bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive detection of vertebral artery dissection.
Authors: Hoffmann M , Sacco R L , Chan S , Mohr J P
Published: June 2011

We sought to identify the use of duplex and transcranial Doppler sonography in the noninvasive diagnosis of vertebral dissection.

Ten patients with a diagnosis of symptomatic vertebral artery dissection confirmed by cerebral angiography were retrospectively analyzed.

Computed tomographic scanning and magnetic resonance imaging together delineated lateral medullary or cerebellar infarcts in 7 patients. Angiography documented a total of 21 vertebral artery lesions (16 stenoses and 5 occlusions), with 7 of 10 patients having multiple sites of vertebral artery dissection. Vertebral Doppler was abnormal in 8 of the 10 patients. A high resistance signal in the relevant vertebral artery was found in 6 patients, no flow in a well-imaged vertebral artery in 1, and bilateral retrograde vertebral artery flow in 1 patient. Transcranial Doppler was abnormal in only 2 patients, with reduced pulsatility index in 1 and high resistance vertebral signal in another. A hyperintense intramural signal of the affected vertebral artery by magnetic resonance imaging was documented in 1 patient in whom Doppler sonography was nondiagnostic.

Vertebral artery dissection can be detected and monitored by noninvasive vertebral Doppler and magnetic resonance imaging in the setting of a clinically suggestive presentation.
Thromboxane antagonism in experimental canine carotid artery thrombosis.
Authors: Rote W E , Mu D X , Lucchesi B R
Published: June 2011

The two objectives of this study were to assess the potential of BAY U 3405 to prevent arterial thrombosis in response to vessel wall injury and to determine the ability of BAY U 3405 to prevent thrombotic reocclusion after thrombolysis with anisoylated plasminogen streptokinase activator complex.

Dogs were instrumented with a carotid flow probe, stimulating electrode, and a stenosis. Current (150 microA) was applied to the intimal surface of the right carotid artery, and time to occlusive thrombus formation was noted. BAY U 3405 was administered, and the procedure for thrombus formation was repeated for the left carotid artery.

BAY U 3405 administration prevented occlusive arterial thrombosis formation. Ex vivo platelet aggregation was inhibited, bleeding time increased, and thrombus weight reduced after BAY U 3405 treatment. In a second group, thrombi were formed initially in both carotid arteries, BAY U 3405 was administered as before, and anisoylated plasminogen streptokinase activator complex was infused in the right carotid artery proximal to the occlusive thrombus. BAY U 3405 did not alter the incidence of rethrombosis compared with the lytic agent alone.

BAY U 3405 prevented primary arterial thrombosis, corresponding to inhibition of platelet aggregation, and increased bleeding times. BAY U 3405, however, did not prevent rethrombosis after successful thrombolysis with anisoylated plasminogen streptokinase activator complex, despite the fact that platelet reactivity was inhibited. The data are consistent with the concept that the residual thrombus represents a more effective thrombogenic stimulus as compared with arterial wall injury alone and that the mechanisms associated with primary versus secondary thrombus formation may require separate therapeutic approaches.
Oxyhemoglobin-induced cytotoxicity and arachidonic acid release in cultured bovine endothelial cells.
Authors: Takenaka K , Kassell N F , Foley P L , Lee K S
Published: June 2011

An impairment of endothelial function is associated with vasospasm after subarachnoid hemorrhage. Oxyhemoglobin is considered to be a critical trigger in the pathogenesis of vasospasm. The present studies examined the direct effects of oxyhemoglobin on cultured endothelial cells from bovine carotid artery.

Confluent endothelial cells were treated with oxyhemoglobin, and the following were studied: 1) cell morphology, 2) cell density, and 3) the release of radiolabel from [3H]arachidonic acid-treated cells.

Endothelial cells exposed to oxyhemoglobin exhibited detachment vacuoles, and cell density was significantly decreased in time- and dose-dependent manners. Superoxide dismutase, a free radical scavenger, provided partial protection against the cytotoxic effects of oxyhemoglobin. The release of radiolabel from [3H]arachidonic acid-treated cells was increased by oxyhemoglobin in time- and dose-dependent manners. Treatment with an inhibitor of phospholipase A2 or a calcium chelator inhibited the effects of oxyhemoglobin on arachidonic acid release and cellular viability.

Oxyhemoglobin exerts a direct cytotoxic effect on cultured endothelial cells, and this effect is associated with increased release from [3H]arachidonic acid-labeled cells. Phospholipase A2 and free radicals appear to participate in the pathogenesis of endothelial cell damage. Oxyhemoglobin-induced compromise of endothelial cells may contribute to cerebrovascular pathology.
The effect of a new calcium antagonist, TA3090 (clentiazem), on experimental transient focal cerebral ischemia in cats.
Authors: Sakaki T , Tsujimoto S , Sasaoka Y , Tsunoda S , Shintomi K
Published: June 2011

TA3090 (Clentiazem) has been shown to have cerebrovascular protective properties in three experimental studies. An in vivo investigation was undertaken to determine its effects on pial arteries and cerebral blood flow and its therapeutic value in transient focal cerebral ischemia.

This experiment was divided into two protocols. In the first, 200 or 400 micrograms/kg per hour TA3090 was administered continuously for 3 hours in cats without ischemic insult (n = 6 for each group). The effects on pial arteries and cerebral blood flow were estimated. In the second protocol, 400 micrograms/kg per hour TA3090 (treated group, n = 14) or physiological saline (control group, n = 10) was administered 5 minutes before 1 hour of middle cerebral artery occlusion in cats. The effects on the pial arteries and cerebral blood flow were observed continuously, followed by autoradiography for a quantitative measurement of cerebral blood flow 5 hours after middle cerebral artery recirculation. The volumes of the cerebral edema and infarct were estimated by planimetry from cerebral preparations made for histological examination.

Pial arteries dilated by up to approximately 10% in the 400-micrograms group and 3% in the 200-micrograms group 30 minutes after administration of TA3090. Increases in cerebral blood flow of about 10% in the 400-micrograms group and 2% in the 200-micrograms group were demonstrated with laser Doppler flowmetry. In the second protocol, dilatation of pial arteries was significantly smaller during and after the ischemic insult in the treated group compared with the control group (p < 0.01). Cerebral blood flow decreased less significantly during ischemia (p < 0.01 at the end of ischemia) and increased less significantly after ischemia (p < 0.01 at the end) in the treated group compared with the control group. Autoradiography showed a more remarkable increase in cerebral blood flow due to luxury perfusion in the cerebral cortex, which was mainly perfused by the middle cerebral artery on the affected side in the control group (p < 0.01). Cerebral blood flow in the cerebral cortex, thalamus, and caudate nucleus on the contralateral side of the treated group increased by about 20% more than that of the control group (p < 0.05). Cerebral edema and infarction were much smaller in the treated group than in the control group (p < 0.01).

1) TA3090 dilates pial arteries and increases cerebral blood flow in normal brain regions in a dose-response fashion; 2) in ischemic regions compared with those in untreated animals, TA3090 results in a lesser reduction of cerebral blood flow during ischemia and in a lesser degree of hyperemia during reperfusion; 3) TA3090 is associated with less pial artery dilatation during ischemia, presumably due to improved collateral flow; and 4) the improved hemodynamic state with TA3090 is associated with significant reduction of cerebral edema and infarct size.
Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group.
Authors: Haley E C , Brott T G , Sheppard G L , Barsan W , Broderick J , Marler J R , Kongable G L , Spilker J , Massey S , Hansen C A
Published: June 2011

Early thrombolytic therapy with recombinant tissue-type plasminogen activator is a theoretically attractive approach to the treatment of acute focal cerebral ischemia. In preparation for a larger multicenter trial, three centers piloted a protocol for a randomized, double-blind, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator begun within 3 hours of the onset of symptoms of acute stroke to test its feasibility and to explore trends.

Eligible patients had pretreatment computed tomographic scanning, gave informed consent, and began treatment with either 0.85 mg/kg recombinant tissue-type plasminogen activator or placebo as soon as possible, but no later than 180 minutes after stroke onset. Patients were stratified by whether treatment was begun within 90 minutes or 91 to 180 minutes from onset. The primary end point was the proportion of patients in each group who improved by 4 or more points on the National Institutes of Health Stroke Scale at 24 hours, as determined by a separate blinded evaluator.

Twenty-seven patients were randomized: 20 (10 recombinant tissue-type plasminogen activator, 10 placebo) within 90 minutes, and 7 (4 recombinant tissue-type plasminogen activator, 3 placebo) from 91 to 180 minutes. Median baseline Stroke Scale scores were 16 (minimum = 5, maximum = 26) for the recombinant tissue-type plasminogen activator-treated group and 11 (minimum = 3, maximum = 21) for the control subjects in the group treated within 90 minutes. Six patients treated with recombinant tissue-type plasminogen activator within 90 minutes improved by 4 or more points at 24 hours compared with 1 patient in the placebo group (P < .05, Fisher's Exact Test). Two patients in each group in the 91- to 180-minute arm improved. One fatal intracerebral hemorrhage occurred in the placebo group.

A randomized, double-blind, placebo-controlled trial of recombinant tissue-type plasminogen activator very early in acute stroke is feasible. Preliminary observations suggest that recombinant tissue-type plasminogen activator treatment within 90 minutes may be associated with early neurological improvement. Larger studies are needed so that the potentially serious short-term risks of this treatment can be assessed in relation to meaningful long-term benefit.
Unilateral amnesic stroke. Six new cases and a review of the literature.
Authors: Ott B R , Saver J L
Published: June 2011

Although persistent amnesia due to bilateral limbic system infarction is well described, reports of amnesic syndromes due to unilateral stroke have appeared infrequently and unsystematically. We report six new cases and review previously published reports to expand and consolidate knowledge regarding amnesic stroke.

Six patients developed acute amnesia associated with unilateral stroke. Brain computed tomography or magnetic resonance imaging revealed lesions in limbic structures, which accounted for the memory deficit. Based on these as well as similar cases in the literature, we delineate three distinct syndromes of unilateral amnesic stroke involving the territories of the posterior cerebral, anterior choroidal, and thalamic penetrating arteries. Eighty-five percent of reported cases have involved the left hemisphere.

Persistent as well as transient amnesia may be the sole or primary manifestation of unilateral hemispheric stroke. The vascular mechanisms of amnesic stroke are diverse. Patients presenting with acute amnesia possibly related to cerebral ischemia should be classified by documented or presumed lesion site as well as the involved vascular territory. Left amygdalohippocampal or diencephalic dysfunction may produce a particular vulnerability to global amnesia.
Regional differences in the vasodilator response to vasopressin in canine cerebral arteries in vivo.
Authors: Suzuki Y , Satoh S , Oyama H , Takayasu M , Shibuya M
Published: June 2011

The aim of this study was to investigate the regional differences in the in vivo vasodilator responses to vasopressin, which is thought to stimulate the release of nitric oxide from the endothelium, in canine cerebral arteries by angiography.

Angiograms were performed through a catheter inserted directly into the right vertebral artery and were taken periodically after the infusion of vasopressin. The diameters of various segments of the major arteries were measured using a computerized image analysis system.

The bolus administration of vasopressin (10 pmol to 1 nmol) into the vertebral artery produced a long-lasting, dose-dependent vasodilation in the major cerebral arteries centering around the circle of Willis. One nanomole of vasopressin appeared to be the optimal dose for producing maximal vasodilation. The internal diameters of the basilar, posterior communicating, and internal carotid arteries experienced the most dilation (approximately 150% that of control) 2 minutes after the infusion of 1 nmol of vasopressin, followed by those of the middle cerebral, the intracranial portion of the vertebral, and the anterior spinal arteries (approximately 130% that of control). The extracranial portion of the vertebral artery (109.8 +/- 4.8% that of control, n = 4) was less sensitive to 1 nmol of vasopressin. Pretreatment with an intracisternal injection of 10 mumol of NG-monomethyl L-arginine suppressed the vasodilator effect of vasopressin and substance P, whereas it did not affect the response to vasoactive intestinal peptide.

These results suggest that the arteries composing the circle of Willis at the base of the brain are more sensitive to nitric oxide release induced by vasopressin compared with other intracranial and extracranial arteries.
Major depression in stroke patients. A 3-year longitudinal study.
Authors: Aström M , Adolfsson R , Asplund K
Published: June 2011

This prospective study was designed to examine the contributions of neurobiological, functional, and psychosocial factors to major depression after stroke. In addition, the prevalence and longitudinal course of major depression were studied.

Major depression, functional ability, and social network were assessed repeatedly for a period of 3 years in a population-based cohort of 80 patients with acute stroke (mean age, 73 years). Cerebral atrophy and brain lesion parameters were determined from computed tomographic scans performed acutely and after 3 years.

The prevalence of major depression was 25% at the acute stage and approximately the same at 3 months (31%). It decreased to 16% at 12 months, was 19% at 2 years, and increased to 29% at 3 years. The most important predictors of immediate major depression were left anterior brain lesion, dysphasia, and living alone. Dependence in activities of daily living was the most important predictor at 3 months. From 12 months on, the patient's having few social contacts outside the immediate family contributed most to depression, and at 3 years cerebral atrophy also contributed. At 1 year, 60% of the patients with early depression (0 to 3 months) had recovered; those not recovered at this follow-up had a high risk of development of chronic depression.

The study has provided evidence of a differentiation of factors likely to be implicated in the development of depression after stroke based or the period of time since the stroke event.
Do anger and aggression affect carotid atherosclerosis?
Authors: Matsumoto Y , Uyama O , Shimizu S , Michishita H , Mori R , Owada T , Sugita M
Published: June 2011

Although a number of metabolic and psychosocial factors have been identified as coronary risk factors, no studies have evaluated the relation between personality and cerebrovascular disease. The purpose of the present study was to elucidate the relation between the characteristics of anger or aggression and the severity of carotid atherosclerosis on the basis of the findings of B-mode ultrasonography.

The Cornell Medical Index was used to measure anger in 34 patients with signs of atherosclerosis or at least one of four recognized risk factors for atherosclerosis (hypertension, hypercholesterolemia, diabetes mellitus, and cigarette smoking). The Rosenzweig Picture Frustration Study and Yatabe-Guilford Personality Test were used to evaluate aggression. High-resolution B-mode ultrasonography was performed, and the severity of carotid atherosclerosis was determined by plaque score. The occurrence of risk factors for carotid atherosclerosis was compared among the patients.

The correlation of plaque score with one item that endorses anger was r = .65 (P < .01) and with "extrapersistive" in aggression was r = .50 (P < .01). Multivariate analysis identified significant correlations between plaque score and age, hypercholesterolemia, and anger.

Our results suggest that anger and, perhaps, aggression may be risk factors for cerebrovascular disease.
Regional cerebral blood flow in chronic hypertension. A correlative study.
Authors: Nobili F , Rodriguez G , Marenco S , De Carli F , Gambaro M , Castello C , Pontremoli R , Rosadini G
Published: June 2011

Cerebral hypoperfusion has occasionally been reported during essential hypertension. We explored regional cerebral blood flow in a large series of neurologically asymptomatic hypertensive patients to determine relations among cerebral blood flow, concomitant main vascular risk factors, and the most common signs of end-organ damage.

Regional cerebral blood flow was measured by the 133Xe inhalation method in 101 hypertensive patients without clinically apparent central nervous system involvement, including 39 mild to moderate untreated and 62 mild to severe treated patients.

Compared with age- and sex-matched normal control subjects, cerebral blood flow was significantly reduced in untreated hypertensive patients (P < .01) and to a lesser extent in treated patients (P = .047). Both regional and global cerebral blood flow reductions were observed in approximately one third of patients in both groups. Analysis of variance failed to show significant correlations between cerebral blood flow and total cholesterol concentration, mean arterial blood pressure, duration of disease, or the presence of retinopathy or left ventricular hypertrophy. In the treated group, the quality of control of hypertension significantly influenced both global cerebral blood flow (P = .007) and cerebrovascular resistance (P < .0001).

Focal or diffuse cerebral hypoperfusion is present even in neurologically asymptomatic hypertensive patients, especially when untreated; good control of blood pressure may preserve cerebral perfusion and reduce cerebrovascular resistance. Regional cerebral blood flow examination represents a relatively simple and low-cost technique to explore the perfusional condition of the brain, one of the main target organs of hypertensive disease.
Cerebral blood flow velocity and systemic vascular resistance after acute reduction of low-density lipoprotein in familial hypercholesterolemia.
Authors: Rubba P , Faccenda F , Di Somma S , Gnasso A , Scarpato N , Iannuzzi A , Nappi G , Postiglione A , De Divitiis O , Mancini M
Published: June 2011

Low-density lipoprotein apheresis is currently used for the treatment of familial hypercholesterolemia, an inherited disorder of metabolism associated with premature development of cardiovascular disease. We wanted to evaluate cerebral blood flow velocity, cardiac output, and systemic vascular resistance in patients with familial hypercholesterolemia before and after low-density lipoprotein apheresis.

Ten patients (age range, 14 to 46 years; 4 males, 6 females) with familial hypercholesterolemia (8 homozygotes, 2 heterozygotes) and 10 healthy control subjects of comparable age and sex distribution participated in the study. Low-density lipoprotein apheresis by dextran sulfate was performed in 8 patients (7 homozygotes, 1 heterozygote). Six patients (4 homozygotes, 2 heterozygotes) underwent a procedure of extracorporeal erythrocyte filtration with the same extracorporeal volume as for low-density lipoprotein apheresis, but with the exclusion of the passage of plasma through the dextran sulfate column. Cerebral blood flow velocity (transcranial Doppler), cardiac output, and systemic vascular resistance (electric bioimpedance cardiography) were determined by noninvasive techniques before and 1 day and 7 days after low-density lipoprotein apheresis or extracorporeal erythrocyte filtration. Plasma and blood viscosities were measured at the same time.

Before apheresis, mean and diastolic cerebral flow velocities were abnormally low in hypercholesterolemic patients (P < .01 and P < .02 vs healthy control subjects, respectively). After apheresis, low-density lipoprotein cholesterol was lowered by 40% to 60% from baseline, and cerebral blood flow velocities (mean, systolic, and diastolic velocities) were increased (P < .01). Cardiac output, systemic vascular resistance, and viscosity values were not significantly modified. Extracorporeal erythrocyte filtration (without passage of plasma through the dextran sulfate column) did not modify serum lipids, hemodynamic parameters, or viscosity values.

Low-density lipoprotein apheresis produces potentially useful hemodynamic effects. They are not adequately explained by changes in blood viscosity alone and might reflect a restoration of endothelium-mediated vasodilation, which is inhibited by high concentrations of low-density lipoprotein.
Brain stem infarction and diaschisis. A SPECT cerebral perfusion study.
Authors: Fazekas F , Payer F , Valetitsch H , Schmidt R , Flooh E
Published: June 2011

We studied six patients suffering from pure, unilateral brain stem infarction to explore the association of remote cerebral and cerebellar blood flow changes with damage at different sites of this region of the brain.

We used single-photon emission computed tomography and [123I]iodoamphetamine to measure regional differences in tracer uptake. Qualitative image analysis and calculated asymmetry indexes were correlated to the location of the infarcted area on magnetic resonance imaging and to the patients' clinical findings.

Significant perfusion asymmetries were noted in the two patients with infarction in the upper pons but not in those with lesions below this level. They comprised a contralateral cerebellar and ipsilateral supratentorial hypoactivity that was most marked in the frontoparietal cortex. There was no clear relation between the patterns of cerebral or cerebellar tracer uptake and specific neurological findings.

Remote perfusion changes after pure brain stem infarction may be seen both infratentorially and supratentorially and depend on the lesion site rather than on the neurological deficit. In this context, our study confirmed damage to the corticopontocerebellar pathways as the key event in the genesis of a crossed cerebellar diaschisis. The exact mechanisms causing ipsilateral cerebral hemispheric diaschisis await further clarification.
Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine and its redistribution in ischemic cerebrovascular disease.
Authors: Odano I , Tsuchiya T , Nishihara M , Sakai K , Abe H , Tanaka R
Published: June 2011

The relation between the redistribution phenomenon and regional cerebral blood flow and its clinical significance were investigated in stroke patients.

Single-photon emission computed tomography studies using N-isopropyl-p-[123I]iodoamphetamine were performed on 16 patients (26 to 77 years old) with chronic infarction and 10 age-matched normal control subjects. Regional cerebral blood flow was quantitatively measured by a microsphere model, and the redistribution on delayed images was analyzed in ischemic lesions.

Supratentorial mean cerebral blood flow and the ratio of gray matter to white matter in normal subjects were 52.7 +/- 5.0 mL/100 g per minute and 2.34, respectively. Low-activity areas of ischemic lesions on early images were classified into two abnormal zones, an infarct area and a peri-infarct area. These regions were characterized by regional blood flow averaging 9 to 20 mL/100 g per minute and 22 to 41 mL/100 g per minute, respectively. Redistribution, which was minimally present in the infarct area, was markedly enhanced in the peri-infarct area. After bypass surgery, we observed a significant increase of blood flow (+22%) in the peri-infarct area.

The data indicate that the redistribution phenomenon depends on the maintenance of a minimal blood flow that would sustain cellular function and that this phenomenon is useful to evaluate bypass surgery in patients with chronic infarction.
Value of single-photon emission-computed tomography in acute stroke therapeutic trials.
Authors: Hanson S K , Grotta J C , Rhoades H , Tran H D , Lamki L M , Barron B J , Taylor W J
Published: June 2011

New therapeutic interventions for acute ischemic stroke are aimed at improving cerebral blood flow in the first 3 to 6 hours after symptom onset. Single-photon emission-computed tomography (SPECT) performed in the setting of clinical therapeutic trials may give us a better understanding of the physiological response to new forms of treatment and could impact acute management decisions.

We prospectively studied 15 patients with hemispheric ischemic stroke with SPECT within 6 hours of symptom onset and again at 24 hours. The ischemic defect was assessed in a semiquantitative manner that used computer-generated regions of interest (SPECT graded scale). This measure was correlated with clinical presentation (National Institutes of Health [NIH] Stroke Scale), initial clinical course (change in NIH Stroke Scale), long-term outcome (Barthel Index at 3 months), and complications of cerebral hemorrhage and edema.

The severity of the SPECT graded scale on the admission scan correlated with the severity of neurological deficit (admission NIH Stroke Scale) (P < .05) and was positively associated with poor long-term outcome as measured with the Barthel Index (P < .001) and the complications of cerebral hemorrhage and massive cerebral edema (P < .005). In fact, there was a threshold value for the SPECT graded scale above which all patients suffered poor long-term outcome and the complications of cerebral hemorrhage and edema.

The measurement of an ischemic defect using SPECT is a valid assessment of hemispheric stroke severity in the hyperacute setting and may be useful for selecting or stratifying patients in clinical therapeutic trials.
Pathogenesis of subcortical hyperintense lesions on magnetic resonance imaging of the brain. Observations in patients undergoing controlled therapeutic internal carotid artery occlusion.
Authors: Awad I A , Masaryk T , Magdinec M
Published: June 2011

Factors associated with the pathogenesis of subcortical hyperintense lesions on magnetic resonance imaging of the brain are not known. We describe four cases of de novo genesis of subcortical hyperintense lesions in patients undergoing controlled therapeutic internal carotid artery occlusion, and we speculate on associated pathophysiological mechanisms.

Twelve consecutive patients underwent controlled therapeutic internal carotid artery occlusion for symptomatic giant cerebral aneurysm using the detachable balloon technique under full anticoagulation. Preocclusion (within 2 weeks) and postocclusion (within 6 weeks) magnetic resonance imaging of the brain was performed in eight cases and evaluated for preexisting and new appearance of subcortical hyperintense lesions.

There were four instances of de novo genesis of subcortical hyperintense lesions after carotid occlusion. New subcortical hyperintense lesions were ipsilateral to carotid occlusion in every instance and in two cases were associated with ipsilateral hemispheric ischemic symptoms despite anticoagulant therapy. In one instance, there were transient hemispheric symptoms without the appearance of new subcortical hyperintense lesions. Age, vascular risk factors, and preexisting subcortical hyperintense lesions did not appear to predispose patients to de novo genesis of new hyperintensities.

This is the first documentation of de novo genesis of subcortical hyperintense lesions in a controlled setting of hemodynamic ischemic insult. Symptomatic and asymptomatic lesions can be detected in this setting. Anticoagulation does not appear to provide protection from this phenomenon. Careful prospective studies are required to further evaluate risk factors and possible clinical consequences associated with the genesis of new subcortical hyperintense lesions.
Decrease in cerebral blood flow with blood pressure reductions in patients with chronic stroke.
Authors: Mori S , Sadoshima S , Fujii K , Ibayashi S , Iino K , Fujishima M
Published: June 2011

Possible effects of changes in blood pressure on the cerebral circulation were studied in patients with chronic stroke and age-matched nonstroke control subjects at 28 +/- 10 months (mean +/- SD) (range, 18 to 54 months) and 27 +/- 6 months (range, 19 to 44 months), respectively, after the first measurement.

Cerebral blood flow was measured by the 133Xe inhalation method in 55 patients (mean +/- SD age, 62 +/- 11 years; 39 with brain infarction and 16 with hemorrhage) and 10 control subjects (mean +/- SD age, 61 +/- 9 years). Correlations between changes in cerebral blood flow and blood pressure were evaluated.

Among brain infarctions, average cerebral blood flow did not change from the first study; however, changes in cerebral blood flow in each individual were closely related to changes in systolic and mean arterial blood pressures (P < .01 and P < .05, respectively). Of these, in 10 patients with cerebral blood flow decreased more than 15% from the initial levels, systolic and mean arterial blood pressures decreased by 25 +/- 32 mm Hg and 16 +/- 14 mm Hg (P < .05 and P < .005, respectively). In contrast, in 29 patients with unchanged or increased cerebral blood flow, changes in systolic (0 +/- 19 or -2 +/- 12 mm Hg, respectively) and mean arterial blood pressures (3 +/- 22 or -1 +/- 11 mm Hg, respectively) were not significant, and their systolic blood pressure levels were maintained above 110 mm Hg.

Blood pressure importantly correlates with cerebral circulatory changes among patients with chronic brain infarction. Early detection of cerebral hemodynamic changes should be useful for determining the most favorable levels of blood pressure and for selecting appropriate therapy.
Angiotensin II administration improves cerebral blood flow in cardiopulmonary arrest in swine.
Authors: Little C M , Brown C G
Published: June 2011

Cerebral blood flow during cardiopulmonary resuscitation is inadequate to meet cerebral metabolic demand. Adrenergic agonists improve cerebral blood flow, but clinical trials of increased doses in adults have not shown improved outcome from cardiac arrest. This may be due to adverse beta-agonist-mediated effects. The purpose of this study was to determine the effect of angiotensin II, a potent nonadrenergic vasopressor, on cerebral blood flow in cardiac arrest.

Eleven immature swine were anesthetized and instrumented for regional blood flow measurements with radiolabeled microspheres. A sagittal sinus catheter was placed for blood gas determination. A blood flow measurement was performed in normal sinus rhythm and ventricular fibrillation induced. After 10 minutes of ventricular fibrillation, cardiopulmonary resuscitation was begun and a blood flow measurement performed. Angiotensin II at a dose of 50 micrograms/kg was administered intravenously at 13 minutes of ventricular fibrillation. A blood flow measurement was performed and defibrillation attempted. A fourth blood flow measurement was obtained if return of spontaneous circulation occurred.

Total cerebral blood flow was 46.4 mL/min per 100 g in normal sinus rhythm. This fell to 6.9 mL/min per 100 g with cardiopulmonary resuscitation alone and rose to 30.8 mL/min per 100 g after the administration of angiotensin II. The improvement following angiotensin II was statistically different (P = .002). Cerebral blood flow further rose in the animals that had return of spontaneous circulation to 73.9 mL/min per 100 g.

Angiotensin II in a dose of 50 micrograms/kg significantly improves cerebral blood flow in this model of cardiac arrest.
Combination therapy protects ischemic brain in rats. A glutamate antagonist plus a gamma-aminobutyric acid agonist.
Authors: Lyden P D , Lonzo L
Published: June 2011

The excitotoxic effects of glutamate can be blocked almost completely with gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, in cell culture, tissue slices, and in some animal models. After stroke in rats, we showed previously that an agonist of GABA, muscimol, was as neuroprotective as MK-801, an antagonist of glutamate. To obtain further neuroprotection and to avoid the side effects associated with high doses of MK-801, we wanted to assess the efficacy of the two agents in combination.

Treatment was administered 5 minutes after embolic cerebral ischemia in Sprague-Dawley rats. The subjects were rated using a neurological evaluation 48 hours later. Visual-spatial learning was measured 8 to 10 weeks after stroke, after which we measured the volume of each cerebral hemisphere and several large cerebral compartments. Treatment groups included saline (n = 27), MK-801 1.0 mg/kg (n = 23), muscimol 1.0 mg/kg (n = 17), and both agents together using a dose of 0.5 mg/kg each (n = 25).

A probit analysis of the neurological ratings revealed a protective effect of muscimol used alone (MK-801 potency ratio, 2.0; P = NS; muscimol potency ratio, 4.0; P < .05) and a protective effect of the combination (potency ratio, 5.0; P < .05). Focal ischemia caused a moderate to severe delay in the acquisition of visual-spatial information, which was completely eliminated by the combination treatment but only partially ameliorated with MK-801 or muscimol alone. Ischemia reduced the cerebral hemisphere volume from 0.42 mm3 to 0.34 mm3 (P < .0001), the volume density of cortex from 22% to 17% of total cerebral volume (P < .01), and that of hippocampus from 4.3% to 3.0% (P < .05). Only the combination was neuroprotective, as measured by the ratio of the lesioned to the contralateral hemisphere volume (P = .013). The combination treatment and MK-801 protected the hemisphere volume, the cortex, and the hippocampus and reduced the size of visible infarction.

Combination therapy, using a glutamate antagonist and a GABA-A agonist, appeared to protect the brain and ameliorate a defect in learning behavior after stroke. The combination may have been more effective than either agent used alone, although further study of higher doses is needed.
Silent infarction in acute stroke patients. Prevalence, localization, risk factors, and clinical significance: the Copenhagen Stroke Study.
Authors: Jørgensen H S , Nakayama H , Raaschou H O , Gam J , Olsen T S
Published: June 2011

Our objective was to study age-specific prevalence, computed tomographic (CT) characteristics, risk factors, and the prognostic influence on stroke outcome of silent infarction in acute stroke patients.

The study was prospective and community-based and included 801 acute stroke patients, of whom 587 had first-ever stroke. A CT scan was performed in 500 (85%) of the 587 patients with first-ever stroke. CT was reviewed blindly, and infarcts were classified according to patient history as silent or symptomatic. Patients were evaluated initially with the Mini-Mental State Examination (MMSE) and weekly with both the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI) from the onset of stroke to completion of rehabilitation. CT characteristics, risk factors, and stroke outcome were compared in stroke patients with and without silent infarction.

The prevalence of silent infarction in patients with first-ever stroke and recurrent strokes was similar, at 29% (group aged 0 to 54 years, 16%; 55 to 64 years, 22%; 65 to 74 years, 30%; 75 years or older, 33%). Silent infarcts were small and subcortical. Independent risk factors were increasing age (odds ratio [OR], 1.95 per 25 years; confidence interval [CI], 1.19 to 3.15), hypertension (OR, 1.75; CI, 1.13 to 2.70), claudication (OR, 1.74; CI, 1.01 to 3.00), and male sex (OR, 1.72; CI, 1.12 to 2.64); other stroke risk factors such as atrial fibrillation and former transient ischemic attack were not independent risk factors. Patients with and without silent infarction did not differ in frequency of prestroke home care (P = .2). MMSE (P = .56), initial BI (P = .62) and SSS score (P = .08), BI (P = .85) and SSS score (P = .75) after completion of rehabilitation, or in the speed of recovery (P = .85). Length of hospital stay, mortality rate, and discharge rate to nursing home also did not differ between the two groups.

This community-based study shows that silent infarction in stroke patients is more related to certain stroke risk factors than others and that silent infarction does not seem to influence the prognosis of stroke.
Dementia after stroke is a predictor of long-term survival.
Authors: Tatemichi T K , Paik M , Bagiella E , Desmond D W , Pirro M , Hanzawa L K
Published: June 2011

The aim of this study was to determine whether dementia after stroke adversely influences long-term survival.

Subjects were 251 patients > or = 60 years of age with ischemic stroke who were given neurological, neuropsychological, and functional examinations 3 months after hospitalization and were followed up prospectively. Using criteria modified from the Diagnostic and Statistical Manual of Mental Disorders-III-R, dementia was found in 66 (26.3%) patients at the 3-month baseline examination. Life-table methods were used to estimate mortality rates in the groups with and without dementia after 1 to 5 years of follow-up, Kaplan-Meier curves to estimate the cumulative proportion surviving with and without dementia, and Cox proportional-hazards analysis to compute the relative risk of mortality associated with dementia at baseline, after adjusting for other potential predictors of stroke mortality.

The mortality rate was 19.8 deaths per 100 person-years with dementia compared with 6.9 deaths per 100 person-years without dementia. The cumulative proportion surviving after a median follow-up of 58.6 months was 38.9 +/- 0.08% for those with dementia and 74.5 +/- 0.04% for those without dementia. The relative risk associated with dementia was 3.11 (95% confidence interval, 1.79 to 5.41) after adjusting for the effects of demographic factors, cardiac disease, severity of stroke (Barthel Index), stroke type (lacunar versus nonlacunar), and recurrent stroke (examined as a time-dependent variable). When the Mini-Mental State Examination score at baseline was examined instead of the diagnosis of dementia, the results of the model were similar.

Our study is the first to demonstrate that dementia or cognitive impairment adversely influences long-term survival after stroke, even after adjusting for other commonly accepted predictors of stroke mortality. Impairment in intellectual function after stroke, independent of physical disability, has a significant impact on prognosis. Both cognitive and physical functions should be assessed in clinical studies of stroke outcome.
Code stroke. An attempt to shorten inhospital therapeutic delays.
Authors: Gomez C R , Malkoff M D , Sauer C M , Tulyapronchote R , Burch C M , Banet G A
Published: June 2011

Significant delays often occur during the treatment of patients with acute stroke. Some of those delays occur in the hospital. We attempted to shorten inhospital treatment intervals by creating a rapid-response system, similar to that available for cardiac arrest, that would allow the stroke team to be available within a few minutes to care for stroke victims.

We connected all beepers (pocket pagers) of stroke team members to a common access number and instructed the emergency staff to activate that number immediately upon arrival of a stroke victim. We monitored the response time and treatment interval for patients who were treated after this system was activated (Code Stroke patients) during the first 3 months of its availability and compared the results to those of patients seen for similar reasons during the study period but without the use of Code Stroke (control patients).

A total of 12 Code Stroke patients were available for analysis, representing 12% of all patients (n = 98) seen in the emergency department for ischemic stroke during the study period. The remaining 86 patients constituted the control group. The mean time to evaluation of a Code Stroke patient by a stroke team member was 4.8 minutes (range, 2 to 7 minutes), and the mean time to treatment institution was 30 minutes (range, 10 to 120 minutes). There were significant differences between the consultation intervals in the two groups (P < .05). There was only a trend of a difference between treatment institution intervals (P = .06).

It is possible to shorten inhospital treatment delays by instituting rapid-response systems within individual institutions.
Pure dysarthria, isolated facial paresis, or dysarthria-facial paresis syndrome.
Authors: Kim J S
Published: June 2011

Pure dysarthria, isolated supranuclear facial paresis, and their combination without somatic motor dysfunction are rarely encountered clinical syndromes and have not yet been clearly characterized.

Thirteen patients (9 men, 4 women; aged 33 to 72 [mean, 56] years) with unilateral strokes who developed dysarthria with or without facial paresis but without somatic motor dysfunction were reviewed in addition to case reports from previous literature.

Computed tomographic scan and/or magnetic resonance imaging showed infarcts on the corona radiata in 4 patients, basal ganglia abutting the internal capsule in 3, basal ganglia-corona radiata in 1, pontine base in 3, and cortical-subcortical bulbar motor area in 2. The dysarthria and facial paresis were usually mild and transient, and either one was likely to be unnoticed.

It is suggested that pure dysarthria or isolated facial paresis syndrome be considered as an extreme continuum of dysarthria-facial paresis syndrome, which is likely to be a variant of dysarthria-clumsy hand syndrome.
Preoperative noninvasive coronary risk stratification in candidates for carotid endarterectomy.
Authors: Urbinati S , Di Pasquale G , Andreoli A , Lusa A M , Carini G , Grazi P , Labanti G , Passarelli P , Corbelli C , Pinelli G
Published: June 2011

Patients with symptomatic carotid stenosis who are candidates for carotid endarterectomy are at high short- and long-term risk of coronary events. To stratify patients at different risk of coronary events we investigated the usefulness of a noninvasive preoperative cardiological workup.

We studied 172 consecutive patients admitted to the Neurosurgical Department for symptomatic high-grade (70% to 99%) carotid stenosis (age, 42 to 74 years; mean, 57.8 years). Patients without history of coronary artery disease (CAD) and able to exercise were submitted to exercise electrocardiographic testing (EET) and, if abnormal, to exercise thallium myocardial imaging (TMI). Patients were classified into four groups: group 1, patients without CAD: no history of CAD, normal EET, or normal TMI in the presence of indeterminant EET (n = 93, 54%); group 2, patients with silent CAD: no history of CAD and concordant abnormal EET and TMI (n = 28, 16%); group 3, patients unable to exercise: no history of CAD and inability to perform adequate EET because of previous stroke or claudication (n = 29, 17%); and group 4, patients with known CAD: history of angina or myocardial infarction (MI) (n = 22; 13%).

The four groups were comparable in regard to age, sex, and computed tomographic scan of the brain. The prevalence of stroke was higher in patients unable to exercise; hypercholesterolemia was more frequent in patients with known CAD. During the perioperative period (< or = 30 days after carotid endarterectomy), coronary events occurred in 3 patients (2%): fatal MI in 2 patients in group 4 and 1 patient in group 3. One hundred percent of patients were followed up for 6.2 years. Coronary events occurred in 23 of the 168 patients discharged from the hospital (13.7%); these were fatal in 11 (6.5%): 3 patients of group 1 (3%; sudden death in 2, fatal MI in 1), 8 patients of group 2 (29%; fatal MI in 5, unstable angina in 3), 8 patients of group 3 (28%; fatal MI in 4, nonfatal MI in 4), and 4 patients of group 4 (18%; fatal MI in 2, sudden death in 1, unstable angina in 1). Kaplan-Meier estimated curves of survival free from fatal and nonfatal coronary events were 97%, 51%, 49%, and 59%, respectively (P < .001, group 1 versus groups 2 and 3; P < .01, group 1 versus group 4).

Among patients undergoing carotid endarterectomy, coronary events occurred twice as often as cerebral recurrences. A preoperative noninvasive cardiac investigation, including EET, can adequately identify groups of patients with diverse short- and long-term prognoses. In addition to patients with known CAD, those with silent CAD or who are unable to exercise represent, without the need of further investigation, groups at high risk of coronary events in long-term follow-up.
Evaluation of delayed treatment of focal cerebral ischemia with three selective kappa-opioid agonists in cats.
Authors: Baskin D S , Widmayer M A , Browning J L , Heizer M L , Schmidt W K
Published: June 2011

The purpose of this study was to determine the therapeutic efficacy of three kappa-opioid agonists used for delayed treatment of experimental focal cerebral ischemia.

Forty halothane-anesthetized cats underwent permanent occlusion of the right intracranial internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital, microsurgical approach. Six hours after occlusion, animals received a blinded bolus injection, and a subcutaneous osmotic pump was implanted to provide continuous release for 7 days. The injection and pump contained either saline or one of three kappa-agonists: dynorphin (1-13), U-50,488, or DuP E3800. Survival, neurological function, tissue damage, and brain weight were assessed.

As a group, kappa-agonist-treated animals had higher survival (P < .02), less tissue damage (P < .02), and lower brain weight (P < .05) than saline controls. U-50,488 more effectively improved survival (P < .03) than dynorphin (P < .07) or E3800 (P < .07). Each of the three kappa compounds improved tissue damage (dynorphin, P < .02; U-50,488, P < .05; E3800, P < .05). Greater improvement in neurological function was seen after treatment with dynorphin (P < .05) than with U-50,488 (P < .6) or E3800 (P < .7). The only significant reduction in brain weight was seen after dynorphin treatment (P < .01).

Compounds that act at the kappa subclass of opiate receptors are effective in increasing survival, improving neurological function, and decreasing tissue damage and edema in a cat model of focal cerebral ischemia. The current study provides support for the benefits of treatment of acute cerebrovascular ischemia with kappa-opioid agonists. The agents may prove to be of superior clinical utility because of efficacy even when administered 6 hours after the onset of stroke.