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[Effect of cardiac embolism sources on origin of territorial cerebral infarcts].

BACKGROUND AND PURPOSE: To test the association of cardiac sources of embolism with territorial type brain infarcts. METHODS: From a prospective cerebral ischemia data base the 106 consecutive patients with territorial type cerebral infarcts on computerized tomography were analyzed. The 85 consecutive patients with lacunar lesions served as a comparison group. The association of cardiac sources of embolism with territorial types infarcts was assessed using univariate Chi Square tests and logistic regression models. Cardiac sources of embolism were defined as:atrial fibrillation, left cardiac thrombi, valvular vegetations, wall motion and valvular abnormalities, left atrial enlargement, open foramen ovale, septal aneurysm, mitral valve prolaps, and aortic arch atherothrombosis (all findings--except for atrial fibrillation--assessed by echocardiography). RESULTS: Atrial fibrillation was significantly associated with territorial type infarcts (odds ratio 2.2, 95% confidence interval 1.01-4.8). This effect was independent of additional cardiac diseases, other cardiac abnormalities, carotid artery stenosis, and patient age. Most likely due to the small sample size, left cardiac thrombi only showed a non-significant trend towards an association with territorial infarcts (odds ratio 3.0, 95% confidence interval 0.7-12.3). The rate of all other cardiac findings did not differ significantly between the comparison groups. CONCLUSION: Atrial fibrillation and cardiac thrombi showed an association with territorial type infarcts. Other so-called cardiac sources of embolism--except for mechanical valves and bacterial endocarditis which were not represented in our sample--revealed no clinically relevant association with embolic brain infarct pattern.

Adult↗

[Pattern of cerebral infarct in computerized tomography. Pathophysiologic concepts, validation and clinical relevance].

Our pathogenetically oriented classification system of hemispheric brain infarctions is reviewed. New data are presented to validate this classification from various points of view. A retrospective analysis of 73 patients with large striato-capsular infarcts demonstrated that two-thirds of them had a source of embolism either in the carotid bifurcation or in the heart. SPECT-imaging in patients with hemispheric brain infarctions of various origin revealed that the area of exhausted cerebral perfusion reserve largely exceeds the area of the infarct visible on CT if a hemodynamically caused low-flow infarction is present. This is not the case in the territorial type. Measurement of the hemispheric vasomotor reactivity to capnic stimuli confirmed this finding by demonstrating a severely reduced VMR in low-flow infarctions, but not in thrombo-embolically caused territorial infarctions. Lacunar infarctions due to occlusion of single long penetrating arteries should be judged as either "unequivocal", "probable" or "possible lacunae" and should be differentiated from small lacunar-like infarctions in the cortex ("non-lacunae") which represent small territorial infarctions due to thromboembolism of small pial arteries. Infarctions in the temporo-parieto-occipital watershed area are difficult to distinguish from territorial infarctions within the posterior part of the middle cerebral artery distribution. For research purposes, such patients should be excluded in order to keep the subgroups homogeneous. Consequences of this classification system for diagnostic and therapeutic strategies in stroke patients are discussed.

Blood Flow Velocity↗

Prognosis of myocardial infarction and brain functional asymmetry.

Seventy-eight men (mean age, 47.0 +/- 1.1 years) who had suffered from myocardial infarction were examined. Blood cholesterol, lipoproteins, triglycerides, insulin and cortisol concentrations were compared in patients with left hemisphere or right hemisphere cerebral dominance. Patients with left hemisphere dominance had more serious disease and much higher levels of blood cholesterol and lipoproteins. Patients with right hemisphere dominance had the highest levels of blood cortisol and insulin. The brain's functional asymmetry may be one of the risk factors for coronary atherosclerosis in subjects under the age of 50 years.

Cholesterol↗

The neural representation of postural control in humans.

Lesion of the "vestibular cortex" in the human posterior insula leads to a tilted perception of visual vertical but not to tilted body posture and loss of lateral balance. However, some stroke patients show the reverse pattern. Although their processing of visual and vestibular inputs for orientation perception of the visual world is undisturbed, they push away actively from the ipsilesional side (the side of lesion location), leading to a contraversive tilt of the body (tilt toward the side opposite to the lesion) and falling to that side. Recently, the origin of contraversive pushing was identified as an altered perception of the body's orientation in relation to gravity. These patients experience their body as oriented "upright" when actually tilted enormously to the ipsilesional side (18 degrees on average). The findings argued for a separate pathway in humans for sensing body orientation in relation to gravity apart from the one projecting to the vestibular cortex. The present study aimed at identifying this brain area. The infarcted brain regions of 23 consecutively admitted patients with severe contraversive pushing were projected onto a template MRI scan, which had been normalized to Talairach space. The overlapping area of these infarctions centered on the posterolateral thalamus. Our finding necessitates reinterpretation of this area as being only a "relay structure" of the vestibular pathway on its way from the brainstem to the vestibular cortex. The ventral posterior and lateral posterior nuclei of the posterolateral thalamus (and probably its cortical projections) rather seem to be fundamentally involved in the neural representation of a second graviceptive system in humans decisive for our control of upright body posture.

Adult↗

Predictive value of digital subtraction angiography in patients with tuberculous meningitis.

Digital subtraction angiography (DSA) was performed in 24 adults with tuberculous meningitis (TBM) and results were correlated with 24 admission and 16 follow-up CT examinations. 19 MRI studies and clinical outcome at a mean follow-up of 44 weeks. DSA was abnormal in 11 patients. Abnormal DSA was associated with advanced clinical stages of the Medical Research Council classification, admission CT with hydrocephalus or gyral cortical enhancement. MRI disclosed brain infarcts not seen on initial CT in 8 cases. Of seven patients who died, 4 had abnormal and 3 normal DSA. Among patients who survived, those with normal DSA had a better functional outcome by Karnofsky scores. During follow-up infarcts were evident in 16 patients. Abnormal DSA in relation to brain infarcts had a sensitivity of 0.56, specificity 0.75, positive predictive value 0.82 and negative predictive value 0.46. A single arteriogram does not predict the outcome in patients with TBM and its value is limited in the assessment of vascular complications of TBM. Angiography in TBM is justified only in specific clinical trials to assess new therapeutic modalities against infarcts.

Adolescent↗

Variability of the systemic acute phase response after ischemic stroke.

Despite apparent relationships between ischemic stroke and the acute phase response (APR), considerable variation in the APR exists between individuals. We therefore performed post-hoc analysis of individual APR profiles in 31 patients with ischemic stroke in relation to volume of brain infarction. Patients with ischemic stroke had serial blood samples taken within 12 h, and up to 12 months of symptom onset, for analysis of plasma C-reactive protein (CRP) and interleukin-6 (IL-6). Computed tomography (CT) brain infarct volume was measured at 5 to 7 days (median 23.9 cm(3)). An increase in plasma CRP after the admission sample was evident in 94% of patients by day 5 to 7 (median increase 558% of admission value). CRP response, assessed as area under the curve between admission and day 5 to 7, correlated strongly (r=0.62, p<0.001) with CT infarct volume. Those with greater infarct volumes had more evidence of infection, either prior to or during the first week after stroke. The pattern of response was similar for IL-6, although only 77% showed an increase in plasma IL-6 after the admission sample (median increase 148% of admission value). These data suggest that, although infection and other factors may contribute to systemic inflammation, the extent of acute brain injury after ischemic stroke is a major factor influencing the magnitude and variability of the APR.

Acute-Phase Reaction↗

[Moyamoya disease with intraventricular hemorrhage due to rupture of lateral posterior choroidal artery aneurysm: case report].

Intracranial aneurysms associated with moyamoya disease are often reviewed. Aneurysms not around the circle of Willis but on the collateral vessels are rare. A 71-year-old woman presented with sudden onset of severe headache and vomiting. CT scan showed an intraventricular hemorrhage from bilateral lateral ventricle to fourth ventricle. Cerebral angiography showed the occlusion of the terminal portion of the bilateral internal carotid artery with moyamoya vessels and three aneurysms at the distal portion of the left lateral posterior choroidal artery. Clinical symptoms improved day by day, but 17 days later, due to rebleeding of the aneurysms the patient fell into coma. The day after rebleeding, endovascular embolization was performed using liquid particle, and the left lateral posterior choroidal artery and the aneurysm were occluded. Brain infarction with massive brain edema of the left cerebral hemisphere resulted in the patient's death. The management of the aneurysms in the basal ganglia and on the collateral vessels associated with moyamoya disease is controversial. We suggest positive intervention during the acute stage for the peripheral artery aneurysms taking endovascular embolization into consideration to prevent rupture or rebleeding.

Aged↗

Pulmonary and systemic embolism after deliberate intravenous fluorocarbon administration.

After intravenous injection of 0.1 ml Fluorocarbon (FC) into the caudal vein of rats clear droplets which are reminiscent of gas emboli appear in the pulmonary and cerebral arteries. These droplets cannot be stained with Azan, haematoxylin-eosin, Nile blue sulfate, Sudan black B, and Sudan III in Paraplast embedded or frozen sections. Gas chromatography of affected lung tissue reveals a high concentration of FC. The clear droplets are the histological correlates of FC emboli which lead to haemorrhagic lung infarction and ischaemic brain infarcts. After intralienal injection FC induces haemorrhagic infarcts of the spleen near the injection site and massive embolization of the intrahepatic portal veins with consequent liver cell necrosis. FC droplets are phagocytosed by hepatic sinusoidal lining cells. Due to the absence of a specific method for identifying FC embolization of renal vessels is difficult to assess.

Animals↗

Stable expression of the vesicular GABA transporter following photothrombotic infarct in rat brain.

Before exocytotic release of the inhibitory neurotransmitter GABA, this amino acid has to be stored in synaptic vesicles. Accumulation of GABA in vesicles is achieved by a specific membrane-integrated transporter termed vesicular GABA transporter. This vesicular protein is mainly located at presynaptic terminals of GABAergic interneurons. In the present study we investigated the effects of focal ischemia on the expression of the vesicular GABA transporter. Vesicular GABA transporter mRNA and protein expression was examined after photothrombosis in different cortical and hippocampal brain regions of Wistar rats. In situ hybridization and quantitative real-time RT-PCR were performed to analyze vesicular GABA transporter mRNA. Both vesicular GABA transporter mRNA-stained perikarya and mRNA expression levels remained unaffected. Vesicular GABA transporter protein-containing synaptic terminals and somata were visualized by immunohistochemistry. The pattern of vesicular GABA transporter immunoreactivity as well as the protein expression level revealed by semiquantitative image analysis and by Western blot remained stable after stroke. The steady expression of vesicular GABA transporter mRNA and protein after photothrombosis indicates that the exocytotic release mechanism of GABA is not affected by ischemia.

Animals↗

History of infarction of the spinal cord.

In 1825 Astley Cooper described the first account of ligation of the abdominal aorta. The patient developed loss of feeling in his lower limbs, incontinence of urine and died after several days. A post mortem was carried out but not, unfortunately, of the spinal cord. This case was recorded again by Astley Cooper, by Brock in 1940-41, and again by Ellis in 1994. Whilst there was early recognition of infarction of the brain, infarction of the spinal cord was thought to be almost unknown by Charcot in 1883 but it was recorded in the English literature by Bastian in 1886 and Williamson in 1894. There were isolated case reports but it was the advent of major surgery upon the aorta in the Second World War that drew attention to the frequency of this condition. The subsequent evolution of our recognition of infarction of the cord is described. The present situation, where it can be caused by a fall in blood pressure without there being direct interference to the blood supply, is evaluated.

Europe↗

Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy.

We developed human mesenchymal stem cell (MSC) lines that could differentiate into various tissue cells including bone, neural cells, bone marrow (BM) stromal cells supporting the growth of hematopoietic stem cell (HSC), and so-called 'tumor stromal cells' mixing with tumor cells. We investigated the applicability of MSC as therapeutic cell transplanting reagents (cytoreagents). Telomerized human BM derived stromal cells exhibited a prolonged lifespan and supported the growth of hematopoietic clonogenic cells. The gene transfer of Indian hedgehog (Ihh) remarkably enhanced the HSC expansion supported by the human BM stromal cells. Gene-modified MSC are useful as therapeutic tools for brain tissue damage (e.g. brain infarction) and malignant brain neoplasms. MSC transplantation protected the brain tissue from acute ischemic damage in the midcerebral artery occlusion (MCAO) animal model. Brain-derived neurotrophic factor (BDNF)-gene transduction further enhanced the protective efficacy against the ischemic damage. MSC possessed excellent migratory ability and exerted inhibitory effects on the proliferation of glioma cells. Gene-modification of MSC with therapeutic cytokines clearly augmented the antitumor effect and prolonged the survival of tumor-bearing animals. Gene therapy employing MSC as a tissue-protecting and targeting cytoreagent would be a promising approach.

Animals↗