Title: Biomechanical aspects of the dynamics of intracranial pressure in traumatic brain injury Author: Ing. Martin Mayer e-mail: mayercz@seznam.cz Department: Department of Anatomy and Biomechanics Supervisor: doc. PaedDr. Karel Jelen, CSc. This PhD thesis "Biomechanical aspects of the dynamics of intracranial pressure in traumatic brain injury" is about the dynamics of intracranial pressure, particularly in relation to the external mechanical action of the patient. Severe head injury is the leading cause of death in patients under 35 years of age. Despite constantly-improving medical and nursing care only one third of patients, after recovery, regained the ability to live independently in the long term. Two-thirds of patients were severely disabled or died. The lifetime cost of such a patient who was not completely cured has been calculated to be $4,000,000. A significant consequence of craniocerebral injuries are secondary brain lesions, which among other means the rise in intracranial pressure (ICP), which can further exacerbate due to intracerebral or extracerebral causes. Therefore, the objective of the treatment is minimizing secondary injury, optimally at the phase of the primary lesion. However, realization of this requirement, about which we can say that is a conditio sine qua non, sometimes leads...

Introdução: O aumento da pressão intracraniana (PIC) é um problema comum na prática neurocirúrgica, e a monitoração invasiva deste parâmetro faz parte da rotina de unidades de terapia intensiva. O Doppler transcraniano vem sendo testado na avaliação da hemodinâmica cerebral como parâmetro de avaliação não invasiva da PIC, porém há controvérsias na literatura sobre seu real benefício e utilidade nesta situação. Este estudo objetivou correlacionar os dados de avaliação do fluxo sanguíneo cerebral através da técnica de Doppler com as variações da monitoração invasiva da PIC na fase aguda de hipertensão intracraniana em um modelo animal. Métodos: Trata-se de um estudo experimental realizado em suínos. O experimento constou de dois grupos de animais (A e B) com hipertensão intracraniana gerada por insuflação com soro fisiológico de um balão no parênquima cerebral, sendo o grupo A com 4 mL e o grupo B com 7 mL. Nos dois grupos houve uma intervenção clínica com infusão de solução salina a 3% e uma simulação de intervenção cirúrgica (desinsuflação do balão). Em todos os momentos de insuflação do balão e das intervenções foram registrados os valores dos monitores de PIC e do Doppler: velocidades sistólica (VS), diastólica (VD), média (VM) do fluxo sanguíneo cerebral e índice de pulsatilidade (IP). Foram realizadas comparações do comportamento dos parâmetros avaliados pela ultrassonografia Doppler craniana (VS, VD, VM e IP) em relação às variações da PIC intraparenquimatosa. Resultados: Foram estudados 20 suínos sendo 10 no grupo A e 10 no grupo B. Um animal do grupo B foi excluído do estudo, pois foi a óbito antes do término do experimento. Após a insuflação do balão, como era de se esperar, a PIC no grupo B foi superior à do grupo A em todos os momentos, até a desinsuflação do mesmo. Realizada a correlação de Spearman observou-se correlação significativa entre IP e PIC, principalmente logo após insuflação do balão, ou seja, na elevação abrupta da PIC. Não houve correlação entre a PIC e os parâmetros VS, VD e VM. Também não houve variação significativa da PIC após infusão endovenosa de solução salina hipertônica. Conclusão: Este resultado demonstra o potencial do IP como bom parâmetro de avaliação de pacientes com suspeita de elevação hiperaguda e recente da PIC. Não se conseguiu demonstrar os mesmos resultados de correlação entre a PIC e as demais variáveis VS, VD e VM. Diante destes achados, adicionados aos dados conflitantes da literatura disponível até o momento, não se recomenda, por enquanto, a utilização desses parâmetros isoladamente como substitutos da monitoração invasiva da PIC, evidenciando a necessidade de mais estudos clínicos e experimentais / Introduction: Increased intracranial pressure (ICP) is a common problem in neurosurgical practice. Invasive monitoring of ICP in these cases is part of the intensive care unit routine. Transcranial Doppler has been tested in the evaluation of cerebral hemodynamics as a non-invasive evaluation of ICP, but there are controversies in the literature about its real benefit and usefulness in this situation. Thus, this study aimed to correlate the data of cerebral blood flow assessment using the Doppler technique and the invasive monitoring of ICP in the acute phase of intracranial hypertension in an animal model. Methods: This is an experimental study in pigs. During the experiment, an intracerebral expansive mass with an inflatable balloon was simulated. The experiment consisted of two groups (A and B) of animals with intracranial hypertension generated by a ballon inflation inside the cerebral parenchima, group A with 4 mL and group B with 7 mL. In both groups there was a clinical intervention with infusion of 3% saline solution and a simulation of surgical intervention (balloon drain out). The values of ICP and Doppler parameters (systolic (FVs), diastolic (FVd), and mean (FVm) cerebral blood flow velocities) were collected at all moments of balloon inflation and interventions, as well as the pulsatility index (PI). Comparisons of the behavior of the parameters evaluated by Doppler ultrasound (FVs, FVd, FVm and PI) were performed in relation to intraparenchymal ICP. Results: Twenty pigs were studied, 10 in group A and 10 in group B. One pig died in group B and it was excluded. After balloon inflation, as expected, ICP in group B was higher than in group A at all times, until the ballon was empty again. Significant correlation between PI and ICP was obtained when Spearman correlation was performed, mainly shortly after balloon inflation, that is, in the abrupt elevation of ICP. There was no correlation between ICP and FVs, FVd or FVm. There was also no significant change in ICP after intravenous infusion of hypertonic saline solution. Conclusion: These results demonstrate the potential of PI as a good parameter for the evaluation of patients with suspected ICP elevation. It was not possible to demonstrate the same correlation results between the ICP and FVs, FVd or FVm. Due to these results and also to the literature conflicting data to date, the use of these parameters alone as substitutes for the invasive monitoring of ICP is not recommended until now, which shows the need for further clinical and experimental studies

The diploma thesis deals with the assessment of the prediction of brain aneurysm rupture based on its geometrical and material properties. In the first part of the thesis there is a~detailed research study of cardiovascular systems with a focus on the cerebral artery and aneurysm occurring on their bifurcates. The second part of the thesis is focused on the creation of two models of arterial cerebral bifurcation with the presence of aneurysm and on obtaining their geometry in unloaded state. Emphasis is placed on the most realistic constitutive model of the artery wall material based on real data from uniaxial tensile tests and on a suitably chosen blood pressure load. This blood pressure may be step-changed, for example, in bungee jumping. In the work, a calculation of the increase in blood pressure during the step-change is performed, which is subsequently used in calculations of tension in the wall of the cerebral aneurysm. In conclusion, the risk of rupture is evaluated in two model idealized brain aneurysms and a discussion of the credibility of the results is given.

Title: Biomechanical aspects of the dynamics of intracranial pressure in traumatic brain injury Author: Ing. Martin Mayer e-mail: mayercz@seznam.cz Department: Department of Anatomy and Biomechanics Supervisor: doc. PaedDr. Karel Jelen, CSc. This PhD thesis "Biomechanical aspects of the dynamics of intracranial pressure in traumatic brain injury" is about the dynamics of intracranial pressure, particularly in relation to the external mechanical action of the patient. Severe head injury is the leading cause of death in patients under 35 years of age. Despite constantly-improving medical and nursing care only one third of patients, after recovery, regained the ability to live independently in the long term. Two-thirds of patients were severely disabled or died. The lifetime cost of such a patient who was not completely cured has been calculated to be $4,000,000. A significant consequence of craniocerebral injuries are secondary brain lesions, which among other means the rise in intracranial pressure (ICP), which can further exacerbate due to intracerebral or extracerebral causes. Therefore, the objective of the treatment is minimizing secondary injury, optimally at the phase of the primary lesion. However, realization of this requirement, about which we can say that is a conditio sine qua non, sometimes leads...

Methcathinone (MCAT) is the β-ketone analog of methamphetamine, and like its amphetamine analog, MCAT functions as a monoamine releaser that selectively promotes the release of dopamine (DA) and norepinephrine (NE) over serotonin (5-HT). MCAT produces amphetamine-like psychostimulant effects and is classified as a Schedule I drug of abuse by the United States Drug Enforcement Administration (DEA). Recently, synthetic MCAT analogs have emerged as designer drugs of abuse in Europe and the United States and have been marketed under deceptively benign names like “bath salts” in an attempt to evade legal restriction. These dangerous, recently emergent and novel drugs of abuse display varying selectivity to promote release of DA/NE vs. 5-HT, and selectivity for DA neurotransmission is believed to correlate with abuse liability. The goal of this dissertation was to conduct preclinical research to examine structural determinants of abuse-related behavioral and neurochemical effects produced by a series of synthetic MCAT analogs. Specifically, this project focused on one feature of the methcathinone scaffold: the para substituent of the benzene ring. A series of six novel MCAT analogs will be examined to evaluate how physicochemical parameters (steric, Es; electronic, σp; lipophilic, πp) of the para substituent influence in vitro monoamine transporter selectivity as well as in vivo neurochemical and behavioral effects. Results from this body of work implicate steric factors as being particularly important in determining a compound’s abuse-related neurochemical and behavioral effects. Thus, these data not only offer an improved understanding of the mechanism of abuse-related drug effects produced by synthetic MCAT analogs, but also help in the generation of homology models of the human DA and 5-HT transporters (DAT and SERT, respectively).

Though a host of analgesics have been developed to alleviate pain, especially acute pain, significant side effects and a lack of long-term efficacy have encouraged research attempts to pursue novel targets that may be associated with fewer side effects or a more sustained efficacy. Among these new targets are members of the nicotinic family of acetylcholine receptors (nAChRs). The non-selective nAChR agonists nicotine and epibatidine have been shown to function as potent antinociceptive drugs in many acute and chronic preclinical pain models, while nicotine has produced analgesic effects in humans. However, these non-selective nAChRs agonists also produce various side effects, including gastrointestinal and cardiovascular complications that limit clinical utility. To reduce these side effects, recent research has focused on evaluating the potential role of specific nAChR subtypes in the modulation of nociception. Traditionally, assays of pain-stimulated behaviors, or behaviors that increase in rate, frequency or intensity after presentation of a noxious stimulus, have been used to evaluate nAChR agonists and other classes of candidate analgesics pre-clinically. However, clinically relevant pain states are often associated with the depression of behavior; for example in humans, pain is often accompanied by impaired function in daily activities and depression of mood. To address these depressant manifestations of pain, novel preclinical assays have been developed to assess the expression and pharmacological modulation of pain-depressed behaviors, or behaviors that decrease in rate, frequency or intensity after presentation of a noxious stimulus. Additionally, the effects of nAChR agonists in preclinical assays of pain-depressed behavior are unknown. In assays of pain-stimulated behavior, agonism of α4β2* receptors appears to play a prominent role in antinociception produced by drugs that target nAChRs. Recent research suggests that α7 nAChR subtype might be an alternative target. Accordingly, the primary goal of this dissertation was to compare antinociceptive effects of the nAChR agonist nicotine and more selective nicotinic agonists in assays of pain-stimulated and pain-depressed behavior. Results from this body of work show that both nicotine and the more selective α4β2* agonist 5-I-A-85380 produced antinociception in both types of assays, whereas an α7 agonist did not. Taken together, these results suggest that α4β2* nAChR agonists may be especially effective to treat signs of pain-related behavioral depression; however nonselective behavioral effects of these compounds may contribute to apparent antinociception. Studies of nAChR agonist effects on pain-depressed behavior were conducted using an assay of intracranial self-stimulation (ICSS) as a baseline behavior that is depressed by noxious pain stimuli, and pain-related depression of ICSS can be selectively alleviated by clinically effective analgesics. As a prelude to studies of nAChR agonist effects on pain-related depression of ICSS, a preliminary study was conducted to assess effects of nicotine and 5-I-A-85380 on ICSS in the absence of a noxious stimulus. These studies indicated that selective α4β2* agonists may have higher abuse potential than nicotine. Additionally, cognitive function is one domain of behavior that may be impaired by pain, and nAChR agonists are used to treat cognitive impairment produced by other non-pain pathologies. Accordingly, a final goal of this project was to develop an assay of pain-related cognitive impairment in rats that could be used to evaluate effects of nAChR agonists. Although results of this study did provide evidence for pain-related impairment of cognition, the effects of the pain stimuli were sufficiently variable and transient to make this procedure impracticable for use in studies with nAChR agonists.

Esta pesquisa analisa experimentalmente as diferenças de comportamento entre a versão clássica e a modificada da craniotomia subtemporal quanto à retração do lobo temporal. A retração é medida pelo ângulo de visão, através do microscópio, obtido ao mirar-se estruturas previamente estabelecidas. Estudou-se a correlação estatística entre a retração cerebral e os diâmetros transversos do crânio, a profundidade da fossa temporal e a altura da bifurcação medida em relação à tenda do cerebelo e à clinóide posterior. É considerada a relação entre estes achados e os aspectos pertinentes à opção entre as craniotomias pterional e subtemporal para o tratamento cirúrgico dos aneurismas da porção superior da artéria basilar. / This paper is an experimental analysis between the classic and the modified subtemporal procedures, regarding the cerebral retraction required to approach the interpeduncular cistern and the basilar artery bifurcation. The retraction is assumed to be proportional to the angle of sight, through the microscope, required to observe the basilar bifurcation and other structures. The statistical correlations between the degree of brain retraction and the transverse diameters of the skull, the vertical length of the temporal fossa and the position of the basilar bifurcation in relation to the posterior clinoid and the tentorium are analysed. Considerations are made regarding these findings and the many aspects involved in the options between the pterional and the subtemporal approaches in the surgical treatment of the basilar bifurcation aneurysms

Introdução: O acesso pterional é uma das craniotomias mais utilizadas. Entretanto, apresenta algumas desvantagens, como a dissecação ampla do músculo temporal, que pode causar atrofia e deformidade do contorno facial. A craniotomia minipterional descrita em 2007 propiciou exposição anatômica semelhante a da craniotomia pterional clássica. Objetivos: Comparar os resultados clínicos, funcionais e estéticos dos dois acessos cirúrgicos destinados ao tratamento de aneurismas da circulação anterior. Métodos: Cinquenta e oito doentes, com aneurismas rotos (40) e não rotos (18) foram admitidos no estudo. No grupo A, 28 indivíduos foram submetidos à craniotomia minipterional. No grupo B, 30 doentes foram operados com a craniotomia pterional clássica. Doentes com hematomas intracranianos, aneurismas do segmento oftálmico e aneurismas gigantes foram excluídos. Os resultados estéticos foram analisados por meio de dois métodos. No primeiro, uma autoavaliação utilizava uma régua escalonada de 0 a 100, na qual o zero representou o melhor resultado e 100 o pior resultado na percepção do próprio doente. Fotografias dos doentes foram mostradas a dois observadores independentes. Os resultados foram classificados como ótimo, bom, regular e mau (de acordo com uma escala pré-determinada). A gradação da atrofia foi mensurada por meio de três métodos, utilizando a tomografia computadorizada de crânio. No primeiro, observou-se a percentagem de redução do complexo músculo temporal, tecido subcutâneo e pele. No segundo método, a percentagem de redução da espessura do músculo temporal foi analisada isoladamente. O terceiro método foi a mensuração da volumetria do músculo temporal, tecido subcutâneo e pele calculados a partir da margem superior do arco zigomático até a linha temporal superior utilizando-se o software OsiriX (Pixmeo Sarl Geneva/ Suíça OsiriX). Para os resultados clínicos e funcionais, foi utilizada a Escala de Rankin modificada. Outras variáveis, como paralisia do ramo frontal do nervo facial, hemorragia pós-operatória, fistula liquórica, hidrocefalia e mortalidade, também foram analisadas. Resultados: Em ambos os grupos, os dados demográficos e as características pré-operatórias foram similares. A satisfação com o resultado estético foi observada em 79% (19) no grupo A e 52% (13) no grupo B (p=0,07). O valor médio da régua foi 27 no grupo A e 45,8 no grupo B (p=0,03). Quando somente doentes classificados como Rankin modificado 0 ou 1 foram analisados, o valor médio da régua foi de 25,2 no grupo A e 39,4 no grupo B (p=0,11). Dois avaliadores independentes analisaram as fotografias dos doentes e o coeficiente de correlação kappa para os resultados estéticos foi de 0,73. De acordo com os mesmos ótimo e bom, foram observados em 87% (21) no grupo minipterional e 48% (12) no grupo pterional. A percentagem de redução do músculo temporal, subcutâneo e pele (método 1) foi de 14,9% no grupo A e 24,3% no grupo B (p=0,01). Quando somente o músculo temporal foi analisado (método 2), a percentagem de redução foi de 12,7% no grupo A e 22% no grupo B (p=0,005). A redução volumétrica das estruturas (método 3) foi de 14,8% no grupo A e 24,5% no grupo B (p=0,012). Na avaliação clínica no 6? mês, os valores da Escala de Rankin modificada foram similares (p=0,99). O óbito ocorreu em 4 doentes no grupo A e 5 doentes no grupo B (p=1,0). Conclusão: Os resultados clínicos demonstraram que a craniotomia minipterional é um procedimento seguro, com prognóstico similar ao da técnica convencional. Os resultados cosméticos foram melhores com menor deformidade no contorno facial, uma vez que a percentagem de redução da espessura, do volume do músculo temporal, do tecido subcutâneo e da pele foi menor com a técnica proposta. A craniotomia minipterional foi a melhor alternativa em relação à craniotomia pterional clássica para tratar aneurismas rotos e não rotos da circulação anterior / Introduction: The pterional approach is one of the most commonly used craniotomy. However it has disadvantages, such as complete dissection of the temporalis muscle. This may lead to muscular atrophy and facial deformity. The minipterional craniotomy was described in 2007 and the anatomic exposure provided by the pterional and minipterional approaches were similar in the total area of exposure and angular view. Objectives: This prospective randomized study was designed to compare the clinical, functional and aesthetic results of two surgical techniques for microsurgical clipping of anterior circulation aneurysms. Methods: Overall, 58 eligible patients admitted with ruptured and unruptured anterior circulation aneurysms were enrolled in the study. In group A, 28 patients were operated with the minipterional technique. In Group B 30 patients were operated according to the classical pterional craniotomy. Patients with intracranial haematomas, ophthalmic aneurysms and giant aneurysms were excluded. The aesthetic results were analyzed with 2 methods. In the first, the patients were showed to a rule, with a scale from 0 to 100, in which 0 mean the best result and 100 the worst result. Photos were taken and showed to two independent observers, the results were classified as excellent, good, regular or poor, according to a pre-determined scale. The degree of atrophy was measured with three methods. In the first one, the authors observed the percentage of thick reduction in the temporal muscle, subcutaneous tissue and skin. In the second method the percentage of thick reduction of the isolated temporal muscle was observed and the third the volumetric analysis of the temporal muscle, subcutaneous tissue and skin was calculated from the superior edge of zygomatic arch to superior temporal line using the OsiriX software (OsiriX - Pixmeo Sarl Geneva/Suíça). The functional results were compared using the Modified Rankin Score. Others variables such frontal facial palsy, post-operative hemorrhage, cerebrospinal fistulas, hydrocephalus and mortality were also analyzed. Results: In both groups the demographic and pre-operative characteristics were similar. The satisfaction with aesthetic results were observed in 79% (19) in group A and 52% (13) in group B (p=0,07). The mean value observed in the rule was 27 in group A and 45,8 in group B (p=0,03). When patients classified as Rankin Modified Score of 0 or 1 only were included the mean value observed in the rule was 25,2 in group A and 39,4 in group B (p=0,11). Two independent observers analyzed the patients photos and the kappa coefficient correlation for the aesthetic results was 0,73. According to them excellent and good results were observed in 87% (21) in minipterional group and 48% (12) in the pterional group. The degree of atrophy of temporal muscle, subcutaneous tissue and skin (method 1) was14,9% in group A and 24,3% in group B (p=0,01). The measurement of temporal muscle (method 2) revealed that the degree of atrophy was 12,7% in group A and 22% in group B (p=0,005). The volumetric reduction of the structures (method 3) was 14,8% in group A and 24,5% in group B (p=0,012). Rankin Modified Score was similar in both groups in the 6-month evaluation (p=0,99). Mortality occurred in 4 patients in group A and 5 patients in group B (p=1,0). Conclusion: These clinical results indicate that the minipterional is a safe procedure. We can estimate the better cosmetic results with less facial contour deformity since the percentage of thick and volumetric reduction in temporal muscle, subcutaneous tissue and skin were demonstrated. It can be an excellent and better alternative to the classical pterional approach

Made available in DSpace on 2017-07-21T14:35:56Z (GMT). No. of bitstreams: 1 Anderson Jose de Melo Silva.pdf: 2395463 bytes, checksum: ffa3d1c0f5669babc3c89ef037bd4833 (MD5) Previous issue date: 2017-10-06 / The Acute Coronary Syndrome (ACS) defines a range of clinical changes that are compatible with myocardial ischemia, resulting in the death of myocardial cells due functional deficit of blood flow, characterizing the acute myocardial infarction (AMI). The AMI is evidenced through clinical data that are reinforced by electrocardiogram (ECG), imaging and even the biochemical markers (biomarkers) evaluation, such as serum creatine phosphokinase (CK), its isoenzyme MB fraction (CK-MB), troponin and new biomarkers not yet included in routine laboratory tests, such as myeloperoxidase (MPO). In addition to new laboratory markers, science allows the development of new technologies for clinical assessment of patients, providing new information and less risk, such as non-invasive evaluation of intracranial pressure (ICP). This study is justified by the need to predict earlier the complications in patients with suspected AMI, as well as evaluate them as to the diagnosis and prognosis of the event in question. Thus, we sought to study patients with suspected ACS/AMI about the cardiovascular risk and possible PIC change through traditional biomarkers, most current markers ( "gold standard") and new biomarkers and new ICP monitoring technology. Therefore, from a population of 20 patients, randomly selected according to gender and age, separated into two groups: CK-MB≥25 IU (n = 6) and CK-MB<25 IU (n = 14), which were submitted to measurement of PIC and PAS, as well as biochemical and hematological measurements, and specific cardiac biomarkers. As a result, there was correlation of clinical significance between the values of creatine kinase MB fraction (CK-MB) and glycated hemoglobin (HGBA1C). From these data, it started to study two cases that were selected two patients. It was observed that even with changes of CK-MB, troponin and myeloperoxidase (compared to laboratory practice reference values for traditional markers and "gold standard" and MPO value considered normal in the literature), it was found not manifestations that have allowed to observe reduction of cerebral compliance, where the waves P2 are larger than P1, and therefore, there were no PIC changes identified for patients under the conditions studied. Thus, it was concluded that, even without demonstration of PIC change in this work, it is not possible to exclude the value of its inclusion in the clinical evaluation, considering that biases, like the sample universe and the time of collection of PIC or the use of medication at the admission time on hospital, may have contributed to the non-registration of changes in ICP, even in cases where patients had an unfavorable evolution of the clinical picture. / A Síndrome Coronariana Aguda (SCA) define uma gama de alterações clinicas que são compatíveis com um quadro de isquemia miocárdica, acarretando na morte de células do tecido miocárdico devido ao déficit funcional do fluxo sanguíneo, caracterizando o Infarto Agudo do Miocárdio (IAM). O IAM pode se revelar através de dados clínicos que são reforçados pelo eletrocardiograma (ECG), exames de imagem e ainda a pesquisa de marcadores bioquímicos (biomarcadores), tais como Creatinafosfoquinase (CK), sua isoenzima fração MB (CK-MB), troponina e novos biomarcadores ainda não inclusos na rotina laboratorial, tais como mieloperoxidase (MPO). Além de novos marcadores laboratoriais a ciência permite o desenvolvimento de novas tecnologias para avaliação clínica dos pacientes, proporcionando novas informações e menor risco, tais como a avaliação não invasiva da pressão intracraniana (PIC). O presente trabalho justifica-se pela necessidade de se prever intercorrências com maior antecedência em pacientes com suspeita de IAM, assim como em avaliá-los quanto ao diagnóstico e prognóstico do evento em questão. Desta forma, buscou-se estudar pacientes com suspeita de SCA/IAM quanto ao risco cardiovascular e possível alteração de PIC por meio biomarcadores tradicionais, marcadores mais atuais ("padrão ouro") e novos biomarcadores e nova tecnologia de acompanhamento da PIC. Para tanto, de uma população de 20 pacientes, escolhidos aleatoriamente quanto ao gênero e idade, separou-se em dois grupos: CK-MB≥25 UI (n=6) e CK-MB˂ 25 UI (n=14), os quais foram submetidos à aferição de PIC e PAS, além de dosagens bioquímicas e hematológicas, bem como biomarcadores cardíacos. Como resultado, observou-se correlação de significância clinica entre os valores de creatinofosfoquinase fração MB (CK-MB) e hemoglobina glicada (HgbA1C). A partir destes dados, passou-se ao estudo de dois casos clínicos em que foram selecionados dois pacientes. Foi observado que, mesmo com alterações de CK-MB, troponinas e Mieloperoxidase (comparando-se a valores de referencia da prática laboratorial para os marcadores tradicionais e "padrão ouro" e valor de MPO considerado normal em literatura especializada), constatou-se não haver manifestações que permitissem observar redução da complacência cerebral, quando as ondas P2 se dão maiores que ondas P1 e, portanto, não foram identificadas alterações de PIC para os pacientes nas condições estudadas. Com isso, concluiu-se que, mesmo não havendo demonstração de alteração de PIC neste trabalho, não se pode excluir o valor de sua inclusão na avaliação clínica, dado que vieses como universo amostral, bem como o momento da coleta da PIC e ou uso de medicação no momento da admissão hospitalar, podem ter contribuído para o não-registro de alterações da PIC, mesmo em casos que os pacientes tiveram uma evolução desfavorável do quadro clínico.

According to the literature, MRI has been applied to characterize the atherosclerosis in coronary and extracranial internal carotid artery. The cross-sections of MCA were scanned by Magnetic Resonance Imaging (MRI) to assess the accuracy of MRI in identifying MCA stenosis with histopathology as a golden standard, which was performed in the same post-mortem brains as in the second part. The sensitivity and specificity of MRI in detecting more than 30% MCA stenosis were 38.6% and 92.2%, with a positive predictive value of 87.2% and negative predictive value of 52.2%, and the corresponding values of MRI in identifying more than 50% MCA stenosis were 57.1%, 90.8%, 50% and 83.0%, respectively. Stenotic lesions >30% and >50% identified by MRI were found to be associated with infarctions in corresponding MCA territory. / After verification of potential relationship between ischemic stroke and intracranial artery calcification, the incidence of intracranial artery calcification was assessed in the ischemic stroke. One hundred and seventy-five ischemic stroke patients and 182 controls were enrolled. There was a higher prevalence of intracranial artery calcification in ischemic stroke patients than in controls. Hypertension, diabetes, smoking, intracranial artery calcification, hyperlipidemia, and atrial fibrillation were found to be independently associated with ischemic stroke. / Atherosclerotic stenosis is a heterogeneous disorder. The studies performed in extracranial carotid artery and coronary artery showed that the genes associated with lipoprotein metabolism may be associated with atherosclerosis. Thus, we speculated that the genes concerned with lipid metabolism may also be risk factors for MCA atherosclerotic stenosis. In the part of genetic analysis, clinical parameters and the genotypes of polymorphisms in the apolipoprotein E (ApoE), lipoprotein lipase (LPL), and paraoxonase (PON1) genes were compared in patients with and without MCA stenosis. Two hundred and ninety-four ischemic stroke patients were recruited, 136 cases with and 158 without MCA stenosis. Systolic blood pressure (SBP), rather than ApoE, LPL, and PON1 polymorphism was found to be a risk factor of MCA stenosis. / Calcification of intracranial artery, as a common complication of atherosclerosis, was investigated by multi-detector-row computed tomography (MDCT). By this advanced technique, the prevalence and location of calcification in intracranial arteries were determined, and its potential risk factors were also investigated. Four hundred and ninety patients were recruited. The incidence of intracranial artery calcification was 69.4%. The highest prevalence of intracranial artery calcification was seen in internal carotid artery (60%), followed by vertebral artery (20%), middle cerebral artery (5%) and basilar artery (5%). Age, a history of ischemic stroke, and white blood cell count were shown to be independently associated with intracranial artery calcification. / In the present study, genetic, pathological, imaging characterizations and prognosis of MCA stenosis were investigated. The effect of candidate genes has not been confirmed in the present study, but SBP and hypertension appears to contribute a lot to the occurrence of MCA stenosis among Chinese populations. As for the pathology of MCA atherosclerotic plaques, luminal stenosis and also the morphology of atherosclerotic plaque seem to play a cooperative role in leading to ischemic stroke. Imaging studies demonstrated the agreement between ex vivo MRI and histopathology in identifying MCA stenosis, and the correlation between the MCA stenosis identified by MRI and ischemic events. Calcification of intracranial artery, as a common complication of atherosclerosis, may be associated with age, history of ischemic stroke. High incidence of ischemic stroke has been demonstrated in Chinese type 2 diabetes patients. The presence of asymptomatic MCA stenosis plays an important role in the occurrence of ischemic stroke. / Lastly, using a cohort-study, we aimed to investigate stroke incidence of asymptomatic MCA stenosis and its risk factors in Chinese type II diabetic population. Transcranial Doppler was performed to define MCA stenosis. Incident strokes between 1996 and 2006 were ascertained by the database of Clinical Management System of the Hong Kong Hospital Authority. Anthropometric parameters (waist circumference and body mass index), blood pressure, and baseline plasma biochemical profile (lipid and glucose) were recorded to find the risk factors of ischemic stroke in asymptomatic MCA stenosis patients. Totally, 2,197 type II diabetic patients without symptoms of cerebrovascular disease were recruited. The evidence of MCA stenosis was identified in 272 subjects (12.4%), including 146 (53.7%) subjects with single-vessel involvement. Ischemic stroke occurred in one hundred and eighty-four (8.4%, 184/2197) patients. History of ischemic heart disease, MCA stenosis, the presence of retinopathy, lipid total cholesterol and age were independently associated with ischemic stroke. / Secondly, the pathological features of MCA stenosis and their relationship with cerebral infarcts were investigated in a series of post-mortem adults aged 45 years or above. The morphological features of the MCA atherosclerotic plaques were described in detail. The results demonstrated that the degree of luminal stenosis, the percentage of the plaques containing more than 40% lipid area, the values of cap-lipid, cap-lipid-stenosis, and the prevalence of intraplaque hemorrhage, neovasculature and thrombus were higher in the group of plaques associated with infarction. And the mean index of both CD45RO and CD68 were higher in the group of plaques associated with infarction. Binary logistic regression showed that stenosis, lipid area and presence of neovasculature were independent risk factors of MCA infarcts. / Stroke is one of the leading causes of death, disability, and dementia throughout the world. The stenosis of the intracranial large artery, especially the middle cerebral artery (MCA), is common in Chinese, Hispanic, and African populations. But MCA stenosis has been understudied due to its infrequency in the white population and its relative inaccessibility and invasiveness involved in its investigations. The purpose of the study was to investigate the genetic, pathological, imaging characteristics and prognosis of MCA atherosclerotic stenosis in Chinese population. / Chen Xiang-yan. / "September 2006." / Adviser: MH Ng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1460. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 193-212). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.