Legibus almae hujus Academiae, quae, omnes eos lauream Appollinarem ambientes, aliquid progressus sui in scientia medica testimonium, in publicam proferre sanciunt, obtemperanti, de Apoplexia Sanguinea in Paginis sequentibus pauca, mihi in animo est disserere; morbus, quo, sive symptomatum saevitiam, accessus rapiditatem, stragesve luctuosas, quas inter homines quotidie edit, nullus medici attentionem peritiamque majore jure sibi vindicat.

Spontaneous intracerebral haemorrhage (ICH) is one of the most lethal forms of stroke and has a relatively higher morbidity in Asian people. The high disability rate of 50% in all survivors and lack of clinically effective regeneration medicine make ICH a major unanswered problem worldwide. Considerable preclinical evidence suggests that neuroprotective interventions are urgently needed to lessen the effects of this disease. To date, less preclinical researches with proven positive results have successfully translated to the clinical setting, mainly due to poor modelling, a lack of behavioural testing, inadequate experimental design and failure to consider white matter damage. According to the few previous studies, white matter is a key predictor of ICH outcomes and a potential target of recovery. The long-term axonal degeneration in rodent ICH has been ignored for decades, and almost every preclinical study has focused on mechanisms in the acute phase. Clinically ICH patients may suffer a permanent loss of brain function or long-term deficits that take years to recover from. If the preclinical researches target the long-term axon degeneration/regeneration in the chronic stage, it might help to develop successful clinical interventions for functional reconstruction and rehabilitation. / Thus, to obtain the evidence of axonal degeneration and regeneration in the chronic stage of experimental ICH, this study at first systematically assessed the histological and functional outcomes of axonal regeneration in experimental ICH from day 3 to day 56 and secondly find the effective markers and methods for investigation axons in experimental ICH models in vivo. The long-term gait disturbance of a computer-generated CatWalk system, the electrophysiological changes, axonal loss by PKC gamma (PKCγ) immunohistochemistry and axonal degeneration by Bielschowsky silver staining were examined in unilateral striatum lesioned ICH (ST-ICH) rats. As the ST-ICH model demonstrated a spontaneous functional recovery within one or two month, we further developed a modified internal capsule lesioned ICH (IC-ICH) rat model which mimic clinical conditions, and investigated whether an internal capsule lesion leads to long-term axonal damage and long lasting functional deficits. / The finding demonstrated that haematoma in striatum led to severe axonal degeneration/loss in ipsilateral medullary corticospinal tract (CST) and functional deficits in a long-term duration (1-2 months after ICH). PKCγ level was an effective marker to quantify the axonal loss in experimental ICH and it indicated a significant axonal loss on day 56 after ICH in ipsilateral CST. Bielschowsky silver staining was a useful method to illustrate the morphological changes of axonal degeneration and regeneration in longitudinal sections of CST and it clearly showed the process of axon swelling, disrupted and regenerated in 2 months’ duration after ICH. / Somatosensory evoked potentials (SSEPs) and gait analysis were valuable functional assessments to characterize the long-term behavioral deficits resulting from axonal degeneration/regeneration in experimental ICH. The decrease in electrophysiological parameter SSEP amplitudes was observed in experimental ICH. Multiple gait parameters changed after ICH and some of that such as paw print area, paw pressure, stand index, duty cycle can be used as long-term evaluating markers in chronic stage of experimental ICH. / Compared to ST-ICH, the modified IC-ICH model exhibited a relatively smaller lesion volume with consistent axonal loss/degeneration and long-lasting neurological dysfunction at 2 months after ICH. Functionally, the impairment of the mNSS, ratio of contralateral forelimb usage, four limb stand index, contralateral duty cycle and ipsilateral SSEPs amplitude remained significant in the IC-ICH model at 56 days compared with the sham group, and asymmetries in the hind paw print area of the IC-ICH model exhibited significant differences from the ST-ICH model at 56 days. Structurally, the significant loss of PKCγ in ipsilateral CST of IC-ICH and the consistent axonal degeneration with several axonal retraction bulbs and enlarged tubular space was observed at 56 days after ICH. / In summary, the data from this study systematically characterize the histological and functional outcomes (especially gait parameter and SSEPs changes) in the experimental ICH model. A modified internal capsule lesioned ICH model was developed for rats, and proved to have long lasting neurological deficits. A comprehensive understanding of the dynamic progression after experimental ICH should aid further successful clinic translation in animal ICH studies, and provide new insights into the potential biomarkers and therapeutic targets of ICH. / 原發性腦出血（ICH）是一種致死性較高的卒中類型。在亞洲人群眾發病率相對較高。高致殘率和臨床上缺乏有效的治療手段，使得腦出血成為世界範圍內的健康問題。因此需要大量的臨床前研究尋找有效的治療方法。然而，迄今為止，臨床前研究獲得的陽性結果中，只有少數被成功的轉化到臨床應用。臨床轉化存在的部分失敗，歸結於幾個主要的因素包括動物模型的不足，動物行為學實驗的不恰當使用，實驗設計的缺陷以及對白質損傷機制的忽略。有研究認為，腦白質是卒中後功能恢復的關鍵指標和潛在治療靶點。腦出血慢性期的軸索變性在齧齒類動物模型中的研究被忽視了幾十年，而幾乎所有的臨床前研究都關注於急性期的機制。而臨床上倖存的腦出血病人大多罹患永久性的腦功能損傷，往往需要數年才能恢復或者難以恢復。如果臨床前轉化實驗以腦出血後慢性期的神經軸索損傷/再生作為研究目標，也許可以找到有助於卒中後功能重建和康復的治療手段。 / 為了尋找腦出血慢性期神經軸索損傷的證據，本研究首先從組織學和功能行為學兩個方面對對實驗性腦出血後的軸索再生進行了系統的評價。並建立了有效反應慢性期神經軸索再生的一系列方法和標誌物。本研究將步態分析，電生理評價， Bielschowsky銀染和PKCγ組織學染色結合起來對腦出血後的動物模型的軸索蛻變和再生進行長期觀察。結果顯示傳統的紋狀體損傷模型在1到2個月出現自發的功能恢復。本研究進一步假設內囊出血模型可能會獲得更加持久的功能損傷，也更為接近臨床患者的情況。因此，為了更好地研究腦出血慢性期的白質損傷和類比臨床情況，本研究建立了一種改進的內囊出血大鼠模型，並用組織學和行為學方法對其長期的功能損傷進行評價。 / 研究結果顯示，位於紋狀體的血腫可以引起同側的延髓皮質脊髓束(CST)出現嚴重的慢性期退化和變性，並同時伴有神經功能損傷。PKCγ是評價實驗性腦出血後神經軸索損傷程度的有效標誌物，資料表明同側皮質脊髓束PKCγ的表達水準在ICH損傷56天后仍有顯著降低。對延髓椎體CST的Bielschowsky銀染，可以從結構上有效的反應軸索變形和再生的過程，CST縱行切片染色清楚地顯示了腦出血損傷後2個月的時間內軸索水腫、斷裂和再生的過程。 / 體感誘發電位（SSEPs）和步態分析的方法可以從功能上對腦出血後神經軸索損傷進行較為全面的評價和定量分析。單側紋狀體腦出血可以引起同側皮層SSEP波幅的降低。多個步態分析參數在腦出血後也存在明顯的變化，其中前後掌爪印面積（paw print area），爪印壓力（paw pressure），站立指數（stand index），患側肢體站立百分比（duty cycle）都可作為觀察腦出血後慢性期功能損傷和恢復的評價指標。 / 改進後的內囊腦出血模型顯示病灶體積相比較小但神經軸索的損失和神經功能障礙較為持久。從神經功能方面評判，與假手術組相比，神經功能評分（mNSS），對側前肢使用率（cylinder test），四肢站立指數（stand index），患側肢體站立百分比（duty cycle）和患側體感誘發電位波幅（SSEPs amplitude）在出血後2個月仍然顯著降低。後掌的爪印面積（print area）與紋狀體腦出血的動物比較在出血後第56天后仍有顯著差異。從軸索結構評判，內囊出血模型顯示出更為嚴重的神經軸索退變和損傷，表現為在出血後56天PKCγ蛋白表達量的持續降低，軸索斷裂結節和管狀間隙的形成。 / 綜上所述，本研究系統地分析了實驗腦出血後的組織學和功能特點，建立了一個改進的內囊腦出血大鼠模型，並證明該模型存在更為持久的神經功能障礙和神經軸索損傷。 / Liu, Yao. / Thesis Ph.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 168-200). / Abstracts also in Chinese. / Title from PDF title page (viewed on 18, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

L'anevrysme intracrânien (AIC) est une anomalie morphologique spécifique des artères cérébrales exposant au risque, particulièrement grave, de saignement intracrânien. Malgré les progrès établis dans le traitement curatif , aucun traitement préventif de la formation des AIC n’a été prouvé chez l’Homme. L’absence de traitement non invasif et l’absence de consensus sur le traitement des AIC non rompus sont le corolaire direct d’un manque de connaissance des mécanismes physiopathologiques de la maladie anévrysmale.L’ensemble du travail exposé ici a eu pour but de mieux comprendre les mécanismes de la pathologie anévrysmale intracrânienne pouvant être la base de nouvelles stratégies préventive améliorant le traitement des AIC.Nous avons tout d'abord étudié l'influence des anomalies du tissus de soutien des artères cervicales sur la formation des AIC. Au cours de cette étude, nous avons réalisé une étude cas-témoins dont l’objectif principal était d’étudier l’association entre les anomalies morphologiques des artères cervicales et la présence d’un AIC. Les objectifs secondaires étaient premièrement d’examiner si cette association variait selon le caractère rompu ou non de l’anévrisme et deuxièmement d’examiner si la sévérité des anomalies artérielles cervicales était liée à la sévérité de la pathologie anévrismale. Nous rapportons que la prévalence des anomalies angiographiques chez les patients porteurs d’AIC est élevée. De plus l’incidence d’une pathologie rare, la dysplasie fibro-musculaire est très élevée chez les patients porteurs d’AIC comparativement à la population générale. La présence des anomalies angiographiques n’a aucun impact sur l’évolution naturelle des AIC vers la rupture, ni sur d’autres aspect comme leur taille, leurs nombres ou leur forme. Dans le cadre de notre étude, nous pensons que l’association entre les anomalies angiographiques et les AIC semble être expliquée par l’hypothèse d'une vulnérabilité du tissu de soutien pariétal (condition pathologique particulière de la paroi artérielle à l’origine de la formation des AIC). Cette condition pathologique, affecterait de manière diffuse la vascularisation cérébrale et les artères cervicales. Les AIC seraient ainsi des manifestations cliniquement « bruyantes » de pathologies vasculaires plus silencieuses affectant la paroi de l’ensemble des vaisseaux. Les anomalies morphologiques des artères cervicales témoignent de façon sensible mais très peu spécifique de l’association des pathologies du tissu de soutien avec la présence d’AIC.Dans une deuxième partie nous essayons de décrire et de caractériser une voie inédite de la formation et de la croissance des AIC, la voie de la fibrinolyse via l'activateur de plasminogène de type tissulaire (tPA). Nos données suggèrent que le tPA présent dans la circulation sanguine est suffisant pour favoriser la formation et la rupture des anévrismes. Nous avons donc proposé que le tPA vasculaire était un des responsables de la formation des AIC. Nous avons également constaté une certaine continuité dans le temps de l'influence du tPA sur le remodelage matriciel. Nous avons donc proposé le tPA vasculaire comme une nouvelle cible possible pour prévenir la progression et la rupture des AIC. Différentes expériences ont été entreprise pour inhiber sélectivement le tPA et les résultats préliminaires sont encourageants et ouvrent la voie à une stratégie thérapeutique non invasive inédite. On peut aussi imaginer que ces différentes approches puissent être combinées entre elles et avec des agents matriciels ciblant directement l’activité du tPA dans la paroi des AIC. L’amélioration des stratégies thérapeutiques dans la pathologie anévrysmale intracrânienne est définitivement un axe de recherche dont les possibilités sont immenses et les résultats nécessaires et attendus. / Intracranial aneurysm (IA) is a specific morphological abnormality of the cerebral arteries that exposes to devastating intracranial bleeding. Despite the progress made in the curative treatment, no preventive treatment of IA formation has been proven in humans. The lack of non-invasive treatment and consensus on the treatment of unruptured IA are the consequences of the lack of knowledge of the physiopathological mechanisms of aneurysmal disease. All of the work presented here aims to better understand the mechanisms of intracranial aneurysmal pathology, which may be the basis of new preventive strategies improving the treatment of IA.We first studied the influence of cervical artery abnormalities on IA formation. In this study, we performed a case-control study whose main objective was to study the association between morphologic abnormalities of cervical arteries and the presence of IA. The secondary objectives were first to examine whether this association varied according to whether or not the aneurysm was broken, and secondly to examine whether the severity of the cervical arterial abnormalities was related to the severity of the aneurysmal pathology. We report that the prevalence of angiographic abnormalities in patients harboring IA is high. In addition, the incidence of a rare pathology, fibro-muscular dysplasia is very high in patients with IA compared to the general population. The presence of angiographic abnormalities has no impact on the rupture of the IA, nor on other aspects such as their size, numbers or shape. In our study, we believe that the association between angiographic abnormalities and IA seems to be explained by the hypothesis of a vulnerability of the arterial wall (a particular pathological condition of the arterial wall at the origin of IA formation). This pathological condition would affect the whole cerebral vasculature and cervical arteries. IA would thus be the clinical manifestations of more silent vascular pathologies affecting the wall of all vessels. The morphological abnormalities of the cervical arteries testify sensitively but not very specifically of the association of the arterial wall diseases with the presence of IA.In a second study, we try to describe and characterize an unprecedented pathway of formation and growth of IA : the pathway of fibrinolysis via tissue-type plasminogen activator (tPA). Our data suggest that tPA present in the bloodstream is sufficient to promote formation and rupture of aneurysms. We therefore proposed that vascular tPA was one of those responsible for training IA. We also noted a certain continuity in the time of the influence of the tPA on the matrix remodeling. We therefore proposed vascular tPA as a possible new target to prevent progression and rupture of IA. Various experiments have been undertaken to selectively inhibit tPA and the preliminary results are encouraging and open the way to an unprecedented non-invasive therapeutic strategy. It is also conceivable that these different approaches could be combined with each other and with matrix agents directly targeting tPA activity in the AIC wall. The improvement of therapeutic strategies in intracranial aneurysmal pathology is definitely an topic of ​​research whose possibilities are huge and the results necessary and expected.

Cerebral hemorrhages are a type of stroke causing bleeding in the brain from a ruptured brain vessel or an aneurysm. In the emergency department (ED), advanced practice nurses (APNs') play a pivotal role in identifying cerebral hemorrhages. Many APNs' lack the skills necessary to assess, diagnose, and manage this type of stroke. A delay in diagnosis of cerebral hemorrhages carries a high risk of morbidity and mortality and can lead to lifelong disability or death. The framework of this project is the Patricia Benner theory of novice-to-expert, which is a 5-step approach designed to strengthen nursing skills with the goal of developing nurses into experts in the neuroscience field. This project addressed whether a validated educational program for APNs' in the ED will increase knowledge to improve the assessment, diagnosis, and management of the cerebral hemorrhage stroke patient. A panel of experts were provided a comprehensive educational plan with multiple case scenarios. A 5-point Likert questionnaire was administered and a statistical analysis was performed. Results indicated the panel strongly agreed that the educational initiative increased APNs' knowledge and fostered a culture of change for APNs' in the ED. Potential implications of this educational module will be considered in satellite organizations impacting APNs' growth and improving patient care throughout the health system. The project determined that the significance of social change included increased APNs' knowledge and advanced professional growth, lowers mortality rates, and promotes an evidence-based quality improvement project.

Orientador: Carmen Maria Bueno Neme / Coorientador: Maria de Lourdes Merighi Tabaquim / Banca: Dionisia Aparecida Cusin Lamônica / Banca: Tania Gracy Martins do Valle / Resumo: Os acidentes vasculares encefálicos constituem-se um sério problema de saúde, e dados sobre sua prevalência mundial têm chamado à atenção. Dentre os subtipos de AVE, a hemorragia intraparenquimatosa (HIP) configura-se a de pior prognóstico. Frequentes déficits cognitivos e a significativa incidência de sintomatologia depressiva têm sido associados a este insulto neurológico. Entretanto, os expressivos índices de morbimortalidade implicam em dificuldades para a execução de estudos inerentes ao funcionamento neuropsicológico, pós lesão. Este estudo teve como objetivo principal investigar as funções neuropsicológicas executivas, em sujeitos pós acidente vascular encefálico hemorrágico. Como objetivo secundário, buscou verificar as relações entre sintomas depressivos pós infarto cerebral hemorrágico intraparenquimatoso, respostas cognitivas e topografia lesional. Para isso, foram triados 123 pacientes admitidos de modo consecutivo, pelo Serviço de Neurocirurgia do Hospital de Base de Bauru. Destes, foram elegíveis 12 sujeitos, com HIP espontânea e primária, de ambos os sexos, com idade média de 58,5 anos. A avaliação neuropsicológica das funções executivas consistiu na aplicação do Wisconsin Card Sorting Test, do Sudoeste Dígitos (WAIS); Teste Blocos de Corsi; Trail Making Test; Stroop Test, e das provas de fluência verbal fonêmica e categoria semântica. O grau de gravidade do AVE foi medido pela Escala de AVE do National Institutes of health, Escala de Corna de Glasgow e pelo Escore de AVCH. O comprometimento nas AVDs foi medido pelo Índice Barthel, e a sintomatologia depressiva pelo Inventário de Depressão de Beck. As avaliações ocorrem em dois momentos: a primeira, em média 50,4 horas, em internação hospitalar, e a segunda em média 36 dias, após o AVE. Os exames de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Cerebrovascular accident constitutes a serious health problem, and data about its global prevalence have been calling attention. Among the subtypes of strokes, the intraparenchymal hemorthage (IPH) is the one with worst prognosis. Common cognitive deficits and a significant incidence of depressive symptoms have been assossiated with this neuronal injury. However, the significant morbidity and mortability rates imply difficulties for the implementation of study inherent in neuropsychological functioning, post injury. This study aimed to investigate the neuropsychological executive functions in subjects after hemorrhagic cerebrovascular accident. As a secondary objective, we sought to examine relationships between depressive symptoms after cerebral infarction, intraparenchymal hemorrhage, cognitive responses and lesional topography. Thus, 123 patients were screened and admitted in a consecutive manner by the Neurosurgery Service of the Hospital de Base de Bauru. From these, 12 subjects were eligeble with spontaneous and primary HIP, both genders, with and average age of 58.5 years. Neuropsychological assessment of executive functions considered in applying the Wisconsin Card Sorting Test, the Digits Subtest (WAIS), Corsi Blocks Test. Trail Making Stroop Test, and phonemic verbal fluency tests and semantic category. The severity of strokes was measured by the National Institutes of Health Scale Stroke, Glasgow Coma Scale and the Hemorrhagic Stroke score. The impairment in ADLs was measured by the Barthel Index, and depressive symptoms by the Beck Depression Inventory. Evaluations occur in two stages: fisrt, on average 50.4 hours in hospital, and second on average 36 days after stroke. Neuroimaging studies, by Computed Tomography of the skull, were performed on admission, given the diagnosis... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:28:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-08-03Bitstream added on 2014-06-13T19:16:59Z : No. of bitstreams: 1 camargo_apa_me_bauru.pdf: 718368 bytes, checksum: c10be200a238268625ba4577a47ff36c (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os acidentes vasculares encefálicos constituem-se um sério problema de saúde, e dados sobre sua prevalência mundial têm chamado à atenção. Dentre os subtipos de AVE, a hemorragia intraparenquimatosa (HIP) configura-se a de pior prognóstico. Frequentes déficits cognitivos e a significativa incidência de sintomatologia depressiva têm sido associados a este insulto neurológico. Entretanto, os expressivos índices de morbimortalidade implicam em dificuldades para a execução de estudos inerentes ao funcionamento neuropsicológico, pós lesão. Este estudo teve como objetivo principal investigar as funções neuropsicológicas executivas, em sujeitos pós acidente vascular encefálico hemorrágico. Como objetivo secundário, buscou verificar as relações entre sintomas depressivos pós infarto cerebral hemorrágico intraparenquimatoso, respostas cognitivas e topografia lesional. Para isso, foram triados 123 pacientes admitidos de modo consecutivo, pelo Serviço de Neurocirurgia do Hospital de Base de Bauru. Destes, foram elegíveis 12 sujeitos, com HIP espontânea e primária, de ambos os sexos, com idade média de 58,5 anos. A avaliação neuropsicológica das funções executivas consistiu na aplicação do Wisconsin Card Sorting Test, do Sudoeste Dígitos (WAIS); Teste Blocos de Corsi; Trail Making Test; Stroop Test, e das provas de fluência verbal fonêmica e categoria semântica. O grau de gravidade do AVE foi medido pela Escala de AVE do National Institutes of health, Escala de Corna de Glasgow e pelo Escore de AVCH. O comprometimento nas AVDs foi medido pelo Índice Barthel, e a sintomatologia depressiva pelo Inventário de Depressão de Beck. As avaliações ocorrem em dois momentos: a primeira, em média 50,4 horas, em internação hospitalar, e a segunda em média 36 dias, após o AVE. Os exames de... / Cerebrovascular accident constitutes a serious health problem, and data about its global prevalence have been calling attention. Among the subtypes of strokes, the intraparenchymal hemorthage (IPH) is the one with worst prognosis. Common cognitive deficits and a significant incidence of depressive symptoms have been assossiated with this neuronal injury. However, the significant morbidity and mortability rates imply difficulties for the implementation of study inherent in neuropsychological functioning, post injury. This study aimed to investigate the neuropsychological executive functions in subjects after hemorrhagic cerebrovascular accident. As a secondary objective, we sought to examine relationships between depressive symptoms after cerebral infarction, intraparenchymal hemorrhage, cognitive responses and lesional topography. Thus, 123 patients were screened and admitted in a consecutive manner by the Neurosurgery Service of the Hospital de Base de Bauru. From these, 12 subjects were eligeble with spontaneous and primary HIP, both genders, with and average age of 58.5 years. Neuropsychological assessment of executive functions considered in applying the Wisconsin Card Sorting Test, the Digits Subtest (WAIS), Corsi Blocks Test. Trail Making Stroop Test, and phonemic verbal fluency tests and semantic category. The severity of strokes was measured by the National Institutes of Health Scale Stroke, Glasgow Coma Scale and the Hemorrhagic Stroke score. The impairment in ADLs was measured by the Barthel Index, and depressive symptoms by the Beck Depression Inventory. Evaluations occur in two stages: fisrt, on average 50.4 hours in hospital, and second on average 36 days after stroke. Neuroimaging studies, by Computed Tomography of the skull, were performed on admission, given the diagnosis... (Complete abstract click electronic access below)

L'hémorragie intra-cérébrale (HIC) est responsable d’environ 15 % des accidents vasculaires cérébraux. Son incidence augmente avec l’âge et sa mortalité à 3 mois est de 30 % pour atteindre 60% à 1 an .1 La prise en charge de l’HIC représente un défi majeur pour la Santé Publique. <p>Plusieurs attitudes thérapeutiques ont été proposées récemment ;parmi elles l’administration, lors de la phase aigue, de substances neuroprotectrices 1,2 ou de facteurs de coagulation 1,2,3 .<p>En effet, c’est durant cette phase, que surviennent l’inondation ventriculaire, la constitution et la croissance de l’hématome et l’engagement cérébral avec le décès comme conséquence.<p>Le contrôle de l'hypertension intra-crânienne représente la première ligne de traitement ;malheureusement son efficacité s’avère très limitée à l’heure actuelle et aucune nouvelle modalité thérapeutique n’a porté ses fruits. 1<p>Dans ce travail nous avons tenté de définir les éléments cliniques intervenant au cours de la phase aigue de l’hémorragie intracérébrale sur lesquels pourraient agir une prise en charge mieux ciblée plus spécifique.<p>(1) Nous avons comparé la dizaine d’échelles pronostiques proposées depuis celle d’Hemphill en 2001, comprenant des éléments cliniques et radiologiques et utilisées pour la stratification du risque dans l’HIC afin de déterminer la ou les plus adaptée(s).3,4,5,6 <p>Nous avons conclu que ces échelles ne permettent pas une discrimination optimale et qu’elles restent équivalentes dans leur sensibilité et spécificité pronostiques.5<p>(2) Nous nous sommes ensuite concentrés sur les éléments cliniques et biologiques liés à la phase aigue de l’HIC pouvant influencer les décisions thérapeutiques (température, glycémie, dysfonction ionique, état critique,…). <p>Il ressort de l’étude de ces facteurs que seule l'hyperglycémie est associée à un mauvais pronostic.7,8<p> (3) Nous avons également essayé de voir si les caractèristiques de la lésion hémorragique jouent un rôle important ;nous avons noté (a) que la taille de l’hématome proprement dit reste l’élément prédicteur le plus important de mortalité, (b) 9 que la taille de l’ œdème cérébral y est lié (c) 9 qu’il existe une synergie d’effets délétères (surtout pour les petits hématomes) entre la taille de l’hématome et celle de l’œdème (d) 9, que la localisation de l’hématome influence également son extension ventriculaire (d) que la quantité de sang libéré dans les ventricules cérébraux a pour conséquence un pronostic péjoratif (associé à l’élévation de la glycémie à la phase aigue). 6,7<p>(4)Nous nous sommes intéressés à l’existence d’une éventuelle susceptibilité génétique pouvant intervenir dans la cinétique du saignement; nous avons relevé que la simple variation d’une paire de base du génome (SNP single nucleotide polymorphism) au niveau des gènes impliqués dans l’hémostase (gène du facteur de von Willebrand; rs216321) et l’agrégation plaquettaire (rs342286) pourrait influencer la taille de l’hématome lors de la phase aigue et sa croissance au cours des premières heures.10,11,12<p> (5) Enfin, nous avons voulu caractériser l’invalidité liée à l’HIC chez les survivants. Il existe une hétérogénéité des échelles d’évolution clinique mais en les comparant, l’Index de Bartel (qui intègre un large éventail d’activités de la vie de tous les jours) se montre supérieur aux scores de Rankin et de Glasgow. 13 Néanmoins, l’index de Barthel n’intègre pas la mortalité au sein des paramètres d’évolution clinique, risquant ainsi de biaiser l'interprétation en présence d’un nombre élevé de décès dans l’étude.<p> En conclusion, au cours de l’HIC, les caractéristiques s évolutifs de l’hématome au cours de la phase aigue, notamment sa taille, sa croissance et son extension dans les ventricules cérébraux sont responsables d’une série d’événements interactifs conduisant à un effet de masse mais également une cascade d’événements biologiques aggravant le pronostic, surtout chez des patients présentant une susceptibilité génétique La prise en compte de ces facteurs de risque devrait permettre une amélioration de la qualité de prise en charge et donc des résultats cliniques.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Contexte: L’hémorragie intraventriculaire néonatale est associée à des séquelles neuro-développementales, mais le risque à long terme d'autres issues est inconnu. L'association entre l'hémorragie intraventriculaire néonatale et le risque de morbidité durant l’enfance a été évaluée. Méthodes: Une cohorte longitudinale de 794,384 bébés nés entre 2006 et 2016 au Québec, Canada a été analysé. Les nouveau-nés ont été suivis jusqu'à une période de 12 ans après leur naissance, pour identifier les hospitalisations subséquentes. Dans les modèles de régression de Cox, ajustés pour les caractéristiques maternelles et néonatales, les « hazard ratios » et intervalles de confiance (IC) à 95% ont été estimés pour l'association entre l'hémorragie intraventriculaire avec l’hospitalisation ultérieure. Résultats: Au total, 1,322 nourrissons (0,2%) ont développé une hémorragie intraventriculaire de grade I à IV. L'incidence de l'hospitalisation était plus élevée chez les bébés présentant une hémorragie intraventriculaire que chez les bébés sans hémorragie (23,8 vs 5,7 par 100 personnes-années). Comparés aux bébés sans hémorragie, les bébés affectés avaient un risque d'hospitalisation 1,56 fois plus élevé (IC à 95% 1,43-1,70). Le risque était 2,81 fois plus élevé pour les grades III/IV (IC à 95% 2,23 à 3,53) comparés à ceux nés sans hémorragie. Les hémorragies intraventriculaires pré-terme était associée à 1,82 fois le risque (IC 95% 1,66-2,00) comparés aux bébés nés termes sans hémorragie. Les hémorragies intraventriculaires à terme étaient associées à 3,19 fois le risque d'hospitalisation (IC 95% 2,55-4,00), comparativement à ceux nés termes sans hémorragie. Les raisons principales des hospitalisations comprenaient les maladies du système nerveux central, ophtalmologiques, musculo-squelettiques et cardiovasculaires. Conclusion: L'hémorragie intraventriculaire, notamment de grades sévères et parmi les bébés à terme, est un déterminant important du futur risque d’hospitalisation durant l’enfance. / Background: Neonatal intraventricular hemorrhage is associated with neurodevelopmental sequelae, but the long-term risk of other outcomes is unknown. The association between neonatal intraventricular hemorrhage and the risk of childhood morbidity was assessed. Methods: A longitudinal cohort of 794,384 infants born between 2006 and 2016 in Quebec, Canada was analyzed. Infants were tracked over time to identify later hospitalizations with follow-up extending up to 12 years after birth. In Cox regression models adjusted for maternal and infant characteristics, the hazard ratios and 95% confidence intervals (CI) were estimated for the association of intraventricular hemorrhage with future hospitalization. Results: A total of 1,322 (0.2%) infants developed grade I to IV intraventricular hemorrhage. The incidence of childhood hospitalization was higher in infants with intraventricular hemorrhage than in infants without hemorrhage (23.8 vs. 5.7 per 100 person-years). Compared with no hemorrhage, infants with intraventricular hemorrhage had 1.56 times the risk of hospitalization (95% CI 1.43-1.70). The risk was 2.81 times higher for grade III/IV hemorrhage (95% CI 2.23-3.53) compared to those born without hemorrhage. Preterm intraventricular hemorrhage was associated with 1.82 times the risk (95% CI 1.66-2.00) compared to term infants born without hemorrhage. Intraventricular hemorrhage at term was associated with 3.19 times the risk of hospitalization (95% CI 2.55-4.00) compared to those born term without hemorrhaging. Primary reasons for hospitalizations included central nervous system, ophthalmologic, musculoskeletal, and cardiovascular disorders. Conclusion: Intraventricular hemorrhage, especially of higher grades and in term neonates, is an important determinant of the future risk of child hospitalization.