Academic literature on the topic 'Child neurology'

The first African Child Neurology Association meeting identified key challenges that the continent faces to improve the health of children with neurology disorders. The capacity to diagnose common neurologic conditions and rare disorders is lacking. The burden of neurologic disease on the continent is not known, and this lack of knowledge limits the ability to lobby for better health care provision. Inability to practice in resource-limited settings has led to the migration of skilled professionals away from Africa. Referral systems from primary to tertiary are often unpredictable and chaotic. There is a lack of access to reliable supplies of basic neurology treatments such as antiepileptic drugs. Few countries have nationally accepted guidelines either for the management of epilepsy or status epilepticus. There is a great need to develop better training capacity across Africa in the recognition and management of neurologic conditions in children, from primary health care to the subspecialist level.

The aim of this study was to evaluate whether the current state of child neurology education during pediatric residency provides adequate preparation for pediatric practice. A survey was sent to recent graduates from 3 pediatric residency programs to assess graduate experience, perceived level of competence, and desire for further education in child neurology. Responses from generalists versus subspecialists were compared. The response rate was 32%, half in general pediatric practice. Only 22% feel very confident in approaching patients with neurologic problems. This may represent the best-case scenario as graduates from these programs had required neurology experiences, whereas review of Accreditation Council of Graduate Medical Education–accredited residency curricula revealed that the majority of residencies do not. Pediatric neurologic problems are common, and pediatric residency graduates do encounter such problems in practice. The majority of pediatricians report some degree of confidence; however, some clear areas for improvement are apparent.

Background: Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present with many disabling neurological symptoms, the most common being seizures. Although it is a chronic systemic syndrome, healthcare utilization and long-term outcome of subjects with TSC are not well defined. The goal of this study was to evaluate the direct cost and long-term outcome of TSC compared to other forms of epilepsy and healthy controls. Methods: Our provincial health care database was interrogated to determine use of medical services by patients with TSC, epilepsy and healthy controls from 1996-2011. Data on demographics, outcomes and health care utilization were analyzed. Results: 1004 TSC, 41,934 with epilepsy and 41,934 controls were identified. The prevalence of TSC was 1/7,872 compared to 1/189 for epilepsy. TSC experienced more hospitalizations, medical visits and prescription drug use, resulting in higher total health care costs. Their most common admission diagnosis was seizures and age at death was significantly lower: 61,3 years old for TSC vs 69,6 and 76,6 years old for epilepsy and controls, (p<0,001). Conclusions: TSC subjects have a significantly higher burden of disease than other subjects with epilepsy. These results stress the need for specialized services in this population through the lifespan.

Ion channels are macromolecular proteins in cell membranes that control the passage of charged particles including sodium, potassium and calcium ions in and out of cells. Rapid electrical signalling in the nervous system is mediated through the passage of ions through these channels. It is therefore not surprising that genetic mutations in the genes coding for these channels can result in neurological disease. Ion channel disorders or channelopathies have emerged in the last ten to fifteen years as an important new way of understanding neurological disease. Many of these conditions are paroxysmal in nature and include generalised and focal epilepsies, movement disorders and neuromuscular disorders. Some of these conditions follow simple Mendelian inheritance and are rare forms of common disorders such as epilepsy but they provide a useful model for more common neurological diseases with complex inheritance. Some conditions such as Dravet syndrome, a severe infantile onset epilepsy and sodium channelopathy produce devastating consequences for the affected child. In this thesis I will describe the clinical work I have undertaken defining phenotypes of this emerging group of disorders. Detailed phenotyping is the first essential step in characterising new aspects of these genetic disorders. I have collaborated closely with molecular geneticists and cell physiologists in units around the world exchanging ideas in order to better understand the mechanisms of disease and hopefully translate this into better care for patients. The main themes covered in the thesis are episodic ataxias type 1 and 2 (EA1 & 2), benign familial neonatal convulsions, autosomal dominant nocturnal frontal lobe epilepsy, and Dravet syndrome and other SCN1A related epileptic encephalopathies. In the course of this work I have described novel relationships between EA1 and EA2 and epilepsy, described a novel gene and phenotypes associated with frontal lobe epilepsy, a novel presentation of a potassium channelopathy, a family with a new genetic mechanism for their neonatal convulsions and epilepsy, and children with a novel mechanism for Startle disease (hyperekplexia). I have demonstrated the clinical utility of this translational research by establishing a molecular genetic diagnostic service for sodium channel (SCN1A) related infantile epilepsies. A study of the results from this national UK service shows that genetic diagnosis allows early diagnosis of these epilepsies. This can result in earlier focused treatment, and the hope for better epilepsy control and developmental outcome. I discuss the implications of this work and ongoing and future research projects.

Individuals afflicted with childhood and adolescent mental disorders have an increased risk for poor outcome in adulthood. The progression of psychopathology from childhood to adult life may be influenced by a multitude of interacting variables, both biological and psychosocial. There is limited information on the relationships between child psychopathology and adult personality and personality disorders. The main aim of this thesis was therefore to gain better knowledge concerning adult personality outcome in patients with early onset of mental disorders.

Former child psychiatric patients as compared to controls had a significantly higher prevalence of all DSM-IV personality disorders (38.0 vs. 10.9 percent, p<0.001) and also a considerably higher personality disorder co-morbidity. They also had more psychosocial and environmental problems. This was exaggerated in those diagnosed with a personality disorder. Major depression, disruptive disorders and substance use disorders at a young age were strong predictors for adult personality disorder.

Patients with an early onset major depression had more personality disorders and more deviant personality traits than those with a late onset.

Forensic psychiatric male patients diagnosed with a previous conduct disorder as compared to those without had more cluster B personality disorders, and more repeated violent criminality and mixed abuse. They also exhibited more deviant personality traits and higher psychopathy scores.

The instrument "Child and Adolescent Psychiatric Screening Inventory-Retrospect" had acceptable sensitivity and specificity for assessment of child psychiatric disorders. Subscales demonstrated good internal reliability (Crohnbach´s alpha = 0.76-0.93).

The results suggest that adult personality disturbances are prevalent in individuals affected with mental problems at young ages. A better understanding of the transition of psychopathology from childhood to adulthood and a better identification of those at risk will be of help in attempts to prevent permanent impact on the adult personality.

L’àrea de treball de la present tesi doctoral se situa en el context de les malalties genètiques del metabolisme energètic mitocondrial. Són malalties rares i hereditàries que afecten al conjunt de sistemes que fa servir l’organisme per incorporar i transformar els substrats en energia utilitzable per al correcte funcionament cel·lular. El coenzim Q10 és un component lipídic de totes les membranes cel·lulars que realitza un paper essencial a la cadena respiratòria mitocondrial, però també participa en moltes altres funcions cel·lulars, tan dins dels mitocondris com fora. En l’àmbit pediàtric, la deficiència de coenzim Q10 s’associa a estats de malaltia amb expressions fenotípiques heterogènies, i les causes que la expliquen poden ser primàries o bé secundàries (és a dir, per alteració dels gens implicats en la via de síntesi d’aquesta molècula –deficiència primària–, o per alteració d’altres gens no directament relacionats en la via biosintètica del coenzim Q10 –deficiència secundària). Aquesta deficiència bioquímica implica una disfunció del sistema de la fosforilació oxidativa mitocondrial, i normalment es manifesta de forma multiorgànica, alterant en major o menor grau els diferents òrgans, segons els nivells energètics que requereixen els teixits i d’altres factors no massa coneguts. L’objectiu principal d’aquesta tesi ha estat la millora del diagnòstic de pacients amb deficiències de coenzim Q10, a través de l’estudi sistemàtic d’aquest en diverses espècimens biològics i en associació amb dades clíniques, bioquímiques, histoquímiques, enzimàtiques i moleculars. A través de l’estudi i valoració de grans grups de pacients, s’ha pogut intuir la dinàmica d’aquesta molècula en certs tipus de malalties. Hem pogut descriure tres malalties que s’associen a una deficiència de coenzim Q10 de forma secundària, permetent que pacients afectats puguin beneficiar-se de la suplementació oral amb coenzim Q10, la qual ha demostrat millores clíniques de l’estat de pacients afectats amb patologies mitocondrials. També, hem realitzat avenços metodològics i tècnics, a nivell bioquímic i d’anàlisi de dades, que permetran abordar les classificacions actuals dels pacients amb malalties mitocondrials, en les quals és complicat assolir un diagnòstic molecular definitiu degut a la seva immensa complexitat.
Mitochondrial diseases are genetic rare diseases which affect the energetic cellular system to obtain the required energy for basic survival. Coenzyme Q10 is a lipidic antioxidant located in all eukaryotic cellular membranes that is essential for mitochondrial respiratory chain activity, amongst other important roles not strictly related to mitochondrial function. Coenzyme Q10 deficiency is a biochemical trait defined by low coenzyme Q10 levels in tissues, which can manifest in five main classical phenotypes (from isolated nephropathies to fatal infantile multisystemic disease). The ethiology can be primary (when the genetic defect is in a gene affecting the coenzyme Q10 biosynthetic pathway) or secondary (when the altered gene is not directly related to the coenzyme Q10 biosynthesis), and this partially explains the high heterogeneity observed in these patients. The patophysiology is explained because there is a mitochondrial respiratory chain malfunction that affects the oxidative phosphorylation system and unbalances the antioxidant protection, consequently changing normal cellular behaviour. The main objective of this work has been to improve the diagnosis of patients with coenzyme Q10 deficiency, through the systematic analysis of various biological samples in association with clinical, biochemical, histochemical, enzymatic and molecular data. Through the study and evaluation of big cohorts of patients, we could establish that secondary coenzyme Q10 deficiencies are commoner than primary. Furthermore, we have reported an association of three different diseases with secondary coenzyme Q10 deficient states (GLUT-1 deficiency syndrome, pyrivate dehydrogenase deficiency, mucopolysaccharidosis type III), diseases that could benefit from coenzyme Q10 supplementation, which has demonstrated to produce clinical amelioration in mitochondrial patients. Finally, methodological improvements for coenzyme Q10 deficiency diagnosis were done through two different approaches. One is the analysis of coenzyme Q10 in urinary sediment to assess coenzyme Q10 levels of renal system cells, and the other one is the development of a statistical algorithm which shows the potential of coenzyme Q10 as a mitochondrial activity biomarker.

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Several population-based studies have shown been headache as one of the most common symptoms in childhood. These have provided important consequences in headache diagnosis and treatment, since only about 11% of children with chronic headache seek medical treatment. Objectives: This study aimed at selecting a sample of school-aged children who complained headache in the last year, and to assess the headache prevalence in children and adolescents in São José do Rio Preto city (SJRP), SP. Casuistic and Methodology: A total of 5,232 children and adolescents (aged from 6 to 18 years) from SJRP randomly comprised this sample. They have been attended from the 1st to 8th grade in the year of 2004 in 13 schools: 10 public and 3 private. A questionnaire answered by parents and/or responsibles of children and adolescents was handed out in the schools to collect data. The used variables for descriptive demographic profile of the population were: age, gender, color, grade, and school for descriptive analysis of this population s demographic profile. Results: The majority was women (53.3%), white color (74.7%), and attending from the 1st to 4th grade (60%) and from the 5th to 8th grade (40%) of the elementary school. The returning of questionnaires was 61.7% in the public schools and 60% in the private. Out of the children and adolescents who have answered the questionnaire, 70% reported headache complain in the last year, only 7.2% of them did not. Out of the ones who have complained headache in the last year, 51.5% presented it occasionally during the year; 15.5%% once a month at least, 11.9% monthly and 5.2% daily. A significant difference observed in the study was regarding to the complain between the girls and the boys. More frequent headaches were reported by the girls; daily headache was twice higher than the percentile of the boys (6.6% and 3.6%, respectively). A higher headache frequency with the increase of age was observed in relation to headache and age. Our study has pointed out that headache prevalence was high in this studied population; predominantly the frequency being higher (monthly, weekly and daily) in girls and older age group.
Uma série de estudos populacionais tem mostrado que a cefaléia é um dos sintomas mais comuns na infância. Estes estudos têm importantes implicações no diagnóstico e tratamento das cefaléias, desde que somente 11% das crianças com cefaléia crônica procuram atendimento médico. Objetivos: O objetivo deste estudo foi selecionar uma amostra de escolares que declararam ter sentido dor de cabeça no último ano e estimar a prevalência de cefaléia em crianças e adolescentes da cidade de São José do Rio Preto (SJRP), SP. Casuística e Método: O grupo amostral foi constituído por 5.232 crianças e adolescentes (idades de 6 18 anos) de SJRP, que cursaram da 1ª a 8ª série no ano de 2004 em 13 escolas, sendo 10 públicas e 3 particulares, feita por seleção aleatória. A coleta de dados foi realizada por aplicação de um questionário distribuído nas escolas, respondido pelos pais e/ou responsáveis. As variáveis utilizadas foram: idade, gênero, cor, série e escola para a análise descritiva do perfil demográfico desta população. Resultados: O grupo amostral foi composto na maioria por mulheres (53,3%), cor branca (74,7%), cursando da 1ª a 4ª série (60%) e da 5ª a 8ª série (40%) do ensino fundamental. A taxa de devolução dos questionários foi de 61,7% nas escolas públicas e 60,1% nas particulares. Das crianças e adolescentes que participaram do estudo, 70% declararam ter sentido dor de cabeça no último ano, sendo que somente 7,2% nunca se queixaram de dor. Dos que responderam ter sentido cefaléia no último ano, 51,5% apresentaram cefaléia somente algumas vezes ao longo do ano, 15,5% pelo menos uma vez ao mês, 11,9% semanalmente e 5,2% diariamente. Uma diferença significativa observada em nosso estudo foi relacionada à queixa entre meninas e meninos. Cefaléias mais freqüentes foram relatadas pelas meninas, sendo que a queixa de cefaléia diária entre as meninas foi duas vezes maior que o percentual para os meninos (6,6% contra 3,6%). Observou-se uma relação da cefaléia com a idade, indicando que houve um aumento da freqüência da cefaléia com o aumento da idade. Nosso estudo indicou que a prevalência de cefaléia na população estudada foi alta, com maior predomínio de cefaléias mais freqüentes (mensalmente, semanalmente e diariamente) nas meninas e na faixa etária mais velha.

INTRODUÇÃO: Na população infantil, a presença da privação ou de alterações no padrão do sono interfere em diversos processos orgânicos, além de influenciar no comportamento e humor, no desempenho neuropsicomotor, na cognição e nos relacionamentos sociais e familiares, prejudicando sua qualidade de vida. Entre os métodos diagnósticos utilizados na investigação dos distúrbios do sono para essa população incluise a utilização de questionários. Estes são instrumentos de simples administração que facilitam o diagnóstico e determinam a presença de distúrbios do sono e parassônias em crianças. O Questionário do Sono de Reimão e Lefèvre (QRL) é um instrumento de avaliação subjetiva desenvolvido em território nacional, que validado, contribuirá para pesquisas clínicas e epidemiológicas, facilitando também a prática clínica do profissional que atua nessa área. OBJETIVOS: 1)verificar se as propriedades de validade (consistência interna e reprodutibilidade) do QRL permitem que este assuma o papel de um instrumento específico de avaliação de características e distúrbios do sono para a população infantil; 2)determinar a prevalência dos distúrbios do sono relacionados às crianças de três a cinco anos de idade e aos seus diferentes gêneros; 3)estabelecer as características do padrão de sono para crianças de três a cinco anos e; 4)conhecer os principais hábitos e rituais para dormir que crianças com essa faixa etária manifestam. MÉTODOS: Estudo prospectivo e observacional para a avaliação da consistência interna e reprodutibilidade do QRL. Para a avaliação da consistência interna, 60 crianças entre três e cinco anos de idade foram divididas em três subgrupos após diagnóstico médico: GICrianças com diagnóstico de distúrbio do sono; GII- Crianças sem a presença de qualquer distúrbio do sono; GIII- Crianças com ou sem a presença de distúrbio do sono. Os resultados do QRL foram comparados com o diagnóstico feito pelo médico neurologista especialista na área do sono. Para o estudo da reprodutibilidade, o questionário foi aplicado em 1021 crianças entre três e cinco anos de idade de creches municipais de São Paulo e reaplicado após um período que variou entre 14 e 21 dias. RESULTADOS: Os índices de correlação entre o QRL e o diagnóstico médico foram elevados nos três grupos estudados, com alta consistência interna (0,80 a 0,86) segundo Coeficiente Alfa de Cronbach. As questões do QRL apresentaram alta concordância para a reprodutibilidade (0,798 a 1,000) segundo coeficiente Kappa. O tempo total de sono variou entre 10 e 11 horas para as crianças entre três e cinco anos. A movimentação excessiva durante o sono (48,5%), o ronco (35,8%), sonolência diurna (33,2%) e enurese noturna (21,9%), foram os distúrbios com maior prevalência. A maior parte dos distúrbios do sono ocorreu diariamente, foram mais comuns ao gênero feminino e tenderam a diminuir com a idade. CONCLUSÕES: A consistência interna e a reprodutibilidade do QRL indicaram que esse é um instrumento adequado para avaliar a presença de distúrbios do sono na população infantil. A prevalência dos distúrbios do sono variou de acordo com o gênero, idade e frequência da manifestação
INTRODUCTION: The pediatric population, sleep deprivation and disturbance of sleep pattern influences several organic process, also influences behavior and mood, neuropsychomotor performance, cognition and relationships, and it is detrimental to quality of life. The diagnostic method used in this population also includes the use of questionnaires. Sleep questionnaires are instruments which easily assist to diagnose sleep disorders and parasomnias in children. Infant Sleep Questionnaire Reimão and Lefèvre (RLQ) is an instrument of subjective evaluation, developed in Brazil, and if validated, will be very helpful for clinical and epidemiologic research as well as for clinical practice. OBJECTIVES: Is to check validity (internal consistency and reproducibility) of RLQ and to verify if it could be used as specific instrument of evaluation of sleep disorders in children; To check prevalence of sleep disorders in children between three to five years old of both males and females; To establish characteristics of sleep patterns in children between three to five years old and recognize the habits and rituals used by these children to sleep. METHODS: Prospective and observational study for evaluation of internal consistency and reproducibility of RLQ. For the evaluation of internal consistency, 60 children were studied. Age ranged from 3 to 5 years old of both males and females. After medical diagnosis, they were divided in three subgroups: GI- Children with diagnosed sleep disorder; GII - Children without the presence of any sleep disorder; GIII - Children with or without sleep disorders. The results of RLQ were compared with reports from medical neurologist specialized in sleep disorders. For the reproducibility of RLQ, the questionnaire was applied twice to 1021 children between 3 and 5 years old, in public schools in Sao Paulo, during a period that ranged between 14 and 21 days. RESULTS: The questionnaire showed high reproducibility Kappa 0.798 to 1.0, the internal consistency was high for all three groups (080 to 0.86) second coefficient alpha Cronbach. The total sleep time ranged from 10 and 11 hours for children between 3 and 5 years old. The most frequently sleep disorders reported was restlessness during sleep (48.5), snoring (35.8 %), daytime sleepiness (33.2%) and enuresis (21.9 %). Most sleep disorders occurred daily, were more common in females and decreased with age. CONCLUSIONS: The internal consistency and reproducibility of RLQ suggested that this is an adequate instrument for evaluation of sleep disorders in children. The prevalence of sleep disorders varies with gender, age and frequency of this disorder

Orientadores: Maria Valeriana Leme de Moura-Ribeiro, Vanda Maria Gimenes Gonçalves
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A desnutrição intra-uterina tem sido associada à morbidade neurológica em longo prazo, sendo o lactente nascido pequeno para a idade gestacional um modelo de estudo para essa situação. O presente estudo teve por objetivo avaliar e comparar os indicadores do neurodesenvolvimento segundo as Escalas Bayley do Desenvolvimento Infantil, no primeiro ano de vida, entre lactentes nascidos a termo pequenos para a idade gestacional e lactentes nascidos com peso adequado. Foram selecionados 125 neonatos no Centro de Atenção Integral à Saúde da Mulher da UNICAMP, obedecendo aos critérios de inclusão: neonatos cujos pais ou responsáveis legais que assinaram o Termo de Consentimento Informado; que não necessitaram de cuidados especiais; com idade gestacional entre 37 e 41 semanas; com avaliação no 1º, 2º, 3º e 6º, 9º e 12º meses. Foram excluídos neonatos com infecção congênita, malformações diagnosticadas no período neonatal e aqueles resultantes de gestação múltipla. A casuística, composta por 95 lactentes que compareceram para pelo menos uma avaliação programada no 1º ano de vida, foi dividida em dois grupos de acordo com a adequação peso/idade gestacional: grupo PIG, constituído por 33 lactentes com peso ao nascimento abaixo do percentil 10 e grupo AIG por 62 lactentes com peso entre o percentil 10 e 90 da curva de crescimento fetal de Battaglia e Lubchenco (1967). Foram utilizadas as Escalas Bayley de Desenvolvimento Infantil II (1993), aplicadas no 1º, 2º, 3º, 6º, 9º e 12º meses de vida, no Laboratório de Estudos do Desenvolvimento Infantil I. Para a análise de resultados, a casuística do grupo PIG foi reagrupada de acordo com a proporcionalidade corporal ao nascimento em: PIG com crescimento intra-uterino simétrico (PIG-S) e PIG com crescimento intra-uterino assimétrico (PIG-A). Os grupos não apresentaram diferenças na performance nas escalas mental e motora quando classificados em inadequados (Index Score < 85) (IS) e adequados (IS = 85). O grupo PIG apresentou pontuações menores de IS na escala mental nas avaliações do primeiro semestre, sendo que esses resultados foram influenciados pelo grupo PIG-S. No entanto, não houve diferenças estatisticamente significativas em nenhum dos meses analisados. Na escala motora, o grupo PIG apresentou médias menores no 2º e no 12º meses (p = 0,008 e 0,046 Teste Mann-Whitney, respectivamente); e o grupo PIG-S no 2º mês (p = 0,016 Teste Kruskal Wallis). Considerando-se a Escala de Classificação do Comportamento (ECC), observou-se risco de associação à performance inadequada 5,19 vezes maior no grupo PIG (IC95%: 1,03-29,12) no 2º mês de vida. Quando classificados pela proporcionalidade corporal ao nascimento, observou-se risco de associação à performance inadequada 8,39 vezes maior no grupo PIG-S (IC95%: 1,53-57,40) no 2º mês e risco 22,0 vezes maior no grupo PIG-A no 3º mês na ECC. Considerando o perímetro craniano ao nascimento, o lactente nascido com microcefalia apresentou maior proporção com performance inadequada no 1º mês de vida (p = 0,011 Teste Exato de Fisher). Não foram observadas associações na análise univariada considerando-se a associação entre as variáveis biológicas e as relacionadas às condições sócio-demográficas com as performances mental e motora nos meses analisados. No estudo evolutivo comparando-se os resultados obtidos no primeiro semestre e no 9º mês com os resultados do 12º mês observou-se que, em grande proporção, os lactentes que apresentaram performance inadequada nas primeiras três avaliações apresentaram recuperação no 12º mês; os lactentes com performance inadequada no 6º e no 9º mês mantiveram-se inadequados no 12º mês
Abstract: Intrauterine malnutrition has been associated to long-term neurological morbidity and the small for gestational age infant is considered as a model for study this propose. The objective of this study was to evaluate the neurodevelopmental indicators according to Bayley Scales of Infant Development of full-term small-for-gestational age (SGA) infants compared with those born appropriate for gestational age (AGA), in the first year of life. The research design was a prospective study of two cohorts, one of full-term SGA group and other of control AGA group; with cross-sectional data analysis. A hundred and twenty five full-term neonates were selected at Neonatology Service in the Center of Integral Attention to the Woman's Health (CAISM) of the University of Campinas (UNICAMP), São Paulo, Brazil. Ethical permission was obtained from the Research Ethics Committee of the Medical Faculty of UNICAMP and the parents also gave the fully informed consent. They were selected on the following criteria: subjects living in the metropolitan area of Campinas; neonates considered in good health for going home within 2 days after birth; gestational age categorized as full-term (37-41 weeks) by Capurro postnatal method; expected birth weight for determined gestational age by Battaglia and Lubchenco method; birth weight less than the 10th percentile for the SGA group and between the 10th and the 90th percentile for the AGA group. Genetic syndromes, multiple congenital malformations and verified congenital infections (syphilis, toxoplasmosis, rubella, citomegalovirus, herpes) were excluded. The SGA group infants were classified according to body proportionality as symmetric SGA (S-SGA) and asymmetric SGA (A-SGA) for data analysis. All children were scheduled for developmental evaluation by the Bayley Scales of Infant Development II (Bayley, 1993) and two professionals who were unaware of the classification of the neonate's group performed the assessments of the infants, in the presence of their mothers, at 1, 2, 3, 6, 9 and 12 months of age. The infant's score for each item was registered in the Mental and Motor Scale Record Form. A total of 95 infants were performed. No differences were observed in Mental and Motor Scales performance, when classified as adequate (IS = 85) or inadequate (IS < 85). In the Mental Scale, means comparison between the groups showed no statistical differences. Considering the Motor Scale the SGA group showed lower IS means in the 2nd and in the 12th months (p = 0,008 and 0,046, respectively, Mann-Whitney test) and the S-SGA group in the 2hd month of age (p = 0,016 Kruskal Wallis test). Considering the Behavior Rating Scale, the inadequate performance were associated in the 2nd month of life, 5,19 times in higher proportion to SGA group (IC95%: 1,03-29,12) and 8,89 times to S-SGA group (IC95%: 1,53-57,40). In the 3rd month of age, was 22,0 times in higher proportion to A-SGA infants. Considering the occipitofrontal circumference at birth, the microcephalic born infants demonstrated association with inadequate performance in higher proportion in the 1st month of life (p = 0,011 Exact Fisher test) in the Mental Scale. Analyzing the relationship between biologic and socio-demographic variables using the univariate analysis, there was no association with theses variables and mental and motor performances in any month of the first year of life
Doutorado
Neurologia
Doutor em Ciências Médicas

Autism spectrum disorders (ASD) are neurodevelopmental disorders with multiple neurobiological aetiologies, which could be genetic, structural, metabolic or immune-mediated. ASDs are diagnosed with deficits in social communication and restricted and repetitive behaviours, and are associated with sensorial atypicalities. 30% of cases have co-existing epilepsy. A series of in vitro, in vivo and post-mortem investigations were undertaken to examine sensory atypicalities in ASD. In vitro characterisation of hippocampal neuronal cultures using immunofluorescence demonstrated the presence of multiple cell types including neurons, astrocytes and microglia. The distribution of ion channels of the Shaker family and tumour necrosis factor α receptors in astrocytes and neurons were identified but not explored further. Neuroanatomical and neuropathological investigations of primary olfactory cortex, using post-mortem stereology, demonstrated a specific increase in glial cell densities in layer II, which was negatively associated with age in ASD. Increases in glia were also associated with symptom severity and often co-localised with the presence of corpora amylacea in layer I. Qualitative analysis of the olfactory tubercle demonstrated that corpora amylacea did not extend to this neighbouring region of the primary olfactory cortex in ASD. These changes were independent of co-existing epilepsy and not observed in epilepsy without ASD. Preliminary pilot studies of the hippocampus provided a stereological sampling strategy to quantify cell densities in future investigations of this area in ASD. Neurophysiological investigations using collected magnetoencephalography data demonstrated diminished occipital gamma oscillatory synchrony in ASD in a visual time perception task. This did not always predict behavioural outcome but was specific to ASD and could not be explained simply in terms of changes in task performance. Moreover, changes in oscillatory synchrony were associated with symptom severity. These observations in primary sensory domains in post-mortem tissue and in patients suggest possible novel mechanisms in ASD and extend knowledge of the neurobiological bases of these disorders.