Submitted by Simone Souza (simonecgsouza@hotmail.com) on 2017-10-18T12:42:59Z No. of bitstreams: 1 DISS_2014_Leticya Lerner Lopes.pdf: 2057200 bytes, checksum: 5e81c161d271f2cc49db59d9720875b7 (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2017-11-07T15:49:22Z (GMT) No. of bitstreams: 1 DISS_2014_Leticya Lerner Lopes.pdf: 2057200 bytes, checksum: 5e81c161d271f2cc49db59d9720875b7 (MD5) / Made available in DSpace on 2017-11-07T15:49:22Z (GMT). No. of bitstreams: 1 DISS_2014_Leticya Lerner Lopes.pdf: 2057200 bytes, checksum: 5e81c161d271f2cc49db59d9720875b7 (MD5) Previous issue date: 2014-02-28 / CAPES / O vírus da cinomose canina (VCC) é um vírus RNA, que pertence ao gênero Morbillivírus e família Paramyxoviridae. A capacidade de resposta imune, assim como sua virulência são fatores críticos para a invasão viral dos tecidos epiteliais e do sistema nervoso central (SNC). O VCC é o maior responsável pelas encefalites em cães, acometendo diversas idades. O objetivo desse estudo foi detectar o VCC nos cães com sinais neurológicos encaminhados para necropsia no Laboratório de Patologia Veterinária da Universidade Federal de Mato Grosso (LPV-UFMT). Durante um período de um ano, 85% (68/80) dos cães necropsiados tinham lesões microscópicas compatíveis com encefalomielite causada pelo VCC. Desses, 67.6% (46/68) foram confirmadas positivas através da imuno-histoquímica (IHQ). Microscopicamente, as lesões do SNC foram classificadas em encefalite desmielinizante aguda em 15.2% (7/46) dos cães, em subaguda em 73.9% (34/46) e crônica em 10.8% (5/46) dos cães. O cerebelo foi principal órgão a apresentar marcação positiva na IHQ (97.8%). O VCC é responsável pelos sinais neurológicos em cães principalmente abaixo de um ano de idade. A cinomose demonstrou sua relevância dentro da população canina de Cuiabá, sendo necessário ao nosso entendimento, caracterizar a estirpe viral relacionada à região. / Canine distemper virus (CDV) is a RNA virus classified under the genus Morbillivirus within the family of Paramyxoviridae. The time of onset of the immune response and, likely, also the virulence of the virus are critical factors in the extent of viral invasion of epithelial tissues and of the central nervous system. The CDV is the most responsible of encephalitis in dogs from different ages. In this study, the aim was to detected CDV in dogs with neurologicals signs referred for necropsy at the Laboratory of Veterinary Pathology, Federal University of Mato Grosso (LPV-UFMT).Over a period of 1 year, 85% (68/80) of the dogs necropsied had microscopic lesions compatible encephalomyelitis by CDV. Which 67.6% (46/68) were confirmed by immunohistochemistry (IHC). Microscopically, the CNS lesions were classified demyelinating encephalitis in 15.2% (7/46) to acute, 73.9% (34/46) in subacute and 10.8% (5/46) to chronic. The cerebellum (97.8%) was the main target organ to verify positivity in the IHC. Canine distemper virus is a pathogen responsible for neurological clinical signs in dogs mainly under one year of age. Distemper demonstrated its relevance within the canine population of Cuiabá, being necessary to our understanding, characterizing the viral strain related to the region.

Made available in DSpace on 2016-12-06T17:07:20Z (GMT). No. of bitstreams: 1 Cristiane Silva.pdf: 988757 bytes, checksum: c0c07f14bdaac4ac70bccc7ac58aeb23 (MD5) Previous issue date: 2009-04-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Seeking know what neuroevolutivo profile in early childhood of children with a history of prematurity, the objective of this study was to evaluate the follow neuropsychomotor of children 4 to 24 months, with risk of neurological criteria, based on a history of prematurity, with the High Risk Clinic at the Division of Pediatric Neonatology at University Hospital (HU/ UFSC). The research is characterized as descriptive, and longitudinal development. The population was composed of extremely premature children and of prematurity, with the Project "Maturity follow of Children with High Biological Risk" and "Assessment and Intervention neuropsychomotor in children with a history of prematurity, held in the High Risk Clinic at the Neonatology of the HU / UFSC, in the city of Florianópolis / SC, from July 2005 to July 2008. The children were assessed by a standardized form for acquisition of biopshychosocial data, answered by the consultation to the hospitalar handbook and an interview with parents or guardians, and the Psychomotor Development Scale of the Early Childhood (Brunet-Lèzine). The sample comprised 89 infants, and throughout the following assessments were 250 evaluations, which lasted on average 30 minutes and is performed in an office in the presence of parent. The gestational age mean was 216,15 days (MED = 216, standard deviation = 17,2), and birth weight was 1271.9 g with great variation between 515g and 3150g. Regarding gender, 57% were male infants and 43% in female infants. The child's daily permanence have, 84.3% (N = 75) of cases showed the mother as primary caregiver, strengthening the parent-child bond, promoting the prevention of disorders of development. As the pre-natal complications, they were present in 68.3% of pregnancies, and the main one was Pre Eclampsia (25,3% N = 23), followed by infections, present in 12,1% (N = 11) of pregnant women. The newborn classification showed that 27,6% were classified PIG, 51% had very low birth weight and 27% were Extremely low birth weight, increasing the willingness to risk the development of sequelae. There were complications in 85% of neonatal cases, several of which may be negatively influencing the neuropsychomotor development of infants, especially those I had associations of complications (59,3%). In the first evaluation of neuropsychomotor development, had a frequency of 89 infants, however, only 65 infants characterized the follow-up evaluations with 73%, 57.3% (N = 51) with three, 33.7% (N = 30 ) with a fourth assessment, and 16.8% who came to have five evaluations over a period of two years. With the assessment of development, there was QDG (N = 47) classified as normal average (NA), the majority (52.8%), however, draws us to the attention of 28.5% below average. The QDC was NM, to 38.2%, but 43.8% were below expectations. Being the area that showed worse rating, followed by the area of language. After the fifth assessment in an average follow up of 12 months, you can see that the QDP was rated above the norm for 73.3% of cases, with only 1 case (6.6%) of inferiority. For the QDC, the classification in NA was present in 66.6%, decreasing significantly to 6.6%, the classification below normal. Thus, the area that showed greater progress in developing neuropsychomotor. The area of language also made significant progress, with 60% of infants above average, and 20% of cases in NA. QDS has not had cases of inferiority in the fifth assessment, presenting 53.3% classified as NA, and 6.6% in zone limit (n = 1). Thus the development of Global Classification of infants who reached the fifth assessment showed 60% of infants in the middle, NM with rating and 40% above the average, showing no cases of delayed development. The ratio of expansions were analyzed in pairs by paired t test, and differences were not statistically significant. you can see that all the assessments showed the same linearity and is always the area of coordination óculomotriz, the scores of children, followed by the area of language. To correlate the ratios of development, found in most, moderate correlations, statistically significant by Pearson's linear correlation. / Buscando conhecer, qual o perfil neuroevolutivo na primeira infância de crianças com histórico de prematuridade, o objetivo deste trabalho foi avaliar o seguimento neuropsicomotor de lactentes de 4 a 24 meses, com critérios de risco neurológico, com base no histórico de prematuridade, junto ao Ambulatório de Alto Risco em Neonatologia da Divisão de Pediatria do Hospital Universitário (HU/ UFSC). A pesquisa caracteriza-se como descritiva, de desenvolvimento longitudinal. A população foi constituída por crianças prematuras e de extrema prematuridade, acompanhadas nos Projetos Seguimento Maturativo de Crianças de Alto Risco Biológico e Avaliação e Intervenção neuropsicomotora em crianças com histórico de prematuridade , realizado no Ambulatório de Alto Risco em Neonatologia do HU/ UFSC, na cidade de Florianópolis/SC, no período de julho de 2005 a julho de 2008. As crianças foram avaliadas através um formulário padronizado para aquisição de dados biopsicossociais, respondido pela consulta ao prontuário hospitalar e entrevista com pais ou responsáveis e da Escala de Desenvolvimento Psicomotor da Primeira Infância de Brunet-Lèzine. A amostra foi composta por 89 lactentes, e durante todo o seguimento foram realizadas 250 avaliações, que duraram em média 30 minutos, sendo realizadas em um consultório, na presença dos pais ou responsáveis. A idade gestacional (IG) média foi de 216,15 dias (mediana=216, desvio-padrão=17,2), e o peso médio ao nascer foi de 1271,9g com grande variação entre 515g e 3150g. Quanto ao gênero, 57% foram lactentes do sexo masculino e 43% lactentes do sexo feminino. Quanto à permanência diária da criança, 84,3%(N=75) dos casos apresentaram a mãe como principal cuidadora, fortalecendo o vinculo mãe-criança, favorecendo a prevenção de distúrbios de desenvolvimento.Quanto as intercorrências pré-natais, estas estiveram presentes em 68,3% das gestações, e destas a principal foi a Pré Eclampsia (25,3% N=23), seguida das infecções, presentes em 12,1% (N=11) das gestantes. Quanto à classificação do recém nascido evidenciou que 27,6% foram classificados PIG, 51% tinham Muito baixo peso ao nascer, e 27% apresentavam Extremo baixo peso ao nascer, aumentando a predisposição ao risco de seqüelas no desenvolvimento. Houveram intercorrências neonatais em 85% dos casos, das mais diversas, que podem estar influenciando negativamente o desenvolvimento neuropsicomotor dos lactentes, especialmente aqueles eu apresentaram associações de intercorrências (59,3%). Na primeira avaliação do Desenvolvimento Neuropsicomotor, tivemos uma freqüência de 89 lactentes, porém, apenas 65 lactentes caracterizaram o seguimento, perfazendo 73% com duas avaliações, 57,3% (N=51) com três, 33,7% (N=30) com uma quarta avaliação, e 16,8% (N=15) que chegaram a ter cinco avaliações em um período de até dois anos. Com a avaliação do desenvolvimento, observou-se QDG (N=47) classificado em Normalidade Média (NM), na sua maioria (52,8%), porém, chama-nos a atenção os 28,5% abaixo da normalidade. O QDC foi NM, para 38,2%, porém 43,8% ficaram abaixo do esperado. Sendo esta a área que apresentou pior classificação, seguida pela área da linguagem. Após a quinta avaliação, em um seguimento médio de 12 meses, pode-se observar que o QDP foi classificado acima da Normalidade, para 73,3% dos casos, com apenas 1 caso (6,6%) de Inferioridade. Para o QDC, a classificação em NM esteve presente em 66,6%, diminuindo expressivamente para 6,6%, a classificação abaixo do normal. Sendo assim, a área que apresentou maior evolução no desenvolvimento neuropsicomotor. A área da linguagem também apresentou expressiva evolução, com 60% dos lactentes acima da média, e 20% de casos em NM. Já o QDS não apresentou casos de inferioridade na quinta avaliação, apresentando 53,3% classificados em NM, e 6,6,% em zona limite (n=1). Assim sendo a Classificação do desenvolvimento Global dos lactentes que chegaram a quinta avaliação evidenciou 60% dos lactentes dentro da média, com classificação NM e 40% acima da Média, não evidenciando casos de atraso no desenvolvimento. Os Quocientes de Desenvolvimentos foram analisados aos pares, através do Teste t pareado, e não foram encontradas diferenças estatisticamente significativas. pode-se observar, que todas as avaliações apresentaram a mesma linearidade, sendo sempre a área da Coordenação óculomotriz, a de menores escores, seguida pela área da Linguagem. Ao correlacionar os quocientes de desenvolvimento, verificamos na sua maioria, correlações moderadas, estatisticamente significativa, através da Correlação linear de Pearson.

O mecanismo de controle da secreção de GnRH inclui diversas vias neuronais. Estudos em modelos animais identificaram genes que codificam fatores de transcrição, tais como TTF-1 (thyroid transcription factor 1) e EAP1 (enhanced at puberty), que atuam no controle transcricional de genes codificadores de fatores excitatórios (KiSS1 e GnRH) e inibitórios (preproencefalinas) regulando a secreção de GnRH. Em primatas, a expressão de EAP1 e TTF-1 aumenta, no início da puberdade, nas regiões hipotalâmicas envolvidas na secreção de GnRH. Nos modelos animais, a deleção pós-natal de TTF-1 e o silenciamento do EAP1 provocam atraso puberal e prejuízo na função reprodutiva. TTF-1 também está envolvido na morfogênese diencefálica, por meio da via de sinalização da família Sonic-Hedgehog. Anormalidades na secreção de GnRH resultam em distúrbios puberais, que variam de puberdade precoce central (PPC) a hipogonadismo hipogonadotrófico. Hipotetizamos que anormalidades genéticas no TTF-1 e EAP1 estejam envolvidas na patogênese dos distúrbios puberais centrais. A PPC pode ser idiopática ou devido a causas orgânicas, sendo o hamartoma hipotalâmico, uma malformação congênita não neoplásica, a mais conhecida. Os pacientes com PPC devido a hamartoma hipotalâmico podem cursar com alterações neurológicas e cognitivas. Nossos objetivos foram: estudar as regiões codificadora do TTF-1 e do EAP1 e a região promotora do TTF-1 em pacientes com distúrbios puberais centrais; estabelecer a prevalência, taxa de penetrância e modo de herança da forma familial de PPC e caracterizar as manifestações neurológicas e neurocognitivas de pacientes com PPC devido a hamartoma hipotalâmico. Foram selecionados 133 pacientes com distúrbios puberais centrais - PPC idiopática (n=71), PPC devido a hamartoma hipotalâmico (n=15) e hipogonadismo hipogonadotrópico isolado normósmico (HHIn) (n=47) - e controles (n=53). Os genes TTF-1 e EAP1 foram amplificados e submetidos a sequenciamento automático. Os tratos de poliglutamina e polialanina no EAP1 foram estudados por software de análise de tamanho de fragmento (GeneScan). A avaliação neurológica e neurocognitiva dos pacientes com PPC devido a hamartoma hipotalâmico consistiu de exame neurológico, eletroencefalograma, ressonância magnética de encéfalo e aplicação da escala de inteligência (WISC-III, WAIS-III, WPPSIR). Identificamos 25% de casos familiais de PPC, com modo de herança autossômica dominante e taxa de penetrância de 67,5%. Variantes alélicas no TTF-1 não foram identificadas nos pacientes estudados. No gene EAP1 foram identificadas quatro variantes alélicas sinônimas: p.E87E, p.A163A, p.Y415Y e uma nova variante alélica p.C758C, encontradas em pacientes com PPC e HHIn. A distribuição das frequências alélica e genotípica das variantes alélicas do EAP1 não diferiram entre pacientes com PPC, HHIn e controles (p >0,05). Nas regiões poliglutamina e polialanina 5 distal foi identificada variação similar no número de repetições glutamina e alanina em pacientes e controles. Não houve diferença significativa da frequência alélica em relação ao número de repetições glutamina e alanina entre os grupos PPC e HHIn (p >0,05). A avaliação neurológica dos pacientes com PPC devido a hamartoma hipotalâmico revelou epilepsia gelástica e crises focais com generalização em 3/15 (20%) pacientes. Não houve diferença significativa entre a mediana do maior diâmetro dos hamartomas dos pacientes com PPC com e sem epilepsia (13 e 10 mm, respectivamente). Quanto à forma, 10 hamartomas eram sésseis e 5 pedunculados, sendo que a forma pedunculada foi detectada exclusivamente em pacientes sem epilepsia. A avaliação neurocognitiva em 11 dos 15 pacientes com PPC devido a hamartoma hipotalâmico detectou 2 pacientes com epilepsia com QI significativamente menor que o grupo sem epilepsia (p <0,05). Em conclusão, (i) a considerável prevalência de casos familiais de PPC reforça a influência dos fatores genéticos na puberdade humana; (ii) mutações germinativas no TTF-1 e no EAP1 não estão envolvidas na patogênese dos distúrbios puberais centrais; (iii) a função neurocognitiva reduzida nos pacientes com hamartoma e epilepsia sugere um efeito deletério das crises convulsivas no sistema nervoso central / GnRH secretion control involves multiple neuronal pathways. Animal studies have identified genes which codifies transcription factors, such as TTF-1 (thyroid transcription factor 1) and EAP1 (enhanced at puberty), that act in the transcriptional control of genes that codifies excitatory (KiSS1 and GnRH) and inhibitory factors (preproenkephalines) regulating GnRH secretion. In nonhuman primates, expression of EAP1 and TTF-1 are increased at the hypothalamic regions involved in GnRH secretion, at the beginning of puberty. In animal models, post-natal TTF-1 deletion and silencing of EAP1 lead to pubertal delay and damage of reproductive function. TTF-1 is also involved in diencephalic morphogenesis, through signalization via Sonic-Hedgehog family. Abnormalities in GnRH secretion are responsible for pubertal disorders, varying from central precocious puberty (CPP) to hypogonadotropic hypogonadism. We hypothesized that genetic anomalies at TTF-1 and EAP1 are involved in the pathogenesis of central pubertal disorders. CPP may be idiopathic or due to organic alterations and hypothalamic hamartoma, a non-neoplasic congenital malformation, is the most frequent known organic cause. Patients with CPP due to hypothalamic hamartoma may have neurological and cognitive disfunctions. Our aims were: to evaluated the codifying region of TTF-1 and EAP1 and the promoter region of TTF-1 in patients with central pubertal disorders; to establish the prevalence, penetrance rate and inheritance mode of familial CPP and to characterize neurologic and neurocognitive aspects of patients with CPP due to hypothalamic hamartoma. We selected 133 patients with central pubertal disorders idiopathic CPP (n=71), CPP due to hypothalamic hamartoma (n=15) and normosmic isolated hypogonadropic hypogonadism (nIHH) (n=47) - and controls (n=53). TTF-1 and EAP1 genes were amplified and sequenced. Polyglutamine and polyalanine tracts of EAP1 were studied by a fragment size analyser software (GeneScan). Neurologic and neurocognitive evaluation of CPP patients due to hypothalamic hamartoma consisted of neurologic exam, electroencephalogram, brain magnetic resonance and application of intelligence scale (WISC-III, WAIS-III, WPPSI-R). We identified 25% of familial CPP cases with autosomal dominant mode of inheritance and penetrance rate of 67.5%. No TTF-1 allelic variants were identified in the patients analysed. At EAP1 gene, four synonimous allelic variants were identified: p.E87E, p.A163A, p.Y415Y and a new allelic variant p.C758C, found in CPP and nIHH patients. The allelic and genotypic distribution of theses variants of EAP1 did not differ among patients with CPP and nIHH, and controls (p >0.05). At polyglutamine and 5 distal polyalanine region, similar glutamine and alanine repeats variation was found. No significative difference of allelic frequency distribution regarding the number of glutamines and alanines repeats was found among the studied groups (p >0.05). Neurologic evaluation of CPP patients due to hypothalamic hamartoma revealed epilepsy and focal crisis with generalization in 3/15 (20%) of the patients. No significant difference between the median of the larger diameter of hypothalamic hamartoma of CPP patients with and without epilepsy was found (10 mm and 13 mm, respectively). Regarding the shape, 10 hamartomas were sessile and 5 pedunculated, and the pedunculated shape was found only in non epileptic patients. Neurocognitive evaluation performed in 11 of the 15 patients with CPP due to hypothalamic hamartoma detected 2 patients with epilepsy whose IQ were significantly lower than the IQ found in the group without epilepsy (p <0.05). In conclusion, (i) the considerable prevalence of familial CPP cases reinforce the influence of genetic factors in human puberty; (ii) germinative mutations in TTF-1 and EAP1 are not involved in the pathogenesis of central pubertal disorders; (iii) reduced neurocognitive function in patients with hypothalamic hamartoma and epilepsy suggests a deleterious effect of crisis at the central nervous system

Introdução: Transplantes de órgãos ocorrem principalmente devido a doações provenientes de pacientes que apresentam morte encefálica (ME). Algumas situações limitam o diagnóstico de ME baseado apenas no exame neurológico, sendo necessário utilizar um exame de imagem ou gráfico para esta confirmação. No Brasil, o exame complementar é obrigatório por lei para todos os casos suspeitos. A maioria dos métodos complementares utilizados para confirmação de ME não está disponível em muitos locais do Brasil. Neste contexto, a angiografia por tomografia computadorizada (ATC) representaria uma alternativa, devido à presença de equipamentos de tomografia em diversos hospitais brasileiros. Porém, a capacidade de este exame reconhecer a interrupção da circulação intracraniana é desconhecida. Métodos: Realizou-se revisão sistemática para verificar evidência na literatura sobre o uso de ATC como teste avaliador de ME. Foram seguidas diretrizes de busca e extração de dados, sendo o QUADAS 2 utilizado para verificar risco de vieses e qualidade dos estudos. Os dados foram sumarizados para produzir metanálise. Resultados: Dez estudos com alto risco de vieses foram encontrados. Devido à falta de estudos controlados, não se obteve dados de especificidade. Trezentos e vinte e dois pacientes foram elegíveis para metanálise, a qual revelou 84,7% de sensibilidade. Houve variação de protocolos de avaliação das imagens de ATC entre os estudos, sobre a definição de resultados positivos ou negativos. Conclusão: ATC apresenta alta sensibilidade para detectar interrupção de circulação intracraniana entre pacientes com avaliação clínica compatível com ME. Este nível de evidência é similar ao de outros métodos utilizados no mundo. Há falta de estudos bem desenhados neste tema / Background: Organ transplantation depends more often of donation from brain dead (BD) individuals. Several complications make the diagnosis of BD medically challenging and a complimentary method is needed for confirmation. Additionally, in Brazil, the complimentary diagnosis is mandatory by law, despite there are still many areas where these methods are not available. In this context, computed tomography angiography (CTA) could represent a valuable alternative, because of its widespread presence. However, the reliability of CTA for confirming brain circulatory arrest remains unclear. Methods: A systematic review was performed to identify relevant studies regarding the use of CTA as ancillary test for BD confirmation. Guidelines for online search were followed, and the QUADAS 2 tool was used to verify study quality. Data from the studies retrieved were extracted aiming to perform the meta-analysis. Results: Ten low quality studies were found. Due to the absence of controls in all studies, specificity could not be calculated. Three hundred twenty-two patients were eligible for the meta-analysis, which exhibited 84,7% sensitivity. CTA image evaluation protocol exhibited variations between medical institutions regarding which intracranial vessels should be considered to determine positive or negative test results. Conclusions: For patients who were previously diagnosed with BD according to clinical criteria, CTA demonstrated high sensitivity to verify intracranial circulatory arrest. The current evidence that supports the use of CTA in BD diagnosis is comparable to other methods applied worldwide. Considering the importance of this subject, high quality studies are currently missing and needed

Abstract Despite improvements in peri- and neonatal care and an increase in the overall survival of very preterm infants, the incidence of neurologic sequelae has remained high. The pathogenesis of many brain imaging findings, such as white matter damage, WMD, is poorly understood. The factors predisposing to brain damage differ between term and preterm infants. More detailed information is needed of how brain imaging correlates with neurodevelopmental impairment after the neonatal period. The present study investigated the pre- and perinatal factors leading to brain damage and their effects on neurologic and neurodevelopmental outcome in very preterm children. We also analyzed the differences in umbilical cord serum cytokines in term and preterm children with cerebral palsy, CP. Furthermore, the correlations between the findings on diffusion-weighted imaging, DWI, measurements in brainstem auditory evoked potentials, and neurodevelopmental outcome were assessed. We demonstrated that pregnancies complicated by combined histologic chorioamnionitis and placental insufficiency independently predicted abnormal neurologic outcome at 2 years of corrected age. WMD additively predicted poor outcome. Isolated fetal inflammatory response, umbilical cord serum acute phase cytokines (IL-1α, IL-1β, IL-6, IL-8, TNF-α), did not associate with neurologic outcome in either term or preterm children. Instead, a cluster of cytokines different from acute phase cytokines were related to CP, and the protein profile differed between term and preterm children. Disturbed hemodynamics during the pre- and perinatal period affected outcome in very preterm infants. In severe placental insufficiency, fetal cardiac compromise associated with suboptimal neurodevelopmental outcome at 1 year of corrected age. In addition, several clinical factors characterising cardiorespiratory status after birth associated with abnormal neurologic outcome at 2 years of corrected age. We found the apparent diffusion coefficient, ADC, a quantitative measurement of water diffusion, in pons to correlate with the conduction rate of impulses travelling through the auditory tract. We also demonstrated a high value of ADC in corona radiata to associate with poor outcome in gross motor and eye-hand coordination skills at 2 years of corrected age. Both pre- and perinatal factors associate with later outcome in very preterm infants. An isolated fetal inflammatory response does not predict neurologic outcome. Findings on DWI in specific brain regions predict abnormal neurodevelopmental outcome. / Tiivistelmä Huolimatta vastasyntyneisyyskauden parantuneista hoitotuloksista ja että yhä useampi hyvin ennenaikaisena syntynyt lapsi jää eloon, heidän neurologisen vammautuneisuuden ilmaantuvuus on edelleen korkea. Monien aivojen kuvantamislöydösten, kuten valkean aineen vaurion, syntymekanismit tunnetaan huonosti. Aivojen vaurioitumiselle altistavat tekijät eroavat täysiaikaisena ja ennenaikaisena syntyneillä lapsilla. Tarvitaan myös aiempaa yksityiskohtaisempaa tietoa aivojen kuvantamislöydösten merkityksestä lasten vastasyntyneisyyskauden jälkeiseen kehitykseen. Tässä tutkimuksessa selvitettiin raskauden- ja syntymänaikaisia tekijöitä, jotka vaikuttavat aivojen vaurioitumiseen hyvin ennenaikaisena syntyneillä lapsilla sekä näiden tekijöiden merkitystä lasten neurologiseen kehitykseen. Tarkastelimme myös napaveren seerumin välittäjäaineiden, sytokiinien, eroavuuksia täysiaikaisena ja ennenaikaisena syntyneillä CP-lapsilla. Lisäksi selvitimme diffuusiomagneettitutkimus- ja aivorunkoherätevastelöydösten sekä neurologisen kehityksen välisiä yhteyksiä. Tämän tutkimuksen mukaan kohdunsisäinen tulehdus ja istukan vajaatoiminta yhtä aikaa esiintyessään ovat poikkeavan neurologisen kehityksen itsenäisiä riskitekijöitä lapsilla 2 vuoden korjatussa iässä tutkittuna. Valkoisen aivoaineen vaurio edelleen lisäsi näiden lasten huonon neurologisen kehityksen ennustetta. Raskauden kestosta riippumatta, sikiön tulehdusvastetta kuvaavat napaveren akuutin vaiheen tulehdusvälittäjäaineet (IL-1α, IL-1β, IL-6, IL-8, TNF- α) eivät vaikuttaneet lapsen neurologiseen kehitykseen. Sen sijaan, CP-lasten napaverestä löytyi erityinen joukko ei-akuutin vaiheen välittäjäaineita. Nämä valkuaisaineet erosivat toisistaan täysiaikaisena ja ennenaikaisena syntyneillä CP-lapsilla. Raskauden- ja syntymänaikaiset verenkierron häiriöt vaikuttivat hyvin ennenaikaisena syntyneiden lasten myöhempään kehitykseen. Vaikeassa istukan vajaatoiminassa sikiön sydämen toiminnan heikkeneminen liittyi lapsen suboptimaaliin neurologiseen kehitykseen 1 vuoden korjatussa iässä tutkittuna. Lisäksi useat syntymänjälkeiset keuhkojen ja verenkierron tilaa kuvaavat kliiniset tekijät liittyivät lapsen poikkeavaan neurologiseen kehitykseen 2 vuoden korjatussa iässä tutkittuna. Tutkimuksemme mukaan, veden diffuusiota määrällisesti kuvaava diffuusiokerroin, ADC, aivosillasta mitattuna, liittyi impulssien johtumisnopeutueen kuuloradastossa. Lisäksi korkea ADC-arvo aivojen sepelviuhkassa liittyi karkean motoriikan ja silmä-käsi-yhteistyötaitojen huonoon kehitykseen 2 vuoden korjatussa iässä tutkittuna. Sekä raskauden- että syntymänaikaiset tekijät vaikuttavat hyvin ennenaikaisena syntyneiden lasten myöhempään kehitykseen. Yksittäinen sikiön tulehdusvaste ei ennakoi lapsen neurologista kehitystä. Tiettyjen aivoalueiden diffuusiokuvantamislöydökset ennustavat lapsen poikkeavaa neurologista kehitystä.

Introdução: O aperfeiçoamento da assistência pré-natal e dos cuidados intensivos neonatais contribuiu para a redução da mortalidade dos recémnascidos (RN) com riscos para alterações do desenvolvimento neuromotor. Apesar destes avanços, a difícil previsão e prevenção de danos neurológicos está associada ao aumento de crianças com problemas graves como a Paralisia Cerebral (PC). Das avaliações disponíveis atualmente, a que possui melhor valor preditivo de danos neurológicos em bebês até os cinco meses de idade é a \"Avaliação Qualitativa dos Movimentos Generalizados (MGs)\" de Prechtl. No entanto, apresenta pouca aderência na prática clínica devido à sua subjetividade e necessidade de treinamento prévio para aplicação. Objetivos: Desenvolver e analisar a confiabilidade de uma escala de avaliação baseada nos MGs caracterizados a partir da avaliação qualitativa de Prechtl em recémnascidos e lactentes com riscos para alterações no desenvolvimento neuromotor. Método: Estudo observacional transversal com a participação de 30 RNs e lactentes com idade compreendida entre 31 semanas pós-menstrual e 17 semanas pós-termo avaliados no Hospital Universitário da USP. Os MGs normais e anormais foram avaliados segundo a análise qualitativa dos MGs de Prechtl seguindo as três fases: pré-termo (n=7), writhing movements (n=13) e fidgety movements (n=10). A escala foi construída baseando-se nestas fases e foram elaboradas duas versões, sendo analisadas as confiabilidades inter e intra-examinador por meio do ICC e do índice de Kappa. A consistência interna da versão final foi analisada através do alfa de Cronbach. Resultados: Foram analisadas duas versões da escala com três diferentes sistemas de pontuação: respostas do tipo \"SIM ou NÃO\"; do tipo \"SEMPRE, ALGUMAS VEZES e NUNCA\"; e \"SEMPRE, QUASE SEMPRE, ALGUMAS VEZES, QUASE NUNCA E NUNCA\". Os resultados mais significativos foram obtidos com as respostas binárias (SIM ou NÃO), sendo que nas fases pré-termo e writhing movements a pontuação máxima é de 32 pontos e na fase dos fidgety movements é de 12 pontos. A análise da confiabilidade da versão final da escala evidenciou concordância excelente tanto para a confiabilidade intra-avaliador (ICCs: 0.914 a 0.999; Kappa: 0.6 a 1 e 0.606 a 1, considerando a escala binária), como para confiabilidade inter-avaliadores (ICCs: 0.871 a 0.966 para avaliação 1; Kappa: 0.682 a 0.775 para avaliação 1, considerando novamente a escala binária). Apenas o índice Kappa neste caso apresentou concordância boa. Os valores de alfa de Cronbach se mostraram de bons a excelentes (0.866 a 0.980). Verificou-se também que os bebês com MGs anormais apresentaram pontuação abaixo de valores entre 20 e 25 na fase pré-termo e dos writhing movements, e abaixo de valores entre 8 e 12 na fase dos fidgety movements. Conclusão: Foi possível desenvolver uma escala capaz de quantificar os MGs, com pontuação capaz de diferenciar MGs normais de anormais, com excelente confiabilidade inter e intra-avaliador e alta consistência interna. A escala apresenta grande relevância clínica e, aliada ao treinamento no método qualitativo, torna-se um instrumento promissor para a detecção precoce de riscos para atraso do desenvolvimento neuromotor e seleção dos RNs e lactentes para acompanhamento e intervenção precoce / Introduction: The technological improvement of neonatal care and intensive care contributed to reduction of preterm newborn (PTNB) mortality. Despite these improvements, is still difficult to predict and prevent neural damage and neurobehavioral impairments, which are associated to higher proportion of children with severe neurological problems, such as Cerebral Palsy (CP). Between all the available methods of babies\' assessment and examination, the Prechtl´s Method of Qualitative Assessment of General Movements (GMs) shows the higher predictive value to neurological damage. Nevertheless, this assessment is not widely used because of its subjectivity and the necessity of training of the examiners. Objective: To develop a quantitative scale based on GMs in the newborn and infant, and to verify its reliability. Method: Crosssectional observational study involving 30 newborns and infants aged between 31 weeks postmenstrual age and 17 weeks post term age assessed at university hospital of University of São Paulo. The normal and abnormal GMs were evaluated based on the Prechtl´s Method of Qualitative Assessment of GMs following the three phases: preterm GMs (n=7), writhing movements (n=13) and fidgety movements (n=10). The scale was developed based on these phases and Kappa and ICC statistics were applied in the reliability analysis (inter- and intra-observer agreement). Cronbach alpha was applied in the internal consistency analysis. Results: Two versions of the scale were analyzed with three different scoring systems: \"YES or NO\"; \"ALWAYS, SOMETIMES and NEVER; \"ALWAYS, OFTEN, SOMETIMES, ALMOST NEVER and NEVER\". The most significant results were obtained with \"YES or NO\" answers. The total score obtained in preterm and writhing movements phases was 32 points and in the fidgety movements phase was 12 points. Considering the assessment with the final version of the scale, high to very high inter- (ICCs 0.871-0.966; Kappa 0.682-0.775 for the first evaluation, considering \"YES or NO\" answers) and intra-observer reliability (ICCs: 0.914-0.999; Kappa: 0.6-1, considering \"YES or NO\" answers) was found. High to very high Cronbach alpha values was also found (0.866-0.980). The infants showed abnormal GMs score below values between 20 and 25 in preterm phase and writhing movements, and below values between 8 and 12 at fidgety movements age. Conclusion: It was possible to develop a scale able to quantify GMs, with scores that can differentiate normal from abnormal GMs, with excellent inter- and intra-observer reliability and internal consistency. The scale has great clinical relevance and, combined with training in qualitative method, it is a promising tool for early detection of risks for delayed neuromotor development and screening of newborns and infants for monitoring and early intervention

It is increasingly being recognised that agrichemical exposure may have adverse chronic health effects in humans, particularly on central nervous system function. However, much of this evidence sterns from studies relating to the effects of acute intoxications (i.e. short-term high dose exposures) and little data exist on the chronic effects of long-term low-dose exposures to agrichemicals in the absence of acute poisoning. Such a finding would have substantial public health implications for prevention and control of chronic morbidity and mortality. This is particularly important in South Africa, where a sizeable portion of the rural population are employed in agricultural work, often under extremely unhealthy living and working conditions, and where occupational agrichemical exposures appear to be substantial. To address this question, this study investigated the prevalence of neurological and neurobehavioural abnormalities amongst 247 fruit farm workers in the Kouebokkeveld in the Western Cape, of whom 163 were current agrichemical applicators. Outcomes measured included neurological symptoms, peripheral vibration sense, motor tremor, as well as performance on the World Health Organisation Neurobehavioural Core Test Battery (WHO NCTB) and a set of neurobehavioural tests based on the Information Processing model of cognitive psychology. These latter tests have been developed in South Africa for subjects of low educational levels and aim to by-pass the powerful effects of culture that complicate traditional neuropsychological testing, which may mask the smaller effects due to occupational chemical exposures. Cumulative, and average lifetime intensity of exposure to organophosphates were estimated using a job- exposure matrix based on a combination of secondary industry data, interview reports and farmer records. Confounders measured included age, education, smoking and alcohol habits, non-occupational exposure to agrichemicals and other potential neurotoxins, past medical history and usage of personal protective equipment. The study results confirmed low levels of education and high alcohol consumption amongst the sample of farm workers. Multiple logistic and linear regression were used to identify exposure-effect relationships and to control for confounding. Neurological symptoms were significantly associated with a history of previous pesticide poisoning, although this may have arisen as a result of reporting bias. Vibration sense and the neurobehavioural tests exhibited associations with established covariates, and regression modelling of the WHO NCTB tests was remarkably similar to findings in another study of solvent-exposed factory workers in South Africa. None of the vibration sense, tremor or neurobehavioural outcomes were associated with past agrichemical poisoning in the sample, and only two tests showed significant relationships with long-term occupational exposure. These included the Pursuit Aiming subtest of the WHO NCTB and one of the tests of long-term semantic memory in the Information Processing tests. However, the strength of these the associations were small (partial r²s less than 2%) and these findings may have occurred due to chance arising from multiple comparisons. The neurobehavioural tests based on the Information Processing model appeared to offer little improvement on the WHO NCTB in terms of being less sensitive to cultural effects, although some evidence was present that tests of semantic access were able to detect occupational effects and were less sensitive to education. The absence of a demonstrable and consistent long-term agrichemical exposure-effect relationship appears to suggest that long-term agrichemical exposure is not associated with adverse chronic nervous system effects, although the lack of organophosphate specificity in construction of exposure indices in the job-exposure matrix may partly contribute to this finding. Recommendations to improve the characterisation of agrichemical exposures at farming work place are made, as well as suggestions concerning the role of biological monitoring for agrichemicals, improving working and living conditions on South African farms, and methods of neurological and neurobehavioural assessment in occupational health.

In the context of HIV high infection rate in South Africa, an assumption can be made that there is a high prevalence of HIV-associated neurocognitive disorders or cognitive linguistic deficits. The aim of this study was to determine assess whether highly active antiretroviral therapy (HAART) affected the cognitive – linguistic abilities of individuals living with HIV and AIDS before and after HAART use; and to determine whether their functional performance in terms of engaging in activities of daily living was affected by HAART use. Adults living with HIV and AIDs were recruited through purposive convenience sampling to participate in the study. They were divided into three groups. The experimental and cross sectional group included participants who were HIV infected and initiated HAART. The comparison group included participants who elected not to start HAART. Participants in all three group were assessed using the Cognitive – Linguistic Quick Test and were also required to fill out a structured interview scale at baseline, four and eight months. For the experimental group 55 participants were tested at baseline, 55 at four months and 52 at eight months after HAART initiation. The comparison group included 21 participants who tested at baseline, ten at four months and nine at eight months. The cross sectional group included different participants who recruited at baseline (55) before HAART initiation, then again at four (44) and eight months (42) after HAART initiation. Descriptive analysis revealed that the mean scores for both the Cognitive – Linguistic Quick Test (CLQT) and the structured interview schedule (IS) in all the cognitive domains increased for all three groups from four and eight months after testing. However the severity ratings provided by the CLQT indicated that neurocognitive deficits were still prevalent among the participants after HAART intiation. The most impaired cogntive – linguistic ability was executive functions and the least impaired was language. One way ANOVA analysis on the CLQT and IS revealed that was a signiifcant difference in performance between the three groups at baseline, four and eight months. Repeated measures analysis revealed significant differences or improvements within participants across the three time periods. The greatest improvement was observed from baseline to eight months especially on the CLQT. ANCOVA analysis on the Cognitive- Linguistic Quick Test indicated that education had a major impact on cognitive – linguistic abilities followed by age and CD4 count. However, ANCOVA analysis on the structured interview scale revealed that the effect of time, participant group and to a lesser extent age influenced the participants cognitive – linguistic abilities when it came to perfroming activities of daily living. Quantitave inquiry using content analysis showed that participants in all three groups cited attention, followed by visual and language problems as hindering their abilities to perform activities of daily living. The implications from this study revealed that even though HAART improves cognitive –linguistic abilities, neurocognitive deficits were still prevalent. Therefore findings suggest that health professionals need to monitor the neurocognitive impairments of their patients so as determine levels of functional performance.

Contexte : Le décès neurologique se caractérise par une perte permanente des fonctions cérébrales essentielles pour la vie, survenant suite à une lésion cérébrale majeure. Le décès isolé du tronc cérébral est une condition dans laquelle tous les critères cliniques du décès neurologique sont rencontrés, bien qu’il existe une circulation sanguine ou une perfusion tissulaire persistante au niveau du cerveau supratentoriel, tel que documenté par des tests paracliniques (communément appelés des « tests ancillaires »). Les trouvailles aux tests ancillaires soulèvent la possibilité de fonction cérébrale supratentorielle résiduelle, bien que leur réelle signification clinique demeure inconnue. Le décès isolé du tronc cérébral n’est pas considéré compatible avec le décès neurologique dans plusieurs jurisdictions à travers le monde, mais il existe peu de données sur sa prévalence, ses caractéristiques et son évolution parmi les patients admis aux soins intensifs suspectés de décès neurologique. De plus, aucun facteur de risque pour le décès isolé du tronc cérébral n’est actuellement connu. Dans le cadre de ce mémoire, deux projets ont été menés afin de caractériser la prévalence, les caractéristiques et l’évolution du décès isolé du tronc cérébral parmi les patients suspectés de décès neurologique, dans un premier temps, et d’estimer l’association entre l’accident vasculaire cérébral infratentoriel et le décès isolé du tronc cérébral dans cette population, dans un deuxième temps. Méthodes : Nous avons effectué une revue systématique et méta-analyse en suivant la méthodologie Cochrane et en interrogeant quatre répertoires d’articles scientifiques et la litérature grise. Nous avons sélectionné des études de cohorte, des études transversales, et des rapports de cas qui incluaient des patients suspectés de décès neurologique et qui rapportaient la prévalence, les caractéristiques ou l’évolution de patients avec une lésion cérébrale infratentorielle et de patients avec un décès isolé du tronc cérébral. Nous avons calculé la prévalence moyenne du décès isolé du tronc cérébral parmi les patients suspectés de décès neurologique avec une méta-analyse bayésienne hiérarchique à effet mixte. Nous avons aussi décrit les caractéristiques et l’évolution des cas de décès isolé du tronc cérébral publiés dans la litérature. Nous avons ensuite effectué une analyse de l’étude INDex, une étude observationnelle transversale, prospective et multicentrique, dans laquelle nous avons enrôlé de façon consécutive les patients adultes admis aux soins intensifs suite à une lésion cérébrale grave et suspectés de décès neurologique sur la base d’un coma profond. Nous avons identifié les patients avec l’exposition d’intérêt, soit un accident vasculaire cérébral infratentoriel, grâce à la base de données INDex et aux tomodensitométries cérébrales sans contraste. Tous les patients ont subi un examen clinique pour le décès neurologique, ainsi qu’un examen radiologique comportant une angiographie cérébrale et un scan de perfusion cérébrale par tomodensitométrie. Les issues primaires étaient le décès isolé du tronc cérébral basé sur la circulation (examen clinique compatible avec le décès neurologique et présence de circulation sanguine supratentorielle en absence de circulation sanguine infratentorielle à l’angiographie par tomodensitométrie) et le décès isolé du tronc cérébral basé sur la perfusion (examen clinique compatible avec le décès neurologique et présence de perfusion supratentorielle en absence de perfusion infratentorielle au scan de perfusion par tomodensitométrie). Nous avons estimé les associations entre l’accident vasculaire cérébral infratentoriel et les deux définitions de décès isolé du tronc cérébral grâce à des modèles de régression linéaire généralisée utilisant une fonction de liaison logit, un effet aléatoire sur l’ordonnée selon le site participant et une pondération basée sur un score de propension incluant les facteurs de confusion potentiels. Résultats : Un total de 21 études ont été incluses dans la revue systématique et méta-analyse. La prévalence moyenne du décès isolé du tronc cérébral parmi les patients suspectés de décès neurologique était de 1,5% (intervalle de densité à 95% : 0,5-3,9%), bien que le degré de confiance de cet estimé était très bas compte tenu des limitations méthodologiques et de l’hétérogénéité des études regroupées. Dans l’étude observationnelle, la prévalence du décès isolé du tronc cérébral parmi les patients suspectés de décès neurologique était de 12,7% (intervalle de confiance à 95% : 9,1-17,3%) lorsque la condition était définie selon la circulation et de 1,8% (intervalle de confiance à 95% : 0,6-4,2%) lorsqu’elle était définie selon la perfusion. Dans cette étude, nous avons observé une association entre l’accident vasculaire cérébral infratentoriel et le décès isolé du tronc cérébral basé sur la circulation (rapport de cotes ajusté : 2,52; intervalle de confiance à 95% : 1,53-4,17) et entre l’accident vasculaire cérébral infratentoriel et le décès isolé du tronc cérébral basé sur la perfusion (rapport de cotes ajusté : 16,81; intervalle de confiance à 95% : 3,95-71,51). Discussion : Ces trouvailles suggèrent que le décès isolé du tronc cérébral est rare parmi les patients suspectés de décès neurologique et que l’accident vasculaire cérébral infratentoriel pourrait être un facteur de risque dans cette population. / Background: Death by neurologic criteria is characterized by the permanent loss of brain functions essential for life following a severe brain injury. Isolated brainstem death is a medical condition in which all clinical criteria of death by neurologic criteria are fulfilled, but there is persistant supratentorial cerebral blood flow or perfusion on paraclinical testing (“ancillary testing”). These paraclinical findings suggest the possibility that there may be residual supratentorial brain function in isolated brainstem death, although the actual clinical implications of these findings are uncertain. Isolated brainstem death is not considered compatible with death by neurologic criteria in many jurisdictions around the world, but there is little data on its prevalence, characteristics and evolution among patients admitted to the intensive care unit and suspected of neurological death. Furthermore, there are no known risk factors for isolated brainstem death. In this thesis, two projects were conducted in order to characterize the prevalence, caracteristics and evolution of isolated brainstem death among patients suspected of death by neurologic criteria, and to estimate the association between infratentorial stroke and isolated brainstem death in this same population. Methods: We conducted a systematic review and meta-analysis following guidance from the Cochrane group, conducting our searches in four databases and the grey literature. We selected cohort and cross-sectional studies, as well as case reports, including patients suspected of death by neurologic criteria and reporting the prevalence, the characteristics or the evolution of patients with an infratentorial brain injury and of patients with isolated brainstem death. We estimated the mean prevalence of isolated brainstem death among patients suspected by death by neurologic criteria with a hierarchial mixed-effects Bayesian meta-analysis. We decribed the characteristics and evolution of patients with isolated brainstem death published in the literature. We also performed an analysis of the INDex trial, which was an observational, cross-sectional, prospective and multicentric study, in which we enrolled consecutive adult patients admitted to the intensive care unit following a severe brain injury and suspected of death by neurologic criteria based on a deep coma. We identified patients with the exposure of interest, infratentorial stroke, using the INDex database and non-contrast brain CT scans. All patients underwent clinical evaluation for death by neurologic criteria as well as radiologic evaluation with cerebral CT-angiography and CT-perfusion scans. Primary outcomes were isolated brainstem death based on flow (clinical examination consistent with death by neurologic criteria and presence of supratentorial blood flow in the absence of infratentorial flow on CT-angiography) and isolated brainstem death based on perfusion (clinical examination consistent with death by neurologic criteria and presence of supratentorial perfusion in the absence of infratentorial perfusion on CT-perfusion). We estimated associations between infratentorial stroke and both definitions of isolated brainstem death using generalized linear regression models with a logit function, random effects in the intercept according to the participating site, and inverse probability weighting based on a propensity score including all potential confounders. Results: In total, 21 studies were included in the systematic review and meta-analysis. The mean prevalence of isolated brainstem death among patients suspected of death by neurologic criteria was 1.5% (95% highest density interval: 0.5-3.9%), although the level of certainty in this estimate was very low due to methodological limitations and heterogeneity in included studies. In the observational study, the prevalence of isolated brainstem death among patients suspected of death by neurologic criteria was 12.7% (95% confidence interval: 9.1-17.3%) when the condition was based on flow and 1.8% (95% confidence interval: 0.6-4.2%) when it was based on perfusion. In this study, we observed an association between infratentorial stroke and isolated brainstem death based on flow (adjusted odds ratio: 2.52; 95% confidence interval: 1.53-4.17) and between infratentorial stroke and isolated brainstem death based on perfusion (adjusted odds ratio: 16.81; 95% confidence interval: 3.95-71.51). Discussion: These findings suggest that isolated brainstem death is rare among patients suspected of death by neurologic criteria and that infratentorial stroke may be a risk factor for this condition in this population.

<p>UVOD: Početak multiple skleroze (MS) u dečijem uzrastu je dijagnostički i terapijski izazov. I ako rani početak MS-a uglavnom ukazuje na dobru kratkoročnu prognozu, neka deca razviju te&scaron;ku onesposobljenost, fizičku ili kognitivnu, a vi&scaron;e od 50% obolelih uđe u sekundarno progresivnu formu bolesti pre 30. godine života. Rana dijagnoza je neophodna za uvođenje imunomodulatorne terapije, kojom se obezbeđuje dobra dugoročna prognoza. CILJ: Analiza parametara koji bi omogućili ranu dijagnozu multiple skleroza sa ranim početkom u odnosu na simptome, sprovedene dijagnostičke procedure i tok bolesti. Sagledavanje inicijalnih kliničkih manifestacija multiple skleroze, prisustva ologoklonaliteta, nalaza MRI endokranijuma i njihovih osobenosti u dečijoj populaciji uz komparaciju sa inicijalnim kliničkim manifestacijama kod pacijenata obolelih od multiple skleroze u odraslom dobu. MATERIJALI METODE: Ova retrospektivno/ prospektivna studija obuhvata pacijente lečene na Klinici za neurologiju KCV u Novom Sadu u periodu od dvanaest godina, od januara 2003. godine do januara 2015. godine sa znacima i simptomima inicijalne demijelinacione bolesti CNS. Od ove kohorte izdvojeno je dve grupe pacijenata; prva grupa pacijenata kod kojih je bolest nastala pre 18. godine života, i druga grupa uzrasta od 20-55 godina. Pacijenti su epidemiolo&scaron;ki obrađeni prema godinama početka bolesti, polu, porodičnoj istoriji, simptomima na početku bolesti (inicijalni simptom), toku bolesti- pojavi drugog relapsa i vremena do pojave drugog relapsa, nalazu MRI, nalazu evociranih potencijala i prisustvo oligoklonalnih traka u likvoru. Tokom praćenja beleži se vreme do drugog relapsa i tip relapsa. Tražila se korelacija između kliničkih i dijagnostičkih rezultata sa brzinom pojave drugog relapsa. Za testiranje razlika između grupa kori&scaron;ćen je Pirsonov hi-kvadrat test, a za testiranje jačine povezanosti kori&scaron;ćeno je Kramerovo V. Neparametrijski podaci su obrađivani Men-Vitni U testom. REZULTATI: Od ukupnog broja ispitanika, u grupi pacijenata sa ranim početkom MS-a odnos ženskog i mu&scaron;kog pola je bio 1,3:1, a u grupi pacijenata sa uobičajenim početkom MS-a 2,2:1. Iz dobijenih rezultata vidimo da ima manje nego &scaron;to je očekivano pacijenata rođenih u mesecima decembru 4,6% i januaru (5,9%), a vi&scaron;e nego &scaron;to je očekivanu u mesecima martu (11,3%) i julu (10,6%), &scaron;to nije statistički značajno (p=0,726). Prema manifestaciji bolesti kod dece 17,6% ima polisimptomatski početak, a kod odraslih 37,6% ima polisimptomatski početak.Polisimptomatski početak statistički je značajno vi&scaron;e zastupljen kod odraslih pacijenata (p=0,020).Poremećaj piramidnog sistema (P=0,010) i senzorne smetnje (P=0,006) su zastupljeniji kao inicijalni stimptom u grupi odraslih.Nisu nađene statistički značajne razlike u zastupljenosti optičkog neuritisa (p=0,366 ili p&gt;0,05) i ataksije /stablarne simptomatologije (p= 0,791) u ove dve grupe. Najče&scaron;ći inicijalni simptom kod dece, gotovo u istoj razmeri su optički neuritis (35,3%) i ataksija (35,3%). U grupi odraslih pacijenata senzorne smetnje (41,6%) su najče&scaron;ći inicijalni simptom, odmah za njim sledi piramidna simptomatologija (37,6%). Prema nalazu broja lezija na MRI pregledu, u grupi ispitanika sa ranim početkom MS-a vi&scaron;e su zastupljeni oni sa manje od 4 lezije, nego &scaron;to je to slučaj u grupi odraslih. Odnos broja pacijenata sa 4-10 i preko 10 lezija simetričan je u obe grupe. Korelacija između doba početka MS-a i broja lezija viđenih na MRI je statistički značajna i neznatna (P=0,06). Nije nađena statistička značajnost u prisustvu lezija u korpusu kalozumu između ove dve grupe pacijenata ( P=0,920). Primenom Fi&scaron;erovog dvostranog egzaktnog testa koji je u ovom slučaju statistički značajan (p=0,034), možemo reći da se grupa sa ranim početkom MS-a i ona sa uobičajenim početkom statistički značajno razlikuju, tumefaktivne lezije su prisutnije kod ispitanika sa ranim početkom MS-a. Pozitivni oligoklonali su zastupljeniji u grupi odraslih pacijenata ( P= 0,018). U na&scaron;oj grupi ispitanika kada smo pratili vreme pojave drugog pogor&scaron;anja, najkraće godinu dana, u grupi dece 11 pacijenata (21,6%) nije imalo pogor&scaron;anje , dok je 40 pacijenata imalo pogor&scaron;anje (78,4%),. Medijana kod grupe dece za pojavu drugog &scaron;uba bolesti je 12 meseci. U grupi odraslih 22 pacijenta ( 21,8%) nije imalo drugi relaps tokom perioda praćenja, dok je njih 79 (78,2%) imalo drugi relaps. Prosečno vreme u grupi odraslih pacijenata do drugog relapsa je 9 meseci. U grupi dece ne postoje značajne razlike u odnosu broja lezija viđenih na inicijalnom MRI pregledu i vremenu pojave drugog relapsa ( p=0,884) Kod odraslih postoji značajna razlika u vremenu relapsa između grupe sa manje od 4 lezije i grupe sa 4-10 lezija (p=0,09).Korelirali smo pacijente sa pozitivnim i negativnim ologoklonalnim trakama u likvoru u obe grupe sa vremenom nastanka prvog pogor&scaron;anja, pri toj korelaciji nije dobijena statistički značajna razlika ni u grupi dece ( P= 0,598) ni u grupi odraslih (P=0,133). Kod ispitanika sa ranim početkom če&scaron;ća je pozitivna porodična anamneza, u vidu prisustva MS i drugih imunolo&scaron;kih bolesti( P =0,042). ZAKLJUČAK: Polisimptomatski početak je če&scaron;ći kod odraslih, pozitivne oliogoklonalne trake su ređe pozitivne kod dece, kod dece je najče&scaron;ći inicijalni simptom optički neuritis a kod odraslih senzitivne i motorne smetnje. Manje od 4 lezije se če&scaron;će javljaju kod dece na inicijalnom MRI pregledu, &scaron;to je najverovatnije povezano sa vremenom stvarnog početka bolesti i njenom kliničkom manifestacijom. Kod pacijenta sa ranim početkom MS-a duži je period do drugog pogor&scaron;anja. U grupi dece ne postoje statistički značajne razlike u odnosu broja lezija viđenih na inicijalnom MRI pregledu i vremenu pojave drugog relapsa. Kod odraslih postoji značajna razlika u vremenu relapsa između grupe sa manje od 4 lezije i grupe sa 4-10 lezija. Inicijalne manifestacije MS-a u dečijem uzrastu ne razlikuje se u mnogome od MS-a kod odraslih po karakteristikama i toku bolesti.</p> / <p>INTRODUCTION: Тhe onset of multiple sclerosis (MS) in childhood poses diagnostic and therapeutic challenges. Althougth the onset of MS in childhood typically predicts a fevoruable short/term prognosis, some children are severy disabled. Etiher physically or cognitively, and more then 50% are predicted to enter the secondary-progressive phase of the disease by the age of 30 years. Immunomodulatory therapies for MS and their safe application in children can improve long-therm prognosis. AIM: We saught to identifay clinical and diagnostic features in children wich inplicate to early diagnosis of MS in children. We aimd to determine the clinical features, cerebro spinal fluid, magnetic resonance imagin (MRI) features of children and their comparation with adult MS patients. METHODS: In this retrospective/prospective study we present data from 152 patients with clinical isolated syndrom (CIS) for the first time, which are obtained throught Clinic of Neurology , Clinical Centre of Vojvodina, Novi Sad from January 2003 to January 2015g. Patients were divided into two grups - in first group patients 51 with early onset of disease before 18 years, and second group patients with adult onset desease (20-55 year). Patients wer observed for a minimum one year. The common presenting symptoms, gender, MRI finding, oligoclonal band (OCB) and Visual evoked potential findings, corse of disease, family history were compared between the two groups and with thime of second relaps. To test the difference between groups was used Chi-square Pearson product moment test, and to test the strength of connection used is a Kramer V. Population data are processed Men-Whitney U test. RESULTS: Of the total number of respondents, in the Group of patients with early beginning MS the ratio of women and men was 1.3:1, and in the group of adult MS patients 2, 2:1. From the results we can see that fewer than expected has patients born in the months December ( 4.6%) and January (5.9%), and higher than expected in a March (11.3%) and July (10.6%), which is not statistically significant (p = 0,726). According to the manifestation of disease in children 17.6% has a polifocal onset, and in adults 37.6% has a polifocal onset. Polifocal beginning is significantly over represented in adult MS patients (p = 0,020). Motor disorder (P = 0,010) and sensory disabilities (P = 0.006) are more present as the initial manifestation illness in the adult. They not found statistically significant differences in the representation of optic neuritis (p = 0,366 or p &gt; 0.05) and ataxia (p = 0.791) in these two groups. The most common initial symptom in children, almost in the same scale are the optical neuritis (35.3%) and ataxia 6 (35.3%). In a group of adult patients sensory disturbances (41.6%) are the most common initial symptom, right behind him follows a motor disturbens (37.6%). According to the number of lesions on the MRI exam, in a group of subjects with early MS more are they less than four lesions, than is the case in the group adults. The ratio of the number of patients with 4-10 and over 10 symmetrical lesions in both groups. Correlation between the time of the beginning of the MS and the number of lesions seen on MRI is statistically significant and insignificant (P = 0.06). There was no statistical significance in the presence of lesions in the corpus callosum indicates between these two groups of patients (P = 0,920). Application of Fisher the exact test case that is in this case a statistically significant (p = 0.034). We can say that the group with the early start of MS and the one with the usual beginning of significantly different, tumefactiv lesions are present in patients with early onset MS, Positive oligoclonal bands are more present in a group with adult MS patients (P = 0.018). In our group of respondents when we track time appear another relapse, minimum one year, 11 children (21,6%) had no deterioration, while the 40 children had worsening (78,4%). The median at groups of children for the appearance of second relapse is 12 months. In the adult these 22 (21,8%) had another relapse for tracking period, while 79 (78.2%) had another relapse. The average amount of time in the adult patients relapse to another is 9 months. In a group of children there are no statistically significant differences in the relative number of lesions seen on the initial MRI examination and time show up another relapse (p = 0,884). In adults there is a significant difference in relapse time between groups with fewer than four lesions and groups with 4-10 lesions (p = 0.09). Pressures are patients with positive and negative ologoclonal bands in the cerebrospinal fluid in both groups with the time of occurrence of the first downturn, when the correlation is not get statistically significant difference in the children (P = 0.598) or in a group of adults (P = 0,133). In patients with early starting stacks is a negative family history, and often the presence of MS and other immunological diseases (P = 0,042). CONCULSIONS: Polisifocal beginning is more common in adults, positive oliogoklonalne bands are less positive in children, with children being the most common initial symptom is optic neuritis, in adult sensitive and motor disturbances. Tumefactiv lesions are present in patients with early onset MS. Less than four lesions are more common in children on the initial MRI examination, which is probably connected with the time of the real onset of the disease and its clinical manifestation n the group of children there are no statistically significant differences in relation to the number of lesions seen on MRI at the initial examination and the timing of another relapse. For adults there is a significant difference in time of relapse between the groups with less than 4 lesions and groups with 4-10 lesions. Children onset MS does not significantly differ from that it has been typically seen in adults in terms of major clinical manifestations and course of disease.</p>