Partindo do princípio de que existe a necessidade de padronizar os enfermeiros quanto à avaliação do nível de consciência, em pacientes atendidos no Serviço de Emergência (SE), utilizando a Escala de Coma de Glasgow (ECGl), questiona-se quais as técnicas de ensino-aprendizagem mais adequadas. O presente estudo, limitado a medir a aquisição do conhecimento nessa temática, teve como objetivos analisar duas técnicas de ensino-aprendizagem, sendo uma a de exposição oral com slides e a outra, a leitura dirigida, em enfermeiros que atuam nos SE do município de São Paulo, divididos em dois grupos, com vistas a: caracterizá-los, segundo algumas variáveis sócio-demográficas, de aperfeiçoamento profissional e de utilização da ECGl; mensurar o grau de conhecimento, utilizando um teste de conhecimentos sobre a ECGl, antes de aplicar as duas técnicas; verificar o grau de aquisição de conhecimentos, utilizando o mesmo teste de conhecimentos, após a aplicação das duas técnicas. A coleta de dados foi feita com sorteio prévio dos hospitais selecionados quanto `a técnica a ser aplicada e realizada no final de 1999 e início de 2000. Os enfermeiros dos hospitais sorteados para serem submetidos à exposição oral compuseram o Grupo 1 e à leitura dirigida, o Grupo 2. Nas características dos dois grupos de enfermeiros, verificaram-se diferenças estatisticamente significativas nas variáveis idade, tempo de formado e utilização da ECGl. Os enfermeiros do Grupo 1 eram mais jovens, com faixa etária predominante entre 22 a 25 anos (45,5%), graduados há menos de 4 anos (72,7%) e a grande maioria relatou utilizar a ECGl, às vezes (72,7%). Contrariamente, os enfermeiros do Grupo 2 tinham mais de 31 anos (86,3%) e destes, 40,9%, mais que 41 anos; estavam mais distribuídos quanto ao tempo de formado, sendo que mais da metade tinham se graduado há mais de 5 anos; e, acima de um terço (36,4%) relatou nunca usar a ECGl e 40,9%, às vezes. Homogeneidade nas demais variáveis com preponderância do sexo feminino, e solteiros, graduação em escolas da Grande São Paulo e de tempo de experiência em SE menor que 5 anos e cursos de educação continuada variada e baixa, com exceção do Basic Life Support (BLS), freqüentado por 45,5% dos enfermeiros do Grupo 1. Na mensuração do grau de conhecimento prévio dos enfermeiros, constatou-se, na totalização de pontos, os dois Grupos alcançaram mais de 50% de acertos; aqueles do Grupo 1 totalizaram 273 (62,0%) pontos de acertos de um total de 440 pontos; os do Grupo 2 perfizeram 231 (52,5%) pontos. Em relação à aquisição de conhecimentos, após serem submetidos às duas técnicas de ensino-aprendizagem, verificou-se que o Grupo 1, no global, apresentou incremento estatisticamente significativo da fase pré para a pós do processo e ele foi de 29,8%; obteve altos percentuais de acertos, em várias questões, já na fase pré e incremento de conhecimentos estatisticamente significativo, também, na maioria das questões, principalmente naquelas de aplicação prática. O Grupo 2, embora no global tenha obtido incremento estatisticamente significativo da fase pré para a pós da ordem de 8,2%, ficou inconclusivo devido à ocorrência de um importante fator interveniente, caracterizado como não leitura do texto por parte de 55,0% dos participantes. Contudo, na análise por questão, pode-se constatar que o grupo apresentou acerto em menos da metade (41,0%) das questões, na fase pré, demonstrando a precariedade da base de conhecimentos deste Grupo e a necessidade de sanar essas lacunas. Embora os resultados obtidos apontem para a superioridade da técnica de exposição oral com slides em relação à leitura dirigida, incluindo maior adesão em participar, esta conclusão deve ser interpretada com restrição, visto que a leitura para atualização não demonstrou ser uma atividade do cotidiano desses enfermeiros / Considering the fact that there is the need to standardize nurses in relation to evaluating the level of consciousness in patients attended in emergency department (ED), by making use of the Glasgow Coma Scale (GCS), one questions which teaching-learning techniques are more adequate. The present study, limited to measuring the acquisition of knowledge regarding this topic, had the objective of analysing two teaching-learning techniques, one of them through lecturing with slides and the other one through guided reading, among nurses working in ED in the city of São Paulo. These nurses were subdivided into two groups aiming at: classifying them in relation to some variables such as their social-demographic status, professional improvement and use of GCS; measuring their level of previous knowledge by giving them a test about GCS, before applying both techniques; verifying the level of knowledge acquisition using the same test, after applying both techniques. Data collection was carried out with previously-selected hospitals drawn in relation to the technique to be applied; this data collection took place between the end of 1999 and beginning of 2000. Group 1 consisted of nurses from the drawn hospitals where lecturing with slides would be applied, whereas Group 2 was involved with guided reading. When analysing both groups of nurses statistically-significant differences in relation to age brackets, how long they had been graduated for and usage of GCS arose. Nurses in Group 1 were younger, mostly between 22 and 25 (45.5%), had been graduated for less than 4 years (72.7%) and in their great majority mentioned using GCS at times (72.7%). In contrast, nurses in Group 2 were over 31 years old (86.3%) and among these, 40.9% were over 41, had been graduated for a wider range of time (more than half for over a five-year´s time), and over one third (36.4%) of the nurses in this group mentioned never using GCS while 40.9% mentioned using it at times. The other variables were more homogeneous, with a predominance of female single nurses coming from schools in Greater São Paulo with an experience at ED of less than 5 years and a variedly-low attendance in continued education courses, except for Basic Life Support (BLS), frequented by 45.5% of the nurses in Group 1. When measuring nurses´level of previous knowledge, during the adding up of points, it was revealed that both groups scored higher than 50% of the correct answers; those in Group 1 reached 273 points (62%) out of 440; those in Group 2 obtained 231 points (52.5%). In relation to knowledge acquisition, after the application of both teaching-learning techniques, it was noticed that Group 1, as a whole, presented a statistically- significant improvement of 29.8% when comparing the fases before and after the process; this group also presented high rates of correct answers in several questions already during the pre-fase and a statistically-significant increase in knowledge as well in most questions, mainly in those related to practical application. Although Group 2 as a whole presented a statistically-significant increase (8.2%), when comparing the fases before and after the process, this group remained inconclusive due to an important intervening factor: 55% of its members did not read the texts. However, when analysing each question, it became clear that less than half of the questions (41%) were correctly answered by over 50% of the members in this group during the pre-fase, a fact which shows the precariousness of their previous knowledge and the need to bridge these gaps. Even though the results obtained in this research point out the superiority of lecturing with slides in relation to guided reading, including nurses higher interest in participating, this conclusion must be interpreted in terms since reading to update knowledge does not seem to be an everyday activity for these nurses

Après un coma, certains patients restent de manière prolongée dans un état d’éveil non-répondant (éveil sans conscience) ou en état de conscience minimale (éveil et fluctuation de la conscience) (Gosseries & Bruno et al. 2011b). Des travaux antérieurs ont montré que l’évaluation comportementale aboutissait fréquemment à des erreurs diagnostiques. Des études de neuroimagerie en IRM et TEP se sont développées pour mesurer plus objectivement l’état de conscience de ces patients (Gosseries et al. 2011d). Ces techniques ne sont cependant pas encore assez sensibles pour détecter des signes de conscience au niveau individuel. Le premier objectif de ce travail est de valider de nouveaux marqueurs diagnostiques paracliniques en utilisant d’autres outils tels que l’électroencéphalographie et la stimulation magnétique transcrânnienne. D’un point de vue neuroscientifique, les théories de l’information intégrée (Tononi, 2004), de l’espace de travail neuronal global (Dehaene et al, 2006) et du syndrome de déconnexion (Laureys et al. 2005c) émettent l’hypothèse qu’un réseau neuronal largement connecté et spécialisé est requis pour l’émergence de la conscience. Ces modèles proposent un parallèle entre la connectivité au sein d’un large réseau fronto-pariéto-thalamique et le degré de conscience d’un sujet. Le second objectif de notre travail est de tester ces hypothèses, en intégrant nos résultats dans un cadre théorique général de la conscience. <p><p>Evaluation comportementale. Avant de plonger dans le vif du sujet, nous avons évalué des facteurs pronostiques à court terme de la récupération fonctionnelle après un coma. L’intervalle de temps entre la lésion cérébrale et l’admission dans un centre de réadaptation, le score à la Disability Rating Scale à l’admission et l’étiologie semblent de bons facteurs pronostiques. Nos modèles de prédiction ne peuvent cependant pas être utilisés dans le cadre des décisions cliniques individuelles, en raison d’une trop grande variabilité entre les patients (Gosseries & Whyte et al. 2009). <p><p>Evaluations électroencéphalographiques (EEG). Une mesure automatisée d’EEG-entropie a permis de discriminer entre les patients conscients et inconscients dans les stades aigus avec une très bonne sensibilité (Gosseries et al. 2011b). Les valeurs de l’EEG-entropie étaient élevées chez les patients en état de conscience minimale alors qu’elles étaient basses chez les patients en état d’éveil non-répondant, suggérant une diminution de la complexité cérébrale chez ces derniers. Cette technique, qui est facilement applicable en routine clinique, n’a par contre montré aucune valeur pronostique. Une seconde mesure a ensuite été évaluée à l’aide des potentiels évoqués auditifs combinés à des analyses spécifiques de reconstruction de source. Ces données ont montré une altération des connexions cortico-corticales (connexions rétrogrades fronto-temporales) chez les patients en état d’éveil non-répondant (Boly et al. 2011a). Ces résultats nécessitent encore une validation au niveau individuel mais soulignent l’importance des projections neuronales rétrogrades dans l’émergence de la conscience, et confirment les hypothèses de la perte de connectivité effective et du syndrome de déconnexion chez les patients en état de conscience altérée. <p><p>Stimulation magnétique transcrânienne (SMT). Nous avons ensuite utilisé la technique SMT pour mesurer les connexions cortico-spinales. Les mesures électromyographiques ont montré des résultats globalement similaires au niveau périphérique alors que les mesures corticales différaient selon le niveau de conscience. En effet, le seuil moteur, les courbes de recrutement et l’inhibition afférente à courte latence étaient altérés chez les patients, et les deux dernières mesures étaient en lien avec le niveau de conscience des patients (Gosseries & Lapitskaya et al. soumis). Ces résultats suggèrent donc une diminution de l’excitabilité et de l’inhibition cortico-spinale, ainsi qu’un syndrome de déconnexion d’origine corticale chez les patients en état de conscience altérée. Combinaison de la SMT et de l’EEG. Enfin, nous avons évalué directement l’effet de la SMT sur l’activité du cortex cérébral (Gosseries & Rosanova et al. soumis). Cette méthode a permis de différencier au niveau individuel les patients en état d’éveil non-répondant des patients en état de conscience minimale. Chez les premiers, la réponse était initialement plus forte mais s’éteignait rapidement et ne se dispersait pas au-delà du site de stimulation. Chez les patients en état de conscience minimale, une réponse initiale au site de stimulation était suivie par une séquence complexe d’ondes qui se propageaient aux aires corticales adjacentes. Les patients présentant une récupération progressive de la conscience ont quant à eux montré une résurgence d’interactions cérébrales rapides et à longue distance (Gosseries & Rosanova et al. 2012). La SMT-EEG semble être une technique sensible qui pourrait être utilisée comme marqueur diagnostique en routine clinique. Ces résultats confirment également un syndrome de déconnexion au niveau cortico-cortical et une perte de conscience liée à une altération de la connectivité effective entre les différentes aires cérébrales (perte d'intégration et de différentiation de l’activité neuronale). <p><p>Aspects psychologiques liés à la prise en charge des patients sévèrement cérébrolésés. Parallèlement aux études susmentionnées, nous avons évalué le syndrome du burnout parmi le personnel soignant prenant en charge des patients non communicants dans des centres de réadaptation et des maisons de repos. Sur 523 personnes interrogées, 18% présentaient un burnout modéré (15%) à sévère (3%). La profession (équipe infirmière), le lieu de travail (maison de repos) et le nombre d’heures passées avec les patients étaient associés à la présence de burnout (Gosseries et al. accepté). L’importance et la satisfaction de différents besoins des familles des patients ont également été évaluées. Les besoins considérés comme importants étaient le besoin d’information médicale, le soutien émotionnel et social ainsi que l’implication dans les soins. Les familles étaient insatisfaites pour les trois premiers besoins rapportés et présentaient souvent des pensées dépressives et de l’anxiété (Gosseries et al. soumis). Le burnout du personnel soignant et les besoins des familles doivent être pris en compte afin de réduire la détresse psychologique associée à la difficulté de la prise en charge de ces patients et afin de favoriser une qualité optimale des soins prodigués aux patients. Au terme de ce travail, nous proposons des perspectives de futures études sous forme de deux nouvelles approches. La première approche, multimodale et longitudinale, consiste à comparer les différents types de connectivité cérébrale (structurelle, fonctionnelle, effective) lors de la récupération de conscience. La seconde approche est d’ordre thérapeutique, et vise à établir dans quelle mesure la restauration de la connectivité effective est liée à la restauration de conscience lors de traitements pharmacologiques et de stimulation cérébrale. <p><p><p>Summary <p><p>Following a coma, some patients may stay in a chronic unresponsive wakefulness syndrome (wakefulness without awareness) or in a minimally conscious state (wakefulness and fluctuation of awareness) (Gosseries & Bruno et al. 2011b). Previous works showed that behavioral assessments frequently lead to diagnostic errors. Neuroimaging studies using MRI and PET were developed to measure more objectively the state of consciousness of these patients (Gosseries et al. 2011d). However these techniques are not sensitive enough to detect signs of consciousness at the individual level. Our first objective is to validate new diagnostic paraclinical markers using electroencephalography and transcranial magnetic stimulation. At the neuroscientific level, the information integration (Tononi, 2004), the global neuronal workspace (Dehaene et al. 2006) and the disconnection syndrome (Laureys and al, on 2005) theories postulate that activation of a widely connected and specialized neuronal network is required for consciousness to emerge. The level of consciousness can therefore be linked to the level of connectivity in a wide fronto-parieto-thalamic network. Our second objective is to test these hypotheses by integrating our results into a general theoretical frame of consciousness.<p><p>Clinical assessment. Outside the scope of our main objectives, we studied predictors of short-term outcome. The time interval post-injury and the Disability Rating Scale score at enrollment in a rehabilitation centre were predictors of early recovery. Etiology was also a good predictor in some analysis. None of these predictive models could however explain sufficient variance to allow their use in individual clinical decision making (Gosseries & Whyte et al. 2009). <p><p>EEG assessment. We investigated the usefulness of EEG in differentiating unconscious from minimally conscious patients. Automated EEG-entropy could reliably discriminate these patients in the acute setting with a good sensitivity (Gosseries et al. 2011b). EEG-entropy values were high in minimally conscious patients and low in unconscious patients, suggesting a decrease of neural network complexity in the latter. This technique, which is easily applicable in clinical routine, offered however no reliable prognosis information. In a second study, using auditory evoked potentials and specific source reconstruction analysis, we showed that the only difference between unresponsive patients and healthy controls was an impairment of backward connectivity from frontal to temporal cortices. By contrast, minimally conscious patients exhibited near-normal recurrent effective connectivity (Boly et al. 2011a). These results require further validation at the individual level but emphasize the importance of top-down projections in recurrent processing for conscious perception, and confirm the hypotheses of the loss of effective connectivity and disconnection syndrome. <p><p>Transcranial magnetic stimulation assessment (TMS). We assessed cortico-spinal excitability through the stimulation of motor cortices and electromyography recordings. Spinal measurements were globally similar whereas cortical measurements differed according to the level of consciousness. Patients revealed a higher motor threshold, narrower stimulus/response curves and a decreased short afferent inhibition (using an additional electrical stimulation on the median nerve) compared to healthy controls participants. Recruitment curves and short afferent inhibition were associated to the level of consciousness. Our findings suggest decreased cortico-spinal excitability and inhibition as well as a cortical disconnection syndrome in disorders of consciousness (Gosseries & Lapitskaya et al. submitted). <p><p>Multimodal TMS and EEG assessment. To further assess cortical excitability and effective cortico-cortical connectivity, we employed TMS combined with EEG (Gosseries & Rosanova et al. submitted). This technique allowed to reliably discriminate between unresponsive and minimally conscious patients at the individual level. In unresponsive patients, TMS triggered a stereotyped and local response whereas in minimally conscious patients, TMS triggered rapidly changing and long-lasting widespread responses. Through longitudinal measurements, we also showed that this clear-cut change in the brain’s capacity for internal communication occurred at an early stage during recovery of consciousness, before reliable communication could be established with the patient (Gosseries & Rosanova et al, 2012). TMS-EEG seems therefore a trustworthy tool which could be used as a diagnostic marker in clinical routine. These results also confirm the cortico-cortical disconnection syndrome and the loss of consciousness related to altered effective connectivity between brain areas (loss of integration and differentiation of the neuronal activity). <p><p>Psychological issues related to the management of patients with disorders of consciousness. In parallel to the above studies, we also investigated the presence of burnout among healthcare professionals working with unresponsive and minimally conscious patients in rehabilitation centres and nursing homes. Out of 523 caregivers, 18% presented a moderate (15%) to severe burnout (3%). Profession (i.e. nurse/nursing assistants), working place (i.e. nursing home) and the amount of time spent with patients were associated with burnout (Gosseries et al. accepted). We also evaluated the family needs of chronic patients with disorders of consciousness. The most important needs reported were the medical information, the social and emotional support as well as the involvement in the care. Unsatisfaction was nevertheless observed for the emotional and social support as well as for medical information, in addition to frequent depressive thoughts and anxiety (Gosseries et al. submitted). Insufficient consideration of professional workers burnout and family needs may lead to important psychological distress and may favor inadequate quality of care in patients with disorders of consciousness. <p><p>At the end of this work, we propose two new approaches in future studies. The first approach, multimodal and longitudinal, consists in comparing various types of connectivity (i.e. structural, functional and effective) during recovery of consciousness. The second approach is of therapeutic interest, and will allow to evaluate in which measure the restoration of effective connectivity is connected to the restoration of consciousness during pharmacological treatments and during brain stimulation. / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Le coma, l’état végétatif et l’état de conscience minimale sont classés comme « troubles de la conscience ». La caractéristique commune à ces diagnostics est un état de conscience altéré. La technologie permet désormais de maintenir en vie les individus affligés de ces diagnostics. La nature même de leur condition et les soins disponibles pour ces patients conduisent à des dilemmes médicaux et éthiques importants. Ce mémoire propose une brève introduction des troubles de la conscience suivie d’une recension des écrits sur les enjeux éthiques et sociaux en lien avec ces diagnostics. Force est de constater que certains enjeux perdurent depuis des années comme le retrait de traitement. D’autres sont apparus plus récemment, comme l’enjeu lié à l’usage de la neuroimagerie. Un deuxième volet présente les résultats d’une étude qualitative examinant les perspectives et l’expérience des professionnels de la santé face aux enjeux éthiques lors de la prise en charge des patients atteints de troubles de la conscience. Cette étude a été réalisée par le biais d’un court questionnaire et d’entrevues semi-dirigées qui furent enregistrées puis analysées à l’aide du logiciel Nvivo. Les résultats démontrent entre autres que les répondants éprouvent un niveau de certitude élevé face au diagnostic bien qu’il soit souvent signalé comme un défi important dans la littérature. Le pronostic représente un enjeu crucial, y compris sa divulgation aux proches. Enfin, la relation avec la famille est un élément clé dans la prise en charge des patients et celle-ci est teintée par de multiples facteurs. / Coma, the vegetative state and the minimally conscious state are classified as “disorders of consciousness”. The common characteristic of these diagnoses is an altered state of consciousness. Technological advances now allow us to keep people afflicted with these diagnoses alive. The very nature of their condition and the type of care available to them has lead to important medical and ethical dilemmas. First, this thesis proposes a literature review of the ethical and social issues related to disorders of consciousness. Certain issues have persisted for years and others have emerged more recently as that relating to the use of neuroimaging. The second part proposes a qualitative study examining the perspectives and experiences of healthcare professionals dealing with ethical issues in the management of these patients; these aspects are so far poorly documented. We conducted this study using a short questionnaire and semi-directed interviews. The interviews were taped and analyzed using qualitative analysis software Nvivo. Our study showed that our participants experienced a high degree of certainty about the diagnosis, although the latter is often reported as a major challenge in the literature. The prognosis is a critical challenge, including its disclosure to relatives. Finally, the relationship with the family is a key element in the care of patients and it is influenced by multiple factors.

O traumatismo cranioencefálico (TCE) constitui um dos principais problemas de saúde pública mundial e as suas características variam de acordo com a população envolvida, sendo de suma importância o conhecimento de dados demográficos da mesma para que sejam adotadas medidas de prevenção efetivas. Tivemos como objetivos a descrição de dados demográficos e tomográficos em pacientes vítimas de TCE e a correlação entre idade, sexo, escala de Glasgow e dados tomográficos com a mortalidade em curto prazo. Neste estudo transversal e prospectivo realizado em pacientes vítimas de TCE admitidos na Unidade de Emergência Dr. Armando Lages, Maceió, Alagoas, foram incluídos 623 pacientes para descrição dos dados demográficos e 451 pacientes, para a análise de correlação; realizada por meio da Análise de Correlação de Spearman e de análise multivariada através de regressão logística. Foi constatada uma razão masculino/feminino geral de 3,54: 1 e a faixa etária mais acometida foi a de 21 a 30 anos. Os principais mecanismos do trauma foram os acidentes relacionados com meio de transporte motorizado (35,15%), as quedas (32,59%) e as agressões com ou sem armas (22,79%). As alterações mais comuns no TCE leve foram o hematoma subgaleal e/ou palpebral (48,5%), as fraturas (28,3%) e as contusões cerebrais (12,2%). No TCE moderado, as alterações mais freqüentes foram o hematoma subgaleal/palpebral (68,9%), fraturas (43,2%), contusão cerebral (33,7%) e hemorragia subaracnóide (HSA) (28,4%). No TCE grave, as anormalidades mais comuns foram a a HSA (71,1%), o hematoma subgaleal e/ou palpebral (68,9%), as fraturas (64,4%), contusões cerebrais (53,3%) e edema difuso (53,3%). As variáveis relacionadas com a mortalidade, por meio da análise univariada, foram a pontuação 3 na escala de Glasgow, presença de anormalidades tomográficas, de hematoma subdural (HSD), de HSA, apagamento/assimetria de cisternas basais, desvio da linha média, edema difuso, hemorragia intraventricular (HIV), presença de projétil ou estilhaços de arma de fogo. As variáveis sexo, faixa etária e hematoma extradural não apresentaram correlação estatisticamente significante com mortalidade neste estudo. As variáveis preditoras de mortalidade, na análise multivariada, foram valores baixos na escala de Glasgow, presença de anormalidades tomográficas, desvio da linha média e edema difuso. Em conclusão, os pacientes vítimas de TCE apresentaram uma predominância do masculino, numa razão M/F média de 3,54: 1,da faixa etária entre 21 a 30 anos e as causas mais freqüentes de TCE foram a queda de altura, o atropelamento e a agressão física. As características tomográficas mais freqüentes nos grupos de TCE leve e moderado foram: o hematoma subgaleal e/ou palpebral, fratura óssea e contusão cerebral. No TCE grave as lesões mais freqüentes foram a HSA, o hematoma subgaleal e/ou palpebral, fratura óssea, contusão cerebral e edema difuso. Os fatores relacionados com maior mortalidade na análise univariada foram: baixa pontuação na escala de Glasgow, pontuação 3 na escala de Glasgow, presença de anormalidades tomográficas, presença de HSA, presença de HSD, apagamento/assimetria de cisternas basais, desvio linha média, edema difuso, HIV e presença de projétil ou estilhaços de arma de fogo. Na análise multivariada: baixa pontuação na escala de Glasgow, presença de anormalidades tomográficas, presença de desvio da linha média, presença de edema difuso. / The traumatic brain injury (THI) is a major public health concern worldwide. Preventive measures to tackle the problem can be taken after analyzing demographic data and the types of injury affecting the population at hand. Our aim was to outline the demographic and tomographic data from THI victims and determine how tomography findings, age, gender, and Glasgow Coma Scale (GCS) are associated to short-term mortality. The THI patients in this cross-sectional and prospective study had been admitted to the Armando Lages Emergency Care Unit in Maceió, Alagoas. The study comprised 623 patients, who had been clinically diagnosed with THI. A total of 451 patients were included in the investigation into the correlation of computer tomography, age, gender, GCS, and mortality. Both the Spearman Correlation Analysis, and logistic regression multivariate analysis were used. The overall male:female ratio was 3.54, with 78.01% of the victims male and 21.99% female. Most patients fell within the 21 to 30 age bracket. Traffic accidents (35.15%) were the leading cause of head injury, followed by falls (32.59%), and physical assault (22.79%). Tomographic abnormalities were seen in 63.7% of victims of mild THI, the most common being subgaleal and eyelid hematoma (48.5%), skull fractures (28.3%), and cerebral contusion (12.2%). Moderate THI produced tomographic abnormalities in 83.4% of victims, the most frequent being subgaleal and eyelid hematoma (68.9%), fractures (43.2%), cerebral contusion (33.7%), and subarachnoid hemorrhage (SAH) (28.4%). Computer tomography of the skull showed alterations for all victims of severe THI, the most often being subgaleal and eyelid hematoma (68.9%), followed by SAH (71.1%), skull fractures (64.4%), cerebral contusion (53.3%), diffuse brain swelling (53.3%). Univariate analysis attested that a score 3 on the GCS, the presence of tomographic abnormalities, subdural hematoma (SDH), SAH, absent or compressed basal cisterns, midline shift, diffuse brain swelling, intraventricular hemorrhage (IVH), and the presence of a projectile or shell splinters had an statistically significant correlation with short-term mortality. In this study, gender, age group, and large extradural hematoma had no statistical significance as predictive factors for mortality. In a multivariate analysis, the variables that accounted for mortality were low GCS scores, the presence of tomographic abnormalities, midline shift, and diffuse brain swelling. It can be concluded that males were the predominant victims in THI cases, with the M:F ratio at 3.54. Most affected were individuals aged 21 to 30, and the most common causes of THI were falls, being run over by a vehicle, and physical assault. The most frequent tomographic characteristics in the mild and moderate THI cases were subgaleal and/or eyelid hematoma, skull fracture and cerebral contusion. The most common injuries in severe THI patients were subgaleal and/or eyelid hematoma, SAH, skull fracture, cerebral contusion, and diffuse brain swelling. The factors most closely linked to higher mortality after univariate analysis were low GCS scoring, a score 3 on the GCS, the presence of tomographic abnormalities, the presence of SAH, the presence of SDH, absent or compressed basal cisterns, midline shift, diffuse brain swelling, IVH, and the presence of a projectile or shell splinters. After multivariate analysis: low scoring on the GCS and the presence of tomographic abnormalities, midline shift, and diffuse brain swelling.

Foi realizado estudo prospectivo com o objetivo de se determinar a ocorrência de traumatismo raquidiano (TR) em 355 doentes em coma decorrente de traumatismo cranioencefálico (TCE) resultante de acidente de tráfego atendidos no Pronto Socorro de Neurocirurgia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (PSNCHCFMUSP) de 1° de setembro de 2003 a 31 de dezembro de 2009. Todos os doentes foram submetidos ao exame físico e neurológico e à tomografia computadorizada (TC) do corpo inteiro para diagnosticar-se e avaliar-se a gravidade das lesões traumáticas encefálicas, vertebrais ou de outras regiões no momento da admissão ao PSNCHCFMUSP. Em 69 (19,4%) doentes, foi(ram) diagnosticada(s) lesão(ões) na coluna vertebral com o exame de TC da coluna vertebral. As idades dos doentes variaram de 12 a 55 anos (média de 29,0 anos). Eram do sexo masculino 57 (82,6%) doentes. As causas do(s) traumatismo(s) foi(ram) acidente(s) envolvendo motocicleta em 28 (40,6%) casos, atropelamento em 21 (30,5%), colisão de automóvel, caminhão ou caminhonete, em 18 (26,1%) ou acidente com bicicleta em dois (2,9%). Hemorragia subaracnóidea traumática foi a anormalidade intracraniana traumática mais evidenciada no exame de TC do crânio; ocorreu em 57 (82,6%). O(s) processo(s) transverso(s) foi(ram) o(s) segmento(s) vertebral(is) mais acometido(s) pela(s) fratura(s). A sétima vértebra cervical foi a mais lesada; nela identificaram-se fraturas em 24 (34,8%) doentes. Evidenciou-se que a distribuição das fraturas foi similar ao longo das demais vértebras da coluna cervical, quatro primeiras vértebras torácicas e vértebras lombares. Em oito (11,6%) doentes a(s) lesão(ões) neurológica(s) foi(ram) classificada(s) como Frankel A, e nos demais 61(88,4%), como Frankel não-A. Houve necessidade de cirurgia espinal em 24 (34,8%) doentes e de neurocirurgia craniana em 18 (26,0%) doentes. A Escala de Recuperação de Glasgow foi aplicada para avaliar-se as condições neurológicas do doente no momento da alta hospitalar e revelou ocorrência de óbito em dois (2,9%) doentes. Concluiuse que é recomendada a avaliação clínica e também com métodos de imagem da coluna vertebral nos doentes em coma decorrente de TCE / The author presents a prospective study aiming the evaluation of coexistence of spinal injury (SI) in 355 patients presenting coma due to craniocerebral trauma assisted at the Emergency Room of the Hospital das Clínicas of the University of São Paulo Medical School, from September, 1st, 2003 to december, 31th,2009. All patients underwent physical and neurological examination and had computed tomography (CT) scanning of the entire body to diagnose and evaluate the severity of brain and spinal injury at the time of admission. Traumatic lesions of the spine were diagnosed in 69 (19.4%) patients. The ages of patients ranged from 12 to 55 years (mean = 29,0 years).The SI predominated in males, corresponding to 57 (82.6%) patients. The causes of the trauma were motorcycle accident in 28 (40.6%) cases, running over in 21(30.5%), car collision 18 (26.1%) cases and bicycle accident in two (2.9%). Traumatic subarachnoid hemorrhage was the most common traumatic intracranial abnormality in the CT images; it was identified in 57 (82.6%) patients. The transverse process was the most common vertebral part presenting fracture(s). The 7th cervical vertebra was individually the most commonly affected; traumatic lesion of this vertebra presented in 24 (34.8%) patients. The diagnosis of fracture(s) was similar in the other cervical vertebrae and occurred also in the first four thoracic and in the lumbar vertebrae. Severe neurological deficit secondary to spine fracture was diagnosed in eight (11.6%) patients, classified as Frankel A. The others 61(88.4%) patients did not present complete spinal cord or spinal roots neurological deficits were classified as Frankel non A. The Recovery Scale of Glasgow was used to evaluate the neurological status at discharge from hospital. Two (2.9%) patients died. Spinal surgery was necessary in 24 (34.8%) patients and cranial surgery in 18 (26.0%). It was concluded that in addition to clinical evaluation, the CT imaging of the spine is recommended in patients in coma due to mechanical traumatic head injury

Bacillus amyloliquefaciens FZB42 ist ein grampositives Bakterium, das in der Rhizosphäre das Pflanzenwachstum fördert (PGPR - Plant Growth Promotion) und pathogene Organismen hemmt. Abgesehen von dieser Fähigkeit produziert es eine Vielzahl von sekundären Metaboliten, die sowohl ribosomale als auch nicht-ribosomale Peptide umfassen. In dieser Arbeit erfolgte die Untersuchung der transkriptionellen Aktivierung und Regulation der Bacilysin- Biosynthese an den Promotoren der bac- und ywfH- Gene. Durch 5´-Deletionsanalysen wurde der Promotor von Bacilysin identifiziert. Die A (Sigmafaktor A) - abhängige Transkription startet über die konservierten Promotorelemente (-10 und -35) von den bac- und ywfH Genen. Die Untersuchungen der Promotoraktivitäten vom Wildtyp und den erzeugten Regulationsmutanten erfolgten über in vivo ß-Galaktosidase-(Reporter)-Assays. Die Ergebnisse der Reporter-Aktivitäten zeigten, dass Transkriptionsregulatoren die Expression der Bacilysin- Gene aktivieren. Mehrere globale Regulatoren wie DegU, ComA, Hpr und AbrB beeinflussen die Genexpression. In dieser Arbeit wurde mithilfe von DNaseI Footprinting-Analysen die DegU-Bindung an die bac- und ywfH- Promotoren bestätigt.Die negative Regulation der Bacilysin-Biosynthese wird durch den Regulator der transienten Phase Hpr bewerkstelligt. Eine direkte Hpr-Bindung an bac Promotor wurde mit DNaseI Footprint-Analysen gezeigt. Der Promotor des monocistronischen Gens ywfH wurde aber durch Hpr nicht beeinflusst. Die anderen Transkriptionsregulatoren, wie ComA und AbrB, regulieren die Genexpression von Bacilysin indirekt über DegQ und Hpr. In dieser Arbeit konnte demonstriert werden, dass der globale Regulator AbrB den Promotor vom hpr-Gen direkt kontrolliert. Zusammenfassend liefert diese Studie neue Informationen über die genetische Regulation der Bacilysin- Biosynthese in B. amyloliquefaciens FZB42. / Bacillus amyloliquefaciens FZB42 is a Gram-positive, pathogen-suppressing and plant-growth promoting rhizobacterium. Apart from this ability, it produces a vast array of secondary metabolites, which includes both ribosomal and non-ribosomal peptides. In this work, the transcriptional activation and regulation of bacilysin biosynthesis were studied at the promoters of bac and ywfH genes. The promoter of bacilysin was identified using 5''-deletion analysis. Sigma factor A (σA) was found to start transcription via conserved promoter elements (-10 and -35) of bac and ywfH genes. lacZ reporter fusion studies were performed in wild type and regulatory mutants. The results show the involvement of transcriptional regulators to activate the expression of bacilysin genes. Several global regulators such as DegU, ComA, Hpr and AbrB were identified and found to influence gene expression. In particular, I confirmed DegU binding in bac and ywfH promoters using radioactive DNase I footprinting. Furthermore, Hpr, a transition state regulator was found negatively to control bacilysin biosynthesis. Hpr binding to bac promoter was demonstrated using radioactive DNase I footprinting. Remarkably, Hpr does not influence the promoter of the monocistronic gene, ywfH. The other transcriptional regulators, such as ComA and AbrB, were correlated indirectly to affect the gene expression of bacilysin via DegQ and Hpr, respectively. The gene regulation of hpr was studied in this work. It was demonstrated that AbrB, a global regulator, directly controls the promoter of the hpr gene. However, the consensus sequence for AbrB binding was not identified, since it covers the entire promoter region in the DNA-protein interaction study. To conclude, this study provides new information regarding the genetic regulation of bacilysin biosynthesis in B. amyloliquefaciens FZB42.

As consequências do trauma cranioencefálico contuso incluem além da mortalidade, alterações físicas, cognitivas e comportamentais que alteram a qualidade de vida das vítimas pós-trauma. A Escala de Coma de Glasgow é reconhecida na literatura científica, como um indicador com potencial para estimar o prognóstico das vítimas de trauma cranioencefálico contuso e tem sido extensivamente estudada para prever resultados a curto e longo prazos. No entanto, por tratar-se de um índice fisiológico, sujeito a oscilações decorrentes de mudanças nas condições clínicas das vítimas, esta escala suscita divergências em relação ao valor que apresenta melhor desempenho para prognosticar desfechos de interesse clinico. Perante tais divergências, este estudo teve como objetivos: verificar o desempenho dos escores da escala observados nas primeiras 72 horas, após trauma para predizer o estado vital à saída hospitalar e a mudança percebida do estado de saúde; comparar o valor preditivo desses escores para prognosticar esses desfechos e verificar a associação dos escores da Escala de Coma de Glasgow e os domínios da qualidade de vida das vitimas, após um ano do evento traumático. Trata-se de um estudo longitudinal que analisou valores da Escala de Coma de Glasgow nas primeiras 72 horas, após trauma, durante a internação hospitalar e resultados da avaliação de qualidade de vida das vítimas de trauma cranioencefálico contuso, um ano após o evento traumático. Os valores da escala analisados foram os obtidos, após a reanimação inicial intra-hospitalar, além dos piores e melhores resultados da escala nas primeiras 72 horas pós-trauma. A capacidade preditiva dos valores da escala para estado vital à saída hospitalar e a mudança percebida do estado de saúde foi avaliada, utilizando-se a curva Reciever Operator Characteristic. A qualidade de vida das vítimas foi avaliada por meio do Medical Outcome Study 36-item Short Form Health Survey (SF-36), e os resultados da Escala de Coma de Glasgow foram confrontados com os valores dos domínios dessa escala. Foram estudadas 277 vítimas, com trauma cranioencefálico contuso de diferentes gravidades. O desempenho dos escores da Escala de Coma de Glasgow para Estado Vital à Saída hospitalar foi moderado, as áreas sob a curva variaram de 0,74 a 0,79. Para a mudança percebida do estado de saúde, um ano pós-trauma, os valores dessas áreas ficaram entre 0,63 e 0,71. Não houve diferença significativa entre as áreas sob a curva nos valores da Escala de Coma de Glasgow atribuídos pós-reanimação inicial, melhores e piores resultados nas primeiras 72 horas pós-trauma, tanto ao estado vital, como ao estado de saúde atual. Correlação significativa foi observada, porém foi fraca entre os três escores da Escala de Coma de Glasgow e os domínios da SF-36: Capacidade funcional, Aspectos físicos e Aspectos sociais. O pior resultado correlacionou-se com o maior número de domínios. No geral, os resultados indicaram que qualquer um dos três valores da Escala de Coma de Glasgow analisados podem ser aplicados na prática clínica para estimar o prognóstico das vitimas de trauma cranioencefálico contuso, considerando-se, no entanto seu moderado poder discriminatório. / The consequences of blunt traumatic brain injury go beyond high mortality to include, modifications in physical, cognitive and behavioral aspects, thus altering the Quality of Life of the victims. The Glasgow Coma Scale is scientifically recognized as a potential indicator to estimate prognosis and predict short and long term outcomes of blunt traumatic brain injury victims. Although it is a physiological index, and sensitive to changes of clinical variables, the Glasgow Coma Scale attempts to cause divergence in the relationship of values that can better predict clinical outcomes. The aims of this research are, to analyze the performance of three different scores of the Glasgow Coma Scale in the first 72 hours of in-hospital assistance in predicting Hospital Mortality and changes of the health status perception after trauma; to compare the predictive performance of these scores, and correlate them to quality of life subscales after one year of trauma. The Glasgow Coma Scale, chosen in this present study, include the score obtained after initial resuscitation; the highest value and the lowest value in the first 72 hours of in hospital assistance. The capacity of prognosis of the scores, were evaluated by the Receiver Operator Characteristic (ROC) curve. Quality of life was assessed by the Medical Outcome Study- a 36-item Short Form Health Survey (SF-36). All Glasgow Coma Scale scores were confronted with SF36 subscales. This study included 277 victims of different severity blunt traumatic brain injuries. The performance of the three scores, which were analyzed to predict Hospital Mortality, was moderate, with an area under the curve between 0.74 and 0.79. The area under the curve for change of the health status perception, after one year of trauma, ranged from 0.63 to 0.71. There were no significant differences between the Glasgow Coma Scale scores studied in both analyses. A significant, but weak correlation was observed between the Glasgow Coma scale scores and the subscales of SF-36 Physical Functioning, Physical Role and Social Functioning. The worst Glasgow Coma Scale score, obtained in the first 72 hours after trauma, correlated to the dominions of the SF-36 subscales. These findings suggest that any one of the 3 scores studied, can be applied in clinical practice to predict the outcome of victims with blunt traumatic brain injuries, taking into consideration its moderate discriminatory power.

Les objectifs de cette thèse étaient de caractériser les corrélats neuronaux fonctionnels et structurels de l'abolition de la conscience observés pendant le coma et d'identifier les signatures neuronales précoces de la récupération neurologique à partir de cet état. Pour atteindre ce but, nous avons étudié des patients cérébrolésés, recrutés au stade aigu du coma, à l'aide de l'IRM fonctionnelle au repos et IRM structurale. Nos résultats indiquent une réorganisation topologique globale du cerveau des patients, reflétée par une dédifférenciation et une réduction de la résilience des réseaux fonctionnels au repos d'ordre élevé. Ces anomalies sont accompagnées d'une perte de connexions fronto-pariétales à longue distance. Au niveau régional, nous avons observé un schéma complexe de diminution et d'augmentation de la densité de connexion fonctionnelle entre le cortex postéromédial et le cortex préfrontal médial : régions précédemment décrites pour avoir un rôle critique dans la conscience. De manière intéressante, ces modifications de densité de connexion étaient significativement liées à la récupération des patients trois mois après le coma. Enfin, l'analyse multimodale a permis de démontrer une association significative entre la connectivité fonctionnelle et l'intégrité structurelle cérébrales antéro-postérieure, fournissant des informations importantes sur le lien structure/fonction au décours de ces troubles acquis de la conscience. / The aim of the present thesis was to characterize the functional and structural neural correlates of acute consciousness abolition induced by severe brain injury and identify early neural signatures of long-term neurological recovery. To do so, we studied brain-injured patients, recruited in the acute stage of coma, using resting-state functional and structural MRI. Our findings indicated a global topological brain reorganization in coma patients, reflected in dedifferentiated and less resilient high-order resting-state functional networks, paralleled with a loss of long-range fronto-parietal connections. On a regional level, we found a complex pattern of voxel-wise decrease and increase in functional connection density between the posteromedial cortex and the medial prefrontal cortex, regions previously described to have a critical role in conscious processing. These connection density patterns seemed to permit outcome prediction in patients, assessed three months post-coma. Furthermore, the multi-modal MRI analysis demonstrated a significant association between antero-posterior functional connectivity and structural integrity, providing further insights into the pathological underpinning of conscious processing.

In my work as speech and language pathologist I often meet people emerging from coma andtheir experiences intrigue me. Coma is an eluding human condition that offers a challenge formodern science and our view on body and mind. In my Master project in Creative Writing Iwanted to try to enter this zone that is so hard for a clinician to reach: the personal experienceof being in a coma. By writing HUSK MIDAS I have tried to create a realistic fiction based onresearch on coma state and real-life stories of people waking up from coma.In my exploration of the coma state I found that lucid dreaming is common apart fromdreaming, many patients experience sensory inputs like sound and touch which aremisinterpreted and woven into dreams and creating a feeling of confusion and fear.Coma is a frequent theme in literature and film but is often depicted unrealistically andmisleadingly. A few works like Artur Lundkvist’s Journeys in Dream and Imagination andthe film The Descendents by Alexander Payne show a more reality based fiction. While themedical care has the responsibility to provide accurate information and make important healthcare decisions regardless of possible public misconceptions, fiction helps us to dramatize thecoma experience and bring to life this marginalized and otherwise non-communicable state ofthe human condition.

Le coma, l’état végétatif et l’état de conscience minimale sont classés comme « troubles de la conscience ». La caractéristique commune à ces diagnostics est un état de conscience altéré. La technologie permet désormais de maintenir en vie les individus affligés de ces diagnostics. La nature même de leur condition et les soins disponibles pour ces patients conduisent à des dilemmes médicaux et éthiques importants. Ce mémoire propose une brève introduction des troubles de la conscience suivie d’une recension des écrits sur les enjeux éthiques et sociaux en lien avec ces diagnostics. Force est de constater que certains enjeux perdurent depuis des années comme le retrait de traitement. D’autres sont apparus plus récemment, comme l’enjeu lié à l’usage de la neuroimagerie. Un deuxième volet présente les résultats d’une étude qualitative examinant les perspectives et l’expérience des professionnels de la santé face aux enjeux éthiques lors de la prise en charge des patients atteints de troubles de la conscience. Cette étude a été réalisée par le biais d’un court questionnaire et d’entrevues semi-dirigées qui furent enregistrées puis analysées à l’aide du logiciel Nvivo. Les résultats démontrent entre autres que les répondants éprouvent un niveau de certitude élevé face au diagnostic bien qu’il soit souvent signalé comme un défi important dans la littérature. Le pronostic représente un enjeu crucial, y compris sa divulgation aux proches. Enfin, la relation avec la famille est un élément clé dans la prise en charge des patients et celle-ci est teintée par de multiples facteurs. / Coma, the vegetative state and the minimally conscious state are classified as “disorders of consciousness”. The common characteristic of these diagnoses is an altered state of consciousness. Technological advances now allow us to keep people afflicted with these diagnoses alive. The very nature of their condition and the type of care available to them has lead to important medical and ethical dilemmas. First, this thesis proposes a literature review of the ethical and social issues related to disorders of consciousness. Certain issues have persisted for years and others have emerged more recently as that relating to the use of neuroimaging. The second part proposes a qualitative study examining the perspectives and experiences of healthcare professionals dealing with ethical issues in the management of these patients; these aspects are so far poorly documented. We conducted this study using a short questionnaire and semi-directed interviews. The interviews were taped and analyzed using qualitative analysis software Nvivo. Our study showed that our participants experienced a high degree of certainty about the diagnosis, although the latter is often reported as a major challenge in the literature. The prognosis is a critical challenge, including its disclosure to relatives. Finally, the relationship with the family is a key element in the care of patients and it is influenced by multiple factors.