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With asphyxia, newborns may suffer cardiogenic shock with myocardial dysfunction and dysregulation of vasomotor tone resulting in multiorgan dysfunction. Vasoactive medications are often administered with limited evidence directing clinicians regarding the use of high-dose monotherapy with dopamine relative to combination treatment with dopamine and a second different agent. We hypothesized that the treatment of hypoxia-reoxygenated newborn piglets with combinations of vasoactive medications would improve systemic and regional hemodynamics. Instrumented newborn piglets were subjected to hypoxia-reoxygenation with subsequent infusion of high-dose dopamine or moderate-dose dopamine and one of epinephrine, milrinone or levosimendan. Treatment with high-dose dopamine improved systemic and mesenteric perfusion. The addition of low-dose epinephrine showed some benefits regarding pulmonary hypertension and should a non-catecholamine agent be added to dopamine, milrinone is preferred to levosimendan given benefits to mesenteric perfusion. We conclude that the selection of appropriate vasoactive medical therapy should be directed by the clinical effects desired. / Experimental Surgery

Hypothermia is increasingly being used as a treatment modality for many conditions. Therapeutic hypothermia is any technique in which the body temperature is lowered for reducing oxygen demand and metabolic rate as a means to prevent or minimize organ damage. The purpose of this thesis is to describe current applications of therapeutic hypothermia, including types of cooling techniques, patients who benefit from hypothermia, target temperature, and associated side effects. There are two clinical situations where large randomized studies have demonstrated benefit of therapeutic hypothermia in humans. The first is in treatment of neonates with asphyxia, and the second is for treating survivors of out-of-hospital cardiac arrest. Most cooling research focuses on treatment with mild to moderate hypothermia, 32°C - 34°C. Noninvasive cooling methods include the traditional ice packs, fans, alcohol baths, and cooling blankets not attached to any monitoring device. Invasive cooling techniques consist of the infusion of ice-cold fluids, ice slurries, endovascular, and nasopharyngeal cooling. Patients treated with therapeutic hypothermia require close monitoring due to the increased risk of infections, skin break down, vital sign changes such as bradycardia, and electrolyte balances such as hypokalemia. Optimal depth and duration of hypothermia and optimal rate of re-warming are unknown. Further nursing research is needed for induced hypothermia guidelines as well as education.

INTRODUÇÃO: A asfixia perinatal é uma das principais causa de óbito nos recémnascidos (RN) de termo acima de 2500g no Brasil, sendo também a causa mais importante de encefalopatia e lesão cerebral permanente em crianças. Não existindo ainda um consenso acerca de qual seria o melhor critério para seu diagnóstico. OBJETIVOS: Verificar a prevalência de asfixia e de encefalopatia hipóxico-isquêmica segundo dois critérios diagnósticos, avaliar influência do tipo de parto e a evolução neurológica. MÉTODO: Corte transversal prospectivo, onde foram incluídos 30 recém-nascidos que apresentaram asfixia segundo dois critérios diagnósticos: critério 1 foi preconizado pela AAP/ACOG de 1996 (pH de cordão 7,0, disfunção múltipla de órgãos, manifestações neurológicas na primeira semana de vida além do Apgar entre 0-3 no quinto minuto); o critério 2 foi de Buonocore em 2002, modificado (pH de cordão 7,2, Apgar de 4-6 no quinto minuto e necessidade de fração de oxigênio inspirada 0,40 manter saturação de 86%); num período de dois anos (2004/2006) sendo excluídos aqueles que pudessem apresentar encefalopatia por outras causas como malformações, infecções congênitas, erro inato do metabolismo. Para realizar o diagnóstico foram colhida gasometria de cordão dos recémnascidos a termo que apresentaram Apgar de quinto minuto 6 e feitas provas de função cardíaca, hepática, renal e controle hematológico além da avaliação neurológica pelos critérios clínicos de Sarnat e Sarnat de 1976, para verificar o grau de encefalopatia. RESULTADOS: Durante este período a prevalência observada de asfixia foi de 3,2 por 1000 nascimentos a termo (IC a 95% - [2,1 por mil; 4,5 por mil]) e de encefalopatia de 1,7 por 1000 nascimentos a termo (IC a 95% - [0,8 por mil; 2,5 por mil]). A taxa de mortalidade foi de 16,7% e 36,7% evoluíram com encefalopatia grave. Não houve correlação estatística da asfixia e nem da encefalopatia quanto às características maternas, exceto uma tendência maior nas nulíparas e primíparas com parto normal. Quanto à indicação do parto 46,7% apresentava trabalho de parto sem intercorrências, mas pelo critério 1 houve maior número com sofrimento fetal relacionado à maior gravidade da asfixia. O sexo mais freqüente foi o masculino e em ambos os grupos apresentaram acidose metabólica e respiratória e alterações enzimáticas principalmente cardíacas e hepáticas e, função renal com aumento da creatinina. Foi observado que para Sarnat estágios 1 e 2, leve e moderada, houve uma maior proporção de recém-nascidos no critério 2 enquanto que para o Sarnat estágio 3, grave, a maior proporção foi com o critério 1 Resumo (p = 0,016). Enquanto o Apgar de primeiro minuto não mostrou correlação com a gravidade da encefalopatia, 85% dos recém-nascidos com encefalopatia leve/moderada tiveram Apgar de quinto minuto entre 4-6 e a maioria com quadro grave o Apgar foi entre 0-3 (p = 0,018). Houve uma tendência de acordo com o aumento da gravidade da encefalopatia a uma redução do dióxido de carbono sanguíneo, bicarbonato e aumento negativo do excesso de base além do aumento de enzima cardíaca (creatina fosfoquinase), mas não foi estatisticamente significante. CONCLUSÃO: Não houve correlação estatística entre asfixia e a gravidade da encefalopatia com fatores maternos. Todos os recém-nascidos apresentaram acidose respiratória e metabólica e entre as alterações enzimáticas cardíacas foram as mais importante. Em relação ao índice de Apgar, a nota de quinto minuto mostrou melhor correlação com a gravidade evolutiva dos pacientes. Com o critério 1 (Academia Americana de Pediatria) houve melhor correlação com a mortalidade, no entanto por ser muito rigoroso acaba por excluir recém-nascidos que evoluem com quadros de encefalopatia grave / INTRODUCTION: The perinatal asphyxia is one of the main causes of death in newborns and also the most important cause of encephalopathy and permanent cerebral lesion in children. OBJECTIVES: To check the prevalence of asphyxia and of hypoxic-ischemic encephalopathy in term newborns, using two diagnostic criteria; to assess whether the diagnostic criterion used and the type of obstetric assistance are related to the grade of seriousness of the asphyxia and of the encephalopathy. Methods: Prospective transversal cut study carried out in a public hospital in the East Zone of São Paulo, in which 30 term newborns with perinatal asphyxia were included and classified in two groups, according to two diagnostic criteria adopted: criterion 1 recommended by American Academy of Pediatrics (1996), and which considers as bearer of perinatal asphyxia the newborn presenting: cord pH 7.0, multiple organ dysfunction, neurological manifestations in the first week of life and Apgar value in the fifth minute of life between 0-3. Criterion 2 defined by Buonocore in 2002 and which consists in: cord pH 7.2, Apgar value in the fifth minute of life between 4-6 and fraction inspired of oxygen need 0.40 to maintain a saturation of 86%. To confirm the diagnosis, the following laboratorial examinations were carried out: gasometry, hepatic, renal and cardiac function tests, besides the hematological control. To assess the neurological function and verify the grade of hypoxic-ischemic encephalopathy, the clinical criteria of Sarnat and Sarnat were used. RESULTS: The prevalence of perinatal asphyxia observed in this case was of 3.2 per 1,000 term births (IC at 95% - [2.1 per one thousand; 4.5 per one thousand]) and of hypoxic-ischemic encephalopathy was of 1.7 per 1,000 term births (IC at 95% - [0.8 per one thousand; 2.5 per one thousand]). As regards the criteria used, the newborns of criterion 1 statistically presented more fetal suffering when compared to those of criterion 2, and this fact was also related to the grade of seriousness of the asphyxia. The newborns of the two groups presented cardiac changes with elevation of the specific enzyme, hepatic changes with elevation of the glutamic pyruvic and oxaloacetic transaminases and renal changes proven by elevation of creatinine, besides the relevant respiratory and metabolic acidosis. The newborns with serious metabolic acidosis and high levels of creatine phosphokinase had a greater degree of neurological impairment. In 85% of newborns with light/moderate encephalopathy was verified an Apgar value at fifth minute of life between 4-6, and in newborns with serious encephalopathy this value was between 0-3 (p = 0.018). A positive trend for Summary the presence of asphyxia and encephalopathy was found in children of primiparous mothers and born during normal parturition. When assessing the degree of neurological impairment through the criteria of Sarnat and Sarnat, A greater proportion of newborns of criterion 2 were found in the lighter degrees. In degree 3, which is the most serious, a greater proportion of newborns of criterion 1 (p = 0,016) was found. The mortality rate in these cases was of 16.7%, and most of the newborn were of criterion 1. CONCLUSION: The prevalence of perinatal asphyxia and hypoxic -ischemic encephalopathy is as mentioned in the world literature, and smaller than found in Brazil. Criterion 1 was the one that showed a better correlation with the mortality of patients. However, as it is too rigorous, it may exclude the newborn that survive and develop hypoxic-ischemic encephalopathy. As regards the type of obstetric assistance, despite the fact that no statistically significant difference was observed, there was a positive trend to the presence of asphyxia and encephalopathy in children of primiparous mothers born during normal parturition

A anóxia neonatal, considerada problema clínico mundial, é importante causa de lesão encefálica em neonatos que pode apresentar consequências graves e permanentes, como déficits cognitivos e comportamentais. O objetivo deste estudo foi analisar longitudinalmente possíveis alterações na morte, proliferação e diferenciação neuronais no hipocampo de ratos submetidos à anóxia neonatal. Para tanto, utilizamos modelo adaptado e validado em nosso laboratório. Os resultados mostraram que a anóxia neonatal causa morte neural em CA1 e CA2-3, detectadas pela maior quantidade de células TUNEL+ em CA1 e CA2-3 e FJB+ em CA2-3, além de diferentes tipos de morte neuronal em CA1 e GD, 24 horas após a anóxia,observadas por microscopia eletrônica. Houve aumento do volume de CA1 em P14 no grupo anóxia, porém o padrão de proliferação na zona subgranular não foi alterado. Enfim, a anóxia neonatal promoveu diminuição da neurogênese em animais adultos, o que poderia estar associado aos déficits de memória espacial e aprendizagem descritos em literatura para modelos similares. / Neonatal anoxia, considered a worldwide clinical problem, is a major cause of brain injury in neonates and may present serious and permanent consequences such as cognitive and behavioral deficits. The aim of this study was to analyze possible changes longitudinally in neural death, proliferation and neuronal differentiation in the hippocampus of rats submitted to neonatal anoxia. We used an adapted model validated in our laboratory. The results showed that neonatal anoxia cause neural death in CA1 and CA2-3 detected by the TUNEL+ cells in CA1 and CA2-3 and FJB+ in CA2-3, and different types of neuronal death in CA1 and GD 24 hours of anoxia, observed by electron microscopy. There was an increase in the volume of CA1 in the P14 anoxia group but the pattern of proliferation in the subgranular zone was not changed. Anyway, neonatal anoxia caused decrease in neurogenesis in adult animals, which could be associated with deficits in spatial memory and learning described in the literature in similar models.

INTRODUÇÃO: A asfixia perinatal é uma das principais causa de óbito nos recémnascidos (RN) de termo acima de 2500g no Brasil, sendo também a causa mais importante de encefalopatia e lesão cerebral permanente em crianças. Não existindo ainda um consenso acerca de qual seria o melhor critério para seu diagnóstico. OBJETIVOS: Verificar a prevalência de asfixia e de encefalopatia hipóxico-isquêmica segundo dois critérios diagnósticos, avaliar influência do tipo de parto e a evolução neurológica. MÉTODO: Corte transversal prospectivo, onde foram incluídos 30 recém-nascidos que apresentaram asfixia segundo dois critérios diagnósticos: critério 1 foi preconizado pela AAP/ACOG de 1996 (pH de cordão 7,0, disfunção múltipla de órgãos, manifestações neurológicas na primeira semana de vida além do Apgar entre 0-3 no quinto minuto); o critério 2 foi de Buonocore em 2002, modificado (pH de cordão 7,2, Apgar de 4-6 no quinto minuto e necessidade de fração de oxigênio inspirada 0,40 manter saturação de 86%); num período de dois anos (2004/2006) sendo excluídos aqueles que pudessem apresentar encefalopatia por outras causas como malformações, infecções congênitas, erro inato do metabolismo. Para realizar o diagnóstico foram colhida gasometria de cordão dos recémnascidos a termo que apresentaram Apgar de quinto minuto 6 e feitas provas de função cardíaca, hepática, renal e controle hematológico além da avaliação neurológica pelos critérios clínicos de Sarnat e Sarnat de 1976, para verificar o grau de encefalopatia. RESULTADOS: Durante este período a prevalência observada de asfixia foi de 3,2 por 1000 nascimentos a termo (IC a 95% - [2,1 por mil; 4,5 por mil]) e de encefalopatia de 1,7 por 1000 nascimentos a termo (IC a 95% - [0,8 por mil; 2,5 por mil]). A taxa de mortalidade foi de 16,7% e 36,7% evoluíram com encefalopatia grave. Não houve correlação estatística da asfixia e nem da encefalopatia quanto às características maternas, exceto uma tendência maior nas nulíparas e primíparas com parto normal. Quanto à indicação do parto 46,7% apresentava trabalho de parto sem intercorrências, mas pelo critério 1 houve maior número com sofrimento fetal relacionado à maior gravidade da asfixia. O sexo mais freqüente foi o masculino e em ambos os grupos apresentaram acidose metabólica e respiratória e alterações enzimáticas principalmente cardíacas e hepáticas e, função renal com aumento da creatinina. Foi observado que para Sarnat estágios 1 e 2, leve e moderada, houve uma maior proporção de recém-nascidos no critério 2 enquanto que para o Sarnat estágio 3, grave, a maior proporção foi com o critério 1 Resumo (p = 0,016). Enquanto o Apgar de primeiro minuto não mostrou correlação com a gravidade da encefalopatia, 85% dos recém-nascidos com encefalopatia leve/moderada tiveram Apgar de quinto minuto entre 4-6 e a maioria com quadro grave o Apgar foi entre 0-3 (p = 0,018). Houve uma tendência de acordo com o aumento da gravidade da encefalopatia a uma redução do dióxido de carbono sanguíneo, bicarbonato e aumento negativo do excesso de base além do aumento de enzima cardíaca (creatina fosfoquinase), mas não foi estatisticamente significante. CONCLUSÃO: Não houve correlação estatística entre asfixia e a gravidade da encefalopatia com fatores maternos. Todos os recém-nascidos apresentaram acidose respiratória e metabólica e entre as alterações enzimáticas cardíacas foram as mais importante. Em relação ao índice de Apgar, a nota de quinto minuto mostrou melhor correlação com a gravidade evolutiva dos pacientes. Com o critério 1 (Academia Americana de Pediatria) houve melhor correlação com a mortalidade, no entanto por ser muito rigoroso acaba por excluir recém-nascidos que evoluem com quadros de encefalopatia grave / INTRODUCTION: The perinatal asphyxia is one of the main causes of death in newborns and also the most important cause of encephalopathy and permanent cerebral lesion in children. OBJECTIVES: To check the prevalence of asphyxia and of hypoxic-ischemic encephalopathy in term newborns, using two diagnostic criteria; to assess whether the diagnostic criterion used and the type of obstetric assistance are related to the grade of seriousness of the asphyxia and of the encephalopathy. Methods: Prospective transversal cut study carried out in a public hospital in the East Zone of São Paulo, in which 30 term newborns with perinatal asphyxia were included and classified in two groups, according to two diagnostic criteria adopted: criterion 1 recommended by American Academy of Pediatrics (1996), and which considers as bearer of perinatal asphyxia the newborn presenting: cord pH 7.0, multiple organ dysfunction, neurological manifestations in the first week of life and Apgar value in the fifth minute of life between 0-3. Criterion 2 defined by Buonocore in 2002 and which consists in: cord pH 7.2, Apgar value in the fifth minute of life between 4-6 and fraction inspired of oxygen need 0.40 to maintain a saturation of 86%. To confirm the diagnosis, the following laboratorial examinations were carried out: gasometry, hepatic, renal and cardiac function tests, besides the hematological control. To assess the neurological function and verify the grade of hypoxic-ischemic encephalopathy, the clinical criteria of Sarnat and Sarnat were used. RESULTS: The prevalence of perinatal asphyxia observed in this case was of 3.2 per 1,000 term births (IC at 95% - [2.1 per one thousand; 4.5 per one thousand]) and of hypoxic-ischemic encephalopathy was of 1.7 per 1,000 term births (IC at 95% - [0.8 per one thousand; 2.5 per one thousand]). As regards the criteria used, the newborns of criterion 1 statistically presented more fetal suffering when compared to those of criterion 2, and this fact was also related to the grade of seriousness of the asphyxia. The newborns of the two groups presented cardiac changes with elevation of the specific enzyme, hepatic changes with elevation of the glutamic pyruvic and oxaloacetic transaminases and renal changes proven by elevation of creatinine, besides the relevant respiratory and metabolic acidosis. The newborns with serious metabolic acidosis and high levels of creatine phosphokinase had a greater degree of neurological impairment. In 85% of newborns with light/moderate encephalopathy was verified an Apgar value at fifth minute of life between 4-6, and in newborns with serious encephalopathy this value was between 0-3 (p = 0.018). A positive trend for Summary the presence of asphyxia and encephalopathy was found in children of primiparous mothers and born during normal parturition. When assessing the degree of neurological impairment through the criteria of Sarnat and Sarnat, A greater proportion of newborns of criterion 2 were found in the lighter degrees. In degree 3, which is the most serious, a greater proportion of newborns of criterion 1 (p = 0,016) was found. The mortality rate in these cases was of 16.7%, and most of the newborn were of criterion 1. CONCLUSION: The prevalence of perinatal asphyxia and hypoxic -ischemic encephalopathy is as mentioned in the world literature, and smaller than found in Brazil. Criterion 1 was the one that showed a better correlation with the mortality of patients. However, as it is too rigorous, it may exclude the newborn that survive and develop hypoxic-ischemic encephalopathy. As regards the type of obstetric assistance, despite the fact that no statistically significant difference was observed, there was a positive trend to the presence of asphyxia and encephalopathy in children of primiparous mothers born during normal parturition

A anóxia neonatal, considerada problema clínico mundial, é importante causa de lesão encefálica em neonatos que pode apresentar consequências graves e permanentes, como déficits cognitivos e comportamentais. O objetivo deste estudo foi analisar longitudinalmente possíveis alterações na morte, proliferação e diferenciação neuronais no hipocampo de ratos submetidos à anóxia neonatal. Para tanto, utilizamos modelo adaptado e validado em nosso laboratório. Os resultados mostraram que a anóxia neonatal causa morte neural em CA1 e CA2-3, detectadas pela maior quantidade de células TUNEL+ em CA1 e CA2-3 e FJB+ em CA2-3, além de diferentes tipos de morte neuronal em CA1 e GD, 24 horas após a anóxia,observadas por microscopia eletrônica. Houve aumento do volume de CA1 em P14 no grupo anóxia, porém o padrão de proliferação na zona subgranular não foi alterado. Enfim, a anóxia neonatal promoveu diminuição da neurogênese em animais adultos, o que poderia estar associado aos déficits de memória espacial e aprendizagem descritos em literatura para modelos similares. / Neonatal anoxia, considered a worldwide clinical problem, is a major cause of brain injury in neonates and may present serious and permanent consequences such as cognitive and behavioral deficits. The aim of this study was to analyze possible changes longitudinally in neural death, proliferation and neuronal differentiation in the hippocampus of rats submitted to neonatal anoxia. We used an adapted model validated in our laboratory. The results showed that neonatal anoxia cause neural death in CA1 and CA2-3 detected by the TUNEL+ cells in CA1 and CA2-3 and FJB+ in CA2-3, and different types of neuronal death in CA1 and GD 24 hours of anoxia, observed by electron microscopy. There was an increase in the volume of CA1 in the P14 anoxia group but the pattern of proliferation in the subgranular zone was not changed. Anyway, neonatal anoxia caused decrease in neurogenesis in adult animals, which could be associated with deficits in spatial memory and learning described in the literature in similar models.

L’imagerie IRM de perfusion par Arterial Spin Labeling (ASL) ou marquage des spin artériels a pour principal avantage d’être une méthode d’imagerie non invasive (non irradiante et sans injection de produit de contraste exogène), particulièrement adaptée à l'imagerie cérébrale pédiatrique. Sa facilité de mise en œuvre explique l’engouement pour cette séquence et de nombreuses applications cliniques émergentes. Cette technique initialement développée chez l’adulte nécessite une adaptation à la population pédiatrique, aussi bien des paramètres d’acquisition et de quantification que des algorithmes de traitement d’images. La perfusion cérébrale globale et régionale évolue physiologiquement, parallèlement à l’âge et au développement neurocognitif. Il existe plusieurs méthodes d’étude de la perfusion cérébrale pédiatrique. Dans ce contexte, deux revues de littérature ont été réalisées et publiées : l’une portant sur les différentes techniques d’imagerie de la perfusion cérébrale chez les nouveau-nés, l’autre se focalisant sur la technique d’ASL en pédiatrie et ses applications cliniques. Puis la chaîne de traitement des images morphologiques et de perfusion ASL, développée chez l’adulte au sein de notre unité, a été adaptée aux enfants puis aux nouveau-nés. Ces deux populations ont effectivement des problématiques différentes, en particulier le rapport signal sur bruit de l’ASL est très bon chez les enfants, mais nettement moins bon chez les nouveau-nés, et les images morphologiques ont un contraste différent en raison d’une myélinisation incomplète à la naissance. Grace à l’adaptation de la chaîne de traitement, des travaux de recherche clinique ont pu être finalisés (2 publiés, 1 soumis) illustrant l’intérêt de l’étude de la perfusion cérébrale dans 3 situations : l’étude de l’évolution de la perfusion cérébrale normale chez l’enfant entre 6 mois et 15 ans ; l’étude de la perfusion cérébrale chez les enfants souffrant d’une première crise de migraine avec aura ; et enfin l’étude de l’évolution de la perfusion cérébrale entre le 3ieme et le 10ieme jour de vie chez les enfants souffrant d’asphyxie périnatale et traités par hypothermie. Plusieurs projets restent en cours sur le sujet, avec d’autres challenges de traitement et d’analyse d’image (enfants de neurochirurgie avec modifications morphologiques du cerveau, ou enfants prématurés par exemple), dans la continuité ce qui a été fait au cours de cette thèse. / Physiological changes in overall and regional cerebral perfusion are related to age and neurocognitive development. Brain perfusion in the pediatric population can be assessed using a number of imaging techniques. Two literature reviews were undertaken and published on this topic: one based on brain perfusion imaging techniques in neonates, and the other based on the ASL technique in the pediatric population and its clinical applications. The Arterial Spin Labeling (ASL) MRI perfusion sequence is one of the most suitable imaging techniques for children given that the procedure is non-irradiating and non-invasive (without exogenous contrast agent injection). There are many emerging cerebral perfusion imaging applications for children due to the highly convenient implementation of the ASL sequence, which can be easily incorporated into standard brain MRI protocols following acquisition of morphological images. Certain technical adjustments to the imaging parameters are required to account for the fundamental differences between the pediatric and adult populations. Measuring cerebral blood flow (CBF) in neonates and children using ASL therefore requires a number of adaptations to acquisition and related parameters.The processing of ASL data also requires specific adaptations, in particular regarding the automated segmentation of brain tissues, and the parameters used for CBF quantification models. The processing pipeline for both anatomical and perfusion images that had been previously developed by our team for adult data was adapted firstly for children and secondly for neonates. These two populations notably have specific age-related concerns; in particular the signal-to-noise ratio of ASL is very good in children, but much less so in neonates, and the morphological images have inverted contrast due to incomplete myelination at birth. Following adaptation of the processing pipeline, several studies were completed (2 original articles published and 1 under review), showing the clinical benefits of studying cerebral perfusion in three situations: first physiological changes in cerebral perfusion in children between 6 months and 15 years; secondly changes in cerebral perfusion in children with a first attack of migraine with aura; and lastly changes in brain perfusion between day of life 3 and day of life 10 in asphyxiated neonates. Following adaptation of the processing pipeline, several studies were completed (2 original articles published and 1 under review), showing the clinical benefits of studying cerebral perfusion in three situations: first physiological changes in cerebral perfusion in children between 6 months and 15 years; secondly changes in cerebral perfusion in children with a first attack of migraine with aura; and lastly changes in brain perfusion between day of life 3 and day of life 10 in asphyxiated neonates. Several studies are still in progress, and these present new image processing challenges, involving, for example, children with neurosurgical conditions and morphological changes in the brain, or premature babies, in line with the work undertaken for this thesis.

Contexte théorique : L’encéphalopathie hypoxique ischémique (EHI) est une condition du nouveau-né dans laquelle les mécanismes des variables métaboliques ne sont pas totalement compris. Cette population est particulièrement à risque d’hypo- ou d’hyperglycémie néonatales (HHN). Devant le manque de données sur le fonctionnement métabolique à la suite d’une EHI, cette étude vise à déterminer l’association entre une HHN et l’activité cérébrale mesurée par électroencéphalographie (EEG). Méthodologie : 49 participants avec EHI ont été recrutés au CHU Sainte-Justine peu après leur naissance. Ils ont été monitorés en continu à l’aide de l’EEG et des segments d’intérêt se retrouvant dans les 48 premières heures de vie ont été analysés. L’anormalité de l’activité cérébrale est déterminée selon une analyse quantitative du niveau de discontinuité caractérisée par une proportion de faibles amplitudes (seuils de 25, 15, 12,5, 10 et 7,5 uV) dans le tracé EEG. Les données de glycémie ont été recueillies de façon intermittente par le biais de prises de sang et de glucomètres de chevet. Les participants ont été répartis en 4 groupes : normoglycémie, hyperglycémie, hypoglycémie et glycémie variable (hypo- et hyper-). Résultats : L’analyse de covariation non -paramétrique a relevé une différence significative entre les ratios de discontinuité pour le seuil de 15 uV (F = 3,070 p = 0,037). Les analyses de comparaisons appariées ont montré une différence positive entre le groupe VARIABLE et le groupe contrôle (NORMO-) pour tous les seuils ainsi qu’une différence positive entre le groupe HYPER- et le groupe contrôle pour 4 des 5 seuils (25, 15, 12,5 et 7,5 uV). Aucune différence n’a été relevé entre le groupe HYPO- et le groupe contrôle pour tous les seuils. Conclusions : La variabilité glycémique et l’hyperglycémie seule ont été montrées comme étant associées à une activité cérébrale altérée caractérisée par un tracé de plus faible amplitude mesurée avec l’EEG. / Background: Hypoxic ischemic encephalopathy (HIE) is a newborn condition in which the underlying mechanisms still require further understanding. This clinical population is particularly prone to neonatal hypo- and hyperglycemia (NHH). Given the need to improve our understanding of metabolic functioning following HIE, this study aims to determine the association of NHH on the brain’s background electrophysiological activity measured by electroencephalography (EEG). Methodology: Forty-nine newborns with HIE were recruited at Sainte-Justine University Hospital Center. Continuous EEG monitoring was started as soon as possible and segments of interest in the first 48h of life were analyzed. Brain activity was quantitatively assessed according to an index of discontinuity characterized by the proportion of low EEG amplitudes per segment (< 25, 15, 12.5, 10 and 7.5 uV cutoffs). Glucose measurements were intermittently collected using blood samples and bedside glucometers and were retrospectively retrieved from medical charts. Participants were separated in 4 groups : normoglycemia, hyperglycemia, hypoglycemia and both (hyper- and hypo-). Results: The non-parametric covariance analyses revealed a significant difference between the discontinuity index for the 15 uV threshold (F = 3.070 p = 0.037). The pairwise comparisons showed a positive difference between the group BOTH and the control group (NORMO-) for every thresholds, the labile glucose group having a higher discontinuity index. A similar difference was found between the HYPERGLYCEMIA group and the control group for 4 out 5 thresholds (25, 15, 12.5 and 7.5 uV). No difference was found between the HYPOGLYCEMIA group and the control group. Conclusion: An abnormal glycemic profile, particularly glucose lability and hyperglycemia alone, were shown to be associated with abnormal brain activity characterized by a higher discontinuity index on the EEG.