Orientador: Antonio Guilherme Borges Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-10T13:43:01Z (GMT). No. of bitstreams: 1 Loureiro_AndersonBarbosa_M.pdf: 1654963 bytes, checksum: d49b2312387926f779b4d3c3fec27cfe (MD5) Previous issue date: 2007 / Resumo: A hemorragia subaracnóide (HSA) aneurismática é causada mais comumente pela ruptura de aneurismas saculares, o que leva a um déficit motor e cognitivo importante afetando as atividades funcionais dos pacientes. A mensuração da função é importante na otimização do tratamento fisioterapêutico e alta hospitalar destes pacientes. Este estudo teve como objetivo descrever os resultados da reabilitação em pacientes submetidos a tratamento cirúrgico de clipagem aneurismática admitidos no Hospital das Clínicas da Universidade Estadual de Campinas. Os pacientes foram avaliados por meio dos seguintes instrumentos: escala clínica de Hunt ¿ Hess (na internação hospitalar), que avalia o estado clínico do paciente; a escala neurorradiográfica de Fisher (na internação hospitalar), que avalia a quantidade de sangue no espaço subaracnóide; medida de independência funcional (MIF) (no pós-operatório e alta hospitalar) e escala de prognóstico de Glasgow (na alta hospitalar). Os pacientes foram submetidos ao tratamento fisioterapêutico durante todo o período de internação (dois atendimentos diários). Para comparar os valores da MIF entre admissão e alta foi realizado o teste de Wilcoxon, para verificar a correlação entre os instrumentos de avaliação foi utilizado o coeficiente de correlação de Spearman. Foram avaliados 13 pacientes, 12 (92.31%) mulheres e um homem, com predomínio de aneurismas na artéria cerebral média (53.85%). A idade média foi de 51.62 (DP 13.04) anos. Ocorreu diferença estatística significativa entre as avaliações da MIF (admissão 56.92 ± 23.42; alta 91.77 ± 20.32; p < 0.001). Não foi encontrada correlação significativa entre a MIF e a escala clínica de Hunt-Hess (r = - 0.16282; p = 0.5951), escala neurorradiografica de Fisher (r = 0.06935; p = 0.8219) e a escala de prognóstico de Glasgow (r = 0.24972; p = 0.4106). Os pacientes apresentaram melhoras funcionais após o procedimento cirúrgico e tratamento fisioterapêutico demonstradas de forma quantitativa por meio da MIF e não foi encontrada relação das medidas clínicas com os resultados funcionais / Abstract: Subarachnoid hemorrhage results in critical motor and cognitive impairment which leads to dysfunctions causing a negative impact in quality of life. The functional independence measure (FIM) scale is the most widely accepted functional assessment measure in use in the rehabilitation community. The aim of this study was to describe the rehabilitation outcome after a surgical aneurysm occlusion realized in patients admitted in the Clinical Hospital of Campinas State University ¿ UNICAMP. Patients were submitted to the Hunt-Hess and Fisher assessment scales after admission in to the hospital; to the FIM after surgery; and to FIM and Glasgow Outcome Scale (GOS) after hospital discharge. The days in the hospital were counted, patients had physical therapy twice a day and the injured arteries were identified. Thirteen patients, 12 woman¿s (92,31%) with aneurysm predominant in middle cerebral artery (53,85%) were evaluated. The mean age was 51, 62 (DP 13,04) years old. The mean FIM rate, between the admission and the discharge period, was 34,85 (DP 20,85), with average of 5-69 points (p<0,001). There was non significant correlation between the FIM, Hunt-Hess, Fisher and GOS. The subarachnoid hemorrhage is a catastrophic neurologic event that results in motor and cognitive impairment. The FIM could have an important role in predict the neurorehabilitation outcome in acute aneurysmal subarachnoid hemorrhage / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

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.

Introdução. As artérias perfurantes comumente são evidenciadas durante a dissecção microcirúrgica para clipagem de aneurismas intracranianos. A oclusão de artérias perfurantes pode ser responsável por infarto encefálico isquêmico e resultados clínicos indesejáveis. O presente estudo objetiva descrever a utilidade da vídeo-angiografia intra-operatória com indocianina verde (VAIICG) na avaliação do fluxo sanguíneo em artérias perfurantes visibilizadas no campo microcirúrgico, durante a clipagem de aneurismas intracranianos. Secundariamente, foi analisada a incidência de artérias perfurantes envolvidas durante a cirurgia de aneurismas intracranianos, e a ocorrência de infarto encefálico isquêmico causado pelo comprometimento das artérias perfurantes. Método. Sessenta pacientes, com 64 aneurismas intracranianos foram tratados cirurgicamente, e prospectivamente incluídos neste estudo. A VAIICG intra-operatória foi realizada com o uso de microscópio neurocirúrgico (Carl Zeiss Co. Oberkochen, Germany) com a tecnologia VAIICG integrada. A presença e o envolvimento de artérias perfurantes foram analisados no campo microcirúrgico durante a dissecção cirúrgica, e durante a clipagem do aneurisma. A patência vascular após a clipagem também foi investigada. Apenas artérias pequenas que não foram visibilizadas nas imagens pré-operatórias de angiografia digital com subtração (ADS) foram consideradas para análise. Resultados. A VAIICG permitiu a visibilização do fluxo sanguíneo em todos os casos que apresentaram artérias perfurantes no campo microcirúrgico. Dentre 36 casos cujas artérias perfurantes estavam visíveis à VAIICG, 11 casos (30,5%) apresentaram relação próxima entre o aneurisma e artérias perfurantes. Em um paciente (9,0%), dentre os 11 casos com relação próxima, a VAIICG evidenciou oclusão de uma artéria perfurante de P1 após a aplicação do clipe, cujo reposicionamento correto restabeleceu imediatamente o fluxo sanguíneo, o qual foi visibilizado com a VAIICG, sem conseqüências clínicas. Quatro pacientes (6,7%) apresentaram infarto pós-operatório em território de artérias perfurantes, sendo que em três deles, as artérias perfurantes estavam ausentes ou distantes do aneurisma clipado. Conclusão. O envolvimento de artérias perfurantes durante a clipagem microcirúrgica de aneurismas intracranianos é comum. A VAIICG intra-operatória fornece informação visual do fluxo sanguíneo em artérias de calibre milimétrico, e seu uso possibilita evitar a oclusão de artérias perfurantes e subseqüente infarto encefálico. / Background. Perforating arteries are commonly involved during the surgical dissection and clipping of intracranial aneurysms. Occlusion of perforating arteries may be responsible for ischemic infarction and poor outcome. The goal of this study was to describe the usefulness of near-infrared indocyanine green videoangiography (ICGA) for the intraoperative assessment of blood flow in perforating arteries that are visible in the surgical field during clipping of intracranial aneurysms. In addition we analyzed the incidence of perforating vessels involved during the aneurysms surgery and the incidence of ischemic infarct caused by compromising of these small arteries. Method. Sixty patients harboring 64 aneurysms were surgically treated and prospectively included in this study. Intraoperative ICGA was performed using a surgical microscope (Carl Zeiss Co. Oberkochen, Germany) with integrated ICGA technology. The presence and involvement of perforating arteries was analyzed in the microsurgical field, during surgical dissection, and during the clip application. Assessment of vascular patency after clipping was also investigated. Only those small arteries that were not visible on preoperative digital subtraction angiography (DSA) were considered for analysis. Results. In all cases in which perforating vessels were found in the microscope field, the ICGA was able to visualize flow. Among 36 cases whose perforating vessels were visible on ICGA, 11 cases (30,5%) presented a close relation between the aneurysm and perforating arteries. In one patient (9,0%), among these 11 cases with close relation, ICGA showed occlusion of a P1 perforating artery after clip application, which led to immediate correction of the clip confirmed by immediate re-establishment of flow visible with ICGA without clinical consequences. Four patients (6,7%) presented with postoperative perforating artery infarct of whom in 3 patients the perforating arteries were either not visible or distant from the aneurysm. Conclusion. The involvement of perforating arteries during clip application for aneurysm occlusion is a usual finding. Intraoperative ICGA provide visual information with regard to patency of these milimetric vessels, which may avoid their occlusion and further ischemic infarction.

Les anévrismes intracrâniens présentent des risques importants en raison de leur taux de rupture élevé et des conséquences qui peuvent être fatales comme lors d’hémorragies méningées. Afin d’effectuer une recherche hémodynamique sur l’anévrisme intracrânien in vitro, un fantôme est indispensable. Jusqu’à présent, des fantômes rigides ou simplifiés sont utilisés dans littérature, peu d’entre eux sont suffisamment fidèle à la réalité. Le travail de cette thèse se concentre sur la méthodologie de fabrication des fantômes patient-spécifiques d’anévrismes intracrâniens ainsi que leur mise en œuvre pour différentes utilisations. Ces fantômes possèdent la forme anatomique de l’artère du patient et une paroi élastique. Ils sont fabriqués en appliquant une technique originale de prototypage rapide. Les fantômes sont vérifiés selon plusieurs aspects. Pour effectuer des recherches hémodynamiques sur les fantômes, un banc d’essai compatible avec différentes modalités d’imagerie a été conçu. L’angiographie par résonance magnétique 2D par contraste de phase a été utilisée pour étudier l’hémodynamique des fantômes. Le comportement dynamique de paroi, les trajectoires 3D du flux et son champ de vélocité sont analysés. L’application potentielle dans domaine clinique du fantôme patient-spécifique a été aussi testée dans cette thèse, des simulations d’intervention sur des anévrismes intracrâniens ont été effectuées sur le banc d’essai et les fantômes, les résultats de différentes méthodes ont été analysés et comparés. / Intracranial aneurysms are a hazard to human health because of their high rupture rate and fatal subsequence, such as subarachnoid hemorrhage. In order to carry out a hemodynamic research in vitro on the intracranial aneurysm, a phantom is indispensable. Until now, rigid or simplified phantoms are mainly used in the literature, few among them possess sufficient properties compared with reality. The work of this thesis focuses on the methodology of manufacturing patient-specific phantoms of intracranial aneurysms as well as their implementation for different uses. The phantoms have an anatomical shape of patient’s artery and an elastic wall. They are manufactured by applying an original rapid prototyping technique. The phantoms are examined and verified in different ways. In order to perform a hemodynamic research of the phantoms, a testing platform compatible with different imaging modalities has been designed and established. 2D phase-contrast magnetic resonance angiography was applied in the hemodynamic study of the phantoms. The dynamic behavior of the artery wall, the 3D path-line of flow and the velocity field of flow were analyzed. The potential application in the clinical domain of the patient-specific phantoms was also tested in this thesis, simulations of intervention on intracranial aneurysms were carried out with the testing platform and the phantoms, the results of different treatment strategies were analyzed and compared.

Background: Impaired homocysteine metabolism is associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms. Methods: Caucasian patients (n = 255) treated at two German hospitals for intracranial aneurysms and local controls (n = 348) were genotyped for the following polymorphisms: methionine synthase (MTR) c.2756A→G, methylenetetrahydrofolate reductase (MTHFR) c.677C→T, MTHFR c.1298A→C, cystathionine β-synthase (CBS) c.844_855ins68, CBS c.833T→C, dihydrofolate reductase (DHFR) c.594 + 59del19bp, glutathione S-transferase Ω-1 (GSTO1) c.428C→A, reduced folate carrier 1 (RFC1) c.80G→A and transcobalamin 2 (Tc2) c.776C→G. Results: The G-allele of the missense polymorphism Tc2 c.777C→G was found to be underrepresented in patients, suggesting that this variant may protect from the formation of cerebral aneurysms [odds ratio per two risk alleles (OR) 0.48; 95% confidence interval (CI) 0.30–0.77; p = 0.002]. We obtained borderline results for the G-allele of RFC1 c.80G→A (OR 1.64; 95% CI 1.01–2.65; p = 0.051) and the insertion allele of DHFR c.594 + 59del19bp (OR 1.61; 95% CI 1.00–2.60; p = 0.059), which were found to be overrepresented in patients. Conclusion: Polymorphisms of homocysteine metabolism are possible risk factors for the formation of intracranial aneurysms. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: There is growing evidence that genetic variants have an impact on the pathogenesis of intracranial aneurysm (IA). Recently, the genetic locus around the elastin gene (7q11) has been identified as linked to IA in a Japanese population. Our aim was to confirm these results in Caucasian populations. Methods: We conducted a case-control study in 120 Caucasian patients with IA and 172 controls to investigate 8 single nucleotide polymorphisms (SNPs) and various haplotypes within the elastin gene, which were frequently found and associated with the phenotype in the Japanese populations. Real-time PCR and melting curve analysis were used for the detection of genotypes. Results: Allele frequencies and genotypes were equally distributed between Caucasian cases and controls. We failed to identify haplotypes that are associated with the phenotype in our population, which is in contrast to the Japanese study. However, allele frequencies in control populations differ between Caucasians and Japanese. Conclusions: We found no association between SNPs and haplotypes of the elastin gene and the occurrence of IA in our Caucasian populations. However, our data provide strong evidence for racial/ethnic differences in the association of SNP and specific haplotypes of the elastin gene with the phenotype. There might be other genetic variants of the elastin gene associated with IA in Caucasians. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20983号 / 医博第4329号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 竹内 理, 教授 杉田 昌彦, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background and Purpose: Flow diversion is increasingly used as an endovascular treatment for intracranial aneurysms. In this retrospective multicenter study, we analyzed the safety and efficacy of the treatment of intracranial, unruptured, or previously treated but recanalized aneurysms using Flow Re-Direction Endoluminal Device (FRED) Jr with emphasis on midterm results. Materials and Methods: Clinical and radiological records of 150 patients harboring 159 aneurysms treated with FRED Jr at six centers between October 2014 and February 2020 were reviewed and consecutively included. Clinical outcome was measured by using the modified Rankin Scale (mRS). Anatomical results were assessed according to the O’Kelly-Marotta (OKM) scale and the Cekirge-Saatci Classification (CSC) scale. Results: The overall complication rate was 24/159 (16%). Thrombotic-ischemic events occurred in 18/159 treatments (11%). These resulted in long-term neurological sequelae in two patients (1%) with worsening from pre-treatment mRS 0–2 and mRS 4 after treatment. Complete or near-complete occlusion of the treated aneurysm according to the OKM scale was reached in 54% (85/158) at 6-month, in 68% (90/133) at 1-year, and in 83% (77/93) at 2-year follow-up, respectively. The rates of narrowing or occlusion of a vessel branch originating from the treated aneurysm according to the CSC scale were 11% (12/108) at 6-month, 20% (17/87) at 1-year, and 23% (13/57) at 2-year follow-up, respectively, with all cases being asymptomatic. Conclusions: In this retrospective multicenter study, FRED Jr was safe and effective in the midterm occlusion of cerebral aneurysms. Most importantly, it was associated with a high rate of good clinical outcome.

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease with mean age of 59 years. SAH accounts for 5% of all stroke and more than one quarter of potential life years lost through stroke. With the advanced neurosurgical methods of today two thirds of the patients survive. We know, however, that various cognitive, psychiatric and physical impairments are common that affect quality of life, social life, and the ability to work in the aftermath of SAH. The overall aim constituting this PhD dissertation is to better understand some of the challenges often faced by those surviving SAH. Two SAH patient cohorts have been studied. The first followed 96 consecutively included patients during the first year after ictus. Spasticity and cognitive impairment was assessed after 6 months and the Swedish stroke register follow-up form was used to investigate family support and the use of medical and social services. Return to work was assessed at 12 months. The second cohort assessed attention deficits using the test of variables of attention (T.O.V.A.) at 7 months after ictus in 19 patients with moderate to good recovery. Spasticity was just as common in our SAH patients as after other stroke, though it was rarely treated pharmacologically. By assessing cognitive impairment at 6 months after ictus using the Montreal cognitive assessment, 68% of the patients could be correctly predicted as having returned/not returned to work at 12 months. Seventeen percent of the patients had not had a follow-up appointment 6 months after ictus. These patients were older, more often living alone, had a lower quality of life, more depressive symptoms and more cognitive impairment compared to those having had a follow-up appointment. Twenty percent had had a follow-up in primary care. Seventy-eight percent of those with moderate to severe disability were living in their own accommodations. Fifty-eight percent of the patients had attention deficits. Challenges after SAH were common and often dealt with in the home environment of the patients. The results of this thesis highlight the importance of assisting the patients and their relatives in their struggle back to life after SAH.

Para desenvolver e avaliar a aplicabilidade de uma escala técnica prognostica das dificuldades no tratamento microcirúrgico dos aneurismas gigantes e complexos da circulação anterior do polígono de Willis, 50 lesões foram operadas. Um valor numérico foi dado a cada uma das 8 variáveis da escala. Somando-se os valores para cada variável, uma nota (de 1 a 14) foi obtida, para cada uma das 50 cirurgias. Dois grupos, portanto, foram definidos: cirurgia difícil (nota de 1 a 8) e cirurgia extremamente difícil (nota de 9 a 14). Foi feita análise estatística comparando-se os 2 grupos em relação a diversas variáveis demográficas e clínicas. Concluiu-se que a escala proposta é útil no planejamento pré-operatório, intra-operatório e prognóstico neste tipo de aneurisma / In order to develop and verify the applicability of a technical and prognostic scale of the difficulties in the microsurgical treatment of giant and complex aneurysms of the anterior circulation of the Cicle of Willis, 50 lesions were operated. A numeric amount was given for each of 8 variants of the scale. By adding each amount for each variant a score(from 1 to 14) was achieved, for each of the 50 surgeries. Two groups, therefore, were established: difficult surgery (scores from 1 to 8) and extremely difficult surgery (scores from 9 to 14). Statistical assessment comparing both groups in relation to several demographic and clinical variants was done. It was concluded that the proposed scale is useful in preoperative, intraoperative and prognostic planning in microsurgery for this kind of aneurysms