bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiographic detection of carotid plaque ulceration. Comparison with surgical observations in a multicenter study. North American Symptomatic Carotid Endarterectomy Trial.
Authors: Streifler J Y , Eliasziw M , Fox A J , Benavente O R , Hachinski V C , Ferguson G G , Barnett H J
Published: June 2011

Carotid plaque ulceration is used as one of the determinants in deciding which patients should be submitted to carotid endarterectomy. Uncertainties about its importance persist. Its detection by angiography is an important consideration.

The detection of ulceration by angiography was compared with observations during endarterectomy in the first 500 patients recruited into the North American Symptomatic Carotid Endarterectomy Trial. This represents the first multicenter compilation of data on this subject and the largest series of patients with both arteriographic and direct surgical observation.

Sensitivity and specificity of detecting ulcerated plaques were 45.9% and 74.1%, respectively. The positive predictive value of identifying an ulcer was 71.8%. These results remained unchanged with differing degrees of carotid stenosis and were confirmed by analyses based on receiver operating characteristic (ROC) methodology. The area under the ROC curve (Az) was estimated to be 0.61 (95% confidence interval, 0.55 to 0.67).

These observations from a multicenter study confirm that little agreement exists between angiography and surgical observation in detecting carotid plaque ulceration.
Rehabilitation of walking with electromyographic biofeedback in foot-drop after stroke.
Authors: Intiso D , Santilli V , Grasso M G , Rossi R , Caruso I
Published: June 2011

Alterations of gait cycle and foot-drop on the paretic limb are characteristic of stroke patients. Electromyographic biofeedback treatment has been used in rehabilitation of walking, but results are controversial. We performed gait analysis to evaluate the efficacy of electromyographic biofeedback compared with physical therapy.

Sixteen patients with ischemic stroke were enrolled in the study. The experimental group (4 men, 4 women) received electromyographic biofeedback treatment together with physical therapy. The control group (5 men, 3 women) was treated with physical therapy only. Clinical and functional evaluations before and after treatment were performed using Canadian Neurological, Adams, Ashworth, Basmajian, and Barthel Index scales. Computerized gait analysis was performed in all patients.

Electromyographic biofeedback patients showed significantly increased scores on the Adams scale (P < .05) and Basmajian scale (P < .01). Gait analysis in this group showed a recovery of foot-drop in the swing phase (P < .02) after training.

Our data confirm that the electromyographic biofeedback technique increases muscle strength and improves recovery of functional locomotion in patients with hemiparesis and foot-drop after cerebral ischemia.
Patterns of cerebrovascular reactivity in patients with unilateral asymptomatic carotid artery stenosis.
Authors: Fürst H , Hartl W H , Janssen I
Published: June 2011

Intracranial hemodynamic status varies in patients with unilateral significant carotid artery stenosis. It ranges from normal, because of sufficient collaterals, to poor, because of a severely reduced blood supply that puts the patient at an increased risk of stroke or cerebral ischemia. The present study examined patterns of abnormal cerebrovascular hemodynamics in patients with asymptomatic carotid artery stenosis.

The CO2 reactivity of the cerebral resistance index (CRi) and of mean blood flow velocity (vmean) was determined via transcranial Doppler sonography in 91 patients with unilateral high-grade to threadlike carotid artery stenosis and in 37 control subjects. The interhemispheric asymmetry of CRi reactivity of the control group was used to differentiate between normal and abnormal findings.

We found that 64.8% of the patients demonstrated normal CRi asymmetry with comparable CRi reactivity (ipsilateral, 4.42 +/- 0.44 %CRi/vol%CO2; contralateral, 4.51 +/- 0.39 %CRi/vol%CO2) and vmean reactivity (ipsilateral, 0.080 +/- 0.004 m/s per vol%CO2; contralateral, 0.079 +/- 0.005 m/s per vol%CO2) at both hemispheres. In 16.5% of the patients, CRi reactivity was supranormal at the affected hemisphere. This phenomenon was due to an exaggerated dilatory response of the ipsilateral hemisphere and was combined with an absent CRi reactivity of the contralateral hemisphere (ipsilateral, 6.63 +/- 1.03 %CRi/vol%CO2; contralateral, -1.16 +/- 1.78 %CRi/vol%CO2). In contrast, hemispheric vmean reactivities were comparable (ipsilateral, 0.078 +/- 0.008 m/s per vol%CO2; contralateral, 0.077 +/- 0.008 m/s per vol%CO2). The remaining 18.7% showed severely diminished ipsilateral CRi reactivity (ipsilateral, 1.91 +/- 0.83 %CRi/vol%CO2; contralateral, 8.48 +/- 1.00 %CRi/vol%CO2) and vmean reactivity (ipsilateral, 0.073 +/- 0.007 m/s per vol%CO2; contralateral, 0.108 +/- 0.012 m/s per vol%CO2; P < .01), compatible with a significantly reduced perfusion pressure at the poststenotic hemisphere.

Most asymptomatic patients do not suffer from severely abnormal hemodynamics at the poststenotic hemisphere. One small subgroup of patients presented with severely disturbed ipsilateral hemodynamics; another small subgroup demonstrated a steal phenomenon with secondary dilation of large cerebral vessels at the contralateral hemisphere. These subgroups require specific evaluation of proper treatment.
Internal carotid artery redundancy is significantly associated with dissection.
Authors: Barbour P J , Castaldo J E , Rae-Grant A D , Gee W , Reed J F , Jenny D , Longennecker J
Published: June 2011

Redundant internal carotid arteries have been considered a risk factor in tonsillectomy, adenoidectomy, and surgical treatment of peritonsillar abscess and also a potentially treatable cause of stroke. However, an association between internal carotid artery redundancy and spontaneous dissection has not yet been clearly demonstrated.

We reviewed, for spontaneous carotid artery dissection, records of all patients admitted to our institution during the period from 1986 through 1992 with the diagnosis of stroke or transient ischemic attack. We also reviewed 108 percutaneous cerebral arteriograms performed between September 1992 and December 1992 for presence of carotid artery redundancies.

Thirteen patients exhibited spontaneous dissection. Of these, 8 of 13 (62%) patients and 13 of 20 (65%) internal carotid arteries, viewed to the siphon, had significant redundancies, kinks, coils, or loops. Of 108 consecutive arteriograms of patients without dissection, in which 187 internal carotid arteries were viewed to the siphon, there were 20 (19%) patients and 22 (12%) of 187 vessels with significant redundancy. Five patients in the dissection group and 2 in the nondissection group had bilateral internal carotid artery redundancy (P = .0019 and P = .0001, respectively).

We found a significant correlation between internal carotid artery redundancy and dissection, particularly if redundancy is present bilaterally.
The competitive NMDA antagonist MDL-100,453 reduces infarct size after experimental stroke.
Authors: Hasegawa Y , Fisher M , Baron B M , Metcalf G
Published: June 2011

The competitive N-methyl-D-aspartate antagonist MDL-100,453 was used to determine whether a neuroprotective effect is demonstrable when the drug is administered beginning 30 minutes after the initiation of focal ischemia and whether the effect is related to blood levels of the drug.

Forty-eight Sprague-Dawley rats were randomly assigned to one of four intravenous treatment categories: a bolus of 100 mg/kg MDL-100,453 followed by a saline infusion for 24 hours, isotonic saline as a bolus and 100 mg/kg per 24 hours of MDL-100,453 as an infusion over 24 hours, active drug in the bolus and 24-hour infusion, and control treatment of an isotonic saline bolus and infusion. Focal cerebral ischemia was induced by the intraluminal suture, middle cerebral artery occlusion method. The drug infusion was accomplished by an osmotic minipump implanted under the skin and attached to the jugular vein, which delivered drug or vehicle over a period of 24 hours. Infarct volume was calculated using 2,3,5-triphenyltetrazolium chloride staining after 24 hours of middle cerebral artery occlusion.

Infarct volume of animals that received the MDL-100,453 bolus injection followed by MDL-100,453 infusion was significantly smaller than that of controls (P < .01). A significant effect of infusion on the reduction of extent of infarct size was also demonstrated (P = .015). Moreover, a statistically significant inverse correlation was demonstrated between the infarct volume and blood levels of MDL-100,453 at 60 minutes and 120 minutes after injection (r = -.33 and r = -.49, respectively).

We demonstrated a significant neuroprotective effect of MDL-100,453 when treatment was initiated 30 minutes after ischemia began and was maintained for 24 hours.
A pediatric case of carotid rete mirabile.
Authors: Fuwa I
Published: June 2011

Carotid rete mirabile (CRM) is a physiological network between the external carotid and internal carotid systems in lower mammals. Very rarely, these arterial channels are observed in humans.

We describe a 13-year-old girl with CRM who presented with acute hemiplegia after an operation for Dieulafoy's ulcer, a submucosal vascular anomaly of the stomach. Angiogram revealed hypoplasia of the bilateral internal carotid arteries. The abnormal network from the external carotid system was seen around the cavernous portion of the internal carotid arteries. The ophthalmic arteries were developed as the collateral pathway.

To our knowledge, this is the first pediatric case reported in the literature. CRM sometimes accompanies intracranial or systemic vascular disorders such as cerebral aneurysm and pseudoxanthoma elasticum. CRM is a unique pathological condition that presents as a hemorrhagic or ischemic cerebrovascular disorder.
Internal carotid artery dissection after remote surgery. Iatrogenic complications of anesthesia.
Authors: Gould D B , Cunningham K
Published: June 2011

Subintimal dissection with acute occlusion of the internal carotid artery resulting in acute cerebral infarction has not been reported as an iatrogenic complication of general anesthesia.

An anesthetist stretched the neck of a 44-year-old man by anchoring an anesthesia mask posterior to the angle of the jaw with overlying fingers as the patient struggled during an insufficient inhalational mask anesthetic. A 33-year-old man received an endotracheal anesthetic without struggle, but as he was turned from a supine to a prone position, his head and neck were not immobilized to rotate with his torso during the move. The next day both patients suffered acute cerebral infarctions secondary to ICA dissections and occlusions (angiographically demonstrated).

Stretching the soft neck tissues of anesthetized patients can cause internal carotid artery dissection and acute cerebral infarction.
A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke.
Authors: Kaste M , Fogelholm R , Erilä T , Palomäki H , Murros K , Rissanen A , Sarna S
Published: June 2011

A randomized, double-blind, placebo-controlled multicenter trial was conducted to test the hypothesis that nimodipine would improve the functional outcome in acute ischemic hemispheric stroke.

A total of 350 patients were randomized to nimodipine 120 mg/d PO or matching placebo for 21 days. Randomization was stratified by onset of therapy, age, and stroke severity. Treatment was begun within 48 hours of onset. The patients had neurological evaluation on admission, on days 1, 7, and 21, and at 3 and 12 months. The primary end points were Rankin grade, neurological score, and mobility at 12 months.

We did not find any differences in the functional outcome between the treatment groups or between the stratified subgroups. We were also unable in post hoc analyses to find any groups of patients who benefited from nimodipine. During the first month and at 3 months the case-fatality rate was higher in the nimodipine-treated patients than in those on placebo (P = .004 and P = .030, respectively), but at the 1-year follow-up this difference had lost statistical significance. During the first week nimodipine had a statistically significant lowering effect on both systolic (P = .005) and diastolic (P = .013) blood pressure.

Nimodipine did not improve the functional outcome of acute ischemic hemispheric stroke. The early case-fatality rate was higher in the nimodipine group, possibly due to the blood pressure-lowering effect of nimodipine.
Arterial enlargement in the atherosclerosis risk in communities (ARIC) cohort. In vivo quantification of carotid arterial enlargement. The ARIC Investigators.
Authors: Crouse J R , Goldbourt U , Evans G , Pinsky J , Sharrett A R , Sorlie P , Riley W , Heiss G
Published: June 2011

The relation between arterial wall (intimal-medial) thickness and lumen narrowing is complex and has previously been studied predominantly at autopsy. B-mode ultrasound affords the opportunity to visualize both wall and lumen of the extracranial carotid arteries in vivo. Several studies have quantified the relation of various independent variables to wall thickness of carotid arteries in population-based samples, but the relation of age and wall thickness to interadventitial and lumen diameter has not previously been investigated in these samples.

We used B-mode ultrasound to quantify the relation of arterial lumen diameter to age, arterial wall thickness, and arterial size (interadventitial diameter) of the extracranial carotid artery in 13,711 members of the Atherosclerosis Risk in Communities (ARIC) cohort.

Men had greater interadventitial diameters, thicker walls, and wider lumens than women. Wall thicknesses of the common carotid artery were greater by 21% in men and 22% in women aged 60 to 64 years compared with those aged 45 to 49 years (P < .001). However, lumen diameters were also greater in older individuals because interadventitial diameters were greater. Wall thickness of the internal carotid artery was also associated positively with age, but the lumen diameter of the internal carotid artery was smaller in older individuals. Diameters of the carotid artery segments also differed in their relation to arterial wall thickening. The lumen of the internal carotid artery was uniformly progressively narrower with increasing wall thickness. For the common carotid artery greater wall thickness bore only a small correlation with narrower lumen diameter for thickening of the arterial wall up to 1.2 mm, but the association was more marked for the range of thicknesses between 1.2 mm and 2.5 mm.

When arterial enlargement accompanies increased wall thickness, less lumen constriction results than expected. Quantification of these complex relations in vivo may provide new insight into the pathogenesis of symptoms related to vascular disease. Narrowing of the internal carotid artery lumen associated with thicker walls is consistent with the observation that stenosis develops in this region and often leads to symptoms.
Intracranial blood flow velocities in acute ischemic stroke.
Authors: Alexandrov A V , Bladin C F , Norris J W
Published: June 2011

Transcranial Doppler sonography (TCD) can evaluate noninvasively the blood flow velocities and patency of the main trunk of the middle cerebral artery (MCA). Using TCD we evaluated MCA patency and patterns of flow through the circle of Willis in patients with acute stroke.

Patients with symptoms of hemispheric stroke were evaluated with serial TCD tests during admission. The Canadian Neurological Scale was used to assess neurological deficits. In all cases computed tomographic scan, 99mTc hexamethylpropyleneamine oxime single-photon emission computed tomography, and carotid duplex were performed, and in some cases cerebral angiography.

Seventy-five consecutive patients with symptoms of acute ischemic stroke (mean time, 8 +/- 4 hours) were studied. Four circle of Willis perfusion patterns were observed: normal, collateral, stenotic, and occlusive. MCA occlusion or stenosis was seen in 70% of initial TCD studies in the stroke group (n = 50) but not in patients with transient ischemic attacks (n = 25). Eighty-six percent of the initial MCA occlusions had recanalized by 2 weeks after onset. Four patients, evaluated within the first 4 hours after onset, illustrated different patterns of MCA flow. TCD findings were compared with cerebral angiography, computed tomography, and single-photon emission computed tomography.

TCD allows early differentiation of patency and natural history of MCA thromboembolic events. This may have important implications in the decision for thrombolytic therapy.
Glucose given after hypoxic ischemia does not affect brain injury in piglets.
Authors: LeBlanc M H , Huang M , Patel D , Smith E E , Devidas M
Published: June 2011

Giving glucose before hypoxic ischemia worsens brain injury in piglets. Does giving glucose after hypoxic ischemia affect severity of injury?

Forty-three 0- to 3-day-old pigs were used. All piglets received 2 U/kg insulin before injury to prevent stress-induced hyperglycemia. Hypoxic ischemic brain damage was induced by clamping both carotid arteries and reducing arterial blood pressure to two thirds of normal by hemorrhage at time 0. At 15 minutes the fraction of inspired oxygen (FIO2) was reduced to 6%. At 30 minutes FIO2 was increased to 100%, the carotids were released, and the withdrawn blood was reinfused. The piglets were then randomized to receive either 2 mL/kg of 50% dextrose followed by 2 mL/kg per hour for 2 hours or an equal volume of saline.

Neurological examination scores (20 is normal, 5 is brain dead, by blinded observer) at 1 day postinjury were similar in the two groups: glucose, median 15.5 (25th percentile, 12.2; 75th percentile, 18); controls, 15.6 (9.3, 18). Piglets were killed at 3 days with brain preservation at death. Pathological examination scores (sum of scores from cortex, hippocampus, and basal ganglia: 30 is normal, 3 is total necrosis) by blinded observer were similar in the two groups: glucose, 26 (18, 28); controls, 25 (16.5, 28); NS.

Although elevated glucose levels during hypoxic ischemic injury worsen brain injury in the piglet, elevated glucose levels after injury do not affect the severity of the injury.
Tumor necrosis factor-alpha expression in ischemic neurons.
Authors: Liu T , Clark R K , McDonnell P C , Young P R , White R F , Barone F C , Feuerstein G Z
Published: June 2011

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with diverse proinflammatory actions, including endothelial leukocyte adhesion molecule expression. Since leukocytes infiltrate into ischemic brain lesions, the present study was conducted to examine whether TNF-alpha messenger RNA (mRNA) and peptide are expressed in the brain after experimental focal stroke and before leukocyte accumulation.

TNF-alpha mRNA and protein expression were monitored in the ischemic and nonischemic cerebral cortex of rats after focal ischemia produced by permanent middle cerebral artery occlusion. The effect of TNF-alpha administered by microinjection into the brain cortex on leukocyte adherence to brain capillaries was also studied.

Induction of TNF-alpha mRNA, normalized to a standard reference rat macrophage TNF-alpha mRNA, was detected as early as 1 hour after middle cerebral artery occlusion. TNF-alpha mRNA was elevated by 3 hours (29 +/- 6% versus 2 +/- 1% in sham-operated rats) only in the ischemic cortex, with peak expression at 12 hours (104 +/- 8%; P < .01). Five days after middle cerebral artery occlusion, TNF-alpha mRNA levels in ischemic cortex were still significantly elevated (38 +/- 5%; P < .05). Also, TNF-alpha mRNA expression was greater in the ischemic cortex of spontaneously hypertensive rats than in normotensive rats (P < .05). Double-labeling, immunohistochemical studies revealed the presence of TNF-alpha protein localized within nerve fibers in the evolving infarct at 6 and 12 hours after ischemia and further expression in the tissues immediately adjacent to the infarct 24 hours after ischemia. After 5 days, the neuronally localized peptide had diminished greatly, but macrophages located within the infarcted tissues were immunoreactive. Cortical microinjections of TNF-alpha (10 ng in 1 microL) produced a significant neutrophil adherence/accumulation in capillaries and small blood vessels 24 hours later.

These results represent the first demonstration that focal cerebral ischemia in rats results in elevated TNF-alpha mRNA and protein in ischemic neurons. The neuronal expression of peptide appears to facilitate the infiltration of inflammatory cells that can further exacerbate tissue damage in cerebral ischemia and might contribute to increased sensitivity and risk in focal stroke.
Differentiation between gaseous and formed embolic materials in vivo. Application in prosthetic heart valve patients.
Authors: Georgiadis D , Mackay T G , Kelman A W , Grosset D G , Wheatley D J , Lees K R
Published: June 2011

Doppler emboli detection is an established technique, but the nature of the underlying embolic material remains unclear. The intensity and spectral distribution of emboli signals could help to distinguish between signals arising from formed and gaseous emboli. We undertook this study to develop and evaluate a differentiation algorithm based on the spectral characteristics of emboli signals. Subsequently the algorithm was applied to patients with mechanical prosthetic cardiac valves.

Emboli signals detected in patients with carotid disease, acute stroke, and atrial fibrillation were used as formed emboli data, and signals detected in patients undergoing cardiac catheterization studies were used as gaseous emboli data. For each embolus signal, the maximal amplitude, the sum of amplitudes, and the spectral intensity distribution were calculated. Two hundred emboli signals from each category were used to develop a differentiation algorithm, which was subsequently evaluated on 501 additional solid and 995 gaseous emboli signals. The same algorithm was used to analyze 5958 emboli signals detected in 60 patients with mechanical prosthetic valves.

The best results were obtained with an algorithm based on both the maximal amplitude and the sum of amplitudes (sensitivity, 99%; specificity, 96.5%). On subsequent evaluation, the sensitivity and specificity of the algorithm were 99.6% and 89.8%, respectively. Of the 5958 emboli signals detected in prosthetic valve patients, 92.4% were classified as gaseous.

Differentiation between gaseous and formed emboli signals, as detected by transcranial Doppler in vivo, is feasible by means of spectral analysis. Application of the differentiation algorithm in prosthetic valve patients suggests that the embolic material in these patients is gaseous. The possibility of distinguishing between different formed embolic materials with this technique remains to be evaluated.
Hypertension and risk of stroke recurrence.
Authors: Alter M , Friday G , Lai S M , O'Connell J , Sobel E
Published: June 2011

Hypertension is a risk factor for initial stroke, but its relation to stroke recurrence is unclear. Therefore, we sought to analyze the effect of hypertension and its control on risk of stroke recurrence.

Within 1 month of onset, a population-based cohort of 662 patients from the Lehigh Valley with an initial stroke were enrolled. Hypertension was determined at enrollment by history. Blood pressure was also measured at enrollment and at each follow-up at 4- to 6-month intervals for up to 48 months (mean, 24 months). Stroke recurrence was verified by history, examination, and review of medical reports. Various criteria for control of blood pressure were defined. History of hypertension, measured blood pressure, and its control were analyzed in relation to stroke recurrence frequency using Kaplan-Meier and univariate, multivariate, and time-dependent Cox proportional hazards models.

At enrollment, 59.4% of the cohort had a history of hypertension and 81 patients had a second stroke. Those with a history of hypertension had a significantly higher stroke recurrence rate than those without such a history (P = .01). Among those with measured diastolic blood pressure at enrollment > or = 95 mm Hg, 43% had a stroke recurrence by the end of the study compared with only 19% below this cutoff (P = .005). Recurrence risk was reduced in a multivariate analysis as quality of diastolic blood pressure control increased (relative risk = 8.4, 3.9, and 2.0 among those with poor, fair, and good control, respectively, compared with nonhypertensive subjects). Systolic blood pressure and its control appeared less or not significantly associated with stroke recurrence.

History of hypertension and elevated measured diastolic pressure after the initial stroke were associated with an increased risk of second stroke. Controlling diastolic pressure substantially reduced this risk.
Trends in survival after stroke among Medicare beneficiaries.
Authors: May D S , Casper M L , Croft J B , Giles W H
Published: June 2011

Most strokes occur among people aged 65 years and older. The increasing proportion of persons who are in this age group underlines the importance for health-care providers to be aware of trends in poststroke survival. We investigated poststroke survival trends from 1985 to 1989 among Medicare beneficiaries.

Medicare hospital claim records and enrollment data were obtained on 1 901 439 Medicare patients with a principal diagnosis of stroke occurring during the years 1985 through 1989. Cox proportional hazard techniques were used to compare the 2-year poststroke survival for strokes occurring in 1986, 1987, 1988, and 1989 relative to strokes occurring in 1985. Poststroke survival trends were examined among groups defined by age, race, region, type of stroke, and, for a 20% subset, history of stroke.

We observed a modest improvement in poststroke survival from 1985 to 1989 (1989:1985 hazard ratio, 0.96; P < .05). Trends for persons with hemorrhagic stroke showed more improvement (hazard ratio, 0.88; P < .05) than those for persons with ischemic stroke (hazard ratio, 0.98; P < .05). Improvement was also greater among persons without known prior hospitalization for stroke (hazard ratio, 0.94; P < .05) and during periods of follow-up shorter than 2 years.

The variations in poststroke survival among subgroups of the population have important implications for the quality of life of stroke survivors and for the future medical and nursing needs of these populations.
Fibrin content of carotid thrombi alters the production of embolic stroke in the rat.
Authors: Halvorsen A M , Futrell N , Wang L C
Published: June 2011

Mechanical denudation of the endothelium of the carotid artery in animals produces a nonocclusive thrombus, but the brains of these animals have not been examined for the presence of embolic stroke.

The endothelium of the right carotid artery of 16 Wistar rats was denuded using a balloon catheter. Phosphotungstic acid hematoxylin (PTAH) staining and scanning electron micrographs of the nonocclusive thrombi in the carotid arteries were compared with those produced by photochemical methods, and brains were examined for infarcts.

Although nonocclusive thrombi were present in the carotid arteries of 4 of 4 rats killed at 4 hours and in 8 of 12 killed at 24 hours, neither cerebral infarcts nor emboli were seen in the 14 brains evaluated by light microscopy. PTAH demonstrated a high fibrin content in the thrombus produced by the endothelial denudation, with almost no fibrin seen in photochemically induced thrombi. Scanning electron microscopy confirmed dense networks of fibrin in the thrombi produced by balloon denudation.

The composition of a nonocclusive thrombus may determine the embolic potential of this thrombus. A low fibrin content in a nonocclusive platelet thrombus may enhance the embolic potential. This suggests that platelet inhibition may also be indicated in patients with carotid artery disease who are being treated with anticoagulant.
Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury.
Authors: Shapira Y , Lam A M , Eng C C , Laohaprasit V , Michel M
Published: June 2011

The aim of this study was to determine the time and dose response of the therapeutic effects of the N-methyl-D-aspartate receptor antagonist ketamine in experimental head injury.

Sixty-six male Sprague-Dawley rats were divided into eight groups. Groups A, B, and C were surgically prepared but received no trauma. Groups D through H received a nonpenetrating impact to the left cranium. Group A (n = 7) received no treatment. Groups B (n = 4) and C (n = 5) received 60 and 120 mg/kg IP ketamine, respectively. Group D (n = 8) received no treatment. Groups E (n = 8) and F (n = 7) received 120 and 180 mg/kg IP ketamine, respectively, 1 hour after head trauma. Groups G (n = 7) and H (n = 9) were treated with 180 mg/kg IP ketamine 2 and 4 hours after head trauma, respectively. Neurological severity score (NSS, 0 through 25 from no injury to severe injury) was determined at 1, 24, and 48 hours after head trauma. After death at 48 hours, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites in the contralateral hemisphere for determination of tissue specific gravity and water content. Brains were then placed in 4% formaldehyde, and the volume of hemorrhagic necrosis was measured 4 days later. NSS was compared within and between groups using the Kruskal-Wallis test for repeated measurements and Mann-Whitney U test for post hoc testing. Water content, specific gravity, and hemorrhagic necrosis were compared within and between groups using two-way ANOVA followed by Fisher's protected least significant difference procedure. A value of P < .05 was considered statistically significant.

Head trauma alone increased NSS, decreased specific gravity, increased water content, and caused cerebral infarction in the injured hemisphere. Ketamine given in two time-dose regimens, 180 mg/kg IP at 2 hours (group G) and 120 mg/kg IP at 1 hour (group F) after trauma, improved NSS from 11.6 +/- 1.7 and 14.4 +/- 0.8 at 1 hour to 4.4 +/- 1.3 and 8.0 +/- 1.4 (mean +/- SEM) at 48 hours, respectively (P < .03). Compared with the untreated group (group D), 180 mg/kg IP ketamine given at 2 and 4 hours after head trauma decreased the volume of hemorrhagic necrosis from 37.1 +/- 9.5 mm3 to 10.1 +/- 3.8 and 15.3 +/- 3.6 mm3, respectively (P < .05). Brain tissue specific gravity and water content at 48 hours were not significantly different between treated and untreated groups. There was no difference in rectal and temporalis muscle temperature between groups.

We conclude that 180 mg/kg IP ketamine was effective in ameliorating neurological dysfunction after head trauma in rats when the administration time was delayed for 1 hour to 2 hours but not after 4 hours. When given at 1 hour after head trauma, ketamine at 120 mg/kg but not 60 mg/kg is effective in reducing neurological damage after head trauma.
Correlation between angiogenesis and basic fibroblast growth factor expression in experimental brain infarct.
Authors: Chen H H , Chien C H , Liu H M
Published: June 2011

Cerebral endothelial cells are quiescent under normal conditions; they are stimulated to proliferate around an infarct, although the mechanism is unclear. In the present study we explored the relation between angiogenesis and the expression of basic fibroblast growth factor (bFGF) by participating cells in brain infarct.

Brain infarct was created in rats by ligation of a branch of the left middle cerebral artery followed by permanent occlusion of the left common carotid artery and temporary occlusion of the right common carotid artery. The brains were removed after 1 to 14 days and studied with histological and immunohistochemical methods. Bromodeoxyuridine (BRdU) was used as an S-phase marker for the proliferative cells.

Enhanced bFGF immunoreactivity was observed in neurons adjacent to the infarct after 1 day, and the change subsequently spread to distant neurons in the ipsilateral hemisphere. After 2 days blood vessels and glial cells around the infarct began to incorporate BRdU. During the first week new capillaries accompanied by macrophages extended into the infarct. The macrophages, endothelial cells, and reactive astrocytes expressed mild to moderate bFGF immunoreactivity.

The spatial and temporal correlation between bFGF expression and angiogenesis in conjunction with the well-known biological properties of bFGF suggest that bFGF produced by neurons, macrophages, and glial cells may participate in angiogenesis in brain infarct.
Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats.
Authors: Yang G Y , Betz A L
Published: June 2011

The integrity of the blood-brain barrier may play an important pathophysiological role during postischemic reperfusion. To determine the factors that lead to exacerbation of brain injury by reperfusion, we investigated changes in cerebral blood flow, blood-brain barrier permeability, edema formation, and infarction in permanent or temporary middle cerebral artery occlusion in rats and studied the relation between local cerebral blood flow and blood-brain barrier disruption.

Middle cerebral artery occlusion was performed with the rat suture model, allowing either permanent (6 hours) or temporary occlusion (3 hours of occlusion and 3 hours of reperfusion). We measured brain water, ion contents, and infarct volumes and determined cerebral blood flow using laser Doppler flowmetry and blood-brain barrier permeability with [3H] alpha-aminoisobutyric acid.

During occlusion, cerebral blood flow was reduced to 7% to 15% (permanent) and 10% to 17% (temporary) of the baseline. During 3 hours of reperfusion, it returned to 47% to 80% (lateral cortex) and 78% to 98% (medial cortex) of the baseline. Compared with the contralateral hemisphere, the water content in the ischemic area increased in both permanent and temporary groups (P < .05, P < .01). Both infarct volume and blood-brain barrier disruption were greater in the reperfusion group compared with the permanent occlusion group (P < .05). Blood-brain barrier disruption correlated with cerebral blood flow during reperfusion (P < .05).

These findings demonstrate that brain infarct and blood-brain barrier disruption are exacerbated after reperfusion in this model of focal ischemia. Blood-brain barrier disruption may relate to the degree of cerebral blood flow recovery. Thus, although early reperfusion in focal ischemia may preserve penumbra tissue, late reperfusion may increase the tissue injury.
Differential effect of three cyclooxygenase inhibitors on human cerebral blood flow velocity and carbon dioxide reactivity.
Authors: Markus H S , Vallance P , Brown M M
Published: June 2011

Prostaglandins are believed to play an important role in maintenance of cerebral blood flow and possibly in the vasodilatory response to carbon dioxide. Therefore, the nonsteroidal anti-inflammatory drugs and aspirin, which inhibit cyclooxygenase, might be expected to reduce cerebral blood flow and the response to hypercapnia. This could induce cerebral ischemia in patients with a hemodynamically critical circulation. It would also interfere with the measurement of cerebrovascular reserve using carbon dioxide.

The effect of a single dose of indomethacin and of two other cyclooxygenase inhibitors (aspirin and sulindac) on the cerebral circulation was measured using transcranial Doppler ultrasonography of the middle cerebral artery. Seven normal adults were studied in each drug group. Resting blood flow velocity and the responses to hypercapnia and to hyperventilation were measured.

Indomethacin resulted in a fall in basal middle cerebral artery flow velocity from a mean of 48.9 cm/s to 34.0 cm/s (P < .002). It also reduced the vasoconstrictor response to hypocapnia (induced by hyperventilation) from 37.5% to 20.7% (P < .003). There was a nonsignificant reduction in the vasodilatory response to 8% carbon dioxide (mean: predrug, 87.7%; postdrug, 61.0%), with marked intersubject variability. In contrast, basal middle cerebral artery velocity and vasoconstrictor and vasodilatory responses to changes in carbon dioxide were unchanged after aspirin or sulindac administration.

The lack of effect of aspirin on basal cerebral blood flow velocity and on vasodilatory reserve is reassuring; aspirin will not reduce cerebral blood flow or the response to a reduced perfusion pressure in patients with critically impaired cerebral hemodynamics. However, indomethacin should be avoided in such patients.
Spatial distribution of carotid intimal-medial thickness as measured by B-mode ultrasonography.
Authors: Espeland M A , Hoen H , Byington R , Howard G , Riley W A , Furberg C D
Published: June 2011

Measurements of intimal-medial thickness (IMT) of the carotid artery by B-mode ultrasonography are widely used as markers of atherosclerosis. This report describes empirical features of these measurements to characterize their distribution within arterial wall segments, to explore their potential as study outcome measures, and to examine their links with traditional risk factors for cardiovascular disease.

Sequential transverse measurements of IMT in the carotid arteries were made in 899 participants from the Asymptomatic Carotid Artery Progression Study (ACAPS) at baseline. Data from 17 intrasegment sites in each of 12 arterial wall segments were used to describe patterns of thickness and visualization and to characterize cross-sectional area, severity, and roughness/irregularity by the intrasegment averages, maxima, and SDs of IMT, respectively.

Serial correlations of IMT measurements indicated localized and diffuse features of disease. The spatial distribution of IMT had two dominant features: overall mass and mass relative to roughness. The validity of these features was demonstrated by their correlation to known risk factors for carotid atherosclerosis: body mass index, age, high-density lipoprotein cholesterol, systolic blood pressure, smoking, and sex.

Both the mean and maxima of intrasegment measurements appear to be good candidates for use in clinical studies. B-mode ultrasonography has validity for the description of IMT roughness and shape. Both of these features are linked to cardiovascular risk factors, which supports the multifaceted nature of atherosclerosis.
Fibrin contributes to microvascular obstructions and parenchymal changes during early focal cerebral ischemia and reperfusion.
Authors: Okada Y , Copeland B R , Fitridge R , Koziol J A , del Zoppo G J
Published: June 2011

Ischemic cerebral injury is associated with activation of the blood coagulation cascade. To elucidate the contribution of fibrin formation to microvascular injury during focal cerebral ischemia and reperfusion, we have studied the time course and the localization of fibrin deposition in cerebral microvessels and the surrounding tissues during ischemia/reperfusion in a well-described nonhuman primate model.

Cerebral tissues from adolescent male baboons were examined after 2-hour middle cerebral artery occlusion (n = 3) and after 3 hours of middle cerebral artery occlusion and 1-hour (n = 6), 4-hour (n = 3), and 24-hour (n = 4) reperfusion; tissues from control primates (n = 3) also were examined. Fibrin deposition was detected by immunohistochemical techniques using the fibrin-specific monoclonal antibody MH-1. The number and size distribution of microvessels associated with fibrin were quantified by video-imaging microscopy.

Fibrin was associated with microvessels only in the ischemic zone where severe neuronal injury was documented, its frequency increasing with the reperfusion period (F4,26 = 3.80, P < .05). Extravascular fibrin deposition was significantly increased by 24-hour reperfusion compared with the other subjects (P < .05). Preischemia infusion of the anti-tissue factor monoclonal antibody TF9-6B4 resulted in significant reduction of intramicrovascular fibrin (P < .038 versus no intervention) at 1-hour reperfusion but had no effect on extravascular fibrin deposition.

These results suggest that microvascular fibrin deposition accumulates in a time-dependent manner during focal cerebral ischemia/reperfusion and that exposure of focal cerebral ischemia/reperfusion and that exposure of plasma to perivascular tissue factor is partially responsible for occlusion formation. During ischemia the large plasma protein fibrinogen extravasates and interacts with parenchymal tissue factor, forming significant extravascular fibrin by 24 hours of reperfusion.
Cerebral hyperemia in MELAS.
Authors: Gropen T I , Prohovnik I , Tatemichi T K , Hirano M
Published: June 2011

The pathophysiology of stroke-like episodes in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is uncertain.

We studied a 24-year-old man with MELAS who had fluent aphasia and right hemianopia. Magnetic resonance imaging and computed tomography showed a large infarction in the parietal, temporal, and occipital lobes. We performed serial planar 133Xe regional cerebral blood flow studies and single-photon emission computed tomography. Fifteen and 26 days after the stroke-like episode, there was generalized hyperperfusion, highest in infarcted areas. Four and 8 months after the stroke-like episode, the brain was still hyperemic, with highest flow in noninfarcted tissue. Reactivity to CO2 was less than normal within the infarct at 26 days but improved thereafter. In the noninfarcted region, vasomotor reactivity was impared at 4 months, when resting flows were at their peak.

We observed generalized cerebral hyperemia and fluctuating CO2 reactivity in MELAS, possibly a consequence of local lactic acid production. In addition, this case suggests that nonquantitative functional imaging may be misleading in MELAS.
Improved Survival of Stroke PatientsDuring the 1980s
Authors: Shahar Eyal , McGovern Paul G. , Sprafka J. Michael , Pankow James S. , Doliszny Katherine M. , Luepker Russell V. , Blackburn Henry
Published: June 2011

Background and Purpose
The underlying reasons for the decline in stroke mortality in the United States are not well understood and have been the subject of ongoing debate. This study was undertaken to determine whether survival of hospitalized stroke patients has changed during the 1980s, thereby contributing to the decline in stroke mortality during that period.

Methods
For the years 1980, 1985, and 1990, we obtained listings of discharge diagnoses from hospitals in the Minneapolis-St Paul metropolitan area and identified all hospitalizations with a discharge diagnosis code of acute cerebrovascular disease according to the
International Classification of Diseases, 9th Revision.
A 50% random sample of men and women aged 30 to 74 years was selected in each survey for detailed medical record abstraction. Standardized sets of criteria for stroke were then used to validate acute stroke events throughout the 1980s. Each of the three period cohorts of hospitalized stroke patients (1980, 1985, and 1990) was followed for at least 2 years for all-cause mortality end point.

Results
A total of 1853 patients met minimal criteria for acute stroke: 564 patients in 1980, 598 patients in 1985, and 691 patients in 1990. Controlling for age, the odds of death within 2 years after stroke were approximately 40% lower in 1990 than in 1980. The relative odds of 2-year death in 1990 (versus 1980) were 0.65 (95% confidence interval, 0.47 to 0.89) and 0.60 (95% confidence interval, 0.42 to 0.85) for men and women, respectively. The improved survival was evident in the short term (28 days) as well as for stroke patients who survived that period. Analysis according to stroke subtype revealed that improved survival of ischemic stroke and specifically of stroke with no apparent cardioembolic source largely accounted for the overall trend. The prognosis of stroke patients who were admitted in a comatose state has not changed during that decade.

Conclusions
Despite the absence of any clear major advances in acute stroke therapy, survival of stroke patients substantially improved during the 1980s. The underlying reasons for this unexpected yet remarkable trend remain uncertain but may include improved supportive and rehabilitative care of stroke victims as well as a change in the natural history of the disease.
Monitoring Combined Antithrombotic Treatments in Patients With Prosthetic Heart Valves Using Transcranial Doppler and Coagulation Markers
Authors: Sturzenegger Matthias , Beer Juerg H. , Rihs Frank
Published: June 2011

Background and Purpose
The combined use of coumarin and low-dose aspirin appears to reduce the risk of systemic embolism at a low risk of bleeding. The remaining incidence of embolism of approximately 2%/y is still high. Methods for real-time detection of embolic events have not been used thus far to monitor the efficacy of therapeutic strategies. They might permit individually tailored, effective treatments.

Methods
The frequency of embolic signals in both middle cerebral arteries was monitored using a two-channel 2-MHz transcranial Doppler system. We examined five patients with mechanical prosthetic heart valves suffering from recurrent cerebral ischemic symptoms despite adequate anticoagulant therapy (international normalized ratio, 3.0 to 4.3). Measurements were performed on coumarin alone (four baseline values) and subsequent to the addition of intravenous (500 mg bolus) and oral (100 mg/d for 10 days) aspirin or intravenous (5000 IU bolus) heparin. The prothrombotic markers thrombin–antithrombin III complex, fibrinopeptide A,
d
-dimer, and platelet β-thromboglobulin were measured simultaneously.

Results
None of the combined drug regimens led to a significant reduction of the emboli count. The values of thrombin–antithrombin III complex, fibrinopeptide A, and
d
-dimer were already within normal limits with coumarin alone. The β-thromboglobulin levels, however, were increased, and additional aspirin or heparin did not reduce them. There was no correlation between the emboli count and the prothrombotic markers or between the prothrombotic markers and the different drug regimens.

Conclusions
The rate of cerebral emboli measured with transcranial Doppler in the group of high-risk patients studied was not influenced by additional antiplatelet therapy. The emboli are likely to be composed at least in part of platelets, and their generation seems not dependent on thrombin or cyclooxygenase. There is an apparent discrepancy between the unchanged rate of emboli during Doppler monitoring found in this and other studies and the partial efficacy of combined treatment with coumarin and aspirin in clinical long-term studies. This may be explained by differences in the composition or size of the emboli.