A avaliação histopatológica de uma lesão se baseia nas alterações microscópicas predominantes no tecido, e descreve a gravidade, cronicidade, distribuição, localização, e natureza da lesão. Entretanto, no campo da Neurologia, a obtenção de amostras para avaliação histopatológica de tecidos pode causar danos irreversíveis ao paciente, o que torna extremamente importante a utilização de exames menos invasivos, como os de imagem. A Ressonância Magnética (RM) é uma ferramenta diagnóstica bastante sensível para lesões neurológicas de uma forma geral, devido ao contraste que suas imagens fornecem aos tecidos moles. Todavia, os achados histopatológicos, que são a base para um diagnóstico definitivo, não podem ser observados diretamente pelas técnicas imaginológicas. Por se tratar de uma técnica de aplicação relativamente recente, ainda é escassa a literatura que correlaciona os achados imaginológicos com os histopatológicos de lesões neurológicas. Foram incluídos neste estudo 17 animais, entre cães e gatos, que foram a óbito com sinais neurológicos e que foram submetidos a um exame por RM antemortem. O sistema nervoso central (SNC) de todos os animais foi avaliado histologicamente, e de um deles, imunoistoquimicamente. Foram diagnosticadas doenças de múltiplas naturezas: vasculares, inflamatórias, traumáticas, neoplásicas e degenerativas; e seus achados imaginológicos foram correlacionados com a histopatologia. O presente estudo demonstrou que a técnica de RM pode ser utilizada como ferramenta diagnóstica antemortem de lesões no SNC de pequenos animais em ampla diversidade de acometimentos, demonstrando o potencial da RM de antecipar o diagnóstico de lesões no SNC, permitindo intervenções mais precoces e melhorando, dessa forma, o prognóstico desses animais. / The histopathological evaluation of a lesion is based on the predominant microscopic changes in the tissue, and describes the gravity, chronicity, distribution location and nature of the lesion. Nevertheless, in the field of Neurology, obtaining samples for the histopathological evaluation of tissues can cause permanent damage to the patient, making the usage of less invasive techniques, like imaging exams, extremely important. Magnetic Resonance Imaging (MRI) is a very sensitive diagnostic tool for neurological lesions in general, given the contrast between soft tissues it provides. Despite that, histopathological findings, which are the basis for a definitive diagnosis, cannot be directly seen in imaging exams. Because of its relatively recent application, literature on the correlation between imaging and histopathological findings is still scarce. In the present study, 17 animals, among dogs and cats, which died with neurological signals and were submitted to MRI examination antemortem, were included. The central nervous system (CNS) of all animals was evaluated histologically, and one of them, immunohistochemically. Diseases of multiple natures were diagnosed: vascular, inflammatory, traumatic, neoplastic and degenerative; and their imaging features were correlated to their histopathological findings. The present study demonstrated that MRI can be used as an antemortem diagnostic tool for CNS lesions in small animals, allowing prompt interventions and improving, therefore, the prognosis for these animals.

INTRODUÇÃO: As neoplasias do sistema nervoso central são frequentes nafaixa etária pediátrica e o tratamento antineoplásico pode resultar em efeitos adversos agudos ou tardios na cavidade oral. As anormalidades dentárias de forma, tamanho e número de dentes podem ocorrer se o tratamento por radioterapia de crânio e coluna, quimioterapia ou ambas forem coincidentes com a época de formação dentária em pacientes pediátricos. A gravidade das alterações depende do tipo de tratamento e da idade do paciente ao diagnóstico. OBJETIVOS: Avaliar a frequência de anormalidades dentárias em pacientes tratados para neoplasias do sistema nervoso central. MÉTODOS: Neste estudo transversal foram avaliados 31 pacientes com diagnóstico de neoplasia do sistema nervoso central que estavam fora de terapia há pelo menos um ano, comparativamente com um grupo controle composto por 31 pacientes saudáveis, pareados por idade com o grupo de estudo. As anormalidades dentárias foram avaliadas por meio de radiografias panorâmicas. RESULTADOS: A idade média ao diagnóstico dos pacientes do grupo de estudo foi de 7,3 ± 3,9 anos e as neoplasias mais frequentemente observadas foram meduloblastoma (58,1%), astrocitoma (25,8%) e ependimoma (3,2%). Não se observou diferença na frequência de anormalidades dentárias entre os grupos. As anormalidades mais frequentemente observadas nos pacientes do grupo de estudo foram microdontia (9,7%) e encurtamento radicular grau III (16,1%). Microdontia foi mais frequente em crianças que tiveram o diagnóstico antes dos 5 anos de idade, com diferença significante. Encurtamento radicular grau III foi observado em pacientes com mais de 10 anos de idade no momento do exame radiográfico, também com diferença significante. Pacientes tratados por radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias, comparativamente com pacientes tratados somente por radioterapia ou quimioterapia isoladamente. Microdontia apresentou alta correlação com os dentes segundos premolares e segundos molares em pacientes tratados para neoplasias do sistema nervoso central. CONCLUSÕES: Pacientes tratados para neoplasias do sistema nervoso central apresentam alta frequência de anormalidades dentárias, porém neste estudo não houve diferença entre os grupos de estudo e controle. Microdontia foi a anormalidade dentária mais frequente em pacientes submetidos ao tratamento antineoplásico antes dos 5 anos de idade, com significância estatística. Encurtamento radicular grau III foi observado nos pacientes com mais de 10 anos de idade no momento do exame radiográfico, com diferença estatisticamente significante. Pacientes submetidos à radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias / INTRODUCTION: Central nervous system neoplasms are frequent in pediatric patients and antineoplastic treatment may result in acute or late adverse effects in the oral cavity. Tooth abnormalities of shape, size and number of teeth can occur if craniospinal irradiation, drug therapy or both are coincident with the time of tooth development. Severity of these alterations depends on the type of treatment and the patient´s age at diagnosis. OBJECTIVES: To evaluate the frequency of tooth abnormalities in pediatric patients treated for central nervous system neoplasms. METHODS: This cross-sectional study assessed 31 patients with central nervous system neoplasms, who were off therapy for at least one year, comparatively with a control group of 31 healthy patients matched for age with the study group. Tooth abnormalities were evaluated by panoramic radiographs. RESULTS: Study group´s mean age at diagnosis was 7.3 ± 3.9 years and the most frequent neoplasms were medulloblastoma (58.1%), astrocytoma (25.8%) and ependyoma (3.2%). There was no difference in the frequency of tooth abnormalities between groups. The most frequently tooth abnormalities observed in the study group were microdontia (9.7%) and root shortening grade III (16.1%). Microdontia was the most common abnormality in children who were diagnosed before 5 years of age, with a significant difference. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, also with a significant difference. Patients treated with craniospinal irradiation combined with drug therapy presented more frequency of tooth abnormalities compared with patients treated only by craniospinal irradiation or drug therapy alone. Microdontia was highly correlated with the teeth second premolars and second molars. CONCLUSIONS: Patients treated for central nervous system neoplasms present high frequency of tooth abnormalities; however in this study there was no difference between study and control groups. Microdontia was the most frequent tooth abnormality in patients submitted to antineoplastic treatment before 5 years of age, with statistical significance. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, with statistically significant difference. Patients undergoing craniospinal irradiation combined with drug therapy showed high frequency of tooth abnormalities

A família de Siluriformes Neotropicais Cetopsidae possui cinco gêneros e 43 espécies válidas, com ampla distribuição nas regiões norte e central da América do Sul, tanto cis- como trans-andina. Cetopsidae é proposta como um grupo monofilético, suportado pela maioria dos estudos morfológicos e moleculares. Os estudos evolutivos sobre o sistema nervoso de bagres neotropicais são bastante escassos, apesar desse complexo apresentarimportantes modificações potencialmente informativas para estudos de inferência filogenética. Para testar a significância dos caracteres neuroanatômicos em filogenias, a morfologia externa das principais subdivisões encefálicas de Cetopsidae foi descrita, ilustrada e interpretada. Além disso, análises comparativas do desenvolvimento desse complexo foram realizadas em Helogenes marmoratus e Cetopsis gobioides com o intuito de estabelecer homologias e compreender suas modificações ontogenéticas. Os caracteres foram delimitados e testados separadamente em análises filogenéticas e posteriormente combinados com caracteres morfológicos e moleculares com diferentes métodos de análise. Para determinar o volume de cada região analisada, um modelo elipsoide foi utilizado. Amplas comparações baseadas no formato, posição relativa e volume das principais regiões encefálicas são apresentadas para a maioria das espécies representativas de todos os gêneros de Cetopsidae. As mesmas comparações também foram realizadas ao longo do desenvolvimento de Helogenes marmoratus e Cetopsis gobioides. Além disso, comparações com integrantes de outras famílias filogeneticamente relacionadas em Siluriformes forneceram um amplo contexto para um maior entendimento das principais modificações evolutivas que moldaram o encéfalo doscetopsídeos. Análises filogenéticas de todos os caracteres morfológicos foram primeiramente conduzidas em separado, e posteriormente em matrizes concatenadas sob o critério da Parcimônia. Análises Bayesianas com sequências alinhadas e concatenadas de três genes mitocondriais (COI, 16S e Cytb) foram implementadas. Por fim, análises filogenéticas com todos os dados combinados foram conduzidas sob os critérios da Parcimônia e Bayesiano. Padrões morfológicos distintos foram definidos para cada uma das duas principais subdivisões de Cetopsidae, as subfamílias Helogeninae e Cetopsinae. Poucas variações intraespecíficas na morfologia externa do encéfalo xii existem entre todas as espécies examinadas aqui. As modificações observadas ao longo do desenvolvimento do encéfalo de Helogenes marmoratus e Cetopsis gobioides foram utilizadas para a formulação correta de caracteres e seus estados. Todos os gêneros foram recuperados como grupos monofiléticos pelos caracteres neuroanatômicos.Mapeamentos filogenéticos revelaram alguns padrões morfológicos sugestivos com especializações alimentares e outras características de história de vida correlacionadas ao sistema nervoso central. Os caracteres morfológicos e moleculares se mostraram bastante congruentes nas hipóteses filogenéticas, comas incongruências restritas à tribo Cetopsini. Todas as análises recuperaram Helogeninae como grupo-irmão dos demais cetopsídeos, seguido por Cetopsidiini, Denticetopsini e Cetopsini como grupos-irmãos sucessivos.Os resultados obtidos no presente estudo suportam a ideia de que análises amplas e concatenadas de dados morfológicos e moleculares resultam em hipóteses de relacionamentos robustas e bem suportadas. Os caracteres neuroanatômicos são altamente informativos para inferências filogenéticas, que podem ser exploradospara uma maior compreensão da evolução de Otophysi. / The Neotropical South American catfish Cetopsidae is a family of Siluriformes that includes five genera and 43valid species distributed over a large portion of northern and central regions of South America, on both sides of the Andean cordilleras. The monophyly of the family is supported by several previous studies, based on both morphological and molecular characters. Despite the scarcity of evolutionary studies on the nervous system of neotropical catfishes, that complex shows great variation potentially informative for phylogenetic inference. In order to test the significance of neurological traits in a phylogenetic framework, the gross morphology of brain subdivisions in the catfish family Cetopsidae is described, illustrated and interpreted. In addition, comparative analyzes of the development of this complex were carried out in Helogenes marmoratus and Cetopsis gobioidesin order to establish homologies and ontogenetic transformations. Characters were delimited and tested separately in phylogenetic analyzes and later combined with other morphological and molecular characters with different methods of analysis. The volume of major brain subdivision was calculated by an ellipsoid model. A comprehensive comparison based on shape, relative position, and volume of the main brain subdivisions is presented for representative species of all genera and most available species in the family. The same comparisons were also made throughout the development of Helogenes marmoratus and Cetopsis gobioides. Comparisons with other phylogenetically related siluriform families provide a broader context for the understanding of the main evolutionary transformations which shaped the cetopsid brain. Phylogenetic analyzes of all morphological characters were first conducted separately, and later in matrices concatenated under the Parsimony criterion. Bayesian analyzes of three aligned and concatenated mitochondrial gene sequences (COI, 16S and Cytb) were implemented. Analyzes of all the data combined were conducted under both Parsimony and Bayesian criteria. Profoundly distinct morphological patterns are identified for each of the two main cetopsid subdivisions, subfamilies Helogeninae and Cetopsinae. Little intraspecific variation on major subdivisions of the brain exists in species examined herein. The modifications observed throughout the development of the brain inHelogenes marmoratus and Cetopsis gobioides were used for the correct delimitation xiv of characters and their states. The monophyly of all genera is supported by putative neuroanatomic characters. Phylogenetic mapping reveals recurrent morphological patterns suggestive of an association with specific feeding specializations and other life-history traits. Morphological and molecular characters were highly congruent in phylogenetic hypotheses, with inconsistencies restricted to the tribe Cetopsini. All analyzes recovered Helogeninae as thesister group toall remaining cetopsids, followed by Cetopsidiini, Denticetopsini and Cetopsini as successive sister groups. Results of the present study support the idea that large and concatenated analyzes of morphological and molecular characters result in robust well-supported hypotheses of relationships. Neuroanatomical characters are highly informative for phylogenetic inferenceand area promising field to be explored in understanding the evolution of Otophysi.

Introdução: A microcefalia é um sinal clínico associado à heterogeneidade etiológica. As principais causas de microcefalia são as infecções congênitas e as anomalias congênitas. Em 2015, após o surto do zika vírus (ZIKV) e o aumento de casos de microcefalia, o Ministério da Saúde (MS) instituiu notificação compulsória para os recém-nascidos (RN) com microcefalia e/ou alterações do Sistema Nervoso Central (SNC). No Brasil, a distribuição geográfica do ZIKV ocorreu de maneira diferenciada nas regiões norte e sul, sendo que no extremo sul do país houve um menor número de infecções por esse vírus. Assim, o estado do Rio Grande do Sul (RS) tornou-se um local importante para a avaliação sistemática das causas de microcefalia neste país, independente da presença de transmissão continuada do ZIKV. Objetivos: Avaliar e descrever as causas de microcefalia dos RN notificados por microcefalia e/ou alterações do SNC no RS. Métodos: Estudo descritivo dos 162 RN com microcefalia notificada no período de dezembro de 2015 a dezembro de 2016. Destes, 99 casos foram avaliados de forma retrospectiva com base em revisão de banco de dados, e 63 casos foram avaliados de forma prospectiva em ambulatório específico do HCPA-Brasil. As etapas propostas para a avaliação (ou informações coletadas dos bancos de dados) foram: 1) histórico da gestante; 2) exame físico do RN; 3) exames para pesquisa de infecção congênita – toxoplasmose, rubéola, ZIKV e CMV (reação de cadeia da polimerase - PCR ou sorológicos); 4) exames de imagem do SNC; 5) avaliação genética (para os casos com história familiar ou suspeita de alteração genética). As crianças foram avaliadas do nascimento até conclusão diagnóstica, seguimento perdido ou término do estudo. O período de avaliação das crianças não foi superior a quatro meses. Resultados: Noventa e cinco casos (58,6%) apresentavam microcefalia grave, resultando em uma prevalência desta complicação ao nascimento de 6.5/10.000 RN. A causa foi definida em 73 dos 162 casos. Destes eram infecções congênitas 31 casos (19.3%), síndromes genéticas 19 casos (11.7%), e malformação isolada do sistema nervoso central 20 casos (12,4%). E a causa não foi identificada em 89 (54,9%). Dos 31 casos com infecções congênitas, três (9.7%) foram diagnosticados com ZIKV, seis (19.3%) com citomegalovírus, oito (25,8%) com toxoplasmose, e 14 (45.2%) com sífilis congênita. Nenhum caso de rubeola congênita foi diagnosticado e a imunidade adquirida para rubeola das mães dos RN notificados foi de 91.6%. Destes casos 14 (45.1%) apresentaram baixo peso ao nascer e 21 (66.7%) eram pequenos para idade gestacional. A microcefalia grave foi identificada em 12 (38.7%) e 6 59.2% dos casos apresentaram alterações cerebrais, o que reforça a gravidade da ação das doenças infecciosas. Conclusão: Este é o primeiro estudo a avaliar os casos de microcefalia e/ou alterações do SNC durante o surto de ZIKV no RS. A prevalência de casos de ZIKV no RS foi inferior a estados do Nordeste do Brasil. A maioria dos casos de infecção congênita apresentaram lesões neurológicas graves, principalmente os casos de ZIKV, o que pode ocasionar atraso no desenvolvimento neurológico e sequelas nestas crianças ao longo da primeira infância. No entanto, salientamos a importância das demais infecções congênitas e causas desconhecidas associadas à microcefalia no RS, independente da presença de ZIKV. / Introduction: Microcephaly is a clinical sign associated with etiological heterogeneity. The main causes of microcephaly are congenital infections and congenital anomalies. The Ministry of Health (MOH) has instituted compulsory notification for newborns with microcephaly and / or Central Nervous System (CNS) disorders in 2015, following the zika virus (ZIKV) outbreak and the increase in cases of microcephaly. In Brazil, the geographical distribution of ZIKV occurred in a differentiated way in the northern and southern regions, and in the southernmost part of the country there were fewer infections due to this virus. Thus, the state of Rio Grande do Sul (RS) has become an important site for the systematic evaluation of the causes of microcephaly in this country, regardless of the presence of continuous transmission of ZIKV. Objectives: To evaluate and describe the causes of microcephaly of newborns notified by microcephaly and / or CNS changes in RS. Methods: Descriptive study of the 162 newborns with microcephaly reported from December 2015 to December 2016. Of these, 99 cases were retrospectively evaluated based on a database review, and 63 cases were evaluated prospectively in an outpatient clinic specific to HCPA-Brazil. The proposed steps for the evaluation (or information collected from the databases) were: 1) history of the pregnant woman; 2) physical examination of the newborn; 3) screening tests for congenital infection - toxoplasmosis, rubella, ZIKV and CMV (polymerase chain reaction - PCR or serological); 4) imaging studies of the CNS; 5) genetic evaluation (for cases with family history or suspected genetic alteration). The children were evaluated from birth to completion of diagnosis, missed follow-up or termination of the study. The evaluation of them was not more than four months. Results: Ninety-five cases (58.6%) presented severe microcephaly, resulting in a prevalence of this complication at birth of 6.5 / 10,000 newborn. A definite cause was established in 73 of the 162 causes. The leading etiology was congenital infections in 31 cases (19.3%), genetic syndromes in 19 cases (11.7%), and isolated central nervous system malformation in 20 cases (12.4%). Of the 31 cases with congenital infections, three (9.7%) were diagnosed with ZIKV, six (19.3%) with cytomegalovirus, eight (25.8%) with toxoplasmosis, and 14 (45.2%) with congenital syphilis. No case of congenital rubella was diagnosed and the acquired immunity to rubella from the mothers of the newborns was 91.6%. Of these, 14 (45.1%) had low birth 8 weight and 21 (66.7%) were small for gestational age. Severe microcephaly was identified in 12 (38.7%) and 59.2% of the cases presented cerebral alterations, which reinforces the severity of the action of infectious diseases. Conclusion: This is the first study to assess the cases of microcephaly and / or CNS changes during the outbreak of ZIKV in RS. The prevalence of ZIKV cases in RS was lower than in the northeastern states of Brazil. Most cases of congenital infection have severe neurological lesions, especially cases of ZIKV, which can cause delay in neurological development and detectable sequelae in these children throughout their first infancy. However, we emphasize the importance of other congenital infections and unknown causes associated with microcephaly in RS, regardless of the presence of ZIKV.

OBJETIVO: Pacientes com distrofia muscular de Duchenne apresentam alterações neuronais em regiões do sistema nervoso central como no giro pós-central e cerebelo. Para entender a sua influência sobre o controle motor, nós investigamos a somestesia e destreza manual, com e sem a informação visual. MÉTODO: Participaram deste estudo quarenta meninos com diagnóstico confirmado de distofia muscular de Duchenne (idade média = 9,68; DP = 2,23 anos), sem comprometimento dos membros superiores, e quarenta e nove meninos saudáveis (idade média = 8,14 anos; DP = 1,94 anos). Para avaliar a somestesia foi utilizado o teste de discriminação entre dois pontos e o teste de estereognosia, e para avaliar a destreza manual, foi utlilizado o Pick up test de Moberg com olhos abertos e olhos fechados e o teste do erro de localização. Os resultados foram submetidos pela análise de variância (ANOVA), sendo considerado estatisticamente significante p<0,05. RESULTADOS: Os resultados demonstraram que em meninos com distrofia muscular de Duchenne, a estereognosia estava comprometida em ambas as mãos (p<0,001), no entanto não houve diferença significativa no teste de discriminação entre dois pontos (p=0,313) quando comparado aos meninos saudáveis. A destreza manual estava pior nos meninos com distrofia muscular de Duchenne quando dependia de informações somestésicas, ou seja, no Pick up test de Moberg de olhos fechados e no teste do erro de localização (p<0,001). INTERPRETAÇÃO: Os resultados demonstraram que a discriminação tátil estava intacta em meninos com distrofia muscular de Duchenne, sugerindo que a via sensorial não está prejudicada. Ao contrário, tarefas que envolviam a função cerebelar, ou seja, a percepção sensorial durante o reconhecimento ativo do objeto e o controle de alcançar e agarrar, estavam prejudicadas. Abordagens terapêuticas específicas devem ser delineadas para melhorar o controle motor e, portanto, a funcionalide de pessoas com distrofia muscular de Duchenne / AIM: Neuronal alterations were reported in the postcentral gyrus and cerebellum of patients with Duchenne muscular dystrophy. To understand their influence over motor control, we investigated somesthesis and manual dexterity, with and without visual information. METHOD: Forty boys with Duchenne muscular dystrophy (mean age = 9.68; SD = 2.23 years), with no upper limb dysfunction, and 49 healthy boys (mean age = 8.14; SD = 1.94 years) participated in the study. To assess somesthesis we used the twopoint discrimination test and the six-object stereognosis test, and to assess manual dexterity, the Moberg Pick up test with the eyes opened and closed and the localization error test. The results were submitted to ANOVA, considering statistically significant a value of p<0.05. RESULTS: Boys with Duchenne muscular dystrophy had impaired stereognosis with both hands (p<0.001), but two-point discrimination did not differ between the groups (p=0.313). Manual dexterity was much worse in Duchenne muscular dystrophy boys when somesthesic information was necessary, i.e., during the Pick up test with the eyes closed and the localization error test (p<0.0001). INTERPRETATION: Tactile discrimination is intact in children with Duchenne muscular dystrophy, suggesting that the somatic pathway may not be impaired. Unlike, tasks involving cerebellar function, i.e., sensory perception during active object recognition and reach and grasp control, are impaired. Specific therapies should be delineated to improve motor control, and therefore functionality, of people with Duchenne muscular dystrophy

Diversos estudos demonstram que o aumento da osmolaridade é capaz de causar simpatoexcitação e aumento da pressão arterial, estando o núcleo paraventricular do hipotálamo (PVN) envolvido em tal resposta. Evidências recentes demonstraram um papel da VP modulando a atividade de neurônios do PVN envolvidos com o controle da atividade simpática. Deste modo, o objetivo deste estudo foi investigar o papel da vasopressina, por meio de sua ação no PVN, sobre as alterações na atividade simpática em situações de hiperosmolaridade. Nossos resultados demonstraram que a VP microinjetada bilateralmente no PVN foi capaz de promover um aumento significativo NA ansl. O antagonismo bilateral dos receptores V1a no PVN em animais submetidos à sobrecarga de sal promoveu uma queda significativa na ANSL, a qual não foi observada em animais normohidratados. O conjunto dos resultados nos permite afirmar que a VP agindo diretamente em neurônios do PVN é capaz de alterar a atividade simpática, participando da resposta simpatoexcitatória observada durante aumento da osmolaridade. / Diverse studies demonstrated that osmorality increase is able of causing simpatoexcitação and increase in arterial pressure, with paraventricular hypothalamic nucleus (PVN) involved in this response. Studies showed an role of VP modulating the activity of neurons in the PVN involved in the control of sympathetic activity. In this way, the aim of this study was to investigate the role of the vasopressina, through it\'s action in the PVN, over the alterations in the sympathetic activity induced by hiperosmolality.The results showed that bilateral microinjection of VP into the PVN is able of increase significatively the lumbar sympathetic nerve activity. Moreover, the bilateral block of the V1a receptors into PVN of animals subjected to osmotic stimulus showed a decrease in sympathetic activity not observed in normohydrated animals. Overall, the results allow to assert that the centrally released VP plays an important role in the development of the simpatoexcitation raised by increased osmolarity, through an action on the PVN neurons.

Afin de poursuivre une cible en mouvement, le système nerveux central (SNC) utilise deux types de mouvements oculaires: la poursuite et les saccades. Les saccades sont des mouvements rapides et brefs de redirection de l’axe visuel d’un centre d’intérêt à un autre. La poursuite est un mouvement lent qui tend à maintenir la cible d’intérêt sur la fovéa. La vitesse de l’œil étant toujours inférieure à celle de la cible, une erreur positionnelle entre l’œil et la cible va croître en l’absence de mouvement correctif. Des saccades de rattrapage sont déclenchées par le SNC pour corriger cette erreur. Alors qu’il est largement reconnu que le système de la poursuite utilise un modèle interne du mouvement de la cible pour améliorer ses capacités, la modalité de contrôle de l’amplitude des saccades de rattrapage est sujette à controverse quant au rôle direct d’afférences sensorielles ou d’un modèle interne de la cible en mouvement. Nous avons développé un nouveau paradigme de transition de poursuite oculaire appliqué à l’Homme sain, dans lequel la cible change de manière imprévisible d’un profil de vitesse non constant périodique à un profil de vitesse non constant apériodique. Nos résultats confirment que le SNC utilise un modèle interne de la cible en mouvement pour contrôler l’amplitude des saccades de rattrapage. Ce modèle se construit progressivement à partir de 168 millisecondes après le changement de profil de vitesse et est utilisé conjointement par les systèmes de la poursuite et saccadique. Le substrat neuronal potentiel de ce modèle interne sera discuté à la lumière des connaissances issues de la littérature concernant le contrôle moteur et oculomoteur. / Two types of eye movements are combined while tracking a moving object: smooth pursuit and saccades. Saccades are rapid redirections of the visual axis between two centers of interest. Because pursuit gain is smaller than one, the eye would increasingly lag behind the target without any correcting movements. Thus, “catch-up saccades” are triggered by the central nervous system (CNS) to cancel this growing position error between the eye and the target. It is widely accepted that an internal model of target motion is used by the CNS to cancel inherent delays between visual input and smooth pursuit motor output, ensuring accurate tracking of moving targets. The amplitude of catch-up saccades triggered during smooth pursuit could be corrected by a delayed sensory signal to account for the ongoing target displacement during catch-up saccades. Yet, recent studies suggested that the correction of catch-up saccade amplitude must also be done through an internal model of target motion. We developed a new paradigm in which the target switches unexpectedly from one target with a non-constant periodic velocity profile to another with a non-constant aperiodic velocity profile. Our results in healthy humans confirm that the CNS uses an internal model of target motion to correct catch-up saccade amplitude. Internal model is being built gradually from 168 ms after the target switch. We show that a common internal model of target motion is shared within the CNS to control smooth pursuit and to correct catch-up saccade amplitude. The potential neuronal substrate of such an internal model will be discussed in the light of the knowledge from the literature on motor and oculomotor control.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) with characteristic multifocal lesions or ‘ plaques’ of demyelination mainly in the white matter of the brain ( involving cerebral cortex, cerebellar, brain stem and spinal cord). These MS plaques vary in size and shape, and are composed of infiltrates of lymphocytes and macrophages - which contain myelin debris. CD8 T cells are more prevalent in CNS lesions and display oligoclonal expansion. However, their role in disease remains unclear with studies showing both protective and pathogenic roles for myelin-specific CD8 T cells in the experimental autoimmune encephalomyelitis (EAE) model. Our studies have demonstrated a disease-suppressive function for CNS-specific CD8 T cells in a model where the antigen is exogenously administered in vivo and used for in vitro CD8 activation. My studies focus on probing the nature of the CD8 response elicited by endogenously presented myelin antigens in vivo utilizing a novel approach, infection with Listeria monocytogenes (LM) encoding for myelin proteolipid protein peptide PLP178-191 (LM-PLP). I show that LM-PLP infection preferentially induces PLP-specific CD8, but not CD4, T cell responses. Despite this, infection does not result in autoimmunity. In fact, routinely induced EAE is significantly ameliorated in LM-PLP-infected mice, compared to controls. Disease suppression is dependent on the presence of CD8 T cells, and the effector molecules IFN-g and perforin. CNS T cell infiltration and inflammatory responses are reduced in LM-PLP-protected mice, and CD4 T cells from LM-PLP-protected mice are less inflammatory than those from controls. Importantly, infection with LM-PLP ameliorates already established disease. My studies indicate that myelin-specific CD8 T cells induced by endogenous presentation of antigen attenuate CNS autoimmunity in multiple mouse models of EAE, implicating the potential of this approach as a novel immunotherapeutic strategy.

It has been a widely accepted belief in scientific and public discourse at the end of the twentieth century that cannibalism was the principal means of transmission of the disease call 'Kuru'.The study argues that other explanations might have been excluded from consideration, in particular, iatrogenic transmission.Circumstantial evidence in support of this proposition is examined.The work begins with an examination of the relationship between a number of diseases including, X disease, poliomyelitis, louping ill, scrapie and kuru through the first half of the twentieth century. Major themes of the work revolve around the boundary between research on animal and human disease, the complexities of research in this area, and the different messages that exist simultaneously in three domains: scientific research and publications, government and institutional archives, and the public domain. The thesis argues that the circumstantial evidence presented needs to be considered seriously and that further research in the area is required before we can come to a reliable understanding of the factors involved in the transmission of kuru / Doctor of Philosophy (PhD)

Master of Veterinary Clinical Studies / Summary Canine Neural Angiostrongyliasis (CNA) is caused by the obligatory neural migration of Angiostrongylus cantonensis larvae in dogs. Characteristically, cases are juvenile dogs with progressive CNS dysfunction characterised by hyperaesthesia and often associated with eosinophilic pleocytosis of the CSF. In Australia, most cases occur between March and June. The rat lungworm, A cantonensis was first described by Chen in 1935 in Canton, China. While initially called Pulmonema cantonensis the parasite was later reclassified as A cantonensis. A disease diagnosed as eosinophilic meningoencephalitis was first described in 1944 in Taiwan. The same disease was reported in 1948 in the East Caroline Islands but it was not until 1961 that A cantonensis was confirmed as the aetiological agent when a patient in a Hawaiian mental institution, who had died of eosinophilic meningoencephalitis, had A cantonensis larvae recovered from the brain and spinal cord. The first reports of animals infected with A cantonensis were made by Mason in 1976 when he described a syndrome occurring in puppies in the Brisbane area, characterised by urinary incontinence, hind limb paresis and hyperaesthesia, often associated with eosinophilic pleocytosis of the CSF. Reports of infection in other species followed including macropods, bats, horses, primates and birds. Twenty-two cases of suspected CNA were collected prospectively to compare with those previously described, including 37 cases published by Mason in 1983, and to examine the accuracy of an ELISA used to diagnose human neural angiostrongyliasis in Australia. Samples were collected from two control populations in an attempt to validate the ELISA results. In the prospective series of cases, there was a significantly older subpopulation of dogs in addition to “classical” young dogs, suggesting that this syndrome can occur at any age and should be considered a differential in any dog with progressive neurological disease. The mortality rate in the prospective group was lower than in the published group, which is a reflection of the severity of the disease in younger animals as is the case with human patients. Definitive diagnosis of neural angiostrongyliasis in human patients has been achieved by identifying A cantonensis larvae within the CSF or aqueous humour. In dogs, the only definitive way to diagnose CNA has been via necropsy. While many cases of CNA are characteristic and presumptive diagnosis can be made based on typical history, signalment, clinical signs, CSF analysis and response to glucocorticoids, there appear to be an increasing number of cases occurring in older dogs, that displaying focal, atypical clinical signs or that develop permanent sequelae. Serology has been a useful tool in diagnosing neural angiostrongyliasis in humans. In its current form the ELISA is not sensitive or specific enough to allow a definitive diagnosis of CNA to be made using serum but is useful when applied to CSF specimens. Further refinement of the antigen or using monoclonal rather than polyclonal antibodies may improve the accuracy of the serology. Alternatively, methods such as Western Blot, Immuno-PCR or dot-blot ELISA, which have been successfully used to diagnoses angiostrongyliasis in humans, may be worthy of investigation The major differential diagnosis for CNA is neosporosis. Other differential diagnoses include idiopathic eosinophilic meningoencephalitis, parasitic infections including Toxoplasma gondii, Taenia solium, Gnathostoma spinigerum, visceral larval migrans (Toxocara canis) and schistosomiasis, fungal, bacterial, viral and rickettsial infections as well as neoplasia, trauma, drug reactions and toxicities. Treatment of CNA has been limited to glucocorticoids, however there may be adjunct therapies including anthelmintices, cyclosporine, and matrix metalloproteinase inhibitors. In Mason’s series of cases the use of anthelmintics significantly worsened the clinical outcome for patients. It does not appear, however, that the use of these agents in species other than the dog exacerbates clinical signs. Acquired immunity is short lived in rats and mice, which would suggest the same is true in dogs. Routine heartworm and intestinal parasite prophylaxis appears to have no influence on the occurrence of CNA.