Differences in guidelines for patients with carotid artery stenosis in some European countries / A nyaki veroér-szukületes betegek ellátási irányelveinek különbségei Európa különbözo országaiban.

Összefoglaló. A tudomány jelenlegi állása szerint - csoportok összehasonlítására épülo matematikai-statisztikai eszközökkel - a leginkább hatékonynak és hatásosnak vélt kezelési módszerek szisztematikus elemzése mentén, a bizonyítékokon alapuló irányelveken nyugvó gyógyító munkát tekintjük követendonek. A nyaki veroérszukület ellátása esetén az utóbbi években elkészült mind a hazai, mind az európai irányelv, mindemellett a társszakmák irányelveiben is megjelentek kezelési javaslatok. Közleményünkben összehasonlítottuk a témában publikált magyar, angol, német és olasz nyelvu, valamint az európai társaságok által kiadott irányelveket. Az irányelvek alapelveikben hasonlóak, formailag és tartalmilag azonban jelentos (idonként egymásnak ellentmondani látszó) különbségeket találhatunk. Az ellentmondások három leggyakoribb oka: 1) az egyes irányelvek által kituzött célok különbözosége, 2) az aszimptomatikus és szimptomatikus betegcsoport definíciói, valamint 3) az eltéro evidenciaszintek. Az irányelvek összevetése alapján a tünetes, szignifikáns nyaki veroérszukületek sebészi ellátása evidenciának tekintheto. A szimptomatikus nyaki veroérszukület a definíció szerint ellenoldali cerebralis ischaemia okozta, tranziens vagy definitív plegia, paresis, aphasia és az azonos oldali arteria centralis retinae embolisatiója miatti amaurosis fugax. A tünetmentes nyaki veroérszukületek ellátása tekintetében az európai és a nemzeti irányelvek nem azonosak, ezen esetek terápiás döntése egyéni mérlegelést igényel. Tünetmentes, 70%-os stenosis esetén vascularteam-konzílium javasolt. Orv Hetil. 2020; 161(51): 2139-2145. Summary. The correct practice is the one that is proven to be the most effective based on systematic statistical analyses of different treatment methods, and is applied according to evidence-based principles. In recent years, not only has the European Society of Vascular Surgery created a guideline about the management of supra-aortic steno-occlusive disease, but some nations' vascular surgical societies and related disciplines have also developed their own guidance. In this paper, the guidelines by the European societies on the clinical care of patients with carotid artery luminal narrowing is compared to national guidelines published in Hungarian, English, German, and Italian. Although the fundamental points of the guidelines are similar, there are some important differences among them both in presentation and in content; as a result, they sometimes appear to be contradictory. The three main sources of inconsistency are the various goals, the discrepancy in the definition of symptomatic and asymptomatic carotid artery stenosis, and the bias arising from the use of distinct evidence levels. A comparison of guidelines suggests that the treatment of symptomatic significant carotid artery stenosis with surgery can be considered evidence. Symptomatic carotid artery stenosis is defined as transient or definite plegia, paresis, aphasia due to cerebral ischemia, and monocular blindness caused by embolism in the central retinal artery. However, in the case of asymptomatic 70% or greater carotid artery stenosis, the guidelines are quite heterogeneous, and these patients require individual consideration and a vascular team decision is recommended. Orv Hetil. 2020; 161(51): 2139-2145.

Cerebral iodized lipid embolization via a pulmonary arteriovenous shunt: rare complication of transcatheter arterial embolization for hepatocellular carcinoma.

We report the first European case of cerebral iodized lipid embolism post transcatheter arterial embolization for hepatocellular carcinoma. Lipiodol emboli and corresponding multifocal brain ischemia were documented with computed tomography (CT) and magnetic resonance (MR) in the acutely symptomatic patient. Transcranial Doppler sonography with contrast indicated a right-to-left shunt, while on a follow-up CT scan lipiodol embolization was detected in both lungs. Dilated pulmonary vessels and thick vascular channels were seen in the vicinity of the right diaphragm suggestive of pulmonary arteriovenous shunt. The patient symptoms regressed with supportive care alone, but he died 5 months later due to hepatic failure unrelated to the procedure.

Time course, distribution and cell types of induction of transforming growth factor betas following middle cerebral artery occlusion in the rat brain.

Transforming growth factor-ßs (TGF-ß1-3) are cytokines that regulate the proliferation, differentiation, and survival of various cell types. The present study describes the induction of TGF-ß1-3 in the rat after focal ischemia at 3 h, 24 h, 72 h and 1 month after transient (1 h) or permanent (24 h) middle cerebral artery occlusion (MCAO) using in situ hybridization histochemistry and quantitative analysis. Double labeling with different markers was used to identify the localization of TGF-ß mRNA relative to the penumbra and glial scar, and the types of cells expressing TGF-ßs. TGF-ß1 expression increased 3 h after MCAO in the penumbra and was further elevated 24 h after MCAO. TGF-ß1 was present mostly in microglial cells but also in some astrocytes. By 72 h and 1 month after the occlusion, TGF-ß1 mRNA-expressing cells also appeared in microglia within the ischemic core and in the glial scar. In contrast, TGF-ß2 mRNA level was increased in neurons but not in astrocytes or microglial cells in layers II, III, and V of the ipsilateral cerebral cortex 24 h after MCAO. TGF-ß3 was not induced in cells around the penumbra. Its expression increased in only a few cells in layer II of the cerebral cortex 24 h after MCAO. The levels of TGF-ß2 and -ß3 decreased at subsequent time points. Permanent MCAO further elevated the levels of all 3 subtypes of TGF-ßs suggesting that reperfusion is not a major factor in their induction. TGF-ß1 did not co-localize with either Fos or ATF-3, while the co-localization of TGF-ß2 with Fos but not with ATF-3 suggests that cortical spreading depolarization, but not damage to neural processes, might be the mechanism of induction for TGF-ß2. The results imply that endogenous TGF-ßs are induced by different mechanisms following an ischemic attack in the brain suggesting that they are involved in distinct spatially and temporally regulated inflammatory and neuroprotective processes.

The neuroprotective functions of transforming growth factor beta proteins.

Transforming growth factor beta (TGF-ß) proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-ß signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-ß subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-ß expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-ßs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-ßs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-ßs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-ßs during different brain lesions will also be discussed.

[Therapy for anti-MuSK antibody positive myasthenia gravis]. / A MuSK-ellenes antitest pozitív myasthenia gravis kezelése.

The authors report the case of a 27-year-old woman with muscle-specific receptor tyrosine kinase antibody positive myasthenia with predominantly ocular and bulbar symptoms. Both edrophonium and low dose (4×30 mg/day) pyridostigmin resulted in cholinergic side effects including fasciculation mainly in the facial and neck muscles, and excessive salivation. The patient responded well to a relatively high dose of chronic corticosteroid treatment (methyprednisolone 64mg/day), but the decrease of the corticosteroid dose below 16 mg/day induced exacerbation of the clinical symptoms. Immunosuppression with azathioprine and methotrexate failed to maintain the clinical improvement. However, plasma exchange was always very effective, and all clinical symptoms improved significantly. The authors conclude that patients with muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis should have an individual treatment protocol differing from those used in patients who do not have this antibody but are positive for acetylcholine-receptor antibody. Identification of the pathogenic antibody in the early stage of myasthenia gravis may help to develop the optimal, individualized treatment strategy, to avoid severe side effects, and to achieve fast improvement.

Distribution of mRNAs encoding transforming growth factors-beta1, -2, and -3 in the intact rat brain and after experimentally induced focal ischemia.

Transforming growth factors-beta1 (TGF-beta1), -2, and -3 form a small group of related proteins involved in the regulation of proliferation, differentiation, and survival of various cell types. Recently, TGF-betas were also demonstrated to be neuroprotective. In the present study, we investigated their distribution in the rat brain as well as their expression following middle cerebral artery occlusion. Probes were produced for all types of TGF-betas, and in situ hybridization was performed. We demonstrated high TGF-beta1 expression in cerebral cortex, hippocampus, central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular nucleus, substantia nigra, brainstem reticular formation and motoneurons, and area postrema. In contrast, TGF-beta2 was abundantly expressed in deep cortical layers, dentate gyrus, midline thalamic nuclei, posterior hypothalamic area and mamillary body, superior olive, areas of monoaminergic neurons, spinal trigeminal nucleus, dorsal vagal complex, cerebellum, and choroid plexus, and a high level of TGF-beta3 mRNA was found in cerebral cortex, hippocampus, basal amygdaloid nuclei, lateral septal nucleus, several thalamic nuclei, arcuate and supramamillary nuclei, superior colliculus, superior olive, brainstem reticular formation and motoneurons, area postrema, and inferior olive. Focal brain ischemia induced TGF-betas with markedly different expression patterns. TGF-beta1 was induced in the penumbral region of cortex and striatum, whereas TGF-beta2 and -beta3 were induced in different layers of the ipsilateral cortex. The expression of the subtypes of TGF-betas in different brain regions suggests that they are involved in the regulation of different neurons and bind to different latent TGF-beta binding proteins. Furthermore, they might have subtype-specific functions following ischemic attack.