bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodilution improves cerebral hemodynamics in internal carotid artery occlusion.
Authors: Yamauchi H , Fukuyama H , Ogawa M , Ouchi Y , Kimura J
Published: June 2011

Hemodilution may be a useful form of therapy for patients with carotid occlusive disease and hemodynamic ischemia. Accordingly, we evaluated the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in patients with carotid artery occlusion.

Using positron emission tomography, we analyzed regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and blood volume before and after isovolemic hemodilution in five patients with unilateral internal carotid artery occlusion and minor stroke. Hemodilution was accomplished by phlebotomy of 400 mL and infusion of 400 mL of hydroxyethyl starch.

Before hemodilution, the patients had a significant decrease in blood flow and oxygen transport along with significantly elevated oxygen extraction fraction in the cerebral hemisphere with carotid artery occlusion compared with six control subjects. After hemodilution, the hematocrit and arterial oxygen content decreased from 41.2% and 18.6 mL/dL to 36.3% and 16.5 mL/dL, respectively. Both cerebral blood flow and oxygen transport were increased and oxygen extraction fraction was decreased without any change in oxygen consumption. The degree of increase in blood flow and oxygen transport was positively correlated with the ratio of oxygen extraction fraction to blood volume before hemodilution.

These findings indicate that hemodilution improves oxygen transport as well as blood flow in patients with internal carotid occlusion and decreased perfusion and that this improvement may be more prominent in patients with a severely compromised hemodynamic state. Thus, hemodilution may be useful in patients with hemodynamic ischemia.
Hematologic abnormalities occur in both cortical and lacunar infarction.
Authors: Kilpatrick T J , Matkovic Z , Davis S M , McGrath C M , Dauer R J
Published: June 2011

Primary hematologic abnormalities are a rare but established cause of ischemic stroke. In addition, activation of hemostatic parameters is often present during the acute phase of stroke. However, it is uncertain whether these abnormalities occur in both cortical and lacunar infarction; this study aimed to further assess this issue.

Hematologic parameters (prothrombin, activated partial thromboplastin, thrombin clotting, and euglobulin lysis times; and fibrinogen, fibrinopeptide A, antithrombin III, protein C, protein S, and plasminogen levels) were measured in 19 patients within 48 hours of the onset of acute cerebral infarction. These patients included 10 with cortical infarcts and 9 with lacunar infarcts, as determined by standard clinical and radiological criteria.

Five patients with lacunar infarction and 7 patients with cortical infarction demonstrated raised fibrinopeptide A levels, indicating enhanced thrombin activity. Fibrinolysis, assessed by the euglobulin lysis time, was impaired in 6 of 9 patients with lacunar infarction and in 2 of 10 patients with cortical infarction. Lupus anticoagulants were detected in 3 patients with lacunar infarction and in 1 patient with cortical infarction. Three patients in each group displayed decreased antithrombin III function, and 1 patient with a lacunar infarction had a low protein C level.

Primary hematologic disorders and secondary hemostatic derangements may occur in patients with either cortical or lacunar infarction.
Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats.
Authors: Linnik M D , Zobrist R H , Hatfield M D
Published: June 2011

Cells die by one of two mechanisms, necrosis or programmed cell death. Necrosis has been implicated in stroke and occurs when the cytoplasmic membrane is compromised. Programmed cell death requires protein synthesis and often involves endonucleolytic cleavage of the cellular DNA. We assessed the potential contribution of programmed cell death to ischemia-induced neuronal death.

Cycloheximide (protein synthesis inhibitor; 1 mg/kg per 24 hours) or vehicle (1 mL/kg per 24 hours) was continuously infused into the right cerebral ventricle of spontaneously hypertensive rats. Neocortical focal ischemia was produced by tandem occlusion of the right common carotid artery and the ipsilateral middle cerebral artery. After 24 hours the brain was stained with 2% 2,3,5-triphenyltetrazolium and the ischemic zone quantitated. Protein synthesis was determined by [3H]methionine incorporation into acid-precipitated protein. DNA integrity was determined in isolated DNA by gel electrophoresis and in whole cells by flow cytometry.

Continuous cycloheximide infusion caused approximately 70% reduction in cortical protein synthesis. Cycloheximide also reduced the size of the infarction produced by focal cerebral ischemia when compared with controls (ischemic brain volume, 147.5 +/- 25.9 and 188.7 +/- 16.8 mm3 for cycloheximide and saline, respectively; P < .01), suggesting that protein synthesis may contribute to cell death. Purified DNA from the ischemic zone showed evidence of endonucleolytic degradation when fractionated by gel electrophoresis. Flow cytometric analysis demonstrated increased propidium iodide fluorescence in intact cells isolated from ischemic cortex, indicating an increased accessibility of degraded DNA to the intercalating dye.

New protein synthesis appears to contribute to ischemic cell death in which endonucleolytic DNA degradation is apparent. These observations implicate programmed cell death in ischemic injury and may open unique therapeutic approaches for the preservation of neurons in stroke.
Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats.
Authors: Zhang Z G , Chopp M , Zaloga C , Pollock J S , Förstermann U
Published: June 2011

The purpose of this study was to measure the temporal profile of expression of the endothelial nitric oxide synthase (NOS) in cerebral microvessels after middle cerebral artery occlusion in the rat.

Middle cerebral artery occlusion was performed on 24 male Wistar rats by extracranial insertion of a 4-0 nylon monofilament into the internal artery. Three additional rats were used as controls. Animals were killed at 1, 2, 4, 6, 24, 48, 72, and 168 hours after middle cerebral artery occlusion (n = 3 per time point). Rat brains were perfused with buffer, frozen, sectioned, and stained with a monoclonal antibody against endothelial NOS. Adjacent sections were stained with hematoxylin and eosin for evaluation of neuronal damage.

The endothelial NOS in the cerebral vessels was upregulated at 1 hour after induction of ischemia throughout the ischemic region. The induction of the endothelial NOS progressively increased up to 24 hours of ischemia. In the periphery of the area of necrosis in the cortex, a delayed (24-hour) upregulation of the endothelial NOS remained constant throughout the duration of ischemia.

The rapid and intense differential expression of the endothelial NOS in the core and peripheral areas of the lesion indicates a role for endothelial NOS in ischemic cell damage and suggests that the increased expression of NOS may mediate changes in the cerebral blood flow.
Diffusion and perfusion magnetic resonance imaging studies to evaluate a noncompetitive N-methyl-D-aspartate antagonist and reperfusion in experimental stroke in rats.
Authors: Minematsu K , Fisher M , Li L , Sotak C H
Published: June 2011

Diffusion magnetic resonance imaging (MRI) can quantitatively detect focal ischemic injury within minutes of onset, and perfusion MRI can evaluate the brain's microcirculation. N-Methyl-D-aspartate (NMDA) antagonists and reperfusion can reduce lesion size in stroke models. We used diffusion and perfusion MRI to evaluate the in vivo effects of a noncompetitive NMDA antagonist, CNS 1102, in a temporary ischemia model.

Sixteen Sprague-Dawley rats underwent suture occlusion of the middle cerebral artery. Fifteen minutes after occlusion, animals were randomly assigned to treatment with CNS 1102 (n = 10) or placebo (n = 6), receiving a bolus of 1.13 mg/kg at that time and an infusion of 0.785 mg.kg-1.h-1 for the next 165 minutes. The placebo group received a saline bolus and infusion. Diffusion MRI studies by a spin-echo technique were initiated 30 minutes after occlusion and repeated every 30 minutes for the next 3 hours. Perfusion MRI studies were obtained using echo-planar imaging after injection of superparamagnetic iron oxide particles, immediately before and 15 minutes after withdrawal of the occluder at 3 hours after middle cerebral artery occlusion. At 24 hours, the animals were clinically evaluated (scale of 0 to 5) and electively killed, and the brain was stained with triphenyltetrazolium chloride to evaluate infarct size.

Diffusion imaging demonstrated markedly reduced ischemic lesion area in the CNS 1102 group during occlusion--10.5 +/- 7.3% (mean +/- SEM) of the ischemic hemisphere (optic chiasm slice) at 30 minutes after occlusion versus 50.0 +/- 2.7% of the hemisphere in controls (P < .02). With reperfusion after 3 hours of temporary ischemia, diffusion imaging documented an additional 29% reduction of the ischemic lesion area in the CNS 1102-treated group (P < .01) compared with the prereperfusion ischemic lesion area, with no change in the placebo group. During occlusion, perfusion imaging demonstrated a relative signal intensity decline of 31.5 +/- 7.7% in controls and 83.4 +/- 7.6% in the CNS 1102 group (P < .005), indicating better perfusion in the latter group. After removal of the occluder, perfusion improved in both groups and was not significantly different. Post mortem infarct volume was 53.8 +/- 20.0 mm3 in the CNS 1102 group and 216.8 +/- 16.1 mm3 in the controls (P < .0001). Clinical outcome at 24 hours was 1.1 +/- 0.4 in the CNS 1102 group and 4.0 +/- 0.5 (scale of 0 to 5) in the controls (P < .005).

This study demonstrates that CNS 1102 reduces early postischemic injury as documented by diffusion MRI and improves perfusion as documented by perfusion MRI and that reperfusion confers additional reduction of ischemic lesion size.
Reversed alterations of hippocampal parvalbumin and protein kinase C-gamma immunoreactivity after stroke in spontaneously hypertensive stroke-prone rats.
Authors: De Jong G I , Van der Zee E A , Bohus B , Luiten P G
Published: June 2011

Aging spontaneously hypertensive stroke-prone rats (SHR-SP) were previously shown to develop neocortical strokes. Because the hippocampal CA1 is selectively vulnerable to abnormal brain perfusion, the neuropathological effects of spontaneous strokes were investigated on specific neurochemical alterations in two major cell types of the hippocampal CA1 in SHR-SP.

The immunoreactivity for the gamma-isoform of protein kinase C (in pyramidal cells) and parvalbumin (in interneurons) was determined in the hippocampal CA1 by applying monoclonal antibodies. Because chronic treatment with the calcium antagonist nimodipine prevents the development of strokes in SHR-SP, we compared SHR-SP (stroke) with age-matched nimodipine-treated rats (nonstroke).

After stroke in control animals, we observed a strikingly enhanced immunoreactivity for protein kinase C-gamma in CA1 pyramidal cells compared with nimodipine-treated rats, which can be interpreted as the result of an increased activation of these cells. The pathological increase of protein kinase C-gamma immunoreactivity was accompanied by a reduced parvalbuminergic innervation of these pyramidal cells in symptomatic SHR-SP.

Because parvalbumin is present in a subset of GABAergic inhibitory interneurons, these data suggest that increased activity of CA1 pyramidal cells after spontaneous stroke may partially be related to a decreased inhibitory input on these cells.
Cerebral infarction due to painless thoracic aortic and common carotid artery dissections.
Authors: Veyssier-Belot C , Cohen A , Rougemont D , Levy C , Amarenco P , Bousser M G
Published: June 2011

Aortic arch dissection is usually lethal unless emergency surgery is performed. The dissection rarely may have a benign outcome or may occur without pain and be revealed by cerebral infarction. It is then likely to be seen primarily by a neurologist. In such cases, the value of new noninvasive diagnostic testing has not been reported.

A 51-year-old man had a sudden left-sided hemiplegia due to hemorrhagic capsular and caudate infarcts on the right side. Cervical ultrasound examination with color flow imaging showed a bilateral common carotid artery dissection extending up to the bifurcation. Transesophageal echocardiography showed an aortic arch dissection, involving the innominate and left common carotid artery origins, which was confirmed by magnetic resonance imaging and aortography. The patient spontaneously fully recovered and is still alive 24 months after the stroke onset.

This case emphasizes the usefulness of new noninvasive techniques such as transesophageal echocardiography and color-coded Doppler echocardiography in the diagnosis and follow-up of painless dissection of aortic and common carotid arteries. This cause of stroke may be underestimated.
Persistent primitive proatlantal intersegmental artery (proatlantal artery I) results in 'top of the basilar' syndrome.
Authors: Bahşi Y Z , Uysal H , Peker S , Yurdakul M
Published: June 2011

Persistent primitive proatlantal intersegmental artery (proatlantal artery I) is an anastomotic channel between the carotid and vertebrobasilar arterial systems. Persistence of this embryonic anastomosis is very rare. The "top of the basilar" syndrome is usually due to occlusion of thalamoperforating arteries by emboli that rise from the vertebrobasilar arterial system. In this case, however, the emboli stemmed from atherosclerotic plaques in the carotid system.

A 55-year-old woman was hospitalized with top of the basilar syndrome. A brain scan showed hypodense lesions extending from the mesencephalon to both thalami. Digital subtraction angiography of the cerebral circulation was performed, which revealed a proatlantal artery I on the left side. In addition, atheromatous plaques were seen along the internal and common carotid arteries on the same side.

The occurrence of proatlantal artery I is extremely rare. Top of the basilar syndrome is also rarely encountered. To our knowledge, this is the first report of a patient with both conditions.
Discrete cortical infarction with prominent impairment of thumb flexion.
Authors: Terao Y , Hayashi H , Kanda T , Tanabe H
Published: June 2011

Intracortical efferent zones in the primary motor cortex for thumb movements, namely thumb flexion, extension, adduction, and abduction, have been described in Macaca mulatta monkeys but not in humans. Even recent cortical mapping based on intraoperative monitoring does not provide information about intracortical efferent zones as it is not ethically possible to search the human motor cortex extensively by punctate electrodes.

A 78-year-old man with discrete cortical embolism over the left central sulcus is described. Only a mild weakness of his right thumb was observed. Thumb flexion was affected to a greater degree than thumb extension, adduction, and abduction. The lesion ran along the bottom of the central sulcus and affected part of the precentral and postcentral gyri on both sides of it. Animal studies in Macaca mulatta monkeys have shown that the intracortical efferent zones for thumb movement, especially for thumb flexion, are located in the part of the motor cortex just adjoining the central sulcus that folds down from the "bank" to the depth of the central sulcus. It was possible to explain the prominent weakness of thumb flexion if we applied the results of the animal studies.

Our case suggests that the same arrangement of intracortical efferent zones found in monkeys may also exist in human beings.
Altered gene expression in cerebral ischemia.
Authors: Kogure K , Kato H
Published: June 2011

Using the techniques of molecular biology, recent experimental studies have shown that cerebral ischemia induces a variety of changes in gene expression in the brain.

During the early postischemic stages, protein synthesis in the brain is generally suppressed, but specific genes are expressed and their corresponding proteins may be synthesized, such as immediate-early gene products (c-fos, c-jun, and zinc finger gene), heat-shock proteins, and amyloid precursor protein. The ability of neurons to induce such stress responses, which depends on both the severity of ischemia and the intrinsic nature of the neuronal populations, may be directly associated with neuronal death and survival after ischemia. Nerve growth factor and fibroblast growth factor are also induced after ischemia and may be related to repair processes, in which a role of glial cells is suggested. Postischemic events that may be associated with the altered gene expression include (1) induction of tolerance to ischemia after pretreatment with sublethal ischemia, (2) slow, progressive neuronal changes and the development of neuronal plasticity after ischemia, and (3) delayed neuronal changes in remote areas outside the cerebral ischemic focus.

Because a variety of harmful stresses, including ischemia, elicit the same stress response and because this response is induced when total protein synthesis in the brain is nearly completely suppressed, this response may be vital to cell survival and repair. A successful induction of this response may induce resistance and survival of neurons after ischemia. However, failure or abortion of the response and persistent stresses may lead to neuronal death and possibly long-term changes and degeneration.
Differentiation of multi-infarct and Alzheimer dementia by intracranial hemodynamic parameters.
Authors: Ries F , Horn R , Hillekamp J , Honisch C , König M , Solymosi L
Published: June 2011

The differentiation between the Alzheimer and multi-infarct types of dementia may still be equivocal considering clinical criteria, neuropsychological tests, and imaging techniques. Cerebral microangiopathic alterations underlying multi-infarct dementia should allow the characterization of dementia subgroups.

Patients with a diagnosis of multi-infarct dementia (n = 17; mean age, 69.1 +/- 8.5 years) or Alzheimer dementia (n = 24, mean age, 65.8 +/- 9.0 years) according to standard testing criteria, clinical findings, and neuroimaging techniques (computed tomography and magnetic resonance imaging) were investigated prospectively by transcranial Doppler sonography and compared with a normal reference group (n = 64; mean age, 61.0 +/- 11.1 years). Transcranial Doppler sonography allows an indirect evaluation of peripheral flow resistance in the microcirculatory bed by quantifying pulsatility characteristics, as reflected in the effective pulsatility range (time-averaged mean blood flow velocity minus the peak-systolic to end-diastolic amplitude, in centimeters per second).

A total of 204 vessels were investigated in 105 subjects. Mean and diastolic blood flow velocities as well as the effective pulsatility range were significantly lower in the multi-infarct dementia group compared with the Alzheimer and the normal reference groups (p < 0.001). By using receiver operating characteristic analysis, a cutoff point for effective pulsatility range values of -5 cm/sec gives a side-dependent sensitivity of 90.48-95.24% and a specificity of 64.71-70.59% in diagnosing Alzheimer-type dementia; the corresponding sensitivity and specificity for a value of -2 cm/sec are 82.35-88.24% and 80.95-90.48%, respectively.

Pulsatility changes as reflected by the effective pulsatility range are a noninvasive additional criterion in the differential diagnosis of dementia.
Predictors of carotid stenosis in older adults with and without isolated systolic hypertension.
Authors: Sutton-Tyrrell K , Alcorn H G , Wolfson S K , Kelsey S F , Kuller L H
Published: June 2011

This study was designed to determine the prevalence of carotid stenosis and atherosclerosis in older adults with and without isolated systolic hypertension and to determine risk factors for carotid artery disease in these two groups.

Duplex scans were performed on 187 participants of the Systolic Hypertension in the Elderly Program and on 187 normotensive control subjects. Doppler measures of blood flow velocity were used to determine the prevalence of internal carotid artery stenosis.

Carotid stenosis was found in 25% of hypertensive participants but in only 7% of normotensive participants (p < 0.001). Among hypertensive participants, carotid stenosis was correlated with lower diastolic blood pressure (p = 0.022). In multivariate analysis, systolic blood pressure of > or = 160 mm Hg was the strongest predictor of carotid stenosis. Other variables independently related to stenosis were diastolic blood pressure of < 75 mm Hg (p = 0.001), alcohol use (p = 0.005), heart rate of > or = 80 beats per minute (p = 0.013), smoking (p = 0.034), high concentration of apoprotein B (p = 0.001), and low concentration of high density lipoprotein cholesterol (borderline significant, p = 0.069). Among hypertensive participants, the strongest predictor of carotid stenosis was low diastolic blood pressure. This relation persisted even after taking into account differences in pulse pressure.

Isolated systolic hypertension is strongly correlated with carotid stenosis, and among those with isolated systolic hypertension low diastolic blood pressure is a marker for carotid stenosis.
Hemorrhagic transformation in cardioembolic cerebral infarction.
Authors: Hornig C R , Bauer T , Simon C , Trittmacher S , Dorndorf W
Published: June 2011

Because the frequency of hemorrhagic transformation of cerebral infarcts is still a matter of controversy, we performed a prospective magnetic resonance imaging study in a series of consecutive patients with cardioembolic stroke.

Among 200 consecutive patients with transient ischemic attack or ischemic stroke, 41 were identified with a computed tomographically proven supratentorial infarct due to cardiogenic embolism. Magnetic resonance imaging (T1-weighted) was performed 3 weeks after the stroke in 35 of these 41 patients. Eight patients received anticoagulants. Magnetic resonance images showed hemorrhagic transformation in 68.6% (24) of the 35 infarcts, always without clinical deterioration. In a stepwise forward logistic regression analysis only the volume of infarction edema on the initial computed tomogram was linked significantly with the risk of hemorrhagic transformation (p = 0.037). Hemorrhages were a regular finding on magnetic resonance images of infarcts exceeding a volume of 10 cm3 (94.4%, 17 of 18).

Hemorrhagic transformation is a regular finding in medium-sized and large cardioembolic infarcts. Thus, in therapeutic and preventive studies of acute stroke the severity, not the frequency, of hemorrhages into brain infarcts should be the matter of interest.
Pseudotumor syndrome associated with cerebral venous sinus occlusion and antiphospholipid antibodies.
Authors: Mokri B , Jack C R , Petty G W
Published: June 2011

Antiphospholipid antibodies are known to be associated with increased risk of venous and arterial thrombotic events, including cerebral venous thromboses. Pseudotumor syndrome can be produced by cerebral venous thrombosis. A patient with cerebral venous thrombosis associated with antiphospholipid antibodies who exhibited pseudotumor syndrome is reported.

A 49-year-old man who noted visual blurring and persistent vertical wavy lines in his fields of vision was found to have papilledema. Cerebrospinal fluid values were normal except for an opening pressure increase to 510 mm of fluid. His visual symptoms improved with lumbar puncture and the use of acetazolamide. Imaging studies showed that the transverse sinus was occluded completely on the left and partially on the right and that there was a small left cerebellar cortical venous infarction.

Antiphospholipid syndrome should be considered in the differential diagnosis of pseudotumor syndrome related to cerebral venous thrombosis.
Prognostic factors in first-ever stroke in the carotid artery territory seen within 6 hours after onset.
Authors: Censori B , Camerlingo M , Casto L , Ferraro B , Gazzaniga G C , Cesana B , Mamoli A
Published: June 2011

We sought to detect prognostic factors related to functional outcome during the first 6 hours after a first-ever stroke in the carotid artery territory.

All patients with these characteristics seen during a 3-year period were included. Outcome was evaluated according to a modified Rankin scale. The following variables were examined at univariate analysis: sex, age, severity of deficit at entry and at day 7, level of consciousness at entry, time after symptom onset, history of smoking, history of hypertension, diabetes, myocardial infarction, atrial fibrillation, rheumatic heart disease, dilated cardiomyopathy, all potential cardioembolic sources, presence of a consistent lesion on computed tomography at entry and at days 5-9, and the size of such lesion.

All entry criteria were met by 172 patients. Age > or = 70 years, a Canadian Neurological Scale score < 6.5 at entry and at day 7, atrial fibrillation, presence of a potential cardioembolic source, and a "large" lesion (involving more than half the cerebral lobe) on computed tomography at days 5-9 were associated with a significantly worse outcome both at 30 days and at 6 months. After multivariate analysis, a Canadian Scale score < 6.5 at entry (p < 0.0001) and atrial fibrillation (p = 0.005) were associated with a significant handicap or death at 30 days, whereas only a Canadian Scale score < 6.5 (p < 0.0001) was associated with a worse prognosis at 6 months. An association of age > or = 70 years with a worse outcome at 6 months was of borderline significance (p = 0.054).

Some prognostic indicators are available during the first few hours after onset of a carotid ischemic stroke and may be useful in the stratification of patients in clinical trials. Severity of deficit is the most important indicator, whereas the presence of atrial fibrillation worsens the prognostic outlook with respect to early handicap but not mortality.
Intracerebral hemorrhage after fibrinolytic therapy for acute myocardial infarction.
Authors: Wijdicks E F , Jack C R
Published: June 2011

Intracerebral hematoma may complicate treatment of acute myocardial infarction in patients treated with fibrinolytic agents. We studied the clinical presentation and computed tomographic characteristics.

We studied eight patients with lobar intracerebral hematomas after fibrinolytic treatment of acute coronary occlusion. All patients had electrocardiographic and laboratory evidence of acute myocardial infarction and were treated with tissue plasminogen activator or streptokinase followed by heparin infusion to prevent reocclusion. Computed tomography scans of 17 patients with cerebral hemorrhage from other causes were used for comparison.

For most patients, outcome was fatal within hours of the ictus. Computed tomography scans showed superficially large lobar hematomas in six patients. One patient had a putaminal hemorrhage, and one had a vermis hemorrhage. Multiple sites of intracerebral hemorrhage were noted in three patients. Fluid levels inside the hematoma suggesting continuing hemorrhage into multiple compartments were common. Radiologically, fluid levels in hematomas, multiple hematomas, and blood in multiple compartments served to differentiate fibrinolysis-induced hemorrhage from hemorrhage of other causes. Severe amyloid angiopathy was found in one patient who was operated on.

Hemorrhages in multiple compartments and the presence of fluid levels inside the hematoma suggest fibrinolysis-associated cerebral hematomas. Severe amyloid angiopathy may be a crucial factor in this clinical entity. Outcome is poor, and a high proportion of patients have rapid progression to brain death. Therefore, emergency neurosurgical evacuation will probably be unsuccessful.
Transforming growth factor-beta 1 reduces infarct size after experimental cerebral ischemia in a rabbit model.
Authors: Gross C E , Bednar M M , Howard D B , Sporn M B
Published: June 2011

The aim of this study was to examine the effect of transforming growth factor-beta 1, a cytokine shown to amelioriate cardiac ischemia, in a rabbit model of thromboembolic stroke.

An autologous clot embolus was introduced intracranially through the right internal carotid artery in 21 New Zealand White rabbits, with seven in each group receiving either vehicle control (albumin) or 10 or 50 micrograms transforming growth factor-beta 1 administered as an intracarotid bolus immediately before autologous clot embolization. Multiple physiological parameters were monitored, including regional cerebral blood flow, arterial blood gases, hematocrit, glucose, core temperature, and mean arterial pressure. The brain was harvested 4 hours after embolization, and infarct size was determined planimetrically as a percentage of the entire hemisphere.

Brain infarct size was reduced in both the 10-microgram (16.7 +/- 4.0% [mean +/- SEM], p < 0.05) and 50-microgram (21.7 +/- 4.5%) transforming growth factor-beta 1-treated groups when compared with the control group (31.9 +/- 6.6%). Regional cerebral blood flow did not show any significant intergroup or intragroup variation over time, although the 10-microgram transforming growth factor-beta 1 group experienced a greater return of cerebral blood flow in the first 2 hours after embolization.

Transforming growth factor-beta 1 reduced brain infarct size in a rabbit model of thromboembolic stroke. This effect was not related to a direct effect on blood flow. Studies are ongoing to determine the mechanism by which transforming growth factor-beta 1 salvages ischemic brain.
Cerebral blood flow and ischemia-induced neurotransmitter release in the striatum of aged spontaneously hypertensive rats.
Authors: Yao H , Ooboshi H , Ibayashi S , Uchimura H , Fujishima M
Published: June 2011

We found age-related vulnerability to cerebral ischemia in the hippocampus and striatum in spontaneously hypertensive rats. Further study revealed that ischemia-induced release of hippocampal taurine, an inhibitory amino acid, was reduced by 40% in aged rats compared with adult rats, which suggested an impaired inhibitory function against excitotoxicity in aged rats. The purpose of this study was to examine whether ischemia-induced neurotransmitter release is altered in the striatum of aged spontaneously hypertensive rats.

Five adult (5-6 months) and five aged (18-22 months) female spontaneously hypertensive rats were subjected to 20 minutes of cerebral ischemia induced by bilateral carotid artery occlusions and 120 minutes of recirculation under amobarbital anesthesia (100 mg/kg i.p.). Cerebral blood flow was determined using the hydrogen clearance method, and extracellular concentrations of neurotransmitters were determined with the brain dialysis technique in the striatum.

During ischemia, cerebral blood flow in aged rats decreased to 8.7 +/- 1.2 (mean +/- SEM) mL/100 g per minute (11% of the resting), which was not different from 5.2 +/- 1.7 mL/100 g per minute (8% of the resting) in adult rats, and extracellular dopamine and amino acids (glutamate, aspartate, and taurine) increased by approximately 170- and 10-30-fold, respectively, and returned to baseline after 20-40 minutes of recirculation. These values of neurotransmitters, however, were not different between aged and adult rats during ischemia and reperfusion.

It is unlikely that a presynaptic mechanism is involved in age-related vulnerability in the striatum of hypertensive rats.
Recurrent ischemic events in two patients with painless vertebral artery dissection.
Authors: McCormick G F , Halbach V V
Published: June 2011

Vertebral artery dissection causes endothelial changes and stenosis that may lead to recurrent ischemic neurological events. The diagnosis may not be obvious because the dissection may be painless and "spontaneous" (no obvious trauma). Magnetic resonance angiography has increasingly been used to screen patients for this disorder, but its accuracy has not yet been established.

Two patients were admitted with repeated transient ischemic attacks and strokes over 11 months and 1 month, respectively. Neither had a history of trauma, cervical pain, or headache. Magnetic resonance angiography failed to visualize vertebral artery dissections that were later revealed by conventional angiography. One patient's events were stopped by balloon occlusion of the vertebral artery proximal to the posterior inferior cerebellar artery branch.

Magnetic resonance angiography is not yet sensitive enough to always visualize vertebral artery dissection. Vertebral artery dissection is a life-threatening condition that requires aggressive evaluation and treatment.
Computed tomographic evidence of an extensive thrombosis and infarction of the deep venous system.
Authors: Rahman N U , al-Tahan A R
Published: June 2011

Massive bilateral infarcts due to deep venous system thrombosis are extremely rare and poorly documented. We present a case with computed tomographic evidence of both thrombosis and infarction of the whole deep venous system.

A previously healthy 30-year-old woman who had taken oral contraceptives for 3 years complained of recurrent headaches and transient visual obscuration. Three months later, she suddenly became comatose and was found to have papilledema. She rapidly worsened, became decerebrate, and died within 48 hours. Noncontrast computed tomographic scan showed the spontaneous hyperdensity of the thrombosed deep veins and a massive bilateral centrobasilar hypodensity suggestive of a deep venous system infarction.

This case shows that cerebral venous thrombosis can masquerade during 3 months as benign intracranial hypertension and then make a dramatic extension to the deep cerebral veins. It illustrates extensive thrombosis of the deep venous system as a possible cause of rapid coma and decerebration and stresses the importance of computed tomographic scan to show both the thrombosed veins and the venous infarct, which allows delineation of the deep venous system territory.
A prospective study of stroke in young adults in Cantabria, Spain.
Authors: Leno C , Berciano J , Combarros O , Polo J M , Pascual J , Quintana F , Merino J , Sedano C , Martín-Durán R , Alvarez C
Published: June 2011

The aim of this study was to determine the incidence, type, and prognosis of stroke in young adults in Cantabria, Spain.

We investigated prospectively all patients aged 50 years or below who were admitted with the diagnosis of a stroke to the University Hospital "Marqués de Valdecilla" from April 1, 1986, to March 31, 1988. This is the main hospital of the region to which all patients with neurological problems are referred. These patients underwent a complete clinical and laboratory assessment for stroke and had 1-year mean follow-up.

The total series included 81 patients. The annual age-specific crude incidence rates of stroke were 17.3 and 10.4 per 100,000 for males and females, respectively. Twenty-four patients (30%) were diagnosed as having nonembolic cerebral infarction, 14 (17%) embolic cerebral infarction, 20 (25%) subarachnoid hemorrhage, 22 (27%) spontaneous cerebral hemorrhage, and one case (1%) cerebral venous thrombosis. Eighteen patients (22%) died within 30 days of the cerebrovascular event, and two others died during the follow-up period. Seventy-nine percent of the survivors recovered and were completely self-sufficient.

The incidence of stroke in the young found in Cantabria is comparable with that in previous studies. The initial hospital mortality was not negligible, but the prognosis among the survivors was favorable.
Coagulation-fibrinolysis system in poststroke patients receiving antiplatelet medication.
Authors: Tohgi H , Takahashi H , Chiba K , Tamura K
Published: June 2011

We studied the activities of the coagulation-fibrinolysis system in the chronic stage of poststroke patients and the effect of antiplatelet medication on the system.

We determined fibrinogen, antithrombin III, thrombin-antithrombin III complex, tissue plasminogen activator antigen, plasminogen activator inhibitor-1, plasmin-alpha 2 plasmin inhibitor complex, and D-dimer in plasma from 153 poststroke patients in the chronic phase (ie, 33 patients not receiving antiplatelet medication, 78 patients receiving 200 mg/d ticlopidine, and 42 patients receiving 40 mg/d aspirin), and compared the results in control subjects and among the treatment groups.

The concentrations of fibrinogen, thrombin-antithrombin III complex, antithrombin III, plasmin-alpha 2 plasmin inhibitor complex, and tissue plasminogen activator were slightly but significantly increased in all treatment groups compared with control subjects (P < .01) but did not differ among the treatment groups. The plasminogen activator inhibitor-1 levels were significantly elevated in patients not receiving antiplatelet medication compared with control subjects (P < .01), whereas they were in the normal range and significantly lower in patients receiving ticlopidine or aspirin than in patients not receiving antiplatelet medication (P < .01). The plasminogen activator inhibitor-1 levels were significantly lower in patients whose platelet aggregation was inhibited by antiplatelet medication than in patients with uninhibited platelet aggregability (P < .05).

These findings suggest that coagulation-fibrinolysis markers are mildly increased in poststroke patients in the chronic phase and that antiplatelet medication is effective in reducing the elevated plasminogen activator inhibitor-1 levels.
Amount of blood on computed tomography as an independent predictor after aneurysm rupture.
Authors: Brouwers P J , Dippel D W , Vermeulen M , Lindsay K W , Hasan D , van Gijn J
Published: June 2011

After admission to the hospital of patients with aneurysmal subarachnoid hemorrhage, we assessed the predictive value of the extent of the hemorrhage on computed tomography in addition to that of clinical grading scales for poor outcome, infarction, and rebleeding.

We studied 471 consecutive patients with aneurysmal subarachnoid hemorrhage and used logistic regression with step-wise forward selection of variables.

On admission, poor outcome was predicted by a low Glasgow Coma Scale score (odds ratio, 0.8; 95% confidence interval, 0.7-0.9); treatment with fluid restriction (2.5; 1.6-4.0); age over 52 (2.6; 1.7-3.9); loss of consciousness at ictus (1.7; 1.1-2.6); or a large amount of subarachnoid blood (2.0; 1.3-3.1). Delayed infarction was predicted by a large amount of subarachnoid blood (1.8; 1.2-2.6) or treatment with tranexamic acid (1.6; 1.1-2.4). Rebleeding was predicted by treatment with tranexamic acid (0.4; 0.3-0.7; protective effect); age over 52 (1.9; 1.2-3.0); loss of consciousness at ictus (1.7; 1.1-2.7); or admission to a neurosurgery service (0.6; 0.3-0.9; protective effect). Comparison of the observed and predicted outcome events showed that inclusion of the amount of subarachnoid blood into a predictive model added little to the prediction of poor outcome in general, but much to the prediction of delayed cerebral ischemia.

The total amount of subarachnoid blood on the initial computed tomogram has independent predictive power for the occurrence of delayed cerebral ischemia.
Combined use of aspirin and heparin inhibits in vivo acute carotid thrombosis.
Authors: Huang Z S , Teng C M , Lee T K , Shun C T , Wang C Y
Published: June 2011

Carotid atherosclerotic thrombosis is an important cause of ischemic stroke in Western countries. The therapeutic efficacy of either aspirin or heparin alone in this setting is still controversial. Recently we developed a simple model, the "clamp" method, to induce acute carotid mural thrombosis in vivo in guinea pigs. In this study, we used this model to evaluate the antithrombotic effects of aspirin, heparin, and their combination.

Sixty-four male guinea pigs were divided equally into control, aspirin, heparin, and combined groups. Physiological saline, aspirin (5 mg/kg body wt), heparin (200 units/kg body wt), or a combination of aspirin and heparin, respectively, was injected via the jugular vein before the use of the clamp method. Thirty minutes after the injection of saline or drug(s), Péan's forceps was used to clamp the carotid artery at a tangent angle for 3 minutes. One hour later, the carotid artery was resected and prepared for observation under a scanning electron microscope or light microscope to evaluate the degree of mural thrombosis.

The results showed that the combination of aspirin and heparin had an excellent effect in inhibiting in vivo acute carotid thrombosis (p < 0.001) and was significantly better than the effect of aspirin alone (p < 0.01) or heparin alone (p < 0.01).

Our study clearly demonstrated that the combined use of aspirin and heparin produced a much better antithrombotic effect than either agent alone at sites of carotid endothelial injury when given before the injury. This combined regimen may be useful clinically in acute carotid thrombosis secondary to carotid diseases or carotid endarterectomy.
Tissue factor contributes to microvascular defects after focal cerebral ischemia.
Authors: Thomas W S , Mori E , Copeland B R , Yu J Q , Morrissey J H , del Zoppo G J
Published: June 2011

Microvascular perfusion defects occur after occlusion and reperfusion of the middle cerebral artery in examples of focal cerebral ischemia. In addition to cellular (eg, polymorphonuclear leukocyte) contributors to the focal "no-reflow" phenomenon, activation of coagulation may also play a role. We have tested a potential role of tissue factor-mediated coagulation in the microvascular perfusion defects seen after focal cerebral ischemia-reperfusion in a baboon model of reversible middle cerebral artery occlusion with the murine anti-tissue factor monoclonal antibody TF9-6B4. Tissue factor is the principal resident procoagulant substance in cerebral tissues and has a distinct perivascular distribution.

Microvascular patency in the basal ganglia after 3-hour middle cerebral artery occlusion and 1-hour reperfusion was quantified by computerized video imaging of carbon-tracer perfused tissues. Animals were randomized to receive intravenous TF9-6B4 (10 mg/kg) 10 minutes before middle cerebral artery occlusion (n = 6) or no treatment (n = 6) in an open study.

In the control animals, a significant decrease in patency was confirmed in microvessels less than 30 microns in diameter. Infusion of TF9-6B4 before middle cerebral artery occlusion produced a stable maximal level of circulating antibody within 10 minutes, which lasted the duration of ischemia and reperfusion. An increase in reflow in microvessels of all size classes occurred after TF9-6B4 infusion, which was significant in those 7.5 to 30 microns (P = .038) and 30 to 50 microns (P = .013) in diameter.

These results indicate that tissue factor-mediated events may also contribute to no-reflow in noncapillary microvessels after focal cerebral ischemia.
Electric injury with cerebral venous thrombosis. Case report and review of the literature.
Authors: Patel A , Lo R
Published: June 2011

A case of accidental electrocution with previously unreported arteriographic evidence of cerebral vein thrombosis is presented. A brief description of early and late neurological complications and current theories attempting to explain the histopathological findings of electric injury are reviewed. The occurrence and persistence of late neurological complications are elucidated.

A report of an accidental electrocution with 800 V of alternating current in a young man is presented. Cerebral angiography showed a cerebral vein thrombosis. The immediate complications included loss of consciousness, confusion, memory loss, and headache. Late complications of right-sided clumsiness, sensory loss, hemianopsia, and neglect persisted for more than 1 year despite the brain being outside the current pathway.

High-voltage electric injury may cause cerebral vein thrombosis with significant early and delayed brain injury even when the brain lies outside the current pathway.
Magnetic resonance imaging findings associated with cardiac arrest.
Authors: Roine R O , Raininko R , Erkinjuntti T , Ylikoski A , Kaste M
Published: June 2011

The frequency and prognostic significance of neuroradiological findings after cardiac arrest are unknown. Using healthy volunteers as control subjects, we studied the magnetic resonance imaging (MRI) findings associated with cardiac arrest, adjusted for confounding factors.

The presence of cerebral infarcts, leukoaraiosis, atrophy, and edema on ultra-low-field MRI was assessed in 88 community volunteers and 52 cardiac arrest survivors enrolled in a placebo-controlled, randomized, double-blind trial of nimodipine in out-of-hospital ventricular fibrillation.

Cardiac arrest was an independent risk factor for the presence of infarcts in a logistic regression model adjusted for age, sex, and history of myocardial infarction, stroke, coronary heart disease, cardiac failure, and hypertension (odds ratio, 3.6; 95% confidence interval, 1.3 to 9.9; P = .01). Leukoaraiosis was associated with increasing age but not with cardiac arrest. Adjusted for age, the delay of advanced life support had an inverse correlation with the degree of atrophy in placebo-treated patients (r = -.62, P < .0001) but not in patients treated with nimodipine (r = -.10, P = .43). Lack of age-related atrophy, possibly implicating the presence of brain edema, predicted poor outcome after cardiac arrest (odds ratio, 4.6; 95% confidence interval, 1.4 to 15.8; P = .01).

Cardiac arrest was associated with deep cerebral infarcts but not with leukoaraiosis. MRI findings did not predict the functional outcome at 1 year. Nimodipine treatment had no significant effect on the MRI findings, but delayed resuscitation was associated with probable brain edema only in placebo-treated patients.
Comparison of diagnostic techniques for the detection of a patent foramen ovale in stroke patients.
Authors: Di Tullio M , Sacco R L , Venketasubramanian N , Sherman D , Mohr J P , Homma S
Published: June 2011

The prevalence of a patent foramen ovale has been shown to be increased in patients with ischemic stroke. Transesophageal echocardiography, transthoracic echocardiography, and transcranial Doppler examination with contrast injection can all be used to search for a patent foramen ovale. We compared the accuracy of these techniques for identifying a patent foramen ovale in 49 patients with acute ischemic stroke or transient ischemic attack.

Transcranial Doppler examination of the right middle cerebral artery was performed during simultaneous transthoracic echocardiography with aerated saline injection, and again during transesophageal echocardiography; the latter was adopted as the "gold standard" for assessing the sensitivity of the other two tests.

Contrast transesophageal echocardiography detected a patent foramen ovale in 19 of 49 patients (39%), during normal respiration in 15 of them and during Valsalva maneuver in 4. Transcranial Doppler correctly identified 13 patients with a patent foramen ovale and all 30 patients without it. Therefore, the sensitivity of transcranial Doppler was 68% (13/19), and its specificity 100% (30/30). The 6 patients misclassified by transcranial Doppler (false negatives) had a very small right-to-left shunt detected by transesophageal echocardiography. Contrast transthoracic echocardiography was found to be the least sensitive test, detecting a patent foramen ovale in only 9 of 19 patients (47%). The specificity of transthoracic echocardiography was 100% (30/30 patients). The low sensitivity of transthoracic echocardiography was principally due to the suboptimal image quality obtained in false-negative patients. Both transcranial Doppler and transthoracic echocardiography were more sensitive in patients with cryptogenic stroke than in patients with stroke of determined origin. This may indicate the presence of larger, more easily detectable shunts in patients with cryptogenic stroke.

Transesophageal echocardiography is more sensitive than transcranial Doppler examination in detecting a patent foramen ovale, but only in cases of minimal right-to-left shunts, the clinical relevance of which remains to be established. The sensitivity of transthoracic echocardiography is heavily hampered by the frequency of inadequate heart visualization.