Plusieurs études de simulation in vitro et in vivo ont été réalisées au cours des dernières décennies afin de clarifier les interrelations des sources corticales avec leurs corrélats électrophysiologiques enregistrés sur l’EEG invasif et l’EEG de scalp. L’amplitude des potentiels corticaux, l’étendue de l’aire corticale impliquée par la décharge, de même que la localisation et la géométrie de la source corticale sont des facteurs indépendants qui modulent l’observabilité et la contribution de ces sources sur l’EEG de surface. L’enregistrement simultané et multi-échelle de l’EEG de scalp et intra-crânien (avec des électrodes sous-durales ou profondes) durant l’exploration pré-chirurgicale des patients épileptiques offre une opportunité unique d’explorer cette question fondamentale. Alors que les études précédentes ont considéré essentiellement des sources néocorticales dans le contexte de l’épilepsie du lobe temporal, notre travail s’est intéressé à l’observabilité et la contribution de sources profondes temporales et frontales. Nous avons pu montrer : (1) que les sources épileptiques profondes enregistrées dans les régions temporales médianes et fronto-basales ne sont pas visibles par l’analyse visuelle de routine mais sont détectables après élimination du bruit de fond physiologique généré par les sources corticales de surface sus-jacentes ; (3) que l’amplitude des pointes enregistrées en surface est corrélée avec la surface d’activation corticale de la convexité et avec des ratios élevés d’amplitude pointes/activité de fond / Several in vitro, in vivo, and simulation studies have been performed in the past decades aiming to clarify the interrelations of cortical sources with their scalp and invasive EEG correlates. The amplitude ratio of cortical potentials to their scalp EEG correlates, the extent of the cortical area involved in the discharge, as well as the localization of the cortical source and its geometry, have been each independently linked to the recording of the cortical discharge with scalp electrodes. Simultaneous multiscale EEG recordings with scalp, subdural and depth electrodes, applied in presurgical epilepsy workup, offer an excellent opportunity to address this fundamental issue. Whereas past studies have considered predominantly neocortical sources in the context of temporal lobe epilepsy, the present work addresses deep sources, in mesial temporal and extra-temporal epilepsies. We showed that deep sources, such as those in mesial temporal or fronto-basal regions, are not visible, but are detectable in scalp EEG. Scalp EEG spikes correlate with extensive activation of the cortical convexity and high spike-to-background amplitude ratios

Die vorliegende Arbeit setzt sich mit der klinischen Anwendung von zwei neuen Monitoringparametern - Hirngewebe-PO2 in der weißen Substanz (PtiO2), und online intrakranielle Compliance (cICC) - im Rahmen des multimodalen zerebralen Monitorings bei Patienten mit schwerem Schädel-Hirn-Trauma auseinander. Bezüglich des PtiO2 konnte erstmalig eine Hypoxiegrenze von 8,5 mmHg durch vergleichende Messungen mit der jugular-venösen Oxymetrie ermittelt werden. Ferner konnte gezeigt werden, dass, bei intakter zerebraler Autoregulation, der PtiO2 bei einem zerebralen Perfusionsdruck (CPP) >60 mmHg über dem pathologischen Grenzwert liegt. Eine forcierte bzw. moderate Hyperventilation hingegen, induziert, trotz adäquatem CPP, eine Reduktion des PtiO2, die im individuellen Fall zur Unterschreitung des hypoxischen Grenzwerts führt. Das PtiO2-Verfahren ist somit v.a. dann indiziert, wenn eine Hyperventilationstherapie zur Kontrolle eines pathologisch erhöhten intrakraniellen Drucks (ICP) eingesetzt werden muss. PtiO2-Messwerte bedürfen aber einer kritischen Interpretation, sofern der PtiO2-Katheter in der Nähe einer Kontusion lokalisiert ist. Hier ist der PtiO2, als Ausdruck des perikontusionell reduzierten zerebralen Blutflusses, signifikant erniedrigt und somit nicht repräsentativ für die globale zerebrale Oxygenierung. Für die cICC konnte ebenfalls ein pathologischer Grenzwert angegeben werden (0,5 ml/mmHg). Die Dateninterpretation ist aber, durch die offensichtliche Abnahme der intrakraniellen Compliance mit zunehmendem Lebensalter, erschwert. Ferner bleibt die cICC bzgl. ihrer Datenqualität weit hinter etablierten Parametern zurück, so dass ihre routinemäßige Anwendung zum jetzigen Zeitpunkt nicht zu empfehlen ist. Basierend auf unseren Untersuchungen hat sich das PtiO2-Verfahren international als Langzeitmonitoring der zerebralen Oxygenierung etablieren können. Die cICC hingegen bedarf umfangreicher Systemänderungen, um eine frühe Risikoabschätzung bezüglich eines drohenden ICP-Anstiegs suffizient zu ermöglichen. / The aim of our clinical and experimental studies was to evaluate two new monitoring parameters -brain tissue PO2 (PtiO2) of cerebral white matter, and online intracranial compliance (cICC) - in patients with severe traumatic brain injury by using a computerized multimodal cerebral monitoring system. By comparing PtiO2 with jugular vein oxygen saturation, we were able to establish the hypoxic PtiO2-threshold of 8.5 mmHg. Moreover, we demonstrated that in case of an intact cerebral autoregulation, PtiO2 was well above the hypoxic threshold as long as cerebral perfusion pressure (CPP) stayed above 60 mmHg. However, forced or moderate hyperventilation carried an individual risk of a PtiO2 reduction below the hypoxic threshold despite an adequate CPP. PtiO2 monitoring is therefore particularly indicated, if hyperventilation therapy is necessary for control of pathologically increased intracranial pressure (ICP). However, PtiO2-values needed critical interpretation, if catheters were placed close to contusions. In these situations, PtiO2 has been shown to be significantly reduced, presumably due to low peri-contusional blood flow. Thus, such PtiO2 measurements cannot be taken as representatives of global cerebral oxygenation. In cICC monitoring, a pathological threshold was accomplished (0.5 ml/mmHg). Due to a stepwise cICC reduction with increasing age, cICC data interpretation was aggravated, and cICC data quality was significantly reduced in comparison to other established monitoring parameters. Hence, a routine use of this device is currently not advisable. Based on ours results, the PtiO2-methode has been established internationally as an ideal tool for long-term monitoring of cerebral oxygenation. On the contrary, the cICC system needs extensive alterations in order to anticipate sufficiently pathological ICP rises.

Made available in DSpace on 2015-03-04T18:57:36Z (GMT). No. of bitstreams: 1 bulant.pdf: 14030619 bytes, checksum: 7bdeb54a02eeadbb90a53496f04a524c (MD5) Previous issue date: 2013-02-26 / This work focuses on tomographic reconstruction and three-dimensional arterial structures segmentation problems, understanding both as fundamentals modules of patient specific-based cardiovascular modeling. Is in this context where the possibility of improving information quality contained in medical images, by means of more accurate reconstruction methods, is of interest because of its impact on segmentation algorithm precision, allowing the construction of more realistic vessel geometrical models. Specifically, in this work, we study the reconstruction from projection inverse problem based on the classic simplified model for x-ray interaction, using the Radon transform, in two and three dimensions with different acquisition geometries. Then, we present the standard methods, which are based on analytic inversion of the Radon transform in the form of back-projection. An iterative reconstruction method based on sensitivity analysis, was studied and adapted to work in a parallel and matrix-free form. In addition, a novel reconstruction method, with foundations given by the theoretical framework of variational formulations, is developed. In view of the characteristics of the methodology, the computational implementation is carried out following a distributed computing paradigm on top of a matrix-free form version of the method. We perform parameter sensitivity analysis for each method, and a quantitative comparative analysis among them, using the well known Shepp-Logan head phantom, is also presented. Some preliminary reconstruction studies with real data are presented. In the context of medical image segmentation, we explore two alternatives for arterial structures segmentation from three dimension images acquired on three-Dimensional Rotational Angiography and Computed Tomography Angiography clinical studies. The first methodology is based on a simple seeded region growing algorithm, combined with thresholding and anisotropic diffusion techniques. The second pipeline uses a Level Set approach, initialized with the colliding fronts algorithm. Now days, Level Set methods variants are gaining popularity for vessel segmentation problems. In this work, we present a qualitative comparison by segmenting a numerical phantom, as well as segmenting arterial structures on different anatomical regions of the head and neck. At last, we present some recommendations for method and parameter choosing, as a function of the anatomical region. / Este trabalho foca-se nos problemas da reconstrução tomográfica e da segmentação de estruturas arteriais em três dimensões, entendendo ambos como blocos fundamentais na modelagem do sistema cardiovascular humano orientada a pacientes específicos. Dentro deste contexto, a possibilidade de melhorar a qualidade das informações contidas nas imagens médicas realizadas em estudos clínicos via métodos de reconstrução mais precisos torna-se atraente porque impacta diretamente na acurácia das técnicas de segmentação, e permite a construção de modelos geométricos mais próximos à realidade. Especificamente, neste trabalho, o problema inverso de reconstrução a partir de projeções é estudado empregando o modelo simplificado clássico, via a transformada de Radon, para duas e três dimensões com diferentes geometrias de amostragem. Logo, os métodos de resolução padrão baseados na inversão analítica desta transformada em forma de back-projection foram estudados. Um método iterativo baseado em análise de sensibilidade, denominado aqui como método baseado no gradiente topológico, foi estudado e adaptado para funcionar com um esquema matrix-free em paralelo. Em seguida, um novo método com fundamentos na teoria de formulações variacionais é desenvolvido. Devido às características do método, o mesmo é implementado computacionalmente empregando paralelismo e um formato matrix-free. Um estudo quantitativo sobre os parâmetros de cada método é fornecido, assim como também um estudo comparativo entre todos eles usando o amplamente difundido fantasma de Shepp-Logan. Por fim, estudos preliminares com projeções de estudos de angiografias rotacionais tridimensionais são apresentados. No contexto da segmentação de imagens médicas, duas alternativas são apresentadas para segmentar estruturas arteriais a partir de imagens tridimensionais provenientes de estudos de angiografia rotacional e tomográfica. A primeira metodologia baseia-se num enfoque simples de crescimento de região, combinado com thresholding e suavizado anisotrópico. A segunda metodologia utiliza um enfoque de Level Set, inicializado por uma técnica denominada colliding fronts. Na atualidade diversas variantes do método de Level Set têm ganhado popularidade na segmentação de estruturas arteriais. Neste trabalho comparam-se qualitativamente ambas alternativas com um fantasma numérico, e na segmentação de estruturas arteriais presentes em imagens médicas localizadas em diversas regiões anatômicas. Por fim, recomendações sobre o método mais conveniente a ser utilizado em cada região junto com valores para os parâmetros são fornecidos.

Introdução: A neurocirurgia minimamente invasiva já é uma realidade em muitos centros em todo o mundo. A aplicação de conceitos antigos com a incorporação de novas tecnologias permite o emprego de medidas menos invasivas, mas com a mesma eficácia e segurança. O real papel destas técnicas e o seu efeito sobre a evolução dos doentes ainda é nebuloso. Objetivos: avaliar a segurança e resultados da técnica minimamente invasiva na clipagem de aneurismas cerebrais de circulação anterior e determinar o momento seguro para alta hospitalar. Materiais: Cento e onze doentes adultos com diagnóstico de aneurismas não rotos de circulação anterior foram randomicamente distribuídos e submetidos a cirurgia por um acesso minimamente invasivo (grupo de estudo - 36 pelo acesso transpalpebral e 34 através de craniotomias minipterional reduzida) ou acesso pterional clássico (grupo controle - 41 doentes). O endoscópio acoplado a um telefone celular foi utilizado juntamente com o microscópio durante as cirurgias do grupo de estudo. Os doentes do grupo de estudo foram submetidos a um protocolo específico para avaliação da segurança da alta hospitalar precoce. Foram avaliados desfechos cirúrgicos, clínicos/funcionais, estéticos e sobre qualidade de vida. Resultados: Em ambos os grupos, os dados demográficos e as características dos aneurismas foram similares. O tempo médio das cirurgias foi menor no grupo de estudo (214 min. vs 292 min, p = 0,0008). A necessidade de transfusão sanguínea foi menor no grupo de estudo (1 doente vs 7 doentes, p = 0,018). O número de eventos isquêmicos foi menor no grupo de estudo (4 doentes vs 8 doentes, p = 0,07), mas os eventos com repercussão clínica foram semelhantes (2 doentes vs 3 doentes, p = 0,53). A presença de colo residual na angiografia controle foi menor no grupo de estudo (6 doentes vs 11, p = 0,021), mas foram todos colos pequenos, 1,75 ± 0,68 mm, sendo que apenas um doente do grupo controle foi reoperado. A paralisia do ramo frontal do nervo facial foi menor no grupo de estudo, tanto a temporária (3 vs 14, p = 0,008) quanto a definitiva (0 vs 4, p = 0,032). A atrofia do músculo temporal foi menos frequente e mais leve no grupo de estudo (9 vs 14, p = 0,012). No grupo de estudo, 91,4% dos doentes receberam alta precoce no dia seguinte da cirurgia e nenhum doente apresentou evento adverso por este motivo. Os doentes do grupo de estudo ficaram assintomáticos mais rapidamente no pós-operatório (pela avaliação da escala de Rankin, p = 0,0026), mas não houve diferença entre os grupos dentre as pontuações acima de 1 na escala de Rankin modificada. Um doente do grupo controle faleceu no pós-operatório (0,9%). Conclusões: Os resultados demonstraram que as alternativas minimamente invasivas propostas são seguras e tem resultados clínicos e cirúrgicos iguais ou superiores ao tratamento clássico em vários quesitos. A alta precoce nestes doentes é possível e segura. O acesso nanopterional ou transpalpebral é uma alternativa melhor em relação à craniotomia pterional clássica para tratar aneurismas não rotos da circulação anterior / Introduction: Minimally invasive neurosurgery is already a reality in many centers across the world. The application of old concepts with the incorporation of new technologies allows the use of less invasive measures with the same effectiveness and safety. However, the real role of these techniques and their effect on the outcome of patients is still obscure. Objectives: To evaluate the safety and results of minimally invasive techniques in brain aneurysm clipping and determine the possibility of early hospital discharge. Methods: 111 adult patients with unruptured anterior circulation aneurysms were randomized and underwent a minimally invasive surgical approach, (36 by transpalpebral approach and 34 through a reduced minipterional craniotomy) or classical pterional approach (41 patients). The endoscope coupled to a smart phone was used along with the microscope during surgery (study group only). Patients in the study group were subjected to a specific protocol for assessment of early hospital discharge. Surgical, clinical/functional and aesthetic outcomes were evaluated along with long term quality of life. Results: In both groups, the demographics and characteristics of aneurysms were similar. The average time of surgery was lower in the study group (214 min. vs. 292 min, p = 0.0008). The need for blood transfusion was lower in the study group (1 patient vs 7 patients, p = 0.018). The number of ischemic events was lower in the study group (patients 4 patients vs. 8, p = 0.07), but events with clinical significance were similar (3 patients vs. 2 patients, p = 0.53). The presence of residual neck on control angiography was lower in the study group (6 patients vs 11, p = 0.021), but only small ones were found, 1.75 ± 0.68 mm, and only one control group patient required reoperation for this reason. The paralysis of the frontal branch of the facial nerve was lower in the study group, both temporary (3 vs 14, p = 0.008) and definitive (0 vs. 4, p = 0.032). The atrophy of the temporal muscle was less frequent and less severe in the study group (9 vs 14, p = 0.012). Most patients in the study group (91.4%), were discharged on the next day of the surgery and no patients had any related adverse events. Patients in the study group got asymptomatic faster (assessed by the Rankin scale, p = 0.26), but there was no difference between the groups among scores above 1 on the modified Rankin scale. One control group patient died postoperatively (0,9%). Conclusions: The results showed that the proposed minimally invasive alternatives are safe. Clinical and surgical results are equal or superior to conventional treatment in several topics. Early discharge in these patients is possible and safe. The described approaches (nanopterional or transpalpebral) are better alternatives to the classical pterional craniotomy to treat unruptured aneurysms of the anterior circulation

O presente estudo avaliou a autorregulação encefálica (ARE) em doentes com insuficiência hepática fulminante (IHF) antes e após transplante hepático. Foram avaliados 25 pacientes com diagnóstico de IHF, 17 foram avaliados antes e após o transplante hepático, sendo seis (24,0%) do sexo masculino e 19 (76,0%) feminino. A média de idade foi de 33,8 anos, que variou de 14 a 56 anos, com desvio padrão de 13,1 anos. A hemodinâmica encefálica foi avaliada pela velocidade de fluxo sanguíneo encefálico (VFSE) nas artérias cerebrais médias e artéria basilar (AB), que usou o ultrassom Doppler transcraniano (DTC), dispositivo de dois canais, com transdutores de 2 mega Hertz (MHz). A autorregulação encefálica foi mensurada pelo índice de autorregulação (IARE) estática que leva em conta os efeitos do aumento da pressão arterial média (PAM) sobre a VFSE. Para isso, promoveu-se o aumento da PAM (20 mmHg a 30 mmHg) com infusão de noradrenalina.. Ao se avaliar o IARE considerando a velocidade de fluxo sanguíneo em quatro momentos (pré-transplante, 1°, 2° e 3° dia após o transplante), observou-se que houve diferença estatística em artéria cerebral média (ACM) à direita (p=0,008), esquerda (p=0,007), máxima (p=0,005), e AB (p=0,006); assim como na análise em cada tempo do IARE, observou-se diferença estatística em ACM à direita (p=0,012), esquerda (p=0,009), máxima (p=0,006), e AB (p=0,011). A análise categórica do IARE na artéria cerebral média e basilar descreveu que a maioria dos doentes reestabeleceu a AR no 2° dia em ACM e 3° na AB (índice > 0,6), enquanto com o índice > 0,8 em ambas as artérias a ARE reestabeleceu no 2° dia. As variáveis sistêmicas como pressão parcial de CO2 e hemoglobina nos tempos da avaliação não apresentaram diferença estatística p=0,100 e p=0,093 respectivamente. Os resultados obtidos apontam para o comprometimento da ARE antes e após transplante hepático, tanto em circulação anterior como posterior, e que tende a ser reestabelecido entre 48 a 72 horas. Os achados deste estudo favorecem o manejo adequado de doentes nestas fases (antes e após transplante) e podem evitar a evolução para complicações neurológicas, como tumefação encefálica e hipertensão intracraniana, que indicam prognóstico ruim para a evolução clínica destes doentes. Estudos futuros necessitam ser realizados para que se consolide o uso da monitoração contínua com métodos não invasivos como o DTC para direcionar o manejo hemodinâmico encefálico na IHF / This study evaluated cerebral autoregulation in patients with fulminant hepatic failure (FHF) before and after liver transplantation. A total of 25 patients comprising six (24.0%) males and 19 (76.0%) females with FHF were evaluated. Seventeen patients were evaluated both before and after liver transplantation. Mean age of the patients was 33.8 years, with a range of 14-56 years and standard deviation of 13.1 years. Brain hemodynamics was assessed by cerebral blood flow velocity in the middle cerebral arteries (MCA) and basilar artery (BA) using transcranial Doppler ultrasound on a two-channel device with 2 MHz transducers. Cerebral autoregulation was measured by static cerebral autoregulation index (SCAI), which accounts for the effects of increase in mean arterial blood pressure (ABP) on cerebral blood flow velocity. An increase in ABP (20 mmHg to 30 mmHg) was induced with norepinephrine infusion. Evaluation of SCAI based on blood flow velocity (BVF) at four timepoints (pre-transplant and on 1st, 2nd and 3rd days post-transplant) revealed a statistical difference in the MCA right (p = 0.008) left (p = 0.007), maximum (p = 0.005) and the BA (p = 0.006). In addition, analysis by timepoint showed a statistical difference in MCA (p = 0.012), left (p = 0.009), maximum (p = 0.006) and in the BA (p = 0.011). Categorical analysis of autoregulation in the MCA and BA showed that most patients reestablished autoregulation in the MCA on the 2nd day post-transplant and in the BA (index > 0.6) on the 3rd day, while autoregulation was reestablished in both arteries (index > 0.8) on the 2nd day. On the assessment by timepoint, the systemic variables CO2 partial pressure and hemoglobin showed no statistically significant differences (p = 0.100 and p = 0.093, respectively). The results reveal impaired SCAI before and after liver transplantation, both in anterior and posterior circulation, with a tendency to reestablish at 48 to72 hours. The findings of this study can help improve management of patients at these stages (pre and post transplantation), preventing neurological complications such as brain swelling and intracranial hypertension, associated with poor prognosis for the clinical course. Future studies should be conducted to consolidate the use of continuous monitoring with noninvasive method (TCD), to provide more accurate information to guide brain hemodynamic management in FHF

Made available in DSpace on 2016-01-26T12:51:25Z (GMT). No. of bitstreams: 1 marcosluiztostesdossantos_dissert.pdf: 2066322 bytes, checksum: 9abf4b93ab3ce79b49c60b4edd0f3b0c (MD5) Previous issue date: 2007-11-06 / Brain arteriovenous malformations (BAVM) are morphological and neurovascular abnormalities characterized by direct communication between arteries and veins, without interposition of capillary bed, therefore without resistance to blood flow. OBJECTIVE: The purpose of this research was to characterize morphologically brain arteriovenous malformations aiming correlation with clinical presentation. CASUISTIC AND METHOD: A total of 170 patients with brain AVM, 78(46%) males and 92(54%) females, were studied from January 2001 to January 2007 at the Vascular and Endovascular Neurosurgery Unit of the Hospital de Base of São José do Rio Preto, SP. Univariate and multivariate analyses were conducted to test the associations among demographic (sex, age), clinical (hemorrhage, seizure, focal neurological deficit, and headache), and morphological features (anatomical localization; superficial, deep, infratentorial or supratentorial location; nidus size; number of feeding arteries, compartments, and draining veins; type of venous drainage; presence of stenosis, venous ectasias, and arterial aneurysms; Spetzler-Martin classification). RESULTS: The main clinical presentations at the moment of diagnosis included hemorrhage in 89 (52%) patients, headache in 79 (46%), focal neurological deficit in 54 (32%), and seizure in 52 (31%). According to the Spetzler-Martin classification, grade I was found in 15 (9%) patients, grade II in 49 (28%), grade III in 55 (33%), grade IV in 41 (24%), and grade V in 10 (6%) patients. There was a statistically significant association among hemorrhage and small nidus size (p = 0.002), single feeding artery (p = 0.007), single draining vein (p = 0.003), and single compartment (p = 0.040). Seizure was positively correlated with medium (3-6 cm) and large nidus size (>6cm), and negatively with small nidus size (<3cm) (p = 0.021). CONCLUSIONS: Brain AVM with small nidus size, Spetzler-Martin grade I, single feeding artery and draining vein are associated with hemorrhage. Spetzler-Martin grade V was negatively associated with hemorrhage. In the braim AVM there is no association between aneurysm and hemorrhage. On the other hand, seizure show positive correlation with large nidus size and negative with small nidus size. / Malformações arteriovenosas (MAV) encefálicas são anomalias morfológicas neurovasculares caracterizadas por comunicação direta entre artérias e veias, sem interposição do leito capilar, portanto sem resistência ao fluxo sangüíneo. OBJETIVO: O objetivo desta pesquisa foi caracterizar morfologicamente MAV encefálicas, visando correlação com apresentação clínica. CASUÍSTICA E MÉTODO: Foram estudados 170 pacientes portadores de MAV encefálicas, sendo 78 (46%) do sexo feminino e 92 (54%) do masculino, no período de janeiro de 2001 a janeiro de 2007, atendidos na unidade de Neurocirurgia Vascular e Endovascular do Hospital de Base de São Jose do Rio Preto, SP. Análises univariada e multivariada foram efetuadas para testar associações entre características demográficas (sexo, idade), clínicas (hemorragia, convulsão, déficit focal, cefaléia) e morfológicas (localização anatômica; posição superficial, profunda, infratentorial ou supratentorial; tamanho do nidus; número de aferências, compartimentos e eferências; padrão de drenagem venosa; presença de estenose, ectasias venosas e aneurismas arteriais; classificação de Spetzler-Martin). RESULTADOS: As principais formas de apresentação clínica no momento do diagnóstico incluíram hemorragia em 89 (52%) pacientes, cefaléia em 79 (46%), déficit focal em 54 (32%) e convulsão em 52 (31%). De acordo com a classificação de Spetzler & Martin, 15 (9%) pacientes tinham MAV grau I, 49 (28%) grau II, 55 (33%) grau III, 41 (24%) grau IV, e 10 (6%) grau V. Houve associação estatisticamente significativa entre hemorragia e tamanho pequeno do nidus (p = 0,002), aferência única (p = 0,007), eferência única (p = 0,003) e compartimento único (p = 0,040). Convulsão foi correlacionada positivamente com nidus de tamanho médio (3-6 cm) e grande (>6cm) e negativamente com tamanho pequeno (<3cm) (p = 0,021). CONCLUSÕES: MAV encefálicas com nidus de tamanho pequeno, grau I, aferência e eferência únicas estão associados à hemorragia. MAV encefálicas grau V estão associadas negativamente à hemorragia. Na MAV encefálica observa-se ausência de associação entre aneurisma e hemorragia. Por outro lado, convulsão mostra correlação positiva com nidus de tamanho grande e negativa com nidus de tamanho pequeno.

A monitoração intraventricular da pressão intracraniana (PIC) com drenagem contínua do líquido cefalorraquiano (LCR) já é um procedimento difundido na prática da neurocirurgia e considerado de grande importância diagnóstica, terapêutica e prognóstica por sua precisão. Entretanto, por se tratar de um método invasivo, apresenta riscos potenciais de complicações, sendo a infecção a mais freqüente. O presente estudo teve como objetivo verificar e analisar as taxas de infecções decorrentes deste método de monitoração da PIC, assim como as taxas de seus fatores de risco. As informações obtidas através de prontuários e arquivo dos exames laboratoriais foram registradas em duas fichas de coleta de dados próprias e posteriormente submetidas a testes estatísticos como o de Kruskal-Wallis, de Mann-Whitney, de qui-quadrado, teste exato de Fisher e o coeficiente de correlação de Spearman. Obtidas as freqüências relativas e absolutas, médias e desvio-padrão, sendo de 5% o nível de significância utilizado para os testes. A população deste estudo foi de 79 pacientes dos quais 70.9% eram do sexo masculino com média de 33.7 anos, sendo que os diagnósticos presentes em 82.3% eram referentes ao trauma craniencefálico (TCE) seguido de tumores intracranianos e acidentes vasculares cerebrais (AVCs). Todos fizeram uso de antibioticoprofilaxia. A taxa de ventriculite foi de 26.6%, permanecendo o cateter, em média, 6.7 dias e apresentando taxas diárias desta infecção variáveis. Não encontramos associação estatisticamente significativa entre tempo de monitoramento e infecção, porém houve um aumento no índice diário de ventriculite após os três primeiros dias e picos no 6°, 9° e 12° dia indicando uma provável ligação não acumulativa ou linear. Outras variáveis avaliadas neste estudo que apresentaram associação direta com a ocorrência de ventriculite foram o sexo masculino, hemorragia subdural e infecções em outros sítios, principalmente a sepses. Variáveis como idade, procedimentos invasivos, TCE aberto, fístulas liquóricas, hemorragia intraventricular, múltiplas ventriculostomias, presença de PIC acima de 20mmHg, intercorrências durante a cateterização ou manutenção desta não apresentaram associação com a taxa ventriculite, no entanto muitas destas variáveis estiveram presentes em poucos casos dificultando uma conclusão definitiva. / Intraventricular monitoring of the intracranial pressure (ICP) with continuous drainage of cerebrospinal fluid (CSF) is already a widespread procedure in neurosurgical practice and considered as of great diagnostic, therapeutic and prognostic importance due to its precision. However, as it is an invasive method, it presents a potential risk of complications, the infection being the most frequent. The present study aims at verifying and analyzing the rates of infection originating from this monitoring method of ICP, as well as the rates of its risk factors. The information obtained from case histories and laboratory test files were recorded on two own separate data collection cards and later submitted to statistical tests like the Kruskal-Wallis, Mann-Whitney, Chi-Square, Fisher’s exact test, and Spearman correlation coefficients. Relative and absolute, average and standard deviation frequency were verified, 5% was the significance level utilized for the tests. The population of this study was of 79 patients, 70.9% of which were male averaging 37.7 years of age, this being so that the diagnostics present in 82.3% are related to traumatic head injury followed by intracranial tumors and stroke. All of them made use of antibioticprophylaxis. The ventriculitis rate was of 26.6 %, the catheter remaining, on average, 6.7 days and showing variable daily rates of this infection. We have not found a statistically meaningful association between monitoring time and infection, however there was an increase in the daily ventriculitis rate after the first three days and peaks on the 6th, 9th and 12th days showing a probable non-cumulative or linear link. Other variables evaluated in this study which presented a direct association with the occurrence of ventriculitis were the male sex, subdural hemorrhage and infections at other sites, mainly sepsis. Variables such as age, invasive procedures, open traumatic head injury, CSF leaks, intraventricular hemorrhage, multiple ventriculostomies, presence of ICP above 20mmHg, intercurrences during catheterization or its maintenance did not show association with the ventriculitis rate, nevertheless many of these variables were present in few cases making a definite conclusion difficult.

This thesis explores physiological changes occurring after acute brain injury. The first two chapters focus on traumatic brain injury (TBI), a significant cause of disability and death worldwide. I discuss the evidence behind current management of secondary brain injury with emphasis on partial brain oxygen tension (PbtO2) and intracranial pressure (ICP). The second chapter describes a subgroup analysis of the effect of hypothermia on ICP and PbtO2 in 17 patients enrolled to the Eurotherm3235 trial. There was a mean decrease in ICP of 4.1 mmHg (n=9, p < 0.02) and a mean decrease in PbtO2 (7.8 ± 3.1 mmHg (p < 0.05)) in the hypothermia group that was not present in controls. The findings support previous studies in demonstrating a decrease in ICP with hypothermia. Decreased PbtO2 could partially explain worse outcomes seen in the hypothermia group in the Eurotherm3235 trial. Further analysis of PbtO2 and ICP guided treatment is needed. The third chapter focuses on delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH), another form of acute brain injury that causes significant morbidity and mortality. I include a background of alpha-calcitonin gene-related peptide (αCGRP), a potential treatment of DCI, along with results from a systematic review and meta-analysis of nine experimental models investigating αCGRP. The meta-analysis demonstrates a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls (p < 0.0005, 95% CI 23.7 to 57.9). Neurobehavioural scores were reported in four publications and showed a Physiological responses to brain tissue hypoxia and blood flow after acute brain injury standardised mean difference of 1.31 in favour of αCGRP (CI -0.49 to 3.12). I conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes. A review of previous trials of αCGRP administration in humans is included, in addition to an original retrospective analysis of CSF concentrations of αCGRP in humans. Enzyme-linked immunosorbent assay of CSF (n = 22) was unable to detect αCGRP in any sample, which contrasts with previous studies and was likely secondary to study methodology. Finally, I summarise by discussing a protocol I designed for a dose-toxicity study involving the intraventricular administration of αCGRP to patients with aSAH and provide some recommendations for future research. This protocol was based upon the systematic review and was submitted to the Medical Research Council's DPFS funding stream during the PhD.

Hemorragia subaracnoidea aneurismática (HSAa) é considerada causa importante de morte e de sequelas neurológicas. A taxa de mortalidade desta doença pode alcançar 50% nos primeiros dois meses após sangramento de aneurisma encefálico. Apesar dos avanços científicos da modernidade, o resultado do tratamento da HSAa não mudou nos últimos anos. O presente estudo avaliou o papel de 14 biomarcadores genéticos, incluindo o polimorfismo (SNP) do gene eNOS, em pacientes da Amazônia com HSAa, para verificar as alterações alélicas associadas ao risco de vasoespasmo encefálico e déficit neurológico tardio. Avaliou-se a ancestralidade desta amostra de pacientes em que se utilizou 48 marcadores para identificar possível etnia associada à predisposição ao VE. Investigou-se 14 biomarcadores genéticos no tocante à resposta inflamatória encefálica na HSAa. Foram avaliados 265 doentes que foram divididos em dois grupos: grupo I (pacientes com vasoespasmo encefálico) e grupo 2 (pacientes sem vasoespasmo). A média das idades foi 51 anos, havia 224 mulheres (84%) e 124 pacientes (46,79%) apresentaram vasoespasmo encefálico (VE). A maior incidência de VE ocorreu na idade entre 50 e 59 anos. Tabagismo e hipertensão arterial sistêmica foram os fatores de risco mais associados à VE. Aneurismas encefálicos de tamanho pequeno e médio predominaram nesta casuística. As escalas amarela e vermelha do VASOGRADE associaram-se ao risco de VE (p < 0,001). Não houve variação na distribuição ancestral entre os grupos estudados e o que ocorre na população brasileira saudável na região Amazônica. O gene da eNOS com seus respectivos polimorfismos T-786C e 27VNTR4 correlacionaram-se com VE. Outros marcadores observados foram TP53, CASP8, ACE2, IL4 e XRCC1. O gene TP53 (modelo recessivo alelo 1) mostrou-se ser um fator protetor de VE, enquanto que genes com mutações INDEL CASP8 (modelo recessivo alelo 2) e o XRCC1 (modelo recessivo alelo 1) mostraram tendência ao desenvolvimento de VE com risco 2 vezes maior e 1,4 vezes maior que o grupo II (p < 0,001). Conclui-se que SNPs da eNOS se correlacionam com desenvolvimento de VE sintomático pós-HSAa. Este estudo também mostrou o papel dos marcadores inflamatórios na HSAa, o que auxiliaria na condução da terapia clínica. / Aneurysmal subarachnoid hemorrhage (aSAH) is a leading cause of premature death and neurological disability. It is considered as a devastating condition that accounts to 50% of mortality during the first two months after a hemorrhagic event. Despite foremost advances in the clinical management of post-aSAH patients, the rates of mortality and morbidity have not changed in recent years. This study appraised the role of 14 genetic biomarkers, including the eNOS polymorphism (SNP) between Amazon\'s patients with aSAH, as means to document how variant alleles are related to a higher disposition to cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). 265 patients were evaluated and then divided into two clusters: Group I (with symptomatic CV) and group II (presenting no symptomatic CV). The median ages of patients were 51.61 years of age, 224 (84.52%) were women and 124 patients (46.97%) had symptoms of cerebral vasospasm (CV). Tobacco smoking and systemic arterial hypertension are the risk factors most associated to CV. In the course of this research, most aneurysms found were small and medium-sized. The score VASOGRADE yellow and VASOGRADE red presented a high risk of CV (p < 0.001). We established a panel of 48 ancestry informative markers for estimating which ethnicity could present a predisposition to CV. There was no variation in the ancestral distribution between study groups and healthy brazilian folk over the Amazon region. The eNOS gene with its polymorphisms T-786C and 27 VNTR4 were correlated to CV. Other markers were accomplished: TP53, CASP8, ACE2, IL4, and XRCC1. The TP53 gene (recessive genetic model allele 1) supporting evidence of the protective role to CV. Whilst other genes with INDEL mutation like as CASP8 (recessive model allele 2) and the XRCC1 (recessive model allele 1) indicated a propensity to spread out CV with odds 2-fold higher, and 1.414 times greater than group II (p < 0.001). It follows that eNOS SNPs correlate to a positive association with a syntomatic CV post-aSAH. Also, this study showed up the role of inflammatory markers at aSAH to a further educated therapeutic choice for a better clinical response

<p>Traumatic brain injury (TBI) is a major cause of death and disability. Intracranial secondary insults (e.g. intracranial haematoma, brain oedema) and systemic secondary insults (e.g. hypotension, hypoxaemia, hyperthermia) lead to secondary brain injury and affect outcome adversely. In order to minimise secondary insults and to improve outcome in TBI-patients, a secondary insult program and standardised neurointensive care (NIC) was implemented. The aim of this thesis was to describe patient outcome and to explore the occurrence and prognostic value of secondary insults after the implementation.</p><p>Favourable outcome was achieved in 79% and 6% died of the 154 adult TBI patients treated in the NIC unit 1996-97. In an earlier patient series from the department, 48% made a favourable outcome and 31% died. Hence, the outcome seems to have improved when NIC was standardised and dedicated to avoiding secondary insults. </p><p>Secondary insults counted manually from hourly recordings on surveillance charts did not hold any independent prognostic information. When utilising a computerised system, which enables minute-by-minute data collection, the proportion of monitoring time with systolic blood pressure > 160 mm Hg decreased the odds of favourable outcome independent of admission variables (odds ratio 0.66). Hyperthermia was related to unfavourable outcome. Hypertension was correlated to hyperthermia and may be a part of a hyperdynamic state aggravating brain oedema. </p><p>Increased proportion of monitoring time with cerebral perfusion pressure (CPP) < 60 mm Hg increased the odds of favourable outcome (odds ratio 1.59) in patients treated according to an intracranial pressure (ICP)-oriented protocol (Uppsala). In patients given a CPP-oriented treatment (Edinburgh), CPP <60 mm Hg was coupled to an unfavourable outcome. It was shown that pressure passive patients seem to benefit from an ICP-oriented protocol and pressure active patients from a CPP-oriented protocol. The overall outcome would improve if patients were given a treatment fit for their condition.</p>