Orientador: Maria Valeriana Leme de Moura Ribeiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T12:23:12Z (GMT). No. of bitstreams: 1 Airoldi_MarinaJunqueira_M.pdf: 5702275 bytes, checksum: 3c2bd8bd99c4abe1bd021c54e7de91e9 (MD5) Previous issue date: 2012 / Resumo: Objetivos: O Objetivo deste estudo foi descrever apresentação clínica da doença, a evolução neuromotora, assim como a epilepsia. Métodos: Foram incluídas no estudo 18 crianças nascidas a termo. A avaliação ocorreu nas idades entre 6 e 16 anos utilizando se o teste EB Teste. O estudo foi retrospectivo quanto aos dados relacionados a antecedentes, diagnóstico do AVC e evolução quanto à epilepsia e transversal quanto à avaliação neuromotora. Resultados: Das 18 crianças estudadas, 4 (22%) foram diagnosticadas com AVCI depois dos 3 meses de idade, principalmente pelos sinais de assimetria; 14 crianças (77%) foram diagnosticadas na fase aguda, sendo que 11 (79%) apresentaram convulsões, 5 (36%), hipotonia e 3 (21%) sucção débil. Na evolução das 18 crianças, 11 (61%) desenvolveram epilepsia. As crianças que tiveram crises na fase aguda apresentaram probabilidade significativamente maior de evoluir com epilepsia (p <0.05). Em relação à neuroimagem, 17 indivíduos apresentaram comprometimento na Artéria Cerebral Média, com acometimento do hemisfério esquerdo em 13. Foram diagnosticadas com Paralisia Cerebral com hemiparesia 16 crianças. Em relação à escala neuromotora aplicada, EB teste, todas as crianças avaliadas apresentaram déficit em todas as dimensões estudadas. Crianças com lesões mais extensas apresentaram pior desempenho motor. Não houve recorrência do AVC. Conclusão: É importante identificar sintomas e sinais na fase aguda, permitindo que profissionais confirmem com imagem o comprometimento vascular no período perinatal. É necessário valorizar acompanhamento ambulatorial, identificando anormalidades neuromotoras e epilepsia na evolução, promovendo tratamento adequado para melhora da qualidade de vida destas crianças / Abstract: Objectives: The aim of this study was to describe clinical presentations, neurodevelopmental and epilepsy outcomes of IPS in children. Methods: A retrospective study was conducted in a children population and it was evaluated term infants ! 38 weeks gestational age, aged between 6 and 16 years, with diagnosis of IPS. The diagnosis was confirmed in 18 cases by Neuroradiology (CT or MRI). We studied the neuroimaging and data from acute phase as well as the evolution of these children through neuromotor scale IB Test. Results: In 18 cases, 4 (22%) was diagnosed with brain infarction after 3 months of age, especially for signs of asymmetry. Of the 14 remaining patients (77%) diagnosed early, 11(79%) had seizures, 5 (36%) had hypotonia and 3 (21%) had signs of low suction. In the group of 18, 11 (61%) evolved with epilepsy and children with seizures in the acute phase were more likely to develop epilepsy (p <0.05). Large cortically based infarcts were the most common pattern and, in 17 cases, it affected the middle cerebral artery territory involving the left size in 13. 16 children were diagnosed with cerebral palsy hemiparetic. In neuromotor scale applied, IB Test, all children presented deficit in all dimensions studied. Children with more extensive lesions had worse motor performance. There was no recurrence of stroke. Conclusion: It is important to understand symptoms and signs of acute allowing professionals to carry out identification of vascular involvement in the perinatal period. It is necessary to enhance outpatient identifying neuromotor abnormalities and epilepsy in the evolution promoting appropriate treatment to improve quality of life for these child / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

Magister Scientiae (Physiotherapy) - MSc(Physio) / Bell’s palsy (BP), a fairly common disorder predominantly prevalent in the adult age group, affects nerves and muscles in the face causing paralysis or dropping of one side of the face. Clients with Bell’s palsy face many challenges, including psychological, physical and emotional. A long recovery period and/or delayed complete healing could lead to a negative effect on many aspects of an individual's life. How society perceives the person could negatively influence the client’s self-confidence. The management of Bell’s palsy depends on the individual case and may include medication, physiotherapy and as a last option, surgery. The aim of the study was to investigate the management of Bell’s palsy at primary health care level in the Cape Metropolitan District of the Western Cape. The study specific objectives was to investigate the management or treatment protocol of clients with Bell’s palsy, to determine the tendency for referral for physiotherapy, to determine whether an association exists between the type of management or treatment received and the recovery of clients with Bell’s palsy and to explore the impact Bell's Palsy has on the clients. The over-arching design of the study was the sequential explanatory mixed methods design where qualitative data was used to assist in explaining and interpreting the findings of a primarily quantitative study. Stratified random sampling was done proportionately to ensure equal representation. A self-administered questionnaire, comprising of four sections, was used to collect quantitative data that was analysed using SPSS version 21. Descriptive statistics was employed to summarise the data on the socio-demographic information of the clients. Inferential statistics was used to determine the distributions of cases in the various groups. Significant differences tested for using the Chisquare test and effect size through Cramer’s V tests. A semi-structured interview guide was developed based on the results of the analysis of the quantitative data. Focus group discussions were employed to a sub-sample of the clients with Bell’s palsy. Permission an ethical clearance will be obtained from Senate Higher Degrees Committee at the University of the Western Cape (UWC), the Western Cape Department of Health and the facility managers of the participating CHCs.

INTRODUCTION: Cerebral Palsy (CP) is the most common disabling motor disorder found during childhood, occurring in 2.1-3.2 of every 1,000 births. Motor functionality of children with CP is commonly compromised and is classified with a gross motor function classification score (GMFCS) and with the gross motor function measure (GMFM). Balance ability has typically been assessed using single leg stance test (SLST) time but more recently, center of pressure excursion (COPE) has shown to be a more valid measurement in populations with altered motor abilities. However, COPE has not been used to test balance in the CP population, yet. This study aimed to determine if relationships were present between COPE measurements, functionality measurement scores (GMCS and GMFM) and reported fall frequency. It was hypothesized that i) larger COPE measurements would be associated with a higher GMFCS level and lower GMFM score, and that ii) COPE measurements would be significantly higher in children with a high reported incidence of fall frequency. METHODS: Gross functionality was measured using a GMFM score and GMFCS level. Balance ability was assessed using COPE measurements on a force plate and SLST time. Fall frequency was determined by a short questionnaire. A Pearson correlation analyzed COPE measurements vs. mean GMFM score. A one-way ANOVA was used to compare COPE measures between GMFMCS levels, with a Bonferroni post-hoc test. Lastly, an independent sample t-test analyzed differences in COPE measurements and SLST time between fall frequency groups. RESULTS: Significantly larger COPE velocities were demonstrated in children who reported a greater number of falls in the past month and were considered high risk for falling (p = 0.02). No relationships were demonstrated between COPE measurements and GMFM score. GMFCS level III participants demonstrated statistically significant lower COPE velocity compared to GMFCS level II participants (p = 0.05). There were no significant differences in SLST between high and low risk fall groups (p = 0.07). DISCUSSION: Children with higher reported fall frequencies demonstrated a 60% increase in COPE velocity, compared to those with little to no falls. Clinical GMFM scores did not demonstrate significant correlations to COPE measurements and may not be an appropriate identifier for falling in children diagnosed with CP. This is the first trial to evaluate COPE measurements and reported fall frequencies in children diagnosed with CP. The use of a force plate to determine COPE velocity during a SLST is useful in identifying children with CP who may be at an elevated risk for experiencing a fall. COPE velocity was able to provide intricate quantitative data regarding fall risk that could not be obtained during a normal SLST.

Cerebral Palsy is a complex, non-progressive condition that manifests in various forms of motor impairments. This life-long condition holds numerous challenges for the entire family throughout the family life-cycle. While the challenges that these families have to face are many, families seem to have the ability to "bounce back" and to be resilient. Research on the construct of resilience and more specifically family resilience has increased in recent times. South African family resilience research is relatively limited. This study aimed to identify, explore and describe the resiliency factors that facilitate adjustment and adaptation in families that include a child living with Cerebral Palsy. The Resiliency Model of Family Stress, Adjustment and Adaptation was used to conceptualise the level of family adaptation. The study was triangular in nature, with an exploratory, descriptive approach. Non-probability purposive and snowball sampling techniques were employed. The sample consisted of 30 female caregivers. Biographical questionnaires with two open-ended questions, in conjunction with seven structured questionnaires were used to gather the data. Descriptive statistics were used to analyse the biographical information. Correlation and regression analysis was used to analyse the quantitative data, while content analysis was used to analyse the qualitative data. The results of the quantitative component of the study indicated five significant positive correlations with the FACI8. These variables were family hardiness (measured by the FHI), family time together and routines (measured by the FTRI), social support (measured by the SSI), relative and friends support (measure by the RFS), and spiritual support (measured by the F-COPES). The results of the qualitative analysis revealed that social support, the caregivers' acceptance of the condition, and spirituality and religion were the most important strength factors that contributed to the families' adjustment and adaptation. Although the sample was small and the study has limitations, it could be used as a stepping-stone for future research on resilience in families living with a child with a physical disability and will contribute to the broader context of family resilience research in South Africa.

The primary tauopathies are a group of neurodegenerative diseases affecting movement and cognition. In this thesis I study Progressive Supranuclear Palsy (PSP) and the Corticobasal Syndrome (CBS), two parkinsonian disorders associated with accumulation of hyperphos- phorylated and abnormally folded tau protein. I contrast these two disorders with Parkinson’s disease (PD), which is associated with the accumulation of alpha-synuclein but has a genetic association with the MAPT gene encoding tau. Understanding the tauopathies to develop effective treatments will require a better grasp of the relationships between clinical syndromes and cognitive measures and how the anatomical and neurochemical networks that underlie clinical features might be altered by disease. I investigate simple clinical biomarkers, showing that a two-minute test of verbal fluency is a potential diagnostic biomarker to distinguish between PD and PSP and that the ACE-R and its subscores could play a role in monitoring cognition over time in PD, PSP and CBS. I assess the implementation of network analysis in Functional Mag- netic Resonance Imaging (fMRI) data, introduce Maybrain software for graphical network analysis and visualisation. I go on to show an overlap between graph theory network measures and I identify three main factors underlying graph network measures of: efficiency and distance, hub characteristics, network community measures. I apply these measures in PD, PSP and the CBS. All three diseases caused a loss of functional connectivity in com- parison to the control group that was concentrated in more highly connected brain regions and in longer distance connections. In ad- dition, widely localised cognitive function of verbal fluency co-varied with the connection strength in highly connected regions across PD, PSP and CBS. To take this further, I investigated specific functional covariance networks. All three disease groups showed reduced connectivity between the basal ganglia network and other networks, and between the anterior salience network and other networks. Localised areas of increased co- variance suggest a breakdown of network boundaries which correlated with motor severity in PSP and CBS, and duration of disease in CBS. I explore the link between gene expression of the tau gene MAPT and its effects on functional connectivity showing that the expression of MAPT correlated with connection strength in highly connected hub regions that were more susceptible to a loss of connection strength in PD and PSP. I conclude by discussing how tau protein aggregates and soluble tau oligomers may explain the changes in functional brain networks. The primary tauopathies are a group of neurodegenerative diseases affecting movement and cognition. In this thesis I study Progressive Supranuclear Palsy (PSP) and the Corticobasal Syndrome (CBS), two parkinsonian disorders associated with accumulation of hyperphos- phorylated and abnormally folded tau protein. I contrast these two disorders with Parkinson’s disease (PD), which is associated with the accumulation of alpha-synuclein but has a genetic association with the MAPT gene encoding tau. Understanding the tauopathies to develop effective treatments will require a better grasp of the relationships between clinical syndromes and cognitive measures and how the anatomical and neurochemical networks that underlie clinical features might be altered by disease. I investigate simple clinical biomarkers, showing that a two-minute test of verbal fluency is a potential diagnostic biomarker to distinguish between PD and PSP and that the ACE-R and its subscores could play a role in monitoring cognition over time in PD, PSP and CBS. I assess the implementation of network analysis in Functional Mag- netic Resonance Imaging (fMRI) data, introduce Maybrain software for graphical network analysis and visualisation. I go on to show an overlap between graph theory network measures and I identify three main factors underlying graph network measures of: efficiency and distance, hub characteristics, network community measures. I apply these measures in PD, PSP and the CBS. All three diseases caused a loss of functional connectivity in com- parison to the control group that was concentrated in more highly connected brain regions and in longer distance connections. In ad- dition, widely localised cognitive function of verbal fluency co-varied with the connection strength in highly connected regions across PD, PSP and CBS. To take this further, I investigated specific functional covariance networks. All three disease groups showed reduced connectivity between the basal ganglia network and other networks, and between the anterior salience network and other networks. Localised areas of increased co- variance suggest a breakdown of network boundaries which correlated with motor severity in PSP and CBS, and duration of disease in CBS. I explore the link between gene expression of the tau gene MAPT and its effects on functional connectivity showing that the expression of MAPT correlated with connection strength in highly connected hub regions that were more susceptible to a loss of connection strength in PD and PSP. I conclude by discussing how tau protein aggregates and soluble tau oligomers may explain the changes in functional brain networks.

Background: Persons with developmental disabilities (DDs) represent about 1-3% of the total population in Canada; however, very little statistical data exists regarding this population in the context of long-term care (LTC). As the life expectation of these individuals increases, the distinct needs they have that are associated with aging should be addressed in LTC to help improve the quality and relevancy of the care they receive. Methods: An exploratory qualitative study. Semi-structured interviews were conducted. Open coding of interview transcripts, and content analysis was completed. Descriptive statistics of the sample were calculated using Excel. Results: All participants had experienced earlier functional decline which resulted in changes in their care needs. Often this meant needing to change their assistive devices. Many participants feared losing their independence as they aged. Conclusion: There is insufficient understanding of the unique needs that face people aging with DDs or how they access LTC. The preference for these individuals is to age in place, their independence must be maintained in order for this to be successful. Three factors help to facilitate this: assistive devices, attendant care and accessibility of health care services. Contexte: Les personnes ayant un handicaps developmental représentent environ 1-3% de la population totale au Canada. Cependant, très peu de données statistiques concernant cette population existent dans le contexte de soins de longue durée. L’espérance de vie de ces personnes augmente, les besoins distincts associés au vieillissement devraient être examinés pour aider à améliorer la qualité et la pertinence des soins qu'ils reçoivent dans les soins de longue durée. Méthodes: Une étude qualitative exploratoire. Des entrevues semi-structurées ont été menées. Les transcriptions d'entrevues ont été codées en utilisant un style de codage ouvert et l'analyse de contenu a été accomplie. Les statistiques descriptives des participants ont été calculées. Résultats: Plusieurs thèmes sont devenus apparents. Tous les participants avaient connu un déclin fonctionnel à un jeune âge qui a entraîné des changements dans leurs besoins de soins. Souvent, cela signifit avoir à changer leurs appareils et accessoires fonctionnels. De nombreux participants craignaient de perdre leur indépendance en vieillissant. Conclusion: Il y a une méconnaissance des besoins uniques auxquels font face les personnes vieillissant avec un handicap developmental et la façon dont ils accident aux soins de longue durée. La préférence pour ces personnes est de viellir en place, leur indépendance devant être maintenue pour que ce soit un succès. Trois facteurs contribuent à faciliter ceci: les appareils et accessoires fonctionnels, les soins auxiliaires et l'accessibilité aux services santé.

BACKGROUND: It has long been accepted that the environment we experience can impact our well-being; throughout recorded history, the greatest prevalence and severity of disease has been experienced by marginalized and underserved populations. However, the translation of such nontangible influences into biological changes in our health has been elusive until the recent advent of epigenetic studies. Modifications outside of the genome play a critical role in regulating transcription as well as subsequent gene expression without altering DNA sequencing by controlling the accessibility of the DNA for interaction with key initiation proteins and enzymes. These modifications, which include DNA methylation, histone acetylation, and small noncoding microRNA regulation, have increasingly been found to have a fluid, adaptive response to experiences throughout life. Based on the literature supporting societal stressors negatively impacting neurologic outcome, as well as elucidating an association between epigenetic changes and adverse neurologic outcome, we hypothesize that alterations in CpG methylation sites associated with socioeconomic adversity will also be correlated with the incidence of Neurodevelopmental Disorders. METHODS: 889 of the 1,506 neonates initially recruited from 14 medical centers throughout the United States at their time of birth qualified to participate in this study. Placental samples were taken immediately following delivery and neonatal blood samples were taken within the first month of life. Children that survived were followed at 2 years old and 10 years old to evaluate for the presence of four possible Neurodevelopmental Disorders: cognitive impairment, Cerebral Palsy, Autism Spectrum Disorder, and epilepsy. Taking this data as well as demographic information into consideration, the entire cohort included in this study was first evaluated for aberrant methylation levels at 33 CpG sites previously associated with socioeconomic adversity to analyze the degree of significant correlation between altered methylation status and Neurodevelopmental Disorder prevalence. A secondary Epigenome-Wide Association Study was conducted for each of our 889 participants to pinpoint significant changes in CpG methylation in order to evaluate the relationship between altered methylation of particular genes and incidence of Neurodevelopmental Disorders. Taking the previous finding that cognitive impairment imposes a greater burden on both the individual and society than non-cognitive impairment into consideration, both analyses were categorized based on this measure of impairment severity: No Impairment, Non-Cognitive Impairment (diagnosed with Cerebral Palsy, Autism Spectrum Disorder, and/or epilepsy without cognitive deficit), and Cognitive Impairment (cognitive deficit with or without other neurodevelopmental disorders present). RESULTS: Primary analysis of the 33 CpG sites previously associated with socioeconomic adversity did not reveal any significant associations with Non-Cognitive or Cognitive Impairment. However, cg15519318 and cg10613063 (located in the PCCB gene) were marginally associated with Non-Cognitive Impairment while cg02765535 (located in the NTN4 gene) was marginally associated with Cognitive Impairment. Secondary analysis of the entire epigenome found 4 CpG sites significantly associated with Non-Cognitive Impairment (cg07322235, cg13592565, cg13723879, and cg24387818) as well as 4 CpG sites significantly associated with Cognitive Impairment (cg23081580, cg14134658, cg00762003, and cg08546514). DISCUSSION: We were not able to define a significant relationship between the CpG methylation sites related to socioeconomic adversity and adverse neurodevelopmental outcomes. This could stem from several causes, including insufficient power as well as limiting our evaluation of the extensive list of environmental influences to the four measures of societal stress focused on in this study (low educational attainment, single relationship status, public health insurance, and receiving supplemental nutrition assistance). Investigating the epigenome for differential methylation that was significantly associated with the incidence of Neurodevelopmental Disorders identified CpGs associated with several important genes, including genes coding for Neuregulin-3 (NRG3) and Premature Ovarian Failure Actin Binding Protein 1B (POF1B) region with Non-Cognitive Impairment as well as genes coding for Six-Transmembrane Epithelial Antigen of Prostate 2 Metalloreductase (STEAP2), Ly1 Antibody Reactive (LYAR), 1-Acylglycerol-3-Phosphate O-Acyltransferase 3 (AGPAT3), and Ninein-like protein (NINL) with Cognitive Impairment.

Cerebral palsy is the most common physical disability among children. Children diagnosed with bilateral cerebral palsy (BCP) have limited mobility and hand use due to a neurological insult in utero or during the first year of life, resulting in hypertonicity or uncontrolled movements which impede upon optimal performance and participation in daily life. Although occupational therapists evaluate and provide interventions throughout a child’s development, only two validated assessment tools exist for children with BCP: Melbourne Assessment 2 and Both Hands Assessment, and ABILHAND-Kids questionnaire. The purpose of this study was to (a) develop an observational tool to evaluate upper extremity functioning in children with BCP during everyday tasks, and (b) determine the tool’s content validity, preliminary inter-rater reliability, and internal consistency. The Hand-object Observation Tool (HOOT) was developed, standardized, and evaluated for content validity via expert review and feedback regarding relevance for children with BCP. Following pilot administration to three children and content validation by expert clinicians (n = 8), the HOOT was administered to six children diagnosed with BCP, GMFCS III, IV, and V. Three licensed occupational therapists and the primary investigator observed and scored video-recordings of the administration. Cohen’s kappa was used to determine inter-rater reliability among three pairs of clinician raters and the gold standard. Internal consistency of items was analyzed using Cronbach’s alpha coefficient. The content of the HOOT is consistent with expert opinions and the Content Validity Index results met criteria for retaining items. This study further suggests that HOOT scores are reliable indicators of upper extremity functioning in children with BCP. Rater agreement between occupational therapy raters and the gold standard was almost perfect when scoring hand-object interaction (touch, grasp, transport, manipulate, place, and release). Rater agreement was substantial to almost perfect for hand use and poor to almost perfect for maintenance of posture during tasks. Further research is required to (a) gather additional data from trained clinicians administering the HOOT in community-based settings to more than 30 children with BCP, and (b) analyze scores and performance to determine internal consistency of HOOT items and complete tool refinement and dissemination.

We investigated the association of Bell's palsy (BP) with the subsequent risk of Parkinson's disease (PD) using a case-control study design. We matched 196 incident cases of PD in Olmsted County, MN, to 196 general population controls with same age (±1 year) and sex, and we reviewed the complete medical records of cases and controls in a medical records-linkage system to detect BP. Six of the 196 patients with PD and none of the 196 controls were diagnosed with BP before PD (exact binomial probability, P = 0.02). The median age at occurrence of BP was 49.5 years (range, 15-84 years) and the median time between BP and the onset of PD was 27.5 years (range, 2-54 years). The findings were similar using a standardized incidence ratio (SIR) approach, but were not statistically significant. This initial association between BP and PD awaits replication.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: Rehabilitation Robotics (RR) has become a more widely used and better understood treatment intervention and research tool in the last 15 years. Traditional research involves pre and post-test outcomes, making it difficult to analyze changes in behavior during the treatment process. Harnessing kinematics captured throughout each treatment allows motor learning to be quantified and questions of application and dosing to be answered. Objective: The aims of this secondary analysis were: (i) to investigate the impact of treatment presentation during RR on upper extremity movement time (mt) in children with hemiplegic cerebral palsy (CP) and (ii) to investigate the impact of training structure (dose and intensity) on mt in children with CP participating in RR. Methods: Subjects completed 16 intervention sessions of RR (2 x week; 8 weeks) with a total of 1,024 repetitions of movement per session and three assessments: pre, post and 6 month f/u. During each assessment and intervention, subjects completed “one-way record” assessments tracking performance on a planar task without robotic assistance. Kinematics from these records were extracted to assess subject performance over the course of and within sessions. Results: For all participants, a significant decrease in mt was found at post-test and follow-up. No significant differences were found in mt for age, severity or group placement. A significant interaction was found between treatment day, block and group (p = .033). Significant mt differences were found between the three blocks of intervention within individual days (p = .001). Specifically, significant differences were found over the last block of treatment (p = .032) and between successive treatment days (p = .001). Conclusion: The results indicate that for children with CP participating in RR, the number of repetitions per session is important. We hypothesized that children’s performance would plateau during a treatment day as attention waned, the opposite proved to be true. Despite the high-number of repetitions and associated cognitive demand, subjects’ performance actually trended upwards throughout the 1,024 repetitions suggesting that children were able to tolerate and learn from a high volume of repetitions.