Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-09-15T18:22:21Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO.pdf: 6914963 bytes, checksum: b59dc4afc22cc256f6af81abdcd285cc (MD5) / Made available in DSpace on 2016-09-15T18:22:21Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO.pdf: 6914963 bytes, checksum: b59dc4afc22cc256f6af81abdcd285cc (MD5) Previous issue date: 2016-02-24 / Introdução: Os aneurismas intracranianos trazem consequências importantes para o paciente acometido. A hemorragia subaracnóidea (HSA) possui uma forte correlação com aneurismas saculares e devido a sua gravidade e alta ocorrência de sequelas, o seu estudo merece importância. Uma alteração sensorial que pode esta relacionada à HSA é o déficit olfatório. Dentre os métodos de avaliação do olfato descritos, os quantitativos são ferramentas que podem ser utilizados a fim de garantir resultados mais fidedignos considerando o quadro clínico desses pacientes. Objetivos: Caracterizar o olfato de pacientes pré e pós tratamento cirúrgico para hemorragia subaracnóidea aneurismática. Método: Esta dissertação está composta por dois artigos. O primeiro constou de um artigo de revisão com título Métodos de avaliação do olfato em pacientes vítimas de hemorragia subaracnóidea: revisão sistemática. O segundo é um artigo original intitulado Avaliação do olfato na hemorragia subaracnóidea aneurismática antes e após o tratamento cirúrgico, neste foram estudados 15 adultos com hemorragia subaracnóidea aneurismática, atendidos no Hospital da restauração de Pernambuco, avaliados em três momentos distintos: Após a hemorragia, com uma semana de pós-operatório e com três meses de pós-operatório. A pesquisa foi iniciada após aprovação pelo Comitê de Ética em Pesquisa do hospital. Após a aplicação do Termo de Consentimento Livre e Esclarecido foi realizada a revisão do prontuário, entrevista com o participante e avaliação do olfato por meio de um teste de soluções aquosas, adaptado de outros estudos, construído pela farmácia escola da UFPE. Resultados: O primeiro artigo mostrou heterogeneidade nos métodos utilizados para avaliação do olfato na hemorragia subaracnóidea, como também no momento selecionado para aplicação das avaliações, com evidencias de déficit olfatório nesta população. Nos resultados provenientes do estudo original desta dissertação foi observado maior número de classificações olfatórias normais, além disso, não foi encontrada correlação significativa entre a pontuação olfatória com as seguintes variáveis (Idade, Intervalo em dias entre a hemorragia subaracnóidea e a avaliação olfatória, escolaridade e topografia do aneurisma). Não houve mudança significativa na pontuação olfatória após a cirurgia. Houve diferença estatística significativa na comparação entre a pontuação olfatória com uma semana de pós-operatório e com três meses de pós-operatório. Considerações finais: Os resultados deste estudo mostram a ocorrência de alteração olfatória após a hemorragia subaracnóidea aneurismática, assim como piora na classificação do olfato após a cirurgia. Foi observada melhora no olfato após três meses de pós-operatório, com significância estatística. Sugere-se a continuação de estudos com o tema, como também que façam investigação da percepção subjetiva do olfato visando o esclarecimento dos prejuízos que a alteração olfatória causa na vida dessa população. / Introduction: Intracranial aneurysms bring important consequences for the affected patient. The subarachnoid hemorrhage (HSA) has a strong correlation with saccular aneurysms and due to its gravity and high occurrence of sequels, its study deserves importance. A sensory change can this ASH-related is the olfactory deficit. Among the methods of valuation of smell described, are quantitative tools that can be used to ensure more reliable results considering the clinical picture of these patients.Objectives: Characterize the smell of patients before and after surgical treatment for aneurysmal subarachnoid hemorrhage. Method: This dissertation is composed of two articles. The first consisted of a review article with title Methods of evaluation of smell in victims of subarachnoid hemorrhage patients: a systematic review. The second is an original article entitled Olfactory evaluation in aneurysmal subarachnoid hemorrhage before and after surgery, this 15 were studied adults with aneurysmal subarachnoid hemorrhage, met at the Hospital da Restauração de Pernambuco, evaluated in three different moments: After the bleeding, a week after surgery and three months postoperatively. The search was started after approval by the Research Ethics Committee of the Hospital. After the application of informed consent was held to review the medical records, interview with the participant and evaluation of smell through a test of aqueous solutions, adapted from other studies, built by the Pharmacy School, Federal University of Pernambuco. Results: The first article showed heterogeneity of the methods used to evaluate the smell in aneurysmal subarachnoid hemorrhage and in the methods selected for application of evaluations, with evidence of olfactory deficits in this population. The results from the original study of this dissertation it was observed as many olfactory normal ratings, moreover, was not found significant correlation between olfactory score with the following variables (age, interval in days between the subarachnoid hemorrhage and the olfactory evaluation, education and topography of the aneurysm). There was no significant change in scoring olfactory after surgery. There was a statistically significant difference in the comparison between the olfactory score with a week after surgery and three months postoperatively. Final considerations: The results of this study show the occurrence of olfactory disfunction after aneurysmal subarachnoid hemorrhage, as well as worsens the classification of smell after surgery. Improvement was observed in the nose after three months postoperatively, with statistical significance. It is suggested a continuation of studies with the theme, but also to make the subjective perception of smell to identify the problems that the disfunction olfactory cause in this population´s life.

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

Orientador: Donizeti Cesar Honorato / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T22:21:39Z (GMT). No. of bitstreams: 1 Kaleff_PauloRoland_D.pdf: 1126011 bytes, checksum: 23cb0c05a54790e4896ebd16d8754941 (MD5) Previous issue date: 2012 / Resumo: A angiotomografia cerebral 3D (ATC) passou a ser uma alternativa à angiografia por subtração digital (ASD) para a detecção dos aneurismas intracranianos. As recomendações atuais para a hemorragia subaracnóidea aguda (HSA) secundária à ruptura de aneurismas intracranianos incluem o tratamento definitivo precoce. O objetivo primário deste estudo foi o de avaliar a contribuição da ATC para a diminuição do tempo entre o diagnóstico da HSA e o diagnóstico do aneurisma, bem como para a diminuição do tempo entre a admissão do paciente e a exclusão do aneurisma, quando comparada com a ASD. Como objetivo secundário buscou-se comparar a sensibilidade de ambos os métodos diagnósticos, comparar os resultados clínicos de dois grupos de pacientes diagnosticados pala ATC e/ou pela ASD e avaliar a contribuição da ATC na abordagem cirúrgica aos hematomas secundários à ruptura de aneurismas intracranianos. Uma análise retrospectiva foi conduzida cobrindo 100 pacientes admitidos com HSA e diagnosticados para aneurisma via ATC (n=60) ou via ASD (n=40). Os dados coletados foram divididos de acordo com o método diagnóstico utilizado inicialmente para a detecção do aneurisma. Os tempos transcorridos entre o diagnostico da HSA e o diagnóstico do aneurisma foi consistentemente inferior para os pacientes submetidos à ATC (p<0.000005). Em relação ao tempo transcorrido entre a admissão e o tratamento definitivo, 70% das ocorrências para pacientes submetidos à ATC ficaram abaixo de 72 horas enquanto 60% das ocorrências para pacientes submetidos à ASD excederam 72 horas (p<0.003). A sensibilidade da ATC para aneurismas rotos foi de 0, 967 e para todos os aneurismas de 0, 931. A maioria dos casos submetidos à ATC antes da drenagem do hematoma teve o aneurisma tratado no mesmo procedimento cirúrgico. A ATC contribuiu para a redução do tempo entre o diagnóstico da HSA e o diagnóstico do aneurisma, bem como para a redução do tempo entre a admissão e o tratamento definitivo do aneurisma. A sensibilidade dos métodos foi equivalente, especialmente para os aneurismas rotos, em exames tecnicamente satisfatórios. Nos casos de hematomas secundários à ruptura de aneurismas intracranianos, a realização da ATC previamente à abordagem cirúrgica contribuiu para o tratamento definitivo do aneurisma no mesmo procedimento cirúrgico da drenagem do hematoma / Abstract: Due to its technical advancements, 3D cerebral computed tomography angiography (CTA) is increasingly being considered as an alternative to digital subtraction angiography (DSA) in the detection of intracranial aneurysms. Actual guidelines for acute subarachnoid hemorrhage (aSAH) recommend early definitive treatment. The primary goal of this study was to evaluate the contribution of CTA in shortening of time span between the diagnosis of the aSAH and the diagnosis of the aneurysm, as well as the shortening of time span between admission and definitive aneurysm treatment, when compared to DSA. As secondary goals we aimed at comparing the sensitivity of both methods, at comparing the clinical results between two studied patient groups diagnosed by CTA and/or by DSA and at evaluating the contribution of CTA to the surgical approach to intracranial hematomas secondary to aneurysm rupture. A retrospective analysis was performed covering 100 patients admitted with aSAH and diagnosed with intracranial aneurysms either by CTA (n=60) or by DSA (n=40). The data collected for both groups were separated according to the method used for the initial diagnosis of the aneurysm. The time spans between the diagnosis of the aSAH and the diagnosis of the aneurism were consistently smaller for CTA patients than for DSA patients (p<0.000005). Regarding the time spans between the admission and the final treatment, 70% of the outcomes for CTA patients remained below 72 hours and 60% of the outcomes for the DSA group exceeded 72 hours (p<0.003). The sensitivity for ruptured aneurysms was 0,967 and for all aneurysms 0,931. In the majority of cases where a CTA was performed previously to the hematoma evacuation the aneurysm could be treated in the same surgical procedure. CTA contributed to the shortening of the time elapsed between the diagnosis of the aSAH and the diagnosis of the aneurysm, as well as to the shortening of the time elapsed between admission and definitive treatment. The sensitivity of the methods was equivalent, especially for ruptured aneurysms, in technically satisfactory CTA. The use of CTA did not have a negative impact in the clinical outcome or the treatment. CTA performed previously to hematoma evacuation contributed to the definitive treatment of the aneurism in the same surgical approach / Doutorado / Neurologia / Doutor em Ciências Médicas

The rupture of an aneurysm in subarachnoid hemorrhage (SAH) is a dramatic event causing a severe impact on the brain and a transient or permanent ischemic condition. Several types of responses to meet the challenges of SAH have been found in the acute phase, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, elevated levels of brain natriuretic peptide (BNP), and disturbances in cerebral and systemic metabolism. Cerebral metabolism and the endocrine stress response in the ultra-early phase was investigated in a novel porcine model of SAH in which autologous blood was injected to the anterior skull base. Early activation of the HPA axis was found with rapid elevation of adrenocorticotrophic hormone, cortisol and aldosterone. The peak values of these hormones were early and may be impossible to catch in patients. There were indications of a sympathetic nervous response with excretion of catecholamines in urine as well as plasma chromogranin-A elevation. Cerebral microdialysis suggested immediate substrate failure followed by hypermetabolism of glucose. The animal model seems suited for further studies of aneurysmal SAH. NT-proBNP was investigated in 156 patients with SAH, there was a dynamic course with increasing levels during the first 4 days of the disease. Factors predicting high NT-proBNP load included female sex, high age, high Troponin-I at admission, angiographic finding of an aneurysm and worse clinical condition at admission. High levels of NT-proBNP were correlated to factors indicating a more severe disease, suggesting the initial injury in aneurysmal SAH is an important factor in predicting high NT-proBNP during the acute stage of the disease. Measurements with indirect calorimetry were performed daily during the first week after SAH on 32 patients with SAH. There was a dynamic course with increasing energy expenditure (EE) the first week after SAH. Comparisons with three predictive equations indicated that measured EE generally is higher than predicted, but considerable variation exists within and between patients, indicating that prediction of EE in SAH is difficult. Altogether, the studies demonstrate a complicated response in acute SAH that needs to be further studied to increase possibility of good outcome in SAH patients.

Objective: This study aims to derive a clinically-applicable decision rule to predict the risk of symptomatic vasospasm, a neurological deficit primarily due to abnormal narrowing of cerebral arteries supplying an attributable territory, in aneurysmal subarachnoid hemorrhage (SAH). Methods: SAH patients presenting from 2002 to 2011 were analyzed using logistic regression and recursive partitioning to identify clinical, radiological, and laboratory features that predict the occurrence of symptomatic vasospasm. Results: The incidence of symptomatic vasospasm was 21.0%. On multivariate logistic regression analysis, significant predictors of symptomatic vasospasm included age 40-59 years, high Modified Fisher Grade (Grades 3 and 4), and anterior circulation aneurysms. Conclusion: Development of symptomatic vasospasm can be reliably predicted using a clinical decision rule created by logistic regression. It exhibits increased accuracy over the Modified Fisher Grade alone and may serve as a useful clinical tool to individualize vasospasm risk once prospectively validated in other neurosurgical centres.

Background Aneurysmal subarachnoid hemorrhage can lead to multi-organ disturbances as a result of central and autonomic nervous system injuries. Alterations in the brain-body interface associated with this cerebrovascular disorder have significant impact on patient morbidity and mortality. Knowledge of the most pertinent brain-body associations, as well as demographic, systemic and neurological prognostic factors on hospital admission, along with their progression during hospitalization can assist the clinician and patient family in the process of treatment decision making. Objectives The goals of this dissertation are to: (1) synthesize and critically appraise the methodologic quality of existing studies that derive clinical predictor tools and clinical predictors used to determine outcome prognosis in patients with aneurysmal subarachnoid hemorrhage (SAH), (2) synthesize and critically appraise the methodologic quality of existing studies that derive pathophysiologic mechanisms of brain-body associations in aneurysmal SAH, (3) provide new insights into the significance of brain-body associations that are essential in influencing outcome in aneurysmal SAH, and (4) create a decision making algorithm for aneurysmal SAH patients that is useful in bedside prognostication and clinical treatment decision making. Methods Existing prospective and retrospective cohort studies and randomized controlled trials were included in the systematic review investigating prognostic factors and clinical prediction tools associated with determining the neurologic outcome in adults patients with aneurysmal SAH. Existing prospective and retrospective cohorts were included in the systematic review investigating the pathophysiologic mechanisms of brain-body associations in patients with ruptured brain aneurysms. The multicenter Tirilazad database (3551 patients) was used to create the aneurysmal SAH prognostic model, in order to elucidate significant brain-body associations. Traditional binary logistic regression models were used. The classification and regression tree analysis technique is applied to the multicenter Tirilazad database in order to create a decision making algorithm. Results Systematic review of the literature confirmed the most frequently retained clinical outcome predictors, namely, age, neurological grade, aneurysm size and blood clot thickness. Systematic review of the literature clarified currently known pathophysiologic mechanisms of brain-body associations in aneurysmal SAH, specifically, sympathetic activation of the cardiopulmonary system with subsequent delayed activation of neuro-cardio-endocrinological responses as part of the secondary injury cascade in response to the primary ictus of aneurysmal SAH. Logistic regression models found the significance of hepatic disease and hypertension in development of brain edema, and the negative consequences of seizures in those with history of myocardial infarction and post admission fever worsening neurological outcome. A clinically useful classification and regression tree revealed prognostic subgroups with important explanatory nodes including neurological grade, age, post admission fever and post-admission stroke. Discussion This dissertation clarified existing information on clinical predictors and pathophysiologic mechanisms of brain-body associations in aneurysmal SAH. It also provides novel information on brain-body associations that are essential in influencing outcome in aneurysmal SAH patients despite scarce existing literature on such important relationships. A clinically useful classification and regression tree was generated to guide both bedside prognostication and clinical treatment decision making in aneurysmal SAH patients. / Thesis / Doctor of Philosophy (PhD)

<p>During brain activity neurons release the major excitatory transmitter glutamate, which is taken up by astrocytes and converted to glutamine. Glutamine returns to neurons for re-conversion to glutamate. This glutamate-glutamine cycle is energy demanding. Glutamate turnover in injured brain was studied using an animal iron-induced posttraumatic epilepsy model and using neurointensive care data from 33 patients with spontaneous subarachnoid hemorrhage (SAH). Immunoblotting revealed that the functional form of the major astrocytic glutamate uptake protein GLT-1 was decreased 1-5 days following a cortical epileptogenic iron-injection, presumably due to oxidation-induced aggregation. Using microdialysis it was shown that the GLT-1 decrease was associated with increased interstitial glutamate levels and decreased interstitial glutamine levels. The results indicate a possible posttraumatic and post-stroke epileptogenic mechanism. Analysing 3600 microdialysis hours from patients it was found that the interstitial lactate/pyruvate (L/P) ratio correlate with the glutamine/glutamate ratio (r =-0.66). This correlation was as strong as the correlation between L/P and glutamate (r=0.68) and between lactate and glutamate (r=0.65). Pyruvate and glutamine correlated linearly (r=0.52). Energy failure periods, defined as L/P>40, were associated with high interstitial glutamate levels. Glutamine increased or decreased during energy failure periods depending on pyruvate. Energy failure periods were clinically associated with delayed ischemic neurological deficits (DIND) or development of radiologically verified infarcts, confirming that L/P>40 is a pathological microdialysis pattern that can predict ischemic deterioration after SAH. DIND-associated microdialysis patterns were L/P elevations and surges in interstitial glutamine. Glutamine and pyruvate correlated with the cerebral perfusion pressure (r=0.25, r=0.24). Glutamine and the glutamine/glutamate ratio correlated with the intracranial pressure (r=-0.29, r=0.40). Glutamine surges appeared upon substantial lowering of the intracranial pressure by increased cerebrospinal fluid drainage. Increased interstitial glutamine and pyruvate levels may reflect augmented astrocytic glycolysis in recovering brain tissue with increased energy demand due to a high glutamate-glutamine turnover.</p>

Introdução: A alta incidência de oclusão incompleta e recanalização dos aneurismas intracranianos de colo largo tratados por via endovascular levaram ao desenvolvimento de novas técnicas, entre elas o uso do Onyx ®. Objetivos: avaliar a eficiência do agente embólico líquido Onyx® em produzir oclusão completa dos aneurismas intracranianos de colo largo e avaliar a estabilidade do tratamento aos 6 meses e aos 18 meses, por meio de controles angiográficos. Casuística e métodos: Esta tese foi realizada na Seção de Neuroradiologia Intervencionista da Med Imagem, do Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, através da revisão de dados clínicos e radiológicos de 69 pacientes tratados pelo autor, com 84 aneurismas intracranianos de colo largo no período de julho de 2002 a fevereiro de 2006. Dez pacientes eram do sexo masculino e 59 do sexo feminino, com idade variando de 24 anos a 86 anos (mediana de 52 anos). Todos os aneurismas tinham origem lateral à artéria e apresentavam pelo menos um dos critérios usados para definir colo largo - colo maior que 4 mm de diâmetro e relação saco/colo menor que 1,5. Cinqüenta aneurismas eram pequenos, 30 grandes e quatro gigantes (diâmetro máximo menor que 12mm, de 12mm a 25mm e maiores que 25mm, respectivamente). As apresentações clínicas mais comuns foram: achado incidental em 34 pacientes, pós-hemorragia sub aracnóide e recanalização após tratamento com espirais destacáveis em 10. A maioria dos aneurismas era da artéria carótida interna (76 aneurismas). Controles angiográficos foram feitos ao final, aos seis meses e aos 18 meses do tratamento (controles I, II e III respectivamente), sendo analisados principalmente o grau de oclusão (completa ou incompleta), incidência de recanalização e complicações clínicas. Avaliação estatística foi feita pelo método de Kaplan-Meier para o percentual cumulativo de oclusão completa e percentual de recanalização e análise univariada e multivariada dos fatores preditivos de oclusão total imediata e tardia através de regressão logística. Resultados: O índice de oclusão completa foi de 65,5%, 84,6% e de 90,3% para todos os aneurismas, nos controles I, II e III respectivamente. Estes índices foram de 74%, 95,1% e de 95,2% para os aneurismas pequenos e de 53,3%, 70% e de 80% para os aneurismas grandes nos controles I, II e III respectivamente. Oclusão completa ocorreu em 50% dos aneurismas gigantes nos controles I e II, sem haver controle III neste grupo. Recanalização ocorreu em 3 aneurismas (4,6%). O porcentual cumulativo de oclusão completa foi de 97,63% (IC de 95% variando de 95,27 a 100) para os aneurismas pequenos aos 9 meses e de 83,86% (IC de 95% variando de 67,73 a 100) para os aneurismas grandes aos 21 meses. Três pacientes faleceram (4,3%), havendo relação com o procedimento em dois (2,9%). Morbidade permanente ocorreu em cinco pacientes (7,2%), sendo incapacitante em um (1,4%). Conclusões: 1. O uso do Onyx® foi eficiente na oclusão completa dos aneurismas intracranianos de colo largo. 2. O tratamento foi estável nos controles angiográficos aos 6 meses e aos 18 meses. / Introduction: The high rate of incomplete occlusion and intracranial large neck aneurysms recanalization lead to the development of new techniques, including the use of Onyx®. Purpose: to evaluate the efficacy of the liquid embolic system Onyx ® to produce completes occlusion of the intracranial large neck aneurysms and evaluates the stability of the treatment at 6 month and 18 month angiographic control. Materials and Methods: this thesis has been performed at Section of Interventional Neuroradiology of Med Imagem, at the Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, based on a review of clinical and radiological records of 69 patients treated by the author, harboring 84 large neck intracranial aneurysms between July 2002 and February 2006. Ten patients were male and 59 female, with age ranging from 24 to 86 years old. All aneurysms were lateral to the parent vessel and were wide neck (neck > 4 mm and/or domus to neck ratio < 1.5). Fifty aneurysms were small (<12 mm), 30 were large (12 to 25 mm) and 4 were giant (> 25 mm). Thirty four aneurysms were incidental, 10 were ruptured and 10 were recanalized after coil treatment and the majority was located in the internal carotid artery (76). Angiographic follow-up was done at the end of the procedure, at six month and at 18 month (controls I, II and III respectively), analyzing the rate of complete occlusion, recanalization and clinical complication. Statically analysis were done by Kaplan-Meier method for cumulative percentage of complete aneurysm occlusion and for recanalization, and univariate and multivariate analysis of predictive factors of immediate and late complete occlusion through logistic regression. Results: Complete aneurysm occlusion was achieved in 65.5% on immediate control, in 84.6% at 6 month, and in 90.3% at 18 month follow-up periods for all aneurysms. This rate was 74%, 95.1% and 95.2% for small and 53.3%, 70% and 80% for large aneurysms at the same follow-up periods. In the giant aneurysm group, two had complete and stable occlusion at six month follow-up angiography. Recanalization was seen in three aneurysms (4,6%). Kaplan Meyer\'s cumulative percentage of complete aneurysm occlusion was 97.63% (CI 95% ranging from 95,27 to 100) for small aneurysms at 9 months and 83.86% (CI 95% ranging from 67,73 to 100) for large aneurysms at 21 months. There were three deaths (4,3%), two procedure-related (2.9%). Overall morbidity was 7.2%, being disabling in one (1,4%). Conclusions: 1. The use of Onyx was efficient in the complete occlusion of wide neck intracranial aneurysms. 2. The treatment was stable at 6 month and 18 month angiographic controls.

During brain activity neurons release the major excitatory transmitter glutamate, which is taken up by astrocytes and converted to glutamine. Glutamine returns to neurons for re-conversion to glutamate. This glutamate-glutamine cycle is energy demanding. Glutamate turnover in injured brain was studied using an animal iron-induced posttraumatic epilepsy model and using neurointensive care data from 33 patients with spontaneous subarachnoid hemorrhage (SAH). Immunoblotting revealed that the functional form of the major astrocytic glutamate uptake protein GLT-1 was decreased 1-5 days following a cortical epileptogenic iron-injection, presumably due to oxidation-induced aggregation. Using microdialysis it was shown that the GLT-1 decrease was associated with increased interstitial glutamate levels and decreased interstitial glutamine levels. The results indicate a possible posttraumatic and post-stroke epileptogenic mechanism. Analysing 3600 microdialysis hours from patients it was found that the interstitial lactate/pyruvate (L/P) ratio correlate with the glutamine/glutamate ratio (r =-0.66). This correlation was as strong as the correlation between L/P and glutamate (r=0.68) and between lactate and glutamate (r=0.65). Pyruvate and glutamine correlated linearly (r=0.52). Energy failure periods, defined as L/P&gt;40, were associated with high interstitial glutamate levels. Glutamine increased or decreased during energy failure periods depending on pyruvate. Energy failure periods were clinically associated with delayed ischemic neurological deficits (DIND) or development of radiologically verified infarcts, confirming that L/P&gt;40 is a pathological microdialysis pattern that can predict ischemic deterioration after SAH. DIND-associated microdialysis patterns were L/P elevations and surges in interstitial glutamine. Glutamine and pyruvate correlated with the cerebral perfusion pressure (r=0.25, r=0.24). Glutamine and the glutamine/glutamate ratio correlated with the intracranial pressure (r=-0.29, r=0.40). Glutamine surges appeared upon substantial lowering of the intracranial pressure by increased cerebrospinal fluid drainage. Increased interstitial glutamine and pyruvate levels may reflect augmented astrocytic glycolysis in recovering brain tissue with increased energy demand due to a high glutamate-glutamine turnover.

Introdução: A alta incidência de oclusão incompleta e recanalização dos aneurismas intracranianos de colo largo tratados por via endovascular levaram ao desenvolvimento de novas técnicas, entre elas o uso do Onyx ®. Objetivos: avaliar a eficiência do agente embólico líquido Onyx® em produzir oclusão completa dos aneurismas intracranianos de colo largo e avaliar a estabilidade do tratamento aos 6 meses e aos 18 meses, por meio de controles angiográficos. Casuística e métodos: Esta tese foi realizada na Seção de Neuroradiologia Intervencionista da Med Imagem, do Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, através da revisão de dados clínicos e radiológicos de 69 pacientes tratados pelo autor, com 84 aneurismas intracranianos de colo largo no período de julho de 2002 a fevereiro de 2006. Dez pacientes eram do sexo masculino e 59 do sexo feminino, com idade variando de 24 anos a 86 anos (mediana de 52 anos). Todos os aneurismas tinham origem lateral à artéria e apresentavam pelo menos um dos critérios usados para definir colo largo - colo maior que 4 mm de diâmetro e relação saco/colo menor que 1,5. Cinqüenta aneurismas eram pequenos, 30 grandes e quatro gigantes (diâmetro máximo menor que 12mm, de 12mm a 25mm e maiores que 25mm, respectivamente). As apresentações clínicas mais comuns foram: achado incidental em 34 pacientes, pós-hemorragia sub aracnóide e recanalização após tratamento com espirais destacáveis em 10. A maioria dos aneurismas era da artéria carótida interna (76 aneurismas). Controles angiográficos foram feitos ao final, aos seis meses e aos 18 meses do tratamento (controles I, II e III respectivamente), sendo analisados principalmente o grau de oclusão (completa ou incompleta), incidência de recanalização e complicações clínicas. Avaliação estatística foi feita pelo método de Kaplan-Meier para o percentual cumulativo de oclusão completa e percentual de recanalização e análise univariada e multivariada dos fatores preditivos de oclusão total imediata e tardia através de regressão logística. Resultados: O índice de oclusão completa foi de 65,5%, 84,6% e de 90,3% para todos os aneurismas, nos controles I, II e III respectivamente. Estes índices foram de 74%, 95,1% e de 95,2% para os aneurismas pequenos e de 53,3%, 70% e de 80% para os aneurismas grandes nos controles I, II e III respectivamente. Oclusão completa ocorreu em 50% dos aneurismas gigantes nos controles I e II, sem haver controle III neste grupo. Recanalização ocorreu em 3 aneurismas (4,6%). O porcentual cumulativo de oclusão completa foi de 97,63% (IC de 95% variando de 95,27 a 100) para os aneurismas pequenos aos 9 meses e de 83,86% (IC de 95% variando de 67,73 a 100) para os aneurismas grandes aos 21 meses. Três pacientes faleceram (4,3%), havendo relação com o procedimento em dois (2,9%). Morbidade permanente ocorreu em cinco pacientes (7,2%), sendo incapacitante em um (1,4%). Conclusões: 1. O uso do Onyx® foi eficiente na oclusão completa dos aneurismas intracranianos de colo largo. 2. O tratamento foi estável nos controles angiográficos aos 6 meses e aos 18 meses. / Introduction: The high rate of incomplete occlusion and intracranial large neck aneurysms recanalization lead to the development of new techniques, including the use of Onyx®. Purpose: to evaluate the efficacy of the liquid embolic system Onyx ® to produce completes occlusion of the intracranial large neck aneurysms and evaluates the stability of the treatment at 6 month and 18 month angiographic control. Materials and Methods: this thesis has been performed at Section of Interventional Neuroradiology of Med Imagem, at the Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, based on a review of clinical and radiological records of 69 patients treated by the author, harboring 84 large neck intracranial aneurysms between July 2002 and February 2006. Ten patients were male and 59 female, with age ranging from 24 to 86 years old. All aneurysms were lateral to the parent vessel and were wide neck (neck > 4 mm and/or domus to neck ratio < 1.5). Fifty aneurysms were small (<12 mm), 30 were large (12 to 25 mm) and 4 were giant (> 25 mm). Thirty four aneurysms were incidental, 10 were ruptured and 10 were recanalized after coil treatment and the majority was located in the internal carotid artery (76). Angiographic follow-up was done at the end of the procedure, at six month and at 18 month (controls I, II and III respectively), analyzing the rate of complete occlusion, recanalization and clinical complication. Statically analysis were done by Kaplan-Meier method for cumulative percentage of complete aneurysm occlusion and for recanalization, and univariate and multivariate analysis of predictive factors of immediate and late complete occlusion through logistic regression. Results: Complete aneurysm occlusion was achieved in 65.5% on immediate control, in 84.6% at 6 month, and in 90.3% at 18 month follow-up periods for all aneurysms. This rate was 74%, 95.1% and 95.2% for small and 53.3%, 70% and 80% for large aneurysms at the same follow-up periods. In the giant aneurysm group, two had complete and stable occlusion at six month follow-up angiography. Recanalization was seen in three aneurysms (4,6%). Kaplan Meyer\'s cumulative percentage of complete aneurysm occlusion was 97.63% (CI 95% ranging from 95,27 to 100) for small aneurysms at 9 months and 83.86% (CI 95% ranging from 67,73 to 100) for large aneurysms at 21 months. There were three deaths (4,3%), two procedure-related (2.9%). Overall morbidity was 7.2%, being disabling in one (1,4%). Conclusions: 1. The use of Onyx was efficient in the complete occlusion of wide neck intracranial aneurysms. 2. The treatment was stable at 6 month and 18 month angiographic controls.