Pathogenesis of Leukoaraiosis: A Review

Leukoaraiosis (LA) represents the most common phenotype of cerebral small vessel disease. It is of undoubted significance regarding its vast prevalence and neuropsychiatric consequences, such as cognitive impairment, higher risk for ischaemic stroke and death. It has been associated with increasing age and conventional vascular risk factors (VRF). Despite huge efforts, LA pathogenesis is still incompletely understood. The hypotheses of ischaemia and malfunctioning blood-brain barrier seem to oppose each other. Hence, the focus has turned to endothelial dysfunction, through which both aforementioned mechanisms could be coupled. The VRF, which are almost universally present in patients with LA, have a detrimental impact on endothelium on their own. However, in LA there may be an additional or even primary endothelial dysfunction at play. This seems to be at the core of LA pathogenesis, leading to chronic ischaemia in cerebral white matter and blood-brain barrier dysfunction culminating in LA. The genetic susceptibility to harmful effects of VRF on endothelial function seems to play an important role. Regarding the burden of LA, interventional approaches should be aimed at decelerating or even halting the progression of the disease. These should focus on strict management of VRF and strategies to enhance endothelial function

Side effects of radiotherapy on the brain

Neželeni učinki radioterapije na možgane so številni in pogosto nepredvidljivi. Lahko gre za neposredno ali posredno okvaro možganov. Okvara se lahko pojavi akutno ali več tednov, mesecev ali celo let po končani radioterapiji. Ločevanje med temi oblikami je pomembno, saj so zgodnji zapleti navadno reverzibilni, pozni pa se večinoma ne popravijo. Incidenco neželenih učinkov radioterapije na možgane je težko oceniti. Razlogi za to so v različnih opredelitvah in metodoloških razlikah v raziskavah ter v klinični sliki, ki se pogosto prekriva z napredovanjem osnovne maligne bolezni. Med mehanizmi radiacijske okvare možganov je v ospredju okvara celic glije in možganskih endotelijskih celic. Za radiacijsko okvaro je zlasti občutljiv hipokampus. Obseg okvare možganov je odvisen od številnih dejavnikov. Dodatna sistemska ali intratekalna kemoterapija pomembno poveča nevrotoksičnost. Diagnosticiranje neželenih učinkov radioterapije na možgane je težavno, saj je časovni interval med radioterapijo in pojavom nevroloških simptomov precej variabilen, klinična slika pa lahko posnema metastatsko, paraneoplastično ali drugo nevrološko bolezen. Zavedati se je treba, da klinično sliko lahko pripišemo neželenim učinkom radioterapije na možgane šele po izključitvi drugih vzrokov. V članku opisujeva različne klinične oblike neposredne in posredne radiacijske okvare možganov. Pri akutni encefalopatiji ima pomembno vlogo okvara krvno-možganske pregrade. Pri zgodnji odloženi encefalopatiji je pomembna demielinizacija, pri pozni odloženi encefalopatiji pa radiacijska nekroza. O kognitivnem upadu kot posledici radioterapije so mnenja še vedno deljena.There are numerous and often unpredictable side effects of radiotherapy on the brain. The damage can be direct or indirect, and becomes apparent acutely or even many years thereafter. The distinction between these forms is important since early side effects are predominantly reversible whereas late ones usually are not. The incidence of radiotherapy-induced side effects is hard to estimate due to the differing definitions and methodologies used in clinical studies. Nevertheless, the clinical picture often resembles the progression of pre-existent malignant disease. The mechanism underlying side effects of radiotherapy is mainly injury to glial cells and cerebral endothelial cells. The hippocampus is especially prone to radiation damage. The burden of radiation damage in a given individual is dependent upon many factors. Concomitant systemic and intrathecal chemotherapy adds significantly to neurotoxicity. Diagnosing side effects of radiotherapy can be a daunting task since the time interval between radiotherapy and the occurrence of neurological side effects is variable. What is more, the clinical picture can resemble metastatic, paraneoplastic or other neurological disease. It is therefore of crucial importance to be aware of the fact that the clinical picture can be ascribed to side effects of radiotherapy only after other possible reasons (mainly tumor progression) have been effectively ruled out. The article entails a broad spectrum of direct and indirect radiotherapyinduced consequences on the brain. Acute encephalopathy is connected to blood-brain barrier disruption. Early-delayed encephalopathy is caused by demyelination. Late-delayed encephalopathy is represented mainly by radiation necrosis. Cognitive decline as a consequence of radiotherapy is still a matter of hot debate

Neželeni učinki radioterapije na možgane

There are numerous and often unpredictable side effects of radiotherapy on the brain. The damage can be direct or indirect, and becomes apparent acutely or even many years thereafter. The distinction between these forms is important since early side effects are predominantly reversible whereas late ones usually are not. The incidence of radiotherapy-induced side effects is hard to estimate due to the differing definitions and methodologies used in clinical studies. Nevertheless, the clinical picture often resembles the progression of pre-existent malignant disease. The mechanism underlying side effects of radiotherapy is mainly injury to glial cells and cerebral endothelial cells. The hippocampus is especially prone to radiation damage. The burden of radiation damage in a given individual is dependent upon many factors. Concomitant systemic and intrathecal chemotherapy adds significantly to neurotoxicity. Diagnosing side effects of radiotherapy can be a daunting task since the time interval between radiotherapy and the occurrence of neurological side effects is variable. What is more, the clinical picture can resemble metastatic, paraneoplastic or other neurological disease. It is therefore of crucial importance to be aware of the fact that the clinical picture can be ascribed to side effects of radiotherapy only after other possible reasons (mainly tumor progression) have been effectively ruled out. The article entails a broad spectrum of direct and indirect radiotherapyinduced consequences on the brain. Acute encephalopathy is connected to blood-brain barrier disruption. Early-delayed encephalopathy is caused by demyelination. Late-delayed encephalopathy is represented mainly by radiation necrosis. Cognitive decline as a consequence of radiotherapy is still a matter of hot debate.Neželeni učinki radioterapije na možgane so številni in pogosto nepredvidljivi. Lahko gre za neposredno ali posredno okvaro možganov. Okvara se lahko pojavi akutno ali več tednov, mesecev ali celo let po končani radioterapiji. Ločevanje med temi oblikami je pomembno, saj so zgodnji zapleti navadno reverzibilni, pozni pa se večinoma ne popravijo. Incidenco neželenih učinkov radioterapije na možgane je težko oceniti. Razlogi za to so v različnih opredelitvah in metodoloških razlikah v raziskavah ter v klinični sliki, ki se pogosto prekriva z napredovanjem osnovne maligne bolezni. Med mehanizmi radiacijske okvare možganov je v ospredju okvara celic glije in možganskih endotelijskih celic. Za radiacijsko okvaro je zlasti občutljiv hipokampus. Obseg okvare možganov je odvisen od številnih dejavnikov. Dodatna sistemska ali intratekalna kemoterapija pomembno poveča nevrotoksičnost. Diagnosticiranje neželenih učinkov radioterapije na možgane je težavno, saj je časovni interval med radioterapijo in pojavom nevroloških simptomov precej variabilen, klinična slika pa lahko posnema metastatsko, paraneoplastično ali drugo nevrološko bolezen. Zavedati se je treba, da klinično sliko lahko pripišemo neželenim učinkom radioterapije na možgane šele po izključitvi drugih vzrokov. V članku opisujeva različne klinične oblike neposredne in posredne radiacijske okvare možganov. Pri akutni encefalopatiji ima pomembno vlogo okvara krvno-možganske pregrade. Pri zgodnji odloženi encefalopatiji je pomembna demielinizacija, pri pozni odloženi encefalopatiji pa radiacijska nekroza. O kognitivnem upadu kot posledici radioterapije so mnenja še vedno deljena

Enhanced Hemodynamic and Clinical Response to αCGRP in Migraine Patients—A TCD Study

Introduction: Sensitisation of the nervous system in a patient with migraine is supposed to be associated with calcitonin gene-related peptide (CGRP) activity. Therefore, the vascular response to human αCGRP (hαCGRP) could be a surrogate marker for the sensitization. We hypothesize that vascular response to hαCGRP is augmented in a patient with migraine.Methods: Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in the middle cerebral artery (vm MCA). Simultaneously, end-tidal CO2 (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. The reconstruction of the signals was made for basal conditions, during and after CGRP infusion which were compared using statistics.Results: In both groups, we found significant decrease between measurement points of vm MCA and Et-CO2 during and after hαCGRP infusion. MAP did not show significant trends during the infusion, but it was significantly increased after the infusion in migraine patients only. Responses to hαCGRP, defined as differences between two measurement points, were significantly higher for vm MCA and Et-CO2 in patients with migraine. A significant difference between groups was found in MAP response. Significant relationships were found between migraine and vm MCA, Et-CO2, and MAP.Conclusion: In patients with migraine, vm MCA responses to hαCGRP are significantly higher and are associated with CGRP-induced headache which indicates that patients with migraine are more prone to sensitization

The Vasodilatory Response to CGRP of the Anterior and Posterior Cerebral Circulation in Migraine

IntroductionMigraine aura can be associated with headache or it may occur without one, which suggests an independent mechanism for the aura and for migraine headache. The role of CGRP in migraine headache is well established, but the connection between CGRP and the aura is still lacking an explanation. Exogenous CGRP can induce CGRP headaches and migraine auras in patients with migraine. The results of our recent study suggest differences in the vascular response to CGRP stimulation between migraine without aura and migraine with aura. Therefore, we hypothesized that the magnitude of the posterior cerebral circulation response in migraine with aura is greater than in migraine without aura and that CGRP stimulation has different effects on the anterior and posterior circulation in migraine with aura and migraine without aura.MethodsBy using transcranial doppler, we studied the hemodynamic effects of CGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on the mean arterial velocity in the middle cerebral artery and in the posterior cerebral artery in twenty patients with migraine and in a control group of twenty healthy subjects. The same CGRP effects on cerebral hemodynamics were analyzed separately for the group of patients with migraine with aura and the group of patients with migraine without aura. Fifteen patients with migraine (75%) had migraine without aura and 5 patients (25%) had migraine with aura.ResultsWe found that migraine has a significant impact on the vasodilatory response of the anterior (B = 4,249, SE = 1.023, r = 0.363, p < 0.001) and posterior cerebral circulation (B = 3.634, SE = 1.461, r = 0.227, p = 0.014). Migraine with aura was significantly associated with changes in the anterior (B = 2.558, SE = 0.880, r = 0.275, p = 0.005) and posterior cerebral circulation (B = 7.565, SE = 2,368, r = 0.359, p = 0.002), while migraine without aura was only significantly associated with changes in the anterior circulation. In addition, we established a significant impact of migraine with aura on VR PCA (B = 5.901, SE = 2,546, r = 0.291, p = 0.024).ConclusionWe conclude that TVR in the posterior cerebral circulation might be enhanced in MA and that aura might be a consequence of TVR enhancement

αCGRP-Induced Changes in Cerebral and Systemic Circulation; A TCD Study

It is known that perivascular application of CGRP induces cerebral vasodilatation. However, it is unclear whether intravenous alfa CGRP (αCGRP) induces changes in cerebral and systemic hemodynamics. Therefore, we studied the influence of an αCGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on mean arterial velocity in the middle cerebral artery (vm MCA) and in the posterior cerebral artery (vm PCA) in twenty healthy subjects using transcranial Doppler (TCD). We found out that αCGRP decreased vm MCA (p < 0.001), vm PCA (p < 0.001), mean arterial pressure (MAP) (p < 0.001) and end-tidal CO2 (Et-CO2) (p = 0.030). The heart rate (HR) increased during αCGRP infusion (p < 0.001). In addition, we found a positive relationship between Et-CO2 and vm MCA (p = 0.001) as well as vm PCA (p = 0.043). In our view, αCGRP induces changes in cerebral and systemic circulation in healthy volunteers. It might cause vasodilatation of MCA and PCA and a compensatory decrease of Et-CO2 to αCGRP related hemodynamic changes

Sestavljeni plaz v dinamičnih alpiskih razmerah: primer plazu Urbas

The alpine environment is characterized by complex geology, high-energy terrain, deeply incised river valleys with high erosional potential, extreme weather conditions and dynamic geomorphic processes. Such settings provide favourable conditions for the formation of composite landslides rather than individual slope mass movement phenomena. As an example, we present the kinematics of the composite landslide Urbas in the North of Slovenia which developed in the complex geological and morphological settings characteristic of the alpine environment. The research combines several monitoring techniques and involves the integration of both surface and subsurface displacements measured in the landslide area. The results indicate that the composite sliding process consists of several simultaneous and interrelated types of movements occurring in different segments of the unstable mass that are governed by different mechanisms of displacements, such as rockfall, sliding and debris flow. The kinematic characteristics of a deep-seated landslide that formed in such conditions vary spatially, but is rather homogenuous vertically, indicating translational type of movement. Spatial kinematic heterogeneity is primarily related to the diverse terrain topography, reflecting in different displacement trends. Based on the revealed kinematic proprieties of the sliding material, the sediment discharge illustrates the sliding material balance which estimates the volume of the retaining material that represents the potential for slope mass movement events of larger scales.Za alpsko okolje so značilni kompleksna geologija, razčlenjeno površje, globoko vrezane rečne doline z visokim erozijskim potencialom, ekstremne vremenske razmere in dinamični geomorfni procesi. Takšne razmere so, bolj kakor za nastanek posameznih pojavov pobočnih premikov, prikladne za razvoj sestavljenih plazov. Kot primer takšnega pojava predstavljamo primer sestavljenega plazu Urbas, ki se nahaja v severnem delu Slovenije in je nastal v zapletenih geoloških in morfoloških razmerah značilnih za alpsko okolje. V raziskavi združujemo več tehnik spremljanja plazov in povezujemo izmerjene površinske premike in premike na območju drsne ploskve. Rezultati kažejo, da proces sestavljenega plazenja vključuje več medsebojno povezanih tipov premikov, ki se, z različnimi mehanizmi premikanja (podor, plazenje, drobirski tok), istočasno odvijajo v različnih delih premikajoče se gmote. Kinematične značilnosti globokega plazu, ki je nastal v takšnih razmerah, se spreminjajo prostorsko, po globini pa so precej homogene, kar nakazuje na translacijski tip premikanja plazu. Prostorska kinematična heterogenost pa je v prvi vrsti posledica oblikovanosti površja, ki se odraža v različnih hitrostih premikov. Na podlagi ugotovljenih kinematičnih lastnosti plazečega materiala smo s pomočjo računanja prehajanja sedimenta ponazorili bilanco plazeče se mase in ocenili prostornino materiala, ki zastaja na območju plazu in ki predstavlja potencial za pojav pobočnih masnih premikov večjih razsežnosti