Malgré les récents progrès dans la prise en charge des patients en réanimation, la mortalité en réanimation reste élevée: environ 30%. L’atteinte cérébrale en est un déterminant majeur. Le concept de l'implication d'un dysfonctionnement du tronc cérébral dans la survenue de la mort en réanimation est bien établi. Cependant, les signatures neurophysiologiques de cette atteinte du tronc cérébral ne sont pas encore bien caractérisées. Certains paramètres de l'électroencéphalogramme (EEG) et des potentiels évoqués (PE) pourraient permettre l'évaluation de l'état fonctionnel du tronc cérébral en réanimation. La réactivité de l'EEG aux stimulations nociceptives permet de tester le fonctionnement du tronc cérébral par la voie extra-lemniscale (spino-thalamique). Les potentiels somesthésiques (PES) et auditifs précoces (PEAP) explorent respectivement les voies lemniscale médiane et lemniscale latérale dans le tronc cérébral.Dans les travaux présentés ici, nous avons évalué les anomalies de réponses neurophysiologiques du tronc cérébral et leur impact sur le pronostic dans différentes cohortes de patients en soins intensifs. En effet, le manque de réactivité de l'EEG à la stimulation douloureuse, ainsi que l'allongement du temps de conduction subcortico-corticale (PES P14-N20_ IPL) ont été chacun indépendamment corrélé à la mort en réanimation. L'allongement du temps de conduction ponto-mésencéphalique (PEAP III-V _ IPL) a tendance à être associé à l'apparition du délire ou du réveil retardé. Nos travaux fournissent des substrats neurophysiologiques des dysfonctionnements du tronc cérébral observés chez les patients gravement malades et leur relation avec le pronostic. Des études avec d'autres marqueurs neurophysiologiques ciblant le tronc cérébral comme les enregistrements du réflexe de clignement, des PE laser et des PE respiratoires, sont nécessaires. / Despite recent progress in the management of critically ill patients, mortality in the ICU remains high (around 30%). Neurological impairment is a major determinant of mortality in ICU. It has been hypothesithed that brainstem dysfunction might play a role in mortality in the ICU. However, neurophysiological signatures of brainstem failure in ICU patients have not yet been characterized. Electroencephalogram (EEG) and sensorial evoked potentials (EP) parameters could enable the assessment of the functional status of the brainstem at the bedside in the ICU. EEG reativity to intense painful stimuli allows testing the proper functioning of the brainstem via the extra-lemniscal pathway (spino-thalamic). Somatosensory (SSEP) and brainstem auditory (BAEP) evoked potentials respectively explore the median lemniscal and the lateral lemniscal pathways within the brainstem.In the works presented here, we assessed brainstem neurophysiological responses' and their impact on prognosis in various cohorts of critically ill patients. A lack of EEG reactivity to painful stimulation as well as the lengthening of subcortico-cortical conduction time (SSEP P14-N20_ IPL) was each independantly correlated with death in the ICU. The lengthening of ponto-mesencephalic conduction time (BAEP III-V _ IPL) tended to be associated with the onset of delirium or delayed awakening. Our work provides neurophysiological substratum for the concept of the brainstem dysfunctions in critically ill patients and their relationship with prognosis. Supplemental studies with other neurophysiological markers involving the brainstem such as recordings of blink reflexes, laser EP and respiratory EP, are needed to confirm these results.

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L’opossum Monodelphis domestica naît très immature et grimpe sans aide de la mère, du sinus urogénital à une mamelle où il va s’attacher pour poursuivre son développement. Des informations sensorielles sont nécessaires pour guider le nouveau-né vers la mamelle et les candidats les plus probables sont le toucher, l’équilibre et l’olfaction. Pour tester l’action des différents systèmes sur la motricité chez l’opossum nouveau-né, des régions céphaliques du trijumeau, du vestibulaire et de l’olfaction ont été stimulées électriquement sur des préparations in vitro en comparaison avec une stimulation seuil T (intensité minimale de la stimulation à la moelle épinière cervicale induisant le mouvement des membres antérieurs). Par comparaison, un mouvement similaire était induit par des stimulations à ~2T du ganglion du trijumeau, à ~20 T du complexe vestibulaire, et à ~600 T des bulbes olfactifs. L’étude de l'innervation de la peau faciale et des voies relayant les informations du trijumeau vers la moelle épinière (ME) a été approfondie en utilisant de l’immunohistochimie pour les neurofilament-200 et du traçage rétrograde avec du Texas-Red couplé à des Dextrans Aminés. De nombreuses fibres nerveuses ont été révélées dans le derme de plusieurs régions de la tête. Quelques cellules du ganglion trigéminal projettent à la ME rostrale, mais la majorité projette vers la médulla caudale où se trouvent les neurones secondaires du trijumeau ou des cellules réticulospinales. Les résultats de cette étude indiquent une influence significative des systèmes du trijumeau et du vestibulaire, mais pas de l'olfaction, sur le mouvement des membres antérieurs des opossums nouveau-nés. / The opossum Monodelphis domestica is born very immature and crawls, unaided by the mother, from the urogenital opening to a nipple where it attaches and pursues its development. Sensory information is needed to guide the newborn to a nipple and studies suggest that the vestibular, trigeminal, and olfactory systems are likely candidates. The trigeminal, vestibular and olfactory regions of the brain were electrically stimulated to test their relative effectiveness at eliciting forelimb movement in newborn opossums, using in vitro preparations of brain-spinal cord with the limbs attached. The minimal stimulation of the cervical spinal cord needed to induce forelimb movement was considered as threshold (T). Similar movement were obtained with stimulations of the trigeminal ganglion at ~2T and of the vestibular complex at ~20 T and at ~600 T for the olfactory bulb. Neurofilament-200 immunohistochemistry and retrograde tracing with Texas-Red conjugated Dextran Amines were used to study trigeminal innervation of the facial skin and pathways by which trigeminal inputs may be relayed to the spinal cord. Numerous nerve fibers were observed in the snout dermis, elsewhere in the head skin. Some trigeminal ganglion cells project to the upper spinal cord, but more project to the caudal medulla where they could contact secondary trigeminal neurons or reticular cells projecting to the spinal cord. These results support a significant influence of the trigeminal and the vestibular systems, but not of olfaction, on forelimb movement of neonatal opossums.

L’opossum Monodelphis domestica naît très immature et grimpe sans aide de la mère, du sinus urogénital à une mamelle où il va s’attacher pour poursuivre son développement. Des informations sensorielles sont nécessaires pour guider le nouveau-né vers la mamelle et les candidats les plus probables sont le toucher, l’équilibre et l’olfaction. Pour tester l’action des différents systèmes sur la motricité chez l’opossum nouveau-né, des régions céphaliques du trijumeau, du vestibulaire et de l’olfaction ont été stimulées électriquement sur des préparations in vitro en comparaison avec une stimulation seuil T (intensité minimale de la stimulation à la moelle épinière cervicale induisant le mouvement des membres antérieurs). Par comparaison, un mouvement similaire était induit par des stimulations à ~2T du ganglion du trijumeau, à ~20 T du complexe vestibulaire, et à ~600 T des bulbes olfactifs. L’étude de l'innervation de la peau faciale et des voies relayant les informations du trijumeau vers la moelle épinière (ME) a été approfondie en utilisant de l’immunohistochimie pour les neurofilament-200 et du traçage rétrograde avec du Texas-Red couplé à des Dextrans Aminés. De nombreuses fibres nerveuses ont été révélées dans le derme de plusieurs régions de la tête. Quelques cellules du ganglion trigéminal projettent à la ME rostrale, mais la majorité projette vers la médulla caudale où se trouvent les neurones secondaires du trijumeau ou des cellules réticulospinales. Les résultats de cette étude indiquent une influence significative des systèmes du trijumeau et du vestibulaire, mais pas de l'olfaction, sur le mouvement des membres antérieurs des opossums nouveau-nés. / The opossum Monodelphis domestica is born very immature and crawls, unaided by the mother, from the urogenital opening to a nipple where it attaches and pursues its development. Sensory information is needed to guide the newborn to a nipple and studies suggest that the vestibular, trigeminal, and olfactory systems are likely candidates. The trigeminal, vestibular and olfactory regions of the brain were electrically stimulated to test their relative effectiveness at eliciting forelimb movement in newborn opossums, using in vitro preparations of brain-spinal cord with the limbs attached. The minimal stimulation of the cervical spinal cord needed to induce forelimb movement was considered as threshold (T). Similar movement were obtained with stimulations of the trigeminal ganglion at ~2T and of the vestibular complex at ~20 T and at ~600 T for the olfactory bulb. Neurofilament-200 immunohistochemistry and retrograde tracing with Texas-Red conjugated Dextran Amines were used to study trigeminal innervation of the facial skin and pathways by which trigeminal inputs may be relayed to the spinal cord. Numerous nerve fibers were observed in the snout dermis, elsewhere in the head skin. Some trigeminal ganglion cells project to the upper spinal cord, but more project to the caudal medulla where they could contact secondary trigeminal neurons or reticular cells projecting to the spinal cord. These results support a significant influence of the trigeminal and the vestibular systems, but not of olfaction, on forelimb movement of neonatal opossums.

Objetivo: Determinar as mudanças nas ondas dos potenciais evocados auditivos de tronco encefálico (PEATE) como indicador de integridade neural em eventos de hipoxia-isquemia cerebral em crianças submetidas à cirurgia cardíaca com circulação extracorpórea (CEC). Método: Participaram deste estudo 09 pacientes pediátricos com idade entre 0 a 2 anos, submetidos à cirurgia cardíaca de alta complexidade no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. A avaliação eletrofisiológica da audição foi realizada no centro cirúrgico do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, durante os respectivos momentos da cirurgia cardíaca: Sedação, Circulação Extracorpórea (CEC) e Hipotermia, e ao Final da Cirurgia, com o registro do potencial evocado auditivo de tronco encefálico (PEATE), por meio do equipamento Nicolet Endeavor CR, conectado a um notebook, duas sondas de espuma, 4 eletrodos de agulha, posicionados na mastóide direita e esquerda, vertex craniano e fronte. Resultados: As crianças tinham média de idade de 10 meses. Dessas 9 crianças, 3 do sexo feminino e 6 do sexo masculino, a média do peso foi de 6,0 Kg, as patologias e ou propostas cirúrgicas foram: Correção de Disfunção Valvar Aórtica e Tricúspide por Valvoplastia, Correção de Drenagem Anômola Total das Veias Pulmonares, Correção de Cor Triatriatum, Operação de Glenn, Implante de Marcapasso Cardíaco Intracavitário de Dupla Câmara, Correção de Disfunção Valvar Mitral por Valvoplastia, Fechamento de Comunicação Interatrial, Fechamento de Comunicação Interventricular, Bandagem e Correção da Persistência Canal Arterial. Duas dessas crianças possuem Síndrome de Down. Foi observado quanto às latências das ondas I, III e V, e seus interpicos da orelha direita e esquerda mudanças dos valores comparadas ao início com CEC e hipotermia, assim como ao início com o final da cirurgia, porém os valores foram estatisticamente não significantes, p > 0,05. Conclusão: Não foram encontradas alterações nas latências absolutas e na latência dos intervalos interpicos do PEATE para as situações de hipotermia e circulação extracorpórea. / Objective: To determine changes in the waves of brainstem evoked response audiometry (BERA) as an indicator of neural integrity in events of brain hypoxiaischemia in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Method: 09 pediatric patients aged 0 to 2 have taken part in this study, who were submitted to highly complex cardiac surgery at Hospital das Clínicas, Medical School of Ribeirão Preto. The electrophysiological assessment of hearing was performed at the surgical center of Hospital das Clínicas of the Medical School of Ribeirão Preto, during the respective moments of the cardiac surgery: Sedation, Extracorporeal Circulation (CPB) and Hypothermia, and at the End of Surgery, by recording the brainstem auditory evoked response (BERA), using the Nicolet Endeavor CR equipment, connected to a laptop, two foam probes, four needle electrodes positioned in the right and left mastoid, cranial vertex and forehead. Results: The mean age of the children was 10 months. Out of these 9 children, 3 were female and 6 were male, and their mean weight was 6.0 kg. The pathologies and or surgical proposals were: Correction of Aortic Valve Dysfunction and Tricuspid by valvuloplasty, Correction of total anomalous pulmonary venous drainage, Color Correction Triatriatum, Glenn Procedure, Double-chambered Intracavitary Cardiac Pacemaker Implantation, Mitral Valve Dysfunction Correction, Interatrial Communication Closure, Interventricular Communication Closure, Bandaging, and Correction of Persistent Arterial Canal. Two of these children have Down Syndrome. As for the latencies of the I, III and V waves and their interpeaks of the right and left ear, it was observed changes in values compared to the onset with CPB and hypothermia, as well as to the beginning with the end of surgery, but the values were not statistically significant, p > 0.05. Conclusion: No alterations were found in the absolute latencies and in the latency of the BERA intervals for situations of hypothermia and cardiopulmonary bypass.

Schleiereulen sind gute Nachtjäger und finden ihre Beute vor allem durch den Hörsinn. Die auditorische Lokalisierung in der horizontalen Ebene basiert dabei auf interauralen Zeitdifferenzen. Diese werden im Hirnstamm durch das Netzwerk von nucleus magnocellularis (NM) und nucleus laminaris (NL) in Orte umkodiert. Im NL kann ein extrazelluläres Potential (EP), das Neurophonpotential (NP) gemessen werden. Dieses hat eine erstaunliche zeitliche Präzision von unter 10 Mikrosekunden, und spiegelt den für die Stimulation benutzten Ton bis zu Frequenzen von 9 kHz wider. Wie kann eine solche Präzision erzeugt werden, und was kann man über den Ursprung des Potentials in dieser neuronalen Struktur lernen? Um diese Fragen zu klären, studiere ich in vivo gemessene NPs. Dadurch kann in Zukunft die Verbindung von neuronaler Aktivität und EP besser verstanden werden. Hunderte neuronale Stromquellen, die alle kohärent mit einer hohen Feuerrate aktiv sind, sind nötig, um ein solches NP zu erzeugen. Dabei sind Anzahl und Stromstärke der Neuronen im NL nicht ausreichend, um das NP zu erzeugen. Der Hauptanteil der Quellen besteht aus den Signalen, die den Input des NL formen: die Ströme der Ranvierschen Schnürringe entlang der Axone aus dem NM, sowie die synaptischen Ströme zu den Dendriten von NL Neuronen. Weiterhin können NPs, die als Antwort auf monaurale Stimulierung aufgenommen wurden, linear addiert werden, um die Antwort auf binaurale Stimulation zuverlässig vorherzusagen. Leichte Abweichungen von der Vorhersage könnten damit erklärt werden, dass einzelne, sehr nah an der Elektrode befindliche Neurone nichtlinear zum NP beitragen. Im Gegensatz zu anderen bisher untersuchten neuronalen Strukturen - auch homologer Hirnregionen - spiegelt das NP der Schleiereule Eingangs- statt Ausgangssignale wider. Dieser strukturelle Unterschied könnte erklären, wieso das Schleiereulengehirn höhere Genauigkeit erreicht, als das anderer Tiere. / The barn owl is a good night hunter and mainly localizes the prey with its auditory system. The auditory localization in the horizontal plane, based on interaural time differences, depends on the auditory brainstem circuit consisting of nucleus magnocellularis (NM) and nucleus laminaris (NL). An extracellular field potential (EFP), named neurophonic, can be recorded in the NL. It has a very high temporal precision of below 10 microseconds and replays the stimulating sound up to 9 kHz. In this thesis I study how an EFP with such a precision can be generated. Furthermore, what can we learn about the system and about the origin of the neurophonic in NL from these recordings? The answers will help connecting the neural activity to the EFP also in general. Firstly, hundreds of sources, all firing with a high rate and in a highly phase-locked manner, are needed to generate the neurophonic in NL. The number of the neurons in NL and the magnitude of their output currents are not high enough to alone give rise to the neurophonic. The majority of the neural sources conveys the input from NM to NL, i.e., the currents from the nodes of Ranvier in the afferent axons from NM, and the synaptic currents to the dendrites of the NL neurons. Furthermore, the neurophonics in response to monaural stimulation sum up linearly and predict accurately the neurophonics in response to binaural stimulation. This implies that the non-linear response of the NL neurons usually cannot be detected in the neurophonic, but that there might be a minor contribution from a single NL neuron when in the immediate vicinity of the electrode. All in all, the neurophonic in the barn owl''s NL seems to reflect the inputs to the nucleus, whereas usually the output is well represented in the EFP. Even in the homologue nuclei in chick and mammals the neurophonic is thought to reflect the output instead of the input. Thus, the exceptionality of the barn owl might be needed for the high precision in its NL.

A pesquisa dos potenciais evocados auditivos de tronco encefálico (PEATE) foi indicada para os casos onde há suspeita ou presença de síndromes genéticas pelo Joint Committee on Infant Hearing em 2007. O comitê fornece as diretrizes para a detecção das perdas auditivas na infância, para as quais as síndromes são fator de risco. A alta prevalência da SD e de alterações auditivas nesta população reforça a importância da identificação das perdas auditivas até os três meses de idade, como forma de minimizar os decorrentes prejuízos na comunicação. Este estudo, aprovado pela Comissão de Ética para análise de projetos de pesquisa do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), teve como objetivo descrever as avaliações da audição de 30 crianças com SD, sem queixas otológicas, das quais 25 bebês (idade média de 2,47 meses) compuseram a amostra. Método: Foram pesquisados os PEATE durante o sono natural. A amostra foi analisada por bebês e por orelhas. Os bebês e as orelhas foram agrupados por intensidade de limiar eletrofisiológico: G1 (<= 30 dBNA), G2 (30 | 40 dBNA), G3 (> 40 dBNA) e registradas as latências absolutas I, III e V e as inter-latências I-III, III-V e I-V. Resultado: Dos 25 bebês, 3 apresentaram alteração neurossensorial ao menos unilateral (12%), 5 alteração condutiva (20%) e 17 (68%) indicaram resultados normais ao PEATE. Limiares eletrofisiológicos foram encontrados em 76% (n=38) das orelhas estavam abaixo, e em 24% (n=12), acima de 40 dBNA. Os grupos G1 e G2 apresentaram respostas equivalentes exceto para a latência absoluta da onda V e inter-latência III-V, que estiveram encurtadas no G2 em relação ao G1 (p<0,02;p=0,04) Discussão: Vários autores sugerem maior ocorrência de alterações condutivas entre portadores de SD. A prevalência de alterações auditivas condutivas e neurossensoriais encontradas nos bebês neste estudo apontam para a importância da investigação da via auditiva até os três meses de idade. Conclusão: A perda auditiva é uma alteração frequente em bebês com SD. Ocorreram alterações tanto condutivas quanto neurossensoriais nas orelhas com limiar alterado. As alterações neurossensoriais encontradas neste estudo reforçam a importância da adoção de procedimentos preventivos de avaliação da audição em bebês com SD e consequente intervenção / Introduction: The study of evoked auditory brainstem response (ABR) was indicated for cases of genetic syndromes by the Joint Committee on Infant Hearing in 2007. These guidelines indicate the detection of hearing loss in the childhood, for which genetic syndromes are a risk factor. The high prevalence of DS and of hearing disorders in this population reinforces the importance of identifying hearing loss by 3 months of age, to minimize the losses arising in communication. The main objective of this study, approved by the Ethics Committee of University of São Paulo, School of Medicine, Clinical Hospital (HCFMUSP) was to characterize the hearing ability of 30 children with Down syndrome, of which 25 babies (mean age 2.47 months), with no history of ear disease, comprised the sample. Method: ABR test has been performed during natural sleep. The babies and the ears were put together in groups by threshold level: G1 (<= 30 dB HL), G2 (30 |40 dB HL), G3 (over 40 dB HL). Results: Out of 25 babies, 3 (12%) had sensory neural hearing disorder in at least one ear; 5 (20%) had conductive hearing disorder in at least one ear and 17 (68%) had normal results on the ABR. Electrophysiological thresholds under 40 dB HL have been obtained in 76% (n = 38) of tested ears under, and in 24% (n = 12) over 40 dB HL. Groups G1 and G2 have had similar response, except for III-V interval shortened in G2 when compared to G1. Discussion: Many authors suggest conductive losses are more frequent than sensory neural losses in this population. The prevalence of sensory neural hearing disorder found in these babies point to the importance of investigating the auditory pathway. The group with thresholds between 30 and 40 dB HL was similar to the normal group, except for shortening of interval III-V. Statistically significant differences were found between normal and abnormal in the ABR. Conclusion: Sensory neural losses found in this study reinforce the importance of adopting preventive procedures for evaluating the hearing and subsequent intervention