bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of cerebrovascular reactivity using transcranial Doppler, including the use of breath-holding as the vasodilatory stimulus.
Authors: Markus H S , Harrison M J 
Published: June 2011

A proportion of individuals with carotid artery stenosis show a reduced cerebrovascular reserve as measured by a reduced cerebral arterial vasodilatory response to carbon dioxide. Two methods of quantifying this vasodilatory response, using transcranial Doppler ultrasonography, have been in general use: the total range of vasodilation between hypocapnia, induced by hyperventilation, and hypercapnia induced by breathing carbon dioxide, and the response to breathing a fixed concentration of 5% carbon dioxide. We studied whether it is possible to use the rise in carbon dioxide occurring during breath-holding as the vasodilatory stimulus.
Using transcranial Doppler, cerebral reactivity to carbon dioxide was measured in 23 subjects undergoing intravenous digital subtraction angiography of their carotid arteries for symptoms of cerebrovascular disease. A breath-holding method was compared with the two previous methods, which required administration of carbon dioxide.
All three methods gave results that correlated highly significantly with the degree of carotid stenosis, although the correlation was highest when the full vasodilatory range was measured. This method was adopted as the gold standard, and the other methods were compared with it. The breath-holding method correlated at least as well (rho = 0.67) as the 5% CO2 method (rho = 0.64). It identified a similar group of low reactors to our gold standard method, whereas the 5% CO2 method gave some discrepant results.
The breath-holding method offers potential as a convenient, well-tolerated screening method of assessing carbon dioxide reactivity not requiring the administration of carbon dioxide, although further validation against more established methods of measuring cerebrovascular reserve is first required.
Amount of smoking independently predicts carotid artery atherosclerosis severity.
Authors: Dempsey R J , Moore R W 
Published: June 2011

Cigarette smoking is correlated with extracranial carotid artery plaque thickness. Our aim in the present study was to determine whether the level of prior cigarette use is a significant predictor of carotid artery plaque thickness when age, history of hypertension, and history of diabetes are controlled.
We studied a continuous sample of 790 patients with a history of smoking referred for diagnostic ultrasound imaging of the carotid arteries. Subjects (mean age 61 years) had an average of 51 pack-years of cigarette use. History of hypertension was present in 44% and history of diabetes in 18%.
Right and left maximum carotid artery plaque thicknesses were averaged for each patient; the average of this value for all 790 subjects was 1.9 mm. In bivariate analysis, age (p less than 0.0001), pack-years (p less than 0.0001), history of hypertension (p = 0.0003), and history of diabetes (p = 0.037) were each positively associated with carotid artery plaque thickness. In multiple regression analysis, age (p less than 0.0001), pack-years (p = 0.0005), and history of hypertension (p = 0.0044) were statistically significant independent predictors of carotid artery plaque thickness, but history of diabetes (p = 0.2451) was not.
In smokers, the level of cigarette use is associated with an acceleration of carotid artery atherosclerosis development. This effect is independent of age, hypertension, and diabetes. These results support smoking abatement as an important element to stroke prevention in clinical practice.
Induction of transient neurological dysfunction in baboons by platelet microemboli.
Authors: Kessler C , Kelly A B , Suggs W D , Weissman J D , Epstein C M , Hanson S R , Harker L A 
Published: June 2011

To investigate experimental mechanisms of reversible cerebral dysfunction, we produced transient focal cerebral ischemia in five baboons by unilateral perfusion of internal carotid territories with platelet microemboli generated endogenously.
Platelet microemboli were formed by incorporating segments of Dacron vascular graft for 1 hour as unilateral carotid arterio-arterial shunts. Platelet embolization was assessed by ultrasonography and isotopic imaging; cerebral function was evaluated by measurements of somatosensory evoked potentials and clinical motor performance.
Platelet microemboli, detected by transcranial Doppler ultrasonography, accumulated rapidly in the shunted carotid hemispheric territory. Indium-111-labeled platelets reached a maximum value of 3.2 +/- 0.8 x 10(9) platelets in the dependent hemisphere of five animals after 20 minutes of carotid blood flow through the grafts when measured in real time by continuous scintillation camera imaging. The retained 111In-platelet microemboli cleared from the cerebral vasculature within 1 hour after removing the grafts. Corresponding blood markers of in vivo thrombus formation, beta-thromboglobulin, platelet factor 4, and fibrinopeptide A, increased eightfold to 20-fold after incorporating graft segments and normalized within 1 hour after removing the grafts. Coincidently, focal neurological function was temporarily impaired, as shown by the ipsilateral loss of somatosensory evoked potentials 5 minutes after initiating platelet microembolization, with restoration 1 hour after removing the grafts in five baboons, and contralateral hemiparesis in two recovered baboons, with complete resolution by 24 hours.
Endogenously generated platelet microemboli accumulate transiently in the dependent cerebral circulation and produce corresponding focal neurological dysfunction that resolves within hours after microembolization.
Inhibition of polymorphonuclear leukocyte adherence suppresses no-reflow after focal cerebral ischemia in baboons.
Authors: Mori E , del Zoppo G J , Chambers J D , Copeland B R , Arfors K E 
Published: June 2011

While polymorphonuclear leukocytes may contribute to the "no-reflow" phenomenon after focal cardiac and skeletal muscle ischemia/reperfusion, their contribution to acute focal cerebral ischemia is unresolved. We have examined the role of polymorphonuclear leukocytes in microvascular perfusion defects after focal cerebral ischemia/reperfusion in a baboon model of reversible middle cerebral artery occlusion with the anti-CD18 monoclonal antibody IB4, which inhibits neutrophil adherence to endothelium.
Microvascular patency in the basal ganglia after 3-hour middle cerebral artery occlusion and 1-hour reperfusion (by india ink tracer perfusion) was quantified by computerized video imaging. Animals were randomized to receive intravenous IB4 infusion 15 minutes before reperfusion (n = 7) or to receive no treatment (n = 6). Binding of IB4 to baboon leukocytes was maximal within 5 minutes of infusion.
In the untreated group, a significant reduction in patency was observed in microvessels less than 30 microns diameter: mean percent reflow was 51% in the capillary diameter class (4.0-7.5 microns) and 39% in the precapillary arteriole and postcapillary venule diameter class (7.5-30 microns). Infusion of IB4 before middle cerebral artery reperfusion increased reflow in microvessels of all size classes, most significantly in those 7.5-30 microns (p = 0.049) and 30-50 microns (p = 0.034) in diameter.
These results suggest that CD18-mediated polymorphonuclear leukocyte-endothelium adherence contributes to no-reflow predominantly in noncapillary microvessels and at least partially to that in capillaries.
Combination therapy with nimodipine and dizocilpine in a rat model of transient forebrain ischemia.
Authors: Rod M R , Auer R N 
Published: June 2011

We explored the effectiveness of dual blockade of calcium channels in preventing ischemic necrosis in a rat model of transient forebrain ischemia.
To assess all the major brain regions, the entire brain was subserially sectioned and examined histologically 1 week after ischemia in 44 male Wistar rats. Brain temperature was monitored and controlled to avoid hypothermia or intergroup temperature differences at the time drugs were administered. All regimens were begun 20 minutes after ischemia. Treated animals received either the L-type calcium channel blocker nimodipine (0.25 microgram/min x 24-hour i.v. infusion), the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine; 5 mg/kg i.v.), or both regimens in combination.
In the neocortex (p less than 0.05) and striatum (p less than 0.05), only double-treated animals showed a statistically significant reduction in neuronal necrosis. Dual therapy eliminated neuronal necrosis in the caudate nucleus entirely. In the septal (densely ischemic) hippocampus, protection was weak and inconsistent (0.012 less than p less than 0.788), but in the temporal (incompletely ischemic) hippocampus, the dual-treated group showed the most significant reduction (p less than 0.006).
We conclude that the combination of nimodipine and MK-801, if begun 20 minutes after ischemia, may offer a neuroprotective effect against neuronal necrosis in transient forebrain ischemia and that protection is maximal in the major extrahippocampal brain regions.
Quantal bioassay and stroke.
Authors: Zivin J A , Waud D R 
Published: June 2011

Experimental investigation of stroke, in particular the evaluation of therapeutic maneuvers, is difficult because even well-controlled experiments show considerable variability. Optimal use of resources requires efficient statistical analysis.
A body of experience in pharmacology that is directly applicable to stroke studies is reviewed. The general approach, though well known to pharmacologists, is less familiar to neurologists. This paper attempts to give a survey so that neurologists encountering studies using this general class of analysis will better be able to put the technique into context. The general nature of a quantal bioassay is described, the underlying conceptual models are discussed, and specific examples are given.
The pharmacologist's approach to the analysis of quantal bioassays can easily be adapted to the quantification of results in studies of stroke.
Histopathological analysis of the mechanisms of intracranial hemorrhage complicating infective endocarditis.
Authors: Masuda J , Yutani C , Waki R , Ogata J , Kuriyama Y , Yamaguchi T 
Published: June 2011

We conducted the present study to elucidate the pathological mechanisms leading to intracranial hemorrhage complicating infective endocarditis.
Neurological, neuroradiological, and histopathological analyses were performed in 16 patients (one surgical and 15 autopsy cases), 12 men and four women 26-68 years of age, who had demonstrated central nervous system complications during the course of infective endocarditis.
Intracranial hemorrhage was found in all cases; parenchymal hematomas were found in 12 cases, hemorrhagic infarcts in four cases, and primary subarachnoid hemorrhages in two cases. Chronological analysis of neurological examination and computed tomographic scan of the brain confirmed that antecedent cerebral ischemic events had occurred in five of 12 patients showing parenchymal hematomas at autopsy. Hemorrhagic infarct, indicated by petechial or diffuse hemorrhages within the infarct, was seen in another four patients, so that hemorrhagic transformation of the ischemic infarct was confirmed in nine patients. Although mycotic aneurysms were found in five patients, only three of these were ruptured; the other two were occluded with septic emboli. Pyogenic arteritis without aneurysm was found to be distributed in the small cortical arterial branches located in the spaces of cortical sulci, with rupture occurring in five patients.
These results suggest that hemorrhagic transformation of the ischemic infarct due to septic emboli is the most frequent mechanism leading to intracerebral hemorrhage encountered in patients dying of infective endocarditis and that rupture of pyogenic arteritis may be responsible for such hemorrhage in many cases, with ruptures of mycotic aneurysms as an alternative mechanism.
Cerebroprotective effect of a non-N-methyl-D-aspartate antagonist, GYKI 52466, after focal ischemia in the rat.
Authors: Smith S E , Meldrum B S 
Published: June 2011

Cerebroprotection after the administration of N-methyl-D-aspartate antagonists has been well documented. The present study sought to determine whether a cerebroprotective effect could be achieved with the administration of a non-N-methyl-D-aspartate antagonist, GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazep ine hydrochloride; molecular weight, 330) after middle cerebral artery occlusion in the rat.
Neurological deficit and infarct volume 24 hours after permanent left middle cerebral artery occlusion in Fischer rats (n = 7-13 per group per dose) were studied. Cerebral infarcts was visualized by the lack of reduction of 2,3,5-triphenyltetrazolium chloride.
GYKI 52466 (10 mg.kg-1 i.p. at 0, 2, 4 hours) after middle cerebral artery occlusion had no effect on infarct volume. GYKI 52466 (10 mg.kg-1 i.v. for 5 minutes followed by 15 mg.kg-1.hr-1 i.v. for 2 hours immediately after middle cerebral artery occlusion reduced cortical infarct volume by 68% (from 69 mm3 in vehicle-treated to 22 mm3 in GYKI 52466-treated animals; p less than 0.05). A 1-hour delay before initiation of drug infusion resulted in a 48% reduction in cortical infarct volume (from 60 mm3 vehicle-treated rats to 31 mm3 in GYKI 52466-treated rats; p less than 0.05). A 2-hour delay before initiation of drug infusion had no effect on cortical infarct volume. Neurological deficits (with blinded assessment after 24 hours) were improved after immediate treatment and after delayed treatment (1 or 2 hours).
The cerebroprotective effect of GYKI 52466 in the rat suggests a possible therapeutic role for non-N-methyl-D-aspartate antagonists given shortly after the onset of stroke.
Small infarctions of cochlear, retinal, and encephalic tissue in young women.
Authors: Schwitter J , Agosti R , Ott P , Kalman A , Waespe W 
Published: June 2011

Recently, a rare syndrome that involves uniformly the brain, inner ear, and retina in previously healthy young women has been described. Brain biopsies and ophthalmologic examinations disclosed small infarcts as a pathoanatomical substrate of the disease. In previous reports, an autoimmune disorder or a coagulopathy have been suggested as possible etiologies.
Both patients (aged 22 and 20 years) had brain involvement with neurological and neuropsychological deficits. Multifocal small hyperintensities were shown in magnetic resonance imaging of the brain. Findings of cerebrospinal fluid examination and electroencephalography were pathological in case 1 and of cerebral angiography in case 2. Both patients had a neurosensory hearing loss and multiple retinal branch arteriolar occlusions. Both women were on fenfluramine before onset of the disease. In case 1, attacks recurred during a follow-up of 34 months. At onset of the disease the 5-hydroxyindoleacetic acid and homovanillic acid levels of the cerebrospinal fluid were reduced; 13 months later the 5-hydroxyindoleacetic acid level was still reduced and the homovanillic acid level was low-normal. In case 2, with the longest follow-up of 13 years, the disease was active during only the initial 2 1/4 years. During this period a combination of oral anticoagulant and antiplatelet agents was ineffective.
Our findings could not support current etiologic hypotheses. Whether changes in 5-hydroxyindoleacetic acid and homovanillic acid levels in the cerebrospinal fluid and/or fenfluramine intake play a role in the pathogenesis of the disease remains to be elucidated.
Treatment of cerebellar infarction by decompressive suboccipital craniectomy.
Authors: Chen H J , Lee T C , Wei C P 
Published: June 2011

We present an anecdotal series of 11 patients without past history of stroke with progressive neurological deterioration while on medical therapy for large cerebellar infarctions. Clinical signs of brain stem compression developed in these patients. Computerized tomography of the head confirmed mass effect from brain edema. It was the clinical judgment of the neurologists and neurosurgeons that each of these 11 patients would expire without surgical intervention.
All 11 patients (seven men, four women; mean age, 54 years) were treated with suboccipital craniectomy for decompression and temporary ventriculostomy for cerebrospinal fluid pressure monitoring and drainage.
Seven patients demonstrated neurological improvement on the first postoperative day. Two patients returned to their previous jobs 3 months after surgery. The Barthel Index indicated that six individuals were functioning with minimal assistance within a follow-up period of 16-60 months. The remaining three were functionally dependent. No mortality was noted in this series.
These results suggest that decompressive suboccipital craniectomy may be an effective, lifesaving procedure for malignant cerebellar edema after a large infarction.
Treatment of acute cerebral hemorrhage with intravenous glycerol. A double-blind, placebo-controlled, randomized trial.
Authors: Yu Y L , Kumana C R , Lauder I J , Cheung Y K , Chan F L , Kou M , Chang C M , Cheung R T , Fong K Y 
Published: June 2011

Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers.
We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months.
At follow-up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean +/- SD improvements in Scandinavian Stroke Study Group scores were 8.35 +/- 16.9 versus 11.55 +/- 15.6 (long-term) and 0.64 +/- 7.3 versus 2.40 +/- 6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72 +/- 24.7 versus 13.95 +/- 23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81 +/- 1.5 and 1.16 +/- 1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted.
In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage.
Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis. The Asymptomatic Carotid Artery Plaque Study.
Authors: Riley W A , Barnes R W , Applegate W B , Dempsey R , Hartwell T , Davis V G , Bond M G , Furberg C D 
Published: June 2011

To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study.
Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n = 405) and between-sonographer (B, n = 453) reproducibility.
The primary end point (mean +/- SD), defined in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31 +/- 0.21 mm (W) and 1.32 +/- 0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was -0.01 +/- 0.13 mm (W) and 0.00 +/- 0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was less than 0.22 mm (W) and less than 0.24 mm (B). Variability of the secondary end point, defined as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small.
The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression.
Measurement of motor recovery after stroke. Outcome assessment and sample size requirements.
Authors: Duncan P W , Goldstein L B , Matchar D , Divine G W , Feussner J 
Published: June 2011

The purpose of this study was to analyze recovery of motor function in a cohort of patients presenting with an acute occlusion in the carotid distribution. Analysis of recovery patterns is important for estimating patient care needs, establishing therapeutic plans, and estimating sample sizes for clinical intervention trials.
We prospectively measured the motor deficits of 104 stroke patients over a 6-month period to identify earliest measures that would predict subsequent motor recovery. Motor function was measured with the Fugl-Meyer Assessment. Fifty-four patients were randomly assigned to a training set for model development; 50 patients were assigned to a test set for model validation. In a second analysis, patients were stratified on basis of time and stroke severity. The sample size required to detect a 50% improvement in residual motor function was calculated for each level of impairment and at three points in time.
At baseline the initial Fugl-Meyer motor scores accounted for only half the variance in 6-month motor function (r2 = 0.53, p less than 0.001). After 5 days, both the 5-day motor and sensory scores explained 74% of the variance (p less than 0.001). After 30 days, the 30-day motor score explained 86% of the variance (p less than 0.001). Application of these best models to the test set confirmed the results obtained with the training set. Sample-size calculations revealed that as severity and time since stroke increased, sample sizes required to detect a 50% improvement in residual motor deficits decreased.
Most of the variability in motor recovery can be explained by 30 days after stroke. These findings have important implications for clinical practice and research.