Background Multiple sclerosis (MS) is an autoimmune disease characterised by inflammatory damage to the central nervous system (CNS). Accumulated CNS injury can be quantified as brain atrophy, definable as a reduction in brain parenchymal fraction (BPF). BPF correlate with disability in MS and is used routinely as an endpoint in clinical trials. In 2009/2010, a new MS clinical care program, that includes follow-up of BPF, was introduced at Umeå University Hospital (NUS). Levels of neurofilament light polypetide (NFL) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) are markers of axonal and astrocytic injury, respectively, and also potential surrogate biomarkers for BPF decline. The goals of this thesis were to establish age-adjusted values of BPF in healthy individuals and to relate these to the BPF values from individuals with MS as well as to the levels of NFL and GFAP in CSF. Another goal was to investigate if expanded disability status scale (EDSS)-worsening could be predicted in a clinical MS cohort and if BPF measurements could contribute to such predictions. Methods A group of 111 healthy individuals volunteered to participate in the studies. A total of 106 of these underwent MRI with BPF measurements, 53 underwent lumbar puncture (LP) with measurement of NFL and GFAP and 48 underwent both MRI and LP. Three different automatic and one manual method were utilised to determine BPF. A literature search on BPF in healthy individuals was performed for the purpose of a systematic review. For studying disability progression in MS, all individuals with MS followed at NUS and included in the Swedish MS registry were included if they had matched data on BPF, EDSS and lesion load as part of clinical follow-up (n=278). Results BPF as well as NFL and GFAP levels in CSF were all associated with age. NFL was associated with BPF and GFAP, but only the association with GFAP was retained when adjusting for age. Significant differences were found between different methods for BPF determination. In the MS population, BPF was associated with EDSS. Only progressive disease course could predict EDSS worsening. Conclusion The data on BPF and levels of NFL and GFAP in CSF of healthy individuals can aid in the interpretation of these variables in the setting of MS. Knowledge on differences in BPF data from different methods for BPF determination can be useful in comparing data across studies, but also highlights the need for a commonly accepted gold standard. The correlation between GFAP and NFL levels in CSF may indicate an association between glial and axonal turnover that is independent of the aging effect on the brain. However, the low number of volunteers for LP precluded clear conclusions. An association between BPF and EDSS was seen in the MS group. The ability to predict EDSS worsening in the clinical MS cohort was limited.

Made available in DSpace on 2016-12-06T17:07:08Z (GMT). No. of bitstreams: 1 02-Elementos Pre-textuais.pdf: 141371 bytes, checksum: 53522240ad7745d208315c98271c3a5a (MD5) Previous issue date: 2005-12-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Neuropsychomotor impairment prevention becomes essential when progresses in obstetrics and neonatology áreas promote larger survival of risk babies. Neonatology High Risk Clinics have been implemented to provide attendance for these children, that usually have prevalence of neurological risk factors. Promoting the attention for their Neuropsychomotor Development, this study aimed to present a proposal of High Neurological Risk Children Clinical Neuropsychomotor Follow up, what is in implantation in Clinic of Neonatolgy High Risk from Academical Hospital at Santa Catarina Federal University. In the evaluation protocol were used: File of Biopsychossocial Data Register (risk factors verification and notes of assessments accomplished in consultations), Neonatal Medical Índex (for preterm neurobehavioral risk categorization), and Brunet-Lèzine Test (in adaptation by SOUZA, 2003, for determination of neuropsychomotors data Developmental Ages and Quotients/ DA and DQ - in Postural, Eye-Hand Coordination, Language, Social and Global areas,). From setember/04 to setember/05, 87 evaluations were accomplished, distributed among 40 infants. Preterm birth was the more frequent risk factor (85%), with Moderate (44,1%) and Extreme (55,9%) degree; NMI III was the more commom manifestation (44,1%) and there was significant lineal relationship between neurobehavioral risk and DQ in Social area /DQS (P=0,026). In follow up analysis, DQs tended to decrease, with smaller scores in Eye-Hand Coordination area, and statistical significance in prematuridade degree (P=0,025) in this area. DQS performance presented significant difference among evaluations of first and second year of life (P=0,019). Females have better neuropsychomotor performance either in the first (Posture and Eye-Hand Coordination, P=0,025 and P=0,008) and second year of life (Posture, Language and Global, P=0,017, P=0,047 and P=0,036). High Neurological Risk Children Clinical Neuropsychomotor Follow up proposal seems to linked child attendance and neurpsychomotor research. Its continuity aim to reinforce the neuropsychomotor intervention program, in order to promote health and quality of life for chidren and their families, with an approach more global and efficient. / Enfatizar a prevenção de distúrbios neuropsicomotores torna-se fundamental à medida que os avanços em obstetrícia e neonatologia promovem maior sobrevivência de bebês de risco. Ambulatórios de Alto Risco em Neonatologia têm sido implementados para proporcionar o acompanhamento dessas crianças, em que geralmente há predomínio de fatores de risco neurológico. Promovendo a atenção ao Desenvolvimento Neuropsicomotor de tal população, este estudo busca apresentar uma proposta de Acompanhamento Neuropsicomotor Ambulatorial de Crianças de Alto Risco Neurológico, que está em implantação junto ao Ambulatório de Alto Risco em Neonatologia do Hospital Universitário, Universidade Federal de Santa Catarina. No protocolo de avaliação foram utilizados: Ficha de Registro de Dados Biopsicossocias (verificação de fatores de risco e registro de avaliações realizadas nas consultas), Neonatal Medical Index (Índice Médico Neonatal, para categorização do risco neurocomportamental em prematuros), e Escala de Brunet-Lèzine (na adaptação de SOUZA, 2003, para determinação de dados neuropsicomotores - Idades e Quocientes de Desenvolvimento/ID e QD - nas áreas Postural, Coordenação Óculo-Motriz, Linguagem, Social e Global). De setembro/04 a setembro/05 foram realizadas 87 avaliações, distribuídas entre 40 lactentes. Nascimento pré-termo foi o fator de risco mais freqüente (85%), com grau Moderado (44,1%) e Extremo (55,9%), sendo que a categoria III no NMI foi de maior manifestação (44,1%) e houve relação linear significativa entre risco neurocomportamental e QD na área Social/QDS (p=0,026). Em análise longitudinal, os QDs tenderam a decrescer, com menores escores na Coordenação Óculo-Motriz, e significância estatística em relação ao grau de prematuridade (p=0,025) nesta área. O desempenho do QDS apresentou diferença significativa entre avaliações de primeiro e segundo ano de vida (p=0,019). Foi observado melhor desempenho neuropsicomotor no sexo feminino, tanto no primeiro (Postura e Coordenação Óculo-Motriz, p=0,025 e p=0,008) como no segundo ano de vida (Postura, Linguagem e Global, p=0,017, p=0,047 e p=0,036). A proposta de Acompanhamento Neuropsicomotor Ambulatorial de crianças de risco parece ter conseguido promover a veiculação da assistência à saúde da criança com a pesquisa sobre o desenvolvimento infantil. Sua continuidade prossegue em termos do fortalecimento do programa de intervenção neuropsicomotora, a fim de promover de forma mais global e efetiva saúde e qualidade de vida das crianças e suas famílias.