hospital and that blood pressure should be checked about 1 month after discharge. We suggest that standing blood pressure also be measured to make an appropriate treatment decision.
Leukocyte infiltration in acute hemispheric ischemic stroke.
Authors: Wang P Y , Kao C H , Mui M Y , Wang S J
Published: June 2011

The dynamics of leukocyte infiltration in human cerebral ischemia were studied using technetium-99m hexamethylpropyleneamine oxime (99mTc HMPAO)-labeled leukocyte brain single-photon emission computed tomography (SPECT).

Twenty-two patients diagnosed as having hemispheric ischemic stroke were examined with 99mTc HMPAO brain SPECT for cerebral blood flow study and 99mTc HMPAO-labeled leukocyte brain SPECT for the study of leukocyte infiltration. Three patients with chronic hemispheric ischemic stroke received one examination. Nineteen patients with acute hemispheric ischemic stroke received their initial examination within the first after onset. Follow-up examinations were performed at intervals of 1-3 weeks whenever possible.

In patients with chronic hemispheric ischemic stroke, leukocyte infiltration was not seen in areas of perfusion defect. In patients with acute hemispheric ischemic stroke, leukocyte infiltration was seen in areas of perfusion defect during the acute stage, which persisted for no less than 5 weeks after onset and then declined.

A new method to study and monitor the process of leukocyte infiltration in acute cerebral ischemia using 99mTc HMPAO-labeled leukocyte brain SPECT is described. This method shows that leukocyte infiltration in acute hemispheric ischemic stroke is a dynamic process that persists for no less than 5 weeks and then declines.
Age as a modifying factor on the effect of antihypertensive therapy in focal stroke in rats.
Authors: Slivka A
Published: June 2011

Antihypertensive treatment with hydralazine for 10 weeks but not 6 weeks reduces infarct size in 13-week-old spontaneously hypertensive rats subjected to focal cerebral ischemia. This study was designed to examine whether the duration of treatment needed to reduce infarct size depends on how long hypertension is present before the initiation of antihypertensive therapy.

Six-week-old spontaneously hypertensive rats were treated for 6 weeks and 10-month-old spontaneously hypertensive rats for 10 weeks with 20 mg/kg hydralazine added daily to the drinking water. The animals were then subjected to focal cerebral ischemia by tandem permanent common carotid and middle cerebral artery occlusion.

Blood pressure in the treated groups was lower than that in the untreated groups for the entire treatment period in both experiments. Infarct volume in 10-month-old spontaneously hypertensive rats treated for 10 weeks, but not in 6-week-old spontaneously hypertensive rats treated for 6 weeks, was significantly less than in untreated controls (p = 0.02).

This study emphasizes the importance of duration of antihypertensive treatment in reducing infarct volume in spontaneously hypertensive rats after focal cerebral ischemia and demonstrates that the effect appears to be independent of the duration of hypertension before the initiation of treatment.
Prophylactic effect of imidapril on stroke in stroke-prone spontaneously hypertensive rats.
Authors: Ogiku N , Sumikawa H , Hashimoto Y , Ishida R
Published: June 2011

It has been reported that some angiotensin converting enzyme inhibitors can prevent stroke-prone spontaneously hypertensive rats from stroke at much higher doses than clinical doses used for hypertension therapy. This study was performed to investigate the prophylactic effectiveness of imidapril against stroke in comparison with enalapril.

Salt-loaded stroke-prone spontaneously hypertensive rats were orally given imidapril (0.5, 1, 2, and 5 mg/kg per day), enalapril (2 and 5 mg/kg per day), or hydralazine (5 mg/kg per day). Stroke signs were scored, and blood pressure, protein concentration, and N-acetyl-beta-D-glucosaminidase activity in urine were measured. After 2 weeks of medication, angiotensin converting enzyme activities in the aorta were measured 24 hours after dosing.

In the control group, severe hypertension developed, and all rats died within 12 weeks because of stroke. Imidapril and enalapril dose-dependently decreased the stroke-related mortality, and both agents at 5 mg/kg per day showed excellent prophylaxis, although they did not inhibit hypertensive development. Imidapril at 0.5 mg/kg per day significantly prevented stroke to almost the same extent as enalapril at 2 mg/kg per day or hydralazine at 5 mg/kg per day. Imidapril dose-dependently suppressed the elevation of the two urinary indexes, which was followed by stroke. Imidapril inhibited enzyme activity in the aorta more strongly than did enalapril at the same dose.

Imidapril prevented the incidence of stroke in stroke-prone spontaneously hypertensive rats at a dose of 0.5 mg/kg per day or more by amelioration of kidney dysfunction. Reduction of blood pressure is not necessary, although enzyme inhibition in the vasculature may partly relate to the effect.
Spatial features of focal infarction after hydralazine treatment in stroke-prone spontaneously hypertensive rats.
Authors: Coyle P , Feng X
Published: June 2011

Rapid occlusion of the middle cerebral artery above the rhinal fissure produces a large ischemic infarct in hypertensive rats, but this occlusion results in a minimal lesion in young normotensive rats. Our purpose was to attenuate rising blood pressure in young stroke-prone spontaneously hypertensive rats with hydralazine before the occlusion to determine if the gross infarct volume is smaller, and if it is, to determine whether length, width, depth, or surface area of the infarct changes, which could suggest a mechanism of protection.

Untreated rats (n = 6) and rats receiving hydralazine for 1.5 (n = 6) or 5 (n = 5) weeks were anesthetized, and the middle cerebral artery was rapidly occluded with a ligature. One day later the rats were killed and the brains were fixed in formalin. Fine-grain-release film that is sensitive to spectral properties of the infarct was used to photograph the tissue. Infarcted areas were traced on paper and then digitized for measurements and computations with a microcomputer.

Compared with untreated rats, tail systolic blood pressure (120 +/- 3 versus 138 +/- 4 mm Hg), infarct volume (61 +/- 4 versus 93 +/- 6 mm3), infarct surface area (39 +/- 1 versus 54 +/- 2 mm2), infarct width (3.8 +/- 0.1 versus 4.8 +/- 0.2 mm), and infarct length (6.0 +/- 0.3 versus 8.1 +/- 0.3 mm) were less in rats receiving hydralazine for 5 weeks (p < 0.05). No change was detected in infarct depth.

Treatment of young stroke-prone spontaneously hypertensive rats with hydralazine for 5 weeks before middle cerebral artery occlusion results in a smaller infarct. The narrower, shorter dimensions indicate increased protection against lateral enlargement of the infarct and the possibility that protection was due to increased collateral blood flow through modified blood vessels.
A new approach to the integrity of dual blood-brain barrier functions of global ischemic rats. Barrier and carrier functions.
Authors: Yoshizumi H , Fujibayashi Y , Kikuchi H
Published: June 2011

We studied the influence of reperfusion on carrier and barrier functions of the blood-brain barrier after transient global ischemia in rats.

We used iodine-125-labeled 3-iodo-alpha-methyl-L-tyrosine and carbon-14-labeled sucrose as tracers for studying carrier and barrier functions of the blood-brain barrier, respectively. Brain uptakes of these two tracers were measured in Wistar rats subjected to either 15- or 30-minute four-vessel occlusion developed by Pulsinelli and Brierly before recirculation for 3, 6, 24, 48, and 72 hours. Tracer (5 microCi) was injected intravenously in each rat 30 minutes before killing the animal.

Following 15- or 30-minute ischemia, [14C]sucrose uptakes were significantly higher at 3 and 6 hours of reperfusion before recovery to control values after reperfusing for 24 to 48 hours in almost all brain regions. However, a rebound in radioligand uptake was significantly manifested in some sites at 72 hours after reperfusion (p < 0.05 to p < 0.01). Uptakes of 125I-3-iodo-alpha-methyl-L-tyrosine were brain site-dependent: significantly (p < 0.05) higher in cortex (3 and 48 hours after reperfusion) and thalamus (3, 6, and 48 hours after reperfusion) but significantly (p < 0.05 to p < 0.01) lower in striatum, cortex (72 hours after reperfusion), and midbrain (6, 24, and 72 hours after reperfusion). Because the [14C]sucrose uptake in brain was 10% lower than that of 125I-3-iodo-alpha-methyl-L-tyrosine, the change in absolute transport of the latter tracer was approximated to its brain uptake.

The carrier and barrier functions of the blood-brain barrier should be evaluated separately. The radioligand 125I-3-iodo-alpha-methyl-L-tyrosine may serve as a useful tool to evaluate the carrier function of the blood-brain barrier after transient cerebral ischemia in rats.
Role of transcranial Doppler in neuroradiological treatment of intracranial vasospasm.
Authors: Hurst R W , Schnee C , Raps E C , Farber R , Flamm E S
Published: June 2011

The expanded role of interventional neuroradiological treatment for post-subarachnoid hemorrhage vasospasm has highlighted the diagnostic utility of transcranial Doppler studies in this condition. The role of transcranial Doppler in follow-up and determining the need for repeat intervention has not been previously emphasized.

Intracranial angioplasty for clinically evident vasospasm after subarachnoid hemorrhage was performed in four patients. In two patients, transcranial Doppler flow velocities remained elevated despite initial anatomic correction of the vasospasm. Reangiography revealed new areas of involvement by vasospasm. Reangioplasty or papaverine infusion treatment of the new lesions resulted in decreased flow velocities and clinical improvement in all patients.

Transcranial Doppler has a more significant role than has been previously emphasized in the management of patients undergoing interventional neuroradiological treatment for intracranial vasospasm. Specifically, the persistence of elevated transcranial Doppler flow velocities after intracranial angioplasty suggests the need for repeat angiographic evaluation and possibly further therapy.
Does cerebral infarction after a previous warning occur in the same vascular territory?
Authors: Cillessen J P , Kappelle L J , van Swieten J C , Algra A , van Gijn J
Published: June 2011

The aim of this study was to compare the territory of cerebral infarcts on follow-up with that of the preceding transient ischemic attack or nondisabling stroke.

The Dutch TIA Trial was a randomized, double-blind, controlled trial, in which the secondary preventive effects of two doses of aspirin were compared in patients with a transient ischemic attack or nondisabling stroke. On the basis of clinical symptoms and computed tomography, qualifying events were classified as pertaining to the left carotid, right carotid, or vertebrobasilar circulation.

In 2,993 patients the territory of the qualifying event was that of the left carotid in 1,281 (43%), the right carotid in 1,090 (36%), and the vertebrobasilar in 444 (15%); the territory was uncertain in 178 (6%). On follow-up (mean, 2.6 years), 184 of the 2,371 patients with a baseline event in the carotid circulation suffered a recurrent ischemic stroke (7.8%), as did 28 of the 444 patients in the vertebrobasilar group (6.3%); 117 of these 212 infarcts (55%; 95% confidence interval, 49-62) occurred in the same territory (108 in the ipsilateral carotid and nine in the vertebrobasilar territory) as the event at baseline, compared with 39% to be expected by chance alone (95% confidence interval, 32-45). In the carotid groups patients were significantly more likely to have a subsequent ischemic event in the same territory as at entry than patients in the vertebrobasilar group (relative risk, 1.8; 95% confidence interval, 1.1-3.2). The average interval between the qualifying event and the subsequent stroke was significantly shorter (mean, 167 days; 95% confidence interval, 77-257) if the vascular territory was the same.

These results suggest that single artery disease accounts for at most one half of the strokes on follow-up, relatively more often in the carotid territory, and that recurrent strokes from the same arterial lesion occur sooner than strokes associated with other lesions.
Lupus anticoagulant and the fibrinolytic system in young patients with stroke.
Authors: Ferro D , Quintarelli C , Rasura M , Antonini G , Violi F
Published: June 2011

Our purpose was to assess the presence of lupus anticoagulant and fibrinolytic system abnormalities in young patients with stroke.

We studied 33 consecutive ischemic patients aged < 50 years. Lupus anticoagulant was screened by four different coagulation tests, and the fibrinolytic system was studied by analyzing tissue plasminogen activator antigen and plasminogen activator inhibitor activity.

Six patients (18%), two of whom were affected by systemic lupus erythematosus, had lupus anticoagulant. Plasminogen activator inhibitor activity was significantly higher in those positive for lupus anticoagulant than in those negative for lupus anticoagulant and control subjects (p < 0.001).

In young patients with stroke, lupus anticoagulant is associated with an imbalance of the fibrinolytic system as a result of higher levels of plasminogen activator inhibitor.
Sustained decrease in brain regional blood flow after microsphere embolism in rats.
Authors: Miyake K , Takeo S , Kaijihara H
Published: June 2011

An experimental model that induces sustained ischemia and infarction may provide useful information relevant to prevention of the development of ischemic brain disease. The purpose of the present study was to elucidate the pathophysiological consequences of cerebral blood flow under sustained cerebral ischemia or oligemia and infarction in rats after microsphere embolism.

We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 146 rats and determined the time course of changes in blood flow of the cerebral cortex, striatum, and hippocampus of both hemispheres by the hydrogen clearance method for a period of 28 days after the operation. Infarct area was determined by triphenyltetrazolium chloride staining and hematoxylin and eosin staining methods.

Cortical and striatal blood flow of the right hemisphere of microsphere-injected rats was significantly decreased after the embolism, and this was sustained throughout the experiment. Hippocampal blood flow of the microsphere-injected hemisphere was also decreased on days 1 and 3 but tended to return toward control levels thereafter. In the left hemisphere, reduction in regional blood flow was detected in the cortex and hippocampus on day 1 and the striatum on day 3. A triphenyltetrazolium chloride-unstained area had developed by day 3 after the embolism. The extent of the area was similar to that on days 7 and 28. Microscopic examination revealed degenerative areas scattered mainly in the parietotemporal cortex, corpus callosum, hippocampus, thalamus, and lenticular nucleus of the embolized hemisphere, demonstrating the induction of widespread necrosis after embolism.

Microsphere embolism resulted in a sustained decrease in regional blood flow and production of cerebral infarction in the brain regions of the microsphere-injected hemisphere.
Dynamic computed tomographic imaging of regional cerebral blood flow and blood volume. A clinical pilot study.
Authors: Steiger H J , Aaslid R , Stooss R
Published: June 2011

The advent of faster computed tomography scanners has evoked considerable interest in using this technology as a more practical method of regional cerebral hemodynamic evaluation than the currently available positron emission and single-photon emission computed tomography. The theoretical concepts have been worked out and validated in the laboratory by several groups. The aim of the present study was the development of a clinically useful system.

Software was developed for dynamic computed tomography-based calculation and color-coded representation of regional cerebral blood flow and blood volume. Normal values, reproducibility, and sensitivity to acetazolamide challenge were established in 13 volunteers. The method was applied to an additional three patients with internal carotid artery occlusion and known decreased vascular reserve capacity as diagnosed by transcranial Doppler ultrasonography.

Normal regional cerebral blood flow was determined as 50 +/- 13 ml/100 ml per minute and normal fractional cerebral blood volume as 58 +/- 12 ml/1,000 ml (mean +/- SD). In five volunteers, two examinations were performed within 15 minutes for determination of reproducibility. Intermeasurement variability of hemispheric blood flow and blood volume was determined as +/- 23% and +/- 16%, respectively. Intravenous administration of 1 g acetazolamide resulted on the average in a 75% increase of blood flow and a 65% increase of fractional blood volume. In the patients with decreased cerebrovascular reserve capacity, baseline fractional blood volume in the ischemic hemispheres was significantly increased. Baseline regional cerebral blood flow in the ischemic territories was overestimated. Reactivity to acetazolamide of both regional blood flow and fractional blood volume was clearly reduced in the ischemic hemispheres.

The present results demonstrate that the method is a simple and effective means of determining regional cerebral blood volume. Spatial resolution is superior to that of the radioactive tracer methods. Hemodynamic evaluation of ischemic conditions can be performed on the basis of increased resting cerebral blood volume and a diminished increase after acetazolamide. Accuracy of cerebral blood flow measurements, on the other hand, is affected by abnormal cerebral blood volume, and corresponding adjustments need to be made in pathological conditions.
Expression of thrombomodulin in patients with spontaneous occlusion of the circle of Willis.
Authors: Ikeda E , Maruyama I , Hosoda Y
Published: June 2011

We examined the expression of thrombomodulin, a recently isolated anticoagulant protein, in endothelial cells from patients with spontaneous occlusion of the circle of Willis (cerebrovascular moyamoya disease) to determine whether lack of the expression of thrombomodulin might lead to the thrombogenicity in patients with this disease.

The intracranial internal carotid arteries, the external carotid arteries, and the vertebral or basilar arteries from 12 autopsied patients who had this disease and eight control autopsied patients were examined immunohistochemically by using the antiserum against human thrombomodulin.

All of the endothelial cells from the patients with this disease and from the control patients were positive for thrombomodulin. Immunoelectron microscopy also disclosed normal localization of thrombomodulin on the luminal plasma membrane. Immunohistochemically, we could find no significant differences in the expression of thrombomodulin among the arteries examined in this study.

We conclude that as far as we investigated immunohistochemically, the thrombogenicity in this disease is almost unlikely to depend on the abnormal expression of thrombomodulin.
Contrast-enhanced transcranial color-coded real-time sonography. Results of a phase-two study.
Authors: Bogdahn U , Becker G , Schlief R , Reddig J , Hassel W
Published: June 2011

Transcranial color-coded real-time sonography has been developed as a promising new bedside procedure to monitor central nervous system parenchymal and vascular pathology; the present study was designed to investigate the potential role of galactose microparticles (SH U 508 A) as a new ultrasound contrast-enhancing agent for transcranial sonography.

Ten patients (four women and six men, 24-63 years of age) with a broad spectrum of central nervous system pathology were investigated by transcranial color-coded real-time sonography in a phase-two clinical study. After conventional ultrasound examination, all patients received a maximum of six injections of 10 ml with 200, 300, or 400 mg/mL SH U 508 A. The intracranial vessels were scanned by color flow imaging in the axial and coronal planes through a transtemporal acoustic bone window; in addition, the vertebrobasilar system was followed through the foramen magnum.

SH U 508 A was well tolerated without side effects. In axial and coronal scans, the application of SH U 508 A resulted in detection of peripheral branches of the anterior, middle, and posterior cerebral arteries, as well as the posterior communicating and superior cerebellar arteries. In addition, the deep cerebral veins (i.e., inferior sagittal sinus, internal cerebral veins, great cerebral vein of Galen, straight sinus, and the confluence sinuum) were revealed. The transforaminal approach led to detection of the main infratentorial branches (anterior inferior, posterior inferior, and superior cerebellar arteries). One patient could not be insonated without contrast, but after SH U 508 A the trunks of the large intracranial arteries were detected. No obvious changes in the ultrasound pattern of the central nervous system parenchyma were observed.

These preliminary data indicate that the use of a transpulmonary ultrasound contrast agent (SH U 508 A) may substantially broaden the spectrum and potential diagnostic utility of transcranial ultrasound by allowing detection of supratentorial peripheral central nervous system arteries, deep cerebral veins, and (through the foramen magnum) the entire vertebrobasilar system, including the cerebellar arteries.
Cardiovascular changes during focal cerebral ischemia in rats.
Authors: Perez-Trepichio A D , Williams J L , Block C H , Jones S C
Published: June 2011

Recent studies have suggested that cerebral infarction influences autonomic activity and may contribute to sudden death. The goal of this study was to examine effects of focal cerebral infarction on mean arterial pressure and heart rate.

Halothane-anesthetized rats were assigned to two groups: stroke (n = 10), in which the middle cerebral artery or an adjacent vessel was embolized with a silicone cylinder, and sham (n = 8), in which rats were sham embolized (saline). Arterial pressure and heart rate were measured for 90 minutes and again 24 hours after vascular occlusion. A change in electroencephalographic amplitude of -45% after embolization was used to determine if a significant degree of infarction was present.

Vascular occlusion produced a significant increase in mean arterial pressure at 10, 60, and 90 minutes (p < 0.05). Changes in heart rate were significantly greater (p < 0.05) than in sham-treated rats at 10 and 30 minutes after embolization. In contrast, mean arterial pressure and heart rate measured 24 hours after embolization were similar in both groups. Anatomic analysis of the infarcted areas demonstrated that either insular cortex or amygdala was affected in all embolized rats.

This study indicates that cerebral infarction produces a transient elevation of mean arterial pressure and heart rate. However, within 24 hours both parameters returned to preinfarcted levels. Our findings are consistent with clinical reports that indicate that mean arterial pressure and heart rate of stroke patients are similar to those of other groups when they are admitted to the hospital, although other cardiovascular parameters are greatly altered.
Protective efficacy of a hypothermic pharmacological agent in gerbil forebrain ischemia.
Authors: Hall E D , Andrus P K , Pazara K E
Published: June 2011

The novel muscarinic cholinergic partial agonist U-80816E was tested in the gerbil brief bilateral carotid occlusion ischemia model based on the rationale that the compound's hypothermic properties might afford effective protection of the selectively vulnerable hippocampal CA1 region.

Male gerbils were subjected to either 10 or 15 minutes of bilateral carotid occlusion, followed by histopathological assessment of the CA1 neuronal survival 7 days later.

In saline-treated animals, 10 minutes of bilateral carotid occlusion resulted in a 30.5% loss of CA1 neurons, whereas a 15-minute insult resulted in a 49.6% loss. Administration of U-80816E (6 mg/kg i.p. 30 minutes before bilateral carotid occlusion and again 2 hours after reperfusion) resulted in a significant protective effect of the CA1 neuronal population with either duration of ischemia; neuronal loss was reduced to 12.6% in the milder model (p < 0.05 versus saline-treated) and 24.9% in the more severe model (p < 0.04 versus saline). However, the 6 mg/kg i.p. dose of U-80816E was found to produce a 1.0 degree C decrease in brain temperature (measured with a tympanic temperature probe) at 10 minutes of ischemia compared with that of saline-treated gerbils. At 10 minutes of reperfusion, after the 10-minute episode of ischemia, the brain temperature of the U-80816E-treated gerbils was 2.2 degrees C lower than that of saline-treated animals. When the U-80816E-treated gerbils were subjected to either 10 or 15 minutes of ischemia but placed in a heated chamber that prevented the hypothermic effects, no cerebroprotection was observed.

These results show that the anti-ischemic efficacy of U-80816E is mediated through its hypothermic properties, thus suggesting the feasibility of pharmacologically induced hypothermia as a cerebroprotective approach.
The antioxidant LY231617 reduces global ischemic neuronal injury in rats.
Authors: Clemens J A , Saunders R D , Ho P P , Phebus L A , Panetta J A
Published: June 2011

In the rat four-vessel occlusion model with 30 minutes of ischemia most agents have failed to be of benefit when given after ischemia. Because postischemia administration is more clinically relevant, we evaluated the antioxidant LY231617 (2,6-bis(1,1-dimethylethyl)-4-[[(1-ethyl)amino]methyl]phenol hydrochloride]) when administered after 30 minutes of four-vessel occlusion.

Male Wistar rats were subjected to 30 minutes of four-vessel occlusion. LY231617 was either given orally 30 minutes before ischemia or intravenously beginning at 30 minutes after the onset of ischemia. Hippocampal CA1 layer and striatal damage were rated on a scale of 0-3 (0, no damage; 3, > 90% cell loss). We also evaluated the ability of LY231617 to prevent iron-dependent lipid peroxidation and to prevent hydrogen peroxide-induced neuronal death of hippocampal neurons in primary culture by exposing cultures to a 50-microM concentration of hydrogen peroxide for 15 minutes in the presence of LY231617.

Oral administration of LY231617 reduced both striatal and hippocampal CA1 damage by > 75% (p < 0.0001). In two separate experiments in which LY231617 was given intravenously beginning 30 minutes after occlusion, hippocampal and striatal damage were reduced by approximately 50% (p < 0.03) in the first experiment and by approximately 41% (p < 0.02) in the second experiment. Addition of 5 microM of LY231617 to primary hippocampal neuronal cultures antagonized the lethal effect of hydrogen peroxide (p < 0.05). Iron-dependent lipid peroxidation was also inhibited in a dose-related fashion.

The significant reduction of ischemia-induced or hydrogen peroxide-induced neuronal damage and inhibition of lipid peroxidation by LY231617 observed in this study suggest that reactive oxygen intermediates play an important role in the events leading to neuronal death after global ischemia/reperfusion.
Geographic variation in the incidence of nonfatal stroke in Finland. Are the observed differences real? FINMONICA Stroke Register Study Group.
Authors: Sarti C
Published: June 2011

We sought to find an explanation for the geographical variation in the incidence of nonfatal stroke detected in the FINMONICA stroke register during the period 1983-1985.

Two separate investigations were made. In the first, a sample of approximately 100 nonfatal events drawn from each of the three monitoring areas (North Karelia, Kuopio, and Turku/Loimaa) participating in FINMONICA was recoded by an independent coder. In the second, 29 nonfatal events from Kuopio and 29 from North Karelia were recorded by the neurologist of the other area. Kappa coefficients (kappa) were calculated to measure the proportion of agreement beyond chance among the different coders.

A good level of agreement with the independent coder was found for each of the three areas; it was best for the cases from Turku/Loimaa (kappa = 0.896), followed by Kuopio (kappa = 0.792) and North Karelia (kappa = 0.616). In the second part of the investigation, agreement was higher for the stroke cases originating from Kuopio (kappa = 0.861) than for those from North Karelia (kappa = 0.563). In the latter there was discrepancy in the classification of the cases originally classified as no stroke.

The results from the first part of the investigation suggest that the lower incidence of nonfatal stroke in Turku/Loimaa was real, confirming findings in previous studies. Differences in data entry, rather than in the interpretation of signs and symptoms of stroke, were the main cause of disagreement in the second part of the investigation, where the disagreement primarily concerned the cases classified as no stroke in North Karelia. The results also indicate that the different proportions of patients submitted to computerized brain tomography conceivably account for a good part of the difference in the incidence rates of nonfatal stroke between Kuopio and North Karelia.